Treating The Top Five Chronic Conditions Chris Kresser

kresserinstitute.
com 1
Introduction
Dear Reader,
Thank you for downloading these case studies.
Throughout my book, Unconventional Medicine, I talk a lot about the concepts of Functional
Medicine and ancestral diet and lifestyle. But concepts are of limited value until you can practically
apply them. That’s where this ebook comes in.
In the following five case studies, you’ll be able to see just how powerful Functional Medicine and
ancestral health can be when applied to real-life patients:
■ How blood sugar control was restored in a 66-year-old patient with diabetes
■ How rheumatoid arthritis in a 46-year-old patient was resolved by treating the gut
■ How hypothyroidism was resolved in a 26-year-old patient by restoring iodine levels
■ How mental and physical performance were optimized in a 41-year-old CEO
■ How HPA axis dysregulation was resolved in a 42-year-old with fatigue, anxiety and
weight gain
I hope these case studies give you a greater insight into how digging deeper and resolving the root
cause of chronic illness can result in true healing rather than symptom suppression.
In health,
Chris Kresser
kresserinstitute.com 2
Inflammatory Joint Pain and
Hormone Imbalance Resolved by
Treating the Gut
CASE SUMMARY
A 46-year-old female experienced a downward spiral after the death of a loved one and the
loss of her job. She complained of joint pain, gastrointestinal symptoms, cold hands and feet,
problems thinking, anxiety, and insomnia. She had been given a diagnosis of rheumatoid
arthritis but did not want to take immunosuppressive drugs. Routine lab tests, HLA-B27, a
stool test, SIBO, and hormone panels showed thyroid dysfunction and genetic predisposition
to autoimmunity. She also had high iron levels and gut dysbiosis. Especially noteworthy was an
overgrowth of Klebsiella, a bacteria known to contribute to inflammatory joint disease.
Treating Michelle’s dysbiosis resolved her joint pain, improved her cognitive function, and
normalized her thyroid markers and cortisol levels.
Michelle, a 46-year-old female, presented with bilateral joint pain in the hands and feet, digestive
symptoms (gas, bloating, constipation), cold hands and feet, brain fog, anxiety, and sleep
disturbance. Her symptoms had worsened in the last three-month period, after she lost her job and
her mother passed away.
She had been given a provisional diagnosis of rheumatoid arthritis by another clinician. She was
prescribed immunosuppressive drugs, which she refused. She occasionally took ibuprofen to
manage the joint pain, but she was concerned about its long-term effects. She had a family history
of autoimmune disease (her mother had Hashimoto’s thyroiditis and her sister had Crohn’s
disease). She believed that she might also have some form of autoimmunity.
I ran a full panel of lab tests on Michelle: a stool test, HLA-B27 blood test, small intestinal bacterial
overgrowth breath test, urinary organic acids, routine lab tests with a thyroid panel, and a urine
hormone profile. I found several pathologies that were contributing to her symptoms.
Initial Testing
FIGURE 1: Comprehensive Stool Analysis. Dysbiotic flora are highlighted in red. Commensal flora, which may
be imbalanced, are highlighted in yellow.
Michelle’s stool test found low levels of Lactobacillus and E. coli, both important species of
beneficial bacteria. In addition, it found a 3+ for two species of pathogenic bacteria, Enterobacter
cloacae and Klebsiella pneumoniae. She was negative for yeast.
The Klebsiella is of particular concern given her symptoms. Klebsiella species are associated with
conditions that are characterized by joint pain, including ankylosing spondylitis, reactive arthritis,
and rheumatoid arthritis. It has also been reported in irritable bowel syndrome (which this patient
would likely meet the diagnostic criteria for) and other digestive conditions such as Crohn’s
disease. The association between Klebsiella and autoimmune disease appears to be mediated—at
least in some cases—by the HLA-B27 protein,1 which is found on the surface of white blood cells.
I tested Michelle for HLA-B27 and she was positive. This finding suggests that she may be more
susceptible to autoimmune conditions, and a Klebsiella infection might be more problematic for
her than for others who are HLA-B27 negative.
FIGURE 2: HLA-B27 Blood Test.
FIGURE 3: Small Intestinal Bacterial Overgrowth Test Results.
Her SIBO breath test results indicated methane overproduction. This suggested bacterial
overgrowth in the small intestine, which was likely contributing to her constipation.
FIGURE 4: Urinary Organix (Organic Acids) from Genova Diagnostics.
Her urine organic acids test confirmed the microbial overgrowth and imbalance in her gut, and
revealed several other issues including:
■ B vitamin deficiency. SIBO and a microbial imbalance decrease the absorption of several
nutrients, including B vitamins.
■ Oxidative stress
■ Impaired carbohydrate metabolism
■ Impaired fatty acid metabolism
■ Impaired detoxification capacity
Her routine blood test was mostly unremarkable, with the following exceptions. She had several
markers of iron overload, including ferritin and UIBC that were out of the reference range, and iron
saturation that was out of the functional/optimal range (<45%). Michelle had excessive iron storage
but not frank hemochromatosis. Many people don’t meet the diagnostic criteria for
hemochromatosis. The iron elevation also wasn’t an artifact of inflammation (inflammation alone
can cause high ferritin levels) because her iron saturation and UIBC were abnormal in addition to
ferritin. High iron levels have been shown to contribute to joint pain, cognitive dysfunction, and
many other symptoms.
Her TSH and thyroid antibodies were normal, but her free T3 (triiodothyronine, free) was low at 1.7
(range: 2.0–4.4 pg/mL). This was likely contributing to her cold hands and feet, constipation, and brain
fog. She also had a low white blood cell count, which is often observed in autoimmune conditions.
FIGURE 5: Routine Laboratory Tests Including Thyroid Function Markers, Iron, and Vitamin D.
In this case, her low free T3 may be secondary to her gut dysfunction. Approximately 20 percent of
T4 is converted into T3 in the gut. Inflammation—which she is clearly experiencing—also reduces
the conversion of T4 to T3.
FIGURE 6: Analysis of HPA-axis Function Using the Dried Urine Test Comprehensive Hormones (DUTCH) from
Precision Analytical.
Finally, Michelle’s urine hormones revealed high-normal free cortisol but low metabolized cortisol
during a 24-hour period. In addition, her diurnal free cortisol production was disrupted, with high
levels at night, high-normal levels upon rising and in the morning, and low levels in the afternoon.
Elevated cortisol levels might have reflected her stress response, consistent with her history of job
loss and the death of her mother. Hypothyroidism impairs the body’s ability to metabolize cortisol,
so this pattern of high free cortisol but low total metabolized cortisol suggested that Michelle had
poor thyroid function, which was consistent with her low free T3.
Treatment
One of the core principles in functional medicine is to address the underlying cause of illness,
rather than just suppressing symptoms. I chose to address her GI issues (the SIBO, dysbiosis, and
Klebsiella/HLA-B27) and then re-test her thyroid markers before taking any specific action for the
thyroid dysfunction, because I believed that it would resolve on its own once her gut function
improved and inflammation decreased.
The primary goals of the treatment protocol were:
■ Reduce overgrowth of Klebsiella and prevent further immune attack against HLA-B27 proteins
■ Reduce levels of methanogenic microbes in the small intestine by treating SIBO
■ Restore nutrient balance and metabolic function by improving digestive absorption  
of nutrients
■ Increase levels of beneficial bacteria and restore a healthy microbial balance in her intestine
■ Bring her iron levels back into a normal range
■ Increase her free T3 levels and improve her thyroid function indirectly by addressing her
GI health
■ Normalize her free and total cortisol levels indirectly by addressing her GI health
For Klebsiella, SIBO, and microbial overgrowth, I used a protocol of antimicrobial botanicals, soil-
based and transient commensal probiotics with specific antimicrobial effects, a biofilm disruptor,
and a potent extract of lauric acid (an antimicrobial fatty acid). For iron reduction, I suggested a
course of phlebotomy (via blood donation) until her ferritin was <100 ng/mL and her iron
saturation was <40 percent. To help with her inflammatory symptoms and balance and regulate
her immune function, I prescribed a liposomal form of curcumin.
TABLE 1: Michelle’s Treatment Protocol with Dosages.
TREATMENT NUTRACEUTICAL BRAND DOSAGE

