Younger You
Younger You
Younger You
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E3-20211209-JV-NF-ORI
Contents
COVER
TITLE PAGE
COPYRIGHT
DEDICATION
PART 1
PART 2
PART 3
APPENDIXES
THE RECIPES
SHOPPING LISTS
INGREDIENT NOTES
NUTRIENT REFERENCE
THE METHYLATION CYCLE
RESOURCES
DNA METHYLATION CLOCKS TO ASSESS BIO AGE
NONTOXIC CLEANING PRODUCTS
ENVIRONMENTAL TESTING
SUPPLEMENTS
ACKNOWLEDGMENTS
DISCOVER MORE
PRAISE FOR YOUNGER YOU
NOTES
For my daughter, Isabella James, with whom I hope to spend many more
years by following this plan as my foundational anti-aging strategy
and for my patients, colleagues, and friends, for your faith in this work
and for everyone who, like me, feels empowered by the idea that we can
start immediately to safely and effectively turn back the biological hands of
time.
Explore book giveaways, sneak peeks, deals, and more.
W hat if I told you, you could be younger tomorrow than you are
today?
Some part of you would probably be very excited. You did, after all,
pick up a book called Younger You. But there’s probably another part of you
that would be thinking something along the lines of, “Yeah, right.”
But what if I followed that up by saying, it’s true? And that you can do it
simply by changing your diet and making some very doable modifications
to your lifestyle—in other words, without expensive or high-risk drugs, or
fasting for twenty-two hours a day, or any other so-called biohacking
strategies?
“No way,” you’d think.
I have two words for you: Yes way.
In fact, I have a two-month program that reversed the bio age of its
participants by over three years.
I am the lead author on the groundbreaking, rigorous clinical pilot trial
that asked participants to eat plenty of delicious food and adopt a handful of
moderate practices—such as getting seven hours of sleep a night and
practicing relaxation for ten minutes twice a day—for eight weeks. We
measured their biological age before the study began and again when it
ended. And frankly, the results blew our doors off—our study
participants lowered their biological age by an average of 3.23 years
(compared to the control group, who received no intervention)!
This is where I need to point out that our study, while rigorous, was
small. It’s technically a pilot study, meaning it’s designed to provide proof
of concept and open the door to larger studies (which we are working on as
I type). And yet, combined with our years of clinical experience using the
program that we studied and that I outline in this book, it is as clear that we
are headed in the right direction as it is that we need to keep researching.
In this book, as I discuss strategies to reverse biological age, you’ll see
that much of the research I cite is on animals or in human cells. While there
is some research in humans (which I cover), there is significantly less
(hence our trial being “first of its kind”). Although this is a young field,
multiple lines of evidence converge on the conclusion that we might be able
to control how long and how well we live through a combination of diet and
lifestyle changes. In this book, I’ll show you how you can follow essentially
the same path that our study partipants and clinical patients have followed
to become healthier and younger, too.
This third option isn’t a new idea—it was first put forth by James Fries,
a professor of medicine at Stanford University School of Medicine who
published a paper on his “compression of morbidity” thesis in the New
England Journal of Medicine in 1980. In it, Fries wrote, “Chronic illness
may presumably be postponed by changes in lifestyle, and it has been
shown that the physiologic and psychologic markers of aging may be
modified.… These considerations suggest a radically different view of the
life span and of society, in which life is physically, emotionally and
intellectually vigorous until shortly before its close.”4
Our Younger You program aims to postpone chronic illness—and the
associated prescription drugs, surgical procedures, and poor quality of life
—and improve the physiological markers of aging that Fries referenced
using nutrient-rich food and time-tested lifestyle practices to empower the
innate and timeless healing systems encoded within your body to slow
down and even prevent chronic illness and the “aging” trajectory. By
following it, you’ll be aiming to influence your epigenome and genetic
expression. No matter your family history, current health status, age, or
weight, you can get on a path to raising your level of health, reducing your
bio age, and extending your health span—maybe even your life span.
So that you understand the power of these diet and lifestyle strategies, in
Part 1 you’ll learn more about how your epigenome directs your genes to
keep you alive and healthy—or contributes to aging and its frequent
companion, illness. I’ll introduce you to DNA methylation, which is a
mechanism of epigenetic expression, as well as the formula to the Younger
You plan.
Whether you’re facing a health challenge or are very motivated to
reverse the hands of time (or both!), you’ll find guidance in Part 2, in which
I’ll share the eight-week Younger You Intensive program—the exact
version that our study participants followed—as well as the more flexible
Younger You Everyday, which you can adopt as your long-term eating plan
after finishing the Intensive. Or if you want a more gradual transition into
the Intensive rather than a full jumping in, you can start with the Younger
You Everyday and then move over to the Intensive.
And in Part 3, I’ll share insights on how to think about your genetic
testing results if you have them, and my thoughts on how to tend to the all-
important tumor-suppressor genes (the most famous one being BRCA) so
that they remain hard at work for you throughout your life, keeping cancer
(and aging) at bay. (As you’ll see, the expression of many genes, including
tumor-suppressor genes, has been shown to be favorably influenced by
specific nutrients; I’ve started thinking of these genes as nutrient-responsive
genes.) And you’ll learn how to optimize your lifestyle at every stage of life
in a way that supports your epigenome, and perhaps even pass those effects
on to your children, whether you already have them, are planning for them,
or even if you have adopted or fostered children. Finally, we’ll take a look
at what other anti-aging strategies are currently in development—their
possibilities and their risks—as well as other ways DNA methylation is
changing health care as we know it.
Our study showed that when you choose to give your body more of the
things that we believe promote healthy DNA methylation, and reduce your
exposure to things that deregulate it, you can give yourself the DNA
methylation patterns of a younger you. And that is how you can minimize
your risk of developing disease in the first place, or how you might be able
to mitigate or even reverse its progression if you are already ill. And, bonus,
you’ll also drop excess pounds, regain lost vitality, and make people wonder
what you’re doing to look so good for your age.
These findings support what we see in our clinical practice when patients
incorporate Younger You principles, including
• Weight loss in those who need to lose weight
• Lower inflammation
• Improved energy and mood
• Resolution of skin issues
• Less joint pain
• Fewer headaches
• Improved gastrointestinal health
• Improved methylation markers—measured by levels of homocysteine,
B12, and folate—without supplementation
Although changes can happen quickly, it’s really the choices you make
every day over a sustained period of time that impact your long-term health
—and even the health of your offspring—most significantly.
Much of what we understand today in terms of the heritability of
epigenetic changes and the role of nutrition in what gets handed down was
first illuminated by Randy L. Jirtle, PhD, a professor of epigenetics at North
Carolina State University and senior scientist at the McArdle Laboratory for
Cancer Research at the University of Wisconsin at Madison. A true pioneer
in the field of epigenetics, Jirtle conducted an experiment on female agouti
yellow mice—a strain of mouse that has an expressed (i.e., not
hypermethylated and thus inhibited) agouti gene that makes the mice obese
and gives them a distinctive yellow coat. Jirtle, and his postdoc Robert
Waterland, supplemented their diets with vitamin B12, folic acid, choline,
and betaine—these are key players in the methylation process, known as
methyl donors, which I’ll explain in a bit—before, during, and after
pregnancy. Three generations of offspring of these mothers were normal
weight and their coats were either mottled with brown or fully brown, rather
than the distinctive yellow. The methyl donors had in effect shut the agouti
gene off. It was a true “wow” moment; his paper describing this study has
gone on to be the most cited study in the history of science.10
We already knew that a mother’s nutrient levels had a huge impact on the
health of her child. For example, we’ve long known that mothers with low
levels of folate have a higher rate of giving birth to babies with birth defects,
which is why grains have been required to be fortified with folic acid since
1998 (and why rates of birth defects have come down, although there are
perils to folic acid supplementation, too—more on this here). Turns out
that’s because folate is an important component of the methylation process
throughout the body, including DNA methylation.
But our understanding of just how impactful the nutrition of pregnant
human mothers is on the health outcomes of their children was furthered by
three fairly recent epidemiological studies.
The first, a 2013 study, looked at children who were born to women who
were pregnant during what’s known as the Dutch Hunger Winter. In
September 1944, at the tail end of World War II, train workers in the
Netherlands went on strike, hoping to slow the movements of Nazi troops
and give the Allies a leg up. The Nazis retaliated by implementing a
blockade that prevented food supplies from reaching the country, plunging
the Western half of the Netherlands into famine conditions. Until the country
was liberated in May 1945, most people in the affected area subsisted on
somewhere between four hundred and eight hundred calories a day. More
than twenty thousand Dutch people died of starvation.
Perhaps not surprisingly, scientists who evaluated the health of the people
who were born during and just after the Dutch Hunger Winter found that
they experienced health issues that even their own siblings (who were not in
utero during the winter in question, either because they were already born or
hadn’t been conceived yet) didn’t. What is a surprise is that this cohort, in
adulthood, was more likely to be overweight and have higher levels of LDL
cholesterol and triglycerides—all things associated with eating too much
food, not too little. They also had obesity, diabetes, and interestingly,
schizophrenia at higher rates, as well as a 10 percent higher incidence of
death from any cause by the time they were sixty-eight.11 Put simply, the
early life experiences caused accelerated biological aging and early
mortality.
These findings flummoxed the scientists who first observed the higher
incidence of obesity. And then, in 2018, thanks to advances in science that
allow lab researchers to observe the methylation marks present on over
350,000 different spots on the genome, came a big “Aha!” moment:12 they
saw evidence that those who were in utero during the Dutch Hunger Winter
were more likely to have more methyl groups on a gene known as PIM3,
which is involved in metabolism, and different methylation patterns on other
genes implicated in cell growth, lipid metabolism, and glucose tolerance.
Perhaps the mothers’ hunger caused hypermethylation on this gene and
imbalancd methylation patterns on other genes, and thus their children’s
metabolism always ran a little slower in an effort to hang on to food a little
longer (that thrifty epigenotype I referred to earlier), leading to gaining
weight.13
Another foundational study found a similar result. The Överkalix cohort
study analyzed multiple environmental factors on the population of
Överkalix, a small city in Sweden where they kept copious records, such as
the size of the harvest and the price of food, for decades. The researchers
were seeking to determine the effect of the amount of food readily available
on epigenetic inheritance in populations born in 1890, 1905, and 1920, as
well as in those populations’ children and grandchildren. The researchers
found that eating too much in childhood—specifically in boys in
preadolescence, when sperm are actively maturing—in generation zero
correlated with diabetes and diabetes-related mortality in the subsequent
three generations! Interestingly enough, the same study shows a protective
effect from eating less, suggesting that there is a sweet spot of food
consumption—not too much, not too little, but just right.14
The third study that has shaped our understanding of the inheritance of
epigenetic changes came in 2014, when Moshe Szyf, Suzanne King, and
team conducted a study called Project Ice Storm. In it, they evaluated the
DNA methylation of children born to mothers who lived in Montreal and
were pregnant during a severe two-week 1998 ice storm that cut the power
off in large swaths of Ontario, Quebec, upstate New York, and Maine. The
mothers did not starve, but rather experienced profound physical and
psychological stress. King’s team found that these children were likely to
develop a distinctive DNA methylation pattern on the genetic code in their T
cells—an important immune system cell—and were more prone to
displaying symptoms of asthma and autism.15
It may seem like bad news that if your mother was exposed to stress or
trauma when she was pregnant, you’re doomed to have genes that don’t
work as well as they could. When in truth, the opposite is true: knowing that
you can influence DNA methylation, and how to do it, can help you make
mindful choices that optimize the genetic—and the circumstantial—hand
you’re dealt. Even genetic conditions where your fate seems carved in stone
can be minimized by bolstering your DNA methylation.
Obesity
The truth is that weight—as measured by BMI—is associated with
accelerated aging, as measured by DNA methylation.16
Based on what we saw in our research study with a few participants
(most didn’t need to lose weight as they were healthy at the start) and in our
clinical practice, those who follow the Younger You Intensive, certainly, and
even the Younger You Everyday, and who can benefit from weight loss do
lose weight. The Younger You Intensive employs the well-established
weight-loss guidelines of being a low-glycemic, keto-leaning program that
incorporates mild time-restricted eating (otherwise known as intermittent
fasting). It’s also free of allergenic foods, such as dairy and gluten, so it’s
also anti-inflammatory. Taken altogether, the Younger You Intensive lowers
inflammation and increases energy and satiety, which allows for weight loss,
if needed.
Following the Younger You principles of avoiding toxins (more on this in
Chapter 7) also reduces your exposure to endocrine-disrupting chemicals,
also known as obesogens, that contribute to the epigenetic dysregulation that
is associated with metabolic impairment and weight gain.
On top of these direct influences on weight loss (and this doesn’t even
include the weight-loss benefits of regular moderate exercise, improved
sleep, and boosted relaxation), modulating your DNA methylation may also
affect expression of obesity-associated genes that influence what your body
does with calories.17 If these genes are shut off due to hypermethylation,
you’re more than twice as likely to be obese. Because the Younger You
program includes ample amounts of foods that affect the methylation-
demethylation balance, the eating plan may help turn back on the genes that
promote a healthy weight.
By the same mechanism, eating the DNA methylation–supportive
nutrients that are a hallmark of the Younger You program may help to
change the epigenetic patterns that you’ve inherited from parents,
grandparents, and great-grandparents.18 It gives you hope of breaking the
cycle of “The chubby gene runs in our family.”
Alzheimer’s Disease
Having a family member with Alzheimer’s can feel like receiving that
diagnosis is an unavoidable part of your future. Yet, while there can be a
genetic component to Alzheimer’s disease, 95 percent of those who have it
have the nongenetic form. That means epigenetics dictate the vast majority
of cases.
As with obesity, it’s known that epigenetic mechanisms play a variety of
crucial roles in the development of Alzheimer’s disease, to the extent that
several epigenetic-based therapies are being considered now.
Most broadly, accelerated biological age is associated with Alzheimer’s,
and patients with Alzheimer’s are biologically older than same-aged healthy
folks.19 Alzheimer’s and other neurodegenerative diseases are accompanied
by marked global methylation decrease overall (very often this population
has elevated homocysteine, a marker of decreased methylation), along with a
higher expression of genes you don’t want to be turned on and a lower
expression of genes you do want in the on position.
More specifically, a number of genes involved in Alzheimer’s disease
have been found to have aberrant methylation patterns in those with the
disease as compared to those without the disease, meaning some genes are
on when they should be off, or off when they should be on.20
The APP (amyloid precursor protein) gene gives rise to amyloid beta
protein when it is in the on position, and APP is often in abundance in the
brains of Alzheimer’s patients. When we’re young, this gene tends toward
the off position; as we age, it can turn on, which likely plays a role in higher
levels of beta amyloid in the brain and, thus, higher risk of Alzheimer’s
disease. Furthermore, the gene for the protein that breaks down beta amyloid
is actually hypermethylated and turned off—a double Alzheimer’s whammy.
In addition, the ApoE4 gene, well known to be associated with the disease,
has a complex and unusual pattern of methylation, with some areas
hypomethylated and others hypermethylated. Scientists speculate that these
changes may induce the pathologic alterations seen in the brains of
Alzheimer’s patients.21
From my standpoint, any program effectively addressing Alzheimer’s
disease requires interventions that address DNA methylation and epigenetics
in general, supporting both methylation and demethylation.
The functional medicine approach to Alzheimer’s disease (as developed
by Dale Bredesen, MD) is a powerful intervention for both preventing and
treating Alzheimer’s disease—a 2021 multicenter clinical trial validated its
beneft.22 Much of the Younger You program and the Bredesen program
overlap: Each focuses on healthy, low-carb/keto-leaning, good-fat and
polyphenol-rich foods with time-restricted eating windows. Each prioritizes
exercise, sleep, and stress reduction. And each approach minimizes toxin
exposures, which is essential in protecting brain function and DNA
methylation. Dr. Bredesen also recognizes hypomethylation as an issue and
pays attention to homocysteine levels in his patients.
Where Younger You differs from Bredesen’s approach is its wholesale
focus on balancing DNA methylation.
In our clinic, we use the Bredesen approach as a foundation and then
layer Younger You components onto his program. Our patients with
neurodegenerative conditions routinely experience lower levels of
inflammation, homocysteine, and toxins and demonstrate improved nutrient
status. We see the best outcomes in cognitive scores with mild cognitive
impairment (MCI), although we can see favorable changes in cognition even
in those with advanced disease.
Reducing elevated levels of homocysteine, the biomarker associated with
poor overall methylation, including DNA methylation, has also been shown
to slow the rate of whole brain atrophy and cognitive decline in elderly
people with cognitive impairment.23 And the patients in our clinic routinely
lower their homocysteine to healthy levels when following the Younger You
program.
Heart Health
Cardiovascular disease is the number one cause of death worldwide. We
cannot overstate the significance of heart disease in terms of quality of life
and medical costs: it’s absolutely enormous.
Bio age, as measured by DNA methylation patterns, is well correlated
with risk of cardiovascular disease—the higher your bio or chronological
age, the greater your risk of heart disease.24
In addition, inherited altered DNA methylation patterns—like those seen
in the Dutch Hunger Winter and Överkalix studies—contribute to conditions
including diabetes, hypertension, and obesity that increase your
cardiovascular risk.
Disordered methylation patterns on numerous genes associated with
hypertension, atherosclerosis, heart failure, and myocardial infarction have
been identified in humans.25 What I find most interesting is the connection
between early and midlife stress and altered DNA methylation patterns that
have been associated with later onset heart disease and cognitive decline. Of
particular note is the gene NR3C1, which codes for the human
glucocorticoid receptor (glucocorticoid is a class of steroid hormone that is
released during stressful times and plays many roles, including curbing
inflammation). Different methylation patterns of NR3C1 have been
identified in a broad spectrum of stress disorders, heart disease, and
cognitive decline, making it a common gene of interest in all of these
conditions.26
Elevated homocysteine, a foundational marker of imbalanced total
methylation (including DNA methylation), has long been touted as a risk
factor for cardiovascular disease and stroke. Yet, the research does not
clearly show that simply lowering homocysteine alone will prevent heart
disease.27
So how do we interpret these seemingly conflicting findings? DNA
methylation patterns, changed by broad environmental exposures ranging
from previous generational experience to early and midlife stress exposures,
to diet, toxins, exercise patterns, and more all influence methylation patterns
that in turn influence heart disease risk. Myopic focus on correcting
homocysteine—or limiting treatment to cardiology alone—isn’t enough; as
with all of the conditions discussed in this chapter, a full Younger You
Intensive may favorably influence the occurrence of heart disease in a broad,
beneficial manner, as getting biologically younger reduces risk.
Type 2 Diabetes
In the United States alone, a diabetic is diagnosed every twenty seconds.
This metabolic disease burns through bio age like dry kindling on a hot day:
diabetes is associated with a six- to nine-year increase in biological age!28
It’s well established that type 2 diabetes results in general dysregulation
of DNA methylation with far-reaching effects, including hypermethylation
of important tumor-suppressor genes and antioxidant-regulating genes,29 as
well as a particular gene that impacts insulin, PPARGC1A.30
The obesogenic toxins that play a role in excess weight—like PCBs and
pesticides—even in low doses of exposure, are also potent drivers of
diabetes, in part because they contribute to abnormal DNA methylation
patterns.31 And higher levels of exposure to obesogens are associated with a
whopping thirty-eight-plus-fold increase in diabetes!32
The good news is that type 2 diabetes is very responsive to the Younger
You protocol. One patient in particular is a perfect example of the kinds of
results we see in the clinic.
Linda was fifty-six when I first saw her. A smart, funny university
professor, she’d been diagnosed with type 2 diabetes a decade ago, and her
family history was riddled with diabetes and diabetes-associated conditions
like high blood pressure and heart disease. Despite her best efforts at
lifestyle change and a cocktail of medications, her blood sugar and lipids,
weight, blood pressure, and food cravings were all high. Her mood was low.
Linda was sick and tired of the conventional approach and was looking for a
new approach to her care. At a glance, Linda’s diet looked pretty good: she
was eating a lot of your basic salad-and-protein meals. She also engaged in a
daily meditation practice. Her real struggle came at night, when she got
home from a long, intense day. Her cravings would hit, and she’d go for
sweets and a glass of wine; in fact, her red wine intake was high (as you’ll
learn in Chapter 5, alcohol inhibits methylation).
We placed her on the full Younger You Intensive program, with an
emphasis on even lower carbs, since we needed to get her glucose and
insulin levels down. We had her prioritize eating specific DNA methylation–
supportive nutrients that have a powerful anti-inflammatory effect, including
those found in turmeric, green tea, and rosemary. I also started her on
moderate doses of fish oil, magnesium, and vitamin D supplements. After
her first month on the plan, her morning fasting blood sugar had dropped
from 300 to 90! At four months, she was down twenty pounds and
exercising most days. She was thrilled with her progress and committed to
the journey. We could all see her getting younger before our eyes, and most
importantly, she could see the Younger You coming through in herself!
Depression
Mental health has epigenetic roots. In adults with depression, two key genes
have been found to be hypermethylated and inhibited:
Cancer
Epigenetic aging, left to its own devices, marches us toward all of the
diseases we’ve discussed so far. But nowhere is this march so well studied,
and perhaps so scary, as it is with cancer.
Cancers of all type (brain, bladder, breast, lung, prostate, colon, skin,
ovarian… ) hijack our epigenetic machinery for their own nefarious end, like
expert computer hackers can take down a country’s defenses with chilling
ease.39 Also, even if we do not have cancer present, as our biological (and
chronological) age creeps higher, all-important tumor-suppressor genes
(including the most famous, BRCA1) and tumor repair genes can become
hypermethylated and shut off. In addition, genes that promote cancer (called
“oncogenes”) are hypomethylated and turned on. It’s just not fair: aging
makes us epigenetically vulnerable to developing cancer, and cancer itself
takes over our epigenetics.40
Because problem DNA methylation is a big piece in many conditions,
scientists are working hard on developing DNA methylation tests as
diagnostic tools for many, many disorders. This is most evident in cancer,
where the methylation status of tumor repair and tumor-suppressor genes is
used in diagnosis. Perhaps the best known example of this is the Cologuard
at-home colon cancer screening test, which assesses two genes in particular
that are typically hypermethylated in colon cancer (NDRG4 and BMP3).41
Hypermethylation of tumor-suppressor genes is such a strong factor in
cancer development that there are demethylating drugs for certain cancers.
They can be important players in therapy, but they are riddled with potential
toxicity because they indiscriminately inhibit DNA methylation. After all,
you don’t want to turn genes on, or off, for that matter, willy-nilly. Better to
seek the precision changes that our study suggested diet and lifestyle can
produce—our participants reduced their biological age by moving methyl
groups to DNA sites that are associated with youth (instead of age), and
therefore health (instead of disease, including cancer).
It’s starting to look like many of these cancer-associated genes are what I
suspect are nutrient-responsive genes—meaning, their DNA methylation
patterns change rather predictably in the presence of specific nutrients. There
are certain DNA methylation–supportive nutrients (we call them DNA
methylation adaptogens, which I’ll cover more in depth in Chapter 3) that
have some very exciting benefits for cancer prevention. For example, we’ve
long known that EGCG (a component of green tea) and curcumin (a
component of turmeric) are important interventions in integrative cancer
care. Now we believe that a chief reason is that they favorably influence
epigenetics, and in particular, DNA methylation.
Research is also suggesting that combinations of these supportive
nutrients may be powerful in cancer prevention and treatment, which
strongly reinforces the power of a whole foods diet that provides not only
ample amounts of specific nutrients, but also creates the conditions they
need to work synergistically with each other.42 I look forward to continuing
to research the impact our Younger You program has on cancer epigenetics
via these nutrient-responsive genes.
In our practice, patients come to us most often to be comanaged with
their oncology team. With most patients in active cancer treatment, we
individualize the Younger You to them as appropriate: common
customizations include longer periods of intermittent fasting in association
with their chemo regimen, reducing carbs to make the eating plan more
ketogenic, prescribing extra doses in diet and supplement form of the DNA
methylation adaptogen nutrients I just mentioned and will share many more
details about in Chapter 3, and perhaps prescribing blood sugar–supportive
nutrients or medications as needed.
One final word on working with cancer patients (and anyone with a
chronic illness or simply wanting to reverse biological age): the mind/body
component of care cannot be overlooked. My good friend and colleague Dr.
Patrick Hanaway recovered from stage 4 laryngeal cancer. While he
incorporated the components I’ve discussed above along with radiation and
chemotherapy, he said it was sloshing barefoot through the creek on his
property that grounded him and was, as he says, a turning point in his
healing.
All of this points to one fact: a healthy diet and lifestyle unequivocally
reduces incidence of all chronic disease.43 This is great news. Whether you
are fairly healthy or someone with a chronic condition (and perhaps
wondering if it’s too late to change), it’s always a good time to support your
DNA methylation and your bio age. And interesting research I’ll share later
suggests that the older you are, chronologically and biologically, the more
bang for your buck you’ll get with these changes. Meaning, it’s never too
late.
In the next chapter, we’ll unpack exactly which foods and lifestyle
practices we used in our research study and show evidence that they
favorably influence DNA methylation and reverse bio age.
3
• Methyl donors are the foods that contain the nutrients the body uses
to create methyl groups, which are then used in multiple processes
throughout the body, including DNA methylation. These are the
ingredients of DNA methylation.
2. For folks who can process folic acid into folate efficiently, if there is a
high intake of fortified foods (especially combined with
supplementing extra folate), there is a risk of having more active
folate than needed and pushing DNA methylation into potentially
dangerous territory—resulting in more methyl groups being added to
more DNA, including on beneficial genes like tumor-suppressor and
anti-inflammatory genes, and perhaps even shutting those genes off.
And if cancer is already present, folate can increase the synthesis of
tumor cells and promote DNA methylation in an unhelpful way.
Indeed, the rate of colorectal cancer in the United States started to
tick upward (some researchers called it an “abrupt reversal”5) in 1996
after a fifteen-year decline, peaking in 1998, the very year that all
grain manufacturers were required to fortify their products with folic
acid.6 While mere timing doesn’t prove causation, a 2010 study found
that in individuals with high blood folate, two tumor-suppressor
genes were hypermethylated and turned off.7
There are some countries that are exploring ending folic acid fortification
because of the potential risks (I would not be surprised if the United States
considers this step at some point in the future), and still other countries
deciding against starting fortification programs.
To me, it’s clear that while we need an ample amount of folate, we don’t
need to get it from folic acid–fortified foods or from routine
supplementation. To my view, the best way to obtain our nutrient
requirements is through a whole foods diet, but a healthy microbiome can
play a role, too, although we’re still learning about the extent of the
contributions. Beneficial gut bugs actually make a lot of vitamins, and folate
is just one of them (B1, B2, B12, biotin, B6, vitamin K, and PABA are
others).8 In our study, we increased circulating folate solely via food sources
and by prescribing a probiotic that contains Lactobacillus plantarum, a strain
that has some research to suggest that it makes folate.
To be clear there are rare times when high-dose supplementation with
folate is needed. For example, there is a condition called cerebral folate
deficiency—an autoimmune disease where folate can’t get from the blood
into the brain, which creates a host of neurological issues including memory
loss, vision loss, and hearing loss—that can be completely resolved with
high doses of folinic acid, a type of folate.9 Some other conditions where I
think supplemental folate is warranted (often along with B12 or other
nutrients) include pregnancy, macrocytic anemia, certain neurological
conditions, elevated homocysteine, malabsorptive conditions, and some
dietary limitations.
Otherwise, generally speaking, we don’t want to get our folate through
high-dose supplements.
• The nutrients are housed within the complex matrix of a whole food
and work synergistically with each other, improving the absorption
and actions of individual nutrients.
Whole foods, which are exactly what they sound like—foods in their
original form like vegetables, fruits, nuts, seeds, and quinoa—have
incredible healing abilities, not just because of their superstar nutrients, but
also because of their full roster of components and the interplay that happens
between them that we are only beginning to understand. Honestly, we may
never fully grasp all the nuances of how the components of whole foods
influence physiology, because the complexity of nature’s wisdom truly is
mind-boggling. In fact, there is a concept known as the “dark matter of
nutrition,” which reminds us that, as extraordinary as the components of
whole foods that we already know about are, most of what is contained
within a whole food hasn’t yet been defined.
Take an apple, for example. Just one bite contains an extraordinarily
complex packet of information, as opposed to a drug or a supplement, which
is typically only one thing. Its primary component is carbohydrates, mostly
in the form of sugar—a medium apple has 25 grams of carbs, of which 19
are naturally occurring sugar. It also has a scant amount of protein (1 gram)
and 3 grams of fiber, which serve to slow the release of those sugars once in
your digestive tract so that your blood glucose levels don’t rise and then
crash quickly. Much of the fiber comes from an apple’s pectin content;
pectin is a source of soluble fiber, meaning it is broken down in the digestive
tract and stimulates elimination. It is also fermented by your gut bugs, a
process that produces short-chain fatty acids such as butyrate that
researchers have shown play a role in preventing some cancers and bowel
diseases.
That’s not nearly all. An apple also contains many, many phytochemicals
(primarily in the skin), including quercetin, a known antihistamine that can
also help lower cholesterol and protect against viruses. Quercetin is a
senolytic compound, too, meaning it wards off aging. And it helps optimize
genetic expression.
And that’s just one phytochemical component of an apple. Others include
epicatechin, cholorogenic acid, and anthocyanin. These and other
biologically active compounds in apples are beneficial for most chronic
diseases—from cancer, dementia, and diabetes to heart disease and lung
disease—via a variety of mechanisms, including helping to process the
higher sugar content in apples through improved insulin sensitivity. Most of
them can also regulate genetic expression (they’re what’s known as DNA
methylation adaptogens, a concept I’ll explain more in just a moment). And
of course, an apple contains ascorbic acid, also known as vitamin C, which is
an essential antioxidant, as well as a very important regulator of DNA
methylation that helps get rid of methyl groups where they shouldn’t be.
As soon as you turn that whole apple into something else, you modify
these components and hamper their benefit. Removing the skin from the
apple also removes much of the fiber and the majority of the quercetin and
most of its other potent phytochemicals—buh bye, short-chain fatty acids,
hello, blood sugar spike. Drying the apple concentrates the sugar and
evaporates most of the vitamin C. Juicing an apple also concentrates the
sugar, and removes the fiber and most of the phytochemicals.
Beyond the magnificence of its components, the process of eating an
apple—or any whole food—kicks off a cascade of events that can’t even
compare to swallowing a pill.
First, just thinking about the food triggers a chain reaction in your brain
that preps your entire digestive system for the incoming work to be done.
Just think about applesauce—peels on!—simmering on the stove, its scent
wafting through the house. Congrats, you just started activating your
digestive enzymes!
Next, seeing and smelling the food cues the release of saliva, which
contains the digestive enzyme amylase, which alerts your stomach to make
acid, your pancreas to make digestive enzymes, and your microbiome to
ready itself to further break down and transform the food. Chewing that bite
begins to liberate the nutrients and further prompts the digestive chemical
cascade.
As the food passes through your digestive tract, your microbiome
population will take what it needs to produce neurotransmitters, fatty acids,
and vitamins. In fact, one of your gut bacteria’s most important roles is to
take the phytochemicals in your food and ready them to do their important
work, which often includes regulating gene expression. Meanwhile, your gut
lining readies itself to absorb these transformed packets of information.
Right on the other side of your gut, your immune system reviews what’s
been ingested and determines what the immune response will be, whether
it’s to trigger inflammation or not. Isn’t it just astounding how beautifully
complex our internal interaction with food is? And just take one more
moment and imagine what happens when you eat a big garden salad, with
apple slices and maybe some seeds on top. The potential benefit of
thousands upon thousands of nutrients from this full meal interacting with
each other, your microbiome, and you, is nothing short of extraordinary.
Eating whole food ensures you get a balance of synergistic nutrients in
ample, but not excessive, amounts. The beauty of mother nature’s design,
and how it falls in lockstep with what we need to flourish, blows me away
every day. And our understanding of whole foods and how they benefit all
the systems of the body is only continuing to grow.
Let’s look at the three components of the Younger You formula—the two
categories of whole foods that comprise the bulk of the Younger You
program, as well as the lifestyle practices that have been shown to positively
influence DNA methylation.
Curcumin Turmeric
Sleep
OK, all you insomniacs out there. Let me attempt to not stress you out by
haranguing you with how important sleep is to health; especially epigenetic
health. (Believe me, as someone who struggles with sleep and whose child is
still a toddler, sleep has not been my self-care strong suit.) Just keep in mind
as you read that you don’t need to get epic amounts of slumber. In fact, in
our study, we advised our participants to get a very moderate seven hours of
sleep a night, which is generally considered to be healthy.19 They didn’t have
to completely overhaul their lives or their sleep habits in order to reap the
benefits of healthy sleep and reduce their bio age. So if you’ve given up on
ever being able to get eight hours regularly, let me just start by lowering the
bar a bit.
That being said (here it comes), sleep is a vital piece of your health.
There is an emerging body of science in humans and animals looking at
changes to the epigenome that poor sleep triggers in everyone from infants
to adults, and it’s not pretty. For instance, sleep and accelerated aging: one
fairly large study of over two thousand women showed insomnia (chronic
sleep deprivation) significantly accelerated DNA methylation age.20 A
similar, smaller study showed the same thing again: a consistent sleep record
of short duration and poor quality accelerated aging.21 Changes noted
include accelerated cognitive deficits, metabolic changes (think weight gain
and diabetes), and changes to circadian rhythm genes.
What’s interesting—and concerning—is that changes can be noted
quickly. As in, after one poor night’s sleep.22 I know—painful! Rather than
fixating on how a bad night’s sleep can wreak epigenetic havoc (especially
while you’re lying there, awake), remember that what you do consistently
matters more than what you do once in a while. Meaning, it’s chronic
deprivation that we’re concerned about. I’ll cover many ways to optimize
sleep so that you get more of it in Chapter 7.
Exercise
You may think of exercise as a way to burn calories, build muscle, improve
cardiovascular health, or clear your head. Exercise is all of these things, yet
it is so much more. Because exercise is such great nourishment to your DNA
methylation, it is also an anti-aging elixir.
Exercise is well known to be broadly beneficial for almost every aspect
of health—regulating insulin sensitivity, decreasing inflammation, and
lowering homocysteine—and has been shown to extend mean life span in
animal models. Exercise triggers what’s known as hormesis, or a biological
process where a beneficial effect is triggered by a limited exposure to
something harmful or challenging to the body. You probably know that
lifting weights causes microtears in the muscle that the body then knits back
together to make it bigger and stronger. A similar process happens on the
cellular level, too: exercise causes increased free radicals in the
mitochondria, which are the energy factories within your cells that you may
recall learning about in high school biology class. Free radicals are
destructive molecules, which might seem like a bad thing until you consider
that those free radicals induce a hormetic response where your antioxidant
system is turned on to put out the fires. As a result, every time you exercise,
your mitochondria are drenched in the potent antioxidant elixirs that only
our body can make. It’s important to note that you want just enough
exposure to free radicals, as too many can be definitively damaging. Like
most things, exercise has a U curve of benefit, and exercise that is too
extreme breaks the body down in greater amounts than it can recover from.
A 2018 study found that Polish elite athletes, especially those involved in
power sports (such as competitive weight lifting), were significantly
biologically older than healthy controls of similar mean ages.23 This
suggests a sweet spot for exercise, which may be more or less than what you
are currently doing.
When it comes to DNA methylation, research suggests that reasonable
exercise is nearly always beneficial, with changes that can be seen almost
immediately. Multiple studies have shown exercise reduces methylation of
tumor-suppressor genes. This mechanism is probably a big reason why
exercise is an important preventative measure for cancer, as well as an
invaluable intervention if diagnosed, as was shown in a 2012 study looking
at breast cancer.24
Just as knocking yourself out at the gym to the point that you can barely
walk the next day is counter-productive, so is not moving enough. Being
sedentary is as woven into the typical American experience as a diet of
highly refined foods, and it is another piece of our collective way of living
that we have to consciously move away from. Luckily, you don’t need to
attend a CrossFit class, buy a Peloton bike, or hire a trainer to ensure you’re
moving enough. Even cleaning house showed anti-aging DNA methylation
changes (not that I recommend this one…)!25 Generally speaking, moderate
and consistent movement is the name of the game when it comes to helping
your genes be the best they can be.
In our study we had people exercise at least thirty minutes a day, five
days a week, at only 60 to 80 percent of perceived exertion, doing some
activity that they truly enjoyed. It was a potent part of the mix that led to
their significant reduction in bio age.
Stress-Reducing Practices
Stress plays an enormous role in DNA methylation. In fact, almost 25
percent of the methylation sites in the specific epigenetic clock that we used
in our study to determine biological age are related to stress. Research has
shown that cumulative life stress,26 PTSD,27 and even how much stress your
mother was exposed to when she was pregnant with you (recall the Project
Ice Storm study I mentioned in Chapter 2) can all negatively impact your
epigenome. And you can hand this pattern down to your offspring.
I know this probably sounds like a big fat bummer—after all, the world is
a stressful place and much of the stress you’ve been exposed to you had no
control over whatsoever (you may not even have been alive). Yet there is
good news.
We may not be able to control the things that cause us stress, but we do
have quite a lot of influence over our own response to stress. There are many
practices that induce the relaxation response.
Research has found alterations in DNA methylation in long-term
practitioners of tai chi28 or meditation,29 and even in “regular” people who
started a yoga class and practiced only one hour a week.30 A 2019 study by
Italian researchers demonstrated that sixty days of relaxation practice—such
as meditation or listening to peaceful music—for twenty minutes twice per
day significantly reduced the biological age in their group of healthy
participants (though not in their “patient” group).31 In our study, we had the
participants complete ten to twenty minutes of breath-focused meditation
twice a day. (I’ll share more of the specifics about that practice in Chapter
7.)
The more stress you have encountered, the more vital it is that you adopt
relaxation-inducing practices. I get the paradox in that—being stressed out
can make it seem mighty hard to pursue anything that isn’t absolutely vital
to survival. I’m arguing that doing things that reduce your stress, and doing
them consistently for the long term, are vital to your survival. They are a
huge part of how you heal from the stressors you’ve endured.
We absolutely have the ability to reverse stress-induced epigenetic
programming. These favorable changes can be detected even after a single
contemplative practice.32 Yet, like anything else, the longer you practice, the
longer lasting and more profound your results.
Even as a functional medicine practitioner, who is trained to see a patient
as a complex being, I find it awe-inspiring to see just how many things can
alter our DNA methylation—it shows just how many levers we have to
improve our own health. While that could sound overwhelming, that you
have more to take care of in order to be healthy, think of it this way: if any
one of these levers is a little off, you have a lot of other tools you can use to
shore yourself up. If your diet goes off the rails, for example, you can ramp
up your relaxation practices and your sleep to keep yourself in a good place
until you can get back on track. Or if you go through a spate of poor sleep,
you can make sure you’re eating plenty of methyl donors and DNA
methylation adaptogens and keep your epigenetics in a good place.
T here have been many attempts over the years to define biological age,
which, as I’ve covered, is not how old you are in years, but how old your
physiology suggests you are.
Over the past decade or so, telomeres (pronounced TEE-loh-meers) have
gotten a lot of attention from the scientific and medical community as
indicators of biological age, particularly thanks to the work of Elizabeth
Blackburn, PhD, professor of biology and physiology at the University of
California, San Francisco, who won the Nobel prize for her work on
telomeres, and Elissa Epel, PhD, professor of psychiatry at the University of
California, San Francisco, authors of The Telomere Effect. These sequences
of genetic material are found at the end of the strands of our chromosomes—
they protect DNA by keeping it from fraying and from fusing with other
strands. They are often compared to the plastic tips that seal the end of
shoelaces.
Telomeres are made out of pairs of the same nucleic acid bases that DNA
is comprised of: guanine (G), adenine (A), thymine (T), and cytosine (C).
Every time a cell divides, it replicates its DNA, and with each replication,
the telomere loses some of its base pairs and gets a little shorter; so as we
age, the length of our telomeres goes down. And the shorter our telomeres,
the greater our risk of diseases.
Telomere length seems like a great way to assess how old you truly are,
and it certainly is an important consideration when taking stock of how
healthy your whole being is. But the length of your telomeres only has a .4
correlation with your actual age (with 1 being perfect correlation). That
means they have a 60 percent chance of being wrong. Not great odds.
In 2013, Steve Horvath, a professor of human genetics and biostatistics at
UCLA, published findings that he could determine biological age by
analyzing the DNA methylation on hundreds of sites on the genome with
only a cheek swab or a drop of blood. Extraordinarily, the results of that test
had a correlation of .96 with chronological age. Even more impressive:
much of that missing .04 is not a mistake—it’s the difference between your
calendar age and your biological age. He essentially discovered an
epigenetic clock—one that has become the gold standard of determining true
physiological age, which he titled the DNAmAge clock, and which is now
colloquially known as the Horvath clock.
Horvath’s DNAmAge epigenetic clock works by looking at methylation
at hundreds of specific sites on DNA that change with age. Some get more
and more methylated as you live longer, and some are the opposite—they get
less and less so the older you get. By looking at the methylation status of
these specific sites on the genome, the clock can calculate your bio age by
assessing how old the methylation patterns on your genes are. The
DNAmAge clock is what has made possible studies—like ours—that
measure the impact of different strategies on bio age.
Since we began our study, many second-generation epigenetic clocks
have been released, including the GrimAge clock and the PhenoAge clock,
which correlate with disease and mortality risk, not chronological age. In
fact, research into the world of epigenetic clocks has galloped forward since
we began our study, and it’s all quite exciting. There are clocks that can
measure the age of skeletal muscle, the brain’s cortex, and the immune
system.1 We will be using some of these second-generation clocks in our
next study, which will be larger and include men and women, although we
will also include the Horvath clock again, since it correlates most closely
with true chronological age. We suspect that these second-generation clocks
may be even more responsive to our program because they track with health
and disease rather than the Horvath clock, which tracks with chronological
age.
As I began writing this book, assessing bio age with the DNAmAge (or
any other) epigenetic clock had been accessible only to researchers and was
very expensive. Only a year later, this technology is becoming available and
more affordable for both clinicians and individuals, empowering you to
objectively assess the epigenetic effects of any diet or lifestyle interventions.
(See the Resources, here, for more information on how to gain access to bio
age testing.)
So that you can measure the changes you make to your bio age over the
next eight weeks (and beyond), I am including three different ways to assess
and keep tabs on your bio age. While none of them can match the accuracy
of a bio age test that analyzes your individual DNA methylation patterns,
they can give you a detailed look at your current state of health.
The first is the Bio Age Self-Assessment (BASA), which gauges how
your daily habits and basic biometrics are collectively influencing your rate
of aging. The second is the Medical Symptoms Questionnaire (MSQ), which
is a standard tool in functional medicine that every patient at our clinic fills
out regularly to give us a window into how our interventions are impacting
overall health and quality of life. And the third is guidance on which basic
blood tests to ask your doctor for (if you haven’t had these done in the last
three to six months), as well as how to interpret those results. While none of
these tools replaces DNAmAge testing, taken together, they are a quick,
low-cost way to objectively evaluate both the steps you’re taking to improve
your health (with the BASA) and the results of those steps (with the MSQ
and the lab results).
I suggest taking both of these self-assessments—and, if you can, getting
your bloodwork done—now, before you start implementing any Younger
You program changes (be they from the Intensive or the Everyday version),
so that you can capture your “before” and give yourself a baseline to help
gauge your progress and incentivize you to stay on track.
Ideally, you’d do the BASA again in four weeks (halfway through the
Younger You Intensive) and then again at the end of the eight weeks; and
you’d do the MSQ every week during the Intensive so that you can evaluate
the fruits of your efforts as you go, which should give you great motivation
to keep going. I know that lab tests typically require a doctor’s order to get,
but if you are able, I suggest getting your blood tested again at the end of
eight weeks.
