REVISTA Life Extension (2020.04abr)

F E A T U R E A R T I C L E S
7 Why Arginine Failed as a Heart Drug

32 Epidemic of Male Osteoporosis
42 Relief from Digestive Upsets
54 Beautify Skin from Within
LifeExtension.com April 2020
65 Lactoferrin Promotes Bone Growth
Restore
YOUTHFUL
Arterial
Function
PLUS: New Method to Boost Nitric Oxide

n n e c t ions Between You
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Reference: *Gerontology. 1996;42(3):170-80.
Magtein® is a registered trademark of Magceutics, Inc. and is distributed exclusively by AIDP, Inc.
Magtein™ is protected under U.S. patents 8,178,118; 8,142,803; 8,163,301 and other patents pending.
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CONTENTS
LifeExtension.com April 2020
REPORTS
22 ON THE COVER
BOOST NITRIC OXIDE
TO IMPROVE CIRCULATION
An age-related decline in nitric
oxide levels contributes to inner
arterial wall dysfunction.
A blend of aronia berries and a sus-
32 42 54 65
tainable form of L-arginine boosts
the body’s production of nitric oxide, 32 EPIDEMIC OF OSTEOPOROSIS IN MEN
helping to improve blood flow. Men are at a higher risk of osteoporosis than most realize. Healthy lifestyle
choices, along with bone-building nutrients, can protect and restore bone
22
density.
42 IMPROVE DIGESTION OF PLANT-BASED FOODS

The trend toward plant-based diets often requires special enzymes to
digest the fiber in these foods to avoid gastrointestinal bloating, gas,
diarrhea, and cramping.
54 IMPROVE SKIN APPEARANCE FROM THE INSIDE

Oral intake of clinically effective doses of collagen peptides and hyaluronic
acid restores skin hydration and elasticity, reducing eye wrinkle depth up
to 20%.
65 LACTOFERRIN HELPS BUILD NEW BONES

Lactoferrin provides vital signals that enables an increase in new bone
formation. In one study, lactoferrin increased markers of bone-forming
activity 24% more than placebo.
D E PA R T M E N T S
75 HEALTHY EATING
Open-air markets called shuks sell the
7
seasonal ingredients for Israeli home
7 WHY ARGININE FAILED cooking. Of the 140 recipes in Shuk,
AS A CARDIOVASCULAR DRUG we feature a flavorful four.
Back in the 1980s, there was interest
about using L-arginine for athero-
sclerosis treatment. Arginine, however,
83 AUTHOR INTERVIEW
In his book, The Switch, and in his
15
quickly degrades in the body. A new interview, James Clement outlines how
83
sustained-release arginine offers to activate your body’s metabolic switch
support for vascular health. to boost weight loss, cut disease risk,
and slow aging.
13 IN THE NEWS
Oral hygiene reduces heart failure risk; 89 SUPER FOODS
PEA alleviates knee discomforts; tea Hemp seeds are high in protein, can lower
boosts brain health; blueberries cut
cardiovascular risk.
the risk of heart disease, improve skin
health, and more. 75
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MEDICAL ADVISORY BOARD
Gustavo Tovar Baez, MD, operates the Life Mitchell J. Ghen, DO, PhD, holds a doc- Herbert Pardell, DO, FAAIM, practices internal
Extension Clinic in Caracas, Venezuela. He is torate in holistic health and anti-aging medicine at the Emerald Hills Medical Center
the first physician in Caracas to specialize in and serves on the faculty of medicine in Hollywood, FL. He is a medical director of
anti-aging medicine. at the Benemerita Universidad Autonoma the Life Extension Foundation®.
Ricardo Bernales, MD, is a board-certified pedia- De Puebla, Mexico, as a professor of Lambert Titus K. Parker, MD, an internist and a
trician and general practitioner in Chicago, IL, cellular hematopoietic studies. board- certified anti-aging physician, practices
focusing on allergies, bronchial asthma, and Gary Goldfaden, MD, is a clinical dermatolo- integrative medicine from a human ecology
immunodeficiency. gist and a lifetime member of the American perspective with emphasis on personalized
Mark S. Bezzek, MD, FACP, FAARM, FAAEM, is Academy of Dermatology. He is the founder of brain health, biomarkers, genomics and total
boardcertified in internal medicine, emergency Academy Dermatology of Hollywood, FL, and health optimization. He serves as the Medical
medicine, and anti-aging/regenerative medi- COSMESIS Skin Care. Director of Integrative Longevity Institute of
cine. He is the director of Med-Link Consulting, Miguelangelo Gonzalez, MD, is a certified Virginia, a 501(c)3 Non-Profit Medical Research
which specializes in bioidentical hormone plastic and reconstructive surgeon at the Institute. He also collaborates on education
replacement therapy, natural alternatives, anti- Miguelangelo Plastic Surgery Clinic, Cabo and research for Hampton Roads Hyperbaric
aging, and degenerative diseases. He holds San Lucas. Therapy.
U.S. patents for a multivitamin/mineral supple- Garry F. Gordon, MD, DO, is a Payson, Arizona- Ross Pelton, RPh, PhD, CCN, is scientific director
ment, an Alzheimer’s/dementia compilation, based researcher of alternative approaches for Essential Formulas, Inc.
and a diabetic regimen. to medical problems that are unresponsive Patrick Quillin, PhD, RD, CNS, is a clinical nutri-
Thomas F. Crais, MD, FACS, a board-certified plas- to traditional therapies. He is president of the tionist in Carlsbad, CA, and formerly served as
tic surgeon, was medical director of the micro- International College of Advanced Longevity vice president of nutrition for Cancer Treatment
surgical research and training lab at Southern Medicine. Centers of America, where he was a consultant
Baptist Hospital in New Orleans, LA, and cur- Richard Heifetz, MD, is a board-certified anesthe- to the National Institutes of Health.
rently practices in Sun Valley, ID. siologist in Santa Rosa, CA, specializing in the Allan Rashford, MD, graduated from the
William Davis, MD, is a preventive cardiologist delivery of anesthesia for office-based, plastic/ University of Iowa Medical School. Upon com-
and author of Wheat Belly: Lose the Wheat, cosmetic surgery, chelation therapy, and pain pleting medical training, he became chief
Lose the Weight and Find Your Path Back to management. of medicine at St. Francis Hospital in South
Health. He is also medical director of the online Roberto Marasi, MD, is a psychiatrist in Brescia Carolina, and he was later named president of
heart disease prevention and reversal program, and in Piacenza, Italy. He is involved in anti-ag- the Charleston Medical Society.
Track Your Plaque (www.trackyourplaque.com). ing strategies and weight management. Marc R. Rose, MD, practices ophthalmology in
Martin Dayton, MD, DO, practices at the Sunny Maurice D. Marholin, DC, DO, is a licensed chiro- Los Angeles, CA, and is president of the Rose
Isles Medical Center in North Miami Beach, FL. practic physician and board-certified osteo- Eye Medical Group. He is on the staff of Pacific
His focus is on nutrition, aging, chelation ther- pathic family physician.While training at the Alliance Medical Center, Los Angeles, and
apy, holistic medicine, and oxidative medicine. University of Alabama, he completed fel- other area hospitals.
John DeLuca, MD, DC, is a 2005 graduate of St. lowships in Clinical Nutrition and Behavioral Michael R. Rose, MD, a board-certified ophthal-
George’s University School of Medicine. He Medicine. He is currently in private practice mologist with the Rose Eye Medical Group
completed his internal medicine residency at in Clermont, FL. in Los Angeles, CA, is on the staff of the
Monmouth Medical Center in Long Branch, NJ, Professor Francesco Marotta, MD, PhD, of University of Southern California and UCLA.
in 2008 and is board-certified by the American Montenapoleone Medical Center, Milan, Italy, Ron Rothenberg, MD, is a full clinical profes-
Board of Internal Medicine. Dr. DeLuca is is a gastroenterologist and nutrigenomics sor at the University of California San Diego
a Diplomate of the American Academy of expert with extensive international university School of Medicine and founder of California
Anti-Aging Medicine and has obtained certifi- experience. He is also a consulting profes- HealthSpan Institute in San Diego.
cations in hyperbaric medicine, pain manage- sor at the WHO-affiliated Center for Biotech Roman Rozencwaig, MD, is a pioneer in research
ment, nutrition, strength and conditioning, and & Traditional Medicine, University of Milano, on melatonin and aging. He practices in
manipulation under anesthesia. Italy and honorary resident professor, Nutrition, Montreal, Canada, as research associate at
Sergey A. Dzugan, MD, PhD, was formerly chief Texas Women’s University. He is the author of Montreal General Hospital, Department of
of cardiovascular surgery at the Donetsk more than 130 papers and 400 lectures. Medicine, McGill University.
Regional Medical Center in Donetsk, Ukraine. Philip Lee Miller, MD, is founder and medical Michael D. Seidman, MD, FACS, is the director
Dr. Dzugan’s current primary interests are anti- director of the Los Gatos Longevity Institute of skull base surgery and wellness for the
aging and biological therapy for cancer, cho- in Los Gatos, CA. Adventist Health System in Celebration, FL.
lesterol, and hormonal disorders.
Michele G. Morrow, DO, FAAFP, is a board-certified Ronald L. Shuler, BS, DDS, CCN, LN, is involved
Patrick M. Fratellone, MD, RH, is the founder family physician who merges mainstream and in immunoncology for the prevention and
and executive medical director of Fratellone alternative medicine using functional medicine treatment of cancer, human growth hormone
Associates. He completed his internal med- concepts, nutrition, and natural approaches. secretagogues, and osteoporosis. He is board-
icine and cardiology fellowship at Lenox
Filippo Ongaro, MD, is board-certified in anti- certified in anti-aging medicine.
Hill Hospital in 1994, before becoming the
aging medicine and has worked for many Paul Wand, MD, Fort Lauderdale, FL, is a clinical
medical director for the Atkins Center for
years as flight surgeon at the European neurologist with special expertise in treating
Complementary Medicine.
Space Agency. He is a pioneer in func- and reversing diabetic peripheral neuropathy
Norman R. Gay, MD, is proprietor of the Bahamas tional and anti-aging medicine in Italy and brain injuries from various causes.
Anti-Aging Medical Institute in Nassau, where he also works as a journalist and
Bahamas. A former member of the Bahamian a writer.
Parliament, he served as Minister of Health
and Minister of Youth and Sports.

SCIENTIFIC ADVISORY BOARD
Örn Adalsteinsson, PhD, is chairman of the Life Peter H. Langsjoen, MD, FACC, is a cardiologist
Extension® Scientific Advisory board. He holds a specializing in congestive heart failure, primary and
master’s and doctorate from the Massachusetts statin-induced diastolic dysfunction, and other heart
Institute of Technology (MIT). He has specialized in diseases. A leading authority on coenzyme Q10, Dr.
human therapeutics including vaccines, monoclonal Langsjoen has been involved with its clinical appli-
antibodies, product development, nutraceuticals, cation since 1983. He is a founding member of the
formulations, artificial intelligence, hormones, and executive committee of the International Coenzyme
nutritional supplementation. He has also authored Q10 Association, a fellow of the American College of
articles and contributed to peer-reviewed publica- Cardiology, and a member of numerous other medi-
tionzs and served as an editor for the Journal of cal associations.
Medicinal Food. Dipnarine Maharaj MD, MB, ChB, FRCP (Glasgow), FRCP
(Edinburgh), FRCPath., FACP, is the Medical Director of
Richard Black, DO, is a dedicated nuclear medicine
the South Florida Bone Marrow Stem Cell Transplant
physician practicing as an independent contractor
Institute and is regarded as one of the world’s
out of Cleveland, Ohio. Dr. Black is board certified
foremost experts on adult stem cells. He received
in internal medicine and nuclear medicine, and is
his medical degree in 1978 from the University of
licensed to practice medicine in multiple states
Glasgow Medical School, Scotland. He completed
throughout the United States.
his internship and residency in Internal Medicine
John Boik, PhD, is the author of two books on can- and Hematology at the University’s Royal Infirmary.
cer therapy, Cancer and Natural Medicine (1996) L. Ray Matthews, MD, FACS, is a professor of surgery
and Natural Compounds in Cancer Therapy (2001). and director of Surgical Critical Care at Morehouse
He earned his doctorate at the University of Texas School of Medicine in Atlanta, GA, and a trauma and
Graduate School of Biomedical Sciences with critical care surgeon at Grady Memorial Hospital. He
research at the MD Anderson Cancer Center, focus- has published widely and is known as one of the top
ing on screening models to identify promising new vitamin D experts. Dr. Matthews has spoken before
anti-cancer drugs. He conducted his postdoctoral the U.S. Food and Drug Administration several times,
training at Stanford University’s Department of presenting a recent update about clinical research
Statistics. on vitamin D.
Aubrey de Grey, PhD, is a biomedical gerontologist Ralph W. Moss, PhD, is the author of books such as
and Editor-in-Chief of Rejuvenation Research, the Antioxidants Against Cancer, Cancer Therapy,
world’s highest-impact, peer-reviewed journal Questioning Chemotherapy, and The Cancer
focused on intervention in aging. He received his Industry, as well as the award-winning PBS doc-
BA and PhD from the University of Cambridge in umentary The Cancer War. Dr. Moss has inde-
1985 and 2000 respectively. Dr. de Grey is a Fellow pendently evaluated the claims of various cancer
of both the Gerontological Society of America and treatments and currently directs The Moss Reports,
the American Aging Association and sits on the an updated library of detailed reports on more than
editorial and scientific advisory boards of numerous 200 varieties of cancer diagnoses.
journals and organizations. Michael D. Ozner, MD, FACC, FAHA, is a board-certi-
fied cardiologist who specializes in cardiovascular
Deborah F. Harding, MD, is founder of the Harding
disease prevention. He serves as medical direc-
Anti-Aging Center. She is double board-certified in
tor for the Cardiovascular Prevention Institute of
internal medicine and sleep disorder medicine. She
South Florida and is a noted national speaker on
also earned the Cenegenics certification in age man-
heart disease prevention. Dr. Ozner is also author
agement medicine. She is a faculty member of the
of The Great American Heart Hoax,The Complete
University of Central Florida Medical School.
Mediterranean Diet and Heart Attack Proof. For
Sandra C. Kaufmann, MD, is a fellowship-trained and more information visit www.drozner.com.
board-certified pediatric anesthesiologist as well Jonathan V. Wright, MD, is medical director of the
as the Chief of Anesthesia at the Joe DiMaggio Tahoma Clinic in Tukwila, WA. He received his MD
Children’s Hospital in Hollywood, Florida. She is the from the University of Michigan and has taught
founder of The Kaufmann Anti-Aging Institute and natural biochemical medical treatments since 1983.
the author of the book The Kaufmann Protocol: Why Dr. Wright pioneered the use of bioidentical estro-
we Age and How to Stop it (2018). Her expertise is gens and DHEA in daily medical practice. He has
in the practical application of anti-aging research. authored or co-authored 14 books, selling more than
1.5 million copies.
Steven B. Harris, MD, is president and director of
Xiaoxi Wei, PhD, is a chemist, expert in supramolecular
research at Critical Care Research, a company
assembly and development of synthetic transmem-
that grew out of 21st Century Medicine in Rancho
brane nanopores with distinguished selectivity via
Cucamonga, CA. Dr. Harris participates in ground-
biomimetic nanoscience. She has expertise in ion
breaking hypothermia, cryothermia, and ischemia
channel function and characterization. She founded
research. His research interests include antioxi-
X-Therma Inc., a company developing a radical
dant and dietary-restriction effects in animals and
new highway towards non-toxic, hyper-effective
humans.
antifreeze agents to fight unwanted ice formation in
regenerative medicine and reduce mechanical icing.

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AS WE SEE IT
Why Arginine Failed as

a Cardiovascular Drug
L-arginine increases nitric oxide, With age, the activity of arginine-
degrading enzymes increases in
which enables arteries to many tissues, most notably the
expand with youthful elasticity.1 cardiovascular system.4,5
I was pleased to learn of a novel
method to protect L-arginine from
degrading in the stomach and
Back in the 1980s, there was
enhance nitric oxide availability.
excitement about using the amino
acid L-arginine to prevent and treat This new formula utilizes a low-dose
atherosclerosis. arginine compound to sustain higher
arginine plasma levels, plus a berry
Boosting nitric oxide improves
extract that helps stabilize endo-
circulation throughout the body.2
thelial nitric oxide.
A drug company obtained a patent
The berry extract alone was shown
to sell an L-arginine powder to
to increase a validated measure of
cardiologists for coronary heart
WILLIAM FALOON circulation.6
disease patients.
Low-dose, sustainable L-arginine
Others promoted the sex-enhanc-
combined with aronia berry extract
ing effects of improved blood flow
offers intriguing potential to support
ARGININE to male and female genitalia.
circulatory health.
L-arginine, however, has some
Cardiologists may eventually pre-
major limitations.
scribe this novel approach now that
Much of it gets degraded by longer-acting, low-dose arginine
enzymes before being converted plus aronia polyphenols can be
to nitric oxide in the arterial wall.3 conveniently taken together.
ARONIA BERRY
HUMAN ARTERY

AS WE SEE IT
Nitric Oxide: Discovering Nitric Oxide’s

L-arginine has demonstrated
“Molecule of The Year” Health Effects
other benefits, such as accelerat-
In 1992, the journal Science In 1987, scientists were seeking to ing wound healing, and helping to
nominated nitric oxide as the “relax” the inner wall of arteries, called maintain kidney function.16-18
“Molecule of the Year.”7 the endothelium. 11 After more than four decades
Not only does nitric oxide A major advance occurred when of study, it appears that the most
support the inner arterial wall to nitric oxide was found to be released important role of L-arginine is its
enable healthy circulation, but it is from the endothelium. ability to produce nitric oxide, and
also a neurotransmitter.8,9 The release of nitric oxide induces thus protect against endothe-
Over the past three decades, relaxation of the lining of the lial dysfunction (and subsequent
nitric oxide has demonstrated value artery.8,12 atherosclerosis).19-21
through its diverse applications Nitric oxide is now understood The elderly often suffer from
in medicine. Dr. Solomon Snyder, to be a principal regulator of blood accelerated atherosclerosis.22
founder of the Solomon H. Snyder pressure. One reason is that nitric oxide-
Department of Neuroscience at blocking compounds in the body
Johns Hopkins Medical School increase with age, thus causing dis-
wrote:
Arginine Needed
ruption to the artery’s endothelial
to Make Nitric Oxide lining.
“In my 25 years of research, Nitric oxide is synthesized It is encouraging to know that
I have never seen a in the body from the amino acid arginine is able to help reverse this
molecule [nitric oxide] L-arginine.13 particular atherogenic event.20
Since the mid-1980s, arginine
that so pervasively
has been a popular supplement for
influences normal and
body builders,14,15 along with aging Reversing
abnormal body functions.”10 people wanting to protect against Arterial Stiffness
nitric oxide deficit.
The age-related decline in
L-arginine bioavailability reduces
nitric oxide production.4,5
The result is a disruption of
healthy endothelial function and
structure.22
Endothelial dysfunction inhibits
the ability of arteries to expand and
contract (vasodilation). This contrib-
utes to hypertension.23
Arginase is an enzyme present in
multiple tissues in the body.24
In the intestinal tract, the arginase
enzyme degrades about 40% of
ingested arginine before it can be
absorbed into the bloodstream.
Once in the bloodstream,
L-arginine is further degraded by
three other enzymes with only a
small amount remaining that can be
converted to nitric oxide.3,25
In one study, when the argi-
nase enzyme was blocked in rat
arteries, L-arginine levels went up.