1 packet BID (with breakfast
Antimicrobial GI Synergy Apex Energetics
and dinner)
3-4 capsules BID on an
Antimicrobial Interfase Plus Klaire Labs
empty stomach
One BID upon rising and
Probiotic Prescript-Assist Prescript-Assist
before bed
Probiotic/anti-
MegaSporeBiotic MegaSporeBiotic One capsule with lunch
microbial
L. plantarum for
Probiotic Ideal Bowel Support Jarrow Formulas
methanogens
Med-Chem 1 scoop three times daily with
Antimicrobial Lauricidin
Laboratories meals
3 billion CFU twice daily at
Probiotic Saccharomycin DF Xymogen
lunch and before bed
One capsule three times a
day on an empty stomach for
Anti-inflammatory Optimized Curcumin ProHealth
seven days, then decrease to
one capsule daily.
After the antimicrobial protocol was completed, I prescribed a combination of fermented foods,
fermentable dietary fibers, probiotics, and prebiotics to restore a healthy gut ecosystem.
Follow-up Testing and Clinical Outcome
FIGURE 7: Comprehensive Stool Analysis Follow-Up.
Michelle received treatment for 60 days and then I ran another set of tests to check on her
progress. Michelle’s follow-up test results indicated a significant improvement. As you can see from
her stool test, the Klebsiella and Enterobacter (dysbiotic flora) were gone. Her beneficial bacteria
improved, with the exception of Lactobacillus, which still needed attention.
She had a 3+ for Saccharomyces boulardii, which is marked as “dysbiotic flora” and a moderate
(Mod) level of yeast in the microscopic section. At first glance this might suggest fungal
overgrowth. However, one of the probiotics I treated her with was Saccharomyces boulardii, so this
result is simply showing the presence of that in her stool. It is not a pathological finding.
FIGURE 8: Follow-up Test Results for SIBO.
Her follow-up SIBO results were normal.
Her organic acids urine test also improved significantly, with only two markers in the low-normal
range. This shows that treating the gut effectively supplied Michelle with critical nutrients
(especially B vitamins) that improved her metabolism.
FIGURE 9: Urinary Organic Acids Follow-up Test.
Her iron saturation dropped to 28 percent after two blood donations. Her ferritin returned to the
reference range, but it remained high normal. Further blood donations would be indicated
provided that hemoglobin and iron saturation do not drop too low.
FIGURE 10: Follow-up Results for Routine Laboratory Testing, Including Thyroid and Iron Markers.
Her free T3 improved dramatically without any specific focus on her thyroid, supporting the
functional medicine principle of addressing the underlying cause. That said, both her TSH and
reverse T3 are high-normal, which may suggest an ongoing thyroid issue or chronic stressor that is
not influenced by her GI function. This would not be surprising given her family history of thyroid
disease and her recent stressful experiences.
Finally, her DUTCH test results normalized. Her free cortisol decreased to 111 (range: 80–180) her
metabolized cortisol increased to 2,779 (range: 2240–4300), and her diurnal cortisol rhythm
improved. This also illustrates the importance of addressing the deepest cause(s) of the signs and
symptoms you observe first in the treatment process.
FIGURE 11: Follow-up Results for DUTCH Test
Most importantly, Michelle’s symptoms improved dramatically. Her joint pain was reduced by 80 to
90 percent, and she no longer needed ibuprofen or any other OTC pain medication to manage it.
Her body temperature normalized and she no longer had cold hands and feet. Her constipation,
which had been present for over a decade, resolved—as did her gas and bloating. She was able to
think more clearly and concentrate for longer periods, and she no longer felt anxious. For the first
time in many years she was sleeping deeply through the night and waking up in the mornings
feeling refreshed and energized.
Discussion
Michelle presented with joint pain, gut dysfunction, and cognitive and thyroid symptoms.
Gastrointestinal testing revealed a Klebsiella pneumoniae overgrowth, and genetic testing showed
that she was positive for HLA-B27, indicating susceptibility to autoimmunity.
The association between Klebsiella and autoimmune disease appears to be mediated—at least in
some cases—by the HLA-B27 protein,1 which is found on the surface of white blood cells. HLA-B27
is encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6 and
presents antigenic peptides (derived from self and non-self antigens) to T cells.
The genetic prevalence of HLA-B27 varies significantly according to ethnicity, ranging from as low
as 0.1 percent in people of Japanese descent to 24 percent of people in Northern Scandanavia.
Ninety-two percent of Caucasian people with ankylosing spondylitis (AS) have HLA-B27, but only a
small percentage of people with HLA-B27 will go on to develop AS, rheumatoid arthritis, Crohn’s
disease, or other autoimmune conditions.1 This suggests that an environmental factor must be
driving the connection observed between HLA-B27 and these diseases.
Recent research suggests that Klebsiella may be this factor. Dr. Alan Ebringer at Middlesex Hospital
in London found that Klebsiella has molecules resembling the HLA-B27 blood group.2,3 Although
Klebsiella is a normal resident of the digestive tract, it can overgrow when the gut microbiota is
disrupted or out of balance.
Elevated levels of antibodies to Klebsiella have been found in AS patients, especially during flare-
ups. Researchers speculate that the body produces antibodies to attack the Klebsiella bacteria, but
these antibodies also act upon HLA-B27 proteins in a phenomenon known as “molecular mimicry.”1
The destruction of the HLA-B27 proteins is what causes the joint pain3 and inflammation that
characterizes rheumatic diseases like AS and rheumatoid arthritis, as well as Crohn’s disease.
Michelle’s urine hormone test results showed that she had trouble metabolizing cortisol, which is a
sign of hypothyroidism. Again, cortisol and thyroid markers were not addressed directly in this
case. Instead, restoring gut function normalized cortisol patterns and thyroid function.
Michelle’s case illustrates why I prefer DUTCH testing to saliva testing for cortisol and HPA axis
assessment. Thyroid hormone is required for the metabolic clearance of cortisol. Patients with
hypothyroidism or low T3 levels will have trouble metabolizing cortisol. They often present with
high free cortisol but low cortisol metabolites in the urine. In fact, the ratios between free and
metabolized cortisol as well as cortisol and cortisone are being investigated as markers of
subclinical thyroid hypofunction.4
If you only did a saliva test on this patient for cortisol, you’d assume that her cortisol was high
(because of the high free cortisol). However, metabolized cortisol is a better marker for overall
production. Less than 5 percent of the cortisol in the body is in the free (unbound) form; the rest is
cleared by several metabolic pathways and excreted in the urine.
If you gave this patient supplements to lower cortisol levels, as indicated by the saliva test results,
she would probably get worse. Her metabolized cortisol was low. Cortisol is a potent anti-
inflammatory hormone, and her low levels could be one of the driving factors behind her joint pain
and other inflammatory symptoms.
At the same time, giving her supplements to increase cortisol might also have an adverse effect.
She already had high free cortisol levels, and free cortisol is the most potent form of that
hormone. In this case, the best strategy was once again to address the underlying cause of the
dysfunction, which was the poor thyroid function. But as mentioned earlier, the poor thyroid
function was itself likely a “symptom” of a deeper problem: the disrupted gut microbiota and
microbial overgrowth. A successful and focused functional medicine diagnosis and treatment is
sometimes like peeling an onion!
Metabolic testing (organic acids) showed that she had widespread nutrient insufficiencies. By
treating the gut alone, her nutrient status improved. It is safe to assume that she was able to digest
and assimilate nutrients better once we resolved her gut dysbiosis.
Michelle showed high iron markers, suggesting iron overload, even though she did not meet the strict
diagnostic criteria for hemochromatosis.5 There are many potential causes of iron overload, many of
which are still poorly understood. Also, studies have shown that even people who are heterozygous
for HFE (human hemochromatosis protein) gene mutations can have higher than normal levels of
iron. Because high iron levels can cause symptoms, phlebotomy treatments to lower her iron likely
contributed to her improved sense of wellbeing.
Addressing Michelle’s GI health had far-reaching consequences: it reduced joint inflammation,

improved nutrient status, and normalized cortisol and thyroid markers. Clinically, her improvement
was dramatic. She no longer complained of joint pain, hypothyroid symptoms, gut symptoms, or
cognitive problems.  
References
1. Brent LH, Diamond HS. Ankylosing spondylitis and undifferentiated spondyloarthropathy. Drugs & Diseases
2015; http://emedicine.medscape.com/article/332945-overview. Accessed May 14, 2015.
2. Ebringer A, Wilson C. HLA molecules, bacteria and autoimmunity. Journal of medical microbiology.
2000;49(4):305-311.
3. Rashid T, Ebringer A. Gut-mediated and HLA-B27-associated arthritis: an emphasis on ankylosing

spondylitis and Crohn's disease with a proposal for the use of new treatment. Discovery medicine.
2011;12(64):187-194.
4. Vantyghem MC, Ghulam A, Hober C, et al. Urinary cortisol metabolites in the assessment of peripheral
thyroid hormone action: overt and subclinical hypothyroidism. J Endocrinol Invest. 1998;21(4):219-225.
5. Makker J, Hanif A, Bajantri B, Chilimuri S. Dysmetabolic hyperferritinemia: all iron overload is not
hemochromatosis. Case reports in gastroenterology. 2015;9(1):7-14.
Diabetes and Other Blood Sugar
Disorders Case Study
Restored Blood Sugar Control in a Diabetic Woman
with Gastrointestinal Complaints and  
Nutritional Deficiencies
CASE SUMMARY
Chandra, a 66-year-old woman with type 2 diabetes and gastrointestinal complaints,
experienced a wake-up call when her mother died of diabetes-related complications. Chandra
had a poor diet and a sedentary lifestyle and complained of abdominal pain, nausea, vomiting,
bloating, decreased appetite, and heartburn. Testing confirmed her high blood sugar and
hemoglobin A1c (HbA1c). It also revealed systemic inflammation, low vitamin D and vitamin
B12, and disrupted cortisol patterns. There was evidence of autoimmune attack of thyroid
proteins and intrinsic factor. Her stool test showed bacterial and fungal overgrowth,
Helicobacter pylori, and a significant inflammatory and immune response in the gut. The
treatment protocol included a Paleo diet, physical activity, supplementation to increase
vitamin B12 and vitamin D, and treatment for gastrointestinal (GI) dysbiosis. Finally, there were
supplement and lifestyle interventions to balance thyroid function, HPA axis, and blood sugar.
Over the course of treatment, Chandra had an 80 percent improvement in her GI symptoms;
she lost 19 pounds; and she reported much better energy. Her fasting blood glucose went from
156 mg/dL to 90 mg/dL and hemoglobin A1c went from 8.0% to 5.8%. This case demonstrates
that the progression of diabetes can be prevented with careful attention to diet, physical
activity, hormonal balance, gut health, and nutrition.
Initial Presentation and Lab Testing

Chandra, a 66-year old female, came to see me with the following concerns: abdominal pain with
nausea and vomiting at night, bloating, decreased appetite, heartburn, and type 2 diabetes.
She worked as a software engineer and spent about eight to 10 hours a day sitting in front of a
computer. She did not exercise other than an occasional walk with friends on the weekend. Her diet
was poor and she rarely cooked her own food. Breakfast was usually coffee and a muffin in the car on
the way to work. For lunch, she grabbed something quick from the company cafeteria or a local
restaurant and ate quickly at her desk. For dinner she would get take-out from a local restaurant
most nights during the week and go out to eat on the weekends.
Chandra had a family history of type 2 diabetes and had been diagnosed herself nearly 10 years
before she came to see me. However, she had a strong mistrust of conventional Western medicine
and chose not to take the medications that were prescribed by her primary care physician. She
intermittently took Ayurvedic herbs, which she was more comfortable with, but they failed to bring
her blood sugar down to normal levels.
Although she was not following a diet when she came to see me, she had previously made several
attempts to follow the low-fat, high-carbohydrate diet recommended by organizations like the
American Diabetes Association (ADA). She reported difficulty sticking with this approach: She
always felt hungry, gained weight, and experienced a worsening of her blood sugar.
Chandra’s mother had passed away six months prior to our appointment, largely from
complications related to type 2 diabetes. This served as a wake-up call for Chandra, and she felt
more motivated to address the root causes of her condition, including making the necessary
dietary and lifestyle changes.
Chandra’s poor diet and sedentary lifestyle were obviously contributing to her high blood sugar. I
ran a full panel of laboratory tests to identify any other underlying conditions that may have been
provoking metabolic dysfunction, as well as digestive distress.
TABLE 1A: Routine Laboratory Test Results. Includes standard laboratory ranges and functional (or optimum)
ranges. Results highlighted in yellow are outside of the functional ranges. Results highlighted in red are outside
of the standard lab ranges. Results in orange are outside of the functional range and the laboratory range.
TABLE 1B: Routine Laboratory Test Results, continued.
As expected, Chandra’s fasting glucose (156 mg/dL) and hemoglobin A1c (8.0%) were in the diabetic
range. Surprisingly, her triglycerides and HDL were within the laboratory reference range, although
they were slightly outside of the functional (optimal) range. Other notable findings included:
■ Depressed BUN/creatinine ratio. This is often caused by low muscle mass, which in
Chandra’s case was a result of her sedentary lifestyle.
■ Borderline high LDH. Lactate dehydrogenase (LDH) is an enzyme that is elevated in a
variety of conditions, including liver disease, kidney disease, and pernicious anemia (which
was the likely cause in Chandra’s case, as you’ll see below).
■ Low serum B12. This is more common in people following vegetarian or vegan diets, but does
still occur in omnivores—especially those with gastrointestinal issues or pernicious anemia.
■ Extremely low 25(OH)D. Chandra had one of the lowest vitamin D levels I have ever observed.
■ Moderately elevated total and LDL cholesterol. Chandra’s slightly elevated total and LDL
cholesterol would not concern me on their own, but given her multiple markers of
metabolic dysfunction, further investigation was warranted.
■ Borderline high hs-CRP. High-sensitivity C-reactive protein is a marker of systemic inflammation
that is consistently associated with type 2 diabetes and other metabolic diseases.1
■ Elevated homocysteine. Homocysteine is a sticky, inflammatory protein associated with
metabolic and cardiovascular disease.
■ Elevated TSH, with borderline low T4 and T3. A high thyroid-stimulating hormone (TSH)
level is the most sensitive indicator of hypothyroidism. Chandra’s T4 and T3 levels were
within the lab reference range, but below the functional range.
■ Borderline low zinc-copper ratio. The zinc-copper ratio is best understood as a marker of
inflammation, rather than as a marker of nutritional status of either element. 2
■ Borderline low hemoglobin and hematocrit. This likely signals the early stages of
megaloblastic anemia caused by B12 deficiency.
Based on these initial findings, I ordered additional blood tests, including a more complete thyroid
panel with free T4, free T3, and thyroid antibodies (to determine if Chandra had Hashimoto’s),
post-meal blood sugar testing with a glucometer, and a comprehensive metabolic panel.
FIGURE 1: Thyroid Function Markers and Thyroid Antibodies.
The thyroid panel revealed low levels of free T3, the most active form of thyroid hormone. They
also found elevated thyroglobulin antibodies, which are indicative of Hashimoto’s thyroiditis.
FIGURE 2A: The MetSyn Profile from Genova Diagnostics measures glucose, HbA1c, lipids, inflammation,
and metabolism.
FIGURE 2B: MetSyn Profile, continued.
The MetSyn profile from Genova Diagnostics has a number of markers for diabetes and metabolic
dysfunction. Chandra had elevated LDL particle number, small LDL particle number, insulin, pro-
insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), C-peptide, and leptin
levels. She also had elevated inflammatory markers, such as hs-CRP, interleukin-6 (IL-6), interleukin-8
(IL-8), tumor necrosis factor-alpha (TNF-a), and plasminogen activator inhibitor-1 (PAI-1).
TABLE 2: Glucometer Readings Taken at Home. Blood sugar was measured under fasting conditions, one hour
after eating, or two hours after eating. The suggested ranges are <99 mg/dL fasting, <140 mg/dL one hour
after a meal, and <120 mg/dL two hours after a meal. Colors separate days with multiple readings.
HIGH
HIGH
HIGH
HIGH
NORMAL/BORDERLINE HIGH
NORMAL
NORMAL
I asked Chandra to use a glucometer to test her blood sugar over several weeks, both before and
after meals. Post-meal blood sugar is considered to be a more sensitive predictor of type 2
diabetes progression. The suggested cutoffs are <99 mg/dL fasting, <140 mg/dL one hour after a
meal, and <120 mg/dL two hours after a meal. As you can see, both her fasting and post-meal
glucose readings were consistently elevated, though on a relative basis, her fasting glucose is
higher than her post-meal glucose.
FIGURE 3: Organix Comprehensive Profile from Genova Diagnostics measures urinary markers of B vitamins.
Chandra’s urine organic acids test revealed elevated levels of methylmalonic acid (MMA). The
conversion of succinic acid to methylmalonic acid requires methylcobalamin, an active form of B12.
High levels of MMA suggest active B12 deficiency, which supports the finding of low B12 in
Chandra’s blood work.
FIGURE 4: Intrinsic Factor Antibody Test.