You can also take the BASA and MSQ, and input the values of your
blood work, in our 3 Years Younger (3YY) app, the digital version of the
Younger You program, which will keep track of your scores and, through our
program nutritionists, give you personalized recommendations based on
your results. And if you are interested in learning your bio age via a
DNAmAge test, and learn more about the methylation patterns on some of
the genes I mention throughout the book, including the nutrient-responsive
tumor-suppressor genes, you can do that through our 3YY digital program as
well. See Resources, here, for more information.
SECTION 2: Lifestyle
1. How often do you engage in an activity you would consider to be
“play” (e.g., playing tennis with a friend, playing a board game with
your children or grandchildren, etc.)?
Never (+2)
Once per month (0)
1–2 times per week (-1)
3+ times per week (-2)
2. How often do you engage in moderate or high-intensity
cardiovascular exercise (that gets your heart rate up, causes you to
break a sweat, and have some difficulty in talking)?
Never (+2)
Once per month (0)
1–2 times per week (-2)
3+ times per week (-3)
3. How often do you do exercise that makes your muscles work as
hard as they can (e.g., pushups, situps, lifting weights, using bands)?
Once per month or less (+1)
1–2 times per week (-1)
3+ times per week (-2)
4. How many hours do you spend sitting every day?
8 hours or more (+2)
5–8 hours (+1)
Less than 5 hours (-1)
5. How many hours do you sleep on an average night?
0–4 hours (+2)
5–6 hours (+1)
7–9 hours (-2)
10+ hours (+1)
6. How do you rate your quality of sleep (do you wake up feeling
refreshed and well rested)?
Poor (+2)
Fair (+1)
Good (-1)
7. How would you describe your overall level of toxin exposure (e.g.,
regular exposure to construction materials, gasoline, eating or
heating food stored in plastic, cleaning chemicals, mercury dental
fillings, lead paint)?
Very high (+3)
High (+2)
Moderate (+1)
Low (0)
8. Do you smoke cigarettes or live with somebody who does?
1 pack per day or more (+3)
Half a pack per day (+2)
1–5 cigarettes per day (+1)
None (0)
9. Were you ever a smoker? If yes, how long ago did you quit?
Less than 1 year ago (+3)
1–5 years ago (+2)
6–10 years ago (+1)
More than 10 years ago (0)
10. How much time do you spend in nature (hikes, hanging out in the
yard, or visiting a city park all qualify)?
Almost never (+2)
1–3 times per month (0)
1–3 times per week (-1)
Daily (-2)
SECTION 4: Anthropometrics
1. What is your waistline?
MEN:
Greater than 40 (+2)
37–39 (+1)
32–36 (0)
Less than 32 (-1)
WOMEN:
Greater than 35 (+2)
33–34 (+1)
28–32 (0)
Less than 28 (-1)
2. What is your BMI?
(Use the calculator at
https://www.nhlbi.nih.gove/health/educational/lose_wt/BMI
/bmicalc.htm; if your waistline doesn’t add to your bio age, and you
have a lot of muscle, your BMI will be falsely high, as muscle is heavy
—if that’s you, choose the next lowest answer.)
35+ (+3)
31–34 (+2)
20–30 (0)
Less than 20 (+1)
3. Your blood pressure is two numbers. What is the lower number
(diastolic)?
90+ (+2)
80–90 (+1)
60–79 (-1)
Point scale:
0 Never or almost never have the symptom
1 Occasionally have it, effect is not severe
2 Occasionally have it, effect is severe
3 Frequently have it, effect is not severe
4 Frequently have it, effect is severe
Digestive Tract
___________Nausea, vomiting
___________Diarrhea
___________Constipation
___________Bloated feeling
___________Belching, passing gas
___________Heartburn
___________Intestinal/stomach pain
Total ___________
Ears
___________Itchy ears
___________Earaches, ear infections
___________Drainage from ear
___________Ringing in ears, hearing loss
Total ___________
Emotions
___________Mood swings
___________Anxiety, fear, nervousness
___________Anger, irritability, aggressiveness
___________Depression
Total ___________
Energy/Activity
___________Fatigue, sluggishness
___________Apathy, lethargy
___________Hyperactivity
___________Restlessness
Total ___________
Eyes
___________Watery or itchy eyes
___________Swollen, reddened, or sticky eyelids
___________Bags or dark circles under eyes
___________Blurred or tunnel vision (does not include near- or
far-sightedness)
Total ___________
Head
___________Headaches
___________Faintness
___________Dizziness
___________Insomnia
Total ___________
Heart
___________Irregular or skipped heartbeat
___________Rapid or pounding heartbeat
___________Chest pain
Total ___________
Joints/Muscle
___________Pain or aches in joints
___________Arthritis
___________Stiffness or limitation of movement
___________Pains or aches in muscles
___________Feeling of weakness or tiredness
Total ___________
Lungs
___________Chest congestion
___________Asthma, bronchitis
___________Shortness of breath
___________Difficulty breathing
Total ___________
Mind
___________Poor memory
___________Confusion, poor comprehension
___________Poor concentration
___________Poor physical coordination
___________Difficulty in making decisions
___________Stuttering or stammering
___________Slurred speech
___________Learning disabilities
Total ___________
Mouth/throat
___________Chronic coughing
___________Gagging, frequent need to clear throat
___________Sore throat, hoarseness, loss of voice
___________Swollen or discolored tongue, gums, lips
___________Canker sores
Total ___________
Nose
___________Stuffy nose
___________Sinus problems
___________Hay fever
___________Sneezing attacks
___________Excessive mucus formation
Total ___________
Skin
___________Acne
___________Hives, rashes, dry skin
___________Hair loss
___________Flushing, hot flashes
___________Excessive sweating
Total ___________
Weight
___________Binge eating/drinking
___________Craving certain foods
___________Excessive weight
___________Compulsive eating
___________Water retention
___________Underweight
Total ___________
Other
___________Frequently ill
___________Frequent or urgent urination
___________Genital itch or discharge
Total ___________
For everyone, no matter your total score, notice if your points are clustered
in one category or another. These may be explained by something short-
term. If, for example, it’s pollen season and your sniffles and sneezes are
severe, that’s why your Head and Nose scores might be high; it might also
explain why your sleep is poor. Your scores should drop fairly quickly as the
season changes. And if your condition is acute, like a head cold or a stomach
bug, you will likely see your scores spike and then lower quickly. But if your
symptom scores linger or even start to creep up, you want to monitor the
situation.
If, during the eight weeks, you don’t see a downward trend, the question
is why: are there any foods you might be consuming that aren’t on the diet—
whether knowingly (continuing to drink beer, for example) or unknowingly
(eating out at a restaurant and inadevertently ordering something with hidden
dairy or gluten)? If you don’t see a favorable downward trajectory and
you’re following the plan, or you’re having trouble complying with any part
of the plan, reach out to your care provider or to a practitioner whom you
find through the avenues we list in the Resource section here.
** Fasting test
* Clinicians practicing functional medicine may say that your LDL, HDL, and/or cholesterol
are fine at higher levels when other lipid lab values are in check.
Now that you have a clear picture of where you’re starting from, it’s time
to implement the methyl donor + DNA methylation adaptogen + lifestyle
practices = Y2 formula. This is where you can start making positive changes
to your DNA methylation immediately—and start building long-term health.
5
S usan experienced something so many moms face—she had felt pretty healthy until
she had her first child. Then the rigors of working motherhood had led her to skimp
on sleep, skip exercise, use wine to take the edge off her stress, and rely on carb-
heavy foods like bagels, sandwiches, and sweets to keep her energy up during the
long days of balancing career and parenting. Now that her children were young adults
and out of the house, Susan had the bandwidth to focus on her own health, which was
clearly suffering. At fifty-seven and postmenopausal, Susan had been experiencing
pervasive fatigue, continual hunger, brain fog, blurred vision, hair loss, constipation,
and weight that had accumulated around her middle. Investigating those symptoms
had recently resulted in her being diagnosed with LADA (latent autoimmune diabetes
in adults), and Hashimoto’s thyroiditis.
When I first saw Susan, her fasting blood glucose was very high (335 mg/dL,
when ideally it should be below 90), with a hemoglobin A1C of 12.1 (I like to see this
number around 5 or lower). I took aim at her blood sugar and prescribed her a low-
carb, anti-inflammatory diet. After two months, her blood sugar had dropped to 108,
which was great. However, her homocysteine was 14.0, which was not great—it
suggested she was having issues with all methylation, including DNA methylation.
That’s when I refined her prescription to be the full Younger You Intensive.
Our nutritionist helped Susan prioritize the many DNA methylation superstar
foods; she also worked closely with Susan to help her develop a plan to stay on the
program even on her frequent business trips to Asia. For travel, that guidance
included tips for navigating restaurant food and a list of packable foods to take with
her. We also worked a little bit on sleep hygiene to minimize jet lag—prescribing
melatonin and a little extra magnesium glycinate. Guidance for minimizing toxin
exposure and developing regular exercise habits and a relaxation practice rounded out
Susan’s diet and lifestyle plan.
After four months on the plan, her labs had improved remarkably: her fasting
blood glucose was down to 82 and her homocysteine lowered to 7.1. Best of all,
Susan had never felt better. Her sharp thinking returned. And, not for nothing, she
looked great, too. Her eyes shone, the color in her cheeks returned, her hair started to
grow in thicker, and her relief at knowing exactly what to do to address her health
challenges was palpable. Susan’s renewed energy also gave her the motivation to
stick with the program over the long term. Seeing this transformation, from scared
and overwhelmed to vital and empowered, never fails to give me goose bumps.
This is where your transformation begins, too.
Let’s just pause for a moment, because this, right here, is the oldest your bio age—
relative to your chronological age—is going to be. Following this eating and lifestyle
plan is your ticket to a younger you. No matter what you’re facing in your life or in
your health, the Younger You Intensive will help you bring your most resilient self to
the challenge.
In this chapter, I’m outlining the exact program that enabled our study participants
to achieve the incredible result of shaving three-plus years off their biological clocks
as compared to the study controls. Just a reminder that our study and the Younger You
Intensive is an eight-week program. This is because, while epigenetic changes can
occur after just one meal, in order for them to be lasting, you’ve got to stick with a
DNA methylation–supportive plan for at least eight weeks. In fact, we measured our
study participants’ biological age at four weeks, and while things looked to be headed
in the right direction, there weren’t yet significant changes. You’ve got to stick with
it.
It’s also important to remember that the lifestyle components of the Younger You
Intensive are also vital to its success; they all have powerful, documented anti-aging
benefit, and we believe that our study participants achieved the age turnaround that
they did because these practices were included in the program. But since diet is
probably the single most important, make-or-break strategy for boosting and
balancing DNA methylation, we’re going to start with the eating plan first.
Keto Leaning
A ketogenic diet is lower carb, moderate protein, and higher fat, with the stated goal
of getting your body into ketosis, or the state where it manufactures ketones for fuel
from fat instead of burning glucose. (Again, we can see our participants succeeded in
achieving ketosis because their triglycerides dropped significantly, showing us they
were using fat as fuel.)
Ketones have a powerful anti-inflammatory benefit, and ketosis appears to have a
beneficial influence on the epigenome. We also know ketones are highly beneficial in
brain health—in refractory epilepsy, dementia, and Parkinson’s disease,4 for example.
Further, the ketogenic diet is being used as an adjunct therapy in a wide variety of
cancers, including breast and colon. I have no doubt that the underlying mechanisms
for these conditions include epigenetic changes. In fact, one study discusses ketones
not just as fuel for the body, but “signal molecules” with the ability to reprogram the
epigenome, including DNA methylation.5 I suspect as more research emerges, our
appreciation of ketones will continue to rise.
While getting into ketosis is not a primary goal of the Younger You Intensive, we
designed the diet to allow for some “background” ketones to be created by keeping
simple carbs lower, fats higher, and protein moderate. This macronutrient ratio is also
a great way to keep your blood sugar at a healthy level.
Beyond ketone production, healthy fats are helpful for DNA methylation because,
oftentimes, consuming polyphenols (micronutrients found in plant-based foods, many
of which are DNA methylation adaptogens) with fat yields better absorption,
particularly for resveratrol and curcumin. Thus, eating plenty of fat with your
vegetables (such as a salad with dressing, or a stir-fry with olive or medium-chain
triglyceride [MCT] oil) helps your body absorb the nutrients that support DNA
methylation.
Plant-Forward
Low-glycemic plants (meaning, nonstarchy vegetables and low-sugar fruits) are
primary sources of methyl donors and DNA methylation adaptogens—the two
categories of food that contain the ingredients we want in copious amounts. In
addition, they are high in fiber, low in calories, and easier on the environment. As
such, the vast majority of the foods included in the Younger You Intensive are
vegetables, with a smattering of fruits. In fact, your target is to eat seven cups of
various types of vegetables per day.
Eating a broad array of vegetables and fruit (in moderation) is also helpful because
research suggests that eating polyphenols in combination is better than alone,
particularly when it comes to exerting anticancer benefits.6
If you are vegetarian or vegan, you’ll need additional protein from beans
and legumes (see here for more specific guidance).
Choose from: black beans, chickpeas, edamame, kidney beans, lentils, protein
powder, tempeh, and tofu (see here for more guidance on eating soy)
In addition, you have weekly targets for two methyl donor powerhouses:
Organic liver (3 3-ounce servings per week; these count toward your daily
animal protein total)
Choose from: organic beef, chicken, or lamb liver (see here for insight on how
to do this if you think you don’t like liver)
Eggs (5–10 eggs per week; these are included in your daily animal protein total)
Choose from: pastured and/or omega-3 enriched eggs from chickens, ducks,
or geese
You should also familiarize yourself with the twelve superfoods—the Dynamic
Dozen (see here)—that do the heaviest lifting for supplying these methyl donors and
DNA methylation adaptogens. Because they are such DNA methylation powerhouses,
they should become your go-to foods for the next eight weeks, and beyond.
Basically, for the next eight weeks, you are going to get all the green, cruciferous,
and colorful veggies that you know you should have been eating all along. You’re
going to eat them with delicious dressings, sprinkle them with flavorful nuts and
seeds, and accompany them with an egg or a deck-of-cards-size piece of pastured
chicken or grass-fed steak. You’re not going to worry about counting calories,
because the healthy fats and the high fiber will naturally make and keep you full. You
can still have your morning cup of coffee; all other times you’re going to enjoy
filtered tap or spring water or seltzer, or sip on green tea or a Golden Turmeric Milk,
and enjoy how good it feels to be fully hydrated (without having your hydration
negatively impacted by high-sodium processed foods).
Of course, it’s a shift from the way most of us eat. I get that. It can take a few days
to get into the rhythm of it, which is totally OK. To help you over the hump, my
nutrition team and I have created recipes and a two-week meal plan for you to follow,
which you can see here. We calculated all the totals you could possibly calculate in
that meal plan, from macronutrient breakdowns to amounts of methyl donor and
DNA methylation adaptogens. If you like to cross your Ts and dot your Is, the meal
plan is your road map.
But I know that some of you prefer to wing it. And that is totally possible—just
follow the Cheat Sheet here to make sure you’re hitting your daily targets for green
vegetables, cruciferous vegetables, colorful vegetables, adaptogens, healthy fats, and
clean protein. It really can be as easy as checking a box.
Think of it as a choose-your-own adventure. One is scripted, and one is more of an
improvisation. You can also use our 3YY digital program for super easy tracking and
support (see here for more info).
Ketogenic Diet
The Younger You Intensive is “keto leaning,” so if you follow the program to the
letter it is possible that you will get into ketosis after a couple of days. But because it
isn’t super high fat, nor is the protein or carb or calorie count particularly low, if you
want to be in full-tilt ketosis, you might need to tweak things in order to start
producing ketones. If that is a priority for you, I suggest the following:
• Start by lowering or stopping the colorful fruits and replace those with more
greens.
• You can also increase your fat intake, particularly MCT oil, for a few days.
• Once you are in ketosis, try slowly adding back colorful veggies and berries, as
they are very important sources of DNA methylation adaptogens. Note that
some colorful fruits and veggies may knock you out of ketosis—such as carrots
—while others don’t—like red and orange peppers. You’ll need to gauge what
you can consume based on your ketone production (I use a urine strip, and all
I’m looking for is a small to moderate level of ketones).
• The more consistent you are with the mild intermittent fasting, exercise, sleep,
and stress reduction, the easier it will typically be to stay in ketosis.
If you are on a strict low-calorie, low-protein, very-high-fat keto program (as an
epilepsy intervention or as part of a cancer treatment program, say), you can
absolutely incorporate Younger You–friendly foods, but your overall diet should be
adjusted and managed by a practitioner versed in both protocols. It’s essential that
your dietary plan be nutritionally sufficient.
Paleo
The Younger You Intensive is a paleo program. No modifications are needed!
Elimination Diet
The Younger You Intensive is free of many common allergens, including peanuts,
wheat, and dairy, but it does allow some forms of soy for vegans and vegetarians
(listed here), incorporates many tree nuts plus sesame seeds and shellfish, and relies
on eggs—all foods that can be allergenic.
The easiest way to eliminate any allergens from the Younger You Intensive is to
print the full list of included foods here and simply cross off any foods that you know
you don’t tolerate. You can do this with the recipes as well. If your elimination diet is
very restrictive, get help from a knowledgeable nutritionist to help tailor the program
so that you can ensure that your nutrient intake is sufficient and balanced.
A good way to monitor if the Intensive is triggering your allergies or sensitivities
is to repeat the medical symptoms questionnaire (MSQ) here every seven days. If
your score isn’t trending downward, it could be that there’s an allergen in the diet that
you’re reacting to, or that you have an underlying gut dysbiosis that needs to be
remedied. In either case, it’s helpful to work with a functional medicine practitioner
and/or nutritionist to find the eating plan that is right for you.
Anti-inflammatory Diet
With no processed foods, added sugars, grains, legumes (unless you’re vegan), or
dairy, plenty of antioxidant-rich vegetables and select fruit, and good fats and
proteins, the Younger You Intensive is potently anti-inflammatory.
Note that the Younger You Everyday plan does incorporate gluten-free grains,
clean dairy, and legumes, but for most people, these foods don’t promote
inflammation. If that’s not the case for you, continue to avoid your problematic food
group when you follow that version of the program.
Low-FODMAP Diet
A full low-FODMAP diet layers easily with the Younger You Intensive program. In
my experience, it’s rare that all of the carbohydrate categories (fermentable oligo-
saccharides, di-saccharides, mono-saccharides, and polyols) are problematic. In our
practice, after a short-term full FODMAP elimination, we will have our patients try
one group at a time to identify the type(s) that causes a reaction. Generally, only one
or two categories of carbs require a longer period of elimination.
One note of caution: A long-term low-FODMAP diet can become nutrient
insufficient and/or negatively influence the microbiome. If you’ve been on a low-
FODMAP diet for more than a month, seek out a practitioner (ideally trained in
functional medicine—see the Resources section here for guidance on where to find
one) who can help resolve underlying issues.
Mediterranean Diet
Both Younger You plans are Mediterranean-friendly. The Everyday version, with its
legumes, whole grains, and dairy, is most closely aligned, although the greens and
cruciferous and colorful veggies that the Intensive relies on are also part of the
Mediterranean diet. You’ll just need to make sure you eat more fish for your animal
protein than red meat while on the Intensive or Everyday to stay within the confines
of the Mediterranean guidelines, and of course include lots of fabulous olive oil, too.
Vegetarian or Vegan
You can incorporate legumes into the Younger You Intensive—see here for a more
detailed discussion and look for recipes marked with a “VGT” for vegetarian or “V”
for vegan in the recipe section.
Here are a few ways to sneak in an extra serving of fruits and veggies
during the day:
○ Drink them. Spinach, chard, and beets—not to mention beet
greens, don’t throw them out!—are great in smoothies.
○ Have veggies for breakfast. It’s a thing! Add a side of greens to
your egg(s), or toss in steamed or lightly sautéed spinach, broccoli,
tomatoes, peppers, mushrooms, zucchini, olives, onions, and/or
garlic to an omelet, or treat yourself to a warm cauliflower rice bowl
with more veggies on top.
○ Make them grab-able. Take a container of precut cucumbers,
broccoli, cauliflower, bell peppers, zucchini, jicama, carrots, or
celery with you whenever you leave the house, or just keep them at
the ready in the fridge for when hunger strikes. I find if I put cut
veggies out on the counter before dinner, my daughter and I both
happily eat them—kind of a pre-dinner that doesn’t spoil our
appetites.
○ Blend ’em. Stick some veggies in the Nutribullet to add to your
tomato sauce or tahini dip—it’s an easy hack that amps the nutrition
while not altering the taste.
○ Add at the end. Toss as many extra veggies as you can into soups.
Most extra veggies added toward the end of the cooking process
won’t change the taste of a dish.
○ Turn them into confetti. Here’s a great way to add a pile of veggies
without a lot of prep. Chop an assortment of veggies in a food
processor, then save them in the fridge (in a glass container) to
sprinkle on salads raw, or wilt and serve as a side.
○ Roast them. Prep a pile of roasted veggies at the beginning of the
week so you can easily toss them into salads and soups, use them
as a side dish, add them to your scrambled egg, or eat them as a
snack.
Hydration
What you drink is a key piece of optimizing your DNA methylation. It’s vital that you
stay adequately hydrated, which means we recommend drinking enough ounces of
water, seltzer, or herbal tea per day to equal about half your body weight in pounds—
the standard guideline used in functional medicine. That means, if you weigh 150
pounds, you need to aim for 75 fluid ounces of noncaffeinated, nonalcoholic,
unsweetened beverages every day.
Hydration is a crucial piece of detoxification—without consuming ample amounts
of water, your toxic load will be higher, and toxins are an impediment to healthy
DNA methylation—something I cover more in depth in Chapter 6. Beyond that,
hydration is also crucial for reducing oxidative stress.10
It’s important that the water you drink either be filtered or spring (from a glass,
not plastic, bottle). I recommend carbon-block filters, such as those made by
Aquasauna or Multipure, because they will keep out most toxins and retain most trace
minerals, although you will need to change the filter regularly so that it functions well
and doesn’t get contaminated with bacteria.
In addition to water, other DNA methylation–supportive beverages include:
Chamomile tea (another adaptogen rock star along with all the other teas listed
here)
Coconut water (so loaded with potassium)
Green tea
Oolong tea
Other herbal teas, such as ginger, hibiscus, and rooibos
Seltzer (limit to two 12-ounce servings per day)
Turmeric tea, often known as golden milk, so long as it is sweetened only with
stevia (see our recipe here)
For those of us (me included) who are loath to give up coffee, know that
it’s a DNA methylation adaptogen, thanks to two amazing polyphenols
it contains: caffeic acid and chlorogenic acid. Likely due to this fact,
coffee, like green tea, has been solidly associated with longevity.
Looking at the research, it seems like you could consume quite a bit of
coffee without negative effects and probably some good benefit. The
tricky part is that for most of us (including me), the caffeine content in
both green tea and coffee comes at the cost of lost sleep, or poor-
quality sleep, which is definitely damaging to our DNA methylation and
gene expression in the brain.
Also know that you are getting protein from your daily allotment of pumpkin
seeds, sunflower seeds, and vegetables, as well as the nuts that are allowed on the
Intensive.
In addition, there are certain methylation-supportive nutrients that vegetarians and
vegans will need to give a little extra attention to in order to ensure sufficient intake
while on the Younger You Intensive. This is because they are found primarily in
animal-based foods, or they are present in lesser-quantity in plant foods. These
include B12; choline; the sulfur-containing amino acids methionine, cysteine, and
taurine; the omega-3 fatty acids EPA and DHA; and minerals zinc, iron, and
selenium. Preformed fat-soluble vitamin A (retinol) is derived from animal products,
but may be converted in the body from certain carotenoids. A vegan not converting
carotenoids well (as can happen in hypothyroidism) may require supplemental
vitamin A.
Some nutrient deficits may be addressed in the vegan diet with the increased seed
and nut intake, sea vegetables (nori especially), shiitake and enoki mushrooms, and
the green, colorful, and cruciferous vegetables that are the mainstays of the Younger
You Intensive eating plan. Still, in my experience, even vegans and vegetarians on the
Younger You Intensive benefit greatly from a few specific supplements—refer to here
for a list of those.
In addition, there are two nutrients that vegans can be deficient in that are easy to
get from foods:
• Selenium, which you can easily get from Brazil nuts. One Brazil nut contains
96 ug, or 175 percent of the RDI. Think of the Brazil nut as an edible
supplement.
• Zinc is also easy to get from foods if you’re intentional—refer to here for a list
of zinc-rich foods.
FOODS TO AVOID
Just as important as what to add to your diet are the things to be avoided. While
eating foods high in methyl donors and DNA methylation adaptogens will definitely
help, it’s a little like adjusting your sails when you have holes in your boat. You may
move a little faster in the direction you want to go, but you’re sinking as you go.
While yes, even if you only eat one healthy meal a week it is still beneficial, if you
make that same choice the majority of the time, it will potently bias you (and your
epigenetics) toward long-term longevity and all the things that accompany it, such as
maintenance of a healthy weight, lower risk of disease, and a longer health span.
Inflammatory Foods
Aging and inflammation—the body’s immune response to anything it deems an
invader—are as conjoined as the double helix of DNA. In fact, in the scientific
literature, they call it “inflammaging.” In a nutshell: aging creates inflammation. And
inflammation, in turn, drives all of the diseases of aging. It needn’t be huge amounts
of inflammation in order to be damaging, either. Pesky—but chronic—low-grade
inflammation is a problem, too. And nothing turns on inflammation (high or low)
more efficiently than a lousy diet. Even transient poor nutrition can have long-lasting
impact on the expression of pro-inflammatory genes. Then, if these bad patterns
continue, new daughter cells are created that house the same pro-inflammatory
epigenetic instructions.
What’s worse, we can inherit this tendency toward epigenetic inflammation from
previous generations. Many of us need to double down on a healthy diet because of
the choices of our recent ancestors (I fall into this camp) or the disease risks we have
in our family (cardiometabolic diseases are in mine), especially if we want our health
span and life span to be optimal (I am also a member of this group).13
You probably already have an inkling that there are certain foods and food
combinations that are highly unhealthy because they promote inflammation. These
foods include sugar, refined carbs (such as flour, bread, pasta, pastries, and muffins),
vegetable seed oils (such as sunflower, safflower, and canola), and processed or poor-
quality meats (like deli meats, sausages, and hot dogs). When we combine high sugar,
refined carbs, and high fat, it’s a triple whammy of inflammation.
When you eat a highly processed food, there is a complex cascade of damaging
events that occur body-wide. But specifically, let’s focus on the immune system: your
white blood cells assess the food and register it as foreign. In response, your body
will trigger the release of immune system molecules that kick off an inflammatory
response. We know this thanks to a famous 2004 study where researchers gave
healthy adults either a fast-food-style breakfast of an egg or sausage muffin with two
hash browns (refined carbs and poor-quality fats) or a glass of water. No surprise that
the greasy, salty, and probably, let’s admit, delicious breakfast took more of a toll on
the body, but what was surprising was just how bad it was. The people who ate the
greasy breakfast experienced a significant increase in reactive oxygen species (i.e.,
free radicals) and C-reactive protein, which is used as a gauge to measure the extent
of the body’s inflammatory response, and an upregulation in nuclear factor kappa-B,
or NF-kB, which goes into the nucleus of the cell, lands on the DNA, and tells the
gene to blast out inflammatory compounds. In other words, the body responded to the
fast-food meal as foreign and dangerous, like it would to a toxin such as mercury, a
flu virus, or a strep bacteria. And these changes lasted for longer than three hours; just
long enough for the next meal to come along and do the same thing all over again.14
This study showed the exact mechanisms by which the standard American diet of
fast, processed, nutrient-poor, fried foods put us on a moving sidewalk to disease.
Again, this 2004 study was before scientists were routinely looking at epigenetic
changes. If they repeated this study today, I suspect we would see changes to the
genes regulating inflammation, resulting in turning on these inflammatory genes for
far longer than the meal lasted; maybe even for days longer, as we’ve seen in animal
and cell epigenetic research.15
On the other hand, when you are choosing foods that are low in sugar,
unprocessed, and high in methylation adaptogens and methyl donors, you provide
your body with a whole different set of information that’s nourishing and balancing to
your DNA. As a result, inflammation is lowered, epigenetic processes are enhanced,
and your cells no longer need to defend and repair after every meal. They become
programmed for optimization instead, and your physiological function gets better as
your biological age gets lower.
Sugar
I know, I know. By now you’re probably sick of hearing the advice to stop eating
sugar. Here’s the thing: it’s wildly damaging, and highly inflammatory. And what
sugar your body can’t immediately use for energy, which is most of it, unless you’re
running a marathon or you are a member of a highly physical profession, it stores as
fat. This fat gets tucked inside your cells, your organs, and most visibly, your
abdomen. That fat around your middle is especially inflammatory. As such, it’s linked
to all the top causes of disease and death, including diabetes, Alzheimer’s disease,
heart disease, and cancer. And aging. But we already knew that.
Now we have a new lens on why sugar is so destructive in the body: it disrupts
epigenetic methylation, and not in a good way. A 2008 study showed that a single
high-glucose event had lasting negative effects on methylation of a gene found in
cells from the endothelial lining of the aorta that regulates NF-kB.16 The researchers
administered large amounts of glucose to both endothelial cells from mice in vitro
and to live nondiabetic mice. In both cases, the NF-kB gene experienced increased
expression, which opens the faucet on inflammation, aging, and all of their associated
diseases. Worse yet, these effects lasted at least six days past the time it took to
metabolize the glucose. Although the study only looked for changes for six days, so
who knows how long those effects really lasted? Granted, it was a study performed
on rodents so we can’t say for sure that the same thing happens in humans in the same
way, but we know for sure lasting epigenetic changes do happen in humans and can
happen quite rapidly sometimes. And in healthy (not diabetic) human cell studies, we
see glucose exposure leading to far-reaching, negative changes to insulin- and
glucose-regulating genes via DNA methylation.17
In some ways, knowing this makes it easier to stay away from sugar nearly all the
time, which is ultimately helpful, because sugar is one of those foods where it’s very,
very hard to have just a little. It’s almost easier to avoid it altogether; that way your
taste buds, your brain, and your gut microbiome will reacclimate and that longing for
a sweet taste will abate.
While on the Intensive, you want to limit your sweets consumption to DNA
methylation adaptogen–rich berries, low-sugar citrus fruits, and natural sweeteners
that don’t impact your blood sugar—you can find these listed in the chart here. Once
you’re on the Everyday program, you can expand this to small amounts of natural
forms of sugar such as dates, honey, blackstrap molasses, and maple syrup, but just
for now, use the Intensive as an opportunity to reset yourself away from sweet and
more toward nutrient rich.
That said, there are ways to keep your sweet tooth satisfied during the eight weeks
of the Younger You Intensive. Berries are great DNA methylation adaptogens, as is
cocoa. The recipes for No-Bake Sunbutter Chocolate Squares (here) are totally tasty,
as is our Rosemary Lemon Tart (here), which is my family’s go-to celebratory treat—
it’s always a hit!
It’s like that old punitive saying, “A moment on the lips, forever on the hips,”
except when it comes to sugar, it’s about health span, not your jeans size: “A moment
on the lips, a really long time on the epigenome.”
Artificial Sweeteners
While there isn’t specific research that sheds light on artificial sweeteners’ effect on
DNA methylation—yet—there are still compelling reasons to avoid them as part of
your Younger You plan. Artificial sweeteners still cue insulin (even though they don’t
contain glucose, which is the typical trigger for the release of insulin) and light up
pathways in the brain that seek reward. As a result, eating artificial sugars can cue
cravings for sweets and make it harder to make healthy food choices. They can also
be disruptive to gut health.18 We counsel everyone in our practice to avoid them.
Nonorganic Foods
There’s no debating it: living and eating as cleanly as possible is important for
healthy epigenome and DNA methylation. This means that eating organic and clean
sources of foods as often as possible will help protect epigenetic expression
(including DNA methylation and the DNA genetic material itself). While some
environmental toxins occur elsewhere, a number of them are found in our food supply
and food packaging materials (I talk more about environmental toxins in Chapter 7).
Organic foods, on the other hand, aren’t exposed to most toxins in the first place.
In addition, organic foods have been shown to have higher nutrient levels than their
conventional counterparts, meaning they also have more methyl donor nutrients and
especially DNA methylation adaptogens than chemically grown foods. These
increased epi-nutrients include the polyphenols that help protect the plant from pests
—and our genes from disordered DNA methylation (more on this starting here).
The unfortunate reality is that the presence of toxins is so pervasive in our modern
environment that doing whatever you can to lessen the amount you are exposed to in
the first place—by eating organic, for example, filtering your water, and avoiding
plastics and nonstick cookware (again, more on these strategies in Chapter 7)—is not
only a wise strategy for promoting health, it’s urgently necessary.
Before you despair that toxins are unavoidable, know that research, particularly by
Bernhard Hennig, a professor of nutrition and toxicology at the University of
Kentucky, has shown that many nutrients that are supportive of healthy DNA
methylation and are mainstays of the Younger You Intensive as well as the Younger
You Everyday, such as omega-3 fats, curcumin, and EGCG, can lessen the
inflammatory damage caused by environmental toxins such as polychlorinated
biphenyl compounds (PCBs). So, avoid what toxins you can, and know that the
dietary changes you’re making will help protect you from those you can’t.19
Charred Foods
Cooking foods at a high enough heat to sear them, crisp them, or leave grill marks
may have a tasty result. But those bits of food that turn dark brown during the
cooking process are packed with compounds—known as advanced glycation end
products (AGEs)—that are pro-oxidant, pro-inflammatory, and damaging to cells and
DNA. And since the entire aim of the Younger You Intensive and Younger You
Everyday is to equip the body to fight inflammation, oxidation, and other damage by
turning on the genes that help in these efforts, eating a seared burger—even one made
with beets and grass-fed beef—works against you. Instead of cooking your clean
animal protein in a dry pan at high heat (or on a grill), you want to cook at a lower
temperature with some moisture involved, as this minimizes the formation of AGEs.
In addition to what you eat, the Younger You Intensive guides you to change how you
cook what you eat and to embrace slow-cooked methods, like braising or using a slow
cooker or the ever-popular Instant Pot.
Alcohol
I know many of you reading this will be holding out hope that red wine is supportive
of healthy DNA methylation because of the high levels of the antioxidant resveratrol
you’ve heard about. Sigh… that is not the case. (As a former red wine lover myself, I
feel your pain.)
Alcohol is not sanctioned for the Younger You Intensive, because despite how
much of the well-known DNA methylation adaptogen resveratrol may or may not be
in your nightly glass (or two), alcohol impairs DNA methylation. It does so by
inhibiting the enzymes used in the methylation and folate cycles, which results in a
potentially significant reduction of SAMe (the body’s main methyl donor), lowers
folate absorption, and directly inhibits the enzymes that methylate our DNA.20
I know that giving up alcohol for the rest of your life is a big ask—although many
people do it and find it helpful and discover other ways to relax and celebrate—so
certain alcohol is OK in very moderate amounts on the Everyday version.
Considerations Before You Jump In
In general, both the Younger You Intensive and the Younger You Everyday are
exceedingly healthy eating patterns. But any time you start a new diet and exercise
regimen you want to consult with your primary care provider.
There are two particular instances where you may need to take more care in
adopting the Younger You Intensive:
• If you have a family or personal history of kidney stones, this eating plan may
contribute to the formation of kidney stones because the diet is high in oxalates.
Oxalates are organic acids that occur naturally in many plant foods; they are
especially high in several foods that form the mainstay of the Younger You
Intensive and Everyday, namely spinach, beets, raspberries, and soy (which is
part of the Intensive only if you are a vegetarian or a vegan). Once in your
body, oxalates bind with calcium and can contribute to the formation of kidney
stones. Consuming plenty of citrate, from citrus fruits, and good hydration
lower the amount of oxalates in your blood, and this diet prioritizes both of
those—squeezing lemon and lime into your water covers both bases. However,
if kidney stones are part of your history or you have kidney disease, you should
consult with your doctor to see if this plan is appropriate for you.
GETTING STARTED
Ideally, you would start the Younger You Intensive at a time when you aren’t super
busy. You want extra time at the grocery store to see which veggies look the most
tantalizing and fresh and to cook up a few recipes. Also, if you have been eating a
standard American diet, you may experience some detox symptoms, such as fatigue,
brain fog, gassiness, or bloating. There is a lot of fiber and prebiotic foods on this
eating plan; it’s appropriate to expect that as your microbial population adjusts you
might feel a little bit worse before you feel better. Really prioritize your hydration and
your intake of healthy fats, which will help ward off any sugar cravings that might
flare up now as well.
These symptoms should pass after a few days; if they don’t, consult with your
health-care provider, a functional medicine practitioner, or a nutritionist to assess and
address what’s going on for you.
EACH DAY:
__ 2 cups dark leafy greens, measured raw, chopped, and packed
(see list here)
__ 2 cups cruciferous vegetables, measured raw, chopped, and
packed (see list here)
__ 3 cups additional colorful vegetables (see list here)
__ 1–2 medium beets, cooked or raw
__ ¼ cup pumpkin seeds or pumpkin seed butter
__ ¼ cup sunflower seeds or sunflower seed butter
__ Two-plus servings of DNA methylation adaptogens (see list here)
__ Two 3-ounce servings of clean animal protein (see list here)
(unless you’re over sixty or weigh more than 175 pounds, then
two 5-ounce servings; or vegan or vegetarian, then you want to
get 40–50 grams protein from beans, legumes, or protein powder
—refer to here)
__ 5 tablespoons of healthy fats (see list here)
__ One-plus servings fermented foods (see list here)
__ Half your body weight in fluid ounces of water, herbal tea, or
seltzer (limit seltzer to 24 ounces per day)
EACH WEEK:
__ Three servings of liver (3 ounces per serving), preferably organic*
__ 5–10 eggs, preferably free-range, organic, and omega-3
enriched*
* On days when you eat liver and/or eggs, those count toward your daily clean animal
protein target; one egg is roughly approximate to 1 ounce of meat.
GENERAL GUIDELINES:
○ Eat organic as much as possible
○ Stay hydrated (.5 ounce of water, sparkling water, or herbal tea per
pound of body weight per day)
○ Give yourself a twelve-hour fast each day, typically between 7 p.m.
and 7 a.m.
○ Include healthy oils (coconut, olive, flaxseed, and pumpkin seed)
○ Avoid sugar, dairy, grains, folic acid–fortified foods, legumes/beans,
charred foods, and alcohol
○ Minimize plastic food and beverage containers and nonstick
cookware
Snack Broccoli + 1 boiled Oolong tea Luscious 2 hard- Sunflower Iced oolong
cauliflower egg with Liver Pâté boiled and/or tea
florets + raw + red eggs + pumpkin
seeds broccoli peppers celery seeds and
florets Red
Beet Cabbage,
Bubbly Beet, and
Pomegranate
Slaw
Beet Bubbly
• Stock up on snacks before you go. (See the list that starts here.)
• Check out a restaurant’s menu online before you go. Generally, sticking to a
protein entrée (chicken, fish, beef) with a nonstarchy vegetable side is a good
bet, as is ordering a large salad, or even two salads. Also, roasted cruciferous
veggies are a big thing right now and show up on most menus—order two
servings and hit your numbers easily. Just remember that super-crispy stuff
probably has advanced glycation end products, so eat them only occasionally.
You can also call ahead to see what modifications are available.
• Bring a full glass water bottle with you wherever you go. If you are in a hotel
with a gym, you can usually get unlimited filtered water there.
• Find a grocery store near your lodgings to stock up on fresh, precut veggies,
prepared beets, almond milk, etc. If you don’t have a fridge, you can stock up
on pumpkin and sunflower seeds and/or get cut veggies to snack on.
• Make muffins for your travel day (the Savory Onion and Chard Muffins here
are great for this). Pack sunflower and/or pumpkin seeds; green apples and
blood oranges also make great travel snacks as they aren’t likely to get
squashed in your bag, as do hard-boiled eggs or celery sticks and almond
butter.
1. Keep going with the Younger You Intensive. The Intensive eating plan is a
wonderfully healthy way to eat all of the time—it doesn’t carry any risks of
developing nutritional deficiencies over the long term, as do some eating plans,
such as keto.
2. Stay true to the basic formula but loosen the reins a bit with the Younger
You Everyday. Once you’re done with these first eight weeks, you can shift
gears into the more lenient Younger You Everyday—a long-term maintenance
plan that the patients we see in our clinic who don’t require the Intensive for
some reason are given.
The choice is yours.
If you stay with the Intensive version, you won’t continue to tick younger and
younger indefinitely (do you want to go back to your teen years??). You will position
yourself to be the best, youngest you that you can be—staving off that sixteen-year
drop. Quite honestly, we don’t know what happens to bio age after more than eight
weeks on the Intensive, because we haven’t studied it… yet. We will be gathering
data that we can analyze via the 3YY digital program (from those participants who
explicitly choose to share their data with us). See here for more information.
And if you decide to shift into the Everyday, while your bio age likely may not
continue to trend downward, you will slow your rate of aging and avoid the
accelerated aging that the typical American diet all but guarantees. If you choose the
Everyday, know that you can, and should, return to the Intensive again and again. I
recommend recommitting to the Younger You Intensive at least once, and ideally
twice, a year; once at the start of winter and again at the start of summer.
Remember, the Younger You Intensive isn’t just an eating plan—it also has
lifestyle components that are key for DNA methylation optimization. Because I know
the eating plan is a bit complex and, depending on what your diet was like before you
started it, perhaps a big adjustment, I’ve kept the lifestyle recommendations as simple
as possible, and the same as what we included in our study. There are also a few
supplements that will help ensure you get the baseline of necessary nutrients. We’ll
cover all of those soon. First, let’s look at the Younger You Everyday, so that you can
decide which version of the program is the right one for you at this time.
Footnote
i
See here in Supplements for a list of vegan protein powders we recommend to our patients and here for a sample
one-day vegetarian/vegan menu
6
• As a starting point. It could be that you have been eating the standard
American diet and want to take some baby steps toward improving your
nutritional status and your health. In that case, you can start by
following the list of swaps I include here and prioritizing the Dynamic
Dozen foods I list starting here. Even though it’s just a few changes
here and there, this introductory version of the Everyday will provide
your body with more of the nutrients it needs for balanced DNA
methylation.
• As a finishing point. On the other end of the spectrum, maybe you’ve
just finished up the Intensive, and you’ve adjusted to the diet and you’d
like to retain all the benefits you’ve just created, but you’d also like to
expand your diet to include legumes, a few grains, a little alcohol, and
maybe a little organic dairy. If that’s the case, start at Younger You
Everyday: What’s Different, here. This is where most of our study
participants ended up: they had adjusted to the high vegetable intake,
and had learned to cook liver and eat beets, so they kept that going, but
they also added a few more food options (and the occasional drink).
Beans
Beans are wildly nutritious, and people who live a long time generally eat
beans. They’re rich in many methylation-related nutrients including
magnesium, potassium, folate, choline, and sulfur compounds, as well as a
great source of fiber, which supports a happy and healthy microbiome.
The only reason beans and legumes aren’t on the Intensive (for everyone
except vegans and vegetarians) is that they are higher in nonfiber carbs and
may, in some, promote insulin resistance. In addition, many folks have a hard
time digesting them—although soaking helps with digestibility, which is why
I strongly suggest that you soak or even sprout beans before eating them. (See
here for instructions.) And for a very small subset of folks, beans might
prompt inflammation because they have high levels of lectin—a
phytochemical that impedes the bioavailability of nutrients and can irritate the
digestive tract. The beans on the Everyday plan include:
Adzuki beans
Black beans
Black lentils
Black-eyed peas
Brown lentils
Cannellini beans
Chickpeas/Garbanzo beans
Fava beans
Great northern beans
Green lentils
Kidney beans
Mung beans
Navy beans
Pinto beans
Red beans
Red lentils
Soy (see the next page for guidelines on eating soy)
Split peas
Turtle beans
Note: Eden brand soaks their beans, then pressure cooks them in their cans
and even adds a bit of the sea vegetable kombu to improve digestibility. If you
don’t have time for soaking, seek out this brand, which is available at most
grocery stores.