AS WE SEE IT
Nitric oxide is one important

factor required for the endothelium
to function properly.
The amino acid L-arginine serves
as a precursor to nitric oxide in the
body.
Challenge of
Obtaining Arginine Benefits
A major drawback to L-arginine
supplementation has always been
that, in order to achieve a sustained
blood level, people had to take high
doses throughout the day. It was
difficult to comply with this rigorous
dosing requirement and there may
be side effects with ingesting this
much arginine on a consistent basis.
A more troublesome shortcom-
ing of L-arginine is the age-related
increase in the activity of the argi-
nase enzyme that rapidly degrades
While arterial dilation increased vascular disorders, and how fast
arginine. This means that little
only modestly in young animals, they sometimes accelerate after
ingested arginine is available to pro-
it increased an astounding 680% initial diagnosis.
mote nitric oxide synthesis.3,24
in old animals!26 One problem up to now has
For people with increased
Even more impressive was that been that people could not obtain
arginase activity, supplemental
the arteries of old rats (23 months) arginine’s benefits because of its
L-arginine may not provide ade-
regained the same vasodilation rapid enzymatic degradation in the
quate nitric oxide synthesis to pro-
as young rats (three months) in intestines and blood.3
tect against endothelial dysfunction.
response to blocking the L-arginine-
degrading enzyme called arginase.
This rat study provides evidence Protect Against
of the adverse effects that aging Endothelial Dysfunction
inflicts on the endothelium, including Aging people can slow the break-
elevated blood pressure. down of their delicate endothelium
This study demonstrated that (inner artery wall linings).
aged arteries can be rejuvenated Folate, vitamin C, fish oil, lipoic
by providing the vascular system acid, and pomegranate are a few
with more L-arginine. of the nutrients that help maintain
healthy endothelial function.29-36
It is no coincidence that these
Human Data
same nutrients have been shown
More recent studies show that in some studies to reduce the inci-
70-to-80-year-old humans lose up dence of cardiovascular pathology
to 75% of their endothelial nitric in animals and humans.37-42 Statin
oxide compared to healthy 20 year drugs and agents that suppress
olds.27,28 This helps explain why chronic inflammation also help
so many elderly people suffer protect the endothelium.43-46

AS WE SEE IT
Dual Combination
to Boost Nitric Oxide
In a significant advance, a form
of arginine has been shown to
decrease the arginase enzyme,
allowing L-arginine to remain pres-
ent in the plasma for a greater length
of time.47
In a preclinical study, polyphe-
nols from aronia berries dem-
onstrate the ability to increase
activation of an enzyme called
endothelial nitric oxide synthase
that is responsible for producing
nitric oxide from arginine.48
In addition, these polyphenols
have been shown, in another pre-
clinical study, to stimulate nitric
oxide formation in coronary
arteries.49
This means that lower doses of
L-arginine can be used to enable
References
more sustained nitric oxide synthe- Atherosclerosis is usually associ-
1. Brooks JR, Oketch-Rabah H, Low Dog T,
sis needed for healthy endothelial ated with heart attack risk, but many et al. Safety and performance benefits of
function. of the disorders of aging, including arginine supplements for military person-
nel: a systematic review. Nutr Rev. 2016
kidney impairment and memory Nov;74(11):708-21.
loss, are related to circulatory 2. Boger RH, Bode-Boger SM. The clinical
Support for disorders.52-54 pharmacology of L-arginine. Annu Rev
Aging Arteries Sales of sex-enhancing drugs are
Pharmacol Toxicol. 2001;41:79-99.
3. Wu G, Bazer FW, Davis TA, et al. Argi-
People who follow a healthy life- strong mainly because so many men nine metabolism and nutrition in growth,
health and disease. Amino Acids. 2009
style often develop a false sense suffer from endothelial dysfunction May;37(1):153-68.
of security that they will not suffer that causes erectile dysfunction.55 4. Moretto J, Girard C, Demougeot C. The role
of arginase in aging: A systematic review.
the circulatory disorders that are In this issue of Life Extension®, Exp Gerontol. 2019 Feb;116:54-73.
the leading killers in the Western we describe a novel approach to 5. Santhanam L, Christianson DW, Nyhan D,
et al. Arginase and vascular aging. J Appl
world. help prevent and/or partially reverse Physiol (1985). 2008 Nov;105(5):1632-42.
One reason for this optimism is endothelial dysfunction. 6. Istas G, Wood E, Le Sayec M, et al. Effects
Life Extension® readers take of aronia berry (poly)phenols on vascular
that heart disease death rates have
function and gut microbiota: a double-blind
declined dramatically since 1980.50 aggressive steps to maintain healthy randomized controlled trial in adult men.
Much of this can be attributed to circulation, but haven’t had access Am J Clin Nutr. 2019 Aug 1;110(2):316-29.
7. Koshland DE, Jr. The molecule of the year.
reduced tobacco use, improved to a slowly released, continuous flow Science. 1992 Dec 18;258(5090):1861.
diets and medical treatments, better of L-arginine to boost nitric oxide. 8. Moncada S, Higgs A. The L-arginine-nitric
oxide pathway. N Engl J Med. 1993 Dec
control of hypertension, along with For longer life, 30;329(27):2002-12.
increased use of supplements, and 9. Snyder SH, Bredt DS. Biological roles of
nitric oxide. Sci Am. 1992 May;266(5):68-
drugs that lower heart attack risk.51 71, 4-7.
A lot of people who would have 10. Talan J. The healing powers of nitric oxide.
Montreal Gazette. September 26, 1993: C5.
suffered from blocked coronary
11. Ignarro LJ, Buga GM, Wood KS, et al.
arteries or a heart attack around William Faloon, Co-Founder Endothelium-derived relaxing factor pro-
age 50 are delaying this problem Life Extension Buyers Club duced and released from artery and vein is
nitric oxide. Proc Natl Acad Sci U S A. 1987
until later in life. Dec;84(24):9265-9.

AS WE SEE IT
12. Hurlimann D. The relationship between 30. Tardif JC, Rheaume E. Lipoic acid supple- 45. Ellulu MS. Obesity, cardiovascular
the endothelium and the vessel wall. mentation and endothelial function. Br J disease, and role of vitamin C on inflam-
European Heart Journal Supplements. Pharmacol. 2008 Apr;153(8):1587-8. mation: a review of facts and underlying
2002;4(suppl_A):A1-A7. 31. Wang D, Ozen C, Abu-Reidah IM, et al. mechanisms. Inflammopharmacology. 2017
13. Wilson G, Garthwaite J. Nitric Oxide. In: Vasculoprotective Effects of Pomegranate Jun;25(3):313-28.
Squire LR, ed. Encyclopedia of Neurosci- (Punica granatum L.). Front Pharmacol. 46. Santos-Parker JR, Strahler TR, Bassett CJ,
ence. Oxford: Academic Press; 2009:1151-6. 2018;9:544. et al. Curcumin supplementation improves
14. L-arginine. Monograph. Altern Med Rev. 32. Zehr KR, Walker MK. Omega-3 polyunsatu- vascular endothelial function in healthy
2005 Jun;10(2):139-48. rated fatty acids improve endothelial func- middle-aged and older adults by increas-
15. Available at: https://www.essentialnutrition. tion in humans at risk for atherosclerosis: A ing nitric oxide bioavailability and reducing
com.br/media/artigos/crealift/23.pdf. Ac- review. Prostaglandins Other Lipid Mediat. oxidative stress. Aging (Albany NY). 2017
cessed January 17, 2020. 2018 Jan;134:131-40. Jan 3;9(1):187-208.
16. Gould A, Naidoo C, Candy G. Arginine me- 33. Zanetti M, Gortan Cappellari G, Barbetta D, 47. Komorowski J, Perez Ojalvo S, Sylla S, et
tabolism and wound healing. Wound Heal et al. Omega 3 Polyunsaturated Fatty Acids al. Arginase inhibition by inositol-stabilized
South Afr. 2009 01/01;1:48-50. Improve Endothelial Dysfunction in Chronic arginine silicate (ASI; Nitrosgine); a novel
17. Ghasemi M, Nematbakhsh M, Daneshmand Renal Failure: Role of eNOS Activation and mechanism by which ASI enhances argi-
F, et al. Role of nitric oxide in kidney and of Oxidative Stress. Nutrients. 2017 Aug nine bioavailability. American Society for
liver (as distance organ) function in bilateral 18;9(8):895. Nutrition’s Annual Meeting 2018; 2018;
renal ischemia-reperfusion: Effect of L- 34. Fahs CA, Yan H, Ranadive S, et al. The Boston, MA.
Arginine and NG-nitro-L-Arginine methyl effect of acute fish-oil supplementation on 48. Varela CE, Fromentin E, Roller M, et
ester. Adv Biomed Res. 2015;4:233. endothelial function and arterial stiffness al. Effects of a natural extract of Aronia
18. Tirani SA, Pezeshki Z, Nematbakhsh M, following a high-fat meal. Appl Physiol Nutr Melanocarpa berry on endothelial cell nitric
et al. Effect of L-arginine and L-NAME on Metab. 2010 Jun;35(3):294-302. oxide production. J Food Biochem. 2016
Kidney Tissue Damage in Rats after 24 h 35. Stanhewicz AE, Kenney WL. Role of folic Aug;40(4):404-10.
of Bilateral Ureteral Obstruction. Int J Prev acid in nitric oxide bioavailability and vas- 49. Kim JH, Auger C, Kurita I, et al. Aronia
Med. 2015;6:60. cular endothelial function. Nutr Rev. 2017 melanocarpa juice, a rich source of poly-
19. Strohle A, von Bibra H, Hahn A. L-Arginine Jan;75(1):61-70. phenols, induces endothelium-dependent
and vascular health. Med Monatsschr 36. Ashor AW, Lara J, Mathers JC, et al. Ef- relaxations in porcine coronary arteries via
Pharm. 2016 Dec;39(12):515-20. fect of vitamin C on endothelial func- the redox-sensitive activation of endothelial
20. Gornik HL, Creager MA. Arginine and tion in health and disease: a systematic nitric oxide synthase. Nitric Oxide. 2013
endothelial and vascular health. J Nutr. 2004 review and meta-analysis of randomised Nov 30;35:54-64.
Oct;134(10 Suppl):2880S-7S; discussion 95S. controlled trials. Atherosclerosis. 2014 50. Weir HK, Anderson RN, Coleman King SM,
21. Heffernan KS, Fahs CA, Ranadive SM, et Jul;235(1):9-20. et al. Heart Disease and Cancer Deaths -
al. L-arginine as a nutritional prophylaxis 37. Mohammad A, Ali N, Reza B, et al. Effect of Trends and Projections in the United States,
against vascular endothelial dysfunction ascorbic acid supplementation on nitric ox- 1969-2020. Prev Chronic Dis. 2016 Nov
with aging. J Cardiovasc Pharmacol Ther. ide metabolites and systolic blood pressure 17;13:E157.
2010 Mar;15(1):17-23. in rats exposed to lead. Indian J Pharmacol. 51. Mensah GA, Wei GS, Sorlie PD, et al. De-
22. Wang JC, Bennett M. Aging and ath- 2010 Apr;42(2):78-81. cline in Cardiovascular Mortality: Possible
erosclerosis: mechanisms, functional 38. Cui S, Li W, Lv X, et al. Folic Acid Supple- Causes and Implications. Circ Res. 2017
consequences, and potential therapeutics mentation Delays Atherosclerotic Lesion Jan 20;120(2):366-80.
for cellular senescence. Circ Res. 2012 Jul Development by Modulating MCP1 and 52. Dubois B, Hampel H, Feldman HH, et al.
6;111(2):245-59. VEGF DNA Methylation Levels In Vivo and Preclinical Alzheimer’s disease: Definition,
23. Konukoglu D, Uzun H. Endothelial Dysfunc- In Vitro. Int J Mol Sci. 2017 May 5;18(5). natural history, and diagnostic criteria. Al-
tion and Hypertension. Adv Exp Med Biol. 39. Graham IM, O’Callaghan P. The role of zheimers Dement. 2016 Mar;12(3):292-323.
2017;956:511-40. folic acid in the prevention of cardiovas- 53. Kooman JP, van der Sande FM, Leunissen
24. Ming X-F, Yang Z. Functions and Mecha- cular disease. Curr Opin Lipidol. 2000 KM. Kidney disease and aging: A recipro-
nisms of Arginase in Age-Associated Car- Dec;11(6):577-87. cal relation. Exp Gerontol. 2017 Jan;87(Pt
diovascular Diseases. Current Translational 40. Jain AP, Aggarwal KK, Zhang PY. Omega-3 B):156-9.
Geriatrics and Experimental Gerontology fatty acids and cardiovascular disease. Eur 54. Chade AR, Lerman A, Lerman LO. Kidney
Reports. 2013 2013/12/01;2(4):268-74. Rev Med Pharmacol Sci. 2015;19(3):441-5. in early atherosclerosis. Hypertension. 2005
25. Wu G, Morris SM, Jr. Arginine metabolism: 41. Aviram M, Rosenblat M. Pomegranate Jun;45(6):1042-9.
nitric oxide and beyond. Biochem J. 1998 for your cardiovascular health. Rambam 55. Stein RA. Endothelial dysfunction, erectile
Nov 15;336 ( Pt 1):1-17. Maimonides Med J. 2013 Apr;4(2):e0013. dysfunction, and coronary heart disease:
26. Berkowitz DE, White R, Li D, et al. Arginase 42. Zhang WJ, Bird KE, McMillen TS, et al. the pathophysiologic and clinical linkage.
reciprocally regulates nitric oxide synthase Dietary alpha-lipoic acid supplementation Rev Urol. 2003;5 Suppl 7(Suppl 7):S21-7.
activity and contributes to endothelial dys- inhibits atherosclerotic lesion develop-
function in aging blood vessels. Circulation. ment in apolipoprotein E-deficient and
2003 Oct 21;108(16):2000-6. apolipoprotein E/low-density lipoprotein
27. Torregrossa AC, Aranke M, Bryan NS. receptor-deficient mice. Circulation. 2008
Nitric oxide and geriatrics: Implications in Jan 22;117(3):421-8.
diagnostics and treatment of the elderly. J 43. Oz HS. Chronic Inflammatory Diseases and
Geriatr Cardiol. 2011 Dec;8(4):230-42. Green Tea Polyphenols. Nutrients. 2017
28. Egashira K, Inou T, Hirooka Y, et al. Effects Jun 1;9(6):561.
of age on endothelium-dependent vaso- 44. Margaritis M, Channon KM, Antoniades
dilation of resistance coronary artery by C. Statins as regulators of redox state in
acetylcholine in humans. Circulation. 1993 the vascular endothelium: beyond lipid
Jul;88(1):77-81. lowering. Antioxid Redox Signal. 2014 Mar
29. Heinisch BB, Francesconi M, Mittermayer 10;20(8):1198-215.
F, et al. Alpha-lipoic acid improves vascular
endothelial function in patients with type 2
diabetes: a placebo-controlled randomized
trial. Eur J Clin Invest. 2010 Feb;40(2):148-54.

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IN THE NEWS
In the News
Atrial Fibrillation and Heart
Failure Risk are Lower with
Better Oral Hygiene
How well you take care of your teeth

is linked to your risk of atrial fibrillation
and heart failure, a study published
in the European Journal of Preventive
Cardiology* reported.
Better oral hygiene is associated with
a lower risk of atrial fibrillation and heart
failure, researchers concluded.
The study subjects were 161,286 men
and women from the National Health
Insurance System-Health Screening
Cohort in Korea, aged 40 to 79, with no
prior history of atrial fibrillation, heart fail-
ure, or cardiac valvular diseases. They
were examined by dentists to note the
presence of periodontal disease, con-
dition of teeth, and missing teeth, and
they completed a questionnaire about
their oral hygiene behavior and dental
symptoms.
The median follow-up was 10.5 years,
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(4.9%) cases of heart failure.
Brushing teeth three times a day
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authors stated.
* Eur J Prev Cardiol. 2019 Dec 1.

IN THE NEWS
PEA Safe, Effective for In comparison with the placebo group, participants who
Knee Osteoarthritis received PEA experienced significant reductions in pain
(up to 57.6%) and stiffness (up to 53.7%) scores. Function
The journal Inflammopharmacology reported the out- significantly improved among those who received 600 mg
come of a randomized, double-blind trial that revealed of PEA. Both doses of PEA were associated with improve-
the safety and efficacy of supplementation with PEA ments in pain intensity scores and anxiety.
(palmitoylethanolamide) for individuals with knee osteo- By week eight, the number of participants reporting
arthritis.* no pain had increased by more than two and a half times
The trial included 111 men and women with mild to in both groups, while decreasing slightly among the pla-
moderate osteoarthritis in one or both knees who were cebo group compared to the beginning of the study.
given either a placebo, 300 mg of PEA or 600 mg of Editor’s Note: Palmitoylethanolamide is a fatty acid that is naturally
PEA daily for eight weeks. Pain, stiffness and other fac- produced in the body as part of a healthy immune response.
tors were evaluated at the beginning and end of the trial. * Inflammopharmacology. 2019 Jun;27(3):475-485.

IN THE NEWS
Drinking Tea Supports a

Healthy Brain
Research reported in the jour-

nal Aging revealed a brain benefit
in association with regularly drink-
ing tea.*
Acting on the results of previous
research that found a reduction in
the risk of cognitive decline among
daily tea drinkers, the current study
compared 15 tea drinkers aged 60
and older to 21 participants in the
same age group who did not regu-
larly consume tea.
Neuropsychological tests evalu-
ated cognitive function and mag-
netic resonance imaging assessed
brain connectivity. Participants who
regularly consumed tea had better
organized brain regions and cogni-
tive function compared to those who
were not tea drinkers.
The authors noted that, “Tea
has been a popular beverage since
antiquity, with records referring to
consumption dating back to the
dynasty of Shen Nong (approxi-
mately 2700 BC) in China.” They
went on to say that drinking tea
has become increasingly popular in
western countries today.
The study was led by Research
Assistant Professor Feng Lei, of the
National University of Singapore
School of Medicine, with collabora-
tors from the University of Essex and
University of Cambridge.
Editor’s Note: “Our results offer the first evi-

dence of positive contribution of tea drinking
to brain structure and suggest that drinking
tea regularly has a protective effect against
age-related decline in brain organization,” said
Dr. Feng Lei.
* Aging (Albany NY). 2019 Jun 14;11(11):

3876-3890.

IN THE NEWS
Blueberry Intake May

Reduce Cardiovascular
Disease Risk
A study reported in the American

Journal of Clinical Nutrition found
a lower risk of cardiovascular dis-
ease among men and women with
metabolic syndrome who con-
sumed the equivalent of a cup of
blueberries daily for six months.*
A total of 138 participants
were randomized to groups that
received 26 grams of powdered
blueberries (equivalent to a cup
of fresh blueberries), 13 grams of
powdered blueberries plus ½ cup
of a mock blueberry placebo, or 26
grams of the placebo.
Insulin resistance, flow mediated
dilatation (a measure of endothe-
lial function), augmentation index
(which measures arterial stiffness),
cholesterol, and other factors were
measured before and after the
intervention.
The researchers observed an
improvement in endothelial func-
tion and arterial stiffness in the
group that received 26 grams of
blueberry powder.
Editor’s Note: “The simple and attainable

message to consume one cup of blueber-
ries daily should be given to those aiming
to improve their cardiovascular health,” the
authors concluded.
* Am J Clin Nutr. 2019 Jun 1;109(6):1535-

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Boost Nitric Oxide
to Reduce
Cardiovascular
RISK
BY JACOB ROSE
Nitric oxide is a substance your body naturally

produces.
It signals blood vessels to widen, allowing blood to

flow through freely.
But nitric oxide production decreases with age.1

This contributes to endothelial dysfunction that
leads to the initiation and progression of arterial
disease.2-5
The consequences of endothelial dysfunction are:

1. Diminished circulation
2. High blood pressure
3. Thrombosis
(clots inside blood vessels)
4. Atherosclerosis
These are major causes of stroke and heart

attack.5-8
We can’t get nitric oxide directly from diet or

supplements.
The good news is that L-arginine and aronia
berries help the body make more of it.