RESULT REFERENCE RANGE
Given that Chandra ate meat regularly but still had low B12 levels, I decided to screen her for
pernicious anemia. Pernicious anemia is an autoimmune condition in which the body attacks either
the parietal cells, which produce intrinsic factor; intrinsic factor itself; or both. Intrinsic factor is
required to absorb B12 from diet or oral supplements, so patients with pernicious anemia will become
B12 deficient even if they are eating sufficient amounts of B12 or taking typical oral forms of B12.
Chandra was positive for antibodies to intrinsic factor.
FIGURE 5A: Comprehensive Stool Analysis from Doctor’s Data. Dysbiotic flora are highlighted in red.
Commensal flora, which may be imbalanced, are highlighted in yellow.
FIGURE 5B: Comprehensive Stool Analysis with Helicobacter pylori stool antigen.
FIGURE 5C: Comprehensive Stool Analysis, continued.
Chandra’s stool test revealed low levels of beneficial E. coli, Enterococcus, and Lactobacillus, high
levels of imbalanced flora such as alpha- and gamma-hemolytic streptococcus. Chandra had
dysbiosis. She showed high levels of the pathogenic bacterium Citrobacter freundii (Figure 5a). She
also had significant fungal overgrowth (as seen under the microscope) in all three stool samples and
tested positive for H. pylori (Figure 5b).
Chandra wasn’t digesting or absorbing her food properly. Chandra’s fecal elastase level was low,
and she tested positive for carbohydrate malabsorption (Figure 5c).
Finally, Chandra’s lysozyme and secretory IgA levels were elevated, indicating inflammation
and immune activation in the gut. This was most likely due to her significant dysbiosis and
fungal overgrowth.
FIGURE 6: Small Intestinal Bacterial Overgrowth Breath Test Results.
Chandra’s breath test results showed a classic “double peak” of both hydrogen and methane,
which strongly suggested small intestine bacterial overgrowth (SIBO).
FIGURE 6: Analysis of Hypothalamic–Pituitary–Adrenal Axis Function Using the Dried Urine Test
Comprehensive Hormones (DUTCH) from Precision Analytical
Chandra’s DUTCH hormone profile revealed high levels of metabolized cortisol, free cortisone, and
free cortisol. Her daily free cortisol and cortisone patterns were abnormal, suggesting a disrupted
diurnal cortisol rhythm. She had an elevated cortisone-to-cortisol ratio. All of these findings are
consistent with type 2 diabetes and metabolic dysfunction (see Discussion).
Initial Treatment Plan
Given all of these findings, we had a lot of work to do after the initial appointment! In a situation
like this, starting with diet and lifestyle change is the most important intervention you can do, since
it is likely the root cause of many if not most of the patient’s pathologies.
I suggested that Chandra follow a Paleo Reset Diet for 60 days, without lowering her carbohydrate
intake (see Discussion). I also suggested that Chandra increase her physical activity. Since she was
almost completely sedentary, I recommended a gentle ramp-up including walking 5,000 steps a day
(which she used a FitBit to track) and two to three days of strength training at the gym to increase
her muscle mass and fat-burning capacity. Later, as her exercise tolerance improved, I would suggest
adding some high-intensity interval training to further increase her fat-burning capacity.
In addition to the diet and lifestyle changes, we needed to address Chandra’s pernicious anemia,
Hashimoto’s hypothyroidism, dysbiosis and fungal overgrowth, H. pylori, gut inflammation, SIBO,
and disrupted HPA axis. If we tried to do this all at once, Chandra would have been taking 20-plus
supplements and almost certainly would have been overwhelmed. Part of the “art” of functional
medicine is figuring out how to layer and structure a treatment with complex, multifactorial
presentations like this.
We began by addressing her gut, B12 and vitamin D deficiency, and HPA axis. Digestive symptoms
were her primary reason for coming to see me, and it’s important to address the patient’s chief
complaint or they will not stick around for long! Moreover, a large body of evidence suggests a
strong association between a disrupted gut microbiome and both metabolic and thyroid
dysfunction. B12 deficiency can have potentially irreversible neurological consequences if not
addressed, and given that Chandra was already 66 years old, I wanted to restore normal B12 levels
as soon as possible. I also knew that B12 deficiency causes fatigue, so she’d be more likely to follow
through on her physical activity prescription once I corrected her B12 deficiency. Finally, high
cortisol can contribute to hyperglycemia, poor thyroid function, and gut imbalances, so I felt it was
important to address this in the initial phase of the treatment plan.
For her gut, I used a botanical antimicrobial protocol that included GI Synergy, Lauricidin, InterFase
Plus, Prescript-Assist, Saccharomyces boulardii, and A-FNG to treat the SIBO, dysbiosis, and fungal
overgrowth. For the H. pylori, I added Jarrow BroccoMax (one capsule three times a day with
meals) and 500 mL per day of 100% cranberry juice, unsweetened. 3,4
TABLE 3: Chandra’s Treatment Protocol with Dosages.

One BID upon rising and before
bed
3 billion CFU twice daily at lunch

Probiotic Saccharomycin DF Xymogen
and before bed
1 packet BID (with breakfast and

dinner)
Med-Chem 1 scoop three times daily with

Antimicrobial Lauricidin
Laboratories meals
Slowly build to 20-30 drops BID

Antimicrobial A-FNG Byron White Formulas
with meals
3-4 capsules BID on an empty

Antimicrobial InterFase Plus Klaire Labs
stomach
Microbial
BroccoMax Jarrow Formulas 1 capsule TID with meals
balance
Microbial Cranberry juice,

500 mL/day
balance unsweetened
Extra Virgin Cod Liver

Nutrition Rosita Real Foods 1 tsp/day
Oil
Nutrition Trifolamin Designs for Health 1 lozenge (5 mg)/day
Nutrition Micellized Vitamin D3 Klaire Labs 10,000 IU/day
HPA-axis
HPA Balance Vital Plan 2 caps twice daily with food
support
HPA-axis
Acetyl-CH Apex Energetics 1 cap three times daily with food
support
For B12 deficiency, I used Trifolamin from Designs for Health. Trifolamin provides a synergistic
combination of the three bioavailable forms of B12: methylcobalamin, adenosylcobalamin, and
hydroxycobalamin, in a five mg sublingual lozenge. Sublingual delivery is crucial for patients with
pernicious anemia because their intestinal absorption of B12 from diet or oral supplements is
limited. I had Chandra take one lozenge per day and instructed her to continue this indefinitely.
For vitamin D, I prescribed one tsp/d of Extra Virgin Cod Liver Oil (to provide whole-food forms of
both vitamin D and vitamin A, which work synergistically together), along with 10,000 IU of
Micellized Vitamin D3 from Klaire Labs. I did not think that cod liver oil alone would be sufficient to
raise her vitamin D quickly, and I prescribed a micellized form of D3 because Chandra had several
gut conditions that could lead to malabsorption.
For her HPA axis, I prescribed a number of behavioral and lifestyle modifications, including restricting
exposure to artificial light at night and ensuring at least 20 to 30 minutes of bright light exposure
during the day (which she accomplished by taking a walk for half of her lunch hour), getting at least
eight hours of sleep a night, and practicing mindfulness-based stress reduction at least three times a
week. I also prescribed supplements to regulate her diurnal cortisol rhythm and reduce her cortisol,
including HPA Balance from Vital Plan (two capsules twice a day, with breakfast and dinner) and
Acetyl-CH Active from Apex Energetics (one capsule three times a day, with meals).
Sixty-Day Follow-up: Clinical Outcome and