I know soy has gotten a bad rap for its lectin content, potential
negative estrogenic effects, and for the genetically modified soy
that abounds in processed foods. However, we also know that
○ Soy isoflavones genistein, diadzien, and equol are potently
and beneficially epigenetically active.
○ Equol is protective against dementia.
○ Soy consumption is associated with a protective effect
against breast cancer (perhaps in part because of the
isoflavones’ beneficial effect on demethylating tumor-
suppressor genes).
○ Dr. Randall Jirtle demonstrated that genistein eliminated the
toxic effect of in utero BPA exposure on agouti mice offspring
(by acting like a methyl donor).
○ The modest estrogenic effect is helpful for women in
perimenopause.
○ Soy is helpful for bone health.
○ It’s also a good source of protein.
My read on the literature is that, correctly chosen, soy is a
smart food.
When opting to eat soy, make sure that it is organic, as most
conventional soy is genetically modified and highly
contaminated with pesticides, and preferably fermented—which
includes varieties such as tempeh, miso, tamari, natto, and
pickled tofu—as fermentation makes the nutrients in soy more
bioavailable.
Grains
When chosen carefully, whole grains can be a valuable source of magnesium
and B vitamins, which are important for DNA methylation, and chromium,
which improves blood sugar management. Some grains, such as oats, provide
sulfur, which is important in the methylation cycle and our antioxidant and
detoxification systems. Whole grains are also an excellent source of fiber,
which, again, is great for your microbiome.
That being said, there are two types of grains I recommend greatly
minimizing (or even avoiding altogether if you can)—those that contain
gluten, and those that are fortified with folic acid. So many people don’t
tolerate gluten well, and the incidence of celiac disease—an autoimmune
condition that can be triggered by gluten—has been increasing 7.5 percent a
year for the last several decades according to a 2020 review of eighty-six
studies (rates are higher for women and children than men).1 And I covered
the danger in over-consuming folic acid (the synthetic form of folate) here.
Another very important reason to minimize grain consumption—or at least
approach it carefully—is that for many of us (myself included) grains can
aggressively spike blood sugar, especially processed grains such as wheat
flour. Finally, grains do contain lectins, and if you’ve determined yourself to
be sensitive to these antinutrients, you’ll want to take care in consuming them.
GRAINS TO PRIORITIZE
Amaranth
Buckwheat (technically a seed)
Millet
Oats (look for gluten-free oats)
Quinoa (technically a seed)
Rice (basmati, bran, brown, wild)
Rye (particularly dark rye)
Sorghum
Tapioca
Teff
GRAINS TO MINIMIZE/AVOID
Barley
Bulgur
Kamut
Spelt
Wheat
You can also soak your grains before cooking to improve their digestibility
and nutrient bioavailability (I share soaking instructions here).
Dairy
Dairy from cows, sheep, and goats can be a great source of methylation
nutrients, especially methionine and B12. Other nutrients in fairly good
amounts include protein, calcium, phosphorus, selenium, and zinc. Butyrate is
a very important short-chain fatty acid found in dairy. Also, most dairy sold in
the United States is fortified with D3 and vitamin A (as palmitate). However,
you do want to keep your dairy consumption fairly low, organic, and rbGH-
free, and consider leaning on goat or sheep sources, which are easier to digest
and are generally less inflammatory. The casein family of proteins found in all
dairy sources is problematic for many individuals. In our practice, we see a lot
of instances of dairy allergy or sensitivity, which contributes to everything
from eczema to migraine and inflammatory arthritis. And the milk sugar
lactose is frequently a cause of gas and bloating in individuals with genetic
lactase (the enzyme that digests lactose) deficiency or acquired lactase
deficiency, as commonly seen in adult-onset irritable bowel syndrome (IBS)
or small intestinal bacterial overgrowth (SIBO). Anecdotally, some patients in
our clinic report dairy consumption on a low-carbohydrate diet contributes to
weight-loss resistance and/or difficulty getting into ketosis.
The form of dairy I feel the least conflicted about recommending is ghee, a
form of butter that has been clarified to remove the dairy proteins (including
the problematic casein). This renders it very hypoallergenic and most often
well tolerated even by people who are sensitive to dairy. It is also a good
source of butyrate, which nourishes cells in your digestive tract and directly
modulates genetic methylation to favorably alter gene expression. (Clinically,
we have not seen ghee inhibit ketosis or contribute to weight-loss resistance.)
If you tolerate dairy, stick to moderate amounts (no more than two 1-
tablespoon servings per day, unless otherwise noted below) of the following
dairy products:
Butter
Cottage cheese (¼ cup)
Cream
Ghee
Goat cheese
Gruyère cheese
Kefir
Milk (½ cup)
Parmigiano-Reggiano cheese
Romano cheese
Yogurt (unsweetened, ¼ cup)
Sweeteners
In general, sweeteners of any kind aren’t great for health because they raise
inflammation and drive oxidative stress that can cause injury at the molecular
and cellular level and contribute to the development of long-term diseases.
That’s why there are no added sweeteners included on the Younger You
Intensive.
Since the Everyday is designed to be more doable, even something you
can stick to over the long term, you can have small amounts of natural
sweeteners, listed below. Just keep it to no more than 1 teaspoon at a time,
and no more than twice per day. For some people, the sugar alcohols
erythritol and xylitol cause gas and bloating; if this is your experience, avoid
these noncaloric sweeteners.
Blackstrap molasses
Cane sugar, unrefined
Cocoa (70%+ dark, not Dutch processed)
Erythritol (a few drops)
Honey
Maple syrup
Monk fruit
Stevia (a few drops)
Xylitol (a few drops, and keep it away from pets as it’s toxic to dogs)
(A Little) Alcohol
When you’re on the Younger You Intensive, alcohol really is a no-no, as it’s
known to deplete methylation reserves and interfere with healthy epigenetic
methylation patterns. However, this is the Everyday version. And everyday is
real life. I don’t expect you to never have a drink again unless that’s the
choice that makes the most sense for you.
If you do consume alcohol, keep it to a minimum. This means no more
than one alcoholic drink per day for women and men. If you can drink less, or
none at all, that’s even better, because drinking alcohol does directly inhibit
the methylation cycle, but I understand that we live in the real world.
For clarity’s sake, one alcoholic drink is equivalent to five ounces of wine,
twelve ounces of beer, or one and a half ounces of spirits. When you imbibe, I
suggest drinking organic or biodynamic wine so that you minimize pesticide
exposure (just as you would when selecting a food to eat). Red wine contains
a small amount of resveratrol, an antioxidant and a DNA methylation
adaptogen, but don’t let this fact convince you that your red wine is a health
food—many other foods contain significantly more resveratrol; see here in the
Nutrient Reference for a list. Or enjoy a grain-free spirit such as vodka or
tequila, because they are low carb and, thus, take less of a toll on your body to
metabolize because they don’t spike your blood sugar the same way, say, a
beer does. Obviously, most beer contains gluten. In the best of all worlds, if
you are a devoted beer drinker, you’ll find a beer you like that doesn’t contain
it.
And when you have those drinks, I suggest counterbalancing that DNA
methylation inhibition with a super methylation-supportive snack or meal
either before (a snack of sunflower and pumpkin seeds), during (a big helping
of greens with dinner), and/or the next morning (a blueberry smoothie).
Intermittent Fasting
Because the intermittent fasting portion of the Younger You Intensive is so
moderate and doable, I recommend you continue it on the Everyday version,
as well. To refresh your memory, that means finishing up your last meal at 7
p.m. and then not eating again until 7 a.m. the next morning. If you are more
of a night owl, you can push both of these times back to one that suits you
better, making sure to finish eating at least three hours before bed. If you are
already regularly going longer than twelve hours overnight without eating,
that is fine. Keep it up.
And although these aren’t foods, per se, they influence the chemical
content of your food and beverages, so avoid these too: plastic food storage
containers, plastic water bottles, and nonstick pans (more on this in Chapter
7).
You also want to continue to eat organic as much as you possibly can.
#2: Turmeric
DNA methylation adaptogen
Known as the “king of spices,” turmeric has many potent effects on your
biochemistry and your health, including preventing cancer as well as
neurological and inflammatory diseases.2 Of course, I am most excited about
its impressive ability to modulate genetic expression by changing levels of
DNA methylation, which is a primary way that turmeric exerts its powerful
effects.
A constituent of turmeric is curcumin, which is a powerful DNA
methylation adaptogen. In cell studies, curcumin looks to be able to both add
and reverse excess or erroneous methylation marks on your DNA, like the
clean-up crew for life’s inevitable biochemical messes. While turmeric’s
bright yellow color may stain your fingers and your cookware, it’s worth the
potential cleaning mishaps.
How to eat it: You can buy turmeric fresh—it looks a lot like fresh ginger,
only smaller, and is often found in the produce section of the grocery store.
You can also buy it powdered, but if you choose this option, spring for
organic. Some conventional brands add things like lead (seriously) to keep it
looking bright yellow, and it’s not the color that’s beneficial, it’s the
curcumin. You don’t want your DNA methylation superfood to expose you to
toxic metals, right? You can add turmeric to eggs, salad dressings, stir fries,
soups, and stews (my favorite is our Creamy Coconut Curry recipe here), or
even make a tasty beverage out of it—see here for our Golden Turmeric Milk
recipe (I drink it almost every day!). Just be sure to have it with a little
healthy fat and freshly ground black pepper, which makes the curcumin more
readily used by your body.
Alternative: Curry powder
#3: Blueberries
DNA methylation adaptogen
Blueberries are rich sources of DNA methylation adaptogens, including
anthocyanins, chlorogenic acid, ellagic acid, and quercetin. Plus, they’re
sweet while still being low-sugar and low-glycemic, making them a natural fit
on the Younger You program.
How to eat them: Luckily most berries aren’t a hard sell—they are
delicious on their own, especially when they are in season, and you can eat up
to one cup of them per day (and more if your blood sugar isn’t impacted by
them; less if it is). When they’re not in season, frozen wild or organic versions
are great additions to smoothies and Younger You–approved grain-free baked
goods, like the Blueberry Beet Scones here. I also throw fresh or frozen
blueberries in glasses of water or on my salad. Whenever possible, choose
wild berries, as they typically have higher levels of DNA methylation
adaptogens than their cultivated counterparts.
Alternatives: Blackberries, black currants, raspberries, and strawberries are
all rich in DNA methylation adaptogens, too.
#4: Rosemary
DNA methylation adaptogen
Rosemary is a stealth contender in the health-food world—it doesn’t get near
the attention that turmeric, garlic, or ginger do, but it’s definitely worthy of
your adoration and a place in your daily diet. Rosemary is a potent antioxidant
and anti-inflammatory, it’s anticancer and provides neuroprotection (boosting
memory and cognitive performance) and pain relief.3 It’s even been shown to
be as effective as minoxidil (aka Rogaine) in regrowing hair.4 But most
importantly for our purposes, it’s a powerhouse DNA methylation adaptogen,
thanks to abundant amounts of rosmarinic acid and ursolic acid, among
others. It’s also super easy to grow on a patio (although more challenging to
keep alive on a windowsill, at least in my experience). Choose fresh rosemary
or dried whole-leaf rosemary that you chop or grind just before using, as they
have significantly higher levels of rosemarinic acid than powdered dried
rosemary.
How to eat it: Rosemary goes with so many things—roasted vegetables,
soups, meat dishes, soups, stews. If you don’t like its woody texture you can
put it in one of those spice containers that has a built-in grinder. You can also
buy one with black peppercorns or sea salt in it and add a little rosemary, as
the piperine present in freshly ground pepper may help the rosmarinic acid be
better absorbed. You can also brew a tea with it by steeping two teaspoons of
the whole leaves (whether dried or fresh) in hot water, then garnishing with a
squeeze of fresh lemon or orange. Or try my favorite Rosemary Lemon Tart
for a “legal” sweet way to enjoy it (here)!
Alternatives: Peppermint, spearmint, sage, thyme, lemon thyme, and
oregano are also good sources of rosmarinic acid.
#6: Beets
Methyl donor
Beets get a bad rap, but they are so loveable. Not only for their sweet earthy
taste, but also, and especially, for one specific phytonutrient they contain:
betaine. This important methyl donor plays a big role in keeping the
methylation cycle humming (fundamental for DNA methylation fitness).
Beets are also high in vitamin C (a DNA methylation adaptogen), fiber,
potassium (needed in the methylation cycle, too), protein, folate (another
methyl donor), and manganese. They help lower blood pressure, fight cancer,
and support detoxification. They are smart for so many reasons!
On the Younger You Everyday, I advise eating a minimum of three
medium beets per week. While red beets are the most widely available, all
beet varieties (such as golden beets) have unique polyphenol profiles that
contribute to their lovely colors. It’s my recommendation that you eat a
variety of different types of beets, as you’re able to source them. And if you
can’t stomach eating any variety of beet regularly, opt for a beet supplement
(see here). (True story: red beets will also turn your poop bright red, which
can be startling, I admit, but a good way to gauge how long it takes for your
body to digest and eliminate a meal.)
And while I’m selling you on beets, I can’t neglect raving about beet
greens! Don’t throw these out: they are chock-full of antioxidants and
nutrients, with more iron than spinach and loads of protein, phosphorus, zinc,
fiber, vitamin A, vitamin C, and calcium.
How to consume them: Beets are great roasted or boiled and eaten either
on their own or in salads. They’re also good grated, raw, and used in slaws or
even folded into burgers (see our Not Your Mama’s Burger on here). You can
also get betaine by drinking beet juice, which is a great addition to seltzer or
sparkling water (see the Beet Bubbly here), or even to our Blueberry Beet
Scones (recipe here). Isabella and I both love them boiled, peeled, and
drizzled with a little olive oil (or half extra-virgin olive oil, half MCT oil) and
balsamic. As for those beet greens, you can use them instead of spinach in
many recipes or stir-fry them with olive oil, garlic, and salt; you can also add
them to smoothies.
Alternatives: Quinoa, spinach, and lambsquarters are also excellent
sources of betaine.
#7: Eggs
Methyl donor
Once considered the “bad egg” of the nutrition world, the humble egg—
especially a pastured, organic, and omega-3-enriched egg—is a DNA
methylation darling because it is arguably the best food source of choline.
And choline is a vital methyl donor (in addition to brain food, mood food,
liver food, pregnancy food, and so on), albeit one that works in a bit of a
backdoor way. Choline is tough for your body to make and sucks up S-
adenosylmethionine (SAMe), the universal methyl donor that donates the
methyl groups that get laid down on the genome, along the way. Indeed,
choline is considered “conditionally essential” because it is so hard to make
and pretty much no one eats enough in their diet. So if you supply the body
with choline through food, you preserve SAMe, and in so doing, you plug up
a hole in the methylation process, leaving yourself more SAMe available for
DNA methylation.
On both the Younger You Intensive and Everyday, we suggest eating a
range of between five and ten eggs per week. You can go on the lower end of
that spectrum if you’re willing to eat liver (the other primary source of
choline) once or twice a week. If liver is just a no-go for you—although I
truly do believe our Luscious Liver Pâté recipe (here) can convert most nay-
sayers—then you can double up on your weekly eggs. That being said, eggs
are a common allergen. And of course, vegans don’t eat them. I list some
alternative sources of choline below.
How to eat them: Poaching is the healthiest way to prepare an egg. Aside
from the standard directives to hard boil, scramble, or fry eggs, my best
advice is to eat them with other members of the DNA methylation Dynamic
Dozen—add a teaspoon of turmeric to scrambled eggs, sauté greens in the
same pan, or try our Green Eggs and Shiitake Ham (recipe here). You can also
pop a hard-boiled egg on a salad, or eat it on its own as a snack.
Alternatives: Grass-fed beef, wild salmon. Plant-based sources of choline
include: soybeans (must be organic), lentils, cauliflower, Brussels sprouts,
broccoli, shiitake, and flax seeds. If you are a woman who’s considering
pregnancy, you need choline (the recommended daily intake for pregnant
women is 450 mg and 550 mg for lactating women—likely more than you’re
eating, especially if you are vegan); while the foods listed above do indeed
provide some choline, supplementation might be appropriate for you (see here
and here for more information).
#9: Seeds
Methyl donors
Pumpkin seeds and sunflower seeds are powerhouses of DNA methylation,
since they are rich in zinc, methionine, cysteine, magnesium, potassium, B3,
B6, folate, and betaine. They’re also great sources of polyunsaturated fatty
acids. On the Younger You Everyday, you’ll be eating one tablespoon each of
pumpkin seeds and sunflower seeds every day, which is surprisingly easy to
do.
How to eat them: Seeds are a great addition to salads. You can also eat
them by the handful, or try them in a blend (see our Cinnamon Nut Crunch,
here). For a different texture, you can also use sunflower seed or pumpkin
seed butter, which are just like peanut butter. There are quite a few different
brands on the market, and some contain sugars or added oils, so make sure to
look for one that only contains seeds and salt. You can also easily make them
at home with a little time and a food processor. Go for raw rather than roasted
whenever possible.
Alternatives: Sesame seeds and tahini also pack a DNA methylation
wallop.
#10: Salmon
Methyl donor
Oh salmon, how do I love thee? Let me count the ways. You are a great
source of the omega-3 essential fatty acids DHA and EPA, and DHA helps
indirectly to regulate the methylation cycle. You also deliver healthy amounts
of vitamins D and A, which modulate the function of enzymes involved in
both methylation and demethylation. You are also an excellent source of the
methyl donor B12 (with a massive 236 percent of recommended daily intake!),
as well as other important methylation nutrients choline, zinc, magnesium,
and potassium. Plus you offer selenium, biotin, niacin, iodine, and
phosphorous. This potent cocktail of nutrients makes the omega-3s more
bioavailable, meaning that eating salmon is more effective at elevating levels
of DHA and EPA than taking fish-oil supplements (as fish oil typically only
contains omega-3s, other fats, and some vitamin A and D).
While wild caught salmon is great, I’m also a fan of very cleanly sourced,
humanely raised farmed salmon, of which some varieties have more omega-
3s than wild caught. (Note that organic fish farming is not yet regulated by the
FDA, so if you’re buying “organic” I suggest carefully reviewing just what
the producer is doing to make sure it is indeed organic and regulated by a
reputable certification body.) Correctly raised farmed salmon has an
abundance of good nutrients and is very low in toxins. I regularly eat super-
clean farmed salmon that I buy at Whole Foods (Izzy loves it as much as I
do). It tastes great, and most importantly the standards used in raising the
salmon are humane and the diet is very clean. In addition, the nutrient levels
are verified by a third party.
How to eat it: Salmon is so darn easy to cook—just sprinkle with a little
salt and pepper and sauté in a small amount of avocado oil until opaque
throughout. It goes great with greens (I think you’ll find most things go great
with greens!). If you want a little more flavor variety, try the Spiced Salmon
Cakes with Vegetable Fries here.
Alternatives: Whitefish, roe, and oysters are other DNA methylation
superfoods from the sea. If you are vegetarian or vegan, get omega-3s from
flax and chia seeds and walnuts; you may also want to consider
supplementing with DHA- and EPA-containing algae. I assure you, these fatty
acids are that important.
#12: Spinach
Methyl donor
Really, all dark leafy greens are methylation superstars, but I’m calling out
spinach on this list because it has a mild taste that blends well with other
flavors, making it a great starter green. All greens are rich sources of folate
and betaine, which are methyl donors, and they’re terrific sources of minerals,
including iron, calcium, and magnesium. For the Younger You Everyday,
you’ll be eating one cup of dark leafy greens per day. But consider that two
cups of raw greens cooks down to about one-third of a cup—you can totally
do this. (Also, I include a list of ways to make sure you get your daily veggie
allotment here.)
How to eat it: Sautéed with a bunch of garlic; steamed and sprinkled with
lemon juice; torn up and thrown into smoothies, soups, stews, stir-fries, and
curries; or raw with a dressing made of healthy fats.
Alternatives: kale, Swiss chard, collard greens, dandelion greens, mustard
greens, beet greens—or my favorite, broccoli rabe
Protein Bars
EPIC bars (there are a variety of flavors; find your favorite)
Go Raw Pumpkin Seed Sprouted Bar
Bulletproof Collagen Protein Bars (especially the Vanilla Shortbread and
Fudge Brownie flavors—my personal favorites)
Health Warrior Pumpkin Seed Bars
RXBARs
BHU FIT Vegan or Paleo Protein Bars
Condiments
Sir Kensington’s Avocado Oil Mayo, Vegan Mayo, or Avocado Oil Vegan
Mayo
Primal Kitchen Avocado Oil Mayo
Primal Kitchen salad dressings (made with avocado oil)
Bragg salad dressings (I especially love the organic olive oil)
Primal Kitchen Organic Unsweetened Ketchup
Hellmann’s Real Ketchup sweetened only with honey
Seafood
Wild Planet sustainably caught sockeye salmon, mackerel, and sardines
Safe Catch tuna—their Elite line is lowest in mercury
Vital Choice canned seafood
Here are some labels to look for on farmed and wild-caught seafood:
MSC certified sustainable seafood
ASC certified farmed responsibly
Naturland
Whole Foods Market Responsibly Farmed
Wraps/Tortillas
Blue Mountain Organics Wraps, available in raw basil, raw tomato, and
raw curry flavors
NUCO Organic Coconut wraps
Siete Almond Flour Tortillas
Siete Cassava Flour Tortillas
Dark Chocolate
Just make sure to choose chocolate that is 70 percent cacao or higher,
preferably dairy-free and low sugar or sugar-free (sweetened with stevia or
erythritol). Some of the brands that make bars that meet this criteria are listed
below, but there are others—read the label carefully.
Rawmio
Alter Eco Dark Blackout
Lily’s
Evolved
Crackers
Mary’s Gone Crackers—the whole line is gluten-free
Simple Mills Almond Flour Crackers—they have many flavors and
varieties, all delicious
Bone Broths
Bonafide Provisions
Kettle & Fire
Cauldron Broths
Epic Bone Broth
Ice Cream
Van Leeuwen Vegan Ice Cream
NadaMoo!
EACH DAY:
__ 2 cups dark leafy greens, measured raw, chopped, and
packed
__ 1 cup cruciferous vegetables, measured raw, chopped, and
packed
__ 1–2 cups additional colorful fruits and vegetables (limit fruit
consumption to two servings a day, as they can be high in
sugar)
__ 2 tablespoons pumpkin seeds or pumpkin seed butter
__ 2 tablespoons sunflower seeds or sunflower seed butter
__ One-plus serving of DNA methylation adaptogens (see list
here)
__ Two 3- to 4-ounce servings of clean animal protein (unless
you’re over 60 or weigh more than 175 pounds, then two 5-
to 6-ounce servings; see list here)*
__ 3–5 tablespoons of healthy fats (see list here)
__ One-plus servings fermented foods (see list here)
__ Half your body weight in fluid ounces of filtered or spring
water, herbal tea, or seltzer
EACH WEEK:
__ One serving of liver (3-ounce serving), preferably organic**
__ 5–10 eggs, preferably free-range and organic**
__ Three medium beets
* If you are vegetarian or vegan, aim for 40–50 grams of
additional protein from beans, legumes, or plant-based protein
powder to compensate for the animal protein; see here for a
chart to help you hit this target.
** On days when you eat liver and/or eggs, those count
toward your daily clean animal protein target; one egg is roughly
approximate to 1 ounce of meat.
GENERAL GUIDELINES
• Eat organic as much as possible
• Eat between 7 a.m. and 7 p.m. (or finish eating three hours before bed if
you go to bed after 11:30 p.m., and don’t have your first meal until
twelve hours after your final meal)
• Include healthy oils (coconut, olive, flaxseed, and pumpkin seed)
• Avoid folic acid–fortified foods (including nearly all commercial
products made out of wheat, such as bread, pasta, and baked goods),
vegetable oils, fried foods, and charred foods
• Keep alcohol consumption to two drinks per week or less
• Minimize plastic food and beverage containers, nonstick cookware
Just as with the Intensive, the Younger You Everyday isn’t complete
without the addition of a few powerful lifestyle practices, which I’ll cover in
the next chapter.
7
S ince there’s more to your life than mealtimes, there’s also more to the
Younger You plans than food. The truth is, the way that you take care of
yourself beyond what you eat has incredible power to positively influence
your DNA methylation and your epigenome.
In this chapter, you’ll learn how to optimize your exercise, stress
reduction, sleep, and connection to others so that your DNA methylation
engine is firing on all cylinders. Every one of these pieces I share is
moderate and doable and has been road tested by our patients, our study
participants, and even our staff and family members. Best of all, these are
the types of practices that take all the good inputs you’ve been giving
yourself with your DNA methylation-supporting food choices and lend them
even more power. When you combine high-quality nutrition with sleep,
movement, and relaxation—the lifestyle practices from the formula I
introduced here—you function at your best. And you feel amazing.
EXERCISE
Exercise is an anti-aging elixir that spins the biological clock in reverse:
when you look at the lifestyle habits of healthy centenarians, a commonality
among all of them is that movement is a foundational part of their life. And
in general, it needn’t be intense—gardening, walking, dancing, or bike riding
are truly all it takes to tick the box on your requirements for exercise.
Exercise is the ultimate form of hormesis (beneficial stressor). It turns on
physiologic processes for cellular repair, detoxifies you through your sweat,
burns pro-inflammatory fat for fuel, and builds heart muscle. In fact, not
exercising takes as big a toll on life span as smoking.
A big reason that movement is such a vital component of health and
longevity is that it nourishes the epigenome.1 It acts like yet another epi-
nutrient by turning bad genes off and turning on genes we want activated,
and giving you the DNA methylation patterns of a younger person.2
Specifically, positive, exercise-induced DNA methylation changes have
been found on genes that are related to the following:
• Obesity, diabetes, and fat storage (this particular study showed
profound, beneficial changes in type 2 diabetics who started exercising
in just six months!)3
• The inflammatory response and inflammation-associated diseases4
• Learning, memory, and neuroplasticity (the ability of brain cells to
form new connections)5
• Suppressing cancer—and this effect is more pronounced the older you
are6
“High intensity” means you are going “all out” and reaching 90 percent
or higher perceived exertion—your breathing is strained, it’s impossible to
keep up a conversation, and your muscles are fatiguing quickly. The good
news is that you only maintain this level of intensity for two minutes or less.
You can either incorporate your HIIT into your regular workout—walking
up a few hills as quickly as you can, if you’re walking, or sprinting if you’re
jogging—or you can perform a workout that is specifically designed to
intersperse short intervals of exertion and rest—like the famous seven-
minute workout. If you choose to do HIIT workouts, they should be in
addition to, not in replacement of, your five thirty-plus-minute exercise
sessions per week.
The take-home message here is that when it comes to exercise, what’s
most important is that you do something you can stick with, like my mom’s
faithful daily gardening or my patient Jenny’s daily walk/jog. The thing you
do day in and day out outweighs what you do every once in a while, even if
that once in a while thing is the trendy exercise du jour. We have to start—
and perhaps stick with—“good enough” and trust that even moderate efforts
will improve health span. Our study suggests that it will. Some is always
better than none.
Are You Stressed Out? A Few Common and Less Common Signs
Look at your nails. Are they raggedy and chewed? Are the
cuticles picked? (The medical term for this practice is creepily
apt: autocannibalism). When I think I’m doing well at life, all I
need to do is take a peek at my cuticles to confirm—they
sometimes tell me a whole other story.
Are you yawning, sighing, or feeling like you need to
catch your breath? Stress triggers shallow breathing, which
can result in air hunger.
Having trouble thinking of words? Or conversely, can
you not stop talking, crying, thinking, or ruminating? Stress
impairs cognitive function, and can cause problems with
memory, mood, and anxiety. This is at least in part because
chronic stress and trauma can lead to imbalanced methylation
of one of our key genes involved in memory and learning:
BDNF. As previously mentioned, meditation and exercise both
can improve BDNF availability.
Are you more tuned in to odors, or are certain smells
bothering you? Humans are animals, and we use our sense
of smell to sniff for danger. If you’re stressed, your physiology
is going to turn up the sensitivity of your olfactory system.
Are you getting a lot of tension headaches? Holding
your breath or breathing shallowly results in low oxygenation of
your muscles. Which leads to tightness. Which leads to
tension headaches.
Are your muscles sore? In addition to low oxygenation,
stress causes your muscles to tense in preparation for fleeing
or fighting.
Have you been having heart palpitations? The fight-or-
flight response raises your heart rate.
Are your eyelashes or eyebrows looking scant? Some
folks deal with stress by pulling them out, in a practice known
as trichotillomania.
What I’m going to tell you to do about your stress is the same thing
that Sean and our study participants did, and that is meditate.
You probably already know that meditation helps with emotional
regulation and can even change the size of certain areas of the brain.
Meditation also gives your brain a break from all the emails, texts, and to-
dos that keep your nervous system in a heightened state. But you may not
realize that meditation also supports healthy DNA methylation. This likely
has to do with meditation’s ability to reduce psychological and physiological
stress. When you’re in a stressed-out state, your adrenals pump out the
hormones epinephrine and norepinephrine, which require methylation to be
made, metabolized, and excreted. That means there are fewer methyl donors
on hand for DNA methylation. In fact, a 2017 study found that long-term
meditators had a younger epigenetic age than people who had never or rarely
meditated.26
Clearly, it’s time we all get our meditation on: twice a day, for a total of
twenty to forty minutes, as part of the Younger You Intensive.
It’s common to resist the very idea of meditating, or breathing, almost
like a two-year-old throwing a tantrum (something I know a lot about at this
point in my life). But once you metabolize just how pervasive an effect
stress has on your health and your biological age—and how much
meditation truly can benefit you—you’ll be motivated to actually meditate
and not just read about it.
If you already have a meditation practice, booyah for you! I hope that
knowing that your practice helps promote healthy DNA methylation and
reduces biological age will inspire you to keep going. If you don’t already
have a meditation practice, now is the time to start. You don’t even have to
know how to meditate. I’m including the exact directions that we supplied to
our study participants here. I suggest following them during the eight weeks
of the Younger You Intensive if at all possible. But if you need a little more
in-the-moment guidance, or are following the Younger You Everyday, there
are many meditation apps that can talk you through it. An added bonus of
using a guided meditation app is that it will track your sessions, which helps
keep you accountable. Some good ones include:
• Oak
• Buddhify
• Insight Timer
• Headspace
• Calm
• University of Wisconsin’s Healthy Minds app (completely free and
research-based! I use their guided active mediations when I am biking)
It’s really as simple as taking a seat. You—your sanity and your health—
are worth that time. And every time you do, you’ll be reclaiming a portion of
those sixteen-plus years at the end of life that too many of us spend sick.
SLEEP
Sleep is a fundamental component of health overall and healthy DNA
methylation in particular. Yet it’s well documented that as we age, our sleep
changes, and that these changes start as early as our thirties. Most
significantly, the all-important, restorative deep sleep (the form of sleep we
need to prevent age-related diseases and decline) decreases significantly
over time. Also, the total duration of sleep drops off and it becomes more
fragmented as we have more frequent wake-ups. In fact, as Matthew Walker,
of the Sleep and Neuroimaging Laboratory at UC Berkeley says, “Sleep
changes with aging, but it doesn’t just change with aging; it can also start to
explain aging itself.”28 Let that sink in! Additionally, all of the chronic
diseases of aging have strong causal links to poor sleep. These facts, along
with the epigenetic research into sleep and DNA methylation, make it clear
why paying attention to sleep is so important to biological age and why it
was something that we included in our study. Fortunately, there are ways to
improve sleep—regardless of your age.
Whether you are doing the Younger You Intensive or the Everyday, your
assignment is the same we gave to our study participants—to get at least
seven hours of sleep per night. If that’s lower than you typically get, you can
feel good about knowing that you’ve already got this box checked (and
certainly don’t start sleeping less than you normally do just because I name
seven hours a night as a goal!).
As I covered in Chapter 2, sleep is an important part of the Younger You
program, because it is a powerful—and fast—influencer of DNA
methylation and the epigenome. As I also mentioned in Chapter 2, sleep is
the component of a healthy lifestyle that I struggle with the most. The upside
for you is that my questionable track record of getting good sleep has
motivated me to train for better sleep skills as if I were training for a
marathon. Let’s just say, I’ve learned some things. Namely, rather than
looking for the one thing that will revolutionize your sleep, prepare to try
several smaller adjustments to your daily routine. In my own experience and
the experience of my patients, a lot of little changes add up to a lot of restful
slumber.
I like to think of the daily habits that promote better sleep in terms of
when they should occur. First, it makes it feel less like yet another to-do list.
And second, it helps give your days a regular structure, which helps regulate
your internal clock. And when your internal clock is well tuned, it will make
it easier for you to fall asleep at bedtime and sleep through the night.
• Noon: Stop having any caffeinated drinks. And if you’re very
sensitive to caffeine (many of us don’t metabolize it well), consider
dropping it altogether. Caffeine can stay in your system for as long as
six hours, so put plenty of time between caffeine’s zone of influence
and bedtime.
• 7 p.m.: Finish your last bit of food, as the digestion process can be
stimulating. (As discussed in Chapter 5, time-restricted eating is
favorable for DNA methylation and insulin regulation.) You’ll also
want to finish up any strenuous exercise, as a workout too close to
bedtime can rev your cortisol, which is a stimulant, and make it
difficult to drift off. (For most of us, early morning exercise is best for
deep sleep.) Again if you’re more of a night owl or you’re a shift
worker and go to bed later, you can adjust this time to be later as
needed, just know that the goal is to avoid food at least three hours
before bedtime.
• Three hours before bed: Start to wrap up your screen time. If you
partake in any screen time from here on out, use blue-light blocking
glasses (although as I mentioned above, these are not a free pass to
stare at your screens for hours every night). Make any shows or
movies you watch of the calming variety—no intense thrillers or
horror. For me, an intense thriller can be a recently published research
paper on a topic near-and-dear to me, like epigenetics. I have to save
those for another time, unfortunately.
• Two hours before bed: Have your last glass of liquid so that you are
less likely to need to wake up and pee. And remember, you are
foregoing alcohol altogether for at least the eight weeks of the
Younger You Intensive.
• Sixty minutes before bed: Turn off all screens. Indulge in a pre-
bedtime ritual. Take a bath, do a little light yoga or stretching.
• Thirty minutes before bed: Do your relaxation practice, such as the
meditation here.
• Fifteen minutes before bed: Brush your teeth, wash your face, and
do any other personal care in the same order every night. The
predictability of events will help cue the brain that sleep is coming.
• Ten minutes before bed: Turn on a white noise machine or app
and/or an essential oil diffuser with lavender oil. Regular use will
make this step a powerful cue to your body that it’s time to sleep.
Then read for a bit, take a few deep breaths, or give yourself a foot
massage to further relax before shutting off the light.
One thing that can support your efforts both to relax and to
sleep better are Epsom salt baths. Epsom salt is comprised of
magnesium (a mineral that helps to relax your muscles,
including the muscles of your GI tract, making it a helpful
laxative, too) and sulphate (a form of sulfur and key detoxifier).
Try taking a twenty-minute Epsom salt bath, with 2 cups or
even more of salt, before bed three times per week to reduce
stress and body aches and boost detoxification. In my clinic,
we recommend Epsom salt from Ancient Minerals or
SaltWorks.
Troubleshooting Sleep Issues
I know many people depend on some form of sleep medication, but these
medications take too big a toll on health in general, and DNA methylation in
particular. Benadryl, Unisom, Tylenol PM, and Advil PM all share the same
active ingredient—diphenhydramine, an antihistamine that has scary long-
term effects. It’s a clear contributor to dementia, with the risk increasing
depending on dose and duration of use.31 Being an anticholinergic drug, it
depletes an important neurotransmitter called acetylcholine. Acetylcholine
has a number of important roles, from activating muscles to regulating
autonomic nervous system response. In the brain, it’s involved in arousal,
memory, motivation, and attention. Acetylcholine requires choline to
synthesize it, and choline is an important methyl donor that’s challenging to
get enough of, hence our recommendation for eggs. So if we deplete
acetylcholine, our body will work double time to make it, possibly stealing
methyl donors from DNA methylation, or simply not making enough
acetylcholine for the brain’s high demands. For that matter, sleep
medications including Ambien, Lunesta, and Sonata also deplete
acetylcholine. If you are taking any of these, I recommend that you slowly
taper down and stop.
There are many supplements that are supportive of a good night’s sleep—
I cover them in Chapter 8, so if you feel like you aren’t able to sleep without
some outside help and are ready to find an alternative to sleep meds, be sure
to check them out.
There are some sleep-impeding issues that require a clinician’s
assistance, including hot flashes, sleep apnea, and nocturnal hypoglycemia.
These are sleep dealbreakers and need to be remedied with professional
guidance.
If you regularly wake up in the middle of the night, first, consult your
physician to rule out any issues that might require medical help. Then, are
you experiencing anxiety? I know I tend to wake up thinking about projects
(or responding to a crying toddler). One of the most helpful interventions for
me has been listening to a boring story, a long meditation, or a sleep “talk-
down” podcast. There are literally thousands to choose from on YouTube.
However, you want to keep your exposure both to blue lights and
electromagnetic frequencies to a minimum in the middle of the night, so
download them onto your phone rather than streaming them and use audio
only.
I recognize that I’ve thrown a lot of options at you here, but know this:
it’s worth the time and energy it might take to find the right combination of
practices, daily routines, and supplements that will help you get the sleep
you need to restore yourself.
Of course, we take in toxins via more than just food. Here are other
important strategies to take for reducing overall toxin exposure (again, the
Environmental Work Group, https://ewg.org, is a fabulous resource for
helping you choose nontoxic products):
• Use natural cleaning products for your home and laundry.
• Avoid topical products, like lotions and sunscreens, that contain
chemicals like phthalates, parabens, formaldehydes, and methylene
glycol (a type of formaldehyde).
• If you have a vagina, choose your products with care. Nonorganic
tampons can have chemicals and pesticides sprayed on them, which
leaves a residue that gets introduced to your vagina, and the mucosal
membranes there are very absorbant. Never use talc or baby powder in
your underwear. Do not douche or put any deodorants or other
fragrance-containing items in your vagina. Wear natural fiber
underwear, use organic products (including lube), and consider a
menstrual cup or period underwear to reduce waste and chemical
exposure.
• If you have babies, consider the type of diaper you are using. Many
contain plastics that come in contact with your baby’s skin twenty-four
hours a day, seven days a week. Consider cloth or nontoxic disposable
diapers as an alternative.
• Take off your shoes inside the house so that you don’t track toxic
particulates into your home.
• Because synthetic fragrances are typically some of the most toxic
chemicals, avoid any scented products (except those scented with
essential oils), including air fresheners, odor-masking sprays, candles,
cleaning products, and perfumes.
• Use nontoxic nail polish (or skip it altogether and just buff your nails
until they shine).
• Use organic lawn and pest control in your yard, especially if you have
kids or pets (who are themselves vulnerable to these toxins and can
track them into the house).
• Choose mattresses and pillows made from natural materials—since
you spend up to a third of your life in bed and since you detox during
sleep.
• Don’t carry your cellphone in your pocket or your bra or rest your
laptop in your lap, as the radiation and electromagnetic fields emitted
by these connected devices decrease dramatically with distance.
• Indoor air is nearly always more contaminated than outdoor air; we
breathe far more air than we eat food or drink water. At the minimum,
crack your windows. Also consider an air purifier(s) for your home—
at least for your bedroom, which is where we tend to spend the most
time in our homes, and where we do a lot of detoxifying work while
we sleep.
• Get your water tested, as lead (from old pipes, both in your home and
in the water system that carries water into your home) and other
contaminants are frequently found in drinking water. For example, my
well water is wildly high in iron, so I use a whole-house filtration
system plus a point-of-use filter (at my kitchen sink) to manage it.
(See here for water-testing service recommendations.) Knowing which
contaminants are in your water will help you determine what type of
water filter to use; a good, basic option is to use a carbon filter, as I
mention here. You do have to replace the filter regularly, because
when it is overloaded any contaminants it has previously trapped will
flow right back into the water you’re trying to purify.
Oxytocin is so important that not getting enough of it, whether due to life
circumstances or improper DNA methylation that shuts off oxytocin receptor
genes, is harmful for humans of all ages, from infants to centenarians.
A sad truth is that oxytocin declines with age, and low levels are
associated with many conditions seen in aging, including dementia,
depression, hypertension, diabetes, wrinkles, and muscle loss.43 Fortunately,
it’s easy—and important—to raise oxytocin. Adhering to the Younger You
Intensive and Everyday principles can help—by supporting healthy
methylation patterns of oxytocin receptor genes—as will many lifestyle
practices (see list here).
Of course, there’s a U curve of benefit for oxytocin, too. Some research
in humans suggests that there are negative impacts of oxytocin receptor
genes that are either cranked up (i.e., excessively hypomethylated) or
inhibited (excessively hypermethylated).
Too little oxytocin receptor gene action (thanks to hypermethylation) can
usher in depression, including postpartum depression, disconnection, the
social cognitive deficits seen in autism, and the rigid thinking present in
anorexia. In other words, social, cognitive, and emotional function are all
impaired. Excess oxytocin activity has been associated with anxiety,
perinatal stress, autism, and mood disorders. Korean researchers found that a
hypomethylated oxytocin receptor gene—which suggests that there is an
above-average amount of oxytocin in play—is associated with obsessive
compulsive disorder.44 Another long-lasting result of impaired oxytocin
receptors is that you become more likely to crave carbohydrates—especially
sugar, which then paves the way for inflammation, diabetes, and obesity.45
Because this science is new and evolving, it affirms that the broad, safe
diet and lifestyle choices that comprise the Younger You approach are a solid
game plan, and that there’s yet another reason to eat plenty of DNA methyl
donors and methylation adaptogens, so that your DNA methylation is just
right.46
The data are strong that your every interaction that involves loving touch,
whether with your child(ren), your partner, and/or your pet, gives you
regular doses of oxytocin, which then deliver long-lasting benefits for your
(and your offspring’s) epigenome. Even if your child isn’t yours by blood,
when you each get hits of oxytocin throughout the day, your DNA
methylation—and thus your genetic expression—syncs up, even though you
don’t share actual DNA. Your ongoing, nurturing connection to one another
becomes biologically embedded on your epigenome, creating a shared
genetic expression. This idea is deeply moving to me as an adoptive mom.
Kids who don’t get adequate amounts of physical affection and care have
reduced tolerance for stress, a higher possibility for a lower IQ, a lack of
social development, and a higher risk of obesity and diabetes later in life
because of epigenetic changes. Kids who grow up in a low-contact
household have different methylation patterns on their oxytocin receptor
genes than kids who come from a high-contact home.47 This likely plays a
role in the well-established phenomenon that babies who aren’t held enough
fail to thrive—something we can now understand as being a result of
imbalanced DNA methylation that prevents them from developing
appropriately.
Of course, it’s not just oxytocin receptor genes that are impacted by early
loving touch—or lack thereof. A 2017 paper out of the University of British
Columbia showed that the amount of hugging a child receives as an infant
can influence epigenetic changes in at least five areas of their DNA,
including those related to the immune system and metabolism.48
Luckily, it seems that whenever kids start to get more loving touch, they
will experience benefits, although earlier is better. A 2011 study found that
parentless children who were taken out of an orphanage and placed in foster
homes before they turned two enjoyed “substantial” gains in cognitive
function and social outcomes—much greater than children who stayed in the
orphanage until later ages. This study also found low caregiver contact was
associated with greater infant distress and a lower biological age at 4.5 years
of age (in kids, a lower bio age means they’re not developing appropriately).