BOOST NITRIC OXIDE TO REDUCE CARDIOVASCULAR RISK
Endothelial Dysfunction and How L-Arginine Helps

Cardiovascular Disease Unfortunately, we can’t simply take nitric oxide as
The endothelium is the inner lining of blood ves- a supplement. It has an extremely short half-life, which
sels, and it plays a critical role in regulating the flow of means it’s too quickly metabolized and eliminated from
blood.2-4 the bloodstream to be useful.
It does this by producing nitric oxide, which signals To work properly, blood vessels must make nitric
blood vessels to dilate (widen). That allows greater oxide for themselves. To do so, they need a precur-
blood flow to tissues, including the heart and brain. sor compound. This precursor is an amino acid called
But as we age, our body makes less nitric oxide.1 L-arginine.
That can lead to endothelial dysfunction, which means Aware of this link between L-arginine and nitric
the blood vessels are unable to dilate and constrict as oxide production, researchers evaluated whether
needed, reducing blood flow.2-4 increasing intake of L-arginine improves blood vessel
This condition, referred to as arterial stiffness, con- dilation, lowering risk for disease.13-17
tributes to high blood pressure, formation of athero- One of the main ways to test this is to measure how
sclerotic plaque, and inflammation in the arteries—all much a blood vessel widens in response to an increase
of which can lead to cardiovascular disease.9 in blood flow, something called flow-mediated dilation.
It also greatly increases the risk of abnormal clotting, In a landmark clinical trial published in the
which can block blood vessels, leading to heart attack, International Journal of Cardiology, scientists gave
stroke, and sudden cardiac death.10,11 patients with high blood pressure a single dose of either
Endothelial dysfunction is surprisingly common; L-arginine or a placebo.15 While the placebo group had
one study showed it affected about one third of people no change in their blood vessel function, those receiv-
without any prior history of cardiovascular disease.12 ing L-arginine had an improvement in their flow-medi-
The elderly, diabetics, the obese, smokers, people with ated dilation from an average of 1.7% to 5.9%.
cardiovascular disease, and those with high cholesterol Considering that each 1% improvement in flow-
or high blood pressure have a higher risk.2-4 mediated dilation correlates with a 12% lower risk of
But if we can increase the amount of nitric oxide in cardiovascular events like heart attacks and strokes,18,19
our blood vessels, it may stop, and even reverse endo- this would suggest a 50% reduction in risk of cardio-
thelial dysfunction. vascular events if the effect is sustained over time.
Other longer-term clinical studies have shown that
taking L-arginine can lower blood pressure and reduce
symptoms associated with coronary artery disease.16,20
A New, Better Form of L-Arginine

Life Extension® has written about L-arginine for the
past 38 years. But in the last few years, scientists have
developed and tested a new form.
Known as inositol-stabilized arginine silicate, this
novel form is more bioavailable, which means more of
it is absorbed into the bloodstream after ingestion.
Studies show that L-arginine blood levels increase
within one hour after supplementation with inositol-
stabilized arginine silicate and stay there for many
hours.21,22
It appears to do this by inhibiting the enzyme argi-
nase, which breaks down L-arginine in the digestive
tract, allowing more of the L-arginine to enter and cir-
culate in the blood longer.23

WHAT YOU NEED TO KNOW
Boost Nitric Oxide to

Support Endothelial
Function
Q The endothelium is a layer of cells lining
Aronia Berry Improves Endothelial Function the inside of blood vessels. It produces
Aronia berries are small, dark purple berries native nitric oxide, a gas that signals the
to North America. They’re high in anthocyanins, ben- vessel to dilate, allowing blood to flow
eficial polyphenols. through and preventing abnormal
Scientists discovered that like L-arginine, aronia can clotting.
improve endothelial function. Q With age and other risk factors, nitric
While L-arginine provides the precursor needed oxide production declines, contribut-
to form nitric oxide, polyphenols from aronia berries ing to endothelial dysfunction. This
appear to increase the activity of the enzyme that con- increases risk for the development of
verts the L-arginine into nitric oxide. cardiovascular disease events, includ-
It does this by inducing the modification of the ing heart attack and stroke.
enzyme, called endothelial nitric oxide synthase, in
a way that turns the enzyme “on.”24 Q L-arginine is a precursor the body
In one randomized, controlled trial, daily supplemen- needs to make nitric oxide. A new form,
tation with 500 mg of aronia whole fruit berry for 12 inositol-stabilized arginine silicate,
weeks resulted in improved flow-mediated dilation.25 improves its bioavailability and supports
Subjects taking the aronia had a 0.9% improvement higher levels in the bloodstream for a
in flow-mediated dilation compared to those taking a longer time.
placebo.
Q Aronia berries help activate the
That may sound small, but bear in mind that each 1%
enzyme that converts L-arginine into
improvement in flow-mediated dilation correlates with a
nitric oxide.
12% lower risk of cardiovascular events,18,19 suggesting
that this corresponds to a nearly 11% reduction in risk Q These two ingredients work to boost
for cardiovascular events. nitric oxide production, helping blood
The enhanced bioavailability of inositol-stabilized vessels dilate more efficiently. This may
arginine silicate coupled with the increased endothe- significantly reduce risk for heart attack,
lial nitric oxide synthase activity from aronia berries stroke, and other cardiovascular events.
make this a potent duo in the production of nitric oxide.

Summary 17. Melik Z, Zaletel P, Virtic T, et al. L-arginine as dietary supplement

for improving microvascular function. Clin Hemorheol Microcirc.
Our bodies produce nitric oxide, which signals 2017;65(3):205-17.
blood vessels to dilate. With age, its production 18. Matsuzawa Y, Kwon TG, Lennon RJ, et al. Prognostic Value of
Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery
declines, contributing to endothelial dysfunction. for Cardiovascular Events: A Systematic Review and Meta-Analy-
Endothelial dysfunction increases the risk of cardio- sis. J Am Heart Assoc. 2015 Nov 13;4(11).
19. Shimbo D, Grahame-Clarke C, Miyake Y, et al. The association
vascular disease, including heart attacks and strokes. between endothelial dysfunction and cardiovascular outcomes
Two ingredients, L-arginine and aronia berries, in a population-based multi-ethnic cohort. Atherosclerosis. 2007
May;192(1):197-203.
boost the body’s production of nitric oxide. 20. McRae MP. Therapeutic Benefits of l-Arginine: An Umbrella Review
Human studies show that they improve the flow of of Meta-analyses. J Chiropr Med. 2016 Sep;15(3):184-9.
blood through the vessels, which can reduce the risk 21. Kalman DS, Feldman S, Samson A, et al. A clinical evaluation to
determine the safety, pharmacokinetics, and pharmacodynam-
for cardiovascular disease. • ics of an inositol-stabilized arginine silicate dietary supplement in
healthy adult males. Clin Pharmacol. 2015;7:103-9.
22. Komorowski J, Perez Ojalvo S. A pharmacokinetic evaluation of
If you have any questions on the scientific the duration of effect of inositol-stabilized arginine silicate and
content of this article, please call a Life Extension® arginine hydrochloride in healthy adult males. FASEB J. 2016;30
Wellness Specialist at 1-866-864-3027. (1_suppl).
23. Komorowski J, Perez Ojalvo S, Sylla S, et al. Poster Presentation
presented at the American Society for Nutrition’s Annual Meeting
2018. Arginase inhibition by inositol-stabilized arginine silicate
References (ASI; Nitrosigine); a novel mechanism by which ASI enhances
arginine bioavailability. Current Developments in Nutrition. 2018.
1. Torregrossa AC, Aranke M, Bryan NS. Nitric oxide and geriatrics: 24. Varela CE, Fromentin E, Roller M, et al. Effects of a natural extract
Implications in diagnostics and treatment of the elderly. J Geriatr of Aronia Melanocarpa berry on endothelial cell nitric oxide pro-
Cardiol. 2011 Dec;8(4):230-42. duction. J Food Biochem. 2016 Aug;40(4):404-10.
2. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclero- 25. Istas G, Wood E, Le Sayec M, et al. Effects of aronia berry (poly)
sis. Circulation. 2004 Jun 15;109(23 Suppl 1):III27-32. phenols on vascular function and gut microbiota: a double-blind
3. Widlansky ME, Gokce N, Keaney JF, Jr., et al. The clinical impli- randomized controlled trial in adult men. Am J Clin Nutr. 2019 Aug
cations of endothelial dysfunction. J Am Coll Cardiol. 2003 Oct 1;110(2):316-29.
1;42(7):1149-60.
4. Widmer RJ, Lerman A. Endothelial dysfunction and cardiovascular
disease. Glob Cardiol Sci Pract. 2014;2014(3):291-308.
5. Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial
function in humans. Clin Sci (Lond). 2011 May;120(9):357-75.
6. Fordjour PA, Wang Y, Shi Y, et al. Possible mechanisms of C-reac-
tive protein mediated acute myocardial infarction. Eur J Pharmacol.
2015 Aug 5;760:72-80.
7. Eelen G, de Zeeuw P, Simons M, et al. Endothelial cell metabo-
lism in normal and diseased vasculature. Circ Res. 2015 Mar
27;116(7):1231-44.
8. Huveneers S, Daemen MJ, Hordijk PL. Between Rho(k) and a
hard place: the relation between vessel wall stiffness, endothe-
lial contractility, and cardiovascular disease. Circ Res. 2015 Feb
27;116(5):895-908.
9. Namba T, Masaki N, Takase B, et al. Arterial Stiffness Assessed by
Cardio-Ankle Vascular Index. Int J Mol Sci. 2019 Jul 26;20(15).
10. Aykan AC, Hatem E, Kalaycioglu E, et al. Assessment of arterial
stiffness in patients with venous thromboembolism: Separate or
continuous circuits? Phlebology. 2017 Jun;32(5):316-21.
11. Cooper JN, Evans RW, Mori Brooks M, et al. Associations between
arterial stiffness and platelet activation in normotensive overweight
and obese young adults. Clin Exp Hypertens. 2014;36(3):115-22.
12. Toggweiler S, Schoenenberger A, Urbanek N, et al. The prevalence
of endothelial dysfunction in patients with and without coronary
artery disease. Clin Cardiol. 2010 Dec;33(12):746-52.
13. Cooke JP, Singer AH, Tsao P, et al. Antiatherogenic effects of
L-arginine in the hypercholesterolemic rabbit. J Clin Invest. 1992
Sep;90(3):1168-72.
14. Hambrecht R, Hilbrich L, Erbs S, et al. Correction of endothelial
dysfunction in chronic heart failure: additional effects of exercise
training and oral L-arginine supplementation. J Am Coll Cardiol.
2000 Mar 1;35(3):706-13.
15. Lekakis JP, Papathanassiou S, Papaioannou TG, et al. Oral L-
arginine improves endothelial dysfunction in patients with essential
hypertension. Int J Cardiol. 2002 Dec;86(2-3):317-23.
16. Lerman A, Burnett JC, Jr., Higano ST, et al. Long-term L-arginine
supplementation improves small-vessel coronary endothelial func-
tion in humans. Circulation. 1998 Jun 2;97(21):2123-8. ARONIA BERRIES

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SAFELY
SAF E L AL
ELY ALLEV
ALLEVIATE
L IATE
LEV IAT
T E 11
1 1 SYM
S
SYMPTOMS
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MPT
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How Men Can Fight

OSTEOPOROSIS

BY SUSAN CUMMINGS
Osteoporosis has long been viewed as a disease

that primarily affects women, turning their bones
weak and prone to fractures as they age.
But men are at a far higher risk of osteoporosis than

most realize. About one-third of all hip fractures
worldwide occur in men.1
And while women do get osteoporosis more fre-
quently, fractures in men result in more severe, and
deadly complications.2-4
The rate of bone loss in osteoporosis is closely asso-
ciated with increased mortality.5-8
And all men can strengthen bones and help pre-

vent fractures with a few simple measures, including
increased physical activity, weight-bearing exercises,
resistance training, and ensuring proper intake of
nutrients including magnesium, calcium, vitamin
D, vitamin K, and more.
Together, these actions can help maintain healthy

bones well into advanced age.
HOW MEN CAN FIGHT OSTEOPOROSIS
Osteoporosis in Men Assessing Fracture Risk

Healthy bone is constantly being remodeled. This Osteoporosis in men usually results from a combina-
means that old bone is broken down and new bone is tion of risk factors, rather than from a single cause (like
formed. menopause in women).2
For people with osteoporosis, bone loss outweighs The most frequent causes of osteoporosis in men
bone growth. The result is low bone mass, deterioration are alcohol abuse, excessive use of corticosteroids
of bone tissue, and bone fragility that leads to increased (medications often used to treat inflammatory disorders),
fracture risk.9,10 and low testosterone and estrogen from aging, or from
Osteoporosis usually produces no symptoms until androgen-deprivation therapy for prostate cancer.2
a fracture occurs,2,11-13 so it remains underdiagnosed Once osteoporosis has developed, many factors
and undertreated. Many men, in particular, believe raise the risk of bone fractures in men, including:1,2,9,12
osteoporosis affects mostly aging women and ignore
• Increasing age,
their own risks.14
But rates in men are striking: • Low body mass index,
• Up to 1/3 of all hip fractures worldwide • A history of fragility fractures in the
occur in men.1 individual or a parent,
• Half of male hip fractures occur before • Low testosterone and estrogen,
the age of 80.1,15
• Prolonged immobilization or inactivity,
Hip fractures are the most serious of all broken • High alcohol intake,
bones resulting from osteoporosis.2
In a study in men aged 60 and over, the mortality • Smoking,
rate at one year from hip fractures was 37.5%,3 while • Glucocorticoid treatment,
another study found that men are more than twice as
likely as women to die from infection during the first • Type I diabetes,
two years after a hip fracture.4
• Rheumatoid arthritis,
Fractures of the spinal vertebrae are much harder
to detect than hip fractures. They may cause little pain • Thyroid disorders, and
at first, but can gradually lead to severe discomfort and
• Chemotherapy treatment for cancer.
risk of serious spinal cord injury.2,16

Weight-bearing and resistance exercises help build

strong bones.17 And there are a variety of nutrients that
can help slow bone loss and prevent fractures.
Nutrients to Promote Bone Strength

The standard nutritional “building blocks” of bone
are calcium and vitamin D3.18
Calcium provides the bulk of the mineral content of
bones, and vitamin D promotes calcium uptake from
the gut.
But bones aren’t simple structures that can be built
and left alone.
They’re dynamic, living tissue, with all the vulnerabili-
ties to damage as any other tissue. It’s now recognized
that healthy bones require additional nutritional support.
• Magnesium regulates calcium movement into

and between bone cells, increasing bone min-
eral density.19
Q
• Zinc stimulates new bone formation and helps
calcium consolidate in bone.20
WHAT YOU NEED TO KNOW
• Manganese functions as an essential cofactor
(helper molecule) for enzymes that promote Building and Protecting
Strong Bones
the growth of bone and prevent damaging oxi-
dative stress.21
• Silicon improves the quality of bone matrix (the Q Osteoporosis is no longer thought
non-mineral part of bone composed of collagen of as a disease that just affects older
and other proteins) and facilitates the bone- women. About one-third of all hip
building process known as mineralization.22 fractures worldwide occur in men.
• Boron regulates the proper metabolism of Q Men have a higher death rate from
calcium and other bone-forming minerals and hip fractures than women, and higher
influences the metabolism of vitamin D.23-25 rates of bone loss are associated
with higher mortality.
• Vitamin K is essential for activating a bone
hormone (osteocalcin) needed to maintain Q All men can benefit from ensuring
bone strength.26,27 Low vitamin K status is adequate intake of vitamins and min-
associated with decreased bone density and erals that build up bone strength and
increased fracture risk.28 help minimize risk of fracture, includ-
ing calcium, vitamin D3, vitamin
New evidence is also emerging for two other com- K, magnesium, manganese, zinc,
pounds that support bone health. silicon, and boron.
1. Curcumin, an extract of the turmeric plant, Q The nutrients curcumin and PQQ
has powerful anti-inflammatory properties. also play important roles in reducing
Chronic systemic inflammation is now being the oxidative stress and inflammation
recognized as a contributor to osteoporosis that contribute to bone loss.
risk.29,30

• Newer studies have found that curcumin acts If you have any questions on the scientific
in multiple ways to increase bone mineral content of this article, please call a Life Extension®
density and boost resistance to fractures.31-35 Wellness Specialist at 1-866-864-3027.
In one human study, curcumin in combination
with calcium added to the effects of a pre-
References
scription osteoporosis drug, alendronate.34
1. Herrera A, Lobo-Escolar A, Mateo J, et al. Male osteoporosis: A
review. World J Orthop. 2012 Dec 18;3(12):223-34.
2. PQQ (pyrroloquinoline quinone) is a vita- 2. Giusti A, Bianchi G. Male osteoporosis. Reumatismo. 2014 Jul
min-like nutrient with anti-aging properties 28;66(2):136-43.
3. Jiang HX, Majumdar SR, Dick DA, et al. Development and initial
related to its ability to help mitochondria (the
validation of a risk score for predicting in-hospital and 1-year
“powerhouses” of the cells) use energy more mortality in patients with hip fractures. J Bone Miner Res. 2005
efficiently.36 Mar;20(3):494-500.
4. Wehren LE, Hawkes WG, Orwig DL, et al. Gender differences in
mortality after hip fracture: the role of infection. J Bone Miner Res.
• Studies of PQQ in osteoporosis-prone mice 2003 Dec;18(12):2231-7.
show that it enhances the activity of bone- 5. Lee P, Ng C, Slattery A, et al. Preadmission Bisphosphonate and
forming osteoblast cells while reducing the Mortality in Critically Ill Patients. J Clin Endocrinol Metab. 2016
May;101(5):1945-53.
activity of bone-destroying osteoclast cells, 6. Lenchik L, Register TC, Russell GB, et al. Volumetric bone mineral
resulting in increased bone mass and density of the spine predicts mortality in African-American men
with type 2 diabetes. Osteoporos Int. 2018 Sep;29(9):2049-57.
density.36-39 7. Masunari N, Fujiwara S, Kasagi F, et al. Height loss starting in
middle age predicts increased mortality in the elderly. J Bone
Ensuring adequate daily intake of all these nutrients Miner Res. 2012 Jan;27(1):138-45.
can minimize the risk of developing osteoporosis and 8. Bliuc D, Tran T, van Geel T, et al. Reduced Bone Loss Is Associ-
ated With Reduced Mortality Risk in Subjects Exposed to Nitrogen
related fractures. Bisphosphonates: A Mediation Analysis. J Bone Miner Res. 2019
Nov;34(11):2001-11.
9. Pisani P, Renna MD, Conversano F, et al. Major osteoporotic fragil-
ity fractures: Risk factor updates and societal impact. World J
Summary Orthop. 2016 Mar 18;7(3):171-81.
Osteoporosis is a progressive loss of bone density
and strength, leading to sharply raised risk of fractures.
It was once thought mostly to affect older women.
But about one-third of all hip fractures worldwide occur
in men.
And because of the high osteoporosis risk, all men
should regularly exercise to strengthen their bones, and
should ensure they are getting the nutrients required to
build and maintain strong bones.
Those include calcium, vitamin K, and vitamin D3,
along with the minerals magnesium, manganese, zinc,
silicon, and boron.
Further bone support can be obtained from cur-
cumin and PQQ, which fight inflammation, improve
bone cell energy use, and produce stronger bones. •