Additional Testing
After 60 days of this protocol, Chandra’s digestive symptoms were 80 percent resolved, her energy
levels improved significantly, she lost 19 pounds, and her blood sugar had dropped from the
diabetic range to the pre-diabetic range. Her follow-up tests results also showed significant
improvements across the board.
FIGURE 8: Follow-up Thyroid Function Markers, Iron, and Vitamins D and B12.
Her free T3 levels were now well within the normal range. Inflammation and poor gut health reduce
the conversion of T4 to T3, so it is likely that the dietary and lifestyle changes Chandra made
improved her thyroid function. This is why I often do not address thyroid directly in the first step of
the treatment in situations like this. Her vitamin D upon follow-up was firmly within the normal
range, as was her serum vitamin B12.
FIGURE 9: Urinary Organic Acid Markers Show Adequate Vitamin B12 Levels after 60 Days of Treatment.
Her urine methylmalonate normalized, indicating that she had sufficient levels of active vitamin B12.
FIGURE 10A: Comprehensive Stool Analysis Results after 60 Days of Treatment.
FIGURE 10B: Comprehensive Stool Analysis Results after 60 Days of Treatment, continued.
FIGURE 10C: Comprehensive Stool Analysis Results after 60 Days of Treatment, continued.
Chandra’s follow-up stool test showed much-improved levels of beneficial bacteria and eradication
of Citrobacter freundii and fungal overgrowth. Previously, her stool test showed many fungal cells
under the microscope for all three stool samples. In this test, no fungal cells were seen for any of
the samples. The Candida parapsilosis at 1+ growth did not strike me as a clinically relevant issue
for her. Her follow-up stool antigen test for H. pylori was negative, indicating that the infection had
been cleared.
Chandra’s digestion improved. Her elastase and carbohydrate absorption markers normalized. Her
gut inflammation decreased: Both lysozyme and sIgA decreased significantly. This suggests that
her immune reactivity normalized, most likely because Citrobacter, fungus, and H. pylori had been
removed. At the time of this writing, there were no follow-up results on Chandra’s systemic
inflammatory markers. But considering that dysbiosis and inflammation decreased in the gut,
systemic markers of inflammation could have easily improved. Her sIgA was low on this test,
whereas it was high on the initial test. This is not uncommon, in my experience, and sIgA is often
one of the last markers to improve when addressing gut health.
FIGURE 11: Follow-up SIBO Test Results
Her SIBO breath test results were normal after 60 days of treatment. Her hydrogen and methane
breath gases normalized, suggesting that bacterial overgrowth in the small intestine was no longer
an issue for Chandra. 
FIGURE 12: Follow-up Results for HPA Axis Function using the DUTCH Test.
Her DUTCH hormone profile revealed completely normal cortisol production. Frankly, I was quite
surprised by this, as it often takes much longer to address HPA axis dysfunction, especially if it is a
primary cause of symptoms. It is possible that Chandra’s mother’s death caused an unusual spike in
her cortisol levels on her initial DUTCH test (Figure 7) that naturally normalized as time passed. It is
also possible that interventions to normalize sleep patterns, remove gut infections, reduce body
weight, and increase physical activity had a significant impact on Chandra’s HPA axis function.
Treatment Plan Modifications Made after 60 Days

Even after 60 days of treatment, Chandra’s TSH was still elevated. I felt that her thyroid needed
additional support at that point. I prescribed a desiccated thyroid glandular supplement (from Nutri-
Meds) because Chandra preferred not to take pharmaceuticals. Antimicrobials were discontinued at
this time but other interventions continued, including HPA axis support and dietary changes.
120-Day Follow-up: Clinical Outcome and

Additional Testing
After 60 days on the desiccated thyroid, we re-tested Chandra’s thyroid numbers again, and they
were normal. I also re-tested her blood sugar. After 120 days of overall treatment, Chandra’s fasting
glucose and HbA1c were still elevated, but they were significantly improved. Her results were
toward the bottom of the pre-diabetic range, rather than well within the diabetic range.
FIGURE 13: Follow-up Results for Thyroid Markers after 120 Days of Treatment.
FIGURE 14: Chandra’s Glucose and HbA1c after 120 Days of Treatment.
Ideally, I’d like to get Chandra’s blood sugar levels into the normal ranges. However, not all cases of
diabetes can be reversed with natural interventions. In cases where type 2 diabetes has been
present for many years and beta cell destruction may have occurred, it may not be completely
reversible with diet and lifestyle changes and supplementation alone. This is particularly true if
leptin and insulin are as elevated as they were for Chandra on her initial test (Figure 2b). The drug
metformin may be a good option to further improve glucose control in cases like Chandra’s,
though the potential benefits of the small reduction in fasting glucose and A1c that we’d be likely
to observe would have to be weighed against the side effects and risks of the medication.
Treatment Plan Modifications after 120 Days

Nutraceuticals are another option for further reduction of blood sugar in cases like this. I prescribed
two supplements: Metabolic Synergy (two capsules three times a day with meals) and GlucoSupreme
(two capsules twice a day with meals) from Designs for Health. These products contain a number of
nutrients and botanicals that support blood sugar regulation. No other changes were made to the
treatment protocol at this time.
FIGURE 15: One Hundred Eighty-Day Follow-up Testing: Blood Glucose Regulation.
After an additional 60 days on these supplements (amounting to 180 days total of treatment),
Chandra had a fasting glucose <100 mg/dL for the first time in 10 years. Her HbA1c was still
elevated, as were some of her post-meal glucose levels. However, this is a remarkable
improvement using only diet and lifestyle changes and supplements.
Discussion
Chandra was a 66-year-old untreated diabetic woman with significant gastrointestinal symptoms
and poor dietary and lifestyle habits. Chandra had marked improvement of GI symptoms, energy,
and blood sugar after six months of a Paleo diet, normalization of HPA axis function, nutritional
supplementation for pernicious anemia and vitamin D, treatment for GI dysbiosis and
inflammation, and supplements to support thyroid function and blood sugar regulation.
Dietary Recommendations
I suggested that Chandra follow a Paleo Reset Diet for 60 days. Numerous studies have shown
that Paleo is effective for reducing blood sugar and improving inflammatory markers and that it
is more satiating per calorie than Mediterranean or low-fat diets, which makes it easier for
patients to follow.5 ,6
I did not specifically instruct Chandra to lower her carbohydrate intake for two reasons. First, the
Paleo diet studies that showed significant improvement in metabolic function were not very-low-
carb diets; they typically ranged between 20 and 30 percent of calories from carbohydrate. I
believe that carbohydrate quality (e.g., eating whole-food, unrefined carbohydrates rather than
highly refined carbohydrates) is more important than carbohydrate quantity in most cases, and if
significant weight loss and metabolic improvement is possible without severely restricting an entire
macronutrient category, that is preferable from a general health and compliance perspective.
Second, most patients that follow a Paleo diet naturally eat fewer carbohydrates, since their
choices of carbohydrate are limited to starchy plants like sweet potatoes and fruits.
Nutrition
VITAMIN D
Chandra had one of the lowest vitamin D levels I have ever observed—8.3 ng/mL (Table 1a). I
recommend vitamin D serum levels of 25–50 ng/mL. Chandra spent very little time outdoors and
did not take a vitamin D supplement. She was of East Indian descent and had relatively dark skin,
which means she produced less 25(OH)D in response to sun exposure than people with lighter
skin. Low levels of vitamin D are associated with metabolic dysfunction in numerous studies.7
VITAMIN B12 AND PERNICIOUS ANEMIA

Chandra had very low levels of vitamin B12, high urinary methylmalonate (Figure 3), very high
homocysteine, low hemoglobin, and low hematocrit. Homocysteine is a sticky, inflammatory
protein associated with metabolic and cardiovascular disease (Table 1a). Vitamin B12 and folate are
required to convert homocysteine back into methionine in the methylation cycle; thus, Chandra’s
B12 deficiency was the likely cause of her high homocysteine level.
Given that Chandra ate meat regularly but still had low B12 levels, I decided to screen her for
pernicious anemia. Pernicious anemia is an autoimmune condition in which the body attacks either
the parietal cells, which produce intrinsic factor; intrinsic factor itself; or both. Intrinsic factor is
required to absorb B12 from diet or oral supplements, so patients with pernicious anemia will
become B12 deficient even if they are eating sufficient amounts of B12 or taking typical oral forms
of B12. Chandra was positive for antibodies to intrinsic factor (Figure 4). This test approaches 100
percent specificity, which means that if it is positive, it is almost certain that the patient has
pernicious anemia. (Note that although intrinsic factor antibodies are highly specific, they are only
50 to 70 percent sensitive. This means that 30 to 50 percent of patients with pernicious anemia
will not have antibodies to intrinsic factor.)8
Borderline low hemoglobin and hematocrit (Table 1b) likely pointed to the early stages of
pernicious anemia caused by B12 deficiency. B12 deficiency progresses in four stages, and it is only
in the final stage that the patient becomes anemic. This is one of many reasons that it is important
to test B12 levels on a routine blood panel. Unfortunately, this is rarely done in conventional
medicine. Chandra had no idea that she was B12 deficient and had pernicious anemia prior to her
appointment with me, and she was 66 years old!9
HPA DYSFUNCTION AND DIABETES