So lack of early contact can have significant long-term effects.49
For parents, the steady stream of oxytocin that parenting provides means
a lower risk of dying from any cause. I know those tough, sometimes
sleepless, days in parenting can make it feel like your kids are shaving years
off your life, but science suggests the opposite is true: a 2012 Danish study
that followed over twenty-one thousand women undergoing in vitro
fertilization found that the women who went on to have children had a risk
of dying from any cause that was a full four times lower than those women
who didn’t.50 And a 2006 study analyzed life span in the Amish community
and found that life span for both fathers and mothers extended in proportion
to how many children they had—except for women, whose life span
increases petered out if they had more than fourteen children.51
Josh Mitteldorf, a brilliant statistician who assisted in analyzing the data
in our study, published a statistical analysis of the Centenarian Study in
Boston that showed that women having children after forty were a whopping
four times more likely to live to one hundred!52 The argument that women
who conceive after forty are metabolically stronger isn’t sufficiently strong
to explain the full four-fold increase. Yes, likely these women are healthier,
but the will to live and the deep ineffable connection to your offspring is
also, likely, a big piece.
While having a child definitely gives you a strong will to live, which
certainly has an impact on life span, it’s the regular doses of oxytocin—big
and small—that parenting provides that create healthier DNA methylation
patterns, which then delay aging (which is, remember, the single biggest
cause of chronic disease).
Of course, you don’t have to have children to give yourself regular doses
of oxytocin.
There is just one more piece to explore when it comes to rounding out the
full Younger You program—and that is ensuring that you are getting plenty
of the nutrients needed for healthy DNA methylation. Although of course I
strongly advocate for getting as many nutrients as possible through the diet,
there are instances where a moderate dose of a well-chosen supplement is
helpful for keeping DNA methylation humming. I’ll guide you through what
supplements to consider, how to choose the ones that are right for you, and a
prudent dosage.
8
SUPPLEMENT SUPPORT
O f course in general I want you to get your nutrients from whole foods
wherever and whenever possible. As evidence, in our study, we only
prescribed our participants a single-strain probiotic and an organic greens
powder—the lion’s share of nutrients came from food. After all, I spent most
of Chapter 2 explaining why we don’t want to rely on high-dose
supplements to meet our need for methyl donors. And yet. If only medicine
followed binary logic—supplements were always bad, and foods were
always good. It just doesn’t work that way. There is a time and place for
everything, and that includes a few well-chosen, moderately dosed
supplements.
Yes, you can get ample, yet safe, amounts of methyl donors from your
diet. And yes, that is the optimal approach to take. But there may be
nutrients that come packaged in foods that you just don’t like, or don’t eat
for a reason. Say you have an allergy to eggs, for example: unless you’re
paying very close attention to alternative choline sources, you will not be
likely to eat enough of them to cover your choline needs. Or, if you never eat
salmon or other fatty fish, because you don’t like it or are a vegetarian or
vegan, you are probably not getting enough of the omega-3 essential fatty
acids EPA and DHA that those foods contain. Or maybe you don’t absorb
some nutrients optimally (if you’re on an acid-blocking medication, for
example) or burn through others fast (I always, always need extra
magnesium). In my clinical practice, using the broad nutrient testing that we
use, it’s the rare day that someone’s levels are perfect from food alone.
In this chapter, I’m sharing the supplements I recommend in the
following situations:
• You are following the Younger You Intensive; these are the
supplements our study participants took, and therefore something
everyone who follows the eight-week eating plan should consume.
• You are following the Younger You Intensive and are vegetarian or
vegan; in addition to the supplements listed above, these are the
supplements that will rectify any potential insufficiencies of DNA
methylation–supportive nutrients due to your minimal intake or
complete avoidance of animal-based foods.
• You want to support your overall health and shore up your epigenome
even further; these include basic nutrients most people are deficient in,
such as vitamin D and omega-3s, as well as key DNA methylation
adaptogens that provide further epigenetic support.
• You want to preserve the methyl donors you already have—a more
prudent strategy for boosting your level of methyl donors than
supplementing with them directly, something we refer to in our clinic
as “backdoor methylation.”
• Other anti-aging supplements that I’m rather bullish on for myself,
that you may want to consider also.
• In addition, I’ll cover supplements that help you sleep, so that you can
get your seven hours of sleep a night without having to rely on
prescription sleep medications.
Senolytic Adaptogens
SLEEP-SUPPORTING SUPPLEMENTS
Sleep is such a vital component of health and a cornerstone of both the
Younger You Intensive and the Younger You Everyday. I discuss
nonsupplement strategies for getting more sleep, as well as the reasons why
you don’t want to rely on sleep meds, in Chapter 7. If you need more help
getting your zzzs, try these:
• Melatonin: Melatonin is a potent antioxidant and is considered a
longevity agent. Start lower and see how you tolerate it; for some,
melatonin causes strange dreams. For most, it’s a very useful sleep-
supporting supplement with a solid safety record.
Dosage: 300 ug to 10 mg about twenty minutes before bedtime
• Magnesium glycinate: Magnesium is relaxing. Taking it as
magnesium glycinate gives you the added benefit of the anxiolytic
amino acid glycine. You can also try glycine alone—Metabolic
Maintenance sells a three-gram stick of glycine powder that we love in
our practice.
Dosage: 200–600 mg at bedtime (I take about 600 mg most
nights.)
• L-theonine: This is a main ingredient in green tea, but it’s not
stimulating. In fact, research shows it to promote relaxation and
reduce anxiety. While you can use it at bedtime, you can take it during
the day, too, and it won’t make you drowsy.
Dosage: 100–200 mg, taken at bedtime (if you want to promote
sleep; otherwise you can take it during the day whenever you’re
feeling, or anticipate feeling, anxious).
Taken together with the eating plans and lifestyle practices outlined in
Chapters 5, 6, and 7, these supplements round out the full Younger You diet
and lifestyle. In the remaining chapters, I’ll share how DNA methylation
changes over the course of your life—and how and when to support it during
each life stage. I’ll also give you a glimpse into the future—your own
personal future, the future of your family, and the future of the role of
epigenetics on individual and public health.
PART 3
Adolescence (Fourteen–Twenty-four)
Puberty and sexual maturation are also a sensitive time period for epigenetic
activity, and perhaps more so in girls, given that oocytes—which are cells
that can go on to develop into eggs—are finishing their development now.
Thus, supporting the best genetic expression patterns as possible in girls is
an important goal. However, we don’t want to exclude the boys:
physiologically, for both sexes, lots of changes are happening, and anytime
we are developing and bringing new systems online (think: new cells, new
DNA, new DNA methylation) it’s a vital time for eating DNA methylation–
friendly foods.
In adolescence, hormones swoop in, triggering physiologic changes so
that we become physically capable of reproducing. And our brain isn’t fully
developed until our midtwenties, meaning this epigenetically potent time
lasts for nearly a decade. One study looked at hundreds of thousands of
DNA methylation sites in boys and girls in pre- and postadolescence and
found the adolescent transition to be associated with changes in fifteen
thousand DNA methylation sites! These were associated with immune
system development and cell growth. Other factors associated with DNA
methylation changes included BMI in the slow-growth period, smoking, and
the use of nonsteroidal anti-inflammatory drugs (pain-relieving medication)
during this time.11
As many teens and college students experience a lot of school-related and
social stresses, the teen years and early twenties are an excellent time to
establish a meditation habit or other relaxation practice, like yoga or
breathing. The many meditation apps can make this more accessible and
appealing to young adults—refer back to here for a list of them.
Sleep is also vital at this time, and only about 8 percent of adolescents
actually get the sleep they need.12 We know sleep deprivation changes DNA
methylation patterns for the negative, both in the brain and body.13 Research
also shows that when a pattern of poor sleep continues in teenagers (think
video games, TikTok, homework) they tend to eat more carbs, eat more food
in general, and have more belly fat. Less sleep also increases depression in
teens.
It’s important to know that staying up late and then sleeping in is not just
your teen being willful: fluctuating hormones drive that tendency to stay up
late and sleep in, and school schedules generally squash that impulse
(although some schools are moving toward delaying start times). Teens can
also have erratic levels of melatonin, the chief sleep hormone. Thus, a
melatonin supplement can be a helpful sleep support for them—refer back to
here for more on this and other supplements to support sleep, and here for
lifestyle strategies that can also help teens get more zzzzzs. And the structure
that we, as parents, enact around bedtimes, study times, and screen time is
essential.
It’s also important to tend to brain health now, since it is still developing
until the midtwenties. The brain is about 70 percent fat, making omega-3
fatty acids—and especially DHA—essential for healthy brain function.
Fortunately, salmon isn’t a difficult fish to eat for most kids, and it’s loaded
with good fats. (Just follow the shopping guidelines for salmon I shared
here.) Researchers suspect that epigenetics might be a key mechanism that
drives the benefits of omega-3 supplementation, including those exerted on
brain development as well as warding off the development of metabolic
syndrome in childhood.14 Much remains to be understood, especially with
regard to kids and teens, but the science is strong enough to recognize
omega-3s as an important class of fatty acids to get both through food intake
and, when necessary, supplementation.
Because adolescence is often when we first begin drinking alcohol, many
times in binge drinking patterns, it’s worth reiterating that alcohol inhibits all
forms of methylation and the absorption of folate.15 So chronic alcohol use
is going to ultimately wreak havoc on all types of methylation, including
DNA methylation. If you are the young adult reading this, every drink you
don’t have will help support your DNA methylation. And when you do
drink, consume some extra methyl-donor foods that day and the day after—
such as greens, eggs, beets, and liver. If you are the parent of an adolescent
or young adult, share this information with your kids, and it may be a new
way into a conversation about imbibing responsibly.
For anything hormone-related, such as migraines that start in puberty or
occur in tandem with the premenstrual phase of the cycle, painful periods, or
premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD),
the Younger You Intensive or Everyday will be helpful with balancing and
detoxing hormones thanks to their high content of cruciferous veggies
(which contain the compound DIM that helps the body process estrogen) and
lack of pro-inflammatory foods. Exercise and stress management are also
both documented to be helpful in PMS and PMDD. And it is extra-important
that you avoid toxins as much as you can, as many of them are “endocrine
disruptors,” which means they can aggressively disrupt our own hormonal
system and drive not just PMS and PMDD, but also, with both early
exposure and years of exposure, cancer. This link between cancer and
endocrine-disrupting chemicals is driven in part by hypermethylation (and
inhibition) of tumor-suppressor genes, such as BRCA in breast cancer. All
the more reason to eat plenty of DNA methylation adaptogens, which clean
up hypermethylation and allow for the re-expression of those inhibited
genes. All the toxin-avoiding advice I shared here–here applies here.
Younger You strategies for adolescence:
• Introduce your teen to relaxation practices, such as meditation, yoga,
and breathing, to help them manage their stress.
• Encourage them to exercise regularly.
• Consider magnesium or a melatonin supplement to help aid them in
getting the sleep they need, and refer back to the sleep strategies I
shared starting here to see which could help your teen get the sleep
they need.
• Enact boundaries around screen time, especially at night.
• Talk to your teens about alcohol’s potentially lasting, negative effects
on their brain DNA methylation patterns.
• Prioritize omega-3-rich foods, such as salmon, and consider a
supplement for them if needed (refer back to here).
• Encourage them to eat plenty of cruciferous vegetables and avoid
personal care products and home-cleaning products that have the
potential to contain endocrine-disrupting chemicals to help promote
hormonal balance.
Pre-conception
Following some version of the Younger You program all of the time is smart,
but there are a few times when it moves beyond smart to essential, and
trying to conceive is one of them—for both women and men. If you can
nudge your genetic expression into tip-top shape, you’ll be handing a
pristine-as-possible imprint to your offspring. That’s because your diet and
lifestyle choices affect the germ cells that you pass on to your child, which
will, in turn, impact the germ cells that your children will pass on to their
offspring (aka your grandchildren), and likely, generations beyond that, too.
Because your epigenetic status has such a direct impact on your
descendants, ideally you (meaning both the mother- and father-to-be) will
follow the Younger You Hybrid: combine the nutrient targets of the Intensive
(greens, liver, eggs, fish, beets, DNA methylation adaptogens, and
superfoods) with the legumes and whole grains of the Everyday. If you want
dairy or sugar occasionally, and you tolerate them, that’s OK. An important
exception is if you or your partner has a demonstrated carbohydrate
intolerance such as insulin resistance, polycystic ovary syndrome (PCOS), or
diabetes. If that’s the case, stick with the Intensive and keep carb intake
lower during pre-conception.
For everyone, when you’re trying to conceive, as with pregnancy, I
would skip alcohol because it inhibits methylation across the board,
including DNA methylation.
If you are inclined, work with a functional medicine practitioner to take a
full medical history and suite of labs so that you can be sure you are hitting
all of your nutrient targets and that your inflammation, blood sugar, and
toxin exposures are all in a healthy range. I have done many of these pre-
conception workups on my patients over the years—they are informative and
rewarding. Your practitioner can further individualize the Younger You
program for your needs.
Even small DNA methylation–friendly improvements to your diet in this
pre-conception time can have a big impact: a 2020 study found that men
who ate 60 grams (about two ounces) daily of mixed nuts (a blend of
almonds, walnuts, and hazelnuts; all rich in methyl donors) without changing
any other aspect of their standard Western diet for fourteen weeks
experienced beneficial DNA methylation changes, and their sperm count, as
well as the size, motility, and viability of their sperm, improved.19 That’s
pretty impressive for one small tweak, and yet another illustration of the
power of the epi-nutrients contained within food and the epigenome’s
responsiveness to those epi-nutrients.
Conversely, now is an important time to clean up your intake of toxins,
tobacco, and marijuana: research has shown that a man’s exposure to both
nicotine and tetrahydrocannabinol (THC, the psychoactive compound in
marijuana) can negatively change DNA methylation in sperm on seven
genes that play a role in neurodevelopment, many of which are associated
with autism.20 In a recent animal study, the herbicide glyphosate (the active
ingredient in Roundup) was “shown to promote the epigenetic
transgenerational inheritance of pathology and disease in subsequent great-
grand offspring [three generations!].”21 If you’re not eating organic yet, now
is the time.
Younger You strategies for pre-conception:
• Follow the Younger You Hybrid—unless you have PCOS or diabetes,
then follow the Younger You Intensive—as much as possible.
• Skip alcohol as much as you possibly can.
• Consider working with a functional medicine practitioner to do a
thorough assessment of your current health and nutrient status.
• Reduce your exposure to toxins, nicotine, and THC as much as
possible—eat organic, stop using marijuana, and follow the
suggestions starting here to lower your toxin exposure.
Pregnancy
Once you conceive, the window for influencing your baby’s epigenome, in
what’s called “gestational programming,” is open wide. You can see how
important it is to support DNA methylation in the earliest trimester when
you look at the outcomes of the children whose mothers were pregnant with
them during the Dutch Hunger Winter: the babies of the women who were in
their first trimester of pregnancy experienced more and longer-lasting
negative impacts to their health outcomes (as did their children) than those
born to women whose pregnancies were further along.
In earliest stage of embryogenesis, there’s an all-important demethylation
process that happens on the DNA that’s been donated from the egg and the
sperm. Essentially, the DNA donated by the egg and the sperm is scrubbed
clean of methyl groups. Or almost clean, as about 30 percent of epigenetic
marks remain after the demethylation process is complete. It’s this remaining
30 percent that contains some of the experience of the previous generations,
which is sometimes referred to as the “imprintome” because it carries the
imprint of our parents’ epigenome. It’s here that our past generations’
nutrients, life experiences, stressors, and toxin exposures influence our
epigenome.
As with pre-conception, I recommend following a Younger You Hybrid
plan—hit the daily/weekly nutrient targets of the Younger You Intensive, but
include the legumes and well-chosen grains and occasional dairy of the
Younger You Everyday. In general, you want to be eating heartily, as
pregnancy is a calorically demanding time: a full-term pregnancy requires
about 77,000 calories!22 It’s a good thing there is no calorie counting on the
Younger You program; you can eat until you are satiated and nourished.
An important deviation from both the Younger You Intensive and
Everyday for pregnant women is that you want to eat more protein—15
percent more in the second trimester and a whopping 25 percent more by the
third trimester. And these numbers increase for twins and triplets. But in
general, for a single pregnancy, you want to be at a minimum of 1.1 grams of
protein per kilogram of body weight from week sixteen through delivery.
This is at least 70 grams/day for a 140-pound woman, and it will rise as you
and the baby put on weight. Protein during pregnancy should be about 15–25
percent of total food intake, increasing intake as time progresses. (Note that
the Younger You plan is 15–20 percent protein, so you’ll be above our
requirements as your pregnancy progresses. This is, of course, correct to do.)
During the earliest part of the first trimester, vitamins C and A and iron
are hugely important for epigenetic programming, as they support the
enzymes responsible for demethylation. While you want to get as many
nutrients as you can through food, in my experience, almost all pregnant
women need supplemental iron—refer back to here for guidance on how to
do it.
Equally important: as the DNA is scrubbed clean, shiny new methylation
marks are being placed down. This is part of the process that tells the
embryo’s stem cells what to be when they grow up—whether they’ll be a
skin cell, a nerve cell, a muscle cell, or a brain cell, etc. And determining
that fate requires a lavish sprinkling of methyl donors—which means plenty
of folate, vitamin B12, betaine, and choline. (You likely have questions about
folate and folic acid, since it is often advised as a key prenatal supplement.
I’ll talk about that in just a bit.)
Both the Centers for Disease Control (CDC) and the World Health
Organization (WHO) recommend pregnant women take a minimum of 400
ug of folate, either as synthetic folic acid or naturally occurring folate, in
addition to consuming a diet high in folate-rich and folic acid–fortified
foods.24 And if there is a family history of neural tube defects, the WHO and
CDC recommendation jumps ten-fold, to 4,000 ug per day for the first
trimester. Meanwhile, the National Institutes of Health (NIH) recommends
600 ug folate daily, including folic acid from fortified foods.25
There has been no upper limit of daily folate intake set for pregnancy,
although the NIH states that adults nineteen years and older should not
exceed 1,000 ug/day. Yet, potential issues in offspring exposed to excess
folate/folic acid in utero in animal and human studies include asthma,
metabolic syndrome, obesity, and autism.26 Because of these findings, the
Society for Endocrinology recognizes that an upper limit recommendation
for pregnant women—especially in the first trimester—is urgently needed.
Where does that leave us? When I look at the CDC, WHO, and NIH
recommendations, in combination with the remarkable birth outcome data
from GrowBaby Health that I include in this section, I make the following
recommendations:
COMMON ALLERGENS
Eggs*
Dairy**
Finned fish*
Nightshades*
Peanuts**
Sesame*
Shellfish*
Soy**
Tree nuts*
Wheat
* Foods allowed on the Younger You Intensive
** Foods allowed on the Younger You Everyday (except for soy, which is also
allowed on the Younger You Intensive for vegetarians and vegans)
N o matter what genetic hand you have been dealt, nourishing your DNA
methylation can mitigate the risks and help you find your level of optimal
health, as Melissa’s story exemplifies so well.
As a twenty-eight-year-old New Yorker with a career in the fashion
industry, Melissa prided herself on being able to power through twelve-hour
workdays—even those times when she was jet-lagged after flying back from
Paris Fashion Week. A lifelong athlete and dancer, Melissa worked out for at
least an hour every day. She was also a vegetarian who never smoked and
rarely drank anything other than water. Her resilience kept her healthy even
when her coworkers got sick. In addition, Melissa was newly engaged. Life
was great.
Melissa took her dedication to living a healthy life so seriously that she
also performed a daily breast self-examination; a ritual she’d performed
since she was eighteen. Breast cancer ran in her mother’s side of the family
—despite being healthy overall, Melissa’s mother had been diagnosed with
stage 1 breast cancer at thirty-six. And Melissa’s grandmother had been
diagnosed with breast cancer at age twenty-nine; ovarian cancer took her life
just before her fortieth birthday.
Melissa’s awareness of her increased risk fueled her devotion to
exercising, eating well, and monitoring her breast health. Yet one jet-lagged
morning, Melissa found a lump during her daily breast exam. She got an
appointment with her gynecologist for later that same day.
Melissa’s Ob/Gyn confidently told her she was too young to have breast
cancer, regardless of her family history. Melissa wanted to believe her, but
couldn’t shake the feeling that something was wrong. So she sought a
second opinion. When this doctor said Melissa’s mini-lump had no tumor-
like characteristics, and that there was only a 1 percent chance it was
cancerous because she was so young and healthy, Melissa wanted to believe
her, too. Just to confirm what she already knew to be a correct diagnosis, the
doctor did a needle biopsy and sent Melissa home.
About a week later, Melissa got the call that everyone dreads. The tiny
bump was malignant. Worse yet, her young age meant that her cancer was
highly aggressive and reoccurrence was likely. That meant she’d need
chemo and radiation—although not a bilateral mastectomy. The treatments
would cause her to lose her hair, the skin on her breast to harden (making
any future reconstruction extremely difficult), and one or both of her arms to
potentially swell indefinitely. On top of that, the treatment was expected to
bring post-treatment menopause and all of its symptoms, with only a 25
percent chance of ever getting pregnant. They also recommended genetic
testing and, if Melissa had the BRCA 1 or 2 gene, that she should have an
elective oophorectomy (removal of her ovaries) before she turned forty in
order to ensure the best odds of survival.
Melissa contacted a work colleague who, she remembered, had been
diagnosed with breast cancer in her midthirties. That colleague detailed the
treatment plan she had followed—surgery, a staggered chemotherapy
protocol, and IV therapy. Her protocol also included dietary interventions,
supplement regimens, and relaxation practices. Melissa booked an
appointment with her friend’s oncologist, and it changed everything.
This oncologist devised a treatment plan that included surgery and an
open-ended chemotherapy course that they would develop collaboratively.
Melissa would work with a nutritionist to create a dietary plan focused on
detoxification, immune support, and genetic expression. This sounded
especially appealing to Melissa as she had since learned that she had the
BRCA1 gene mutation. The plan included intermittent fasting (to protect
healthy cells but kill fast-growing tumor cells); an antioxidant-rich diet that
consisted of nine to ten cups of colorful, low-glycemic fruits and vegetables
each day; regular intake of bioactive food components such as genistein,
curcumin, choline, and sulforaphane (which we now recognize as DNA
methylation adaptogens); and a daily sleep journal to record time spent not
just sleeping but also resting. Ultimately, the goal of Melissa’s treatment
plan was to reset her future genetic expression away from cancer and toward
health, and its pillars very closely resembled the Younger You Intensive.
No other provider had mentioned diet, nutrients, or relaxation to Melissa.
And while the idea of favorably influencing genetic expression (rather than
being a victim of “bad genes”) was new to her, it also made sense to treat the
root cause, and not just target the tissues.
After four rounds of strong, but staggered chemotherapy, an elective
bilateral mastectomy, new daily routines that included a plant-based diet
with small amounts of organic animal protein, an emphasis on stress
reduction, at least eight hours of daily sleep, plus meditation and
acupressure, Melissa no longer had signs of any health issues and was
pronounced cancer-free. What she did have was
• Menstrual regularity throughout the entire course of treatment without
a single sign of menopause
• An absence of swelling, discomfort, or physical restriction in both
arms
• Enough energy and resilience to continue working full time without
restriction and remain active
• A head of hair that grew back quickly and surgical scars that are now
barely detectable
• The opportunity to plan her wedding without fear or trepidation
• And last, but certainly not least, a renewed trust in herself, her
instincts, and her body
Now, over twenty years later, Melissa has two children and a master’s
degree in clinical nutrition, and she is currently one of the functional
nutrition residents in my clinic (in fact, she developed many of the vegan
recipes in this book).
I love Melissa’s story for many reasons—that she survived an early-onset
and aggressive cancer, of course. But also that she was an early adopter of
diet and lifestyle practices aimed at improving genetic expression, and that
they helped her get rid of cancer and have kept her cancer-free in the
decades since. And not least, Melissa’s story proves that even a genetic
mutation like BRCA1 doesn’t have to dictate your fate.
In this section I’ll talk through how to approach genetic variations and
mutations (there’s a difference), including perhaps the best-known genetic
mutation of all—the one that occurs on the BRCA genes so closely
associated with significantly increased risk of hormone-related cancers. I
hope to dispel some of the mystery and fear you may have encountered after
receiving your own genetic testing, or if you’re facing disease with a genetic
component.
Did you know that there are more than five hundred known
BRCA mutations that are of “unknown clinical significance,”
which means we don’t know whether the mutation increases
cancer risk or not?6 A 2020 study argues that routine, broad
genetic testing for mutations on BRCA and other tumor-
suppressor genes could prevent up to an estimated 2,666
cases of breast cancer per million women, and up to 449
ovarian cases per million women.7
Beyond mutations, assessing the methylation patterns on
BRCA genes will become quite useful for determining risk. In
time, careful, broad assessments of DNA methylation patterns
will help guide breast and ovarian cancer prevention and
treatment, too—catching unfavorable changes and reversing
them well before disease is present.8 If we look for the gene
mutations plus the DNA methylation patterns, how many more
cancers could be prevented?
Once you have cancer, we know that it hijacks epigenetic machinery for
its own nefarious aims (namely, rampant growth). Tests of the DNA
methylation patterns present in breast cancer tumor cells shows that tumors
are older, epigenetically, than the surrounding, normal tissue. Specifically,
genes that inhibit the cancer are turned off, and genes that allow cancer to
grow unchecked are on—which, unfortunately, is the same pattern we see in
aging in general.9
This is all to say it needn’t be a BRCA1 or BRCA2 gene mutation that
increases your risk of cancer. In fact, more likely, it’s your epigenetics, and
how it is affecting whether those genes are turned on or turned off. The
typical pattern associated with cancer is hypermethylation of tumor-
suppressor genes, which essentially turns those all-important protector genes
off. The trick, then, is to reverse that hypermethylation via demethylation.
There are so-called dirty demethylating drugs that can serve this purpose,
but so far, most of them demethylate indiscriminately, and can have much
broader effects than simply turning tumor-suppressor genes back on. They
are kind of like bringing a gun to a knife fight. Also, we have such a strong,
safe option available to us, and that is consuming ample amounts of DNA
methylation adaptogens, as Melissa did.
These polyphenolic epi-nutrients appear to be super important for
keeping the BRCA genes well functioning: Two in vitro studies have shown
that exposure to toxins does indeed contribute to the silencing of BRCA1 via
hypermethylation, and that resveratrol—the antioxidant present in red and
purple grapes, red wine, blueberries, cranberries, and more—reversed the
effect.10 Other studies show that, in addition to resveratrol, the flavanols
EGCG (from green tea) and genistein (from soy) also reverse
hypermethylation of BRCA1.11 Another component of soy is the isoflavone
daidzein, which is transformed by your gut microbes into equol. And equol
has been shown to not only demethylate BRCA1 and BRCA2 genes, and
thus promote re-expression of these genes, but also upregulate production of
the all-important, protective proteins that the BRCA1 and BRCA2 genes
code for.12 (About 70 percent of people don’t have the microbiome to make
equol—although those ingesting a highly polyphenol-rich, plant-based diet,
including soy, are much more likely to have the right microbiome to produce
it, another reason to follow the Younger You program.13) In other in vitro
studies, quercetin and curcumin together epigenetically enhanced BRCA1
expression via multiple mechanisms.14 These effective phytochemicals are
all parts of the Younger You Intensive and Everyday plans.
In addition, every one of us has a lot of other tumor-suppressor genes.
Luckily, many of them, including BRCA 1 or 2, have been shown to have
their genetic expression favorably altered by certain nutrients; I call any
gene for which this is true a nutrient-responsive gene. So even if you have a
BRCA 1 or 2 genetic mutation, you can support your other nutrient-
responsive tumor-suppressor genes by taking care of your DNA methylation
with the Younger You approach, and it can help all of your important
anticancer genes function their best. (And know that we are researching how
the Younger You diet and lifestyle practices influence specific nutrient-
responsive genes in humans, so our understanding will only continue to
evolve. See drkarafitzgerald.com to stay tuned for details of this important
and interesting work.)
Now that you hold in your hands a playbook for keeping your DNA
methylation balanced and younger, you know how to exert a powerful
protective influence on your genes and your risk for disease. Even cancer.
When you start making new choices, bathing your cells in the ingredients
for optimal DNA methylation and lowering the volume on outside influences
—such as pesticides, chemicals, and stress—that impair DNA methylation,
you start to clean up the epigenetic marks on your nutrient-responsive genes
and pass those improved patterns on to your own daughter cells, essentially
creating a younger, healthier, less-prone-to-cancer version of yourself.
FUTURE YOU
It’s difficult to study longevity in humans because we live for such a long
time, so there is no evidence to suggest a safe and effective dosage of
rapamycin when used to extend life. Deciding how much to take for
longevity purposes remains a guess. Biohackers are experimenting with
doses less than 6 mg per week, and some are doing this just a few weeks of
the year. The dosage prescribed for organ transplant recipients is about 5 mg
per day, continuing indefinitely; this is the dosage that triggered the
warnings about infection and cancer. But still; if extended health span is the
goal, one needs to ask, are these risks truly worth it? For some of us, it’s an
unequivocal yes. For others, it’s a “no way,” especially when there are
dietary practices and natural compounds found in food that may also inhibit
the production and accumulation of old, pro-inflammatory cells.
Another wildly popular medication taken for possible life extension (and
often also taken by those on rapamycin) is metformin, the diabetes drug that
Fahy included in his TRIIM study, which I covered in Chapter 1, and that is
the most commonly prescribed medication worldwide for type 2 diabetes
because it very effectively lowers blood sugar. It also has been shown to
inhibit mTOR and beneficially affect the microbiome, making it capable of
producing more short-chain fatty acids that reduce inflammation and support
weight loss. In animals, metformin potently extends life span and health
span; in humans, it reduces age-related diseases beyond type 2 diabetes,
including cancer and neurodegenerative diseases like Alzheimer’s.5 It’s no
wonder we’re interested in it.
While metformin is pretty well tolerated, both as a treatment for diabetes
and as an anti-aging strategy, it also has its side effects. Documented less-
than-desirable accompaniments of metformin include vitamin B12 deficiency
(which, paradoxically, negatively impacts DNA methylation); GI issues such
as diarrhea or constipation, nausea, and vomiting (a deal-breaker issue for
many); and an increased risk of lactic acidosis (which can lead to coma and
even death). While living with GI issues has its own undesirability, what
concerns me is the admittedly rare increased risk of lactic acidosis, which is
caused by metformin impairing function of mitochondria, the organelles that
metabolize macronutrients into energy, via a protein called complex 1.6
Lactic acid is produced when cellular respiration (the molecular process
of creating energy from oxygen that occurs within the mitochondria) is
inhibited. While it’s totally normal to make some lactic acid when you’re
using extra energy—like during a workout, after which that buildup of lactic
acid will make your muscles feel sore—if you are making a lot without
reason, it’s a clue that something’s going wrong within the mitochondria.
When you see very high levels of lactic acid being excreted in the urine or
circulating in the blood, it can be a full-tilt emergency known as lactic
acidosis, or, if it’s in a subclinical range, it suggests that the mitochondria are
struggling. It’s essential that our mitochondria be in great health as we age so
we want to tread lightly regarding interventions that might impair function.
While diabetics are known to biologically age more rapidly than their
nondiabetic counterparts, and metformin may be playing a role in mitigating
the accelerated aging that accompanies diabetes, science is not at all clear on
metformin’s benefits to healthy, nondiabetic individuals in terms of life span
and health span.7 To that end, a 2019 study showed that older, basically
healthy people prescribed both an aerobic exercise program and metformin
displayed problems with skeletal muscle mitochondrial respiration,
cardiorespiratory fitness, and insulin sensitivity.8 This suggests that
metformin may reduce the benefits of exercise in healthy people. If the
choice is between exercise and metformin, I recommend exercise! This and
other studies seem to suggest that metformin’s use may be best limited to
those with a chronic condition like diabetes or cancer and avoided if you are
healthy.
Testosterone has been the subject of a major marketing campaign for
men, with claims that supplementing with the male sex hormone can
increase energy, boost mental sharpness, and restore sexual function. It’s
pretty compelling stuff, and can be true in some cases, until you consider
that testosterone may also increase risk of cardiovascular problems,
including heart attack, stroke, and death from heart disease, and these risks
are more pronounced the older the men are. The risk is so significant that
researchers in a 2010 study looking at the effects of testosterone replacement
in older men (who, admittedly, had higher rates of chronic disease) pulled
the plug on the study when the participants had a noticeable uptick in heart
problems.9
Some men who take testosterone also experience acne, irregular
breathing while sleeping, and a tendency toward high red blood cell counts,
which can increase the risk of clotting. Also, once you supplement with
testosterone, the body stops producing it, making it hard to wean off. And
perhaps most troubling is the fact that testosterone is a growth promoter. It
ramps up mTOR, which rapamycin, metformin, and caloric restriction all
inhibit. Anything that pushes growth forward carries a risk of also pushing
forward cancer, because cancer is growth gone wild.
Testosterone is undeniably important, but testosterone replacement comes
with some risks. Like many other compounds we’ve discussed, the benefits
of testosterone have a U curve: too little isn’t good, but neither is too much.
A study of over three thousand men found that older men with midrange
testosterone levels tend to live longer and experience fewer bone fractures.10
That means that whether or not testosterone replacement is useful depends
on where your levels currently are.
T he majority of these recipes are appropriate for the Younger You Intensive,
although I’ve also included some that are only suited for the Younger You
Everyday.
Of course, you can eat Intensive recipes when you are following the
Everyday—and they are so tasty that I’m guessing you’ll want to add them to
your daily rotation! But unless you’re a vegetarian or a vegan and you need to
eat some legumes in order to meet your daily protein requirements while on the
Younger You Intensive (refer back to here for details), skip the Everyday recipes
while you are on the Intensive.
I’ve coded each recipe so that you can see at a glance which phase of the
program the recipe is appropriate for, as well as whether it’s keto-friendly, paleo-
friendly, vegan, or vegetarian. All recipes are gluten-free and dairy-free.
Remember that some foods are both methyl donor and DNA methylation
adaptogens, as different compounds within a food can play different, and
multiple, roles in the body. So don’t let the fact that one food appears on two
different lists confuse you (or think that we’ve made a mistake!).
RECIPE KEY:
K keto-friendly
KL keto-leaning (low carb, but not necessarily adherent to a strict keto diet)
P paleo-friendly
V vegan
VGT vegetarian
YYI Younger You Intensive
YYE Younger You Everyday
Breakfast
Basic Smoothie (YYI)
Sunberry Smoothie Bowl (YYE)
Rainbow Breakfast Bowl (YYE)
Berry Muesli (YYI)
Matcha Coconut Crunch (YYI)
Cranberry Apple Cinnamon Oatmeal (YYE)
Salmon and Spinach Omelet (YYI)
Green Eggs and Shiitake Ham (YYI)
Baked Eggs Two Ways (YYI)
Veggie-Wrap Breakfast Burrito (YYI)
Savory Onion and Chard Muffins (YYI)
Zucchini Banana Muffins (YYE)
Almond and Tartary Buckwheat Muffins (YYI)
Blueberry Beet Scones (YYI)
Chocolate Avocado Banana Bread (YYE)
Main Courses
Mix-and-Match Stir-Fry (YYI)
Spiced Salmon Cakes with Vegetable Fries (YYI)
Rosemary Chicken with Tomato, Avocado, and Bacon (YYI)
Creamy Garlicky Chicken with Cauliflower Rice (YYI)
Creamy Coconut Curry with Chicken and Vegetables (YYI)
Red Lentil and Tempeh Curry (YYE)
Epigenetic Chili (YYI for vegans and vegetarians, otherwise YYE)
Mediterranean Stuffed Pork Tenderloin with Green Beans (YYI)
Not Your Mama’s Burger with Kohlrabi Mash (YYI)
Simple Pan-Fried Steak with “Creamed” Greens (YYI)
Pan-Fried Cauliflower Steak with Creamy Lemon Garlic Greens (YYI)
DNA Methylation Minestrone (YYI)
Wild Mushroom Ragout (YYI)
Lemon Garlic Broccoli Rabe and White Bean Stew (YYI for vegans
and vegetarians, otherwise YYE)
Broccoli Pesto with Pasta (YYE)
Turkey Meatballs (YYI)
Veggie Balls in Marinara Sauce (YYI for vegans and vegetarians,
otherwise YYE)
Crispy Garlicky Tempeh with Cauliflower Rice (YYI for vegans and
vegetarians, otherwise YYE)
Cauliflower-Crust Pizza (YYI)
Beverages
Energy Boost Green Smoothie (YYI)
Vegan Megaboost Shot (YYI)
Golden Turmeric Milk (YYI)
Matcha Latte (YYI)
Beet Bubbly (YYI)
Iced Oolong Tea with Orange and Rosemary (YYI)
Calming Herbal Tonic (YYI)
Exercise Recovery Drink (YYE)
Fire Cider (YYI)
BREAKFAST • • • • • • • •
BASIC SMOOTHIE
YYI | K, P, V (if not using honey), VGT
1 serving
Prep time: 6 minutes
Smoothies are a great, easy, and delicious way to get a lot of your
methyl donors and DNA methylation adaptogens in one fell swoop—and
you only need to clean the blender! Vary these ingredients as you like,
or based on what you have on hand.
Methyl donors: green leafy vegetables (spinach, kale, Swiss chard), berries, avocado,
seeds (sunflower, pumpkin, flax, chia, hemp), shredded coconut
DNA methylation adaptogens: green leafy vegetables (that are also cruciferous, such as
collard greens, Swiss chard, kale), berries, avocado, coconut oil, seeds (sunflower,
chia), lemon, lime, shredded coconut
NUTRIENTS
(calculated using almond milk, spinach, blueberries, collagen protein, MCT
oil, 1 tablespoon pumpkin seeds, 1 tablespoon shredded coconut)
Fat: 55.8%
Carb: 19.1%
Protein: 25.1%
Calories: 351.5 kcal
Fat: 23.5 g
Carbohydrates: 18.1 g
Fiber: 4.8 g
Sugar: 9.9 g
Protein: 23.7 g
NUTRIENTS
Fat: 24.1%
Carb: 67.9%
Protein: 8%
Calories: 536.2 kcal
Fat: 15.4 g
Carbohydrates: 100.1 g
Fiber: 26.3 g
Sugar: 53.4 g
Protein: 13 g
This smoothie bowl is almost too pretty to eat! And it’s positively
loaded with methylation donor foods and adaptogens. Although all
these fruits are typically available year round, this is a dish that’s best in
summer when fruits are at their freshest.
Methyl donors: banana, apple, mango, pumpkin seeds, flax seeds
DNA methylation adaptogens: bananas, blueberries, strawberries, mango, kiwi, apple,
pumpkin seeds
NUTRIENTS
Fat: 35.2%
Carb: 54.8%
Protein: 10%
Calories: 500.3 kcal
Fat: 21 g
Carbohydrates: 73.8 g
Fiber: 15.4 g
Sugar: 43.9 g
Protein: 14.4 g
BERRY MUESLI
YYI | P, V, VGT
2 servings
Prep time: 2 minutes
This no-cook option is great for busy mornings when you don’t have
much time, and lazy mornings when you just want something easy. It
also helps you meet your daily seed requirement first thing in the
morning. This fact also makes it pretty calorically dense, meaning it will
fill you up for a long time, so it’s also good for days when you’ll be on
the go or in back-to-back meetings without easy access to food.
Using a food processor lets you adjust the consistency to your liking,
but if you don’t have one, you can dice the apple and toss it with the
other ingredients right in the bowl, top with almond milk and berries, and
voilà—breakfast!
Methyl donors: apple, sunflower seeds, pumpkin seeds, shredded coconut
DNA methylation adaptogens: apple, sunflower seeds, pumpkin seeds, shredded coconut,
berries
1. Add the apple, seeds, coconut, and salt to a food processor and
pulse until finely chopped.
2. Transfer to a bowl, pour the milk over it, and top with fresh
berries. Enjoy immediately.
NUTRIENTS
Fat: 63.7%
Carb: 25.2%
Protein: 11.1%
Calories: 376.2 kcal
Fat: 28.6 g
Carbohydrates: 23.7 g
Fiber: 7.7 g
Sugar: 11.3 g
Protein: 12 g
1. Preheat the oven to 300°F and line a large baking sheet with
parchment paper.
2. In a large bowl, combine the seeds, nuts, coconut, salt, and
matcha. Mix well.
3. In a small saucepan, melt the coconut oil until completely liquid
(unless it’s over 78 degrees in your kitchen, in which case the
coconut oil will likely already be liquid). Add the water and
sweetener and stir through.
4. Add the melted coconut oil mixture to the dry mix and toss
several times to evenly distribute. Hands work great for this!
5. Spread the mixture onto your baking sheet and press it down so
that the surface is even.
6. Bake for 12 to 15 minutes or until the nuts and seeds are toasted
and turning a light golden brown.
7. Remove from the oven and allow to cool before serving.
8. Keeps in an airtight container for several weeks.
NUTRIENTS
Fat: 75.5%
Carb: 13.9%
Protein: 10.7%
Calories: 408.8 kcal
Fat: 36.6 g
Carbohydrates: 14 g
Fiber: 6.1 g
Sugar: 3.4 g
Protein: 12.4 g
This flavorful oatmeal is like eating fall in a bowl. While all the
ingredients are health promoting, it is on the hearty side—I recommend
saving it for days when you’ll be on the go so that you can burn off
some of the carbs. (It will give you long-lasting energy, so go on that
hike or big bike ride!)
For more specific information on soaking, see here.
Methyl donors: rolled oats, apple, walnuts, maple syrup
DNA methylation adaptogens: extra-virgin olive oil, coconut oil, apple, cranberry,
cinnamon, walnut
1. Heat the oil in a pot for a couple of minutes. Add the oats to the
oil and stir to coat. Toasting the oats like this gives them more
flavor and helps prevent the oatmeal from getting clumpy.
2. Add the water and cover the pot. Allow to boil and then simmer
on low for 5 to 7 minutes.
3. Add apples, cranberries, cinnamon, and salt and stir the oatmeal
well. Continue to simmer on low-medium heat for another 5 to 10
minutes, stirring occasionally.
4. Remove from heat when the liquid is absorbed and it has
reached the consistency you like. Top with walnuts and maple
syrup and serve.
NUTRIENTS:
Fat: 27.9%
Carb: 62.8%
Protein: 9.3%
Calories: 477.6 kcal
Fat: 15.8 g
Carbohydrates: 75.4 g
Fiber: 12.7 g
Sugar: 14.6 g
Protein: 12.8 g
NUTRIENTS
Fat: 67.6%
Carb: 2.9%
Protein: 29.6%
Calories: 355.7 kcal
Fat: 26.9 g
Carbohydrates: 2.8 g
Fiber: 0.9 g
Sugar: 1.3 g
Protein: 24.7 g
NUTRIENTS
Fat: 67.3%
Carb: 7.8%
Protein: 24.9%
Calories: 235.3 kcal
Fat: 17.7 g
Carbohydrates: 5.1 g
Fiber: 2 g
Sugar: 1.7 g
Protein: 14 g
BASE OPTION 1:
½ cup shiitake mushrooms
2 cloves garlic, minced
Splash of extra-virgin olive oil
Pinch of red pepper flakes
BASE OPTION 2:
2 chicken livers, rinsed and patted dry, then chopped
1 small onion, sliced
1 tablespoon chives, chopped
Splash of extra-virgin olive oil
OPTION 1 NUTRIENTS
Fat: 70.5%
Carb: 10.2%
Protein: 19.3%
Calories: 309 kcal
Fat: 24.4 g
Carbohydrates: 8.7 g
Fiber: 1.7 g
Sugar: 4 g
Protein: 14.5 g
OPTION 2 NUTRIENTS
Fat: 57.9%
Carb: 9.5%
Protein: 32.6%
Calories: 464.1 kcal
Fat: 30 g
Carbohydrates: 11.7 g
Fiber: 1.8 g
Sugar: 6.1 g
Protein: 35.7 g
VEGGIE-WRAP BREAKFAST BURRITO
YYI | P, V, VGT
1 serving
Prep time: 10 minutes
Cook time: 10 minutes
NUTRIENTS
Fat: 66.6%
Carb: 26.4%
Protein: 7%
Calories: 546.9 kcal
Fat: 42.8 g
Carbohydrates: 38.6 g
Fiber: 11.3 g
Sugar: 18.3 g
Protein: 11.4 g
For those of you who don’t like sweet in the morning, these give you
the portability of a muffin without the cloying sweetness. Their airy
texture makes them a cross between a muffin and a frittata. And their
crunchy topping means they still give you something to sink your teeth
into with a satisfying mouthfeel. Bake these on a Sunday afternoon and
you’ll have breakfast at the ready for most of the next week.