10. Kanis JA, McCloskey EV, Johansson H, et al. European guidance for
the diagnosis and management of osteoporosis in postmenopausal
women. Osteoporos Int. 2013 Jan;24(1):23-57.
11. Nih Consensus Development Panel on Osteoporosis Prevention D,
Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA.
2001 Feb 14;285(6):785-95.
12. Drake MT, Khosla S. Male osteoporosis. Endocrinol Metab Clin
North Am. 2012 Sep;41(3):629-41.
13. Consensus development conference: diagnosis, prophylaxis, and
treatment of osteoporosis. Am J Med. 1993 Jun;94(6):646-50.
14. Dy CJ, Lamont LE, Ton QV, et al. Sex and gender considerations
in male patients with osteoporosis. Clin Orthop Relat Res. 2011
Jul;469(7):1906-12.
15. Chang KP, Center JR, Nguyen TV, et al. Incidence of hip and other
osteoporotic fractures in elderly men and women: Dubbo Osteopo-
rosis Epidemiology Study. J Bone Miner Res. 2004 Apr;19(4):532-6.
16. Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008
Jun;29(4):441-64.
17. Available at: https://www.bones.nih.gov/health-info/bone/bone-
health/exercise/exercise-your-bone-health. Accessed January 27,
2020.
18. Moyer VA, Force* USPST. Vitamin D and calcium supplementa-
tion to prevent fractures in adults: U.S. Preventive Services Task
Force recommendation statement. Ann Intern Med. 2013 May
7;158(9):691-6.
19. Mammoli F, Castiglioni S, Parenti S, et al. Magnesium Is a Key
Regulator of the Balance between Osteoclast and Osteoblast Dif-
ferentiation in the Presence of Vitamin D(3). Int J Mol Sci. 2019 Jan
17;20(2).
20. Yamaguchi M. Role of nutritional zinc in the prevention of osteopo-
rosis. Mol Cell Biochem. 2010 May;338(1-2):241-54.
21. Available at: https://lpi.oregonstate.edu/mic/minerals/manganese.
Accessed January 23, 2020.
22. Price CT, Koval KJ, Langford JR. Silicon: a review of its potential
role in the prevention and treatment of postmenopausal osteoporo-
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23. Devirian TA, Volpe SL. The physiological effects of dietary boron.
Crit Rev Food Sci Nutr. 2003;43(2):219-31.
24. Naghii MR, Samman S. The role of boron in nutrition and metabo-
lism. Prog Food Nutr Sci. 1993 Oct-Dec;17(4):331-49.
25. Nielsen FH. Studies on the relationship between boron and mag-
nesium which possibly affects the formation and maintenance of
bones. Magnes Trace Elem. 1990;9(2):61-9.
26. Fujita Y, Iki M, Tamaki J, et al. Association between vitamin K intake
from fermented soybeans, natto, and bone mineral density in
elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men 33. French DL, Muir JM, Webber CE. The ovariectomized, mature rat model
(FORMEN) study. Osteoporos Int. 2012 Feb;23(2):705-14. of postmenopausal osteoporosis: an assessment of the bone sparing
27. Bullo M, Estruch R, Salas-Salvado J. Dietary vitamin K intake is effects of curcumin. Phytomedicine. 2008 Dec;15(12):1069-78.
associated with bone quantitative ultrasound measurements but 34. Khanizadeh F, Rahmani A, Asadollahi K, et al. Combination therapy
not with bone peripheral biochemical markers in elderly men and of curcumin and alendronate modulates bone turnover markers and
women. Bone. 2011 Jun 1;48(6):1313-8. enhances bone mineral density in postmenopausal women with
28. Rodriguez-Olleros Rodriguez C, Diaz Curiel M. Vitamin K and osteoporosis. Arch Endocrinol Metab. 2018 Aug;62(4):438-45.
Bone Health: A Review on the Effects of Vitamin K Deficiency 35. Li G, Bu J, Zhu Y, et al. Curcumin improves bone microarchitecture
and Supplementation and the Effect of Non-Vitamin K Antagonist in glucocorticoid-induced secondary osteoporosis mice through the
Oral Anticoagulants on Different Bone Parameters. J Osteoporos. activation of microRNA-365 via regulating MMP-9. Int J Clin Exp
2019;2019:2069176. Pathol. 2015;8(12):15684-95.
29. Al-Daghri NM, Aziz I, Yakout S, et al. Inflammation as a contributing 36. Huang Y, Chen N, Miao D. Effect and mechanism of pyrrolo-
factor among postmenopausal Saudi women with osteoporosis. quinoline quinone on anti-osteoporosis in Bmi-1 knockout mice-
Medicine (Baltimore). 2017 Jan;96(4):e5780. Anti-oxidant effect of pyrroloquinoline quinone. Am J Transl Res.
30. Fang H, Zhang H, Wang Z, et al. Systemic immune-inflammation 2017;9(10):4361-74.
index acts as a novel diagnostic biomarker for postmenopausal 37. Geng Q, Gao H, Yang R, et al. Pyrroloquinoline Quinone Prevents
osteoporosis and could predict the risk of osteoporotic fracture. J Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative
Clin Lab Anal. 2020 Jan;34(1):e23016. Stress and Osteocyte Senescence. Int J Biol Sci. 2019;15(1):58-68.
31. Chen Z, Xue J, Shen T, et al. Curcumin alleviates glucocorticoid-in- 38. Wen H, He Y, Zhang K, et al. Mini-review:Functions and Action
duced osteoporosis by protecting osteoblasts from apoptosis in vivo Mechanisms of PQQ in Osteoporosis and Neuro Injury. Curr Stem
and in vitro. Clin Exp Pharmacol Physiol. 2016 Feb;43(2):268-76. Cell Res Ther. 2018 Dec 10.
32. Chen Z, Xue J, Shen T, et al. Curcumin alleviates glucocorticoid- 39. Wu X, Li J, Zhang H, et al. Pyrroloquinoline quinone prevents testos-
induced osteoporosis through the regulation of the Wnt signaling terone deficiency-induced osteoporosis by stimulating osteoblastic
pathway. Int J Mol Med. 2016 Feb;37(2):329-38. bone formation and inhibiting osteoclastic bone resorption. Am J
Transl Res. 2017;9(3):1230-42.

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Improve
DIGESTION
of Plant-
Based Foods
BY MICHAEL DOWNEY
Digestion is a complicated process.
Enzymes are needed to break down each of the major

food groups: carbohydrates, proteins, and fats.
The recent trend toward eating more plant-based foods

has brought along with it the need for additional enzymes
to break down hard-to-digest, fiber-rich foods.
As we age, internal production of digestive enzymes

declines.1 As a result, undigested foods may pass into
the large intestine,2,3 causing bloating, gas, diarrhea,
and cramping.
Researchers have identified additional enzymes that

specifically promote digestion of high-fiber plant foods.
When combined with a specific probiotic, these benefits

can be further enhanced.

IMPROVE DIGESTION OF PLANT-BASED FOODS
Common Causes of Digestive Problems digestion of foods in the stomach. Since then, studies
Many health problems plaguing aging adults, includ- have validated the beneficial effects of digestive enzyme
ing digestive discomfort like gas and diarrhea, impaired supplementation.7-9
immunity, and nutritional deficiencies, can often be Optimal digestion of major food types, including pro-
attributed to poor digestion. teins, fats, dairy, and plant cellulose (fiber), requires dif-
Two important causes of digestive problems are:1-5 ferent digestive enzymes, such as:
1. Age-related declines in production of endogenous • Protease,

digestive enzymes, and
• Lipase,
2. Imbalances in the gut microbiota.
• Lactase,
Digestive enzymes are needed to break down the
foods we eat and extract essential nutrients from them. • Cellulase, and
And a proper balance of bacteria must be present in
the gut to prevent bloating, gas, and other unpleasant • Bromelain.
digestive symptoms.
Drugs such as Alka-Seltzer® and Pepto-Bismol® can
temporarily relieve some symptoms but do nothing to The Challenge of Plant-Based Diets
address the underlying problem. In recent years, diets have changed. More people
are reducing their meat and other animal-derived food
intake and increasing their intake of plant-based foods.
The Power of Digestive Enzymes The cell walls of these foods contain complex poly-
To help break down food more completely by the saccharides and fibers. While fiber is an important part
time it reaches the end of our small intestine, substantial of a healthy diet, it may also bind to minerals and other
amounts of all required digestive enzymes are needed. nutrients, blocking their bioavailability and preventing
This helps prevent undigested food from passing into their absorption.
the colon and causing gastrointestinal problems. Humans do not produce the enzymes required to
About 70 years ago, scientists first discovered6 that break down fiber and depend on enzymes produced
taking digestive enzymes orally leads to more complete by intestinal microorganisms.10,11

Protease 3.0 is an enhanced form of the protease

enzyme that helps digest gliadin found in wheat.
To properly break down other plant-based foods
requires:
• Alpha-galactosidase,
• Hemicellulase,
• Cellulase,
• Xylanase, and
• Pectinase.
General Purpose Enzymes

The enzymes described next have long been used to
improve digestion. Each has a specific, targeted func-
tion that helps break down complex foods into nutrient
components that can be readily absorbed. WHAT YOU NEED TO KNOW
Protease
Protease breaks down proteins. Research shows Boost Digestion
that giving protease to animals enhances their
digestion.12 Q Poor digestion can result in bloating,
Aging individuals may receive tremendous poten- gas, and discomfort, and compromises
tial benefits from supplementing with protease the absorption of key nutrients.
enzymes in order to increase the efficiency of protein
digestion. Q Digestive problems can be caused by an
age-related decline in digestive enzymes
Lactase and an imbalance in the all-important
gut microbial ecosystem.
Lactase breaks down lactose, or milk sugar. Older
people are often deficient in this enzyme,13 resulting in Q Increasing your intake of plant-based
cramps, bloating, gas, and diarrhea after consuming foods creates special challenges to your
dairy products.14 But avoiding dairy can cause calcium digestion but special enzymes that spe-
deficiency, increasing the risk of osteoporosis and bone cifically target these high-fiber foods can
fractures.15-18 help your body better handle a plant-
Studies show that taking lactase reduces or elimi- based diet.
nates post-meal abdominal cramping, belching, flatu-
lence, bloating, and diarrhea in people with lactase Q Digestive enzymes can help break down
insufficiency. It also promotes better overall nutrition.19 and digest food while preventing gastro-
intestinal distress and promoting better
Lipase overall health.
Lipase breaks down fat into individual fatty acids Q Adding Bacillus coagulans to a broad
and related substances. It helps the body absorb vital range of digestive enzymes may provide
fat-soluble nutrients, such as omega-3 fatty acids, protection against several gastrointesti-
carotenoids like lycopene and lutein, and vitamins A, nal discomforts.
D, K, and E.20

Without sufficient lipase, incompletely digested better at promoting the digestion of proteins in acidic
fats can cause greasy, fatty stools and cramping. conditions such as those found in the stomach.
Inadequate fat digestion also blocks absorption of key This enzyme may also help some people with gluten
vitamins, leading to deficiencies. sensitivity or intolerance since it specifically promotes
Taking oral lipase promotes fat digestion.21,22 In one digestion of gliadin, a protein found in gluten in wheat,
study, pancreatic lipase enzymes were given to sub- and some other grains.
jects eating a high-fat meal, resulting in significant
reductions in bloating and gas.22 Alpha-Galactosidase
Alpha-galactosidase is a digestive enzyme that
Bromelain breaks down oligosaccharides, carbohydrates found in
Bromelain is extracted from pineapple stem and fruit. plant foods including beans and cruciferous vegetables
It helps with digestion of proteins.23,25 (such as cauliflower, broccoli, and cabbage).
Scientists studied adults with an inability to fully Taking this enzyme substantially reduces bloating,
digest and absorb fats and proteins. Taking an enzyme discomfort, and flatulence associated with eating these
mix containing bromelain improved digestion and foods.26,27
absorption of both these food groups.25 In one study, scientists recruited volunteers with irri-
table bowel syndrome (IBS). For three days they ate a
diet high in a type of oligosaccharide that triggers IBS
Digestive Enzymes to symptoms. The group that took oral alpha-galactosi-
Support Plant-Based Diets dase had a clinically significant reduction in gastro-
The enzymes described so far support basic digestion. intestinal symptoms compared to a placebo group.28
But the trend toward plant-based foods means
additional enzymes can help improve the breakdown of Cellulase
hard-to-digest types of plant fibers. Cellulase is not produced naturally in the human
The following digestive enzymes deliver potent body. It allows humans to digest most cellulose, or
support for high-fiber, plant-based diets. plant fiber.
This allows for smoother digestion of tough vegetable
Protease 3.0 fiber and minimizes the excessive flatulence that deters
Traditional protease breaks down most proteins. But many people from eating healthy, high-fiber foods like
a specialized protease known as protease 3.0 is even broccoli and beans.

Hemicellulase, Xylanase, and Pectinase One particular probiotic, Bacillus coagulans strain
Additional digestive support is found in three MTCC 5856, has been shown to effectively treat both
enzymes specific for the breakdown of plant foods constipation and diarrhea, along with other symptoms
high in fiber: of irritable bowel syndrome.30,31
In a double-blind, placebo-controlled study, patients
• Hemicellulase breaks down hemicellulose, with irritable bowel syndrome took tablets containing
a complex carbohydrate that is a major 2 billion spores of Bacillus coagulans strain MTCC
component of cell walls in plants. 5856 daily. This led to a significant decrease in bloat-
ing, vomiting, diarrhea, abdominal pain and discomfort,
and stool frequency.31
• Xylanase breaks down xylan, another complex
Addition of this probiotic strain to a broad range of
sugar found in plant cell walls. When undigested,
digestive enzymes may provide comprehensive protec-
xylan can impair nutrient absorption.29
tion against several types of gastrointestinal discomfort.
• Pectinase breaks down pectin, a naturally

occurring substance found in pears, apples, Summary
guavas, plums, oranges, and other fruits.
As we age, the levels of digestive enzymes in our
bodies decline. This triggers digestive problems, includ-
An optimal selection of enzymes should include: ing bloating, gas, and diarrhea, and prevents absorp-
tion of nutrients.
• The full range of traditional digestive enzymes, The recent shift toward eating more plant-based
and additional enzymes that target high-fiber foods can increase this problem, because the increased
and gas-producing plant foods. amount of difficult-to-digest plant fiber components
requires specialized enzymes.
Digestive enzymes can boost the body’s ability to
A Probiotic for Digestive Health
fully break down food and may prevent gastrointestinal
Even greater digestive health is possible with the distress and promote better overall health.
addition of a targeted probiotic. Addition of the probiotic Bacillus coagulans to a
Probiotics are microorganisms that, taken in ade- broad range of digestive enzymes may provide a high
quate amounts, have a health benefit. Like enzymes, level of protection against several gastrointestinal
they are vital to the digestion process. discomforts. •

If you have any questions on the scientific content 17. Di Stefano M, Veneto G, Malservisi S, et al. Lactose malabsorp-
of this article, please call a Life Extension® tion and intolerance and peak bone mass. Gastroenterology. 2002
Jun;122(7):1793-9.
Wellness Specialist at 1-866-864-3027.
18. Hodges JK, Cao S, Cladis DP, et al. Lactose Intolerance and Bone
Health: The Challenge of Ensuring Adequate Calcium Intake. Nutri-
ents. 2019 Mar 28;11(4):718.
References 19. Sanders SW, Tolman KG, Reitberg DP. Effect of a single dose of
lactase on symptoms and expired hydrogen after lactose challenge
1. Remond D, Shahar DR, Gille D, et al. Understanding the gastroin- in lactose-intolerant subjects. Clin Pharm. 1992 Jun;11(6):533-8.
testinal tract of the elderly to develop dietary solutions that prevent 20. Layer P, Keller J. Lipase supplementation therapy: standards, alter-
malnutrition. Oncotarget. 2015 Jun 10;6(16):13858-98. natives, and perspectives. Pancreas. 2003 Jan;26(1):1-7.
2. Di Stefano M, Veneto G, Malservisi S, et al. Lactose malabsorp- 21. Dominguez-Munoz JE, Iglesias-Garcia J, Iglesias-Rey M, et al. Effect
tion and intolerance in the elderly. Scand J Gastroenterol. 2001 of the administration schedule on the therapeutic efficacy of oral
Dec;36(12):1274-8. pancreatic enzyme supplements in patients with exocrine pancre-
3. Laugier R, Bernard JP, Berthezene P, et al. Changes in pancreatic atic insufficiency: a randomized, three-way crossover study. Aliment
exocrine secretion with age: pancreatic exocrine secretion does Pharmacol Ther. 2005 Apr 15;21(8):993-1000.
decrease in the elderly. Digestion. 1991;50(3-4):202-11. 22. Suarez F, Levitt MD, Adshead J, et al. Pancreatic supplements
4. Bures J, Cyrany J, Kohoutova D, et al. Small intestinal bacte- reduce symptomatic response of healthy subjects to a high fat meal.
rial overgrowth syndrome. World J Gastroenterol. 2010 Jun Dig Dis Sci. 1999 Jul;44(7):1317-21.
28;16(24):2978-90. 23. Pavan R, Jain S, Shraddha, et al. Properties and therapeutic appli-
5. Lin HC. Small intestinal bacterial overgrowth: a framework for under- cation of bromelain: a review. Biotechnol Res Int. 2012;2012:976203.
standing irritable bowel syndrome. JAMA. 2004 Aug 18;292(7):852-8. 24. Available at: https://nccih.nih.gov/health/bromelain. Accessed Janu-
6. Howell E, National Enzyme Company C. The status of food enzymes ary 9, 2019.
in digestion and metabolism. Chicago, Ill.: National Enzyme Co.; 1946. 25. Knill-Jones RP, Pearce H, Batten J, et al. Comparative trial of
7. Roxas M. The role of enzyme supplementation in digestive disorders. Nutrizym in chronic pancreatic insufficiency. Br Med J. 1970 Oct
Altern Med Rev. 2008 Dec;13(4):307-14. 3;4(5726):21-4.
8. Glade MJ, Kendra D, Kaminski MV, Jr. Improvement in protein utili- 26. Di Stefano M, Miceli E, Gotti S, et al. The effect of oral alpha-galac-
zation in nursing-home patients on tube feeding supplemented with tosidase on intestinal gas production and gas-related symptoms.
an enzyme product derived from Aspergillus niger and bromelain. Dig Dis Sci. 2007 Jan;52(1):78-83.
Nutrition. 2001 Apr;17(4):348-50. 27. Zhang S, Song J, Deng Z, et al. Effects of combined alpha-galac-
9. Karani S, Kataria MS, Barber AE. A double-blind clinical trial with a tosidase and xylanase supplementation on nutrient digestibility
digestive enzyme product. Br J Clin Pract. 1971 Aug;25(8):375-7. and growth performance in growing pigs. Arch Anim Nutr. 2017
10. Supplier Educational Articles. Enzymes 101. Data on File. 2020. Dec;71(6):441-54.
11. Supplier Educational Articles. Probiotics 101. Data on File. 2020. 28. Tuck CJ, Taylor KM, Gibson PR, et al. Increasing Symptoms in Irri-
12. Eun JS, Beauchemin KA. Effects of a proteolytic feed enzyme on table Bowel Symptoms With Ingestion of Galacto-Oligosaccharides
intake, digestion, ruminal fermentation, and milk production. J Dairy Are Mitigated by alpha-Galactosidase Treatment. Am J Gastroen-
Sci. 2005 Jun;88(6):2140-53. terol. 2018 Jan;113(1):124-34.
13. Lee MF, Krasinski SD. Human adult-onset lactase decline: an up- 29. Polizeli ML, Rizzatti AC, Monti R, et al. Xylanases from fungi: proper-
date. Nutr Rev. 1998 Jan;56(1 Pt 1):1-8. ties and industrial applications. Appl Microbiol Biotechnol. 2005
14. Available at: https://www.medicinenet.com/script/main/art. Jun;67(5):577-91.
asp?articlekey=6201. Accessed January 9, 2019. 30. Lactobacillus sporogenes. Altern Med Rev. 2002 Aug;7(4):340-2.
15. Newcomer AD, Hodgson SF, McGill DB, et al. Lactase deficiency: 31. Majeed M, Nagabhushanam K, Natarajan S, et al. Bacillus coagu-
prevalence in osteoporosis. Ann Intern Med. 1978 Aug;89(2):218-20. lans MTCC 5856 supplementation in the management of diarrhea
16. Birge SJ, Jr., Keutmann HT, Cuatrecasas P, et al. Osteoporosis, predominant Irritable Bowel Syndrome: a double blind randomized
intestinal lactase deficiency and low dietary calcium intake. N Engl J placebo controlled pilot clinical study. Nutr J. 2016 Feb 27;15:21.
Med. 1967 Feb 23;276(8):445-8.