Chandra had high levels of metabolized cortisol, free cortisone, and free cortisol. Her daily free
cortisol and cortisone patterns were abnormal, suggesting a disrupted diurnal cortisol rhythm. She
had an elevated cortisone-to-cortisol ratio. This was consistent with research showing an association
between metabolic dysfunction, high cortisol levels, and excess weight and type 2 diabetes.10,11
Fat tissue can contribute to HPA axis dysfunction. Fat tissue itself releases cortisol. 12,13 The
relationship between HPA axis function and obesity is bi-directional and most studies have not
been able to show a causal relationship between high free cortisol (HPA axis dysfunction) and
obesity. However, studies do show increased clearance of cortisol (and thus higher cortisol
metabolites) with increasing weight.14 There is a stepwise relationship between urinary cortisol
metabolites and body BMI, even at levels that aren’t obese.15 In addition, the conversion of
cortisone to cortisol is impaired in obesity, which leads to a high ratio of cortisone to cortisol in
these patients.16
THYROID FUNCTION
Chandra had high TSH, low-normal T4 and T3 (Table 1b), and low levels of free T3, the most active
form of thyroid hormone (Figure 1). She had elevated thyroglobulin antibodies, which are
indicative of Hashimoto’s thyroiditis. This suggested that Chandra’s thyroid dysfunction was
caused by autoimmunity. Some studies suggest that thyroid autoimmunity may contribute to
endothelial dysfunction and other metabolic and cardiovascular abnormalities.17
GASTROINTESTINAL HEALTH AND DIABETES
Chandra had very low fecal pancreatic elastase, suggesting difficulty with digestion (Figure 5c).
Studies have found a strong correlation between low fecal elastase and type 2 diabetes.18 She also
had SIBO (Figure 6). One study found an association between delayed orocecal transit time/SIBO
and patients with type 2 diabetes, but it was unclear whether SIBO contributed to type 2 diabetes,
or the other way around.19 Nevertheless, I frequently see these conditions appear together in
clinical practice, and the relationship is likely bi-directional.
Conclusions
Chandra had a strong family predisposition to diabetes that was compounded by a sedentary
lifestyle and a poor diet. She was diabetic and headed down a path of diabetes-related
complications and an increased risk of death. Chandra had significant gastrointestinal symptoms
including abdominal pain with nausea and vomiting, bloating, decreased appetite, and heartburn.
Lab testing showed elevated blood glucose and HbA1c, extremely low vitamin D, inflammation,
pernicious anemia, Hashimoto’s thyroiditis and associated thyroid dysfunction. She had gut
dysbiosis including bacterial and fungal overgrowth and colonization with H. pylori. She wasn’t
digesting or absorbing her food and showed signs of inflammation and immune upregulation in
the GI tract. Finally, her cortisol diurnal rhythm and cortisol metabolism were disturbed.
Treatment primarily focused on diet and physical activity, gut dysbiosis, vitamins B12 and D, HPA
axis function, and thyroid support. After 60 days, Chandra had an 80 percent reduction in her GI
symptoms and had lost 19 pounds. She reported significant energy improvements. After 180 days
of treatment, thyroid function markers had normalized, and her fasting glucose was < 100 mg/dL
for the first time in 10 years. Laboratory markers confirmed that blood glucose was better
regulated, vitamin levels improved, gut dysbiosis resolved, and HPA and thyroid function
normalized. This case demonstrates that the course of diabetes and pre-diabetes can be halted,
and even reversed, with careful attention to diet, physical activity, hormonal balance, gut health,
and customized nutrition.
References 
1 Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of
developing type 2 diabetes mellitus. JAMA. 2001;286(3):327-334.
2 Malavolta M, Giacconi R, Piacenza F, et al. Plasma copper/zinc ratio: an inflammatory/nutritional biomarker
as predictor of all-cause mortality in elderly population. Biogerontology. 2010;11(3):309-319.
3 Fahey JW, Haristoy X, Dolan PM, et al. Sulforaphane inhibits extracellular, intracellular, and antibiotic-
resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl
Acad Sci U S A. 2002;99(11):7610-7615.
4 Shmuely H, Domniz N, Yahav J. Non-pharmacological treatment of Helicobacter pylori. World J
Gastrointest Pharmacol Ther. 2016;7(2):171-178.
5 Mellberg C, Sandberg S, Ryberg M, et al. Long-term effects of a Palaeolithic-type diet in obese
postmenopausal women: a 2-year randomized trial. Eur J Clin Nutr. 2014;68(3):350-357.
6 Jonsson T, Granfeldt Y, Erlanson-Albertsson C, Ahren B, Lindeberg S. A paleolithic diet is more satiating per
calorie than a mediterranean-like diet in individuals with ischemic heart disease. Nutrition & metabolism.
2010;7:85.
7 Dhas Y, Mishra N, Banerjee J. Vitamin D Deficiency and Oxidative Stress in Type 2 Diabetic Population of
India. Cardiovasc Hematol Agents Med Chem. 2016.
8 Carmel R. Pepsinogens and other serum markers in pernicious anemia. Am J Clin Pathol. 1988;90(4):
442-445.
9 Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr. 1994;59(5 Suppl):
1213S-1222S.
10 Costa DS, Conceicao FL, Leite NC, Ferreira MT, Salles GF, Cardoso CR. Prevalence of subclinical
hypercortisolism in type 2 diabetic patients from the Rio de Janeiro Type 2 Diabetes Cohort Study. Journal of
diabetes and its complications. 2016.
11 Abraham SB, Rubino D, Sinaii N, Ramsey S, Nieman LK. Cortisol, obesity, and the metabolic syndrome: a
cross-sectional study of obese subjects and review of the literature. Obesity (Silver Spring).
2013;21(1):E105-117.
12 Stimson RH, Andersson J, Andrew R, et al. Cortisol release from adipose tissue by 11beta-hydroxysteroid
dehydrogenase type 1 in humans. Diabetes. 2009;58(1):46-53.
13 Rask E, Walker BR, Soderberg S, et al. Tissue-specific changes in peripheral cortisol metabolism in obese
women: increased adipose 11beta-hydroxysteroid dehydrogenase type 1 activity. J Clin Endocrinol Metab.
2002;87(7):3330-3336.
14 Abraham SB, Rubino D, Sinaii N, Ramsey S, Nieman LK. Cortisol, obesity, and the metabolic syndrome: a
cross-sectional study of obese subjects and review of the literature. Obesity (Silver Spring).
2013;21(1):E105-117.
15 Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH. Cortisol metabolism in human obesity:
impaired cortisone-->cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab.
1999;84(3):1022-1027.
16 Ibid.
17 Isguven P, Gunduz Y, Kilic M. Effects of Thyroid Autoimmunity on Early Atherosclerosis in Euthyroid Girls
with Hashimoto's Thyroiditis. Journal of clinical research in pediatric endocrinology. 2016;8(2):150-156.
18 Kangrga RN, Ignjatovic SD, Dragasevic MM, Jovicic SZ, Majkic-Singh NT. Pancreatic Elastase Levels in
Feces As A Marker of Exocrine Pancreatic Function in Patients With Diabetes Mellitus. Lab Med. 2016;47(2):
140-148.
19 Rana S, Bhansali A, Bhadada S, Sharma S, Kaur J, Singh K. Orocecal transit time and small intestinal
bacterial overgrowth in type 2 diabetes patients from North India. Diabetes Technol Ther. 2011;13(11):1115-1120.
Thyroid Disorders Case Study
Hypothyroidism Resolved by Restoring Iodine Levels
CASE SUMMARY
A 26-year-old woman complained of classic hypothyroid symptoms, had been given a
hypothyroid diagnosis, and wanted to investigate natural alternatives to treatment with
levothyroxine. Thyroid function tests, iron, and vitamin D were abnormal. Testing of
gastrointestinal health suggested dysbiosis, especially bacterial overgrowth, and inflammation.
She had difficulty metabolizing cortisol, a feature of hypothyroidism. Her diet was extremely
low in iodine and she was eating goitrogenic foods, which pointed to iodine deficiency.
Treatment included kelp tablets, selenium-rich foods, cod liver oil, an antimicrobial protocol,
probiotics, and lifestyle changes and supplements to support HPA axis function. After three
months on this program, her hypothyroid symptoms improved dramatically and her TSH and
other thyroid markers normalized—without any medication at all.
Janel, 26, came to see me after being diagnosed with hypothyroidism. She was overweight, her
hands and feet “felt like icicles,” her hair was falling out, and she was constipated.
Her doctor prescribed levothyroxine, a synthetic thyroid hormone, but Janel wanted to know why
her thyroid wasn’t working properly and whether there was something she could do to address her
condition without resorting to medication.
I ran a thyroid panel (TSH, T3, T4, free T3, free T4), complete blood count (CBC), comprehensive
metabolic panel, and some other blood tests available through standard laboratories such as iron
and vitamin D. Because of her constipation and hypothyroid symptoms, I also ran tests on her
gastrointestinal function using a small intestinal bacterial overgrowth (SIBO) breath test, a stool
analysis, and urinary organic acids to look for dysbiosis. I ordered a panel to look at her
hypothalamic-pituitary-adrenal (HPA) axis function and a urine iodine test.
My panel of initial tests returned the following notable results.
FIGURE 1: Thyroid Function Tests and Complete Blood Count.
Janel’s thyroid-stimulating hormone (TSH) was significantly elevated at 23.77. Her total and free T4
were well within the normal reference range, but both her total T3 and free T3 were low-normal.
Total T3 was 77 ng/dL (range: 71–180) and free T3 was 2.3 pg/mL (range: 2–4.4). These levels are
below what I consider to be optimal (i.e., outside of the functional range). Janel also had low levels
of vitamin D and high levels of iron, both of which are associated with poor thyroid function.
FIGURE 2: Preliminary Testing Including Serum Iron, Vitamin D, Lipids, C-Reactive Protein, and Homocysteine.
FIGURE 3: Small Intestinal Bacterial Overgrowth Breath Test Results.
Breath testing revealed the presence of bacterial overgrowth in the small intestine. The SIBO test is
based on this concept: an oral lactulose challenge will be fermented by small intestinal bacteria
and excreted by the body in the form of hydrogen and methane breath gases. Janel’s results
showed high methane and hydrogen breath gases.
SIBO may impair the absorption of several nutrients that are important for thyroid health, such
as zinc, selenium, and iodine. On the other hand, some studies have shown that hypothyroidism
may contribute to SIBO by decreasing intestinal motility.1 It is therefore difficult to know if SIBO
caused Janel’s hypothyroidism or if her hypothyroidism caused SIBO. 
FIGURE 4A: Comprehensive Stool Analysis & Parasitology from Doctor’s Data. Dysbiotic flora are highlighted
in red. Opportunistic, or imbalanced, flora are highlighted in yellow.
Janel’s stool test showed a 3+ growth for Citrobacter koseri, a species of bacteria that can be
pathogenic when overrepresented in the GI tract. Janel had adequate levels of beneficial flora
(Bifidobacteria and Lactobacillus, for example) but some imbalanced flora were accumulating
(Pantoea species, Comamonas kerstersii, etc.). These may or may not have contributed to her
symptoms. No fungi or parasites were detected on her test.
FIGURE 4B: Comprehensive Stool Analysis & Parasitology (continued) Showing Markers of Digestion,
Inflammation, and Immune Function.
Janel’s stool test revealed elevations in lactoferrin and lysozyme. When significantly elevated, these
markers are indicative of active inflammatory bowel disease (IBD). When only mildly elevated,
however, they often represent inflammation secondary to pathogenic microbes or other causes.
She had a very high secretory immunoglobulin A (sIgA), a marker of immune function in the GI
tract. This high level suggested that her immune system was in overdrive, possibly due to bacterial
overgrowth (C. koseri) or another underlying inflammatory pathology. 
FIGURE 5: Urine Organic Acids from Great Plains Laboratory, Showing Markers of Bacterial and Yeast Metabolism.
Her urine organic acids test (OAT) had several markers for gut dysbiosis, particularly an
overgrowth of Clostridia species (HPHPA) that produce known neurotoxins and a marker that may
be associated with fungal overgrowth (5-hydroxymethyl-2-furoic acid). The SIBO, stool, and
organic acids tests showed that Janel had moderate dysbiosis (primarily bacterial). 
FIGURE 6: Analysis of HPA-axis Function Using the Dried Urine Test Comprehensive Hormones (DUTCH) from
Precision Analytical.
A hormone test assessing her hypothalamic-pituitary-adrenal (HPA) axis function revealed high
free cortisol, but low metabolized (total) cortisol. Janel’s free cortisol was 31 (range: 11–31) and her
metabolized cortisol was 2184 (range: 2240–4300). Hypothyroidism impairs the body’s ability to
metabolize cortisol, so this pattern of high free cortisol but low total metabolized cortisol
suggested that Janel had poor thyroid function and could not metabolize cortisol properly. This
test also showed a disrupted diurnal cortisol rhythm. The normal range is represented by the two
black lines on the bar graph. Janel’s cortisol results, represented by the red line, showed high
cortisol in the morning, afternoon, and night samples.
As I reviewed Janel’s dietary survey, I noticed that she didn’t eat seafood or seaweed (because of
an allergy), and that she used sea salt rather than iodized salt. I also noted that she was consuming
a green smoothie with large amounts of raw kale every morning. Kale is a goitrogen that can
inhibit iodine uptake in the thyroid gland. Because of her low intake of iodine and high intake of
raw kale, I suspected she was iodine deficient, which I confirmed with a 24-hour urine iodine test.
For treatment, I started Janel on an iodine protocol and asked her to eat more selenium-rich food,
such as Brazil nuts. (She was already eating a “Paleo template” diet.) I told her to limit her
goitrogenic foods to three to six servings a week and make sure to cook those foods to reduce
their effects on thyroid function. I also prescribed a high-vitamin, extra-virgin cod liver oil to bring
up her vitamin D levels (while also providing vitamin A and omega-3 fatty acids).
I treated her SIBO, bacterial overgrowth, and inflammatory markers by using a botanical
antimicrobial protocol for 30 days. GI Synergy (Apex Energetics) and InterFase Plus (Klaire Labs)
are designed to remove bacteria, fungi, and parasites in the gastrointestinal tract. MegaSporeBiotic
is a probiotic and antioxidant formula that rebuilds beneficial gut bacteria but also has an
antimicrobial effect (it contains Bacillus species probiotics, which some pharmaceutical antibiotics
have been isolated from). Because Janel had elevated methane breath gases, I gave her Ideal
Bowel Support (Jarrow Formulas), which is a beneficial bacteria (Lactobacillus plantarum) that
degrades methane.
I addressed her HPA axis dysregulation with a comprehensive program including circadian
regulation (controlling exposure to light during day and evening), stress management, adaptogens,
and other nutrients to support HPA axis function and improve cortisol metabolism.
Finally, I had her donate blood to reduce her iron levels into an optimal range.  
TABLE 1: Janel’s Treatment Protocol with Dosages.
Two tablets, once a day.