Methyl donors: almond flour, rosemary, eggs, red onion, Swiss chard, pumpkin seeds,
garlic
DNA methylation adaptogens: almond flour, rosemary, eggs, extra-virgin olive oil, red
onion, Swiss chard, pumpkin seeds, garlic, red pepper flakes
NUTRIENTS
Fat: 75%
Carb: 15.5%
Protein: 9.5%
Calories: 374.9 kcal
Fat: 32.6 g
Carbohydrates: 14.6 g
Fiber: 3.8 g
Sugar: 2.5 g
Protein: 9.8 g
1. Preheat the oven to 350°F. Line two twelve-cup muffin tins with
cupcake liners or grease well with olive oil.
2. Combine all wet ingredients in a medium mixing bowl (banana,
zucchini, applesauce, olive oil, lemon juice, and vanilla).
3. Separately, thoroughly combine the dry ingredients in a large
mixing bowl (flour, sugar, baking soda, baking powder, cinnamon,
nutmeg, cloves, and salt).
4. Add the wet ingredients to the dry and stir well. Scoop about ¼ to
⅓ cup of the mixture into each muffin cup. Bake for 20 to 30
minutes until just beginning to brown and a toothpick inserted
comes out clean.
5. Let cool completely on a wire rack before storing.
Note: These can be frozen if needed and defrosted individually.
NUTRIENTS:
Fat: 23.7%
Carbs: 72.5%
Protein: 3.1%
Calories: 191.2 kcal
Fat: 5.2 g
Carbs: 34.8 g
Fiber: 1.7 g
Sugar: 9 g
Protein: 1.8 g
Muffins are such a great, tasty, and portable way to get your DNA
methylation–supportive nutrients, and these pack an extra punch thanks
to the Tartary buckwheat flour they contain. Thanks to Barb Schiltz, MS,
RN, CN, of the Big Bold Health FoodLab, who developed and
contributed this recipe.
Methyl donors: Tartary buckwheat, almond flour, egg
DNA methylation adaptogens: Tartary buckwheat, almond flour, egg, coconut oil
NUTRIENTS
Fat: 53.1%
Carbs: 35.4%
Protein: 12.3%
Calories: 362.2 kcal
Fat: 22.0 g
Carbs: 32.1 g
Fiber: 2.7 g
Sugar: 3.2 g
Protein: 11.2 g
These tasty (and purple!) scones come together quickly and can
satisfy an urge for something sweet without grains and with a heaping
helping of methylation-supportive nutrients. If you can’t find beet juice,
blend a roasted beet with water to thin it out to a liquid consistency. Or,
use the cooled cooking liquid after boiling your beets—while the nutrient
content hasn’t been verified by research, I suspect it has benefit. And if
you can find beet juice but balk at the price, know that it makes a great
DNA methylation adaptogen–rich addition to a glass of sparkling water
or in our Beet Bubbly (here).
Tip: This recipe can be made vegan by replacing the egg with 1 flax egg—
combine 1 tablespoon ground flax seeds with 2½ tablespoons water and let sit for
5 minutes before adding to the recipe along with the wet ingredients.
DRY INGREDIENTS:
1¼ cups almond flour
¼ cup coconut flour
¼ cup arrowroot powder
1 teaspoon baking powder
¼ teaspoon salt
1 teaspoon monk fruit sweetener or stevia powder (or 1
tablespoon honey if you are following the Younger You
Everyday)
WET INGREDIENTS:
1 teaspoon real vanilla extract (or the inside scrapings of one
vanilla pod)
1 egg
2 tablespoons coconut oil, melted
¼ cup beet juice, room temperature or slightly warm
LAST-MINUTE ADD:
½ cup blueberries, room temperature
1. Preheat the oven to 350°F. Line a baking sheet with parchment
paper.
2. Mix the dry ingredients in a medium mixing bowl until thoroughly
combined (a whisk works well at this stage).
3. In a smaller bowl, mix the wet ingredients together until well
combined.
4. Add the wet mixture to the dry mixture and stir with a spoon until
there are no more dry patches and everything is pink.
5. Add the blueberries and gently fold through.
6. Using your hands, first form the mixture into a ball and then press
down into a disc shape on your lined baking sheet. You should
get a disc that is around 6 to 7 inches diameter and about 1 inch
thick.
7. Cut the disc into eight wedges and separate them from each
other slightly.
8. Bake for around 20 minutes or until lightly golden.
9. Once done, transfer to a cooling rack and let cool completely
before enjoying.
Note: Once cooled, these can be stored in an airtight container for up to 3 days.
NUTRIENTS
Fat: 60.8%
Carb: 28.6%
Protein: 10%
Calories: 378.6 kcal
Fat: 26.8 g
Carbohydrates: 27.5 g
Fiber: 7.6 g
Sugar: 9.9 g
Protein: 10.4 g
NUTRIENTS
Fat: 67%
Carb: 23.4%
Protein: 9.6%
Calories: 304 kcal
Fat: 23.4 g
Carbohydrates: 20 g
Fiber: 6.2 g
Sugar: 5.5 g
Protein: 7.7 g
LIGHT DISHES • • • • • • • •
BASIC TEMPLATE:
TOTAL OF 5 CUPS VEGETABLES:
1–2 cups dark leafy greens
1–2 cups cruciferous vegetables
1–3 cups colorful vegetables
½ cup seeds
½ cup berries
2 cloves garlic, minced
1–2 teaspoons dried herbs or 1–2 tablespoons fresh herbs
(e.g., sage, thyme, oregano, rosemary, dill)
3–6 ounces protein of choice (e.g., salmon, chicken, pork, or if
you’re vegetarian or vegan, organic tempeh, organic tofu, or
your cooked bean of choice)
2 tablespoons extra-virgin olive oil and squeeze of lemon
TIPS/VARIATIONS
Start your own mini herb garden to have these fresh herbs
available anytime.
Use immediately or store on the countertop for up to one week.
NUTRIENTS
Fat: 90.8%
Carbs: 6.2%
Protein: 3%
Calories: 158.6 kcal
Fat: 16.9 g
Carbohydrates: 2.8 g
Fiber: 1 g
Sugar: 0.4 g
Protein: 1.4 g
1. Place all the ingredients in a clean glass jar, shake well. Or blend
in a high-powered blender for creamier dressing.
TIPS/VARIATIONS
Use immediately or store on the countertop for up to one week.
You can double or triple batch and store in the refrigerator for a
week.
NUTRIENTS
Fat: 93.9%
Carb: 5.7%
Protein: 0%
Calories: 254.9 kcal
Fat: 7.1 g
Carbohydrates: 4.1 g
Fiber: 0.3 g
Sugar: 2.2 g
Protein: 0.3 g
TURMERIC-PICKLED DAIKON
YYI | P, V, VGT
72 servings (1 serving = 1 tablespoon)
Prep time: 5 minutes
Cook time: 20 minutes
Fermenting time: 4–5 days
2 cups water
¼ cup sea salt
¼ cup unrefined organic sugar
1 teaspoon turmeric
3 medium daikon radishes, about 2 pounds
¼ cup apple cider vinegar or rice vinegar
1. Bring 1 cup of water to a simmer and add the salt, sugar, and
turmeric. Stir to dissolve the salt and sugar.
2. Meanwhile, grate the radishes and pack into a glass food jar,
leaving about 2 to 3 inches of space at the top.
3. Add the remaining cup of water and the vinegar to the brine and
let cool. Pour gently over the radishes, making sure they are
completely covered. If needed, place a small glass container or
cleaned cabbage leaf inside the top of the jar to keep the
radishes completely submerged.
4. Seal and keep in a dark, room-temperature place for 4 to 5 days.
Every couple of days, open the jar to release pressurized air and
to mix the daikon to distribute the turmeric color evenly.
Note: Store the jar in the refrigerator, where it will last up to 1 month.
NUTRIENTS
(per tablespoon serving)
Fat: 2%
Carb: 93.9%
Protein: 4.1%
Calories: 15.4 kcal
Fat 0 g
Carbohydrates: 3.8 g
Fiber: 0.6 g
Sugar: 3.2 g
Protein: 0.2 g
1. Lay your mushrooms out on a flat cookie sheet and leave out in
the sun for at least 15 minutes but up to 6 hours for maximum
vitamin D production.
2. Place all the ingredients (except saltwater brine) in a 32-ounce,
wide-mouthed Mason jar, squeezing in as much as possible.
3. Add enough brine to cover, but be sure to leave about 1 inch of
space at the top.
4. Mushrooms like to float, so weigh them down. You can use a
smaller jar or a cup inside your Mason jar.
5. Allow to sit on your counter for 5 days. After 5 days, your
mushrooms are ready to eat. Any leftovers should be stored in
the fridge.
NUTRIENTS
Fat: 11.8%
Carb: 71.1%
Protein: 17.1%
Calories: 164.7 kcal
Fat: 2.3 g
Carbohydrates: 33.1 g
Fiber: 11.7 g
Sugar: 10.9 g
Protein: 10.6 g
If you have any resistance to cabbage and/or beets, try this rich, ruby-
colored slaw. It has a knockout flavor, thanks to the cinnamon and
pomegranate seeds, that will surprise you. It also keeps well in the
fridge for up to three days; the leftovers make it easy to meet your daily
beet, colorful vegetable, and cruciferous vegetable requirement without
any additional chopping. If you’re on the Everyday version, you can add
½ cup of crumbled goat or feta cheese for an another flavor element.
(This recipe was inspired by and adapted from Edible Rhody to make it
Younger You–friendly.)
Methyl donors: cayenne pepper, shallot, cabbage, beet, parsley, walnut, pecan, pine nut
DNA methylation adaptogens: red wine vinegar, extra-virgin olive oil, cinnamon, shallot,
cabbage, beet, pomegranate, parsley, walnut, pecan
1. Mix all the vinaigrette ingredients in a small bowl and set aside.
2. Soak the sliced shallots in a small bowl with the vinegar and a
pinch of salt. Set aside.
3. Combine cabbage and beets in a large bowl and season with salt
and pepper. Add pomegranate seeds and half the vinaigrette.
Toss to coat the vegetables and let sit for 5 minutes.
4. Drain the shallots and add to cabbage mixture and toss again.
5. To serve, sprinkle with garnishes and additional vinaigrette as
desired.
NUTRIENTS
Fat: 79.9%
Carb: 17.4%
Protein: 3%
Calories: 353.1 kcal
Fat: 31.8 g
Carbohydrates: 16.8 g
Fiber: 5 g
Sugar: 9.1 g
Protein: 3.6 g
You’ve gotta love a one-pan meal. You’ll also love how the tomatoes,
parsley, capers, and chives brighten up this easy weeknight dinner.
Tip: I’m a modest green thumb at best, but I can attest that chives are a super-
easy-to-grow perennial herb (that my daughter endlessly picks and eats). It comes
back every year and has cute, puffy, purple flowers in the spring to boot.
NUTRIENTS
Fat: 58.3%
Carb: 13.9%
Protein: 27.8%
Calories: 437.1 kcal
Fat: 28.5 g
Carbohydrates: 17.5 g
Fiber: 5.9 g
Sugar: 8.9 g
Protein: 30.3 g
Methyl donors: lentils, quinoa, garlic, cumin, ginger, red onion, carrots, egg, parsley,
arugula
DNA methylation adaptogens: lentils, extra-virgin olive oil, lemon, garlic, cumin, ginger, red
bell pepper, red onion, carrot, egg, parsley, arugula
1 cup lentils
½ cup quinoa
1 cup water
1 cup vegetable broth
1 tablespoon extra-virgin olive oil, plus extra for drizzling
Juice of 1 lemon
1 or 2 cloves garlic, pressed
¼ teaspoon cumin
¼ teaspoon dried ginger
Salt and freshly ground black pepper, to taste
1 red bell pepper, diced
¼ red onion, diced
2 medium carrots, grated
3 eggs, hard boiled, roughly chopped
¾ cup roughly chopped parsley
3 cups arugula
1. In a pot, bring the water and broth to boil. Add the soaked quinoa
and lentils and reduce heat to simmer. Allow to cook for about 12
to 15 minutes until both are soft. Stir occasionally. When done,
cover and set aside to cool.
2. Prepare the dressing: In a large mixing bowl, stir together the
olive oil, lemon juice, garlic, cumin, ginger, salt, and pepper. Add
the red bell pepper, onion, carrots, eggs, and parsley and toss
with the dressing.
3. When the quinoa and lentils have cooled, add to the veggies and
mix thoroughly. Divide the arugula between two plates and top
with the quinoa lentil salad. Drizzle with olive oil and serve.
NUTRIENTS
(main dish serving size)
Fat: 37.9%
Carb: 45%
Protein: 17.1%
Calories: 577.4 kcal
Fat: 24.5 g
Carbohydrates: 66.5 g
Fiber: 13.8 g
Sugar: 12.7 g
Protein: 26.8 g
QUINOA TABBOULEH
YYE | V, VGT
2 servings
Prep time: 15 minutes, plus presoak and resting time for the quinoa
Cook time: 30 minutes
NUTRIENTS
Fat: 51.5%
Carb: 40.6%
Protein: 7.9%
Calories: 537.8 kcal
Fat: 31.3 g
Carbohydrates: 56.8 g
Fiber: 9.4 g
Sugar: 13.1 g
Protein: 12.1 g
Methyl donors: red lentils, onion, garlic, chicken stock, cumin, turmeric, butternut squash
DNA methylation adaptogens: red lentils, onion, garlic, chicken stock, cumin, turmeric,
cinnamon, butternut squash, lemon
1. Place all ingredients except the lemon juice, salt, and spices in a
large, deep saucepan.
2. Bring to a boil and simmer until everything is tender, about 20
minutes. The squash should start to melt into the soup.
3. Add the lemon juice, salt, and spices and stir to combine.
NUTRIENTS
Fat: 38%
Carb: 47.5%
Protein: 14.6%
Calories: 512.9 kcal
Fat: 23 g
Carbohydrates: 62.1 g
Fiber: 11.1 g
Sugar: 11.7 g
Protein: 20.9 g
Crackers just make life better. And since these have no grains and no
gluten and are chock-full of methyl donor and DNA methylation
adaptogens, they also help make your DNA methylation better. I
recommend using Bob’s Red Mill coconut flour here because it has a
mild flavor; some other brands have a stronger coconut taste.
Tip: You can make these crackers vegan by replacing the two eggs with 2
tablespoons of ground flax seeds soaked in 6 tablespoons of water for 15
minutes. You can also replace the sesame seeds, poppy seeds, dried onion, dried
garlic, and salt with a scant 2 tablespoons of an “everything” spice blend.
Methyl donors: coconut flour, flax seeds, sesame seeds, poppy seeds, garlic, onion, eggs,
almond butter
DNA methylation adaptogens: coconut flour, garlic, onion, almond butter, coconut oil
1. Preheat the oven to 350°F and prepare a baking tray lined with
greased parchment paper or a silicone liner.
2. Combine the dry ingredients in a medium bowl and mix until
evenly distributed.
3. In a separate bowl, whisk together the eggs, almond butter, and
coconut oil.
4. Add the wet mixture to the dry and mix until a thick ball of dough
forms. Press the ball of dough onto a piece of parchment paper
and flatten as much as possible with your hands.
5. Place another piece of parchment paper over the top of the
dough to avoid sticking and roll it out with a rolling pin until it is
about ⅛ inch thick. Remove the top layer of parchment and
transfer dough to prepared baking tray.
6. With a sharp knife or pizza cutter, deeply score the dough with
vertical and horizontal lines to create individual crackers that are
around 1½ inches square.
7. Bake in the oven for about 15 minutes, watching closely so that
they don’t brown. You’re looking for a golden color.
8. Remove the crackers from the oven and let them cool on the tray
for about 5 minutes, until you can handle them easily. Break the
crackers along the scored lines and let them finish cooling on a
wire rack.
Note: Once completely cooled, the crackers can be stored in an airtight container
for up to 3 days.
NUTRIENTS
Fat: 71.5%
Carb: 16.2%
Protein: 12.2%
Calories: 321.1 kcal
Fat: 26.6 g
Carbohydrates: 12.6 g
Fiber: 7.8 g
Sugar: 2 g
Protein: 10.4 g
These are similar to the “Everything” Seed Crackers (here), but since
crackers are so handy for snacks or light meals, and travel well, I think
you’ll enjoy having an additional cracker recipe with a different flavor
profile in your repertoire.
Tip: You can make these crackers vegan by replacing the egg with 1 tablespoon
of ground flax seeds soaked in 3 tablespoons of water for 15 minutes.
1. Preheat the oven to 350°F and prepare a baking tray lined with
greased parchment paper or a silicone liner.
2. In a medium bowl, combine the almond flour and baking soda
until the baking soda is evenly distributed.
3. In a separate bowl, beat the egg, stir in the garlic, and then add
to the dry mixture.
4. Work the egg through the flour mixture with your hands and form
into a ball of dough.
5. Press the ball of dough onto a piece of parchment paper and
flatten as much as possible with your hands.
6. Place another piece of parchment paper over the top of the
dough to avoid sticking and roll it out with a rolling pin until it is
about ⅛ inch thick. Remove the top layer of parchment and
transfer dough to the prepared baking tray.
7. Using a pastry brush, brush the olive oil evenly over the top of
the dough. Sprinkle the rosemary and sea salt evenly over the
top and lightly press with your hands.
8. With a sharp knife or pizza cutter, deeply score the dough with
vertical and horizontal lines to create individual crackers that are
about 1½ inches square.
9. Bake in the oven for 15 to 20 minutes until golden, watching
closely so that they don’t get too brown.
10. Remove the crackers from the oven and let them cool on the tray
for about 5 minutes, until you can handle them easily. Break the
crackers along the scored lines and let them finish cooling on a
wire rack.
Note: Once completely cooled, the crackers can be stored in an airtight container
for up to 3 days.
NUTRIENTS
Fat: 75.1%
Carb: 12.3%
Protein: 12.6%
Calories: 501.7 kcal
Fat: 44.4 g
Carbohydrates: 15.3 g
Fiber: 7.9 g
Sugar: 3.4 g
Protein: 17.6 g
NUTRIENTS
Fat: 76.4%
Carb: 14.2%
Protein: 9.3%
Calories: 294.1 kcal
Fat: 26.6g
Carb: 10.8g
Fiber: 7.2g
Sugar: 1.6g
Protein: 8g
If you don’t think you’re a liver person, this makes a great gateway dish.
Inspired by a luxurious pâté that our chief nutritionist, Romilly Hodges,
had at a restaurant in the South of Spain, this version delivers a
sumptuous richness and a heaping helping of methylation-supportive
nutrients. Serve it with either “Everything” Seed Crackers or Rosemary
and Sea Salt Crackers, or with crudités.
Tip: Don’t skip the step of presoaking the cashews—it helps make this spread so
creamy. (See here for more information on soaking.)
1. In a medium saucepan on low heat, add the olive oil and onion
and sauté for 5 to 7 minutes, until the onion has softened.
2. Add the bacon, cashews, and chicken livers to the pan. Continue
to sauté for 12 to 15 minutes, until the livers and bacon are
cooked through.
3. Add the seasonings and stir for another minute or so. Take off
the heat and let cool 5 to 10 minutes.
4. Transfer the mixture to a food processor and process until
completely smooth. You may need to stop intermittently to scrape
down the sides and/or add a little water to achieve a spreadable
consistency.
5. Once cool, store in the refrigerator until ready to use.
Note: Will store in the refrigerator for up to 3 days. It freezes well, too, if you don’t
want to use it all at once. (Thaw in the fridge overnight before serving.)
NUTRIENTS
Fat: 53%
Carb: 7.3%
Protein: 39.6%
Calories: 240.1 kcal
Fat: 14.4 g
Carbohydrates: 4.5 g
Fiber: 0.6 g
Sugar: 1.2 g
Protein: 22.7 g
This dip will delight your taste buds and your eyes. It’s great paired
with sliced vegetables, served on top of a salad, or eaten with our
“Everything” Seed Crackers (here). This recipe was inspired by a recipe
by Melissa Clark in the New York Times—we adapted it to make it
Younger You–compliant and even more DNA methylation–friendly.
Tip: If you hate peeling beets, boil them whole and unpeeled. They will take 45 to
60 minutes to cook through, depending on size, but the peels will slip right off.
1. Place beets in a pot and cover with water and a lid. Place the
walnuts in a small bowl and cover with water; set aside to soak
while the beets cook.
2. Bring beets to a boil, then reduce heat to a simmer. Cook the
beets for 15 to 20 minutes, until tender.
3. Remove the beets from the water and let them cool. Meanwhile,
drain and rinse walnuts.
4. Place all of the ingredients in a food processor and puree.
Note: Will keep in the refrigerator for up to 5 days.
VARIATIONS:
Substitute sunflower seeds for the walnuts.
Add a dash of cayenne pepper if you want a little kick.
NUTRIENTS
Fat: 49.3%
Carb: 43.9%
Protein: 6.8%
Calories: 81 kcal
Fat: 4.7 g
Carbohydrates: 9.6 g
Fiber: 1.8 g
Sugar: 4.4 g
Protein: 1.6 g
Methyl donors: sunflower seeds, pumpkin seeds, garlic, rosemary, flaxseed oil
DNA methylation adaptogens: sunflower seeds, garlic, rosemary, pumpkin seeds
NUTRIENTS
Fat: 80.5%
Carb: 10.1%
Protein: 9.4%
Calories: 168.7 kcal
Fat: 15.9 g
Carbohydrates: 4.2 g
Fiber: 1.8 g
Sugar: 0.5 g
Protein: 4.6 g
NUTRIENTS
Fat: 53.2%
Carb: 38.2%
Protein: 8.5%
Calories: 297.2 kcal
Fat: 18.6 g
Carbohydrates: 32.8 g
Fiber: 12.4 g
Sugar: 16.4 g
Protein: 8.9 g
Tantalize your taste buds and give your cells a boost with this fragrant
spiced rice. I like Lundberg rice as a base for this, since it is grown
organically and tested for heavy metal contamination (rice can easily
pick up heavy metals such as arsenic from the environment, so a good
quality source is important). It goes perfectly as a side dish with
chicken, lamb, whitefish, or legumes.
Methyl donors: cardamom, turmeric, cumin, curry, chili powder, onion, garlic, brown rice,
cilantro
DNA methylation adaptogens: coconut oil, cinnamon, turmeric, cumin, curry, onion, garlic,
cilantro
1. In a large sauté pan, heat the oil over medium heat. Add the bay
leaf, cardamom pods, cinnamon stick, turmeric, cumin seeds,
and curry, if using. Warm the spices gently until they become
fragrant.
2. Add the onion and sauté for 7 to 10 minutes until translucent.
Add the garlic and cook another few minutes before adding the
rice.
3. Stir frequently until the rice is fully heated through and completely
coated in the spices.
4. Take off the heat, remove the bay leaf, and add salt and pepper
to taste. Transfer to a serving dish and top with the cilantro
leaves.
NUTRIENTS
Fat: 25.8%
Carb: 67.8%
Protein: 6.4%
Calories: 308 kcal
Fat: 9 g
Carbohydrates: 51.4 g
Fiber: 4.4 g
Sugar: 2.1 g
Protein: 5.9 g
NUTRIENTS
Fat: 48%
Carb: 20.6%
Protein: 31.4%
Calories: 255.3 kcal
Fat: 14.5 g
Carbs: 12.3 g
Fiber: 4.2 g
Sugar: 6.1 g
Protein: 23.1 g
MAIN COURSES • • • • • • • •
MIX-AND-MATCH STIR-FRY
YYI | K, P, [V], [VGT]
1–2 main dish–sized servings or 2–4 side dish–sized servings
Prep time: 20 minutes
Cook time: 20 minutes
This is an adaptive recipe where you can use most of the ingredients
from the Mix-and-Match Rainbow Salad (here) and easily turn them into
a warm stir-fry—a nice change for when the weather is cold. It is easily
adaptable to vegetarian and vegan diets, too. Together, these two
recipes (really, more like templates) can cover the majority of your
meals if you, like me, like to keep your meal prep as simple as possible.
Methyl donors: kale, spinach, carrots, cabbage, pumpkin seeds, sunflower seeds, thyme,
parsley, oregano, rosemary, sage, salmon, chicken, pork, tofu
DNA methylation adaptogens: kale, spinach, cruciferous vegetables, red bell pepper,
carrots, cabbage, sunflower seeds, berries, extra-virgin olive oil, thyme, parsley,
oregano, rosemary, sage, salmon, chicken, pork, tempeh, tofu, coconut oil, lemon
BASE TEMPLATE:
TOTAL OF 5 CUPS VEGETABLES:
1–2 cups dark leafy greens
1–2 cups cruciferous vegetables
1–3 cups colorful vegetables
½ cup seeds
2 cloves garlic, minced
2 teaspoons fresh or dried herbs (e.g., sage, thyme, oregano,
rosemary, dill)
3–6 ounces protein of choice (e.g., salmon, chicken, pork,
scallops, or, if you’re vegetarian or vegan, organic tempeh,
organic tofu, or your favorite cooked bean)
1. Heat oil in a large sauté pan over medium heat. Add garlic and
cook for 2 minutes, stirring frequently.
2. Add carrot, purple cabbage, and red bell pepper and cook for 3
to 5 minutes. Add kale and spinach (and plant-based protein, if
using) and cook for an additional 3 to 5 minutes. Remove from
heat.
3. For the salmon, heat coconut oil on medium heat in a medium
sauté pan. Cook the salmon on one side for 3 to 5 minutes until
lightly brown, then flip and cook another 3 to 5 minutes, until
thoroughly done.
4. Squeeze lemon on top, season with salt and pepper, and serve
alongside vegetables, garnished with seeds.
VARIATIONS:
Switch up your veggies, including a variety of dark leafy greens
and cruciferous and colorful vegetables.
Top with various herbs and spices, such as chives, oregano, dill,
rosemary, sage, thyme, and cilantro, or with the Herbal
Epigenetic Dressing (here).
Add coconut aminos for additional flavor.
NUTRIENTS
(main dish serving size)
Fat: 66.4%
Carb: 15.1%
Protein: 18.4%
Calories: 626.9 kcal
Fat: 47.7 g
Carbohydrates: 25.2 g
Fiber: 7.9 g
Sugar: 11.2 g
Protein: 29.7 g
Yes, salmon is great cooked simply, with just a little extra-virgin olive
oil, salt, and pepper. But when you want a full taste sensation, try these
flavorful salmon cakes.
Tip: Kohlrabi can be hard to find. Peeled broccoli stems make a great substitute,
as they have a similar texture and taste. Plus, using them reduces food waste.
Methyl donors: kohlrabi, broccoli, beets, salmon, garlic, eggs, arrowroot powder, turmeric,
sesame seeds, chives, avocado, onion powder
DNA methylation adaptogens: extra-virgin olive oil, kohlrabi, broccoli, summer squash,
beets, salmon, red bell pepper, scallions, garlic, eggs, turmeric, chives, avocado,
flaxseed oil, lemon, onion powder, red pepper flakes
NUTRIENTS
Fat: 60.3%
Carb: 19.5%
Protein: 20.2%
Calories: 780.8 kcal
Fat: 53.4 g
Carbohydrates: 40.7 g
Fiber: 14.7 g
Sugar: 15 g
Protein: 39.5 g
There’s nothing fancy about this dish—it’s really just baked chicken
thighs with simple accompaniments that, except for the bacon, don’t
need to be cooked. But the luscious combination of the fat from the
avocado, the salty crunch of the bacon (which should be nitrite-free and,
ideally, organic), and the brightness of the tomato makes this weeknight
meal an embodiment of comfort food.
Methyl donors: chicken, rosemary, pork, avocado, tomato, garlic
DNA methylation adaptogens: chicken, pork, rosemary, tomato, avocado, garlic, olive oil
NUTRIENTS
Fat: 54.6%
Carb: 9.7%
Protein: 35.6%
Calories: 637.4 kcal
Fat: 39.5 g
Carbohydrates: 17.2 g
Fiber: 7.9 g
Sugar: 7 g
Protein: 54.8 g
This flavorful meal warms the body on a cold day and can easily be
made vegetarian by substituting legumes or organic tempeh for animal
protein, or simply omitting the chicken, and vegan by also omitting the
optional honey. You can also mix and match any vegetables you have
on hand, such as cauliflower, kale, carrots, and cabbage, making it a
great way to use up your produce before it goes bad. It’s one of my
favorite Younger You Intensive meals (and Izzy’s, too!).
Methyl donors: bok choy, broccoli, carrot, arrowroot powder, cashew, cauliflower, chicken,
cilantro, cumin, curry, garlic, ginger, onion, pumpkin seeds, turmeric
DNA methylation adaptogens: bok choy, broccoli, carrot, cashew, cauliflower, cilantro,
coconut oil, cumin, curry, garlic, ginger, lime, onion, turmeric, zucchini, red pepper flakes,
pumpkin seeds
NUTRIENTS
(calculated using pumpkin seeds)
Fat: 49%
Carb: 21.3%
Protein: 29.7%
Calories: 651.2 kcal
Fat: 36.9 g
Carbohydrates: 38 g
Fiber: 13.3 g
Sugar: 16.4 g
Protein: 51.3 g
NUTRIENTS
Fat: 35.7%
Carb: 47.8%
Protein: 16.6%
Calories: 600.2 kcal
Fat: 25.1 g
Carbohydrates: 70.9 g
Fiber: 11.4 g
Sugar: 6.2 g
Protein: 29.1 g
EPIGENETIC CHILI
YYE | YYI (V or VGT) | [V], [VGT]
8 servings
Prep time: 20 minutes, plus presoak time for the beans
Cook time: 1 hour
This filling but still brightly flavored (i.e., not heavy-tasting) chili makes
a large portion that is perfect for feeding the entire family, or for having
leftovers for later in the week. It tastes great eaten warm, of course, but
it’s also great served cold on a hot summer day. And it’s easy to make
vegetarian or vegan by swapping the turkey for steamed and crumbled
tempeh and opting for vegetable broth or water instead of bone broth.
Methyl donors: tomatoes, garlic, red onion, turkey, cumin, chili powder, thyme, sage, black
beans, kidney beans, maple syrup
DNA methylation adaptogens: tomatoes, coconut oil, bell peppers, garlic, red onion, cumin,
chili powder, thyme, sage, black beans, kidney beans, green onion
NUTRIENTS
Fat: 42.9%
Carb: 31.9%
Protein: 25.2%
Calories: 309.5 kcal
Fat: 14.8 g
Carbohydrates: 26.5 g
Fiber: 7.8 g
Sugar: 10.3 g
Protein: 21.1 g
If you’ve ever felt pork tenderloin was too bland, or too dry, this recipe
will change your mind. Stuffed with flavor-rich DNA methylation
adaptogens, including sun-dried tomatoes, sunflower seeds, and
capers, this dish tastes like it takes a lot more time to prepare than it
does. Although it’s easy enough for a weeknight dinner, it’s tasty
enough for entertaining—and your guests will never suspect you’re
serving them a health-focused dinner.
Tip: If you don’t have butcher’s twine, you can use toothpicks to keep the
tenderloin together—just leave enough of them sticking out that they are easy to
remove before slicing and eating.
Methyl donors: pork, sunflower seeds, tomatoes, garlic, rosemary, flax seeds
DNA methylation adaptogens: pork, sunflower seeds, tomatoes, garlic, capers, Mexican
oregano, rosemary, red chili pepper, extra-virgin olive oil, lemon, green beans
NUTRIENTS
Fat: 49%
Carb: 12.9%
Protein: 38.1%
Calories 393.9 kcal
Fat: 22.1 g
Carbohydrates: 14.6 g
Fiber: 5.2 g
Sugar: 5.5 g
Protein: 36.8 g
Methyl donors: beef, beets, rosemary, apple cider vinegar, garlic, kohlrabi, turnip
DNA methylation adaptogens: beets, rosemary, coconut oil, extra-virgin olive oil, apple
cider vinegar, garlic, grapefruit, lemon, kohlrabi, turnip
NUTRIENTS
Fat: 71.3%
Carb: 8.9%
Protein: 19.8%
Calories: 487.1 kcal
Fat: 38.3 g
Carbohydrates: 11.1 g
Fiber: 4 g
Sugar: 6.5 g
Protein: 24.1 g
SIMPLE PAN-FRIED STEAK WITH “CREAMED”
GREENS
YYI | KL, P
2 servings
Prep time: 5 minutes
Cook time: 30 minutes plus 3 minutes resting time for the steaks
NUTRIENTS
(calculated without the optional coconut milk)
Fat: 47.2%
Carb: 13.9%
Protein: 38.9%
Calories: 564.1 kcal
Fat: 30.7 g
Carbohydrates: 21.6 g
Fiber: 7.6 g
Sugar: 4.9 g
Protein: 57.2 g
Methyl donors: cauliflower, onion, spinach, kale, garlic, pine nuts, cashews
DNA methylation adaptogens: cauliflower, extra-virgin olive oil, onion, spinach, kale, garlic,
Mexican oregano, lemon, cashews
FOR THE GREENS:
¼ cup pine nuts (optional)
1 tablespoon extra-virgin olive oil
1 medium onion, diced
5 ounces frozen chopped spinach (or 11 cups fresh, cleaned
and chopped)
5 ounces frozen chopped kale (or 8 cups fresh, cleaned, de-
stemmed, and chopped)
2 cloves garlic, minced
¼ cup low-sodium vegetable broth
2 tablespoons fresh Mexican oregano, finely chopped
Salt and freshly ground black pepper, to taste
NUTRIENTS
Fat: 59.7%
Carb: 30.1%
Protein: 10.2%
Calories: 502 kcal
Fat: 35 g
Carb: 40.6 g
Fiber: 13.1 g
Sugars: 12.8 g
Protein: 18 g
1. In a food processor, blend the turkey and liver. Place the ground
meat into a bowl and mix in the egg, parsley, salt, and pepper by
hand. Allow mixture to set, covered, in the refrigerator for at least
1 hour.
2. Once the meat has set, form small meatballs, about 1 inch in
diameter.
3. In a large stockpot or Dutch oven, heat 2 tablespoons olive oil
over medium-low heat. Cook the meatballs until golden all over, 6
to 8 minutes. Set aside.
4. In the same stockpot, heat the remaining 2 tablespoons of oil.
Add the garlic, onions, carrots, celery, and mushrooms. Sauté,
stirring occasionally, for 3 to 5 minutes.
5. Add the tomatoes, water, zucchini, butternut squash, asparagus,
bay leaf, oregano, and rosemary and bring to a low simmer.
6. Carefully place the turkey meatballs in the soup, covering them
with as much broth as possible.
7. Simmer for 15 minutes. Test one meatball to make sure the meat
has cooked through.
8. Once meatballs are done, turn off the heat and remove the
rosemary sprig if you used one (the leaves should have fallen off)
and the bay leaf. Add the spinach and stir the soup until the
spinach wilts. Season with salt and pepper to taste.
9. Garnish with parsley and serve.
NUTRIENTS
Fat: 53.1%
Carb: 20.3%
Protein: 26.6%
Calories: 411.4 kcal
Fat: 24.5 g
Carbohydrates: 23 g
Fiber: 7.9 g
Sugar: 8.5 g
Protein: 28.8 g
The more I learn about mushrooms, with their high quantities of methyl
donors and DNA methylation adaptogens, the deeper I fall in love with
them. This dish puts them front and center. It also proves how hearty a
plant-based meal can be. Try serving it over garlicky sautéed greens
with some Rosemary and Sea Salt Crackers. (And if you’re not vegan, a
fried or poached egg is great with it, too.) If you can’t find kohlrabi, try
peeled broccoli stems—they have a similar taste and texture and are
also DNA-methylation friendly.
Methyl donors: onions, carrots, kohlrabi, broccoli, shiitake mushrooms, tomatoes, garlic,
arrowroot powder, parsley
DNA methylation adaptogens: extra-virgin olive oil, onions, carrots, broccoli, kohlrabi,
tomatoes, garlic, parsley
1. In a large saucepan with a lid, gently heat the oil over medium
heat and add the onions, carrots, kohlrabi, and mushrooms.
2. Cover and cook, stirring intermittently, until everything is soft,
about 30 minutes.
3. Add the tomatoes, garlic, and arrowroot powder. Stir well and
cook 1 to 2 minutes more.
4. Add the vegetable broth and season to taste. Bring to a boil, then
turn the heat down low and cook for another 10 minutes, until the
flavors have mellowed and blended together.
5. Serve in two bowls topped with the parsley.
NUTRIENTS
Fat: 39.5%
Carb: 53.1%
Protein: 7.4%
Calories: 345 kcal
Fat: 15.5 g
Carbohydrates: 48.8 g
Fiber: 10.7 g
Sugar: 15.7 g
Protein: 9.6 g
1. Steam the broccoli rabe in a large covered pot until stalks are
fork soft (5 to 7 minutes), adding the sliced garlic with 2 to 3
minutes remaining.
2. Transfer the broccoli rabe and garlic to a large skillet over
medium heat. Add the MCT oil, ⅛ cup of the olive oil, lemon, salt,
and pepper, making sure to fully coat the broccoli rabe. Cook and
occasionally stir for about 3 minutes until lemon is soft and
slightly brown. Broccoli rabe should be a vibrant green and
slightly crisp.
3. Add the beans and water and heat until everything begins to boil.
Reduce to a low heat and simmer; continue to cook and carefully
stir occasionally (for about 3 to 4 minutes) until the flavors
combine and the liquid is reduced by half (the remaining liquid
acts as a light sauce).
4. Transfer everything to a serving plate or bowl, sprinkle the
remaining olive oil and rosemary over the top, and serve.
NUTRIENTS
(main dish serving size)
Fat: 44%
Carb: 41.5%
Protein: 14.6 %
Calories: 425.8 kcal
Fat: 21.7 g
Carbs: 44.2 g
Fiber: 13.2 g
Sugars: 1.2 g
Protein: 19 g
This pesto, inspired by a recipe in the New York Times, gets additional
depth from broccoli florets (which, as a cruciferous vegetable, are both
a methyl donor and a DNA methylation adaptogen) and from some of
our favorite DNA methylation adaptogenic herbs. It makes a great dip
on its own, or serve it over chickpea, lentil, mung bean, or kelp pasta.
Top it with Rosemary, Garlic, and Lemon Olives (here) for even more
flavor.
Methyl donors: broccoli, garlic, basil, oregano, thyme, walnuts, sunflower seeds,
chickpeas, lentils, mung beans, kelp
DNA methylation adaptogens: broccoli, garlic, basil, oregano, thyme, walnuts, sunflower
seeds, lemon, extra-virgin olive oil, chickpeas, lentils, kelp, red pepper flakes
8 cups water
4 cups broccoli florets
1 (8-ounce) package gluten-free chickpea, lentil, mung bean,
or kelp pasta
2 cloves garlic
2 cups fresh basil leaves
2 tablespoons oregano
2 tablespoons thyme
½ cup walnuts or sunflower seeds, soaked in water for at least
1 hour
1 lemon, zested and juiced
½ cup extra-virgin olive oil, plus more for serving
Salt and freshly ground black pepper, to taste
Red pepper flakes (optional)
NUTRIENTS
(includes 2 ounces of dry chickpea pasta per serving)
Fat: 74.8%
Carb: 17.9%
Protein: 7.3%
Calories: 429.1 kcal
Fat: 36.8 g
Carbohydrates: 20.2 g
Fiber: 5.6 g
Sugar: 3.5 g
Protein: 8.9 g
TURKEY MEATBALLS
YYI | K, P
2 servings
Prep time: 15 minutes
Cook time: 25 minutes
NUTRIENTS
Fat: 63.9%
Carb: 8.7%
Protein: 27.3%
Calories 524.6 kcal
Fat: 38.5 g
Carbohydrates: 11.5 g
Fiber: 7 g
Sugar: 1.7 g
Protein: 37.4 g
VEGGIE BALLS IN MARINARA SAUCE
YYE | YYI (VGT and V) | VGT, V
4 servings
Prep time: 20 minutes plus 15 minutes to cook the quinoa
Cook time: 45 minutes
These veggie balls are little nuggets of deliciousness. Try serving them
over zucchini noodles for a full pasta-like experience. If you can’t find
Mexican oregano, regular oregano is a good substitute; it’s not as high
in luteolin (a powerful DNA methylation adaptogen) as Mexican
oregano, but it does have some adaptogenic compounds in it.
Methyl donors: tomatoes, onion, garlic, shiitake mushrooms, broccoli, beets, quinoa,
almond, eggs
DNA methylation adaptogens: tomatoes, onion, garlic, red pepper flakes, Mexican
oregano, extra-virgin olive oil, broccoli, beet, almond, eggs, broccoli sprouts
TO GARNISH:
Broccoli sprouts
NUTRIENTS
Fat: 43.3%
Carb: 44.6%
Protein: 12.1%
Calories 287.2 kcal
Fat: 14.4 g
Carbohydrates: 34 g
Fiber: 10.1 g
Sugar: 11 g
Protein: 10.2 g
NUTRIENTS
Fat: 59.3%
Carb: 23.4%
Protein: 17.3 %
Calories: 552.5 kcal
Fat: 38.1 g
Carbs: 33.6 g
Fiber: 9.9 g
Sugars: 14.4 g
Protein: 28.9 g
CAULIFLOWER-CRUST PIZZA
YYI | KL, P, VGT
2 servings
Prep time: 40 minutes
Cook time: 30 minutes
This yummy pizza has only a mild cauliflower flavor that supports the
tangy tomato and red onion sauce. And the dough holds together well.
You could make it even more DNA methylation–friendly by adding some
mushrooms and colorful bell peppers as toppings.
Methyl donors: cauliflower, eggs, garlic, red onion, tomatoes, basil
DNA methylation adaptogens: cauliflower, eggs, garlic, red onion, tomatoes, basil
1. Set the oven to 400°F and line a baking sheet with parchment
paper. If you have a pizza stone, place it in the oven.
2. If you are using fresh cauliflower, chop it into 2-inch pieces and
then pulse in a food processor until you have a texture that
resembles rice.
3. Steam the cauliflower for fifteen minutes until tender. Allow to
cool so that you can handle it, then transfer to a clean kitchen
cloth, wrap it up and squeeze it well to remove as much water as
possible.
4. In a medium mixing bowl, beat the eggs with the arrowroot
powder, then add the garlic and salt. Stir to combine.
5. Add the riced cauliflower to the egg mixture, season with salt and
pepper, and keep stirring until everything is well distributed.
6. Press the mixture onto your prepared baking sheet, forming a
circular pizza shape. Aim for about ½-inch thickness. Bake the
crust for about twenty minutes.
7. Meanwhile, stir the marinara sauce and tomato paste together
until evenly combined.
8. Remove the crust from the oven and spread the tomato sauce
carefully over it. Top with the red onions and bake for another 10
to 12 minutes or until the edges are a touch browned and the
onions slightly toasted.
9. Garnish with basil and serve immediately.
NUTRIENTS
Fat: 22.1%
Carb: 60.1%
Protein: 17.8%
Calories 260.1 kcal
Fat: 6.4 g
Carbohydrates: 41.8 g
Fiber: 9.5 g
Sugar: 16.3 g
Protein: 14.3 g
SNACKS AND SWEETS • • • • • • • •
Methyl donors: cauliflower, tahini, tomato, apple cider vinegar, cayenne pepper, garlic
powder, onion powder, turmeric
DNA methylation adaptogens: cauliflower, extra-virgin olive oil, tomato, apple cider vinegar,
garlic powder, onion powder, turmeric
1 head cauliflower
1 tablespoon tahini
1 tablespoon extra-virgin olive oil
1 tablespoon tomato paste
1 tablespoon apple cider vinegar
1 teaspoon cayenne pepper (omit if you don’t want it spicy)
1 teaspoon garlic powder
1 teaspoon onion powder
1 teaspoon turmeric
1 teaspoon salt
Freshly ground black pepper, to taste
¼ cup water
1. Preheat the oven to 350°F and lightly oil a large baking sheet.
2. Chop the cauliflower into bite-size pieces. (It makes it easier to
slice off any leaves first, then start separating the florets from
underneath.)