Clinical trials demonstrate that
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OPTIMIZE
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INTESTINAL
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The body’s production of digestive enzymes decreases with age,

leading to diminished nutrient absorption and bloating, as well as
other intestinal discomforts—especially after eating a large meal.
Enhanced Super Digestive Enzymes and Probiotics

provides a broad range of enzymes required to help break
down proteins, fats, carbohydrates, and other food
nutrients—including enzymes that specifically target the cell
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Enhanced Super Digestive

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RESTORE
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COLLAGEN
PEPTIDES Reverse
Skin Aging
from the Inside
BY MICHAEL DOWNEY
As we age, our skin loses two natural compounds that

keep it smooth, moisturized, and youthful looking:
1. Collagen and
2. Hyaluronic acid.1,2
The loss of these skin components leads to wrinkles,

sagging, and dryness. 1,2
But there’s a way to prevent and even reverse these

changes. Scientists have clinically demonstrated that:
• Oral use of a collagen peptide improves skin
elasticity by an average of 7%3 and reduces the
volume of eye wrinkles by 20%.4
• Oral use of hyaluronic acid significantly increases

skin moisture in those with chronically dry, rough
skin after just 3-6 weeks.1
Researchers have now devised a way to deliver clinically

effective doses of these two nutrients together in a tasty,
fruit-flavored gummy. Working from the inside out, they
can rejuvenate the skin and return it to optimal health.

COLLAGEN PEPTIDES REVERSE SKIN AGING FROM THE INSIDE Collagen Fiber
Collagen Keeps Skin Youthful

The word collagen comes from the Greek kola, “glue.”
Essentially, collagen—the most abundant protein in
the human body—is the glue that holds the entire body
together.
It’s the main component of most connective tissues,
like tendons and muscle, and makes up 70% of the inner
layer of skin by weight.5,6
Collagen provides strength and resilience and is inte-
grated with elastin fibers, the protein that gives skin flex-
ibility and elasticity. Elastin allows the skin to return to its
original shape after it’s been stretched.7
But collagen production begins to decline around age
25. The cells that produce collagen fibers slow down,
and the remaining fibers can stiffen, break, and lose
proper shape over time. Elastin fibers also begin to fray
and lose elasticity.
It is no coincidence that visible skin aging occurs in Cross-section of human skin
many people around age 25, which is when collagen
production begins to drop.
Adults lose about 1% of their skin collagen each year.8 received 2.5 grams of oral collagen daily, one received
While this may not seem like a lot, after several decades, 5 grams daily, and a third received a placebo.3
we may have lost half the skin collagen we had at age After eight weeks, both groups taking the oral colla-
18.8,9 gen had an average 7% improvement in skin elasticity.
This decline accelerates faster in women after meno- Remarkably, those subjects retained higher elasticity
pause. Factors such as smoking, high blood sugar, and than the placebo group even four weeks after the last
sun exposure also decrease collagen levels.10-14 dose. The improvement in skin elasticity was found to
Reduced collagen production has a devastating effect be greater in women over age 49.3
on the skin, resulting in thinning, sagging, and wrinkles.8,9 Next, researchers tested collagen on skin wrinkles.
To solve this problem, scientists developed collagen In a double-blind, placebo-controlled trial, they gave
peptides that provide the building blocks for collagen. oral collagen peptides to 114 women, aged 45 to 65, in
Taken orally, they stimulate the production of new daily doses of 2.5 grams.4
collagen and elastin in the skin. This leads to increased
suppleness and elasticity and reduces wrinkles.4
Results from Human Study
After four weeks, the volume of eye wrinkles for the
Oral Collagen Research
collagen group had decreased by 7.2%, compared with
In animal studies, scientists showed that hydrolyzed placebo recipients. After the full eight-week trial, those
(or partially broken-down) collagen peptides boosted taking oral collagen peptides showed a stunning 20.1%
the creation and activity of collagen.15 This produces reduction in the size of eye wrinkles.4
stronger, more supple skin. In the same trial, scientists studied how collagen
Collagen peptides also decreased the activity of a peptides affected the synthesis of the dermal matrix,
“protein-melting” enzyme (matrix metalloproteinase 2) the structural framework responsible for skin renewal
that degrades collagen and hastens skin aging.15 and vitality. They did so by measuring structural proteins
Human trials have now demonstrated that an oral in the matrix. The more proteins, the healthier and more
collagen peptide is clinically effective in improving skin youthful the skin appears.4
appearance.3,4 The study found that subjects taking collagen had a
Scientists evaluated the effectiveness of collagen 65% increase in essential type-I pro-collagen and an
peptides on skin elasticity. One group of volunteers 18% increase in elastin fibers.4

COLLAGEN PEPTIDES REVERSE SKIN AGING FROM THE INSIDE
Hyaluronic Acid Oral Hyaluronic Acid Rehydrates Skin

Moisturizes Skin Scientists conducted an in-depth analysis of several
Hyaluronic acid is equally critical for maintaining and previous studies of hyaluronic acid. In most, volunteers
restoring youthful-looking skin. had been diagnosed with “chronically rough and dry
It’s a carbohydrate present in most body tissues. skin,” which was not substantially improved by mois-
More than 50% of it is found in the skin, where it helps turizers or other treatments.1
hold in moisture.1,16 In fact, hyaluronic acid can hold up But hyaluronic acid made a radical difference.
to 1,000 times its weight in water.17 Compared to volunteers who received a placebo, those
Hyaluronic acid is an essential part of the extracel- taking oral hyaluronic acid had a significant increase
lular matrix, a network that provides structural integrity in skin moisture after just three to six weeks. And the
and cohesion to skin.18 It supports skin hydration,19 stim- moisturizing effects continued for a full two weeks after
ulates synthesis of collagen and elastin,20-22 promotes they stopped taking it.1
tissue repair,23-26 and combats the effects of ultraviolet Hyaluronic acid also reduced itching that comes
radiation.26 with dry skin.1
In other words, the skin needs hyaluronic acid to
maintain a healthy and youthful appearance.
But the body produces less of it as we age. This
problem is worsened by environmental stress, particu- WHAT YOU NEED TO KNOW
larly chronic sun exposure.27-30 The result is wrinkling,
dryness, and sagging.
In a dramatic finding, however, scientists have dem- Get Healthier,
onstrated that oral hyaluronic acid can slow—and Younger-Looking Skin
even reverse—these effects.
Q Collagen and hyaluronic acid are two
nutrients vital to the health and youthful
appearance of our skin. The body pro-
duces less of them as we age, causing
wrinkling, sagging, and dryness.
Q Taking oral collagen peptides spurs the

synthesis of new collagen, improving
skin elasticity, boosting essential struc-
tural proteins, and reducing the size of
eye wrinkles by as much as 20%.
Q Hyaluronic acid taken orally has been

shown to reverse the loss of moisture
in aging skin, effectively treating dry,
itchy skin and helping to restore a more
youthful appearance.
Q Taking these two nutrients together at

Collagen peptides Hyaluronic acid clinically effective doses can lead to
healthier, smoother, and younger-looking
skin.

Summary
Collagen and hyaluronic acid keep our skin smooth,
supple, moisturized and youthful looking. But, as we
age, we lose both these nutrients.
Taking oral collagen peptides boosts the synthesis
of new collagen in the skin. That improves skin struc-
ture and elasticity, reduces eye wrinkle depth up to 20%,
and increases levels of proteins that provide strength
and resilience to the dermal matrix.
Oral hyaluronic acid also protects and nourishes
skin by boosting moisture content. That can help
treat dry, itchy skin, and make it healthier and younger
looking.
Both of these nutrients can now be taken together in
clinically effective doses, quickly providing noticeable
improvements in the appearance of aging skin. •
If you have any questions on the scientific content

of this article, please call a Life Extension®
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References
1. Kawada C, Yoshida T, Yoshida H, et al. Ingested hyaluronan moistur-
izes dry skin. Nutr J. 2014 Jul 11;13:70.
2. Rittie L, Fisher GJ. Natural and sun-induced aging of human skin.
Cold Spring Harb Perspect Med. 2015 Jan 5;5(1):a015370.
3. Proksch E, Segger D, Degwert J, et al. Oral supplementation of
In fact, the scientists concluded that skin dryness is specific collagen peptides has beneficial effects on human skin
caused by a decrease in hyaluronic acid due to aging, physiology: a double-blind, placebo-controlled study. Skin Pharma-
col Physiol. 2014;27(1):47-55.
sun exposure, smoking, and other factors. Their study 4. Proksch E, Schunck M, Zague V, et al. Oral intake of specific bioac-
found that hyaluronic acid safely and effectively mois- tive collagen peptides reduces skin wrinkles and increases dermal
matrix synthesis. Skin Pharmacol Physiol. 2014;27(3):113-9.
turizes the skin and improves its health.1 5. Available at: https://www.ncbi.nlm.nih.gov/books/NBK507709/. Ac-
You can now orally replenish the skin’s diminishing cessed January 20, 2020.
supplies of both collagen and hyaluronic acid. These 6. Available at: https://emedicine.medscape.com/article/1294744-
overview#showall. Accessed January 20, 2020.
two nutrients have been shown to: 7. Available at: https://www.ncbi.nlm.nih.gov/books/NBK21582/. Ac-
cessed January 24, 2020.
8. Ganceviciene R, Liakou AI, Theodoridis A, et al. Skin anti-aging
• Increase skin moisture, strategies. Dermatoendocrinol. 2012 Jul 1;4(3):308-19.
9. Available at: https://www.scientificamerican.com/article/why-does-
skin-wrinkle-wit/. Accessed January 18, 2019.
• Improve elasticity, 10. Gautieri A, Passini FS, Silvan U, et al. Advanced glycation end-prod-
ucts: Mechanics of aged collagen from molecule to tissue. Matrix
Biol. 2017 May;59:95-108.
• Decrease wrinkle depth, 11. Uitto J. The role of elastin and collagen in cutaneous aging: intrinsic
aging versus photoexposure. J Drugs Dermatol. 2008 Feb;7(2
Suppl):s12-6.
• Boost levels of the skin’s structural proteins, and 12. Danby FW. Nutrition and aging skin: sugar and glycation. Clin Der-
matol. 2010 Jul-Aug;28(4):409-11.
13. Knuutinen A, Kokkonen N, Risteli J, et al. Smoking affects collagen
• Provide more youthful-looking skin. synthesis and extracellular matrix turnover in human skin. Br J Der-
matol. 2002 Apr;146(4):588-94.

14. Bosch R, Philips N, Suarez-Perez JA, et al. Mechanisms of Photo- 23. Jiang D, Liang J, Noble PW. Hyaluronan in tissue injury and repair.
aging and Cutaneous Photocarcinogenesis, and Photoprotective Annu Rev Cell Dev Biol. 2007;23:435-61.
Strategies with Phytochemicals. Antioxidants (Basel). 2015 Mar 24. Noble PW. Hyaluronan and its catabolic products in tissue injury and
26;4(2):248-68. repair. Matrix Biol. 2002 Jan;21(1):25-9.
15. Zague V, de Freitas V, da Costa Rosa M, et al. Collagen hydrolysate 25. Teriete P, Banerji S, Noble M, et al. Structure of the regulatory
intake increases skin collagen expression and suppresses matrix hyaluronan binding domain in the inflammatory leukocyte homing
metalloproteinase 2 activity. J Med Food. 2011 Jun;14(6):618-24. receptor CD44. Mol Cell. 2004 Feb 27;13(4):483-96.
16. Laurent UB, Dahl LB, Reed RK. Catabolism of hyaluronan in rabbit 26. Wang Y, Lauer ME, Anand S, et al. Hyaluronan synthase 2 protects
skin takes place locally, in lymph nodes and liver. Exp Physiol. 1991 skin fibroblasts against apoptosis induced by environmental stress.
Sep;76(5):695-703. J Biol Chem. 2014 Nov 14;289(46):32253-65.
17. Mateo Orobia AJ, Saa J, Ollero Lorenzo A, et al. Combination of 27. Dai G, Freudenberger T, Zipper P, et al. Chronic ultraviolet B irradia-
hyaluronic acid, carmellose, and osmoprotectants for the treatment tion causes loss of hyaluronic acid from mouse dermis because of
of dry eye disease. Clin Ophthalmol. 2018;12:453-61. down-regulation of hyaluronic acid synthases. Am J Pathol. 2007
18. Nusgens BV. [Hyaluronic acid and extracellular matrix: a primitive Nov;171(5):1451-61.
molecule?]. Ann Dermatol Venereol. 2010 Apr;137 Suppl 1:S3-8. 28. Ghersetich I, Lotti T, Campanile G, et al. Hyaluronic acid in cutane-
19. Masson F. [Skin hydration and hyaluronic acid]. Ann Dermatol Vene- ous intrinsic aging. Int J Dermatol. 1994 Feb;33(2):119-22.
reol. 2010 Apr;137 Suppl 1:S23-5. 29. Matuoka K, Hasegawa N, Namba M, et al. A decrease in hyaluronic
20. Beasley KL, Weiss MA, Weiss RA. Hyaluronic acid fillers: a compre- acid synthesis by aging human fibroblasts leading to heparan sulfate
hensive review. Facial Plast Surg. 2009 May;25(2):86-94. enrichment and growth reduction. Aging (Milano). 1989 Sep;1(1):47-
21. McKee CM, Penno MB, Cowman M, et al. Hyaluronan (HA) 54.
fragments induce chemokine gene expression in alveolar mac- 30. Rock K, Grandoch M, Majora M, et al. Collagen fragments inhibit
rophages. The role of HA size and CD44. J Clin Invest. 1996 Nov hyaluronan synthesis in skin fibroblasts in response to ultraviolet B
15;98(10):2403-13. (UVB): new insights into mechanisms of matrix remodeling. J Biol
22. Bukhari SNA, Roswandi NL, Waqas M, et al. Hyaluronic acid, a Chem. 2011 May 20;286(20):18268-76.
promising skin rejuvenating biomedicine: A review of recent updates
and pre-clinical and clinical investigations on cosmetic and nutricos-
metic effects. Int J Biol Macromol. 2018 Dec;120(Pt B):1682-95.
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RESEARCH UPDATE
Lactoferrin Promotes
Bone Growth and Strength
BY RICHARD RYAN
Osteoporosis plagues
millions of older adults,
weakening bones and
leading to fractures.
Our bones are constantly remod-

eled by removing old bone and
replacing it with new bone. It’s how
bones stay strong and youthful.
But as we age, the creation of
new bone doesn’t always keep up
with the destruction of old bone.
That’s osteoporosis, and it
causes bones to become brittle,
weak, and prone to fractures that
can be fatal.1
It’s alarmingly common, striking
30% of women aged 50 or older and
more than 77% of women over 80.
In men, about 16% of those 50 or
above have osteoporosis, and more
than 46% of those over 80 have it.2
Many people are careful to
ensure they get enough of the build-
ing blocks of bone, including cal-
cium, vitamins D3 and K, and other
essential bone nutrients.3-8
However, building new bones
is a complex operation. Research
shows that a protein called lactofer-
rin gives bones the instructions they
need to both reduce bone loss and
increase the building of new bone.
The results can be dramatic. In
one study, a lactoferrin combination
product increased markers of bone-
forming activity by 24% more than
a placebo.9

RESEARCH UPDATE
Lactoferrin and Osteoporosis These signaling molecules In one study, researchers gave
increase the activity of cells called healthy, postmenopausal women
To create and maintain strong osteoclasts that absorb bone and either a placebo or 125 mg/day of
bones, we need certain nutrients decrease the activity of bone-form- lactoferrin coupled with an enzyme
as building blocks and cofactors (or ing cells called osteoblasts. The from milk called ribonuclease.9
“helper molecules”). result: Our bones become weaker, Both groups also received 100%
Calcium and vitamin D3 are the more porous, and prone to fractures. of the recommended daily allowance
best known. We also need sufficient But lactoferrin, a protein found of calcium.9
vitamin K (which turns on bone- in milk,11 has the power to activate After 180 days, women who took
building proteins) and the minerals bone-building signals that normally the lactoferrin-ribonuclease combi-
magnesium, boron, zinc, manga- shut down or weaken with age.12-18 nation had a decrease in a marker of
nese, and silicon.3-8 These vitamins When it comes to bone strength, bone-resorption osteoclast activity
and minerals provide the raw mate- one lactoferrin combination product by 15.6% compared with placebo
rial for healthy bones. was shown to counter the kinds of recipients, and an increase in mark-
But rebuilding weak bones signals that result in weakened bone, ers of bone-forming osteoblast activ-
caused by osteoporosis requires meaning lactoferrin could reduce ity by 7%-33%.9
something more. bone breakdown and increase Another study examined the
As we age, senescent cells new bone formation.9 effect of direct application of lac-
accumulate in our bones and toferrin alone in a rare but trou-
throughout our bodies. These are bling side effect of bisphosphonate
Results of Human Studies drugs used to build bone. This
old, unhealthy cells that can no lon-
ger divide and refuse to die off to bone-destroying side effect is called
make way for new, healthy cells. Human studies show how effec- osteonecrosis of the jaw.19
Worst of all, they secrete harm- tively lactoferrin can restore a proper, In this condition, bone in the
ful signaling molecules that actively healthy balance between bone lower jaw dies for unknown reasons,
weaken bones and hasten body resorption and new bone production. often poking through the gums and
aging.10 skin and allowing infection to set
in.20 Generally, dead bone has to be
removed surgically. Then a gauze
dressing is applied while the wound
heals.19
In this study, researchers satu-
rated the gauze dressing with lac-
toferrin and applied it after surgery,
exposing the healing bone directly to
lactoferrin.19
The surgical wounds healed in just
one to two weeks, compared with
two to three months under usual
treatment,19 a dramatic demonstra-
tion of the powers of lactoferrin to
drive healthy, new bone formation.
Animal studies also show that
lactoferrin promotes stronger, frac-
ture-resistant bones with increased
mineral density.18,21-24 These bones
have a more youthful structure, with
more of the tiny “I-beams” called
trabeculae that internally support
bone.18,22