After three months,
Iodine Kelp tablets NOW
reduce to one tablet, once
a day.
1 packet BID (with

breakfast and dinner)
3-4 capsules BID on an

Antimicrobial InterFase Plus Klaire Labs
empty stomach
One BID upon rising and

before bed
Probiotic/antimi-
MegaSporeBiotic MegaSporeBio- tic One capsule with lunch
crobial
L. plantarum for
Probiotic Ideal Bowel Support Jarrow Formulas
methanogens
2 caps twice daily with

HPA axis support HPA Balance Vital Plan
food
2 caps one hour before

HPA axis support Kavinace Neuroscience
bed
1 cap three times daily

HPA axis support Acetyl-CH Apex Energetics
with food
After three months on this program, her hypothyroid symptoms had improved dramatically and
her TSH and other thyroid markers had normalized—without any medication at all (Figure 7).  
FIGURE 7: Thyroid Function Tests after Treatment.
Her HPA axis function improved, with normalization of her total free cortisol production as well as
the free cortisol diurnal rhythm. On her first test of HPA axis function, Janel had high free cortisol
but low metabolized cortisol. Her follow-up test showed a decreased total free cortisol of 14.0
(range: 11–31) and an increased metabolized cortisol of 2625 (range: 2240–4300), placing her in
the normal ranges for both results. On her initial test, she also had high cortisol in the morning,
afternoon, and night. After treatment, her cortisol levels decreased and she had normal cortisol
upon waking and in the morning, afternoon, and night.  
FIGURE 8: Analysis of HPA Axis Function Using the DUTCH Test after Treatment.
Janel no longer complained of cold hands and feet and her hair loss slowed down dramatically
until it wasn’t an issue anymore. She started having regular bowel movements. She was pleased
and empowered to resolve her thyroid condition without taking medications. 
References
1Patil, A. (2014). Link between hypothyroidism and small intestinal bacterial overgrowth. Indian Journal of
Endocrinology and Metabolism, 18(3), 307.
Digestive Disorders Case Study
High-powered Executive with Dysbiosis and  
Gluten Sensitivity
CASE SUMMARY
A high-powered executive wanted to improve his mental and physical performance, lose
weight, and lower cholesterol. Laboratory testing showed that he didn’t have enough
beneficial flora, he had a parasite, and had fungal overgrowth in his gastrointestinal tract. He
also was sensitive to gluten, wheat, eggs, dairy, and sesame. After removing the foods and
doing a 30-day protocol to remove dysbiotic bacteria, fungi, and parasites, as well as
rebuilding beneficial bacteria, this hard-working professional felt a noticeable mental and
physical improvement. Lab testing reflected the efficacy of treatments. His cholesterol
remained unchanged, however, suggesting familial hypercholesterolemia.
Joe was a 41-year-old, high-powered CEO of a well-known tech corporation. His chief complaint
was very high cholesterol. He didn’t feel unwell; he just wanted to optimize mental and physical
performance and maybe lean out a little bit. Occasionally he experienced post-nasal drip. He also
reported infrequent insomnia and fatigue that seemed mostly lifestyle-related. This was no
surprise; he was burning the candle at both ends, as is often the case with business CEOs.
FIGURE 1: Genova Diagnostics Bacterial Overgrowth of the Small Intestine (BOSI/SIBO).
The concept of the small intestinal bacterial overgrowth (SIBO) breath test is that if a patient takes
a lactulose challenge drink, excessive levels of bacteria in the small intestine will ferment the
lactulose and produce hydrogen and/or methane gas(es). These gases are absorbed into the
bloodstream and released into the breath. An early rise in breath gases, within the first hour or so
after taking lactulose, typically indicates bacterial overgrowth in the proximal small intestine.
If we use the conventional criteria for interpreting Joe’s SIBO breath test results, they would be
negative. However, Dr. Mark Pimentel, a global expert in SIBO diagnosis and treatment, has
suggested that a methane level above three parts per million at any point during the first 120
minutes of the test should be considered a positive result. Using these criteria, Joe’s results would
be positive, since his methane levels were 12 at baseline and 13 ppm, 20 minutes into the test. His
hydrogen levels were normal. With a borderline result like this, and lack of gut symptoms, other lab
findings are necessary to better understand what the breath test means for Joe’s gut health.
FIGURE 2: Doctor’s Data Comprehensive Stool Analysis & Parasitology (DD CSAP).
Joe’s stool test showed significant dysbiosis. He showed no growth at all of beneficial bacteria
such as Bifidobacterium, beneficial E. coli or Lactobacillus. He had mild fungal overgrowth,
reported as “few” on the microscopic yeast exam for all three of his stool specimens. Joe was
positive for the parasite, Dientamoeba fragilis. Its pathogenicity has been somewhat controversial,
but many studies suggest that it can cause symptoms in at least some patients.
Joe’s results were normal for digestion, inflammation, and immune function in the GI tract.
Urinary organic acid results showed that Joe was negative for bacterial or fungal overgrowth in
the small intestine.
FIGURE 3: Gluten, Wheat and Food Sensitivities from Cyrex Laboratories. Array 3 (Wheat/Gluten
Proteome Reactivity & Autoimmunity) measures immune reactions to gluten and other peptides
found in wheat, while Array 4 (Gluten-Associated Cross-Reactive Foods and Food Sensitivity)
measures immune reactivity to proteins in foods, some of which may be cross-reactive with gluten.
For example, in some patients with Celiac disease, antibodies that react with gluten may also react
with casein, whey, or other proteins found in dairy products.
I ran Array 3 and Array 4 from Cyrex Laboratories on Joe to look for immune reactions to wheat
and gluten-associated cross-reactive foods. He wasn’t eating a lot of gluten, but he was eating it
occasionally when he traveled and ate out. Joe wanted to find out whether it was really a problem
for him, and sure enough it was. In Array 3, you can see he’s got IgA antibodies to native and
deamidated gliadin, alpha-gliadin, and gamma-gliadin. Joe is also showing IgA antibodies to
gliadin transglutaminase complex and wheat. On Array 4, he tested positive for dairy, cow’s milk,
casein, and chocolate milk, sesame and egg.
So, interestingly enough, Joe was producing IgA antibodies, rather than IgG antibodies, to wheat
and gliadin proteins. Given his immune reactions to native and deamidated gliadin antibodies,
alpha-gliadin antibodies and the gliadin transglutaminase complex, I suspected Joe had gluten
intolerance, and possibly even celiac disease. Upon my recommendation, Joe agreed to completely
cut out gluten and the other foods he tested positive for on Array 4. He didn’t really see the need
for getting a follow-up test for celiac disease because he was fine with just completely removing
wheat and the other proteins he was reacting to.  
FIGURE 4: Assessment and Diagnosis Based on Lab Findings.
I diagnosed Joe with borderline SIBO, insufficiency dysbiosis (meaning that his good bacteria were
too low), fungal overgrowth, and parasitic infection with Dientamoeba fragilis. Joe also showed
gluten intolerance (possibly celiac disease) and some other food intolerances on the Cyrex panels.
FIGURE 5: Joe’s Treatment Protocol with Dosages.
Joe’s main complaint was high cholesterol; gut issues can be a major contributor to high
cholesterol, and I have seen significant changes in cholesterol levels in the past after addressing
gut dysfunction, even in patients with no gut symptoms.
Joe wanted to approach high cholesterol from a functional perspective, instead of just taking
statins, so he was motivated to address some of these underlying causes to see if that would  
bring down his cholesterol levels. Joe didn’t want to do pharmaceuticals to begin with so we
started with supplements.
I decided to prescribe an antimicrobial botanical protocol for 30 days based on Joe’s borderline
SIBO, the D. fragilis, and the fungal overgrowth. GI Synergy (Apex Energetics), Lauricidin (Med-
Chem Labs), and Interfase Plus (Klaire Labs) are designed to remove bacteria, fungi, and parasites
in the gastrointestinal tract. MegaSporeBiotic is a probiotic and antioxidant formula that rebuilds
beneficial gut bacteria, but also has an antimicrobial effect (it contains Bacillus species probiotics,
which some pharmaceutical antibiotics have been isolated from).
I added a few things based on his presentation. Because he had elevated methane breath gases, I
gave him Ideal Bowel Support (Jarrow Formulas), which is a beneficial bacteria (Lactobacillus
plantarum) that degrades methane. I gave him A-FNG (Byron White Formulas) and Saccharomyces
boulardii (Saccharomycin DF from Xymogen) for the fungal overgrowth. Saccharomyces boulardii
can also help to remove parasites and thereby lower Joe’s D. fragilis.
If it was just insufficiency dysbiosis, I wouldn’t have done antimicrobials. I would have gone right to
prebiotics and probiotics to rebuild his beneficial gut flora.
FIGURE 6: Follow-up Test for Small Intestinal Bacterial Overgrowth (Commonwealth Labs).
A follow-up SIBO breath test with Commonwealth Labs showed all zeroes for hydrogen (negative).
Joe’s methane was lower than it was on the initial test, but still slightly elevated at baseline.
Although these results would still be considered positive according to Dr. Pimentel’s criteria, given
that he had no gut symptoms, and his highest methane value was only three parts per million, I did
not feel that further treatment was necessary.  
FIGURE 7: Follow-up Comprehensive Stool Analysis & Parasitology (DD CSAP) Test
!
Joe’s follow-up stool test showed significant improvement in beneficial bacteria:

