Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – January 2022

by Dr. Ruscio, DNM, DC, Gavin Guard, PA-C, MPAS, CISSN, Pn1, and the Ruscio Institute for Functional Medicine Clinical Team

Medically reviewed & fact checked by a
board-certified doctor
Medically reviewed & fact checked by a
board-certified doctor
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Episode 36

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Featured Study


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Gastrointestinal Studies

  • Association Between the Sulfur Microbial Diet and Risk of Colorectal Cancer
    • Combination of 3 larger prospective cohorts, including 214,797 participants
    • Higher intakes of french fries, red meats, and processed meats and low intakes of fruits, vegetables, whole grains, and legumes was associated with a higher risk of colorectal cancer.
    • Commentary: In other words, a processed foods rich diet is associated w/ a higher colorectal cancer risk.

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Thyroid & Hormones Studies

  • Thyroid Function and the Risk of Alzheimer’s Disease: A Mendelian Randomization Study
    • Mendelian randomization study of 119,715 participants including 71,880 Alzheimer’s Disease (AD) cases
    • Higher levels of genetically predicted TSH within the normal range was associated w/ a decrease of AD risk in younger individuals
    • No relationship between fT4 or hypothyroidism and AD risk
    • Commentary: This study did not find an association between low thyroid function and AD risk.

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Diet & Lifestyle Studies

  • Impact of insufficient sleep on dysregulated blood glucose control under standardised meal conditions
    • 953 healthy adults (41% twins) consumed isoenergetic standardized meals over 2 weeks 
    • Measured sleep variables and continuous glucose monitoring
    • Poor sleep efficiency and later bedtime routines are associated with higher postprandial glycaemic responses to breakfast the following morning
    • Deviation from usual sleep pattern associated with worse postprandial glycaemic control
    • Commentary: Optimal sleep is a vital part of glycemic control.
  • Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease-A randomized controlled trial
    • 30 type 2 diabetic patients w/ kidney disease randomized to:
      • Very low carb (<20g carbs/d)
      • Or low protein, low salt diet
    • After 12 weeks, the low carb group had:
      • No change in serum creatinine
      • More decrease in A1C (-1.3% vs -0.7%)
      • More reduction in insulin dose (-39 IU vs +0 IU)
      • Reduction in LDL-C 
      • Reduction in inflammatory markers (IL-6)
      • More weight loss (-4.0 kg vs +0.2 kg)
    • Commentary: This study demonstrated that a very low carb (e.g. ketogenic) and higher protein diet is both safe and can ameliorate glycemic abnormalities in those w/ kidney disease.

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Episode 35

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Featured Study


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Gastrointestinal Studies

  • Small intestinal bacterial overgrowth in Alzheimer’s disease
    • 45 Alzheimer’s Disease (AD) patients and 27 healthy controls given lactulose breath test
    • SIBO was found in 49% in AD patients, 22% in controls
    • Among those w/ AD, SIBO positivity was NOT associated w/ cognitive impairment
    • Zonulin levels were higher in the AD patients compared to controls (73.5 vs 49.0 ng/ml)
    • Commentary: SIBO and increased zonulin levels are found at higher rates in those w/ AD.
  • Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies
    • 9 studies, 756 FMTs
    • Pooled adverse event rate was 39.3%
      • Most common: Abdominal pain and diarrhea
    • Serious adverse event was 5.3% 
      • Most common: C. diff infection
    • Commentary: FMT has a notable adverse event probability. Ironically, the most common serious adverse event from FMT is C. diff infection which is something FMT is used for. 
      • Dr. Ruscio wanted me to point out this is exactly why we use a foundations up approach for digestive health and do not jump to new/novel.