RESEARCH UPDATE
How Lactoferrin
Strengthens Bones
Lactoferrin is a natural component

of milk, nature’s baby food. Many of
its properties promote cell growth
and differentiation (when stem cells
mature and develop into special-
ized cell types), which is required in
infancy and early childhood.
Lactoferrin can promote bone
health by:
• Preserving bone mass and

improving bone micro-
architecture,22
• Preventing the stress-induced

death of bone-building osteo-
blast cells,25-27
• Promoting the differentiation

of stem cells into bone-build-
ing osteoblast cells, while Summary
suppressing their differen-
tiation into bone-resorption
Osteoporosis plagues millions of If you have any questions on the
osteoclasts,15,25-29 scientific content of this article, please
older adults, weakening bones and
leading to fractures. call a Life Extension® Wellness
• Enhancing the growth of new
It’s vital to get enough of the nutri- Specialist at 1-866-864-3027.
cartilage cells in-vitro, poten-
tially benefiting joint health,26 ents the body uses to make strong
bones, including calcium, vitamins
• Activating youthful signaling
References
D3 and K, as well as essential bone
that stimulates growth of new minerals.
1. Available at: https://www.bones.nih.gov/
bone, suppresses the death But we can also correct the health-info/bone/osteoporosis/overview.
of bone cells, and promotes signals that drive osteoporosis. Accessed January 24, 2020.
2. Wright NC, Saag KG, Dawson-Hughes B,
differentiation leading to new Lactoferrin, a protein derived from et al. The impact of the new National Bone
bone,13,18,21,24,27 and milk, may do just that: It can reduce Health Alliance (NBHA) diagnostic criteria on
the prevalence of osteoporosis in the USA.
signals that promote bone loss, and Osteoporos Int. 2017 Apr;28(4):1225-32.
• Activating transforming
boost signals that promote bone 3. Boyacioglu O, Orenay-Boyacioglu S,
growth factor-beta (TGF- Yildirim H, et al. Boron intake, osteocalcin
growth.
beta), a signaling protein most polymorphism and serum level in post-
As research into this important menopausal osteoporosis. J Trace Elem
active in youth, which pro- Med Biol. 2018 Jul;48:52-6.
compound continues, lactoferrin
motes new bone formation.12 4. Claro da Silva T, Hiller C, Gai Z, et al.
may well take a prominent place Vitamin D3 transactivates the zinc and
Researchers are continuing to among the more familiar bone-build- manganese transporter SLC30A10 via the
Vitamin D receptor. J Steroid Biochem Mol
investigate additional benefits of lac- ing nutrients. Biol. 2016 Oct;163:77-87.
toferrin in promoting youthful cellular In case you do not know, the 5. Gurban CV, Mederle O. The OPG/RANKL
system and zinc ions are promoters of
activity. But it’s already shown great primary benefit of lactoferrin is to bone remodeling by osteoblast prolif-
promise in fighting against the bone enhance healthy immune responses. eration in postmenopausal osteoporosis.
Rom J Morphol Embryol. 2011;52(3
loss that has too often been consid- The bone-building effect is an Suppl):1113-9.
ered an inevitable part of aging. added bonus. •

RESEARCH UPDATE
6. Huang ZB, Wan SL, Lu YJ, et al. Does 14. Li Q, Zhao J, Hu W, et al. Effects of Recom- 22. Guo HY, Jiang L, Ibrahim SA, et al. Orally
vitamin K2 play a role in the prevention and binant Human Lactoferrin on Osteoblast administered lactoferrin preserves bone
treatment of osteoporosis for postmeno- Growth and Bone Status in Piglets. Anim mass and microarchitecture in ovariecto-
pausal women: a meta-analysis of random- Biotechnol. 2018 Apr 3;29(2):90-9. mized rats. J Nutr. 2009 May;139(5):958-64.
ized controlled trials. Osteoporos Int. 2015 15. Cornish J, Naot D. Lactoferrin as an ef- 23. Amini AA, Nair LS. Lactoferrin: a biologi-
Mar;26(3):1175-86. fector molecule in the skeleton. Biometals. cally active molecule for bone regeneration.
7. Mederle OA, Balas M, Ioanoviciu SD, et al. 2010 Jun;23(3):425-30. Curr Med Chem. 2011;18(8):1220-9.
Correlations between bone turnover mark- 16. Chen XW, Li YH, Zhang MJ, et al. Lac- 24. Li W, Zhu S, Hu J. Bone Regeneration Is
ers, serum magnesium and bone mass toferrin ameliorates aging-suppressed Promoted by Orally Administered Bovine
density in postmenopausal osteoporosis. osteogenesis via IGF1 signaling. J Mol Lactoferrin in a Rabbit Tibial Distraction
Clin Interv Aging. 2018;13:1383-9. Endocrinol. 2019 Jul;63(1):63-75. Osteogenesis Model. Clin Orthop Relat
8. Price CT, Koval KJ, Langford JR. Silicon: a 17. Malet A, Bournaud E, Lan A, et al. Bovine Res. 2015 Jul;473(7):2383-93.
review of its potential role in the prevention lactoferrin improves bone status of ovariec- 25. Cornish J. Lactoferrin promotes bone
and treatment of postmenopausal osteopo- tomized mice via immune function modula- growth. Biometals. 2004 Jun;17(3):331-5.
rosis. Int J Endocrinol. 2013;2013:316783. tion. Bone. 2011 May 1;48(5):1028-35. 26. Cornish J, Callon KE, Naot D, et al. Lac-
9. Bharadwaj S, Naidu AG, Betageri GV, et 18. Hou JM, Xue Y, Lin QM. Bovine lactoferrin toferrin is a potent regulator of bone cell
al. Milk ribonuclease-enriched lactoferrin improves bone mass and microstructure activity and increases bone formation in
induces positive effects on bone turnover in ovariectomized rats via OPG/RANKL/ vivo. Endocrinology. 2004 Sep;145(9):
markers in postmenopausal women. Os- RANK pathway. Acta Pharmacol Sin. 2012 4366-74.
teoporos Int. 2009 Sep;20(9):1603-11. Oct;33(10):1277-84. 27. Naot D, Grey A, Reid IR, et al. Lactoferrin-
10. Farr JN, Fraser DG, Wang H, et al. Iden- 19. Calvani F, Cutone A, Lepanto MS, et al. -a novel bone growth factor. Clin Med Res.
tification of Senescent Cells in the Bone Efficacy of bovine lactoferrin in the post- 2005 May;3(2):93-101.
Microenvironment. J Bone Miner Res. 2016 surgical treatment of patients suffering from 28. Montesi M, Panseri S, Iafisco M, et al.
Nov;31(11):1920-9. bisphosphonate-related osteonecrosis of Coupling Hydroxyapatite Nanocrystals with
11. Available at: https://www.sciencedirect. the jaws: an open-label study. Biometals. Lactoferrin as a Promising Strategy to Fine
com/topics/food-science/lactoferrin. Ac- 2018 Jun;31(3):445-55. Regulate Bone Homeostasis. PLoS One.
cessed January 30, 2020. 20. Payne KF, Goodson AM, Tahim AS, et 2015;10(7):e0132633.
12. Li Y, Wang J, Ren F, et al. Lactoferrin al. Why worry about bisphosphonate- 29. Cornish J, Palmano K, Callon KE, et al.
Promotes Osteogenesis through TGF-beta related osteonecrosis of the jaw? A guide Lactoferrin and bone; structure-activity
Receptor II Binding in Osteoblasts and to diagnosis, initial management, and relationships. Biochem Cell Biol. 2006
Activation of Canonical TGF-beta Signaling referral of patients. Br J Gen Pract. 2017 Jun;84(3):297-302.
in MC3T3-E1 Cells and C57BL/6J Mice. J Jul;67(660):330-1.
Nutr. 2018 Aug 1;148(8):1285-92. 21. Fan F, Shi P, Liu M, et al. Lactoferrin
13. Liu M, Fan F, Shi P, et al. Lactoferrin pro- preserves bone homeostasis by regulat-
motes MC3T3-E1 osteoblast cells prolifera- ing the RANKL/RANK/OPG pathway of
tion via MAPK signaling pathways. Int J osteoimmunology. Food Funct. 2018 May
Biol Macromol. 2018 Feb;107(Pt A):137-43. 23;9(5):2653-60.

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References
in your multi-nutrient formulas, you may not need 1. Open Orthop J. 2012;6:143-9.
additional boron. 2. Altern Med Rev. 2004 Dec;9(4):434-7.
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HEALTHY EATING
Shuk: From Market to Table,

the Heart of Israeli Home Cooking
BY EINAT ADMONY AND JANNA GUR
True Israeli home cooking doesn’t start

in the home. It starts in the shuk—the local
open-air market.
Dotted throughout Israel’s towns and
cities, shuks are lively mazes of stalls
that sell the freshest seasonal ingredients,
including fruit and vegetables, meats and
fish, nuts and spices, fresh herbs, cheeses
and yogurts, and everything in between.
The shuk is a feast for your senses as
much as it is for your appetite.
What makes Israeli food unique is its
fusion of Middle Eastern cuisine, combined
with the recipes of immigrants from many
countries.
Celebrating this melting pot of culture
and cuisine, Shuk: From Market to Table,
the Heart of Israeli Home Cooking contains
140 Israeli dishes that have roots in Persia,
Yemen, Libya, the Balkans, and more—and
includes favorites such as hummus, tab-
boulehs, shakshukas, chopped salad, and
couscous.
All of the recipes are based on fresh
ingredients that could be found in any
local shuk.
In this issue, Life Extension® Magazine
features four flavorful recipes that bring
the heart of the shuk into your own kitchen.
—LAURIE MATHENA

HEALTHY EATING
Cauliflower Tabbouleh with Fry the pumpkin and sunflower Add the lemon juice, oil, salt, and
Crunchy Seeds seeds in the same manner; transfer some energetic twists of pepper and
them to the paper towels as well. toss to combine. Taste and adjust
the seasoning, adding more salt,
SERVES 4 TO 6 Pulse the cauliflower florets in a food pepper, lemon juice, and/or oil as
processor until they are broken down needed to make the salad yummy
3 tablespoons sesame seeds to couscous-size crumbles. Transfer and bright.
Olive oil, for frying the cauliflower to a large bowl. If
3 tablespoons pine nuts there are any large pieces left, return Sprinkle the pomegranate seeds on
them to the food processor and top (if using) and serve promptly.
3 tablespoons hulled pumpkin pulse until they reach the desired
seeds (pepitas)
size, then add them to the bowl. Add
3 tablespoons hulled sunflower the sesame seeds, pine nuts, pump-
seeds kin seeds, sunflower seeds, nigella
1 medium cauliflower, cored and seeds, cilantro, mint, and parsley to
cut into large florets the bowl with the cauliflower.
1 tablespoon nigella seeds
2 tablespoons finely chopped
fresh cilantro
fresh mint
fresh parsley
3 tablespoons fresh lemon juice,
plus more as needed
3 tablespoons extra-virgin olive oil,
plus more as needed
1 teaspoon kosher salt, plus more
as needed
Freshly ground black pepper
1/3 cup (60 g) fresh pomegranate
seeds, for garnish (optional)
Toast the sesame seeds in a dry

medium skillet over medium heat,
stirring continuously, for a couple of
minutes, until golden. Transfer to a
small plate and let cool.
Line a plate with paper towels. Heat

a thin layer of oil in the same skillet
over medium-low heat. Add the pine
nuts and sauté, shaking the skillet
frequently, until they just turn light
golden, 3 to 4 minutes. Use a slot-
ted spoon to transfer them to the
paper towels.

HEALTHY EATING
Masabacha
Whole Chickpeas in Warm,

Spicy Tahini Sauce
SERVES 6 TO 8
2 cups (370 g) dried chickpeas

½ teaspoon baking soda
¼ cup (60 ml) boiling water
¾ cup (180 ml) best-quality
raw tahini
1 teaspoon kosher salt
DRESSING
¼ cup (60 ml) extra-virgin olive oil

3 medium garlic cloves, minced
or grated
½ jalapeño chili, cored, seeded, and
finely chopped
¼ cup (60 ml) fresh lemon juice
1 teaspoon ground cumin
Kosher salt and freshly ground
black pepper
FOR GARNISH
Chopped fresh parsley

Extra-virgin olive oil
Pick through the dried chickpeas ¼ teaspoon baking soda. Bring to a Meanwhile, make the dressing:
and discard any little stones (yes, boil over high heat, reduce the heat Whisk together the oil, garlic, jalapeño,
that can happen) or peas that look to medium, and cook at a lively sim- lemon juice, and cumin in a small
very irregular in color or in shape. mer, uncovered, for 1 to 1½ hours. bowl and season with salt and pepper.
Rinse the chickpeas thoroughly Use a slotted spoon to skim off
under cold water. Transfer the chick- Ladle the warm chickpea mixture
any skins that float to the surface.
peas to a large bowl and add cold into a large serving bowl or individual
The chickpeas are ready when they
water to cover them by 3 to 4 inches plates and pour the dressing over
are completely soft, slightly broken
(7.5 to 10 cm). Add ¼ teaspoon of the top. Garnish with chopped pars-
down, and can easily be smooshed
the baking soda. Soak for at least 12 ley and a generous drizzle of oil and
with your fingers. Drain the chick-
and up to 24 hours. serve at once.
peas thoroughly and return them to
the pot. TIP
Drain and rinse the soaked chick-
Masabacha is delicious only when it is
peas under cold water until the water Add the boiling water, tahini, and salt. really warm, so many hummus makers
runs clear. Transfer the chickpeas Cook over medium heat for a couple keep the cooked chickpeas and tahini over
to a large pot, pour in 3 quarts (3 L) of minutes, just until the chickpeas a double boiler until serving and add the
cold water, and add the remaining are warmed through. dressing at the last moment.

HEALTHY EATING
Green Shakshuka with Chard,

Kale, Spinach, and Feta
SERVES 4 TO 6
¼ cup (60 ml) extra-virgin olive oil

2 leeks, white parts chopped, and
green tops very thinly sliced
3 medium garlic cloves, thinly sliced
1 small jalapeño chili, cored, seeded,
and thinly sliced
5 or 6 Swiss chard leaves, leaves
coarsely chopped, stems thinly
sliced
1 small bunch Tuscan kale
(also called lacinato or dino-
saur), stemmed, leaves coarsely
chopped
stirring often, until wilted and soft, 3 Spicy Fish in Cherry Tomato
3 cups baby spinach or trimmed to 4 minutes. Add the caraway and and Harissa Sauce
and coarsely chopped regular
cumin, and season very lightly with
spinach
salt (the feta is quite salty) and sev- SERVES 6
1 teaspoon ground caraway eral twists of pepper.
1/3 cup (80 ml) vegetable oil
1 teaspoon ground cumin
Add the stock and the lemon juice
Kosher salt and freshly ground and cook for 5 to 7 minutes, then 10 garlic cloves, smashed
black pepper reduce the heat to low and cook ¼ cup tomato paste
½ cup (120 ml) homemade or for another few minutes, until the 1 jalapeño chili, cored, seeded,
low-sodium store-bought chicken greens meld into a thick, dark green, and thinly sliced
stock or vegetable stock or water stewy sauce. Taste and adjust the
1 tablespoon harissa, store-bought
1 tablespoon fresh lemon juice seasoning.
or homemade
6 to 8 large eggs Use a large spoon to create little 3 tablespoons sweet paprika
wells in the greens’ mixture. Carefully
1 teaspoon ground caraway
TO SERVE break 1 egg into a cup or ramekin,
then slip it into one of the wells; 1½ teaspoons ground cumin
5 ounces (140 g) feta cheese,
coarsely crumbled repeat with the remaining eggs. 2 pints (910 g) cherry tomatoes
(Cracking the egg into a cup first Kosher salt
Extra-virgin olive oil
lets you inspect it for any runaway
Crusty bread or challah bits of shell.) Cover and simmer until ½ cup (120 ml) water
the egg whites are set but the yolks 1 large bunch fresh cilantro
are still a little runny, about 7 minutes. Freshly ground black pepper
Heat the oil in a large skillet over
Remove the skillet from the heat.
medium heat. Add the leeks, garlic, 6 (7 to 9 ounce/200 to 255 g)
jalapeño, and chard stems and sauté Sprinkle the shakshuka with the fillets flaky white-fleshed fish
until softened and lightly caramelized, feta, drizzle with oil, and sprinkle (grouper, bass, snapper, and
10 to 12 minutes (take care not to generously with za’atar. Serve the halibut are all nice), skin-on, if
brown the garlic). Add the kale, spin- shakshuka directly from the skillet, possible
ach, and the chard leaves and cook, with plenty of crusty bread or challah. Challah or couscous, for serving

HEALTHY EATING
Pour the vegetable oil into a rela- Remove about 3 tablespoons is cooked through, 7 to 8 minutes.
tively deep, large skillet. Immediately of whole leaves from the cilantro Thicker fillets, like halibut, will need
add the smashed garlic cloves and bunch and reserve them for garnish. 2 to 3 minutes more. To check the
cook over very low heat just until Tear up the rest of the bunch and fish for doneness, make a small inci-
fragrant, 3 to 4 minutes. Watch the toss into the pan. Give it a minute sion in the thickest part of the fish
pan closely to make sure the gar- to blend with the sauce, then taste and make sure the flesh is opaque
lic doesn’t brown, or it will become and adjust the seasoning with salt, and flaky.
bitter. pepper, and the remaining jalapeño
Serve straight out of the pan, gar-
and 1½ teaspoons harissa if you
Increase the heat to medium-high, want more heat. Bear in mind that nished with the reserved whole
add the tomato paste, half the jala- cilantro leaves, with a lot of bread
once you add the fish, you won’t be
peño, 1½ teaspoons of the harissa, alongside or with couscous.
able to stir the sauce and play with
and all the paprika, caraway, and the seasonings—make sure the fla-
cumin and stir for a minute or two, vor and level of spiciness are to your
until fragrant. Add 1½ pints (680 g) liking. If you have any questions on the
of the cherry tomatoes (reserve the scientific content of this article, please
rest for later) and season with salt. Add the fish fillets, skin-side up, call a Life Extension® Wellness
Reduce the heat to medium and tucking them gently into the sauce. Specialist at 1-866-864-3027.
cook, stirring occasionally, until the Sprinkle the remaining ½ pint (225 g)
Excerpted from Shuk by
tomatoes start to break down, 7 to cherry tomatoes on top of the fish.
Einat Admony and Janna Gur
8 minutes. Pour in the water, bring to (Artisan Books). Copyright © 2019.
Bring to a simmer over medium heat.
a simmer, cover, and cook over low Photographs by Quentin Bacon.
Reduce the heat to low, cover, and
heat for about 30 minutes, or until
simmer, without stirring, until the fish
thick and saucy. To order a copy of Shuk,
call 1-800-544-4440 or visit
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AUTHOR INTERVIEW
The Switch
Calorie restriction [is] now established
to be the most powerful intervention to
delay aging and increase longevity in
diverse species, from yeast to mammals.
Wouldn’t it be great if losing

weight, easing chronic conditions,
and staying healthier, longer was as
simple as flipping a switch?
As James Clement reveals in his
new book, The Switch, it is.
Our bodies contain a metabolic
switch that, when activated, initiates
fat burning, removes damaged and
dysfunctional cells, and dampens
inflammation.
As a result, activating this switch
© PHOTO BY DAVID STEELE
can help promote weight loss,

reduce the risk of major diseases,
and slow down the aging process.
In this interview with Life
Extension®, Clement shares a few
of the specific details from his highly
acclaimed book on how to activate
your body’s anti-aging switch.
JAMES CLEMENT, J.D., LL.M —Laurie Mathena