3. In a large mixing bowl, stir all the remaining ingredients into a
smooth paste.
4. Add the cauliflower pieces to the mixing bowl and use your
hands to mix them with the paste until it is evenly distributed.
5. Spread the coated cauliflower onto the baking sheet and bake in
the oven for 40 to 45 minutes, until slightly crunchy on the
outside and soft on the inside.
6. Serve immediately, while still warm.
NUTRIENTS
Fat: 51%
Carb: 38.6%
Protein: 10.4%
Calories: 101.6 kcal
Fat: 5.9 g
Carbohydrates: 10.7 g
Fiber: 3.9 g
Sugar: 3.5 g
Protein: 4 g
Earthy. Salty. Crunchy. These beet chips satisfy the urge for a
processed snack without the high sodium and low-quality oils most
chips are cooked in.
Methyl donors: beets
DNA methylation adaptogens: beets, extra-virgin olive oil
1. Preheat the oven to 300°F. Lightly oil two large baking sheets.
2. Cut the ends off and slice the beets very thin. I highly
recommend a mandolin or the slicer disc of your food processor
for this, but a sharp chef’s knife will do in a pinch.
3. Place the beets in a medium bowl and sprinkle with the salt.
Work the salt into the beet slices so that they are all well salted.
Let sit for 30 minutes.
4. Drain any water that comes off the beets and pat them dry with a
paper towel. Drizzle the olive oil over the beets and toss with
your hands to evenly coat them. (Beware—this will turn your
hands purple temporarily!)
5. Lay the beet slices onto the baking sheets and bake for 30
minutes. Then check them every 5 minutes, removing the beets
that have curled and crisped up each time you check. (It could
take up to another 30 minutes for all the chips to finish cooking.)
Note: Any leftover chips can be stored in a glass container on the counter for up to
a week, but they’re so yummy I doubt they’ll last that long!
NUTRIENTS
Fat: 78.1%
Carb: 19.5%
Protein: 2.4%
Calories: 77.3 kcal
Fat: 6.8 g
Carbohydrates: 3.9 g
Fiber: 1.1 g
Sugar: 2.8 g
Protein: 0.7 g
ROSEMARY, GARLIC, AND LEMON OLIVES
YYI | K, P, V, VGT
6 servings
Prep time: 5 minutes
Cook time: 5 minutes plus 5–10 minutes for cooling
Take the flavor of your favorite olives up several notches with garlic,
rosemary, and lemon zest—a great-tasting combination that’s also
superfood for your genes. These olives are yummy as a snack, or pair
with roasted chicken and a green salad for a satisfying meal.
Tip: You can use olives that have been pitted or that still have their pits.
1. To a medium saucepan over medium heat, add the olive oil, zest,
rosemary, and garlic and cook, stirring, until the garlic just starts
to brown, about 5 minutes. Be careful not to let the garlic burn.
2. Remove from the heat and let cool.
3. Stir the olives into the seasoning mixture.
Note: The olives will keep in the refrigerator for up to 5 days. Best served at room
temperature or slightly warmed.
NUTRIENTS
Fat: 95.4%
Carb: 0%
Protein: 3.8%
Calories: 201.7 kcal
Fat: 22.8 g
Carbohydrates: 2.4 g
Fiber: 4.1 g
Sugar: 0 g
Protein: 2.1 g
Nuts and seeds are great to eat completely unadorned. But when you
add a little cinnamon, a touch of sweetener, and just a bit of salt, they
become a taste sensation. You honestly won’t feel like you’re following
any kind of healthy eating plan with these.
Methyl donors: pecans, pumpkin seeds, sunflower seeds, sesame seeds
DNA methylation adaptogens: pecans, sunflower seeds, pumpkin seeds, shredded
coconut, cinnamon, extra-virgin olive oil
NUTRIENTS
Fat: 81%
Carb: 9.6%
Protein: 9.4%
Calories: 610.2 kcal
Fat: 58.8 g
Carbohydrates: 14.5 g
Fiber: 8.5 g
Sugar: 2.4 g
Protein: 16.6 g
NUTRIENTS
Fat: 64.5%
Carb: 25.5%
Protein: 9.5%
Calories: 168.4 kcal
Fat: 12.9 g
Carbohydrates: 11.3 g
Fiber: 2.8 g
Sugar: 6.4 g
Protein: 4.6 g
These gummies have a rich purple color and a tart flavor with a hint of
coconut. You can cut them into squares, or use small cookie cutters to
cut them into kid-friendly shapes. Agar-agar is a plant-based alternative
to gelatin derived from algae. It’s available online and at health food
stores. And coconut butter is a cream spread made of pureed dried
coconut meat that’s rich in protein, carbs, fiber, and healthy fats.
Methyl donors: coconut butter, agar-agar
DNA methylation adaptogens: blueberries, lemon, coconut butter
1 cup blueberries
½ cup lemon juice
½ cup coconut butter
½ teaspoon stevia or monk fruit powder (or 3 tablespoons
maple syrup if you’re on the YYE)
4 tablespoons gelatin or powdered agar-agar
NUTRIENTS
Fat: 67%
Carb: 19.9%
Protein: 13.1%
Calories: 83.9 kcal
Fat: 6.1 g
Carbohydrates: 4.5 g
Fiber: 1.7 g
Sugar: 2.3 g
Protein: 2.8 g
MATCHA GUMMIES
YYI | K, P, [VGT, V] (if you use agar-agar in lieu of gelatin)
12 servings (1 serving = 1 square)
Cook time: 10 minutes plus 3 hours to set
If you don’t love drinking green tea (as I admit, I don’t), these matcha
gummies are a great way to get a concentrated dose of EGCG from
green tea in just a bite. The coconut milk makes them luscious. If you
don’t like or don’t have coconut milk, you can use an unsweetened nut
milk if you prefer. The gummies will be less creamy, but still tasty. And if
you’re vegan, substitute agar-agar for gelatin.
Tip: You can use molds or an 8 x 8-inch pan.
1. Heat the coconut milk and water over medium heat until just
simmering.
2. Add the remaining ingredients except the gelatin and stir.
Sprinkle the gelatin (or agar-agar) over the top and stir until it has
completely dissolved. Continue stirring over the heat for another
3 to 5 minutes.
3. Distribute the mixture into lightly oiled molds or pour into an 8 x
8-inch baking pan that you’ve lined with parchment paper.
4. Chill in the refrigerator for at least 3 hours, until solidified.
5. Lift the parchment paper out of the pan and cut gummies into 12
squares, approximately 1½ inches square each.
Note: Store in a sealed container in the refrigerator for up to 4 days.
NUTRIENTS
Fat: 68.3%
Carb: 19.2%
Protein: 12.5%
Calories: 68.8 kcal
Fat: 5.6 g
Carbohydrates: 3.5 g
Fiber: 0.6 g
Sugar: 2.6 g
Protein: 2.3 g
These luscious, chocolaty treats come together quickly and will kick
any feelings of deprivation straight to the curb. The freeze-dried
raspberries add a little crunch as well as a pop of brightness.
Methyl donors: cocoa, sunflower seed butter, coconut flour
DNA methylation adaptogens: cocoa, raspberries, coconut flour, sunflower seed butter
FOR DUSTING:
3 tablespoons unsweetened cocoa powder
NUTRIENTS
(using stevia)
Fat: 66%
Carb: 25.5%
Protein: 8.3%
Calories: 315 kcal
Fat: 24.3 g
Carbohydrates: 38.5 g
Fiber: 5.9 g
Sugar: 11.1 g
Protein: 7.5 g
These squares are easy to make and deliciously filling (and calorically
dense, which is why the serving size is small). They’re also a tasty way
to meet your seed requirements for the day.
Methyl donors: sunflower seeds, pumpkin seeds, ground almonds, cocoa
DNA methylation adaptogens: sunflower seeds, pumpkin seeds, ground almonds, coconut
oil, cocoa
These Chocolate Almond Cups are really good and super healthy. Use
them for entertaining or gift giving, or just keep them in the refrigerator
for when you need a little treat! I admit that there are a lot of steps to
take, but that work yields forty-eight mini cups—enough to keep you
going for a while.
Thanks to Angela Liddon of the blog Oh She Glows, whose 3-Layer
Dream Cups were the inspiration for this recipe.
Methyl donors: coconut butter, almond flour, almond butter, maple syrup, cocoa, coconut
shavings
DNA methylation adaptogens: coconut butter, almond flour, almond butter, coconut oil,
cocoa
Sometimes you just need something creamy and chocolaty. This chia
pudding satisfies that important need while also doing your body a lot of
good, as every ingredient delivers multiple health benefits, including
optimizing DNA methylation—even the maple syrup contains important
phytonutrients! I do recommend using as little as possible to get a
sweetness that appeals; although the recipe calls for a quarter cup, you
might be able to use less without sacrificing taste.
Methyl donors: maple syrup, cacao, chia seeds
DNA methylation adaptogens: raspberries, blueberries, cacao, chia seeds
¾ cup raspberries
¾ cup blueberries or blackberries
1 can unsweetened, full-fat organic coconut milk
¼ cup pure maple syrup
2 teaspoons real vanilla extract
1 tablespoon cacao powder (unsweetened)
⅓ cup chia seeds
1 bar dairy-free dark chocolate (at least 70 percent cacao) for
grating on top (optional)
Extra berries for top (optional)
NUTRIENTS
Fat: 55.2%
Carb: 39.8%
Protein: 5%
Calories: 248.5 kcal
Fat: 16.3 g
Carbohydrates: 25.7 g
Fiber: 6.9 g
Sugar: 15.6 g
Protein: 3.5 g
Like a kid with a favorite cake, I make this lemon tart for every birthday
and holiday—it is definitely celebration worthy. (It’s also one of the most
commented-upon recipes on my website.) I warn you: the flavor is on
the tart side. But the sweetness of the dates (which are legal on the
Intensive, so long as your fruit consumption for the day stays less than
1 cup total) in the crust tempers the sourness of the lemon filling and
makes a great (and pleasing) combination. To make this recipe vegan,
use agar-agar instead of gelatin.
Methyl donors: sunflower seeds, pumpkin seeds, shredded coconut, cashews, rosemary
DNA methylation adaptogens: sunflower seeds, pumpkin seeds, shredded coconut, dates,
coconut oil, cashews, lemons, rosemary, raspberries
NUTRIENTS
Fat: 63.7%
Carb: 28.4%
Protein: 7.9%
Calories: 480.5 kcal
Fat: 36.2 g
Carbohydrates: 37.1 g
Fiber: 6.2 g
Sugar: 22 g
Protein: 11 g
SUNBERRY SORBET
YYE | P, V, VGT
2 servings
Prep time: 20 minutes
NUTRIENTS
Fat: 26.4%
Carb: 65.2%
Protein: 8.4%
Calories: 241.8 kcal
Fat: 7.6 g
Carbohydrates: 43.3 g
Fiber: 12.4 g
Sugar: 23.1 g
Protein: 6.2 g
BEVERAGES • • • • • • • •
This anytime smoothie has it all: matcha gives a little bit of caffeine for
energy; nutrient-dense avocado and sunflower seeds give you energy
when you need it; and the tanginess of the lemon and turmeric balance
the richness of the avocado—it all makes for a delicious pick-me-up.
Methyl donors: avocado, sunflower seed butter, turmeric
DNA methylation adaptogens: avocado, matcha powder, sunflower seed butter, lemon,
turmeric
½ ripe avocado
1 teaspoon matcha powder
1 tablespoon sunflower butter
Juice and zest of 1 lemon
1 teaspoon turmeric
1 cup almond or coconut milk, unsweetened
Pinch of salt
NUTRIENTS
(almond milk used for calculations)
Fat: 68.3%
Carb: 23.4%
Protein: 8.4%
Calories: 325.2 kcal
Fat: 26.4 g
Carbohydrates: 20.9 g
Fiber: 8.3 g
Sugar: 5.5 g
Protein: 7.8 g
It can be challenging for vegans to get the full suite of amino acids. This
recipe helps you cover those bases with its addition of hemp seeds. It
also contains iron (from the spinach), vitamin C (which helps with iron
absorption, from the mango), and zinc (from the pumpkin seeds)—other
nutrients that are often at risk with vegan diets. If you’re on the
Intensive, omit the banana and know that this recipe will fill your daily
allowance of fruit for the day.
Methyl donors: hemp, spinach, banana, pumpkin seeds
DNA methylation adaptogens: pumpkin seeds, banana, mango, spinach
NUTRIENTS
(pumpkin seeds used in calculation)
Fat: 53.1%
Carb: 31.1%
Protein: 15.8%
Calories: 229.6 kcal
Fat: 13.1 g
Carbohydrates: 19.2 g
Fiber 3.7 g
Sugar: 11.9 g
Protein: 9.3 g
NUTRIENTS
Fat: 46.6%
Carb: 43.6%
Protein: 9.8%
Calories: 67.6 kcal
Fat: 3.6 g
Carbohydrates: 7.8 g
Fiber: 1.9 g
Sugar: 3 g
Protein: 1.8 g
MATCHA LATTE
YYI | K, P, V, VGT
1 serving
Cook time: 5 minutes
NUTRIENTS
Fat: 39%
Carb: 41.5%
Protein: 19.4%
Calories: 59.5 kcal
Fat: 2.7 g
Carbohydrates: 6.7 g
Fiber: 2.9 g
Sugar: 2 g
Protein: 3.3 g
BEET BUBBLY
YYI | KL, V, VGT
1 serving
Prep time: 1 minute
This drink is a great way to use up beet juice from other recipes (such
as the Blueberry Beet Scones, here). Even better, it makes a tasty
spritzer, especially with a squeeze of lemon. For DNA methylation
bonus points, muddle a little fresh rosemary in the bottom of the glass
before pouring in the spring water and beet juice.
Methyl donors: beet juice
DNA methylation adaptogens: beet juice, lemon
NUTRIENTS
Fat: 3.7%
Carb: 82.4%
Protein: 13.8%
Calories: 42.7 kcal
Fat: 0.2 g
Carbohydrates: 9.2 g
Fiber: 1.9 g
Sugar: 4.3 g
Protein: 1.5 g
4 cups water
3 bags oolong tea
1 medium orange, cut into slices
1 sprig fresh rosemary
1 cup ice cubes
1. Bring the water to a boil in a medium saucepan.
2. Add the tea bags, turn off the heat, and let steep for 10 minutes.
Remove the teabags.
3. Place the orange slices and rosemary sprig in a pitcher and pour
the tea over them. Let cool and then put in the fridge to chill.
4. To serve, add the ice cubes, stir gently with a long wooden
spoon, and bring to the table.
NUTRIENTS
Fat: 2.6%
Carb: 90.7%
Protein: 6.7%
Calories: 31.2 kcal
Fat: 0.1 g
Carbohydrates: 7.8 g
Fiber: 1.6 g
Sugar: 6.1 g
Protein: 0.6 g
Take your chamomile tea to the next level—both flavor-wise and DNA
methylation–wise—by adding fresh ginger, lemon, and rosemary.
Methyl donors: ginger, rosemary
DNA methylation adaptogens: chamomile, ginger, lemon, rosemary
4 cups water
4 bags chamomile tea
1-inch piece of fresh ginger, sliced
1 small lemon, quartered
2 sprigs rosemary
NUTRIENTS
Fat: 11.3%
Carb: 77.3%
Protein: 11.3%
Calories: 3.7 kcal
Fat: 0.1 g
Carbohydrates: 1.1 g
Fiber: 0.3 g
Sugar: 0.3 g
Protein: 0.1 g
After exercise, food sources of antioxidants (in other words, all the
ingredients in this recipe) are fabulously regenerative for the body. This
recipe is chock-full of electrolytes (such as the potassium, chloride, and
magnesium in cantaloupe and coconut water) and trace minerals (from
the small pinch of Himalayan pink salt) to replace what you sweated
out; it also delivers protein (in the flax seeds and almonds) to aid in
muscle building and repair.
Tip: Keep your ground flax seed in the freezer to preserve its delicate fat and
antioxidant content.
NUTRIENTS
Fat: 31.3%
Carb: 57%
Protein: 11.7%
Calories: 167.1 kcal
Fat: 6.3 g
Carbohydrates: 25.1 g
Fiber: 8.9 g
Sugar: 16.6 g
Protein: 5.7 g
FIRE CIDER
YYI | [V], VGT
64 servings (1 serving = 1 tablespoon)
Prep time: 30 minutes
Curing time: 30 days
Fire cider is an all-around tonic—the ginger and apple cider vinegar
promote digestion, while the horseradish, cayenne, and garlic boost
immunity. My team of nutritionists turned it into a DNA-methylation
powerhouse by adding rosemary, orange, and turmeric. Just grating the
horseradish will clear your sinuses!
In this version, the flavor of orange shines through immediately,
followed by a mild spicy tingle and flavor of garlic at the end. You can
combine it with olive oil to make a pungent salad dressing, or drink a
small amount straight. Some of my patients have used a morning shot
of this fire cider as a way to help dial down their coffee habit—it
certainly has a pick-you-up kick! The tiny amount of honey per serving
makes this still OK to consume on the Younger You Intensive. If you’re
vegan, either swap the honey for maple syrup or omit.
Methyl donors: ginger, horseradish, onion, garlic, orange, rosemary, turmeric, apple cider
vinegar
DNA methylation adaptogens: ginger, horseradish, onion, garlic, jalapeño, orange,
rosemary, turmeric, apple cider vinegar
1. Prepare your roots, fruits, herbs, and spices and place them in a
32-ounce sterilized glass jar (or two if your jars are smaller),
leaving 2 to 3 inches of room at the top.
2. Pour the apple cider vinegar into the jar until it reaches just below
the top. The other ingredients should be well covered.
3. If you are using a metal lid, place a piece of natural parchment
paper under the lid to keep the vinegar from touching the metal.
Otherwise use a plastic lid if you have one.
4. With the lid on tightly, shake the jar well and then pack down the
solid ingredients again with a spoon.
5. Store in a dark, cool place for a month and remember to shake
daily.
6. After 1 month, strain out the pulp using a cheesecloth, reserving
the liquid. Squeeze out as much liquid from the solids as you
can. Pour the liquids into a fresh, sterilized glass jar or bottle.
7. Add the honey and stir to dissolve.
8. Consume by the tablespoon, or add it to a veggie juice, splash it
over food, or incorporate it into a salad dressing.
Note: Keeps for 3–4 months in the refrigerator.
NUTRIENTS
Calories: 8.4 kcal
Fat: 0 g
Carbs: 1.4 g
Fiber: 0.1 g
Sugar: 0.9 g
Protein: 0.1 g
SHOPPING LISTS
S ome of the foods included on these shopping lists may be new to you or
may be referred to more specifically than you are used to. Here are a few I
wanted to introduce you to.
MCT oil
Made from coconut oil or palm oil, MCT oil is comprised of medium-chain
triglycerides that are absorbed quickly by the bloodstream because they are
easier to digest. I think of it as easy fuel for the body. It offers the following
benefits:
• Improved energy production in cell mitochondria
• Improved satiety and prevention of excess food intake
• Supports cognitive function and overall brain health
• Encourages the production of anti-inflammatory ketones, especially
when used as part of a ketogenic or keto-leaning diet
Mexican oregano
Mexican oregano is from a totally different plant family than the oregano
typically used in Italian cuisine; it’s got a lemony flavor and is one of the
best sources of luteolin, a DNA methylation adaptogen. The same is not
true of regular oregano, although it does have some different DNA
methylation adaptogenic compounds in it. In the United States, you can
typically only find dried Mexican oregano—often at Latin markets or
gourmet markets (and of course, online), although I have seen it at Target.
Stevia
Stevia is three hundred times sweeter than sugar, so it’s best to start with the
smallest amount. Avoid stevia products that have added artificial sweeteners
or dextrose or maltodextrin. Some brands may have a bitter aftertaste, so
you may need to experiment to find one that you like. Stevia comes in both
powdered and liquid forms—powdered tends to work better in baking and
liquid is more easily added to drinks, but in truth you can use them
interchangeably (so if you only want to buy one form to save on costs
and/or storage space, that’s fine). Brands we recommend include:
• NuNaturals NuStevia—Alcohol Free
• SweetLeaf Sweet Drops SteviaClear
• Organic Traditions Stevia Leaf Powder
Erythritol
A sugar alcohol found naturally in fruits, vegetables, and fermented foods,
erythritol is only about 70 percent as sweet as sugar, so you may need to use
more of it. For some people, erythritol may cause gas and bloating. If you
tend to react to sugar alcohols in general, start with a smaller amount of
erythritol to see how it impacts your gut.
• NOW Real Food Erythritol
• Swerve Granular erythritol
Vitamin C Vegetables and fruits: acerola cherry, guava, Key antioxidant and
red bell pepper, currant, spinach, orange, kiwi, infection fighter
lemon, broccoli, strawberry, Brussels sprouts, Cofactor with iron in
grapefruit, kohlrabi, papaya, pineapple, bitter enzymatic reactions,
melon, tangerine, passion fruit, lime, including TET
cantaloupe, chili pepper, mango, cabbage,
Works with vitamin A to
cauliflower, tomato, elderberry, mulberry, bok
increase stem cell
choy, sweet potato, avocado, turnip greens,
reprogramming (mice)
mustard greens, clementine, beet greens,
rutabaga, collard greens, garden cress, Used to make collagen,
raspberry, broccoli rabe, Swiss chard, butternut heal wounds, and
squash, honeydew melon, blackberry, turnip, promote healthy skin
plantain, okra, zucchini, kale, parsnip, potato, Helps burn fat and make
dandelion greens, plum, cranberry, neurotransmitters
pomegranate, jalapeño pepper, green bean, Mitigates the effect of
apricot, artichoke, kale, blueberry, goji berry, toxins and the damage
banana, collard green, watermelon, celeriac, of oxidative stress on
purslane, onion, leek, peach different structures
Legumes/nuts/seeds/grains: Tartary Regenerates other
buckwheat, soybean, green pea, chestnut, lima antioxidants, like vitamin
bean E
Spices/herbs/sweeteners/condiments/drinks: Plays a role in
parsley, fennel, coconut water, coriander reactivating anti-
inflammatory genes and
tumor suppressor genes
as a cofactor for TET
and other epigenetic
enzymes. For this
reason, vitamin C is a
very important player in
the anti-aging space,
and is associated with a
lower risk of all of the
main diseases of aging,
including cancer, heart
disease, hypertension,
stroke
Vitamin D Vegetables and fruits: mushrooms that have Needed for bone,
been exposed to sunlight hormonal, immune, and
Animal protein: trout, mackerel, cod liver oil, heart health
salmon, sardine, flounder, beef liver, egg yolk, An important regulator of
trout, pork, turkey, chicken, oyster the epigenome,
regulating the expression
of hundreds of genes
D deficiency is
associated with
accelerated aging and all
the diseases of aging
A 2019 study of D-
deficient obese African
Americans found that
supplementing with
4,000 IU of vitamin D
dailiy—and no other
interventions—reduced
their age by 1.85 years
on the Horvath clock3
Methyl Donors
These nutrients are also listed in alphabetical order for ease of reference, but
the primary methyl donors are folate, vitamin B12, betaine, and choline. All
the other nutrients included in this section play a support role in the
methylation cycle, either directly or indirectly.
DONOR FOOD SOURCES WHY
In order to understand how methyl donors like B12 and folate actually
work to support DNA methylation, it helps to have a basic understanding of
how methylation—of all types, including DNA methylation—works. The
image below shows you a very simplified version of the methylation cycle.
Ingredients
PRIMARY PLAYERS
Folate
Vitamin B12
Betaine
My Website
My website is home to:
Website: www.drkarafitzgerald.com
GrowBaby Health
This Grants Pass, Oregon, clinic, led by the mother-daughter team of
Ob/Gyn Leslie Stone, MD, and certified nutrition consultant Emily
Rydbom, CN, BCHN, CNP, uses nutrition and a focus on methylation to
improve birth outcomes. They work with women and couples who are
seeking to conceive in person; they also offer online group programs and
educational videos for each trimester.
Website: http://growbabyhealth.com
DNA METHYLATION CLOCKS TO
ASSESS BIO AGE
T hese are the bio age clocks that are available to consumers at the time
of this writing. Note that some laboratories require blood to do their testing
while others require saliva. Whichever lab you choose to take your baseline
bio age measurement, make sure you get your follow-up test from the same
lab using the same specimen type. After you’ve gotten your initial baseline
and follow-up tests, you can change labs for your next series of tests if you
like. Because different laboratories use different DNA methylation clocks,
you cannot expect results from different tests to be the same. Although
whether your bio age is increasing or decreasing should be consistent
regardless of laboratory or test.
YY BioAge Plus
This is the suite of tests that my team and I created; it assesses multiple bio
age clocks as well as the DNA methylation status of select nutrient-
responsive genes.
www.drkarafitzgerald.com
epiAge
This bio age assessment is from Dr. Moshe Szyf’s laboratory.
www.hkgepitherapeutics.com
Epimorphy
www.myDNAge.com
BioViva TimeKeeper
bioviva-science.com/collections/products
NONTOXIC CLEANING PRODUCTS
Water Testing
We recommend National Testing Laboratories for water testing.
https://watercheck.com
Soil Testing
We recommend anyone starting a vegetable garden check for soil
contamination by toxins such as PCBs and lead. In the United States, many
state universities and local governments offer basic soil testing for low or
no cost. Do an internet search for “soil testing” and your state to see what’s
available near you.
SUPPLEMENTS
Beet Supplements
I recognize that beets can also be viewed unfavorably, yet betaine is so
important to DNA methylation that you don’t want to forego them
altogether. If you truly can’t stomach beets—or learn to love them—take
them in supplement form instead, either as powder or capsules. Follow
instructions on label to determine dosage.
Greens Powders
Adding a quality greens powder to a smoothie, plant-based yogurt, or even
a glass of water or Beet Bubbly is a convenient and easy way to help ensure
that you meet your daily greens requirement on both the Younger You
Intensive and Everyday.
PHYTOGANIX® METAGENICS
• Non-GMO, gluten-free, and vegetarian
• Blend of seeds, vegetables, fruits, herbs, mushrooms, green tea,
enzymes, and probiotics
It was around 2013 when I really started to tussle with the literature on
epigenetics and became entranced (and somewhat horrified) by the science
regarding DNA methylation as it relates to cancer. The more I learned, the
more I saw that other chronic diseases—including aging itself—share some
of the same pathological DNA methylation signatures as cancer.
My next question was obvious: how might we tend to DNA methylation,
through a functional medicine lens, in patient care? Unbeknownst to me at
the time, answering this question would change my career. There are so
many people who have helped me expand my understanding and spread the
word about all I’ve learned.
Romilly Hodges, MS, CNS, my sister in science and the founding
director of our nutrition programs at Sandy Hook Clinic, you have been
deeply in the “tussle” with me, as we dialoged endlessly about the meaning
of what we were reading, and how we might favorably, safely influence
DNA methylation patterns. The 2016 e-book that you and I cowrote for
other functional medicine professionals, Methylation Diet and Lifestyle:
Whole Being Support for Healthy Methylation and Epigenetic Expression,
laid the foundation for this book. I am deeply indebted to you for walking
with me for so many years on this methylation journey. You did the heavy
lifting on designing the nutrient ratios to ensure our epi-nutrient targets
were achieved, and that our recipes were palatable and doable in our study
and in the real world.
Jeff Bland, PhD, you have been a mentor to me—as you have for so
many of us in functional medicine—for twenty-plus years, since I was a
medical student and heard your brilliant lecture on the biochemistry of hops
and estrogen. You have been a constant source of strength and
encouragement. Having you as a bedrock of unwavering faith in me and my
team’s ability to execute our vision has been essential to our success.
Brent Eck, CEO, Metagenics, Inc. Thank you, thank you, thank you
for having those early, open, honest, and sometimes scary conversations
with me on how our interventions might be influencing epigenetic
expression (favorably or not) and providing us with the unrestricted funding
and support to dig in and answer our questions. I am forever indebted to
you and the entire Metagenics team, including Nikky Contractor, PhD,
Kim Koch, and Kirti Salunkhe, MD.
Executing a multivariable trial such as ours is no small feat; it takes a
village of brilliant, committed scientists, nutritionists, and support staff.
Thank you to my coprincipal investigator at National University of Natural
Medicine’s Helfgott Research Institute, Ryan Bradley, ND, MPH. You
helmed the ship of this study with the utmost scientific rigor and integrity.
Thank you also to your team at NUNM, Doug Hanes, PhD, and Emily
Stack.
I am deeply indebted to Moshe Szyf, PhD, pioneer in the field of
epigenetics. In 2017 I had the opportunity to podcast with you, where I
introduced you to what was then just a bud of a study idea. Your guidance
in all phases helped it flourish. While I know we’ve written the book for a
broader audience, I hope we’ve done the science sufficient justice. Also at
McGill, David Cheishvili, PhD, assisted us with endless questions and
statistical analysis. I look forward to continued collaborations.
It’s handy to become good friends with a brilliant biostatistician and
gerontologist. Josh Mitteldorf, PhD, worked on the DNAmAge clock data
analysis and continues to be willing to spend a lot of time dialoging with
me on everything pertaining to longevity epigenetics. I look forward to our
continued work together and the successful launch of your DataBeta study.
It’s been argued that our study nutrition team (most of them graduates of
our clinic internship program) were the difference between our study’s
success vs. failure. Of course, I am wildly appreciative to all of you for
volunteering your time and I hope we continue to collaborate: Despina
Giannopoulou, CNS, Janine Henkel, CNS, Josette Herdell, CNS, Sally
Logan, CNS, and Melissa Twedt, CNS.
An extra thanks to Josette Herdell, CNS, for analyzing the epi-nutrient
content on the recipes. Thank you also to our nutrition interns who helped:
Michelle Didner, MS, Miranda Kusi, MS, Jacquelyn Lombari, MS,
Carrie A Newsome, BSN, RN, MSACN, CNS, Meghan Pfiffner, MS,
Andrew Sisisky, JD, MS, Hili Ben-David, MD, IFMCP, Gretchen
DePalma, MS, CNS, CDN, Carrie J. Ettinger, MS, CNS, Tammi Hall,
MS, Ann Haren, MS, Sally Logan, MS, CNS, Karin Michalk, MS, PT,
CN, CNS, Amy Pabbi, MS, INHC, Dione Sordi.
Thank you to Melissa Parker, CNS, who not only worked on our vegan
recipe development (and is another brilliant program graduate), but shared
her own personal journey of recovery from cancer in Chapter 10.
I am indebted to the Institute for Functional Medicine, specifically
Patrick Hanaway, MD, Laurie Hoffman, David Jones, MD, Robert
Luby, MD, Dan Lukaczer, ND, Amy Mack, and Chris D’Adamo, PhD,
for your support of our work. My gratitude runs deep. Thank you to my FM
peeps for your support (and challenges): Cheryl Burdette, ND, Sara
Gottfried, MD, Shalesh Khalsa, MD, PhD, Todd LaPine, MD, Helen
Messier, MD, PhD, Amy Myers, MD, Cass Nelson-Dooley, MS, Joe
Pizzorno, ND, Bob Rountree, MD, Tom Sult, MD, Sam Yanuck, DC,
and the early adopters at Cleveland Clinic Center for Functional
Medicine.
Thank you to Lucia Aronica, PhD, nutritional epigeneticist and
Stanford faculty who has cheerleaded our project since the start. I am so
grateful for your support, insight, understanding, and friendship. Thank you
for your scientific review of Younger You and the late-night responses to my
urgent inquiries. I look forward to our continued collaboration.
To Drs. Michael and Leslie Stone and daughter Emily Rydbom CNP
at Stone Medical and GrowBabyHealth: I am honored that you are
incorporating ideas from Younger You into your program and research.
Thank you to the journal Aging for publishing our first study. We
appreciate your enthusiasm and support.
Stephanie Tade, my agent: thank you, thank you, thank you for your
years-long commitment to our work. I adore you and appreciate your
support and belief in our project.
Renée Sedliar and the team at Hachette: I knew as soon as we all met
that you were the badass team to launch this project. Thank you for your
extraordinary skills in making this book happen.
And to Kate Hanley, my cowriter supreme: could I be working with a
better, more entertaining soul sister and translator of really tough science?
Who hits deadlines and is uberorganized? We wrote this bad boy during
COVID. How ’bout that! You have been more in the trenches with me over
the last year-plus than, really, anyone else! Thank YOU.
Thank you to Victor Chapla, Shai Rosen, and Erica Sanders at
Suggestic. You are bringing the digital platform of Younger You to life,
enabling us to make the bio age testing, program, nutritionists, book,
products, and future research accessible to anyone, anywhere.
To my team at Accelerate360, Weston Gardner and Jonathon Jacobs:
Thank you for walking our work out into the world in such a beautiful way.
As some of you may know, for the last six years, I’ve been hosting the
podcast New Frontiers in Functional Medicine. As I say every episode, I
am interviewing the best minds in functional medicine, specifically Dale
Bredesen, MD, Randy Jirtle, PhD, Volter Longo, PhD, David
Perlmutter, MD, and David Sinclair, PhD. Their interest in this work
bolstered my confidence that we might be onto something. And thank you
to our producer Kate Mayer for making it happen each month.
Thank you to my dearest mentor: Richard Lord, PhD. Without your
mentorship during my time at the laboratory, your endless teaching, your
unending passion for nutritional biochemistry, your thinking outside of the
box, and your “embracing the uncertainty,” I don’t know that these next
phases of my career would’ve happened. I am indebted to you.
To our study participants: Thank you for your time, energy, attention,
and commitment.
To our many patients at SHC practicing the program: Thank you!
THANK YOU to the extraordinary group of super smart, hardworking,
and creative physicians and nutritionists that make our clinic a one-of-a-
kind place to practice medicine. Thank you for hanging in with the insanity
of our study and our book. You are my touchstones, and I practice medicine
better because of all of you: Lizzie Bird, MD, Stacey Cantor-Adkins,
MD, Gretchen DePalma, CNS, Darisa Espinal, ND, Karen Herb, CNS,
Jessica Kovalchik, DC, CNS, Ken Litwin, MD, Rachel Surprenant, ND,
and Lara Zakaria, PharmD, MS, CNS.
Our clinic management team, who have patiently put up with my
madness and absence for the last three-plus-plus years, and who’ve
coordinated a bear of a schedule, juggled crazy finances, and supported all
of us to reach higher and dig deeper in the practice of functional medicine:
THANK YOU, thank you thank you: Sam Bucur, Karen Frank, Karen
Herb, and Rhonda Timmons.
And finally, to my family and my amazing care team.
Yolanda, you are my nanny as much as Isabella’s. You make our lives
work seamlessly. Thank you for loving my daughter and taking such good
care of us. Yo te quiero.
Mom, Evan, Brigid, Dad, Jim, Rob, Chloe, Jay, and Connie: I
appreciate your endless interest in this work. Mom, because “methylation is
good for you,” you make a delish version of our lemon tart at every holiday
occasion. Iz and I can’t get enough. XXOO
Discover Your Next Great Read
Get sneak peeks, book recommendations, and news about your favorite
authors.
YOUNGER YOU
INTRODUCTION
1. S. H. Woolf and H. Schoomaker, “Life Expectancy and Mortality Rates
in the United States, 1959–2017,” JAMA 322, no. 20 (2019): 1996–2016,
doi: 10.1001/jama.2019.16932.
2. World Health Organization, “Top 10 Causes of Death,” May 24, 2018,
www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death.
3. Tim Peterson, “Healthspan Is More Important Than Lifespan, So Why
Don’t More People Know About It?,” May 30, 2017,
https://publichealth.wustl.edu/heatlhspan-is-more-important-than-lifespan-
so-why-dont-more-people-know-about-it/.
4. J. F. Fries, “Aging, Natural Death, and the Compression of Morbidity,”
New England Journal of Medicine 303, no. 3 (July 17, 1980): 130–135, doi:
10.1056/NEJM198007173030304.
CHAPTER 1
1. Zion Market Research, “Anti-Aging Market to Touch US $216.5
Billion by End of 2021, Globally: ZMR Report,” August 30, 2018,
www.globenewswire.com/news-release/2018/08/30/1563523/0/en/Anti-
Aging-Market-To-Touch-US-216-52-Billion-By-the-End-of-2021-Globally-
ZMR-Report.html.
2. Sarah Corapi, “Why Slowing the Aging Process Could Save the U.S.
Trillions,” PBS Newshour, October 7, 2013,
www.pbs.org/newshour/health/why-delaying-aging-might-be-possible-and-
very-important.
3. Rabah Kamal, Daniel McDermott, Giorlando Ramirez, and Cynthia
Cox, “Health System Tracker,” Peterson-KFF, December 23, 2020,
www.healthsystem tracker.org/chart-collection/u-s-spending-healthcare-
changed-time/#item-usspend ingovertime_3.
4. A. J. Scott, M. Ellison, and D. A. Sinclair, “The Economic Value of
Targeting Aging,” Nature Aging 1 (2021): 616–623, doi: 10.1038/s43587-
021-00080-0.
5. Hannah Ashworth, “How Long Is Your DNA?,” BBC Science Focus
Magazine, www.sciencefocus.com/the-human-body/how-long-is-your-dna/.
6. Moshe Szyf, “Episode 22,” New Frontiers in Functional Medicine
(podcast), www.drkarafitzgerald.com/2017/03/15/episode-22-gene-
whispering-with-dr-moshe-szyf/.
7. S. R. Moore et al., “Epigenetic Correlates of Neonatal Contact in
Humans,” Development and Psychopathology 29, no. 5 (December 2017):
1517–1538, doi: 10.1017/S0954579417001213.
8. Dr. Kara Fitzgerald and Dr. David Sinclair, “Understanding Genetics of
Aging with Harvard Professor Dr. David Sinclair, New Frontiers in
Functional Medicine (podcast),
www.drkarafitzgerald.com/2020/08/01/understanding-genetics-of-aging-
with-harvard-professor-dr-david-sinclair/.
9. A. El-Osta et al., “Transient High Glucose Causes Persistent
Epigenetic Changes and Altered Gene Expression During Subsequent
Normoglycemia,” Journal of Experimental Medicine 205, no.10 (2008):
2409–2417, doi: 10.1084/jem.20081188.
10. V. Vigorelli et al., “Abnormal DNA Methylation Induced by
Hyperglycemia Reduces CXCR4 Gene Expression in CD34+ Stem Cells,”
Journal of the American Heart Association 8, no. 9 (2019), doi:
10.1161/JAHA.118.010012.
11. E. Barrón-Cabrera et al., “Epigenetic Modifications as Outcomes of
Exercise Interventions Related to Specific Metabolic Alterations: A
Systematic Review,” Lifestyle Genomics 12, no. 1–6 (2019): 25–44, doi:
10.1159/000503289.
12. Josh Mitteldorf and Dorion Sagan, Cracking the Aging Code (New
York: Flatiron Books, 2017).
13. A. Lu et al., “Universal DNA Methylation Age Across Mammalian
Tissues,” (2021), doi: 10.1101/2021.01.18.426733.
14. G. M. Fahy et al., “Reversal of Epigenetic Aging and
Immunosenescent Trends in Humans,” Aging Cell 18, no. 6 (2019): e13028,
doi: 10.1111/acel.13028.
15. A. A. M. Berendsen et al., “Changes in Dietary Intake and Adherence
to the NU-AGE Diet Following a One-Year Dietary Intervention Among
European Older Adults—Results of the NU-AGE Randomized Trial,”
Nutrients 10, no. 12 (2018): 1905, doi: 10.3390/nu10121905.
16. N. Gensous et al., “One-Year Mediterranean Diet Promotes
Epigenetic Rejuvenation with Country- and Sex-Specific Effects: A Pilot
Study from the NU-AGE Project,” GeroScience 42 (2020): 687–701, doi:
10.1007s11357-019-00149-0.
17. L. Chen et al., “Effects of Vitamin D3 Supplementation on Epigenetic
Aging in Overweight and Obese African Americans with Suboptimal
Vitamin D Status: A Randomized Clinical Trial,” Journals of Gerontology
Series A: Biological Sciences and Medical Sciences 74, no. 1 (January 1,
2019): 91–98, doi: 10.1093/gerona/gly223.
CHAPTER 2
1. Antonio Regaldo, “More Than 26 Million People Have Taken an At-
Home Ancestry Test,” MIT Technology Review, February 11, 2019,
www.technologyre view.com/2019/02/11/103446/more-than-26-million-
people-have-taken-an-at-home-ancestry-test/.
2. National Center for Health Statistics, “Obesity and Overweight,”
Centers for Disease Control and Prevention,
www.cdc.gov/nchs/fastats/obesity-overweight.htm.
3. L. O. Schulz and L. S. Chaudhari, “High-risk Populations: The Pimas
of Arizona and Mexico,” Current Obesity Reports 4, no. 1 (March): 92–98,
doi: 10.1007/s13679-014-0132-9.
4. C. Ling and T. Rönn, “Epigenetics in Human Obesity and Type 2
Diabetes,” Cell Metabolism 29, no. 5 (May 7, 2019):1028–1044, doi:
10.1016/j.cmet.2019.03.009.
5. Jordan Imhoff, “Health Inequality Actually Is a ‘Black and White’
Issue, Research Says,” University of Michigan Health, June 3, 2020,
https://healthblog.uofmhealth.org/lifestyle/health-inequality-actually-a-
black-and-white-issue-research-says.
6. Francine E. Garrett-Bakelman et al., “The NASA Twins Study: A
Multidimensional Analysis of a Year-Long Human Spaceflight,” Science
364, no. 6436 (April 12, 2019): eaau8650, doi: 10.1126/science.aau8650.
7. Erike Hayasaki, “Identical Twins Hint at How Environments Change
Gene Expression,” The Atlantic, May 15, 2018,
www.theatlantic.com/science/archive/2018/05/twin-epigenetics/560189/.
8. Breast Cancer Prevention Partners, “Organic Solvents,”
www.bcpp.org/re source/organic-solvents/.
9. Andrea Baccarelli et al., “Rapid DNA Methylation Changes After
Exposure to Traffic Particles,” American Journal of Respiratory and
Critical Care Medicine 179, no. 7 (April 1, 2009): 572–578, doi:
10.1164/rccm.200807-1097OC.
10. R. A. Waterland and R. L. Jirtle, “Transposable Elements: Targets for
Early Nutritional Effects on Epigenetic Gene Regulation,” Molecular and
Cellular Biology 23, no. 15 (August 2003): 5293–5300, doi:
10.1128/MCB.23.15.5293-5300.2003.
11. E. W. Tobi et al., “DNA Methylation as a Mediator of the Association
Between Prenatal Adversity and Risk Factors for Metabolic Disease in
Adulthood,” Science Advances 4, no. 1 (January 31, 2018): eaao4364, doi:
10.1126/sciadv.aao4364.
12. Ibid.
13. Carl Zimmer, “The Famine Ended 70 Years Ago, but Dutch Genes
Still Bear Scars,” New York Times, January 31, 2018,
www.nytimes.com/2018/01/31/sci ence/dutch-famine-genes.html; Elmar W.
Tobi et al.,“DNA Methylation as a Mediator of the Association Between
Prenatal Adversity and Risk Factors for Metabolic Disease in Adulthood,”
Science Advances 4, no. 1 (January 31, 2018): EAAO4364, doi:
10.1126/sciadv.aao4364.
14. Marcus Pembrey et al., “Human Transgenerational Responses to
Early-Life Experience: Potential Impact on Development, Health and
Biomedical Research,” Journal of Medical Genetics 51, no. 9 (September
2014): 563–572, doi: 10.1136/jmedgenet-2014-102577.