Bifidobacterium, E. coli, and Lactobacillus. Fungi were no longer detected on the microscopic
exam, suggesting that we got his fungal overgrowth under control. There was 1+ for Candida still
showing, but that can be just normal flora, so it didn’t require treatment. Joe’s follow-up test was
negative for the parasite, D. fragilis.
Unfortunately, in this case, Joe’s cholesterol didn’t come down after addressing his gut issues. His
cholesterol was very high, over 300. If cholesterol levels are that high, and they don’t respond to
addressing these underlying problems, it’s most likely genetic in origin. This patient probably has
familial hypercholesterolemia. On the other hand, his mental and physical performance did
improve, and he lost weight and felt better overall, so the treatment was successful from  
that perspective.
The next step with Joe would be to make specific dietary, lifestyle, and supplement
recommendations to manage his high cholesterol levels, and to do further testing to determine his
overall level of risk (e.g. inflammatory markers like Lp-PLA2, L(p)a, ox-LDL and CT scans to
determine his calcium score and carotid intima media thickness).  
Clinician’s Guide to Hypothalamic–
Pituitary–Adrenal Axis Dysregulation:
Case Study
Dietary and Lifestyle Treatments Alone Improve
Energy and Normalize Sleep Patterns in a High-
Performance Mother and Business Owner
CASE SUMMARY
A 42-year-old mother of four and business owner complained of fatigue and exhaustion, sleep
disturbance, anxiety, and weight gain. Analysis of her lifestyle and diet revealed that she was
suffering from hypothalamic–pituitary–adrenal axis dysregulation (HPA-D) due to overtraining;
she was eating a low-carb Paleo diet that was ill suited to her activity level; she had poor sleep
hygiene; and she wasn’t managing her stress appropriately. Ninety days of a customized diet
that was higher in calories and carbohydrates, a temporary break from high-intensity exercise,
better sleep habits, meditation, and changes to her business structure led to marked
improvements in anxiety, sleep patterns, energy, stress tolerance, and weight loss. This case
shows that it is possible to achieve significant improvements in a patient’s symptoms simply
by focusing on the basics: a thorough patient intake and history, coupled with targeted diet
and lifestyle recommendations.
A 42-year-old mother of four and business owner complained of fatigue and exhaustion, sleep
disturbance, anxiety, and weight gain. Analysis of her lifestyle and diet revealed that she was
suffering from hypothalamic–pituitary–adrenal axis dysregulation (HPA-D) due to overtraining; she
was eating a low-carb Paleo diet that was ill suited to her activity level; she had poor sleep
hygiene; and she wasn’t managing her stress appropriately. Ninety days of a customized diet that
was higher in calories and carbohydrates, a temporary break from high-intensity exercise, better
sleep habits, meditation, and changes to her business structure led to marked improvements in
anxiety, sleep patterns, energy, stress tolerance, and weight loss. This case shows that it is possible
to achieve significant improvements in a patient’s symptoms simply by focusing on the basics: a
thorough patient intake and history, coupled with targeted diet and lifestyle recommendations.
INITIAL PRESENTATION
Macy was a 42-year-old female that presented with fatigue, especially in the afternoons, as her
primary complaint. She was a business owner and mother of four children, one of whom was on
the autism spectrum, and she never felt like she had enough energy to make it through the day.
She woke up in the morning feeling unrefreshed, and her sense of exhaustion worsened as the
day progressed.
She also had difficulty sleeping without medication or supplements, anxiety, and high levels of
perceived stress. She worked out at a CrossFit gym a few times a week and reported that her
performance and exercise tolerance had declined steadily over the past eighteen months. She had
also recently started to notice fat gain around her waistline and underneath her chin.
During our appointment, I noticed that several aspects of her current diet and lifestyle could be
either entirely responsible for, or contributing significantly to, her primary complaints. For example:
■ Due to the increasing demands of her business and her ongoing familial obligations, she
was averaging just under six hours of sleep per night.
■ She did high-intensity CrossFit workouts a few times a week, despite increasing feelings
of fatigue.
■ She started a strict Paleo diet 18 months ago. This entirely resolved her acne, digestive
issues, and premenstrual dysphoric disorder (PMDD), but it also corresponded with the
decline in her energy and exercise tolerance.
In short, Macy was burning the candle at both ends—a perfect recipe for HPA axis dysregulation.
What’s more, I suspected that her intake of both calories and carbohydrates was insufficient for
her activity level and energy needs. This is unfortunately common in lean, active women and men
that adopt a strict Paleo diet.
When Macy switched to Paleo, she eliminated all starchy vegetables, fruits, grains, and sugars, and
consumed high levels of protein at each meal. She reported that at first, this regimen worked well
for her; she lost excess weight, was more fit, and felt good about how she looked. As mentioned
above, her longstanding acne, digestive issues, and PMDD also disappeared. But as time
progressed, her energy started to flag, she developed difficulties falling and staying asleep, and her
levels of anxiety and stress increased.
After analyzing Macy’s three-day food diary, I determined that she was significantly undereating
both calories and carbohydrates. Her average calorie intake was about 1,400 to 1,600 per day, with
less than 50 grams of carbohydrate on most days. These were far from optimal for a woman of her
height, weight, and activity level.
There are standardized formulas for calculating calorie needs based on activity level, such as the
Harris-Benedict and Mifflin-St. Jeor formulas. However, a quick and dirty approximation of these
can be obtained by simply multiplying the patient’s weight in pounds by 12 to 14 to establish their
baseline calorie needs, and then adding 100 calories for every 10 minutes of moderate- to high-
intensity activity that they perform per day.
Using this calculation, on her CrossFit training days, Macy should have been eating 2,200 calories—
a full 600 to 800 more than she was typically consuming (1,400 to 1,600 per day). On her resting
days, she should have been eating 1,900 calories, which was still 300 to 500 more calories than
she regularly ate.
Next, we examined her carbohydrate intake. Carbohydrate is the most variable macronutrient for
each patient, depending their condition. The chart below illustrates suggested starting places for
experimentation, given specific populations and goals:
TABLE 1: Dietary Carbohydrate Recommendations for Different Populations.
As you can see, for athletes I suggest a carbohydrate intake of at least 30 percent of total calories,
with a range of 30 to 40 percent being a good starting place for most recreational athletes doing
CrossFit-style training. I also suggest a moderate carbohydrate intake for patients who are
suffering from HPA-D.
At 50 grams of carbohydrate per day, and an average of 1,500 calories total per day, Macy’s
carbohydrate intake was 13 percent—far below the recommended threshold of 30 percent.
In Macy’s case, her low carbohydrate intake was in part due to a fear that eating too many
carbohydrates (even Paleo-friendly ones) would make her gain weight. After all, she had lost
weight when she switched to the Paleo diet and cut out refined carbs.
Macy was shocked when I told her she was eating only 13 percent of calories as carbohydrate, as it
was not her intention to drop this low. Unfortunately, I’ve found that this is all too common,
particularly among women. It’s so common, in fact, that I came up with a name for it (the
“accidental low-carb Paleo diet”) and I wrote an article about it.
TREATMENT PLAN
Here are the targets for total calorie, carbohydrate, fat, and protein intake that I suggested for Macy:
Note that on her training days, I was asking her to eat anywhere from three- to four-fold the
amount of carbohydrate she was eating previously! This is impossible to do on a Paleo-style diet
without including significant amounts of starchy plants like plantain, yuca, taro, and sweet
potatoes, as well as fruit. For this reason, I recommended that Macy add some non-Paleo
carbohydrate sources such as white rice and white potatoes (see Discussion).
In addition to the dietary changes I recommended, I also suggested she get at least eight hours of
sleep. This meant giving up her use of Facebook and other social media at night, which she
typically did after she put her kids to bed, and hiring two employees to help her with her business.
These changes were not easy, but Macy was willing to make them because she was alarmed by the
recent changes in her health—and because I explained to her that healing from HPA-D is not
possible without adequate sleep.
I also suggested that she dial back her exercise routine significantly. This can be difficult for
CrossFitters to do for two reasons. First, the CrossFit gym is more than a place to exercise for
many people; it’s also a source of community and social support. Second, many CrossFit gyms
emphasize competition and personal achievement and unfortunately do not recognize the
potential for serious harm that can come from overtraining. I asked her to avoid CrossFit entirely
until she was able to start sleeping better and her energy levels recovered. Fortunately, Macy was
again willing to make this change.
Finally, I suggested that Macy begin a meditation practice in order to help her to manage her stress
and anxiety. Given her technology orientation (her company was a tech start-up), busy lifestyle,
and several unsuccessful attempts to start meditating in the past, I suggested Macy try using the
Headspace app. This worked very well for her.
NINETY-DAY FOLLOW-UP:
After three months of treatment, Macy experienced some remarkable changes:
■ She began falling asleep without medication or supplements and sleeping through the
night on most nights (with the exception of occasionally waking to attend to her special-
needs child).
■ She woke up feeling refreshed and no longer felt tired during the day or had energy
crashes in the afternoon.
■ Much to her surprise, adding carbohydrates to her diet not only didn’t lead to weight gain,
but it had the opposite effect: the extra fat she had gained around her midsection and
under her chin began to decrease.
■ She reported feeling less background anxiety and greater stress tolerance, despite the fact
that the circumstances of her busy life hadn’t changed much.
■ Her exercise tolerance gradually improved and she was again able to start increasing her
performance at the gym.
Once Macy’s energy levels and sleep were better, I then suggested she work with the trainers at
her gym to create a routine that was more appropriate for her particular circumstances and needs.
She was eventually able to return to training three days a week, but at a much lower intensity than
she was before.
DISCUSSION
So far we’ve focused on relatively complex cases where extensive laboratory testing was needed to
determine the underlying cause(s) of the patient’s symptoms and comprehensive treatment
protocols involving several supplements and botanicals were needed to resolve the pathologies
that were identified. This case study, on the other hand, illustrates the importance of “the basics”—
taking a thorough new patient history and addressing diet and lifestyle before anything else.
Occasionally this is all that’s needed to resolve the patient’s concerns.
Macy’s case is also a good reminder that HPA-D is ultimately a clinical diagnosis. We did run a
panel of tests (including a Dried Urine Test Comprehensive Hormones, or DUTCH, HPA axis
assessment), but the results in most cases were normal or equivocal. Nevertheless, Macy presented
with classic symptoms of HPA-D, and I was confident that approaching her from that perspective
would yield positive results. After treatment, her considerable clinical improvement in the areas of
stress tolerance, sleep, anxiety, and weight loss confirmed that HPA-D was the correct diagnosis.
Paleo Diet, Calories, and Carbohydrates

Strict Paleo is a fantastic starting place for many people, since it removes many of the antigenic
foods that can provoke digestive distress, immune dysregulation, and inflammation. This is why
Macy saw a nearly complete resolution of her acne, digestive issues, and PMDD when she adopted
a Paleo diet.
However, there is no one-size-fits-all approach to diet. Instead, diet must be customized to meet
each individual’s particular genetic predisposition, goals, health status, activity levels, and goals.
For an athlete or active person, calorie and carbohydrate intake are particularly important factors
to address. This is even more true when significant stress is present, since ongoing stress (including
excessive exercise) can have a catabolic effect on the body. Without sufficient calories and
carbohydrates to support activity and stress levels, the body will progressively break down. This is
what was happening with Macy.
Reaching an appropriate carbohydrate level (>30 percent) for athletes, active people, those trying
to gain weight and muscle mass, and pregnant women can be difficult without adding some non-
Paleo carb sources such as white rice and white potatoes. For example, imagine Macy consumed
the following Paleo-style meal plan in one day:
■ Breakfast: two scrambled eggs, two pieces of bacon, and a cup of fresh blueberries
■ Lunch: half of an acorn squash stuffed with ground beef, kale, red peppers, and other non-
starchy veggies
■ Snack: an apple with almond butter
■ Dinner: an 8-ounce New York strip, a medium sweet potato with butter, and steamed broccoli
What would her total carbohydrate intake be? Non-starchy vegetables are excellent sources of
micronutrients and fiber, but overall they are quite low in carbohydrates. Most have fewer than 80
calories of carbohydrates per pound, and those are typically in the form of glucose and fructose.
What’s more, some evidence indicates that the human body expends up to 40 calories for every
pound of non-starchy vegetables consumed. This suggests a net gain of a mere 40 calories per
pound of vegetables eaten.
For this reason, I recommend not counting non-starchy vegetables toward the total carbohydrate
intake. That means that we only count carbohydrates from starchy plants and fruit. If we do that
from the example above, we get the following amounts:
■ 1 cup of fresh blueberries: 21 grams