AUTHOR INTERVIEW
LE: What would you say is the secret growths, and preventing metabolic LE: What is the connection between
to living a long, healthy life? disorders such as obesity and diabe- this switch and lifespan?
tes—which means that by boosting
Clement: In your own grasp of the your body’s autophagy, you dampen Clement: Virtually all health-extend-
“secrets” of living a good, long life, inflammation, slow down the aging ing and lifespan-extending inter-
what comes to mind? My bet is that process, reduce your risk of devel- ventions that we know of have their
you think of blood sugar balance, oping certain diseases, and optimize effects because of their actions to
healthy weight, and physical fitness. your biological function. suppress this switch.
Those are all appropriate goals Much of [my] book [details] how
to achieve, but they miss the main LE: How can autophagy be turned these various interventions, some of
point—they are merely a means of on in the body? which you may have heard of and
sparking a prominent antiaging pro- others of which you haven’t, act on
cess: autophagy. Clement: Autophagy can be trig- this pathway and ultimately regulate
[Autophagy is] how the body gered when a certain complex, called this important switch, periodically
removes and recycles dangerous, mTOR, within cells is turned down. I turning on autophagy in the process.
damaged organelles and particles, refer to the mTOR complex as “the The information is meant to help
as well as pathogens, from inside Switch.” reverse this hastening of aging and
cells, thus aiding your immune sys- mTOR is the switch that nearly put us back onto a more natural
tem and greatly reducing your risk every cell (except blood cells) has, path of consumption and exercise
of developing cancer, heart disease, and it either activates your cell’s that keeps the Switch (mTOR and
chronic inflammation, osteoarthri- self-cleaning mode (autophagy), rid- autophagy) in balance and prevents
tis, and neurological disorders from ding the body of toxic materials and the age-related diseases that were
depression to dementia. fomenting cancers, as well as burn- rare centuries ago but are wide-
Autophagy makes us more physi- ing fat, or allows the body to produce spread now.
ologically efficient by getting rid of more proteins, store as much energy
defective parts, promoting healthy (glucose and fat) as possible, and LE: In your book, you talk about a
metabolism, stopping cancerous build more cells. few specific ways to change the
These anabolic processes, when direction of this metabolic switch:
taken to an extreme level, which our calorie restriction, intermittent fast-
modern lifestyle practices do, can ing, and very-low-carb diets.
trigger illness.
Think of this switch like a dimmer Clement: Researchers discovered
for your lights: turning it toward one nearly 80 years ago that both calo-
end to increase light and the other rie restriction and intermittent fast-
direction to decrease it. ing greatly extended the lives of
Although we evolved to have this test animals, often by reducing their
biological switch move back and vulnerability to cancer and heart
forth continuously between growth disease.
(mTOR) and repair (autophagy, and A ketogenic (very-low-carbo-
sometimes repair for prolonged hydrate) diet, widely used for the
periods), the lifestyles of mod- treatment of neurological diseases,
ern humans keep it turned toward showed somewhat similar antican-
growth constantly and seldom or cer and anti-heart-disease benefits,
never in the repair direction. although it has been investigated
And when it’s in the growth stage, much less than calorie restriction or
internal cell cleansing comes to a intermittent fasting.
halt and our ability to clear out the After three months of reading
biological debris—misfolded pro- through more than 500 scientific
teins, pathogens, and dysfunctional papers, it finally dawned on me that
organelles—falters. all of the papers I’d been reading

AUTHOR INTERVIEW
LE: Another way to encourage

autophagy is through calorie restric-
tion. Can you explain that in more
detail?
Clement: By definition, calorie

restriction involves the consumption
of fewer calories without malnutrition
or deprivation of essential nutrients.
Although the molecular mecha-
nisms that control the effects of cal-
orie restriction are still being studied
and debated, there is more wide-
spread acceptance of the hypothesis
that calorie restriction and lifespan
extension involve a dialing down of
insulin signaling and a dialing up of
autophagy.
about life-extending, disease-pre- When you give your body food, Calorie restriction [is] now estab-
venting genes, therapies, drugs, vita- your insulin level rises and your lished to be the most powerful inter-
mins/supplements, lifestyles, and glucagon level decreases. But the vention to delay aging and increase
so on had one thing in common: opposite happens when you don’t longevity in diverse species, from
they turned down the mTOR cellular eat: your insulin level goes down and yeast to mammals. It is also the most
mechanism and thereby turned up your glucagon level rises. potent and reproducible physiologi-
the autophagy process. When your glucagon level rises, it cal intervention to protect against
I spent another three months read- triggers autophagy. This is why tem- cancer specifically in mammals.
ing 600 more papers focused on porarily denying your body nutrients
mTOR and autophagy and confirmed through the safe practice of intermit- LE: What happens in the body when
my suspicion. tent fasting is one of the best ways it’s deprived of an abundance of
to boost the integrity of your cells. calories?
LE: What is intermittent fasting, and Aside from maintaining your cells’
how does it trigger autophagy? youth, research has shown that inter- Clement: The effects of calorie
mittent fasting promotes greater restriction on growth hormone, and
Clement: Intermittent fasting (a form energy, increased fat burning, and in turn, levels of insulin and IGF-1,
of which is called time-restricted decreased risk of developing dis- are certainly important to keeping
eating) works because it activates eases such as diabetes and heart your “growth” switch (mTOR) turned
the hormone glucagon, which func- disease, all due to its ability to acti- down so that your self-cleaning pro-
tions opposite of insulin to keep your vate autophagy. cess (autophagy) is tuned up.
blood glucose levels balanced. With less growth hormone around,
Here’s a visual to really grasp this LE: How do you put intermittent fast- there’s increased autophagy to clean
concept. Picture a seesaw: when ing into practice? house. And what’s the relationship
one person goes up, the other goes between calorie restriction and
down. This analogy is frequently Clement: You can start with a autophagy?
used to explain the biological insu- very comfortable 12-hour fast just When you put mild stress on the
lin-glucagon relationship. In your by avoiding eating after 7 p.m. (No body in the form of calorie restric-
body, if the insulin level goes up, the midnight snacking!) Then you can tion, it turns up the autophagy dial.
glucagon level goes down and vice stretch it to 16 hours and eventually As that happens, there’s an increase
versa. forgo “break-fast” (breakfast) the in protein turnover and cellular repair.
next morning, so your first meal of In other words, your body is
the day is around 11 a.m. forced to renovate itself!

AUTHOR INTERVIEW
One of insulin’s jobs is to send You’ll want to dial up autophagy

amino acids from broken-down pro- for eight months of the year and
teins into lean tissues such as mus- dial it down during the other four
cle. But here’s the difference: protein months. It doesn’t really matter how
doesn’t supply glucose rapidly, as you break up those months (e.g., you
carbohydrate does. can do two months with autophagy
on and one month off, then repeat for
LE: How does this relate to autoph- a full calendar year).
agy? Remember, autophagy is an
action plan or tool for cellular self-
Clement: When you reduce your fortification, but it also demands a
protein intake, especially animal pro- balance as with so many other things
teins, you will lower your insulin levels in life: too much or not enough can
and in turn boost your glucagon level be harmful to the cell, and thus to
and activate autophagy. This explains you. •
why protein cycling, or reducing your
protein intake in cyclical fashion, has
an effect similar to that of fasting.
In addition to enhancing autoph- If you have any questions on
LE: How does protein restriction agy, protein cycling alongside calorie the scientific content of this article,
factor in? restriction and intermittent fasting will please call a Life Extension® Wellness
help reduce your risk of developing Specialist at 1-866-864-3027.
Clement: Another key dietary strat- the diseases I’ve covered: diabetes,
From THE SWITCH by James W.
egy that is often ignored is protein cancer, and heart disease.
Clement. Copyright © 2019 by James
restriction. That’s right: you don’t Remember, these are the diseases
W. Clement. Reprinted by permission
want to be eating too much protein. of civilization, also known as dis- of Gallery Books, an Imprint of
Although the practice of general eases of overconsumption. Simon & Schuster, Inc.
calorie restriction has benefits for Protein cycling could become your
body weight, it’s really the protein most powerful tool for making over To order a copy of The Switch,
restriction that creates the health your metabolism and increasing your call 1-800-544-4440 or visit
benefits. chances of living a long, disease-free www.LifeExtension.com
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consumption—without restricting LE: These sound like great ways to
calories—is among the most promis- keep the Switch turned off. Is this
ing interventions that have emerged something that should be practiced
to promote healthy aging in humans. all the time?
And it’s not going to feel as though
you’re “restricting” yourself, which Clement: As with most everything
is why it’s better to call it protein in life, you’ll want to strike a balance
cycling. between your Switch being on and
I cannot emphasize the following being off. The body needs periods of
enough: protein stimulates insulin rest from its internal cleansing mech-
release as much as carbohydrate anisms so you can more easily build
does! We often don’t think about that tissues, keep your weight in check
because we tend to relate insulin (not lose too much), and maintain
release with only sugar. your immune system.

Increase AMPK to
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Most people today consume too many excess
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This results in mTOR constantly running at

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Studies show that increasing AMPK activity

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Numerous published studies describe
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how concentrated extracts in Pycnogenol®
 bottle $
help protect against multiple factors
 bottles $ each
related to normal aging.
For full product descriptions and to order Pycnogenol®, Arterial Protect, or VenoFlow™,
*Pycnogenol® and Centellicum® are registered trademarks of Horphag Research.

Use of this product may be protected by one or more U.S. patents and other international patents.
+
Pycnogenol® is a registered trademark of Horphag Research, Ltd.
**CAUTION: Consult your healthcare provider before use of VenoFlow™ if taking medication (especially those affecting blood coagulation
or blood pressure), being treated for a medical condition (especially bleeding disorders), under the age of , pregnant, or lactating.
SUPERFOODS
Hemp Seeds
BY LAURIE MATHENA
Hemp seeds, with their mild, nutty

flavor, have been used in China for
more than 3,000 years, as both food
and medicine.
More recently, hemp seeds (also
called hemp hearts) have experi-
enced a resurgence in the West
because of their unique nutrient pro-
file, which boasts an abundance of
protein, healthy fats, and minerals.
A Top Source of
Plant-Based Protein
About 25% of the total calories in
hemp seeds are from protein. Just
two to three tablespoons of the
seeds provide about 11 grams of
protein.1
In addition, hemp seeds are con-
sidered a complete protein source,
meaning they contain all nine essen-
tial amino acids.
Reduces Heart Disease Risk
Hemp seed consumption can
help reduce the risk of heart dis-
ease. Animal studies have shown
that hemp seeds can lower blood
pressure,2 decrease cholesterol-
induced platelet aggregation,3 and
help the heart recover after a heart
attack.4
Improves Skin Health
Dietary hemp seed oil has been According to Life Extension®, References
1. Available at: https://nutritiondata.self.com/
shown to help improve clinical symp- the optimal ratio of omega-6 to
facts/custom/629104/2. Accessed January
toms in patients with atopic derma- omega-3 consumption is about 4 28, 2020.
titis.5 Researchers attributed these to 1. In fact, hemp seeds boast a 3 2. Eur J Nutr. 2014 Aug;53(5):1237-46.
3. Can J Physiol Pharmacol. 2008
improvements to the abundance of to 1 ratio. Apr;86(4):153-9.
polyunsaturated fatty acids found in You can enjoy hemp seeds sprin- 4. Am J Physiol Regul Integr Comp Physiol.
2007 Mar;292(3):R1198-203.
hemp seed oil, which include both kled on salads, in smoothies, or as 5. J Dermatolog Treat. 2005 Apr;16(2):87-94.
omega-3 and omega-6 fats. a topping on oatmeal.

eye
ULTIMATE
HYDRATION
Moisturize Your Aging Eyes
Brite Eyes III provides a well-established