15. Lei Cao-Lei et al., “DNA Methylation Signatures Triggered by
Prenatal Maternal Stress Exposure to a Natural Disaster: Project Ice Storm,”
PlosOne (September 19, 2014), doi: 10.1371/journanl.pone.0107653; Anne-
Marie Turcotte-Tremblay et al., “Prenatal Maternal Stress Predicts
Childhood Asthma in Girls: Project Ice Storm” Biomedical Research
International 2014 (2014): 201717, doi: 10.1155/2014/201717.
16. D. L. McCartney et al., “Investing the Relationship Between DNA
Methylation Age Acceleration and Risk Factors for Alzheimer’s Disease,”
Alzheimer’s & Dementia (Amsterdam, Netherlands) 10 (2018): 429–437,
doi: 10.1016/j.dadm.2018.05.006.
17. Y. Zhou et al., “FTO Genotype Associations with FTO Methylation
Level Influences Body Mass and Telomere Length in an Australian Rural
Population,” International Journal of Obesity (London, England) 41, no. 9
(2017): 1427–1433, doi: 10.1038/ijo.2017.127.
18. M. Samblas, F. I. Milagro, and A. Martinez, “DNA Methylation
Markers in Obesity, Metabolic Syndrome, and Weight Loss,” Epigenetics
14, no. 5 (2019): 421–444, doi: 10.1080/15592294.2019.1595297.
19. F. H. Xiao, H. T. Wang, and Q. P. Kong, “Dynamic DNA Methylation
During Aging: A ‘Prophet’ of Age-Related Outcomes,” Frontiers in
Genetics 10 (2019): 107, doi: 10.3389/fegene.2019.001707.
20. L. Xiaolei, J. Bin, and S. Lu, “The Epigenetics of Alzheimer’s
Disease: Factors and Therapeutic Implications,” Frontiers in Genetics 9
(2018): 5790, doi: 10.3389/fgene.2018.00579; T. Pi, B. Liu, and J. Shi,
“Abnormal Homocysteine Metabolism: An Insight of Alzheimer’s Disease
from DNA Methylation,” Behavioural Neurology (2020): 8438602, doi:
10.1155/2020/8438602.
21. Y. Zhu et al., “Epigenetic Modification and Its Role in Alzheimer’s
Disease,” Integrative Medicine International 2 (2015): 63–72, doi:
10.1159/000437329.
22. K. Toups et al., “Precision Medicine Approach to Alzheimer’s
Disease: Successful Proof-of-Concept Trial,” medRxiv (preprint), (May
2021), doi: 10.1101/2021.05.10.21256982.
23. A. D. Smith et al., “Homocysteine and Dementia: An International
Consensus Statement,” Journal of Alzheimer’s Disease 62, no. 2 (2018):
561–570, doi: 10.3233/JAD-171042.
24. L. Lind et al., “Methylation-Based Estimated Biological Age and
Cardiovascular Disease,” European Journal of Clinical Investigation 48,
no. 2 (February 2018), doi: 10.1111/eci.12872.
25. C. Soler-Botija, C. Gálvez-Montón, and A. Bayés-Genís, “Epigenetic
Biomarkers in Cardiovascular Diseases,” Frontiers in Genetics 10 (October
2019): 950, doi: 10.3389/fgene.2019.00950.
26. E. M. Vidrascu et al., “Effects of Early- and Mid-Life Stress on DNA
Methylation of Genes Associated with Subclinical Cardiovascular Disease
and Cognitive Impairment: A Systematic Review,” BMC Medical Genetics
20, no. 1 (March 12, 2019): 39, doi: 10.1186/s12881-019-0764-4.
27. S. G. Chrysant and G. S. Chrysant, “The Current Status of
Homocysteine as a Risk Factor for Cardiovascular Disease: A Mini
Review,” Expert Review of Cardiovascular Therapy 16, no. 8 (August
2018): 559–565, doi: 101.1080/14779072.2018.1497974.
28. J. C. Earls et al., “Multi-Omic Biological Age Estimation and Its
Correlation with Wellness and Disease Phenotypes: A Longitudinal Study
of 3,558 Individuals,” Journals of Gerontology, Series A 74 (November 13,
2019 [Suppl. 1]): S52–S60, doi: 10.1093/geronaglz220.
29. S. A. H. Ahmed et al., “The Role of DNA Methylation in the
Pathogenesis of Type 2 Diabetes Mellitus,” Clinical Epigenetics 12 (2020):
104, doi: 10.1186/s13148-020-00896-4.
30. F. H. Xiao, H. T. Wang, and Q. P. Kong, “Dynamic DNA Methylation
During Aging: A ‘Prophet’ of Age-Related Outcomes,” Frontiers in
Genetics 10 (February 18, 2019): 107, doi: 10.3389/fgene.2019.00107.
31. Y. M. Lee, D. R. Jacobs Jr., and D. H. Lee, “Persistent Organic
Pollutants and Type 2 Diabetes: A Critical Review of Review Articles,”
Frontiers in Endocrinology (Lausanne, Switzerland) 9 (November 27,
2018): 712, doi: 10.3389/fendo.2018.00712.
32. D. H. Lee et al., “A Strong Dose-Response Relation Between Serum
Concentrations of Persistent Organic Pollutants and Diabetes: Results from
the National Health and Examination Survey 1999–2002,” Diabetes Care
29, no. 7 (July 2006):1638–1644, doi: 10.2337/dc06-0543.
33. M. Szyf, “The Implications of DNA Methylation for Toxicology:
Toward Toxicomethlomics, the Toxicology of DNA Methylation,”
Toxicological Sciences 12, no. 2 (April 2011): 235–255, doi:
10.1093/toxsci/kfr024.
34. M. Li et al., “What Do DNA Methylation Studies Tell Us About
Depression? A Systematic Review,” Translational Psychology 9, no. 1
(February 4, 2019): 68, doi: 10.1038/s41398-019-0412-y.
35. R. L. Simons et al., “Methylation of the Oxytocin Receptor Gene
Mediates the Effect of Adversity on Negative Schemas and Depression,”
Development and Psychopathology 29, no. 3 (August 2017): 725–736, doi:
10.1017/S0954579416 000420.
36. A. A. Akil et al., “Reading Between the (Genetic) Lines: How
Epigenetics Is Unlocking Novel Therapies for Type 1 Diabetes.” Cells 9,
no. 11 (2020): 2403.
37. S. Vordenbäumen et al., “Methyl Donor Micronutrients, CD40-ligand
Methylation and Disease Activity in Systemic Lupus Erythematosus: A
Cross-sectional Association Study,” Lupus (July 20, 2021):
9612033211034559, doi: 10.1177/09612033211034559.
38. C. Perrier and B. Corthésy, “Gut Permeability and Food Allergies,”
Environmental Health Perspectives 107, no. 10 (November 11, 2010): doi:
10.1111/j.1365-2222.2010.03639.x.
39. G. P. Pfeifer, “Defining Driver DNA Methylation Changes in Human
Cancer,” International Journal of Molecular Sciences 19, no. 4 (April 12,
2018): 1166. doi: 10.3390/ijms19041166.
40. E. M. Michalak et al., “The Roles of DNA, RNA and Histone
Methylation in Ageing and Cancer,” Nature Reviews Molecular Cellular
Biology 20, no. 10 (October 2019): 573–589, doi: 10.1038/s41580-019-
0143-1.
41. Y. Hashimoto, T. J. Zumwalt, and A. Goel, “DNA Methylation
Patterns as Noninvasive Biomarkers and Targets of Epigenetic Therapies in
Colorectal Cancer,” Epigenomics 8, no. 5 (May 2016): 685–703, doi:
10.2217/epi-2015-0013.
42. A. Niedzwiecki et al., “Anticancer Efficacy of Polyphenols and Their
Combinations,” Nutrients 8, no. 9 (September 9, 2016): 552, doi:
10.3390/nu8090552.
43. I. Arora, M. Sharma, and T. O. Tollefsbol, “Combinatorial
Epigenetics Impact of Polyphenols and Phytochemicals in Cancer
Prevention and Therapy,” International Journal of Molecular Sciences 20,
no. 10 (September 14, 2019): 4567, doi: 10.3390/iljms20184567.
CHAPTER 3
1. B. A. Ames, I. Elson-Schwab, and E. A. Silver, “High-dose Vitamin
Therapy Stimulates Variant Enzymes with Decreased Coenzyme Binding
Affinity (Increased Km): Relevance to Genetic Disease and
Polymorphisms,” American Journal of Clinical Nutrition 75, no. 4 (April
2002): 616–658, doi: 10.1093/ajcn/75.4.616.
2. R. A. Waterland and R. L. Jirtle, “Transposable Elements: Targets for
Early Nutritional Effects on Epigenetic Gene Regulation,” Molecular and
Cellular Biology 23, no. 15 (August 2003): 5293–5300, doi:
10.1128/MCB.23.15.5293-5300.2003.
3. L. J. Williams et al. “Prevalence of Spina Bifida and Anencephaly
During the Transition to Mandatory Folic Acid Fortification in the United
States,” Teratology 66, no. 1 (2002): 33–39, doi: 10.1002/tera.10060.
4. M. S. Morris et al., “Circulating Unmetabolized Folic Acid and 5-
Methyltetrahydrofolate in Relation to Anemia, Macrocytosis, and Cognitive
Test Performance in American Seniors” [published correction appears in
American Journal of Clinical Nutrition 92, no. 4 (October 2010):1002],
American Journal of Clinical Nutrition 91, no. 6 (2010): 1733–1744, doi:
10.3945/ajcn.2009.28671.
5. J. B. Mason et al., “A Temporal Association Between Folic Acid
Fortification and an Increase in Colorectal Cancer Rates May Be
Illuminating Important Biological Principles: A Hypothesis,” Cancer
Epidemiology, Biomarkers & Prevention 16, no. 7 (July 2007): 1325–1329,
doi: 10.1158/1055-9965.EPI-07-0329.
6. Ibid.
7. K. Wallace et al., “Association Between Folate Levels and CpG Island
Hypermethylation in Normal Colorectal Mucosa,” Cancer Prevention
Research (Philadelphia) 3, no. 12 (December 2010): 1552–1564, doi:
10.1158/1940-6207.CAPR-10-0047.
8. Confirmed via email exchange with Marvin Singh, MD, coeditor of
Integrative Gastroenterology, Oxford University Press (2019).
9. Z. Sadighi, I. J. Butler, and M. K. Koenig, “Adult-Onset Cerebral
Folate Deficiency,” Archives of Neurology 69, no. 6 (2012): 778–779, doi:
10.1001/archneurol.2011.3036.
10. J. P. van Wijngaarden et al., “Effect of Daily Vitamin B-12 and Folic
Acid Supplementation on Fracture Incidence in Elderly Individuals with an
Elevated Plasma Homocysteine Concentration: B-Proof, a Randomized
Controlled Trial,” American Journal of Clinical Nutrition 100 (2014):
1578–1586.
11. Sadaf Oliai Araghi et al., “Folic Acid and Vitamin B12
Supplementation and the Risk of Cancer: Long-term Follow-up of the B
Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF),” Trial
Cancer Epidemiology, Biomarkers and Prevention 28, no. 2 (February 1,
2019): 275–282, doi: 10.1158/1055-9965.EPI-17-1198.
12. Young-In Kim, “Folate and Cancer: A Tale of Dr. Jekyll and Mr.
Hyde?,” American Journal of Clinical Nutrition 107, no. 2 (February 2018):
139–142, doi: 10.1093/ajcn/nqx076.
13. Dr. Kara Fitzgerald and Dr. Valter Longo, “Episode 43: Fasting
Mimicking Diet: Beyond Caloric Restrictions with Dr. Valter Longo,” New
Frontiers in Functional Medicine (podcast),
www.drkarafitzgerald.com/2018/06/08/fasting-diet-beyond-caloric-dr-
valter-longo/.
14. H. Zheng et al., “Life-Long Body Mass Index Trajectories and
Mortality in Two Generations,” Annals of Epidemiology 56 (2021): 18–25,
doi: 10.1016/j.annepidem.2021.01.003.
15. Dr. Kara Fitzgerald and Dr. Valter Longo, “Episode 43: Fasting
Mimicking Diet: Beyond Caloric Restrictions with Dr. Valter Longo,” New
Frontiers in Functional Medicine (podcast),
www.drkarafitzgerald.com/2018/06/08/fasting-diet-beyond-caloric-dr-
valter-longo/.
16. N. Gensous et al., “One-Year Mediterranean Diet Promotes
Epigenetic Rejuvenation with Country- and Sex-Specific Effects: A Pilot
Study from the NU-AGE Project,” GeroScience 42 (2020): 687–701, doi:
10.1007s11357-019-00149-0.
17. M. Montgomery and A. Srinivasan, “Epigenetic Gene Regulation by
Dietary Compounds in Cancer Prevention,” Advances in Nutrition
(Bethesda, MD) 10, no. 6 (2019): 1012–1028, doi:
10.1093/advances/nmz046.
18. K. A. Kang et al., “Luteolin Promotes Apoptotic Cell Death via
Upregulation of Nrf2 Expression by DNA Demethylase and the Interaction
of Nrf2 with p53 in Human Colon Cancer Cells,” Experimental &
Molecular Medicine 51, 1–14 (2019): doi: 10.1038/s12276-019-0238-y.
19. N. F. Watson et al., “Recommended Amount of Sleep for a Healthy
Adult: A Joint Consensus Statement of the American Academy of Sleep
Medicine and Sleep Research Society,” Sleep 38, no. 6 (2015): 843–844,
doi: 10.5665/sleep.4716.
20. J. E. Carroll et al., “Epigenetic Aging and Immune Senescence in
Women with Insomnia Symptoms: Findings from the Women’s Health
Initiative Study,” Biological Psychiatry 81, no. 2 (January 15, 2017): 136–
144, doi: 10.1016/j.biopsych.2016.07.008, Epub July 26, 2016.
21. M. A. Carskadon et al., “A Pilot Prospective Study of Sleep Patterns
and DNA Methylation-Characterized Epigenetic Aging in Young Adults,”
BMC Research Notes 12, no. 583 (2019), doi: 10.1186/s13104-019-4633-1.
22. R. Massart et al., “The Genome-Wide Landscape of DNA
Methylation and Hydroxymethylation in Response to Sleep Deprivation
Impacts on Synaptic Plasticity Genes,” Translational Psychiatry 4, no. 1
(January 21, 2014): e347, doi: 10.1038/tp.2013.120; J. E. Carroll et al.,
“Partial Sleep Deprivation Activates the DNA Damage Response (DDR)
and the Senescence-Associated Secretory Phenotype (SASP) in Aged Adult
Humans,” Brain, Behavior, and Immunity 51 (2016): 223–229, doi:
10.1016/j.bbi.2015.08.024; E. K. Nilsson et al., “Epigenomics of Total
Acute Sleep Deprivation in Relation to Genome-Wide DNA Methylation
Profiles and RNA Expression,” OMICS 20, no. 6 (2016): 334–342, doi:
10.1089/omi.2016.0041.
23. M. Spólnicka. et al., “Modified Aging of Elite Athletes Revealed by
Analysis of Epigenetic Age Markers,” Aging (Albany NY), 10, no. 2
(February 15, 2018): 241–252. doi: 10.18632/aging.101385.
24. H. Zeng et al., “Physical Activity and Breast Cancer Survival: An
Epigenetic Link Through Reduced Methylation of a Tumor Suppressor
Gene L3MBTL1,” Breast Cancer Research and Treatment 133, no.1
(2012): 127–135, doi: 10.1007/s10549-011-1716-7.
25. A. J. White et al., “Recreational and Household Physical Activity at
Different Time Points and DNA Global Methylation,” European Journal of
Cancer 49, no. 9 (2013): 2199–2206, doi: 10.1016/j.ejca.2013.02.013.
26. A. S. Zannas et al., “Lifetime Stress Accelerates Epigenetic Aging in
an Urban, African American Cohort: Relevance of Glucocorticoid
Signaling” [published correction appears in Genome Biology 19, no. 1 (May
23, 2018):61], Genome Biology 16 (December 17, 2015): 266, doi:
10.1186/s13059-015-0828-5.
27. E. J. Wolf et al., “Accelerated DNA Methylation Age: Associations
with PTSD and Neural Integrity,” Psychoneuroendocrinology 63 (2016):
155–162, doi: 10.1016/j.psyneuen.2015.09.020.
28. H. Ren et al., “Epigenetic Changes in Response to Tai Chi Practice: A
Pilot Investigation of DNA Methylation Marks,” Evididence-Based
Complementary and Alternative Medicine 2012: 841810, doi:
10.1155/2012/841810.
29. R. Chaix et al., “Epigenetic Clock Analysis in Long-Term
Meditators,” Psychoneuroendocrinology 85 (2017): 210–214, doi:
10.1016/j.psyneuen.2017.08.016.
30. K. N. Harkess et al., “Preliminary Indications of the Effect of a Brief
Yoga Intervention on Markers of Inflammation and DNA Methylation in
Chronically Stressed Women,” Translational Psychiatry 6, e965 (2016),
doi: 10.1038/tp.2016.234.
31. S. Pavanello et al., “Exploring Epigenetic Age in Response to
Intensive Relaxing Training: A Pilot Study to Slow Down Biological Age,”
International Journal of Environmental Research and Public Health 16, no.
17 (2019): 3074, doi: 10.3390/ijerph16173074.
32. S. Venditti et al., “Molecules of Silence: Effects of Meditation on
Gene Expression and Epigenetics,” Frontiers in Psychology 11 (2020):
1767, doi: 10.3389/fpsyg.2020.01767.
CHAPTER 4
1. T. Bergsma and E. Rogaeva, “DNA Methylation Clocks and Their
Predictive Capacity for Aging Phenotypes and Healthspan,” Neuroscience
Insights (July 21, 2020), 15:2633105520942221, doi:
10.1177/2633105520942221.
2. J. C. Earls et al., “Multi-Omic Biological Age Estimation and Its
Correlation with Wellness and Disease Phenotypes: A Longitudinal Study
of 3,558 Individuals,” Journal of Gerontology, Series A 74 (November 13,
2019 [Suppl. 1]): S52–S60, doi: 10.1093/geronaglz220.
CHAPTER 5
1. V. Vigorelli et al., “Abnormal DNA Methylation Induced by
Hyperglycemia Reduces CXCR 4 Gene Expression in CD 34+ Stem Cells,”
Journal of the American Heart Association 8, no. 9 (2019): e010012, doi:
10.1161/JAHA.118.010012.
2. E. Hall et al., “The Effects of High Glucose Exposure on Global Gene
Expression and DNA Methylation in Human Pancreatic Islets,” Molecular
and Cellular Endocrinology 472 (September 5, 2018): 57–67, doi:
10.1016/j.mce.2017.11.019; Dr. Charlotte Ling, “Effects of DNA
Methylation on Diabetes,” Epigenetics Podcast, April 1, 2021,
www.podbean.com/ew/pb-t5v7z-ff5853.
3. J. A. Pinzón-Cortés et al., “Effect of Diabetes Status and
Hyperglycemia on Global DNA Methylation and Hydroxymethylation,”
Endocrine Connections 6, no. 8 (2017): 708–725, doi: 10.1530/EC-17-
0199.
4. M. C. L. Phillips et al., “Low-fat Versus Ketogenic Diet in Parkinson’s
Disease: A Pilot Randomized Controlled Trial,” Movement Disorders 33,
no. 8 (2018): 1306–1314, doi: 10.1002/mds.27390, Epub August 11, 2018,
Erratum in: Movement Disorders 34, no. 1 (January 2019): 157.
5. H. B. Ruan and P. A. Crawford, “Ketone Bodies as Epigenetic
Modifiers,” Current Opinion in Clinical Nutrition and Metabolic Care 21,
no. 4 (July 2018): 260-266, doi: 10.1097/MCO.0000000000000475.
6. A. Niedzwiecki et al., “Anticancer Efficacy of Polyphenols and Their
Combinations,” Nutrients 8, no. 9 (2016): 552, doi: 10.3390/nu8090552.
7. V. D. Longo and S. Panda, “Fasting, Circadian Rhythms, and Time-
Restricted Feeding in Healthy Lifespan,” Cell Metabolism 23, no. 6 (2016):
1048–1059, doi: 10.1016/j.cmet.2016.06.001; K. Kessler and O.
Pivovarova-Ramich, “Meal Timing, Aging, and Metabolic Health,”
International Journal of Molecular Sciences 20, no. 8 (2019): 1911, doi:
10.3390/ijms20081911.
8. K. P. Kelly et al., “Eating Breakfast and Avoiding Late-Evening
Snacking Sustains Lipid Oxidation,” PLoS Biology 18, no. 2 (February 27,
2020): e3000622, doi: 10.1371/journal.pbio.3000622.
9. T. Bohn et al., “Mind the Gap—Deficits in Our Knowledge of Aspects
Impacting the Bioavailability of Phytochemicals and Their Metabolites—A
Position Paper Focusing on Carotenoids and Polyphenols,” Molecular
Nutrition & Food Research 59, no. 7 (2015): 1307–1323, doi:
10.1002/mnfr.201400745.
10. A. R. Hillman et al., “Exercise-Induced Dehydration With and
Without Environmental Heat Stress Results in Increased Oxidative Stress,”
Applied Physiology, Nutrition, and Metabolism 36, no. 5 (October 2011):
698–706, doi: 10.1139/h11-080.
11. L. A. Frame, E. Costa, and S. A. Jackson, “Current Explorations of
Nutrition and the Gut Microbiome: A Comprehensive Evaluation of the
Review Literature,” Nutrition Reviews 78, no. 10 (October 2020): 798–812,
doi: 10.1093/nutrit/nuz106.
12. M. Rossi, A. Amaretti, and S. Raimondi, “Folate Production by
Probiotic Bacteria,” Nutrients 3, no. 12 (2011): 118–134, doi:
10.3390/nu3010118; D.-H. Yu et al., “Postnatal Epigenetic Regulation of
Intestinal Stem Cells Requires DNA Methylation and Is Guided by the
Microbiome,” Genome Biology 16, no. 1 (2015): 211, doi: 10.1186/s13059-
015-0763-5.
13. K. S. vel Szic et al., “From Inflammaging To Healthy Aging by
Dietary Lifestyle Choices: Is Epigenetics the Key to Personalized
Nutrition?,” Clinical Epigenetics 7, no. 33 (2015), doi: 10.1186/s13148-
015-0068-2.
14. A. Aljada et al., “Increase in Intranuclear Nuclear Factor KappaB and
Decrease in Inhibitor KappaB in Mononuclear Cells After a Mixed Meal:
Evidence for a Proinflammatory Effect,” American Journal of Clinical
Nutrition 79, no. 4 (2004): 682–690, doi: 10.1093/ajcn/79.4.682.
15. A. El-Osta et al., “Transient High Glucose Causes Persistent
Epigenetic Changes and Altered Gene Expression During Subsequent
Normoglycemia,” Journal of Experimental Medicine 205, no. 10
(September 29, 2008): 2409–2417, doi: 10.1084/jem.20081188, Epub
September 22, 2008, Erratum in Journal of Experimental Medicine 205, no.
11 (October 27, 2008): 2683.
16. Assam El-Osta et al., “Transient High Glucose Causes Persistent
Epigenetic Changes and Altered Gene Expression During Subsequent
Normoglycemia,” Journal of Experimental Medicine 205, no. 10
(September 29, 2008): 2409–2417, doi: 10.1084/jem.20081188.
17. E. Hall et al., “The Effects of High Glucose Exposure on Global Gene
Expression and DNA Methylation in Human Pancreatic Islets,” Molecular
and Cellular Endocrinology 472 (September 5, 2018): 57–67, doi:
10.1016/j.mce.2017.11.019.
18. A. Sharma et al., “Artificial Sweeteners as a Sugar Substitute: Are
They Really Safe?” Indian Journal of Pharmacology 48, no. 3 (May-June
2016): 237–240, doi: 10.4103/0253-7613.182888.
19. J. B. Hoffman, M. C. Petriello, and B. Hennig, “Impact of Nutrition
on Pollutant Toxicity: An Update with New Insights into Epigenetic
Regulation,” Reviews on Environmental Health 32, no. 1-2, (2017): 65–72,
doi: 10.1515/reveh-2016-0041.
20. M. Varela-Rey et al., “Alcohol, DNA Methylation, and Cancer,”
Alcohol Research 35, no. 1 (2013): 25–35.
CHAPTER 6
1. J. A. King et al., “Incidence of Celiac Disease Is Increasing Over Time:
A Systematic Review and Meta-Analysis,” American Journal of
Gastroenterology 115, no. 4 (2020): 507–525. doi:
10.14309/ajg.0000000000000523.
2. S. S. S. Boyanapalli and A. T. Kong, “‘Curcumin, the King of Spices’:
Epigenetic Regulatory Mechanisms in the Prevention of Cancer,
Neurological, and Inflammatory Diseases,” Current Pharmacology Reports
1, no. 2 (2015): 129–139, doi: 10.1007/s40495-015-0018-x.
3. A. E. Connelly et al., “High-Rosmarinic Acid Spearmint Tea in the
Management of Knee Osteoarthritis Symptoms,” Journal of Medicinal
Food 17, no. 12 (2014): 1361–1367, doi: 10.1089/jmf.2013.0189.
4. Y. Panahi et al., “Rosemary Oil vs Minoxidil 2% for the Treatment of
Androgenetic Alopecia: A Randomized Comparative Trial,” Skinmed 13,
no. 1 (Jan–Feb 2015): 15–21.
5. J. Zhou et al., “Sulforaphane-Induced Epigenetic Regulation of Nrf2
Expression by DNA Methyltransferase in Human Caco-2 cells,” Oncology
Letters 18 (2019): 2639–2647, doi: 10.3892/ol.2019.10569.
6. L. Beaver et al., “Broccoli Sprouts Delay Prostate Cancer Formation
and Decrease Prostate Cancer Severity with a Concurrent Decrease in
HDAC3 Protein Expression in Transgenic Adenocarcinoma of the Mouse
Prostate (TRAMP) Mice,” Current Developments in Nutrition 2, no. 3
(2017), nzy002, doi: 10.1093/cdn/nzy002.
7. US Department of Agriculture, “Dietary Guidelines for Americans
2015–2020, Eighth Edition,” December 2015,
https://health.gov/sites/default/files/2019-09/2015-
2020_Dietary_Guidelines.pdf.
8. H. Yang et al., “Preventive Effects of Lentinus Edodes on
Homocysteinemia in Mice,” Experimental and Therapeutic Medicine 6, no.
2 (2013): 465–468, doi: 10.3892/etm.2013.1130.
CHAPTER 7
1. E. Grazioli et al., “Physical Activity in the Prevention of Human
Diseases: Role of Epigenetic Modifications,” BMC Genomics 18
(November 14, 2017 [Suppl 8]): 802, doi: 10.1186/s12864-017-4193-5; F.
Sanchis-Gomar et al., “Physical Exercise as an Epigenetic Modulator:
Eustress, the ‘Positive Stress’ as an Effector of Gene Expression,” Journal
of Strength Conditioning Research 26, no. 12 (2012): 3469–3472, doi:
10.1519/JSC.0b013e31825bb594; I. Dimauro, M. P. Paronetto, and D.
Caporossi, “Exercise, Redox Homeostasis and the Epigenetic Landscape,”
Redox Biology 35, 2020: 101477, doi: 10.1016/j.redox.2020.101477.
2. A. J. White et al., “Recreational and Household Physical Activity at
Different Time Points and DNA Global Methylation,” European Journal of
Cancer 49, no. 9 (2013): 2199–2206, doi: 10.1016/j.ejca.2013.02.013.
3. M. D. Nitert et al., “Impact of an Exercise Intervention on DNA
Methylation in Skeletal Muscle from First-Degree Relatives of Patients
with Type 2 Diabetes,” Diabetes 61, no. 12 (2012): 3322–3332, doi:
10.2337/db11-1653; T. Rönn et al., “A Six Months Exercise Intervention
Influences the Genome-Wide DNA Methylation Pattern in Human Adipose
Tissue,” PLoS Genetics 9, no. 6 (2013): e1003572, doi:
10.1371/journal.pgen.1003572.
4. K. Nakajima et al., “Exercise Effects on Methylation of ASC Gene,”
International Journal of Sports Medicine 31, no. 9 (2010): 671–675, doi:
10.1055/s-0029-1246140; T. Rönn et al., “A Six Months Exercise
Intervention Influences the Genome-Wide DNA Methylation Pattern in
Human Adipose Tissue,” PLoS Genetics 9, no. 6 (2013): e1003572, doi:
10.1371/journal.pgen.1003572.
5. F. Gomez-Pinilla et al., “Exercise Impacts Brain-Derived Neurotrophic
Factor Plasticity by Engaging Mechanisms of Epigenetic Regulation,”
European Journal of Neuroscience 33, no. 3 (2011): 383–390, doi:
10.1111/j.1460-9568.2010.07508.x; P. Z. Liu and R. Nusslock, “Exercise-
Mediated Neurogenesis in the Hippocampus via BDNF,” Frontiers in
Neuroscience 12 (2018): 52, doi: 10.3389/fnins.2018.00052.
6. W. M. Brown, “Exercise-Associated DNA Methylation Change in
Skeletal Muscle and the Importance of Imprinted Genes: A Bioinformatics
Meta-Analysis,” British Journal of Sports Medicine 49, no. 24 (2015):
1567–1578, doi: 10.1136/bj sports-2014-094073.
7. R. Barrès et al., “Acute Exercise Remodels Promoter Methylation in
Human Skeletal Muscle,” Cell Metabolism 15, no. 3 (March 7, 2012): 405–
411, doi: 10.1016/j.cmet.2012.01.001.
8. W. M. Brown, “Exercise-Associated DNA Methylation Change in
Skeletal Muscle and the Importance of Imprinted Genes: A Bioinformatics
Meta-Analysis,” British Journal of Sports Medicine 49, no. 24 (2015):
1567–1578, doi: 10.1136/bjsports-2014-094073.
9. D. Moreau and E. Chou, “The Acute Effect of High-Intensity Exercise
on Executive Function: A Meta-Analysis,” Perspectives on Psychological
Science 14, no. 5 (2019): 734–764, doi: 10.1177/1745691619850568.
10. F. Maillard, B. Pereira, and N. Boisseau, “Effect of High-Intensity
Interval Training on Total, Abdominal and Visceral Fat Mass: A Meta-
Analysis.” Sports Medicine 48, no. 2 (February 2018): 269–288, doi:
10.1007/s40279-017-0807-y.
11. E. G. Trapp et al., “The Effects of High-Intensity Intermittent
Exercise Training on Fat Loss and Fasting Insulin Levels of Young
Women,” International Journal of Obesity 32, no. 4 (2008): 684–691, doi:
10.1038/sj.ijo.0803781.
12. K. S. Weston, U. Wisloff, and J. S. Coombes, “High-Intensity Interval
Training in Patients with Lifestyle-Induced Cardiometabolic Disease: A
Systematic Review and Meta-Analysis,” British Journal of Sports Medicine
(Systematic Review & Meta-Analysis) 48, no. 16 (August 2014): 1227–
1234, doi: 10.1136/bjsports-2013-092576; V. S. Coswig et al. “Effects of
High vs Moderate-Intensity Intermittent Training on Functionality, Resting
Heart Rate and Blood Pressure of Elderly Women,” Journal of
Translational Medicine 18, no. 88 (2020), doi: 10.1186/s12967-020-02261-
8.
13. A. S. Zannas et al., “Lifetime Stress Accelerates Epigenetic Aging in
an Urban, African American Cohort: Relevance of Glucocorticoid
Signaling” [published correction appears in Genome Biology 19, no. 1 (May
23, 2018): 61], Genome Biology 16 (December 17, 2015): 266, doi:
10.1186/s13059-015-0828-5.
14. G. van Steenwyk et al., “Transgenerational Inheritance of Behavioral
and Metabolic Effects of Paternal Exposure to Traumatic Stress in Early
Postnatal Life: Evidence in the 4th Generation,” Environmental Epigenetics
16, no. 4 (October 16, 2018): dvy023, doi: 10.1093/eep/dvy023.
15. Ewen Callaway, “Fearful Memories Passed Down to Mouse
Descendants,” Nature (December 1, 2013),
www.scientificamerican.com/article/fearful-memories-passed-down/.
16. M. J. Meaney and M. Szyf, “Environmental Programming of Stress
Responses Through DNA Methylation: Life at the Interface Between a
Dynamic Environment and a Fixed Genome,” Dialogues in Clinical
Neuroscience 7, no. 2 (2005): 103–123.
17. S. R. Pilkay et al., “Maternal Trauma and Fear History Predict BDNF
Methylation and Gene Expression in Newborns,” PeerJ 8 (May 22, 2020):
e8858, doi: 10.7717/peerj.8858.
18. L. Ramo-Fernández et al., “The Effects of Childhood Maltreatment
on Epigenetic Regulation of Stress-Response Associated Genes: an
Intergenerational Approach,” Scientific Reports, 9, no. 983 (2019), doi:
10.1038/s41598-018-36689-2.
19. M. A. Aristizabal et al., “Biological Embedding of Experience: A
Primer on Epigenetics,” Proceedings of the National Academy of Sciences,
117, no. 38 (September 2020): 23261–23269, doi:
10.1073/pnas.1820838116.
20. D. Mehta et al., “A Systematic Review of DNA Methylation and
Gene Expression Studies in Posttraumatic Stress Disorder, Posttraumatic
Growth, and Resilience,” Journal of Traumatic Stress 33, no. 2 (April
2020): 171–180, Epub January 17, 2020, doi: 10.1002/jts.22472.
21. T. X. Fujisawa et al., “Oxytocin Receptor DNA Methylation and
Alterations of Brain Volumes in Maltreated Children,”
Neuropsychopharmacology 44, no. 12 (2019): 2045–2053, doi:
10.1038/s41386-019-0414-8.
22. D. Mehta et al., “A Systematic Review of DNA Methylation and
Gene Expression Studies in Posttraumatic Stress Disorder, Posttraumatic
Growth, and Resilience,” Journal of Traumatic Stress 33, no. 2 (April
2020): 171–180, Epub January 17, 2020, doi: 10.1002/jts.22472.
23. A. S. Zannas et al., “Lifetime Stress Accelerates Epigenetic Aging in
an Urban, African American Cohort: Relevance of Glucocorticoid
Signaling” [published correction appears in Genome Biology 19, no. 1 (May
23, 2018): 61], Genome Biology 16 (December 17, 2015): 266, doi:
10.1186/s13059-015-0828-5; E. Wolf et al., “Accelerated DNA Methylation
Age: Associations w/PTSD and Neural Integrity,”
Psychoneuroendocrinology 63 (January 2016): 155–162, doi:
10.1016/j.psyneuen.2015.09.020; S. R. Moore et al., “Epigenetic Correlates
of Neonatal Contact in Humans,” Development and Psychopathology 29,
no. 5 (2017): 1517–1538, doi: 10.1017/S0954579417001213; E. M.
Vidrascu et al., “Effects of Early- and Mid-Life Stress on DNA Methylation
of Genes Associated with Subclinical Cardiovascular Disease and
Cognitive Impairment: A Systematic Review,” BMC Medical Genetics 20,
no. 39 (2019), doi: 10.1186/s12881-019-0764-4.
24. R. Chaix et al., “Differential DNA Methylation in Experienced
Meditators After an Intensive Day of Mindfulness-Based Practice:
Implications for Immune-Related Pathways,” Brain, Behavior, and
Immunity 84 (February 2020): 36–44, doi: 10.1016/j.bbi.2019.11.003.
25. S. Venditti et al., “Molecules of Silence: Effects of Meditation on
Gene Expression and Epigenetics,” Frontiers in Psychology 11 (2020):
1767, doi: 10.3389/fpsyg.2020.01767.
26. R. Chaix et al., “Epigenetic Clock Analysis in Long-Term
Meditators,” Psychoneuroendocrinology 85 (2017): 210–214, doi:
10.1016/j.psyneuen.2017.08.016.
27. S. Pavanello et al., “Exploring Epigenetic Age in Response to
Intensive Relaxing Training: A Pilot Study to Slow Down Biological Age,”
International Journal of Environmental Research Public Health 16, no. 17
(2019), doi: 10.3390/ijerph16173074.
28. “No Rest for the Aged: As People Get Older, Sleep Quantity and
Quality Decline,” Cell Press, April 5, 2017,
www.eurekalert.org/pub_releases/2017-04/cp-nrf 033017.php.
29. J. J. Gooley et al., “Exposure to Room Light Before Bedtime
Suppresses Melatonin Onset and Shortens Melatonin Duration in Humans,”
Journal of Clinical Endocrinology and Metabolism 96, no. 3 (March 2011):
E463-72, doi: 10.1210/jc.2010-2098.
30. American Sleep Association, “Deep Sleep: How to Get More of It,”
www.sleepassociation.org/about-sleep/stages-of-sleep/deep-sleep/.
31. Alzheimer’s Drug Discovery Foundation, “Diphenhydramine (e.g.,
Benadryl),” CognitiveVitality.org, August 29, 2017,
www.alzdiscovery.org/uploads/cognitive
_vitality_media/Diphenhydramine-Cognitive-Vitality-For-Researchers.pdf.
32. Y. M. Lee, D. R. Jacobs Jr., and D. H. Lee, “Persistent Organic
Pollutants and Type 2 Diabetes: A Critical Review of Review Articles,”
Frontiers in Endocrinology (Lausanne, Switzerland) 9 (November 27,
2018): 712, doi: 10.3389/fendo.2018.00712.
33. Moshe Szyf, “The Implications of DNA Methylation for Toxicology:
Toward Toxicomethylomics, the Toxicology of DNA Methylation,”
Toxicological Sciences 120, no. 2 (April 2011): 235–255, doi:
10.1093/toxsci/kfr024.
34. M. Manikkam et al., “Pesticide Methoxychlor Promotes the
Epigenetic Transgenerational Inheritance of Adult-Onset Disease Through
the Female Germline,” PLoS One 9, no. 7 (July 24, 2014): e102091, doi:
10.1371/journal.pone.0102091.
35. G. H. Heinz et al., “Enhanced Reproduction in Mallards Fed a Low
Level of Methylmercury: An Apparent Case of Hormesis,” Environmental
Toxicology and Chemistry 29, no. 3 (March 2010): 650–653, doi:
10.1002/etc.64.
36. S. Sutou, “Low-Dose Radiation from A-Bombs Elongated Lifespan
and Reduced Cancer Mortality Relative to Un-Irradiated Individuals,”
Genes and Environment 40, no. 26 (2018), doi: 10.1186/s41021-018-0114-
3.
37. Randy L. Jirtle, “Epigenetic Responses to Low Dose Ionizing
Radiation,” Free Radical Biology and Medicine 124 (2018): 559, doi:
10.1016/j.freeradbiomed.2018.05.014.
38. M. P. Mattson, “Hormesis Defined,” Ageing Research Review 7, no. 1
(January 2008): 1–7, doi: 10.1016/j.arr.2007.08.007. Epub December 5,
2007.
39. D. Lamming, J. G. Wood, and D. Sinclair, “MicroReview: Small
Molecules That Regulate Lifespan: Evidence for Xenohormesis,”
Molecular Microbiology 53 (2004). doi: 10.1111/j.1365-
2958.2004.04209.x.
40. R. E. Hodges and D. M. Minich, “Modulation of Metabolic
Detoxification Pathways Using Foods and Food-Derived Components: A
Scientific Review with Clinical Application,” Journal of Nutrition and
Metabolism 2015 (2015): 760689, doi: 10.1155/2015/760689.
41. B. Hennig et al., “The Role of Nutrition in Influencing Mechanisms
Involved in Environmentally Mediated Diseases,” Reviews on
Environmental Health 33, no. 1 (March 28, 2018): 87–97, doi:
10.1515/reveh-2017-0038.
42. M. Beidelschies et al., “Patient Outcomes and Costs Associated with
Functional Medicine-based Care in a Shared Versus Individual Setting for
Patients with Chronic Conditions: A Retrospective Cohort Study,” BMJ
Open 11 (2021): e048294. doi: 10.1136/bmjopen-2020-048294.
43. R. Huffmeijer, M. H. van Ijzendoorn, and M. J. Bakermans-
Kranenburg, “Ageing and Oxytocin: A Call for Extending Human Oxytocin
Research to Ageing Populations—A Mini-Review,” Gerontology 59, no. 1
(2013): 32-39, doi: 10.1159/000341333; S.-Y. Cho et al., “Impact of
Oxytocin on Skin Ageing,” British Journal of Dermatology 181 (2019):
e148-e148, doi: 10.1111/bjd.18568; C. Elabd et al., “Oxytocin Is an Age-
Specific Circulating Hormone That Is Necessary for Muscle Maintenance
and Regeneration,” Nature Communications 5 (June 10, 2014): 4082, doi:
10.1038/ncomms5082; A. B. Reiss et al., “Oxytocin: Potential to Mitigate
Cardiovascular Risk,” Peptides 117 (July 2019): 170089, doi:
10.1016/j.peptides.2019.05.001.
44. C. I. Park et al., “Reduced DNA Methylation of the Oxytocin
Receptor Gene Is Associated with Obsessive-Compulsive Disorder,”
Clinical Epigenetics 20, no. 1 (2020): 101, doi: 10.1186/s13148-020-00890-
w.
45. A. Klockars, A. S. Levine, and P. K. Olszewski, “Central Oxytocin
and Food Intake: Focus on Macronutrient-Driven Reward,” Frontiers in
Endocrinology (Lausanne, Switzerland) 6 (April 28, 2015): 65, doi:
10.3389/fendo.2015.00065.
46. C. Maud et al., “The Role of Oxytocin Receptor Gene (OXTR) DNA
Methylation (DNAm) in Human Social and Emotional Functioning: A
Systematic Narrative Review,” BMC Psychiatry 18, no. 154 (2018), doi:
10.1186/s12888-018-1740-9.
47. S. R. Moore et al., “Epigenetic Correlates of Neonatal Contact in
Humans,” Development and Psychopathology 29, no. 5 (December 2017):
1517–1538, doi: 10.1017/S0954579417001213.
48. Ibid.
49. C. H. Zeanah et al., “Sensitive Periods,” Monographs of the Society
for Research in Child Development 76, no. 4 (December 2011): 147–162,
doi: 10.1111/j.1540-5834.2011.00631.x.
50. E. Agerbo, P. B. Mortensen, and T. Munk-Olsen, “Childlessness,
Parental Mortality and Psychiatric Illness: A Natural Experiment Based on
In Vitro Fertility Treatment and Adoption,” Journal of Epidemiology &
Community Health 67 (2013): 374–376, doi: 10.1136/jech-2012-201387.
51. P. F. McArdle et al., “Does Having Children Extend Life Span? A
Genealogical Study Of Parity and Longevity in the Amish,” Journals of
Gerontology Series A: Biological Sciences and Medical Sciences 61, no. 2
(February 2006): 190–195, doi: 10.1093/gerona/61.2.190.
52. J. Mitteldorf, “Female Fertility and Longevity,” Age (Dordrecht,
Netherlands: Online) 32, no. 1 (March 2010): 79–84, doi: 10.1007/s11357-
009-9116-1.
53. M. S. Carmichael et al., “Relationships Among Cardiovascular,
Muscular, and Oxytocin Responses During Human Sexual Activity,”
Archives of Sexual Behavior 23 (1994): 59–79, doi: 10.1007/BF01541618.
54. J. A. Barraza and P. J. Zak, “Empathy Toward Strangers Triggers
Oxytocin Release and Subsequent Generosity,” Annals of the New York
Academy of Sciences 1167 (June 2009): 182–189, doi: 10.1111/j.1749-
6632.2009.04504.x.
55. C. Grape et al., “Does Singing Promote Well-Being?: An Empirical
Study of Professional and Amateur Singers During a Singing Lesson,”
Integrative Physiological and Behavioral Science 38, no. 1 (Jan-Mar 2003):
65–74, doi: 10.1007/BF02734261.