■ 1 cup of acorn squash: 30 grams
■ 1 apple: 25 grams
■ 1 medium sweet potato: 37 grams
This plan—even with starchy plants and fruit—provides a total of only 113 grams of carbohydrate.
Remember that Macy needed approximately 160 to 220 grams of carbohydrate on her training
days and somewhere between 100 and 150 grams on her resting days. So, although the meal plan
above might be sufficient on resting days (albeit in the low end of the recommended range), it
would be well below the recommended target for her training days.
You can see that customizing the diet, especially for a patient who needs a higher carbohydrate
intake, is important and requires attention to detail. Knowledge of foods that are high in
carbohydrates can help tailor the diet for a particular patient. I’ve listed the carbohydrate content
of starchy plants and fruits (Tables 2 & 3) below to illustrate the most carbohydrate-dense foods
on a Paleo-style diet. I’ve also included white rice and white potatoes in the starch section to give
you an idea of why these may be helpful carb sources, if tolerated, for athletes and active people.
TABLE 2: Carbohydrate Content of Starchy Plants.

CARBOHYDRATE CONTENT OF SELECTED STARCHY PLANTS
STARCHY PLANT MEASURE CARBOHYDRATE, G
Potato, russet 1 large 64
Tapioca 1/2 cup 63
Plantain 1 cup, slices 48
Taro 1 cup, sliced 46
Yuca* (aka manioc, cassava) 1/2 cup 39
Sweet potato 1 large 37
Yam 1 cup, cubes 37
Breadfruit 1/2 cup 30
Acorn squash 1 cup, cubes 30
Butternut squash 1 cup, cubes 22
Lotus root 10 slices 14
As you can see, the most carbohydrate-dense starches on a strict Paleo diet are tapioca, plantain,
taro, and yuca (also called manioc or cassava)—foods that are not typically consumed by most
Americans, even those on a Paleo diet.
Notice, as well, that white potatoes are higher in carbohydrates than any Paleo source, and white
rice is higher than any Paleo source with the exception of tapioca. If your active patients tolerate
white potatoes and rice, I don’t think there’s any reason to avoid these foods, and in fact, they may
be highly beneficial.
TABLE 3: List of the Carbohydrate Content of Fruits.
CARBOHYDRATE CONTENT OF SELECTED FRUITS
FRUIT MEASURE CARBOHYDRATE, G
Banana 1 medium 27
Pear 1 fruit, medium 27
Pomegranate 1/2 fruit (4-inch piece) 27
Mango 1 cup, pieces 25
Apple 1 fruit (3-inch piece) 25
Pineapple 1 cup, chunks 22
Orange 1 fruit (3-inch piece) 18
Grapes 1 cup 16
Papaya 1 cup, 1-inch pieces 16
Peach 1 medium (2 2/3 inch) 14
Cantaloupe 1 cup, cubes 13
Strawberries 1 cup, halves 12
Watermelon 1 cup, diced 12
Blueberries 1/2 cup 11
Raspberries 1/2 cup 8
Plum 1 fruit (2 1/8 inch) 8
Tomato 1 cup, chopped 7
As you can see, even the most carbohydrate-dense fruits like bananas and pears contain less than
half of the carbohydrate than a serving of potatoes. So, while fruit can certainly contribute to
overall carbohydrate intake, it should not be the sole source for athletes and active people.
Why do so many people who adopt a Paleo diet follow a low-carb version of it? In many cases, it is
simply an unintentional result of removing highly refined carbohydrate sources like bread, flour,
and sugar, and not replacing them with Paleo-friendly starches and fruit.
In other cases, people have been led to believe that carbohydrates—even Paleo-friendly starches
and fruit—are potentially harmful even for healthy people and should be limited as a result. Macy
was afraid that eating too many carbohydrates (even Paleo-friendly ones) would make her gain
weight. There is, however, no research that I am aware of that supports this viewpoint. On the
contrary, the majority of the peer-reviewed studies that have shown the Paleo diet to reduce
weight, blood sugar, total and LDL cholesterol, inflammatory markers, and blood pressure
employed moderate carbohydrate versions of Paleo. For example, in a study of patients with type
2 diabetes, participants experienced significant improvements in metabolic and lipid parameters
following a Paleo diet that averaged 32 percent of calories from carbohydrate.1
In addition, traditional hunter-gatherer societies typically consume between 30 and 40 percent of

their total calories from carbohydrate, though the range can vary between 3 and 50 percent,
depending on the population studied and the latitude at which they live.2,3 The only hunter-
gatherer societies observed to eat fewer than 20 percent of calories as carbohydrate were those
living at latitudes quite distant from the equator, often in marginalized environments where fruits,
vegetables, starches, and honey were not readily available.
Both clinicians and patients need to understand that Paleo-friendly carbs do not affect the body in
the same way that highly refined carbohydrates do. Refined carbohydrates have been shown to
alter our gut microbiota in ways that may predispose us to weight gain.4 They are also much higher
in total calories and lower in nutrients than whole-food sources of carbohydrates, which means
we’re more likely to gain weight when we eat them.
CONCLUSIONS
Macy presented with fatigue, anxiety, sleep disturbance, and weight gain. After a careful intake, it
was clear that she was eating a diet poorly suited to her personal circumstances. She was
undereating calories and carbohydrates because she had inadvertently adopted a low-carb Paleo
diet. Macy was overtraining, had poor sleep hygiene, and needed to make changes at work to
decrease her stress level. Her symptoms suggested HPA axis dysregulation. A straightforward
protocol of dietary and lifestyle changes over three months led to increased energy, restorative
sleep, weight loss, less anxiety, and better stress tolerance. She was eventually able to resume her
active lifestyle (though not high intensity) without diminishing her newfound energy levels.
As clinicians, we have an increasingly sophisticated array of laboratory tests and other diagnostic
methods available to us. In some cases, we’ll need to make full use of these in order to successfully
treat our patients. Yet in a surprising number of cases, such as this one, we can accomplish our
goals simply by focusing on the basics: a thorough patient intake and history, coupled with
targeted diet and lifestyle recommendations. Unfortunately, these are all too often overlooked—not
only in conventional primary care, but also in functional medicine.
As a final note, I encourage clinicians to consider either hiring or developing a referral relationship
with a registered dietitian or nutritionist who is familiar with Paleo-style, nutrient-dense diets.
Calculating the necessary calorie and macronutrient intakes for each patient based on their
individual needs can be time-consuming and beyond what most full-time clinicians will be able to
do in their practice. This is where a well-trained RD or nutritionist can be a fantastic resource for
you, as a clinician, and your patients.
References
1. Jonsson T, Granfeldt Y, Ahren B, et al. Beneficial effects of a Paleolithic diet on cardiovascular risk
factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovasc Diabetol. 2009;8:35.
2. Kuipers RS, Luxwolda MF, Dijck-Brouwer DA, et al. Estimated macronutrient and fatty acid
intakes from an East African Paleolithic diet. Br J Nutr. 2010;104(11):1666-1687.
3. Strohle A, Hahn A. Diets of modern hunter-gatherers vary substantially in their carbohydrate
content depending on ecoenvironments: results from an ethnographic analysis. Nutrition research
(New York, N.Y. 2011;31(6):429-435.
4. Sonnenburg ED, Sonnenburg JL. Starving our microbial self: the deleterious consequences of a
diet deficient in microbiota-accessible carbohydrates. Cell Metab. 2014;20(5):779-786.
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FIGURE 2: HLA-B27 Blood Test.

The primary goals of the treatment protocol were:

TREATMENT NUTRACEUTICAL BRAND DOSAGE

FIGURE 8: Follow-up Test Results for SIBO.

Her follow-up SIBO results were normal.

Addressing Michelle’s GI health had far-reaching consequences: it reduced joint inflammation,

3. Rashid T, Ebringer A. Gut-mediated and HLA-B27-associated arthritis: an emphasis on ankylosing

Initial Presentation and Lab Testing

FIGURE 1: Thyroid Function Markers and Thyroid Antibodies.

FIGURE 4: Intrinsic Factor Antibody Test.

FIGURE 6: Small Intestinal Bacterial Overgrowth Breath Test Results.

TREATMENT NUTRACEUTICAL BRAND DOSAGE

3 billion CFU twice daily at lunch

1 packet BID (with breakfast and

Med-Chem 1 scoop three times daily with

Slowly build to 20-30 drops BID

3-4 capsules BID on an empty

Microbial Cranberry juice,

Extra Virgin Cod Liver

Nutrition Trifolamin Designs for Health 1 lozenge (5 mg)/day

Nutrition Micellized Vitamin D3 Klaire Labs 10,000 IU/day

Sixty-Day Follow-up: Clinical Outcome and

FIGURE 11: Follow-up SIBO Test Results

Treatment Plan Modifications Made after 60 Days

120-Day Follow-up: Clinical Outcome and

Treatment Plan Modifications after 120 Days

VITAMIN B12 AND PERNICIOUS ANEMIA

HPA DYSFUNCTION AND DIABETES

My panel of initial tests returned the following notable results.

TREATMENT NUTRACEUTICAL BRAND DOSAGE

Two tablets, once a day.

1 packet BID (with

3-4 capsules BID on an

One BID upon rising and

2 caps twice daily with

2 caps one hour before

1 cap three times daily

FIGURE 5: Joe’s Treatment Protocol with Dosages.

Joe’s follow-up stool test showed significant improvement in beneficial bacteria:

TABLE 1: Dietary Carbohydrate Recommendations for Diﬀerent Populations.

Paleo Diet, Calories, and Carbohydrates

■ 1 cup of fresh blueberries: 21 grams

TABLE 2: Carbohydrate Content of Starchy Plants.

Tapioca 1/2 cup 63

Plantain 1 cup, slices 48

Taro 1 cup, sliced 46

Yuca* (aka manioc, cassava) 1/2 cup 39

Sweet potato 1 large 37

Yam 1 cup, cubes 37

Breadfruit 1/2 cup 30

Acorn squash 1 cup, cubes 30

Butternut squash 1 cup, cubes 22

Lotus root 10 slices 14

Pear 1 fruit, medium 27

Pomegranate 1/2 fruit (4-inch piece) 27

Mango 1 cup, pieces 25