Item # •  containers
lubricant in every drop, soothing eye
( mL each)
discomfort without irritation.
 box $.
N-acetylcarnosine is used as a stabilizing  boxes $ each
agent.
For full product description and to order Brite Eyes III, call --- or visit www.LifeExtension.com
PRODUCTS
ACTIVE LIFESTYLE & FITNESS 01527 Huperzine A
01529 Creatine Capsules 00020 Lecithin Granules
02318 Keto Brain and Body Boost 02101 Memory Protect
02020 Super Carnosine 00709 Migra-Eeze™
02023 Tart Cherry with CherryPURE® 01603 Neuro-Mag® Magnesium L-Threonate Caps
02146 Wellness Bar–Chocolate Brownie 02032 Neuro-Mag® Magnesium L-Threonate Powder
02147 Wellness Bar–Cookie Dough 00888 Optimized Ashwagandha Extract
02246 Wellness Code® Advanced Whey Protein Isolate Vanilla 01676 PS (Phosphatidylserine) Caps
02221 Wellness Code® Muscle Strength & Restore Formula 01327 Vinpocetine
02127 Wellness Code® Plant Protein Complete & CHOLESTEROL MANAGEMENT
Amino Acid Complex 01828 Advanced Lipid Control
02261 Wellness Code® Whey Protein Concentrate Chocolate 01359 Cho-Less™
02260 Wellness Code® Whey Protein Concentrate Vanilla 01910 CHOL-Support™
02243 Wellness Code® Whey Protein Isolate Chocolate 01030 Red Yeast Rice
02242 Wellness Code® Whey Protein Isolate Vanilla 01304 Theaflavins Standardized Extract
02220 Wellness Shake • Chocolate 00372 Vitamin B3 Niacin Capsules
02219 Wellness Shake • Vanilla
DIGESTION SUPPORT
AMINO ACIDS 53348 Betaine HCI
01039 Arginine & Ornithine Capsules 54160 Black Vinegar
00038 Arginine Ornithine Powder 30747 Digest RC®
01253 Branched Chain Amino Acids 07136 Effervescent Vitamin C - Magnesium Crystals
01829 Carnosine 02021 Enhanced Super Digestive Enzymes
01671 D,L-Phenylalanine Capsules 02022 Enhanced Super Digestive Enzymes and Probiotics
01624 L-Arginine Caps 02033 EsophaCool™
01532 L-Carnitine 01737 Esophageal Guardian
00345 L-Glutamine 01706 Extraordinary Enzymes
00141 L-Glutamine Powder 02100 Gastro-Ease™
01678 L-Lysine 01122 Ginger Force™
00133 L-Taurine Powder 00605 Regimint
00326 L-Tyrosine Tablets 01386 TruFiber®
01827 Taurine
ENERGY MANAGEMENT
BLOOD PRESSURE & VASCULAR SUPPORT 01628 Adrenal Energy Formula • 60 veg capsules
01824 Advanced Olive Leaf Vascular Support with 01630 Adrenal Energy Formula • 120 veg capsules
Celery Seed Extract 01805 Asian Energy Boost
02004 Arterial Protect 00972 D-Ribose Powder
70000 Blood Pressure Monitor Arm Cuff 01473 D-Ribose Tablets
70004 Blood Pressure Monitor Digital Wrist Cuff 01900 Energy Renew
02097 Endothelial Defense™ Pomegranate Complete 01544 Forskolin
00997 Endothelial Defense™ with GliSODin® 00668 Metabolic Advantage Thyroid Formula™
02320 NitroVasc™ Boost 01869 Mitochondrial Basics with PQQ
00984 Optimal BP Management 01868 Mitochondrial Energy Optimizer with PQQ
01953 Pomegranate Complete 01904 NAD+ Cell Regenerator™ • 100 mg, 30 veg capsules
00956 Pomegranate Fruit Extract 02344 NAD+ Cell Regenerator™ Nicotinamide Riboside
02024 Triple Action Blood Pressure AM/PM 300 mg, 30 veg capsules
02102 VenoFlow™ 02348 Optimized NAD+ Cell Regenerator™ and Resveratrol
BONE HEALTH 01500 PQQ Caps • 10 mg
01647 PQQ Caps • 20 mg
01726 Bone Restore
00889 Rhodiola Extract
02123 Bone Restore-Sugar-Free
02003 Triple Action Thyroid
01727 Bone Restore with Vitamin K2
01725 Bone Strength Collagen Formula EYE HEALTH
00313 Bone-Up™ 01923 Astaxanthin with Phospholipids
01963 Calcium Citrate with Vitamin D 00893 Brite Eyes III
01506 Dr. Strum’s Intensive Bone Formula 02323 Digital Eye Support
01476 Strontium Caps 01514 Eye Pressure Support with Mirtogenol®
BRAIN HEALTH 01992 MacuGuard® Ocular Support with Saffron
01993 MacuGuard® Ocular Support with Saffron & Astaxanthin
01524 Acetyl-L-Carnitine
01873 Standardized European Bilberry Extract
01974 Acetyl-L-Carnitine Arginate
01918 Tear Support with MaquiBright®
01008 Blast™
02321 Cognitex® Basics FISH OIL & OMEGAS
02396 Cognitex® Elite 02311 Clearly EPA/DHA Fish Oil
02397 Cognitex® Elite Pregnenolone 00463 Flaxseed Oil
01659 Cognizin® CDP-Choline Caps 01937 Mega EPA/DHA
01540 DMAE Bitartrate (dimethylaminoethanol) 02218 Mega GLA Sesame Lignans
02006 Dopa-Mind™ 01983 Super Omega-3 EPA/DHA Fish Oil,
02212 Focus Tea™ Sesame Lignans & Olive Extract
01658 Ginkgo Biloba Certified Extract™
PRODUCTS
01988 Super Omega-3 Plus EPA/DHA Fish Oil, IMMUNE SUPPORT
Sesame Lignans, Olive Extract, Krill & Astaxanthin 00681 AHCC®
01982 Super Omega-3 EPA/DHA Fish Oil, 02302 Bio-Quercetin
Sesame Lignans & Olive Extract • 120 softgels 01961 Enhanced Zinc Lozenges
01985 Super Omega-3 EPA/DHA Fish Oil, Sesame Lignans & 01704 Immune Modulator with Tinofend®
Olive Extract • 60 enteric coated softgels 00955 Immune Protect with PARACTIN®
01984 Super Omega-3 EPA/DHA Fish Oil, Sesame Lignans & 02005 Immune Senescence Protection Formula™
Olive Extract • 120 enteric coated softgels 29727 Kinoko® Gold AHCC
01986 Super Omega-3 EPA/DHA Fish Oil, Sesame Lignans & 24404 Kinoko® Platinum AHCC
Olive Extract • 240 softgels 00316 Kyolic® Garlic Formula 102
01812 Provinal® Purified Omega-7 00789 Kyolic® Reserve
01640 Vegetarian DHA 01681 Lactoferrin (Apolactoferrin) Caps
FOOD 01903 NK Cell Activator™
02008 California Estate Extra Virgin Olive Oil 01394 Optimized Garlic
02170 Rainforest Blend Decaf Ground Coffee 01309 Optimized Quercetin
02169 Rainforest Blend Ground Coffee 01811 Peony Immune
02171 Rainforest Blend Whole Bean Coffee 00525 ProBoost Thymic Protein A
00438 Stevia™ Organic Liquid Sweetner 01708 Reishi Extract Mushroom Complex
00432 Stevia™ Sweetener 01906 Standardized Cistanche
13685 Ten Mushroom Formula®
GLUCOSE MANAGEMENT 01097 Ultra Soy Extract
01503 CinSulin® with InSea2® and Crominex® 3+ 01561 Zinc Lozenges
01620 CoffeeGenic® Green Coffee Extract
INFLAMMATION MANAGEMENT
02122 Glycemic Guard™
00925 Mega Benfotiamine 01639 5-LOX Inhibitor with AprèsFlex®
01803 Tri Sugar Shield® 02324 Advanced Curcumin Elite™
Turmeric Extract, Ginger & Turmerones
HEART HEALTH 01709 Black Cumin Seed Oil
01066 Aspirin (Enteric Coated) 02310 Black Cumin Seed Oil and Curcumin Elite™
01842 BioActive Folate & Vitamin B12 Caps Turmeric Extract
01700 Cardio Peak™ with Standardized Hawthorn and Arjuna 00202 Boswella
02121 Homocysteine Resist 02467 Curcumin Elite™ Turmeric Extract • 30 veg capsules
02018 Optimized Carnitine 02407 Curcumin Elite™ Turmeric Extract • 60 veg capsules
01949 Super-Absorbable CoQ10 Ubiquinone with 01804 Cytokine Suppress® with EGCG
d-Limonene • 50 mg, 60 softgels 02223 Pro-Resolving Mediators
01951 Super-Absorbable CoQ10 Ubiquinone with 00318 Serraflazyme
d-Limonene • 100 mg, 30 softgels 01203 Specially-Coated Bromelain
01929 Super Ubiquinol CoQ10 01254 Zyflamend™ Whole Body
01427 Super Ubiquinol CoQ10 with Enh Mitochondrial
JOINT SUPPORT
Support™ • 50 mg, 30 softgels
01425 Super Ubiquinol CoQ10 with Enh Mitochondrial 02404 Arthro-Immune Joint Support
Support™ • 50 mg, 100 softgels 02238 ArthroMax® Advanced NT2 Collagen™ & AprèsFlex®
01437 Super Ubiquinol CoQ10 with Enh Mitochondrial 01617 ArthroMax® with Theaflavins & AprèsFlex®
Support™ • 100 mg, 30 softgels 02138 ArthroMax® Elite
01426 Super Ubiquinol CoQ10 with Enh Mitochondrial 00965 Fast-Acting Joint Formula
Support™ • 100 mg, 60 softgels 00522 Glucosamine/Chondroitin Capsules
01431 Super Ubiquinol CoQ10 with Enh Mitochondrial 01600 Krill Healthy Joint Formula
Support™ • 200 mg, 30 softgels 01050 Krill Oil
01733 Super Ubiquinol CoQ10 with PQQ 00451 MSM (Methylsulfonylmethane)
01859 TMG Liquid Capsules 02231 NT2 Collagen™
00349 TMG Powder KIDNEY & BLADDER SUPPORT
HORMONE BALANCE 00862 Cran-Max® Cranberry Whole Fruit Concentrate
00454 DHEA (Dehydroepiandrosterone) 01424 Optimized Cran-Max® with Ellirose™
15 mg, 100 capsules 01921 Uric Acid Control
00335 DHEA (Dehydroepiandrosterone) 01209 Water-Soluble Pumpkin Seed Extract
25 mg, 100 capsules LIVER HEALTH & DETOXIFICATION
00882 DHEA (Dehydroepiandrosterone) 02240 Anti-Alcohol HepatoProtection Complex
50 mg, 60 capsules 01651 Calcium D-Glucarate
00607 DHEA (Dehydroepiandrosterone) 00550 Chlorella
25 mg, 100 tablets (dissolve in mouth) 01571 Chlorophyllin
01689 DHEA (Dehydroepiandrosterone) 01922 European Milk Thistle • 60 softgels
100 mg, 60 veg capsules 01925 European Milk Thistle • 120 softgels
02368 Optimized Broccoli and Cruciferous Blend 01522 European Milk Thistle • 60 veg capsules
00302 Pregnenolone • 50 mg, 100 capsules 02402 FLORASSIST® Liver Restore™
00700 Pregnenolone • 100 mg, 100 capsules 01541 Glutathione, Cysteine & C
01468 Triple Action Cruciferous Vegetable Extract 01393 HepatoPro
01469 Triple Action Cruciferous Vegetable Extract 01608 Liver Efficiency Formula
with Resveratrol 01534 N-Acetyl-L-Cysteine
PRODUCTS
00342 PectaSol-C® Modified Citrus Pectin Powder MULTIVITAMINS
01080 PectaSol-C® Modified Citrus Pectin Capsules 02199 Children’s Formula Life Extension Mix™
01884 Silymarin 02498 Comprehensive Nutrient Packs ADVANCED
LONGEVITY & WELLNESS 02354 Life Extension Mix™ Capsules
00457 Alpha-Lipoic Acid 02364 Life Extension Mix™ Capsules without Copper
01625 AppleWise Polyphenol Extract 02356 Life Extension Mix™ Powder
01214 Blueberry Extract 02355 Life Extension Mix™ Tablets
01438 Blueberry Extract with Pomegranate 02357 Life Extension Mix™ Tablets with Extra Niacin
02270 DNA Protection Formula 02365 Life Extension Mix™ Tablets without Copper
02119 GEROPROTECT® Ageless Cell™ 02292 Once-Daily Health Booster • 30 softgels
02133 GEROPROTECT® Longevity A.I.™ 02291 Once-Daily Health Booster • 60 softgels
02401 GEROPROTECT® Stem Cell 02313 One-Per-Day Tablets
02211 Grapeseed Extract 02317 Two-Per-Day Capsules • 60 capsules
02109 Mediterranean Whole Food Blend 02314 Two-Per-Day Capsules • 120 capsules
00954 Mega Green Tea Extract (decaffeinated) 02316 Two-Per-Day Tablets • 60 tablets
00953 Mega Green Tea Extract (lightly caffeinated) 02315 Two-Per-Day Tablets • 120 tablets
01513 Optimized Fucoidan with Maritech® 926 NERVE & COMFORT SUPPORT
02230 Optimized Resveratrol 02202 ComfortMAX™
01637 Pycnogenol® French Maritime Pine Bark Extract 02303 PEA Discomfort Relief
02210 Resveratrol
00070 RNA (Ribonucleic Acid) PERSONAL CARE
02301 Senolytic Activator 01006 Biosil™ • 5 mg, 30 veg capsules
01208 Super R-Lipoic Acid 01007 Biosil™ • 1 fl oz
01919 X-R Shield 00321 Dr. Proctor’s Advanced Hair Formula
MEN’S HEALTH 00320 Dr. Proctor’s Shampoo
02322 Hair, Skin & Nails Collagen Plus Formula
02209 Male Vascular Sexual Support 01278 Life Extension Toothpaste
00455 Mega Lycopene Extract 00408 Venotone
02306 Men’s Bladder Control 00409 Xyliwhite Mouthwash
01789 PalmettoGuard® Saw Palmetto with Beta-Sitosterol 02304 Youthful Collagen
01790 PalmettoGuard® Saw Palmetto/Nettle Root Formula 02252 Youthful Legs
with Beta-Sitosterol
01837 Pomi-T® PET CARE
01373 Prelox® Enhanced Sex for Men 01932 Cat Mix
01940 Super MiraForte with Standardized Lignans 01931 Dog Mix
01909 Triple Strength ProstaPollen™ PROBIOTICS
02029 Ultra Prostate Formula 01622 Bifido GI Balance
MINERALS 01825 FLORASSIST® Balance
01661 Boron 02125 FLORASSIST® GI with Phage Technology
02107 Extend-Release Magnesium 01821 FLORASSIST® Heart Health
30731 Ionic Selenium 02250 FLORASSIST® Mood Improve
01677 Iron Protein Plus 02208 FLORASSIST® Nasal
01459 Magnesium Caps 02120 FLORASSIST® Oral Hygiene
01682 Magnesium (Citrate) 02203 FLORASSIST® Prebiotic
01328 Only Trace Minerals 01920 FLORASSIST® Throat Health
01504 Optimized Chromium with Crominex® 3+ 52142 Jarro-Dophilus® for Women
02309 Potassium with Extend-Release Magnesium 00056 Jarro-Dophilus EPS® • 60 veg capsules
01740 Sea-Iodine™ 21201 Jarro-Dophilus EPS® • 120 veg capsules
01879 Se-Methyl L-Selenocysteine 01038 Theralac® Probiotics
01778 Super Selenium Complex 01389 TruFlora® Probiotics
00213 Vanadyl Sulfate SKIN CARE
01813 Zinc Caps 80157 Advanced Anti-Glycation Peptide Serum
MISCELLANEOUS 80165 Advanced Growth Factor Serum
00577 Potassium Iodide 80170 Advanced Hyaluronic Acid Serum
00657 Solarshield® Sunglasses 80154 Advanced Lightening Cream
80155 Advanced Peptide Hand Therapy
MOOD & STRESS MANAGEMENT
80175 Advanced Probiotic-Fermented Eye Serum
02312 Cortisol-Stress Balance 80152 Advanced Triple Peptide Serum
00987 Enhanced Stress Relief 80140 Advanced Under Eye Serum with Stem Cells
01074 5 HTP 80137 All-Purpose Soothing Relief Cream
01683 L-Theanine 80139 Amber Self MicroDermAbrasion
02175 SAMe (S-Adenosyl-Methionine) 80118 Anti-Aging Mask
200 mg, 30 enteric coated tablets 80151 Anti-Aging Rejuvenating Face Cream
02176 SAMe (S-Adenosyl-Methionine) 80153 Anti-Aging Rejuvenating Scalp Serum
400 mg, 30 enteric coated tablets
02174 SAMe (S-Adenosyl-Methionine)
400 mg, 60 enteric coated tablets
PRODUCTS
80156 Collagen Boosting Peptide Serum VITAMINS
80169 Cucumber Hydra Peptide Eye Cream 01533 Ascorbyl Palmitate
80141 DNA Support Cream 00920 Benfotiamine with Thiamine
80167 Environmental Support Serum 00664 Beta-Carotene
80163 Eye Lift Cream 01945 BioActive Complete B-Complex
80123 Face Rejuvenating Anti-Oxidant Cream 00102 Biotin
80109 Hyaluronic Facial Moisturizer 00084 Buffered Vitamin C Powder
80110 Hyaluronic Oil-Free Facial Moisturizer 02229 Fast-C® and Bio-Quercetin Phytosome
80138 Hydrating Anti-Oxidant Facial Mist 02075 Gamma E Mixed Tocopherol Enhanced with
00661 Hydroderm Sesame Lignans
80103 Lifting & Tightening Complex 02070 Gamma E Mixed Tocopherol/Tocotrienols
80168 Melatonin Advanced Peptide Cream 01913 High Potency Optimized Folate
80114 Mild Facial Cleanser 01674 Inositol Caps Liquid Emulsified
80172 Multi Stem Cell Hydration Cream 02244 Liquid Vitamin D3 • 2,000 IU, 1 fl oz
80159 Multi Stem Cell Skin Tightening Complex 02232 Liquid Vitamin D3 • 2,000 IU, 1 fl oz, mint
80122 Neck Rejuvenating Anti-Oxidant Cream 01936 Low-Dose Vitamin K2
80174 Purifying Facial Mask 01536 Methylcobalamin • 1 mg, 60 veg lozenges
80150 Renewing Eye Cream 01537 Methylcobalamin • 5 mg, 60 veg lozenges
80142 Resveratrol Anti-Oxidant Serum 00065 MK-7
01938 Shade Factor™ 00373 No Flush Niacin
02129 Skin Care Collection Anti-Aging Serum 01939 Optimized Folate (L-Methylfolate)
02130 Skin Care Collection Day Cream 01217 Pyridoxal 5’-Phosphate Caps
02131 Skin Care Collection Night Cream 01400 Super Absorbable Tocotrienols
80166 Skin Firming Complex 02334 Super K
02096 Skin Restoring Ceramides 02335 Super K Elite
80130 Skin Stem Cell Serum 01863 Super Vitamin E
80164 Skin Tone Equalizer 02028 Vitamin B5 (Pantothenic Acid)
80143 Stem Cell Cream with Alpine Rose 01535 Vitamin B6
80148 Tightening & Firming Neck Cream 00361 Vitamin B12
80161 Triple-Action Vitamin C Cream 02228 Vitamin C and Bio-Quercetin Phytosome
80162 Ultimate MicroDermabrasion 1,000 mg, 60 veg tablets
80173 Ultimate Peptide Serum 02227 Vitamin C and Bio-Quercetin Phytosome
80160 Ultra Eyelash Booster 1,000 mg, 250 veg tablets
80101 Ultra Wrinkle Relaxer 01753 Vitamin D3 • 25 mcg (1,000 IU), 90 softgels
80113 Under Eye Refining Serum 01751 Vitamin D3 • 25 mcg (1,000 IU), 250 softgels
80104 Under Eye Rescue Cream 01713 Vitamin D3 • 125 mcg (5,000 IU), 60 softgels
80171 Vitamin C Lip Rejuvenator 01718 Vitamin D3 • 175 mcg (7,000 IU), 60 softgels
80129 Vitamin C Serum 01758 Vitamin D3 with Sea-Iodine™
80136 Vitamin D Lotion 02040 Vitamins D and K with Sea-Iodine™
80102 Vitamin K Cream
WEIGHT MANAGEMENT & BODY COMPOSITION
SLEEP
00658 7-Keto® DHEA Metabolite • 25 mg, 100 capsules
01512 Bioactive Milk Peptides 02479 7-Keto® DHEA Metabolite • 100 mg, 60 veg capsules
02300 Circadian Sleep 01509 Advanced Anti-Adipocyte Formula
01551 Enhanced Sleep with Melatonin 01807 Advanced Appetite Suppress
01511 Enhanced Sleep without Melatonin 02207 AMPK Metabolic Activator
02234 Fast-Acting Liquid Melatonin 01823 CalReduce Selective Fat Binder
01669 Glycine 02478 DHEA Complete
02308 Herbal Sleep PM 01738 Garcinia HCA
01722 L-Tryptophan 29754 HCActive Garcinia Cambogia Extract
01668 Melatonin • 300 mcg, 100 veg capsules 01292 Integra-Lean®
01083 Melatonin • 500 mcg, 200 veg capsules 01908 Mediterranean Trim with Sinetrol™ -XPur
00329 Melatonin • 1 mg, 60 capsules 01492 Optimized Irvingia with Phase 3™ Calorie Control Complex
00330 Melatonin • 3 mg, 60 veg capsules 01432 Optimized Saffron with Satiereal®
00331 Melatonin • 10 mg, 60 veg capsules 00818 Super CLA Blend with Sesame Lignans
00332 Melatonin • 3 mg, 60 veg lozenges 01902 Waist-Line Control™
02201 Melatonin IR/XR 02151 Wellness Code® Appetite Control
01787 Melatonin 6 Hour Timed Release
WOMEN’S HEALTH
300 mcg, 100 veg tablets
01788 Melatonin 6 Hour Timed Release 01942 Breast Health Formula
750 mcg, 60 veg tablets 01626 Enhanced Sex for Women 50+
01786 Melatonin 6 Hour Timed Release 01894 Estrogen for Women
3 mg, 60 veg tablets 01064 Femmenessence MacaPause®
01721 Optimized Tryptophan Plus 02204 Menopause 731™
01444 Quiet Sleep 02319 Prenatal Advantage
01445 Quiet Sleep Melatonin 01441 Progesta-Care®
01649 Super-Absorbable Soy Isoflavones
HIGHER POTENCY
CARNOSINE
Carnosine is a unique dipeptide that can Super Carnosine provides  mg of Mitochondrial Energy Optimizer
inhibit glycation throughout the body, carnosine per capsule along with provides , mg of carnosine
thereby helping to slow normal aging fat-soluble vitamin B (benfotiamine) in each four-capsule dose along
processes. Suggested dose is one to further impede glycation reactions. with R-lipoic acid, benfotiamine,
 mg Carnosine cap taken twice daily. taurine, and PQQ to provide
broad-spectrum support.
Item # •  vegetarian capsules Item # •  vegetarian capsules *Item # •  capsules
 bottle $  bottle $  bottle $
 bottles $ each  bottles $ each  bottles $ each
Life Extension® was the first to introduce Life Extension carnosine is available in Each formula provides high doses
high-dose ( mg) carnosine back in . three different formulas to allow you to of carnosine to ensure sustained
customize your longevity program. benefits.
For full product description and to order Mitochondrial Energy Optimizer, Carnosine or
Super Carnosine, call --- or visit www.LifeExtension.com
*Bio-Enhanced® is a registered trademark of Geronova Research, Inc.
Higher Potency at
Discount Pricing TM
NAD +
Cell Regenerator
TURN ON YOUR
CELLULAR ENERGY
NAD+ levels plummet with age but
increase in response to nicotinamide
riboside.
Optimized NAD+ Cell Regenerator™
combines  mg of nicotinamide
riboside with resveratrol and other
plant extracts.
For those already taking resveratrol, we
also offer NAD+ Cell Regenerator™
that provides  mg of nicotinamide
riboside.
The only online source of these NAD+
formulas is LifeExtension.com (or by
calling ---).
Optimized NAD+ Cell Regenerator™ NAD+ Cell Regenerator™

Item # •  vegetarian capsules Item # •  vegetarian capsules
 bottle *  bottle *
* For pricing available to readers of this magazine, call 1-800-544-4440 or visit LifeExtension.com/NAD
For full product description and to order NAD+ Cell Regenerator™

or Optimized NAD+ Cell Regenerator™ with Resveratrol,
NIAGEN® is a registered trademark of ChromaDex, Inc., Patents see: www.ChromaDexPatents.com
PO BOX 407198
FORT LAUDERDALE, FLORIDA 33340-7198
IN THIS EDITION OF LIFE EXTENSION® MAGAZINE
7 WHY ARGININE FAILED AS A CARDIOVASCULAR DRUG

L-arginine rapidly degrades in the body. This caused it to fall
out of favor with cardiologists. A new low-dose, sustainable
L-arginine offers support for circulatory health.
22 BOOST NITRIC OXIDE TO REDUCE CARDIOVASCULAR RISK

A blend of aronia berries and an innovative form of L-arginine
7 22 boosts production of nitric oxide, helping to improve blood flow.
32 HOW MEN CAN FIGHT OSTEOPOROSIS

Men are at a higher risk of osteoporosis than most realize.
Healthy lifestyle choices, along with appropriate nutrients and
hormone balance promotes bone formation and strength.
42 IMPROVE DIGESTION OF PLANT-BASED FOODS

The trend toward eating plant-based diets often requires
special enzymes to digest fiber-rich foods to avoid bloating,
32 42 gas, and diarrhea.
54 IMPROVE SKIN APPEARANCE FROM THE INSIDE

65 Oral intake of collagen peptides and hyaluronic acid reduces
eye wrinkle depth up to 20%.
65 LACTOFERRIN HELPS BUILD NEW BONES

Adding lactoferrin to your bone-building supplements
helps reduce bone loss and increase new bone formation.
54 VISIT US ONLINE AT LIFEEXTENSION.COM

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F E A T U R E A R T I C L E S

7 Why Arginine Failed as a Heart Drug

PLUS: New Method to Boost Nitric Oxide

The numbers of synapses that connect

For full product description and to order Neuro-Mag® Magnesium L-Threonate or

LifeExtension.com April 2020

42 IMPROVE DIGESTION OF PLANT-BASED FOODS

54 IMPROVE SKIN APPEARANCE FROM THE INSIDE

65 LACTOFERRIN HELPS BUILD NEW BONES

• The Most Complete Line of Nutrition Center

Life Extension Supplements

Circulation & Distribution

2 | LIFE EXTENSION | APRIL 2020

Curcumin EliteTM utilizes a new patented turmeric extract

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4 | LIFE EXTENSION | APRIL 2020

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Does your multivitamin measure up?

Life Extension®’s Two-Per-Day contains superior forms

Why Arginine Failed as

APRIL 2020 | LIFE EXTENSION | 7

Nitric Oxide: Discovering Nitric Oxide’s

8 | LIFE EXTENSION | APRIL 2020

Nitric oxide is one important

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10 | LIFE EXTENSION | APRIL 2020

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This advanced formula provides:

1. EPA/DHA Fish Oil

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How well you take care of your teeth

Editor’s Note: “Poor oral hygiene can provoke

* Eur J Prev Cardiol. 2019 Dec 1.

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14 | LIFE EXTENSION | APRIL 2020

Drinking Tea Supports a

Research reported in the jour-

Editor’s Note: “Our results offer the ﬁrst evi-

* Aging (Albany NY). 2019 Jun 14;11(11):

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Blueberry Intake May

A study reported in the American

Editor’s Note: “The simple and attainable

* Am J Clin Nutr. 2019 Jun 1;109(6):1535-

16 | LIFE EXTENSION | APRIL 2020

Bone Strength Collagen

Magnesium, silicon, dried plum,

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KoAct® is a patented form of bone collagen with calcium designed to support

Each chewable tablet delivers

Take one to two chewables daily as needed.

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When L-arginine is ingested, about

decline to provide more bioavailable arginine.* 4 boxes $22 each

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For full product description and to order FLORASSIST® Oral Hygiene,