56. Michael J. Poulin and E. Alison Holman, “Helping Hands, Healthy
Body? Oxytocin Receptor Gene and Prosocial Behavior Interact to Buffer
the Association Between Stress and Physical Health,” Hormones and
Behavior 63, no. 3 (2013): 510–517, doi: 10.1016/j.yhbeh.2013.01.004.
57. V. Morhenn, L. E. Beavin, and P. J. Zak, “Massage Increases
Oxytocin and Reduces Adrenocorticotropin Hormone in Humans,”
Alternative Therapies in Health and Medicine 18, no. 6 (Nov-Dec 2012):
11–18.
CHAPTER 8
1. H. Andersson et al., “Oral Administration of Lactobacillus plantarum
299v Reduces Cortisol Levels in Human Saliva During Examination
Induced Stress: A Randomized, Double-Blind Controlled Trial,”
International Journal of Microbiology 2016 (2016): 8469018, doi:
10.1155/2016/8469018.
2. F. Watanabe et al., “Vitamin B12-Containing Plant Food Sources for
Vegetarians,” Nutrients 6, no. 5 (May 5, 2014): 1861–1873, doi:
10.3390/nu6051861.
3. C. Paul and D. M. Brady, “Comparative Bioavailability and Utilization
of Particular Forms of B12 Supplements with Potential to Mitigate B12-
Related Genetic Polymorphisms,” Integrative Medicine: A Clinician’s
Journal 16, no. 1 (February 2017): 42–49.
4. F. L. Crowe et al., “Plasma Concentrations of 25-Hydroxyvitamin D in
Meat Eaters, Fish Eaters, Vegetarians and Vegans: Results from the EPIC-
Oxford Study,” Public Health Nutrition 14, no. 2 (February 2011): 340–
346, doi: 10.1017/S1368980010002454.
5. J. L. Harper and M. E. Conrad, “Iron Deficiency Anemia Treatment
and Management,” Medscape (September 30, 2020),
https://emedicine.medscape.com/article/202333-treatment#d7.
6. I. S. Fetahu, J. Höbaus, and E. Kállay, “Vitamin D and the
Epigenome,” Frontiers in Physiology 5 (April 29, 2014): 164, doi:
10.3389/fphys.2014.00164.
7. E. Roshdy et al., “Treatment of Symptomatic Uterine Fibroids with
Green Tea Extract: A Pilot Randomized Controlled Clinical Study,”
International Journal of Women’s Health 5 (August 7, 2013): 477–486, doi:
10.2147/IJWH.S41021.
8. J. Hu et al., “The Safety of Green Tea and Green Tea Extract
Consumption in Adults—Results of a Systematic Review,” Regulatory
Toxicology and Pharmacology 95 (June 2018): 412–433, doi:
10.1016/j.yrtph.2018.03.019.
9. A. Bielak-Zmijewska et al., “The Role of Curcumin in the Modulation
of Ageing,” International Journal of Molecular Sciences 20, no. 5 (March
12, 2019): 1239, doi: 10.3390/ijms20051239.
10. R. J. Keegan et al., “Photobiology of Vitamin D in Mushrooms and
Its Bioavailability in Humans,” Dermatoendocrinology 15, no. 1 (January 1,
2013): 165–176, doi: 10.4161/derm.23321.
11. R. Cooper et al., “Creatine Supplementation with Specific View to
Exercise/Sports Performance: An Update,” Journal of the International
Society of Sports Nutrition, 9, no.1 (July 20, 2012): 33, doi:10.1186/1550-
2783-9-33.
12. Y. Heianza et al., “Long-Term Changes in Gut Microbial Metabolite
Trimethylamine N-Oxide and Coronary Heart Disease Risk,” Journal of the
American College of Cardiology 75, no. 7 (February 25, 2020): 763–772,
doi: 10.1016/j.jacc.2019.11.060.
13. Y. Heianza and L. Qi, “Reply: TMAO Changes and Coronary Heart
Disease Risk: Potential Impact and Study Considerations,” Journal of the
American College of Cardiology 75, no. 24 (June 23, 2020): 3102–3104,
doi: 10.1016/j.jacc.2020.04.050.
14. Linus Pauling Institute, “Choline,” Micronutrient Information Center,
https://lpi.oregonstate.edu/mic/other-nutrients/choline#safety/; C. Roncal et
al., “Trimethylamine-N-Oxide (TMAO) Predicts Cardiovascular Mortality
in Peripheral Artery Disease,” Scientific Reports 9, no. 15580 (2019), doi:
10.1038/s41598-019-52082-z.
15. R. W. Dellinger et al., “Repeat Dose NRPT (Nicotinamide Riboside
and Pterostilbene) Increases NAD+ Levels in Humans Safely and
Sustainably: A Randomized, Double-Blind, Placebo-Controlled Study,”
NPJ Aging and Mechanisms of Disease 3 (November 24, 2017): 17, doi:
10.1038/s41514-017-0016-9, Erratum in NPJ Aging and Mechanisms of
Disease 4 (August 20, 2018): 8.
16. Wen Li et al., “Emerging Senolytic Agents Derived from Natural
Products,” Mechanisms of Ageing and Development 181 (2019): 1–6, doi:
10.1016/j.mad.2019.05.001.
17. M. J. Yousefzadeh et al., “Fisetin Is a Senotherapeutic That Extends
Health and Lifespan,” EBioMedicine 36 (October 2018): 18–28, doi:
10.1016/j.ebiom.2018.09.015.
18. A. Farsad-Naeimi et al., “Effect of Fisetin Supplementation on
Inflammatory Factors and Matrix Metalloproteinase Enzymes in Colorectal
Cancer Patients,” Food and Function 9, no. 4 (April 25, 2018): 2025–2031,
doi: 10.1039/c7fo 01898c.
19. M. P. K. J. Engelen and N. E. P. Deutz, “Is ß-hydroxy β-
methylbutyrate an Effective Anabolic Agent to Improve Outcome in Older
Diseased Populations?,” Current Opinion in Clinical Nutrition and
Metabolic Care 21, no. 3 (May 2018): 207–213, doi:
10.1097/MCO.0000000000000459.
20. Y. Lin et al., “Luteolin, a Flavonoid with Potential for Cancer
Prevention and Therapy,” Current Cancer Drug Targets 8, no. 7 (November
2008): 634–646, doi: 10.2174/156800908786241050.
21. G. Lai et al., “Alcohol Extracts from Ganoderma lucidum Delay the
Progress of Alzheimer’s Disease by Regulating DNA Methylation in
Rodents,” Frontiers in Pharmacology 10 (March 26, 2019): 272, doi:
10.3389/fphar.2019.00272.
CHAPTER 9
1. G. Du Toit et al.; LEAP Study Team, “Randomized Trial of Peanut
Consumption in Infants at Risk for Peanut Allergy,” New England Journal
of Medicine 372, no. 9 (February 26, 2015): 803–813, doi:
10.1056/NEJMoa1414850, Epub February 23, 2015, Erratum in: New
England Journal of Medicine 375, no. 4 (July 28, 2016): 398; M. R. Perkin
et al.; EAT Study Team, “Randomized Trial of Introduction of Allergenic
Foods in Breast-Fed Infants,” New England Journal of Medicine 374, no 18
(May 5, 2016): 1733–1743, Epub March 4, 2016, doi:
10.1056/NEJMoa1514210.
2. I. C. Weaver et al., “Epigenetic Programming by Maternal Behavior,”
Nature Neuroscience 7, no. 8 (August 7, 2004): 847–854, doi:
10.1038/nn1276.
3. E. C. Dunn et al., “Sensitive Periods for the Effect of Childhood
Adversity on DNA Methylation: Results from a Prospective, Longitudinal
Study,” Biological Psychiatry 85, no. 10 (May 15, 2019): 838–849, doi:
10.1016/j.biopsych.2018.12.023, Epub January 21, 2019, Erratum in
Biological Psychiatry 86, no. 1 (July 1, 2019): 76.
4. K. L. Wisner et al., “Onset Timing, Thoughts of Self-harm, and
Diagnoses in Postpartum Women with Screen-Positive Depression
Findings,” JAMA Psychiatry 70, no. 5 (2013): 490–498, doi:
10.1001/jamapsychiatry.2013.87.
5. M. Kimmel et al., “Oxytocin Receptor DNA Methylation in
Postpartum Depression,” Psychoneuroendocrinology 69 (July 2016): 150–
160, doi: 10.1016/j.psyneuen.2016.04.008.
6. S. Bhattacharya et al., “Stress Across Generations: DNA Methylation
as a Potential Mechanism Underlying Intergenerational Effects of Stress in
Both Post-Traumatic Stress Disorder and Pre-Clinical Predator Stress
Rodent Models,” Frontiers in Behavioral Neuroscience 13 (2019): 113, doi:
10.3389/fnbeh.2019.00113.
7. C. Nagy and G. Turecki, “Sensitive Periods in Epigenetics: Bringing
Us Closer to Complex Behavioral Phenotypes,” Epigenomics 4, no. 4
(August 2012): 445–457, doi: 10.2217/epi.12.37.
8. D. Vågerö et al., “Paternal Grandfather’s Access to Food Predicts All-
Cause and Cancer Mortality in Grandsons,” Nature Communications 9, no.
5124 (2018), doi: 10.1038/s41467-018-07617-9.
9. H. Wu et al., “Environmental Susceptibility of the Sperm Epigenome
During Windows of Male Germ Cell Development,” Current
Environmental Health Reports 2, no. 4 (December 2015): 356–366, doi:
10.1007/s40572-015-0067-7.
10. A. Soubry et al., “A Paternal Environmental Legacy: Evidence for
Epigenetic Inheritance Through the Male Germ Line,” Bioessays 36, no. 4
(April 2014): 359–371, doi: 10.1002/bies.201300113.
11. L. Han et al., “Changes in DNA Methylation from Pre- to Post-
Adolescence Are Associated with Pubertal Exposures,” Clinical
Epigenetics 11, no. 176 (2019), doi: 10.1186/s13148-019-0780-4.
12. D. K. Eaton et al., “Prevalence of Insufficient, Borderline, and
Optimal Hours of Sleep Among High School Students—United States,
2007,” Journal of Adolescent Health 46, no. 4 (April 2010): 399–401, doi:
10.1016/j.jadohealth.2009.10.011.
13. G. V. Skuladottir et al., “One-Night Sleep Deprivation Induces
Changes in the DNA Methylation and Serum Activity Indices of Stearoyl-
CoA Desaturase in Young Healthy Men,” Lipids in Health and Disease 15,
no. 1 (August 26, 2016): 137, doi: 10.1186/s12944-016-0309-1.
14. M. Amatruda et al., “Epigenetic Effects of n-3 LCPUFAs: A Role in
Pediatric Metabolic Syndrome,” International Journal of Molecular
Sciences 20, no. 9 (April 29, 2019): 2118, doi: 10.3390/ijms20092118.
15. M. Varela-Rey et al., “Alcohol, DNA Methylation, and Cancer,”
Alcohol Research 35, no. 1 (2013): 25–35.
16. G. C. Williams, “Pleiotropy, Natural Selection, and the Evolution of
Senescence,” Science of Aging Knowledge Environment 2001, no. 1
(October 3, 2001): cp13,
http://sageke.sciencemag.org/cgi/content/abstract/sageke.2001/1/cp13.
17. S. Bhasin et al., “Age-Related Changes in the Male Reproductive
System” [Updated December 14, 2018], in K. R. Feingold et al., editors,
Endotext, (South Dartmouth, MA: MDText.com, Inc., 2000–),
www.ncbi.nlm.nih.gov/books/NBK278998/; American College of
Obstetricians and Gynecologists, “Having a Baby After Age 35: How
Aging Affects Fertility and Pregnancy,” www.acog.org/womens-
health/faqs/having-a-baby-after-age-35-how-aging-affects-fertility-and-
pregnancy#:~:text=A%20woman’s%20peak%20reproductive%20years,is%
20unlikely%20for%20most%20women.
18. A. Strittmatter, U. Sunde, and D. Zegners, “Life Cycle Patterns of
Cognitive Performance over the Long Run,” Proceedings of the National
Academy of Sciences of the United States of America 117, no. 4 (November
3, 2020): 27255–27261, Epub October 19, 2020, doi:
10.1073/pnas.2006653117.
19. A. Salas-Huetos et al., “Sperm DNA Methylation Changes After
Short-Term Nut Supplementation in Healthy Men Consuming a Western-
style Diet” [published online ahead of print], September 23, 2020,
Andrology 2020, doi: 10.1111/andr.12911.
20. R. Schrott et al., “Sperm DNA Methylation Altered by THC and
Nicotine: Vulnerability of Neurodevelopmental Genes with Bivalent
Chromatin,” Scientific Reports 10, no. 1 (September 29, 2020): 16022, doi:
10.1038/s41598-020-72783-0.
21. M. Ben Maamar et al., “Epigenome-Wide Association Study for
Glyphosate Induced Transgenerational Sperm DNA Methylation and
Histone Retention Epigenetic Biomarkers for Disease,” Epigenetics
(December 9, 2020): 1–18, doi: 10.1080/15592294.2020.1853319.
22. R. Elango and R. O. Ball, “Protein and Amino Acid Requirements
During Pregnancy,” Advances in Nutrition 7, no. 4 (July 15, 2016): 839S-
44S, doi: 10.3945/an.115.011817.
23. L. P. Stone et al., “Customized Nutritional Enhancement for Pregnant
Women Appears to Lower Incidence of Certain Common Maternal and
Neonatal Complications: An Observational Study,” Global Advances in
Health and Medicine 3, no. 6 (November 2014): 50–55, doi:
10.7453/gahmj.2014.053.
24. Centers for Disease Control and Prevention, “Folic Acid,”
www.cdc.gov/ncbddd/folicacid/about.html.
25. National Institutes of Health, Office of Dietary Supplements, “Folate:
Fact Sheet for Consumers,” https://ods.od.nih.gov/factsheets/Folate-
Consumer/#h8.
26. E. Keating et al., “Excess Perigestational Folic Acid Exposure
Induces Metabolic Dysfunction in Post-natal Life,” Journal of
Endocrinology 224, no. 3 (March 2015): 245–259, doi: 10.1530/JOE-14-
0448.
27. D. C. Dolinoy et al., “Maternal Genistein Alters Coat Color and
Protects Avy Mouse Offspring from Obesity by Modifying the Fetal
Epigenome,” Environmental Health Perspectives 114, no. 4 (April 2006):
567–572, doi: 10.1289/ehp.8700.
28. American College of Obstetricians and Gynecologists, “Nutrition
During Pregnancy,” www.acog.org/womens-health/faqs/nutrition-during-
pregnancy.
29. L. P. Stone et al., “Customized Nutritional Enhancement for Pregnant
Women Appears to Lower Incidence of Certain Common Maternal and
Neonatal Complications: An Observational Study,” Global Advances in
Health and Medicine 3, no. 6 (November 2014): 50–55, doi:
10.7453/gahmj.2014.053.
30. M. E. Levine et al., “Menopause Accelerates Biological Aging,”
Proceedings of the National Academy of Sciences of the United States of
America 113, no. 33 (August 16, 2016): 9327–9332, Epub July 25, 2016,
doi: 10.1073/pnas.1604558113.
31. C. L. Kuo et al., “Biological Aging Predicts Vulnerability to COVID-
19 Severity in UK Biobank Participants,” Journals of Gerontology Series
A: Biological Sciences and Medical Sciences (March 4, 2021): glab060,
Epub ahead of print, doi: 10.1093/gerona/glab060.
CHAPTER 10
1. Kirsty J. Flower et al., “DNA Methylation Profiling to Assess
Pathogenicity of BRCA1 Unclassified Variants in Breast Cancer,”
Epigenetics 10, no. 12 (2015): 1121–1132, doi:
10.1080/15592294.2015.1111504.
2. M. C. King et al., “Breast and Ovarian Cancer Risks Due to Inherited
Mutations in BRCA1 and BRCA2,” Science 2003 302, no. 5645 (October
24, 2003): 643–646, doi: 10.1126/science.1088759.
3. Ibid.
4. R. L. Baldwin et al., “BRCA1 Promoter Region Hypermethylation in
Ovarian Carcinoma: A Population-Based Study,” Cancer Research 60, no.
19 (October 1, 2000): 5329–5333.
5. N. Al-Moghrabi et al., “Methylation of BRCA1 and MGMT Genes in
White Blood Cells Are Transmitted from Mothers to Daughters,” Clinical
Epigenetics 10, no. 99 (2018), doi: 10.1186/s13148-018-0529-5.
6. G. A. Millot et al. on behalf of ENIGMA Consortium Functional
Assay Working Group, “A Guide for Functional Analysis of BRCA1
Variants of Uncertain Significance.” Human Mutation 33 no. 11 (November
2012): 1526–1537, doi: 10.1002/humu.22150, Epub July 16, 2012.
7. Ranjit Manchanda et al., “Economic Evaluation of Population-Based
BRCA1/BRCA2 Mutation Testing Across Multiple Countries and Health
Systems,” Cancers (2020), doi: 10.3390/cancers12071929.
8. Kirsty J. Flower et al., “DNA Methylation Profiling to Assess
Pathogenicity of BRCA1 Unclassified Variants in Breast Cancer,”
Epigenetics 10, no. 12 (2015): 1121–1132, doi:
10.1080/15592294.2015.1111504.
9. S. S. Oltra et al., “Acceleration in the DNA Methylation Age in Breast
Cancer Tumours from Very Young Women,” Scientific Reports 9, no. 14991
(2019), doi: 10.1038/s41598-019-51457-6.
10. A. J. Papoutsis et al., “BRCA-1 Promoter Hypermethylation and
Silencing Induced by the Aromatic Hydrocarbon Receptor-Ligand TCDD
Are Prevented by Resveratrol in MCF-7 Cells,” Journal of Nutritional
Biochemistry 23, no. 10 (October 2012): 1324–1332, doi:
10.1016/j.jnutbio.2011.08.001; A. J. Papoutsis et al., “Resveratrol Prevents
Epigenetic Silencing of BRCA-1 by the Aromatic Hydrocarbon Receptor in
Human Breast Cancer Cells,” Journal of Nutrition 140, no. 9 (September
2010): 1607–1614, doi: 10.3945/jn.110.123422.
11. P. Selvakumar et al., “Flavonoids and Other Polyphenols Act as
Epigenetic Modifiers in Breast Cancer,” Nutrients 12, no. 3 (March 13,
2020): 761, doi: 10.3390/nu12030761.
12. R. Bosviel et al., “Epigenetic Modulation of BRCA1 and BRCA2
Gene Expression by Equol in Breast Cancer Cell Lines,” British Journal of
Nutrition 108, no. 7 (2012): 1187–1193, doi:
10.1017/S000711451100657X.
13. B. Mayo, L. Vázquez, and A. B. Flórez, “Equol: A Bacterial
Metabolite from the Daidzein Isoflavone and Its Presumed Beneficial
Health Effects,” Nutrients 11, no. 9 (September 16, 2019): 2231, doi:
10.3390/nu11092231.
14. S. Kundur et al., “Synergistic Anticancer Action of Quercetin and
Curcumin Against Triple-Negative Breast Cancer Cell Lines,” Journal of
Cellular Physiology 234, no. 7 (July 2019): 11103–11118, doi:
10.1002/jcp.27761.
15. N. Petrucelli, M. B. Daly, and T. Pal, “BRCA1- and BRCA2-
Associated Hereditary Breast and Ovarian Cancer,” September 4, 1998
[updated December 15, 2016], in M. P. Adam et al., editors, GeneReviews
(Seattle, WA: University of Washington, 1993–2020)
www.ncbi.nlm.nih.gov/books/NBK1247/.
16. G. Luo et al., “Pancreatic Cancer: BRCA Mutation and Personalized
Treatment,” Expert Review of Anticancer Therapy 15, no. 10 (2015): 1223–
1231, doi: 10.1586/14737140.2015.1086271; J. Mijnes et al., “Promoter
Methylation of DNA Damage Repair (DDR) Genes in Human Tumor
Entities: RBBP8/CtIP Is Almost Exclusively Methylated in Bladder
Cancer,” Clinical Epigenetics 10 (February 6, 2018): 15, doi:
10.1186/s13148-018-0447-6; S. M. Shalaby et al., “Promoter Methylation
and Expression of DNA Repair Genes MGMT and ERCC1 in Tissue and
Blood of Rectal Cancer Patients,” Gene 644 (February 20, 2018): 66–73,
doi: 10.1016/j.gene.2017.10.056; I. Arora, M. Sharma, and T. O. Tollefsbol,
“Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in
Cancer Prevention and Therapy,” International Journal of Molecular
Sciences 20, no. 18 (September 14, 2019): 4567, doi:
10.3390/ijms20184567; A. Wojtczyk-Miaskowska et al., “Gene Expression,
DNA Methylation and Prognostic Significance of DNA Repair Genes in
Human Bladder Cancer,” Cellular Physiology and Biochemistry 42 (2017):
2404–2417, doi: 10.1159/000480182; V. Shilpa et al., “BRCA1 Promoter
Hypermethylation and Protein Expression in Ovarian Carcinoma—An
Indian Study,” Tumor Biology 35 (2014): 4277–4284, doi: 10.1007/s13277-
013-1558-5; A. J. Papoutsis et al., “BRCA-1 Promoter Hypermethylation
and Silencing Induced by the Aromatic Hydrocarbon Receptor-Ligand
TCDD Are Prevented by Resveratrol in MCF-7 Cells,” Journal of
Nutritional Biochemistry 23, no. 10 (October 2012): 1324–1332, doi:
10.1016/j.jnutbio.2011.08.001; P. Selvakumar et al., “Flavonoids and Other
Polyphenols Act as Epigenetic Modifiers in Breast Cancer,” Nutrients 12,
no. 3 (March 13, 2020): 761, doi: 10.3390/nu12030761.
17. M. Imran et al., “Kaempferol: A Key Emphasis to Its Anticancer
Potential,” Molecules 24, no. 12 (June 19, 2019): 2277, doi:
10.3390/molecules24122277.
18. L. J. Fu et al., “The Effects of Lycopene on the Methylation of the
GSTP1 Promoter and Global Methylation in Prostatic Cancer Cell Lines
PC3 and LNCaP,” International Journal of Endocrinology 2014 (2014):
620165, doi: 10.1155/2014/620165; C. Fang et al., “Aberrant GSTP1
Promoter Methylation Is Associated with Increased Risk and Advanced
Stage of Breast Cancer: A Meta-Analysis of 19 Case-Control Studies,”
BMC Cancer 15, no. 920 (2015), doi: 10.1186/s12885-015-1926-1; J. Cui et
al., “GSTP1 and Cancer: Expression, Methylation, Polymorphisms and
Signaling (Review),” International Journal of Oncology 56, no. 4 (2020):
867–878, doi: 10.3892/ijo.2020.4979.
19. N. Mukherjee, A. P. Kumar, and R. Ghosh, “DNA Methylation and
Flavonoids in Genitourinary Cancers,” Current Pharmacology Reports 1,
no. 2 (April 1, 2015): 112–120, doi: 10.1007/s40495-014-0004-8.
20. K. Yari and Z. Rahimi, “Promoter Methylation Status of the Retinoic
Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control
Study and Systematic Review,” Breast Care (Basel, Switzerland) 14, no. 2
(April 2019): 117–123, doi: 10.1159/000489874.
21. R. Chen et al. “Association Between MGMT Promoter Methylation
and Risk of Breast and Gynecologic Cancers: A Systematic Review and
Meta-Analysis,” Scientific Reports 7, no. 1 (October 6, 2017): 12783, doi:
10.1038/s41598-017-13208-3; I. Arora, M. Sharma, and T. O. Tollefsbol,
“Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in
Cancer Prevention and Therapy,” International Journal of Molecular
Sciences 20, no. 18 (September 14, 2019): 4567, doi:
10.3390/ijms20184567.
22. U. Smrdel et al., “Long-Term Survival in Glioblastoma: Methyl
Guanine Methyl Transferase (MGMT) Promoter Methylation as
Independent Favourable Prognostic Factor,” Radiology and Oncology 50,
no. 4 (November 10, 2016): 394–401, doi: 10.1515/raon-2015-0041.
23. G. Tezcan et al., “Olea europaea Leaf Extract Improves the Efficacy
of Temozolomide Therapy by Inducing MGMT Methylation and Reducing
P53 Expression in Glioblastoma,” Nutrition and Cancer 69, no. 6 (Aug-Sep
2017): 873–880, doi: 10.1080/01635581.2017.1339810.
24. M. Beetch et al., “Dietary Antioxidants Remodel DNA Methylation
Patterns in Chronic Disease,” British Journal of Pharmacology 177, no. 6
(March 2020): 1382–1408, doi: 10.1111/bph.14888; E. Collignon et al.,
“Immunity Drives TET1 Regulation in Cancer Through NF-κB,” Science
Advances 4, no. 6 (June 20, 2018): eaap7309, doi: 10.1126/sciadv.aap7309.
25. C. Busch et al., “Epigenetic Activities of Flavonoids in the Prevention
and Treatment of Cancer,” Clinical Epigenetics 7, no. 1 (July 10, 2015): 64,
doi: 10.1186/s13148-015-0095-z.
26. C. Li et al., “OPCML Is Frequently Methylated in Human Colorectal
Cancer and Its Restored Expression Reverses EMT via Downregulation of
Smad Signaling,” American Journal of Cancer Research 5, no. 5 (April 15,
2015): 1635–1648; Y. Cui et al., “OPCML Is a Broad Tumor Suppressor for
Multiple Carcinomas and Lymphomas with Frequently Epigenetic
Inactivation,” PLoS One 3, no. 8 (August 20, 2008): e2990, doi:
10.1371/journal.pone.0002990, erratum in PLoS One 3, no.9 (2008), doi:
10.1371/annotation/f394b95b-c731-41a3-b0dc-be25fb6a227c.
27. A. Torkamani, N. E. Wineinger, and E. J. Topol, “The Personal and
Clinical Utility of Polygenic Risk Scores,” Nature Reviews Genetics 19,
(2018): 581–590, doi: 10.1038/s41576-018-0018-x.
28. C. Sae-Lee et al., “Dietary Intervention Modifies DNA Methylation
Age Assessed by the Epigenetic Clock,” Molecular Nutrition and Food
Research 62 (2018): 1–7, doi: 10.1002/mnfr.201800092.
CHAPTER 11
1. K. Loria, “A Rogue Doctor Saved a Potential Miracle Drug by Storing
Samples in His Home After Being Told to Throw Them Away,” Business
Insider, February 20, 2015, www.businessinsider.com/suren-sehgal-saved-
rapamycin-anti-aging-drug-2015-2.
2. M. Easter, “This Obscure, Potentially Dangerous Drug Could Stop
Aging,” Men’s Health, July 19, 2019,
www.menshealth.com/health/a28440858/anti-aging-rapamycin.
3. M. V. Blagosklonny, “Fasting and Rapamycin: Diabetes Versus
Benevolent Glucose Intolerance,” Cell Death and Disease 10, 607 (2019),
doi: 10.1038/s41419-019-1822-8.
4. Rapamune (Sirolimus) tablets label,
www.accessdata.fda.gov/drugsatfda _docs/label/2010/021110s058lbl.pdf.
5. A. A. Soukas, H. Hao, and L. Wu, “Metformin as Anti-Aging Therapy:
Is It for Everyone?,” Trends in Endocrinology & Metabolism 30, no. 10
(October 2019): 745–755, doi: 10.1016/j.tem.2019.07.015.
6. A. Protti et al., “Metformin Overdose Causes Platelet Mitochondrial
Dysfunction in Humans,” Critical Care (London, England) 1 (2012): R180,
doi: 10.1186/cc1166.
7. A. R. Konopka et al., “Metformin Inhibits Mitochondrial Adaptations
to Aerobic Exercise Training in Older Adults,” Aging Cell 18, no. 1
(February 2019): e12880, doi: 10.1111/acel.12880.
8. Ibid.
9. National Institute on Aging, “Adverse Cardiovascular Events Reported
in Testosterone Trial in Older Men,” June 30, 2010, www.nih.gov/news-
events/news-releases/adverse-cardiovascular-events-reported-testosterone-
trial-older-men.
10. P. E. Norman et al., “Cohort Profile: The Health In Men Study
(HIMS),” International Journal of Epidemiology 38, no. 1 (February 2009):
48–52, doi: 10.1093/ije/dyn041.
11. Y. Li et al., “Reprogramming Somatic Cells to Potency: A Fresh Look
at Yamanaka’s Model,” Cell Cycle 12, no. 23 (2013): 3594–3598, doi:
10.4161/cc.26952.
12. Y. Lu et al., “Reprogramming to Recover Youthful Epigenetic
Information and Restore Vision,” Nature 588, no. 7836 (February 2009):
124–129, doi: 10.1038/s41586-020-2975-4.
13. Harvard Medical School, “Scientists Reverse the Aging Clock:
Restore Age-Related Vision Loss Through Epigenetic Reprogramming,”
December 2, 2020, https://scitechdaily.com/scientists-reverse-the-aging-
clock-restore-age-related-vision-loss-through-epigenetic-reprogramming/.
14. S. Horvath et al., “Reversing Age: Dual Species Measurement of
Epigenetic Age with a Single Clock,” bioRxiv (preprint), (May 8, 2020),
doi:10.1101/2020.05.07.082917.
15. L. Gong et al., “Cancer Cell Reprogramming: A Promising Therapy
Converting Malignancy to Benignity,” Cancer Communications (London,
England) 39 no. 1 (2019): 48, doi: 10.1186/s40880-019-0393-5.
16. M. Müller et al., “The Role of Pluripotency Factors to Drive
Stemness in Gastrointestinal Cancer,” Stem Cell Research 16, no. 2 (March
2016): 349–357, doi: 10.1016/j.scr.2016.02.005.
17. The Royal Swedish Academy of Sciences, “The Nobel Prize in
Chemistry, 2020,” October 7, 2020,
www.nobelprize.org/prizes/chemistry/2020/press-release/.
18. Associated Press, “Lab Tests Show Risks of Using CRISPR Gene
Editing on Embryos,” October 29, 2020,
www.statnews.com/2020/10/29/lab-tests-show-risks-of-using-crispr-gene-
editing-on-embryos/.
19. Natalie Kolfer, “Why Were Scientists Silent over Gene-edited
Babies?,” Nature, February 26, 2019, www.nature.com/articles/d41586-
019-00662-4.
20. Wallace Ravven, “Could Gene Editing Enable Us to Reverse Some of
the Ravages of Aging?,” Stanford Engineering, March 6, 2020,
engineering.stanford.edu/magazine/article/could-gene-editing-enable-us-
reverse-some-ravages-aging.
21. W. Wang et al., “A Genome-Wide CRISPR-Based Screen Identifies
KAT7 as a Driver of Cellular Senescence,” Science Translational Medicine
13, no. 575 (January 2021): eabd2655, doi: 10.1126/scitranslmed.abd2655.
22. J. D. Gillmore et al., “CRISPR-Cas9 In Vivo Gene Editing for
Transthyretin Amyloidosis,” New England Journal of Medicine 385 no. 6
(August 5, 2021): 493–502, doi: 10.1056/NEJMoa2107454.
23. S. Horvath et al., “Reversing Age: Dual Species Measurement of
Epigenetic Age with a Single Clock,” bioRxiv (preprint), (May 8, 2020),
doi: 10.1101/2020.05.07.082917.
24. Kira Peikoff, “Anti-Aging Pioneer Aubrey de Grey: ‘People in
Middle Age Now Have a Fair Chance,’” Leaps.org, January 31, 2018,
https://leaps.org/anti-aging-pioneer-aubrey-de-grey-people-middle-age-
now-fair-chance/particle-11.
THE RECIPES
1. G. Cardwell et al., “A Review of Mushrooms as a Potential Source of
Dietary Vitamin D,” Nutrients 10, no. 10 (October 13, 2018): 1498, doi:
10.3390/nu10101498.
NUTRIENT REFERENCE
1. B. W. Bolling, D. L. McKay, and J. B. Blumberg, “The Phytochemical
Composition and Antioxidant Actions of Tree Nut,” Asia Pacific Journal of
Clinical Nutrition 19 no. 1 (2010): 117–123;
N. Brown, J. A. John, and F. Shahidi, “Polyphenol Composition and
Antioxidant Potential of Mint Leaves,” Food Production, Processing, and
Nutrition 1, no. 1 (2019), doi: 10.1186/s43014-019-0001-8;
C. Busch et al., “Epigenetic Activities of Flavonoids in the Prevention
and Treatment of Cancer,” Clinical Epigenetics 7, no. 1 (2015): 64, doi:
10.1186/s13148-015-0095-z;
J. Cotas et al., “Seaweed Phenolics: From Extraction to Applications,”
Marine Drugs 18, no. 8 (2020): 384, doi: 10.3390/md18080384;
D. Y. Seo et al., “Ursolic Acid in Health and Disease,” Korean Journal of
Physiology & Pharmacology 22, no. 3 (2018): 235. doi:
10.4196/kjpp.2018.22.3.235;
Q. Dong et al., “Comparative Study on Phenolic Compounds,
Triterpenoids, and Antioxidant Activity of Ganoderma lucidum Affected by
Different Drying Methods,” Journal of Food Measurement and
Characterization 13 (2019): 3198–3205, doi: 10.1007/s11694-019-00242-0;
US Department of Agriculture, “FoodData Central,”
https://fdc.nal.usda.gov/;
M. J. Feeney et al., “Mushrooms and Health Summit Proceedings,”
Journal of Nutrition 144, no. 7 (2014): 1128S–1136S, doi:
10.3945/jn.114.190728;
M. Górecki and E. Hallmann, “The Antioxidant Content of Coffee and Its
In Vitro Activity as an Effect of Its Production Method and Roasting and
Brewing Time,” Antioxidants (Basel, Switzerland) 9, no. 4 (2020): 308, doi:
10.3390/antiox9040308;
X. Han et al., “Dietary Polyphenols and Their Biological Significance,”
International Journal of Molecular Sciences 8, no. 9 (2007): 950–988, doi:
10.3390/i8090950;
D. Guo, et al., “Phenolics Content and Antioxidant Activity of Tartary
Buckwheat from Different Locations.” Molecules, 16, no. 12 (2011): 9850–
9867. doi: 10.3390/molecules16129850;
D. G. Hayward, J. W. Wong, and H. Y. Park, “Determinations for
Pesticides on Black, Green, Oolong, and White Teas by Gas
Chromatography Triple-Quadrupole Mass Spectrometry,” Journal of
Agricultural and Food Chemistry 63, no. 37 (2015): 8116–8124, doi:
10.1021/acs.jafc.5b02860;
T. A. Hore, “Modulating Epigenetic Memory Through Vitamins and
TET: Implications for Regenerative Medicine and Cancer Treatment,”
Epigenomics 9, no. 6 (2017), doi: 10.2217/epi-2017-0021;
C. A. Houghton, R. G. Fassett, and J. S. Coombes, “Sulforaphane and
Other Nutrigenomic Nrf2 Activators: Can the Clinician’s Expectation Be
Matched by the Reality?,” Oxidative Medicine and Cellular Longevity
(2016), 7857186: doi: 10.1155/2016/7857186;
Phenol-Explorer: Database on Polyphenol Content in Foods,
http://phenol-explorer.eu/;
D. B. Haytowitz, X. Wu, and S. Bagwat, “USDA Databsae for the
Flavonoid Content of Selected Foods, Release 3.3,” Nutrient Data
Laboratory, Agricultural Research Service, US Department of Agriculture,
March 2018,
www.ars.usda.gov/ARSUserFiles/80400535/Data/Flav/Flav3.3.pdf;
X. Y. Huang et al., “Variation of Major Minerals and Trace Elements in
Seeds of Tartary Buckwheat (Fagopyrum tataricum Gaertn.),” Genetic
Resources and Crop Evolution 61 (2014): 567–577;
S. Ikeda et al., “Nutritional Characteristics of Minerals in Tartary
Buckwheat,” Fagopyrum 21 (2004): 79–84;
J. M. Calderon-Montano et al., “A Review on the Dietary Flavonoid
Kaempferol,” Mini-Reviews in Medicinal Chemistry 11 (2011): 298, doi:
10.2174/138955711795305335;
S. J. Kim et al., “Identification of Anthocyanins in the Sprouts of
Buckwheat,” Journal of Agricultural and Food Chemistry 55, no. 15
(2007): 6314–6318; doi: 10.1021/jf0704716;
Y. B. Kim et al., “Characterization of Genes for a Putative
Hydroxycinnamoyl-coenzyme A Quinate Transferase and p-coumarate 3'-
hydroxylase and Chlorogenic Acid Accumulation in Tartary Buckwheat,”
Journal of Agricultural and Food Chemistry 61, no. 17 (2013): 4120–4126,
doi: 10.1021/jf4000659;
H. E. Khoo et al., “Anthocyanidins and Anthocyanins: Colored Pigments
as Food, Pharmaceutical Ingredients, and the Potential Health Benefits,”
Food & Nutrition Research 61, no.1 (2017): 1361779, doi:
10.1080/16546628.2017.1361779;
L. Machu et al., “Phenolic Content and Antioxidant Capacity in Algal
Food Products,” Molecules (Basel, Switzerland) 20, no.1 (2015): 1118–
1133, doi: 10.3390/molecules20011118;
S. Maina et al., “Human, Animal and Plant Health Benefits of
Glucosinolates and Strategies for Enhanced Bioactivity: A Systematic
Review,” Molecules (Basel, Switzerland) 25, no. 16 (2020), doi:
10.3390/molecules25163682;
D. McCormack and D. McFadden, “A Review of Pterostilbene
Antioxidant Activity and Disease Modification,” Oxidative Medicine and
Cellular Longevity (2013): 575482, doi: 10.1155/2013/575482;
B. Mahayothee at al., “Phenolic Compounds, Antioxidant Activity, and
Medium Chain Fatty Acids Profiles of Coconut Water and Meat at Different
Maturity Stages,” International Journal of Food Properties, 19, no. 9
(2016): 2041–2051, doi: 10.1080/10942912.2015.1099042;
K. H. Miean and S. Mohamed, “Flavonoid (Myricetin, Quercetin,
Kaempferol, Luteolin, and Apigenin) Content of Edible Tropical Plants,”
Journal of Agricultural and Food Chemistry 49, no. 6 (June 2001): 3106–
3112, doi: 10.1021/jf000892m;
L. Němcová et al., “Determination of Resveratrol in Grains, Hulls and
Leaves of Common and Tartary Buckwheat by HPLC with Electrochemical
Detection at Carbon Paste Electrode,” Food Chemistry 126, no. 1 (2011):
374–378, doi: 10.1016/j.foodchem.2010.10.108;
“Dietary Supplement Fact Sheets,” National Institutes of Health,
https://ods.od.nih.gov/factsheets/;
H. C. Pal, R. L. Pearlman, and F. Afaq, “Fisetin and Its Role in Chronic
Diseases,” Advances in Experimental Medicine and Biology 928 (2016):
213–244, doi: 10.1007/978-3-319-41334-1_10;
S. Paul et al., “Dietary Intake of Pterostilbene, a Constituent of Blueberry,
Inhibits the Beta-Catenin/p65 Downstream Signaling Pathway and Colon
Carcinogenesis in Rats,” Carcinogenesis 31, no. 7 (2010): 1272–1278, doi:
10.1093/carcin/bgq004;
P. Qin et al., “Nutritional Composition and Flavonoids Content of Flour
from Different Buckwheat Cultivars,” International Journal of Food
Science & Technology 45, no. 5 (2010): 951–958, doi: 10.1111/j.1365-
2621.2010.02231.x;
P. Qin et al., “Changes in Phytochemical Compositions, Antioxidant and
α-glucosidase Inhibitory Activities During the Processing of Tartary
Buckwheat Tea,” Food Research International 50, no. 2 (2013): 562–567;
doi: 10.1016/j.foodres.2011.03.028;
S. C. Ren and J. T. Sun, “Changes in Phenolic Content, Phenylalanine
Ammonia-lyase (PAL) Activity, and Antioxidant Capacity of Two
Buckwheat Sprouts in Relation to Germination,” Journal of Functional
Foods 7 (2014): 298–304, doi: 10.1016/j.jff.2014.01.031;
S. C. Rha et al., “Antioxidative, Anti-Inflammatory, and Anticancer
Effects of Purified Flavonol Glycosides and Aglycones in Green Tea,”
Antioxidants 8, no. 8 (2019): 278, doi: 10.3390/antiox8080278;
A. M. Rimando et al., “Resveratrol, Pterostilbene, and Piceatannol in
Vaccinium Berries,” Journal of Agricultural and Food Chemistry 52, no. 15
(July 2004): 4713–4719, doi: 10.1021/jf040095e;
K. Szarc vel Szic et al., “Nature or Nurture: Let Food Be Your Epigenetic
Medicine in Chronic Inflammatory Disorders,” Biochemical Pharmacology
80, no. 12 (December 15, 2010): 1816–1832, Epub August 3, 2010, doi:
10.1016/j.bcp.2010.07.029;
C. A. Thomson, E. Ho, and M. B. Strom, “Chemopreventive Properties of
3,3’-Diindolylmethane in Breast Cancer: Evidence from Experimental and
Human Studies,” Nutrition Review 74, no. 7 (2016): 432–443, doi:
10.1093/nutrit/nuw010;
T. Watanabe, M. Kioka, and A. Fukushima, “Biotin Content Table of
Select Foods and Biotin Intake in Japanese,” International Journal of
Analytical Bio-Science 2, no. 4 (2014): 109–125;
Z. Yiming et al., “Evolution of Nutrient Ingredients in Tartary Buckwheat
Seeds During Germination,” Food Chemistry 186 (November 1, 2015):
244–248, doi: 10.1016/j.foodchem.2015.03.115;
F. Zhang et al., “Oleanolic Acid and Ursolic Acid in Commercial Dried
Fruits,” Food Science and Technology Research 19, no. 1 (2013): 113–116,
doi: 10.3136/fstr.19.113;
X. Zhou et al., “Relationships Between Antioxidant Compounds and
Antioxidant Activities of Tartary Buckwheat During Germination,” Journal
of Food Science and Technology 52, no. 4 (2015): 2458–2463, doi:
10.1007/s13197-014-1290-1;
S. Baghwat, D. B. Haytowitz, and J. M. Holden, “USDA Database for the
Flavonoid Content of Selected Foods,” Release 3, Nutrient Data
Laboratory, Beltsville Human Nutrition Research Center, Agricultural
Research Service, US Department of Agriculture, September 2011,
www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf;
C. Ozuna and M.F. León-Galván, “Cucurbitaceae Seed Protein
Hydrolysates as a Potential Source of Bioactive Peptides with Functional
Properties,” BioMed Research International, 2017 (2017): 2121878, doi:
10.1155/2017/2121878;
National Institutes of Health Office of Dietary Supplements, “Iron: Fact
Sheet for Health Professionals,” updated March 30, 2021,
https://ods.od.nih.gove/factsheets/Iron-HealthProfessional/.
2. T. A. Hore et al., “Retinol and Ascorbate Drive Erasure of Epigenetic
Memory and Enhance Reprogramming to Naive Pluripotency by
Complementary Mechanisms,” Proceedings of the National Academy of
Sciences of the United States of America 113 (2016): 12202–12207, doi:
10.1073/pnas.1608679113.
3. L. Chen et al., “Effects of Vitamin D3 Supplementation on Epigenetic
Aging in Overweight and Obese African Americans with Suboptimal
Vitamin D Status: A Randomized Clinical Trial,” Journals of Gerontology
Series A: Biological Sciences and Medical Sciences 74, no. 1 (January 1,
2019): 91–98, doi: 10.1093/gerona/gly223.
4. G. Rizzo and A. S. Laganà, “The Link between Homocysteine and
Omega-3 Polyunsaturated Fatty Acid: Critical Appraisal and Future
Directions,” Biomolecules 10, no. 2 (February 2, 2020): 219, doi:
10.3390/biom10020219.