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Autoimmunity Studies


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Diet & Lifestyle Studies


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Episode 34

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Featured Study

  • Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy
    • Narrative review of treating the nuances of subclinical hypothyroidism (SCH)
    • Treating SCH is fairly common but the majority of cases do not see benefits
      • “Some of this dissatisfaction is unintentionally caused by well-meaning practitioners who enthusiastically begin patients on levothyroxine for minimal hypothyroidism, with the promise that it will address their symptoms. Unfortunately, the evidence suggests that few such patients will experience long-term benefit in their symptoms. And in the elderly, aggressive treatment may possibly cause harm.”
    • Many patients are put on unnecessary thyroid medication
      • “A 2018 study using a United States insurance claims database linked to laboratory data found that 65.7% of patients started on levothyroxine had subclinical hypothyroidism, and the mean TSH level at the initiation of treatment was 5.3 mIU/L.
    • TSH is highly variable. Get a repeat TSH before rushing to treat SCH
      • “Before diagnosing and treating subclinical hypothyroidism, one must ascertain whether steady-state conditions exist, and whether hypothyroidism is transient.” 
      • “Additionally, TSH is released in pulses, which becomes more frequent in the evening; TSH sampled at the time of a pulse might transiently be just above the upper limit of normal, especially in a patient whose baseline TSH levels are in the upper portion of the normal range.” 
      • “Among over 422,000 patients, none of these patients were on thyroid medications, 3% had an elevated TSH; when lab tests were repeated, 62% became normal spontaneously. The European Thyroid Association guideline for management of subclinical hypothyroidism recommends a repeat TSH measurement preferably after a 2–3-month interval.
    • The upper limit of TSH is age-dependent
      • “While it is true that the 97.5 percentile for TSH is 3.6 mIU/L in adult subjects under age 40, the normal range is shifted to higher values with aging, and the 97.5 percentile increases to 7.5 mIU/L in subjects over age 80 with no evidence of thyroid disease (negative thyroid peroxidase [TPO] antibodies, no thyroid history, and no drugs that affect thyroid function).”
    • Most patients w/ a TSH >10 should be treated
      • “…there is general agreement that patients with TSH levels that exceed 10 mIU/L should be treated.”
    • Treating SCH w/ TSH <10 usually does NOT result in symptom improvement
      • “…A large RCT of 737 patients over age 65 with TSH values 4.6–19.99 mIU/L, average TSH 6.4 mIU/L, found no change in cognitive function or improvement in symptoms compared to placebo when the mean TSH was reduced to 3.63 with levothyroxine treatment.” 
      • “Finally, a meta-analysis of 21 RCTs showed no change in quality of life, thyroid-related symptoms, fatigue, or depressive symptoms with levothyroxine treatment”. 
      • “These data suggest that few, if any, patients have improvement in fatigue, depression, or “brain fog” when mild thyroid dysfunction is treated with levothyroxine.”
    • SCH is associated w/ higher cardiovascular disease risk
      • “Another study of subjects over age 65 found the HR for cardiovascular mortality in subjects with subclinical hypothyroidism to be 1.7  if TSH exceeded 6.38 mIU/L. And a third study of 115,746 subjects where 1841 had subclinical hypothyroidism (TSH 5.00–19.96) found a relative risk of 1.30 for all-cause mortality and 1.68 for cardiovascular mortality.”
    • Treating SCH w/ TSH between 7-10 who are younger and at higher risk for cardiovascular disease could be beneficial
      • “While the evidence is far from conclusive, it strongly suggests that younger patients have an overall cardiovascular benefit if subclinical hypothyroidism is treated, whereas older patients may experience no benefit but possibly demonstrate harm.
    • These are the groups of patients the author recommends treating SCH:
      • Younger (<70 yo), TSH between 7-10
      • Older (>70 yo), TSH between 7-10 with significant symptoms
      • TSH >10 regardless of age
    • Commentary: This is a really comprehensive and fair review of the SCH literature. Well worth a read.

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Gastrointestinal Studies

  • Prucalopride in diabetic and connective tissue disease-related gastroparesis: Randomized placebo-controlled crossover pilot trial
    • Crossover study of 15 gastroparesis patients (13 from diabetes, 2 from connective tissue disease), randomized to 2 weeks of prucalopride or placebo, then switched to different group w/ 2 week washout
    • The prucalopride group had:
      • Faster gastric emptying time
      • Higher weekly bowel movements (10.5 vs 7.5)
      • NO difference in gastroparesis symptoms
    • Commentary: This study showed that prucalopride (a 5-HT4 serotonin agonist prokinetic) had favorable effects on gastric motility but NO significantly better improvement in symptoms when compared to placebo.

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Thyroid & Hormones Studies


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Diet & Lifestyle Studies


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Episode 33

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Featured Study

  • Objective Evidence of Gastro-Esophageal Reflux Disease is Rare in Patients with Autoimmune Gastritis
    • 172 patients w/ autoimmune atrophic gastritis (AAG)
    • 38 (22%) had reflux symptoms
      • But the majority of them (79%) had a normal endoscopy
    • Compared to those without reflux symptoms, those w/ reflux symptoms had: 
      • NO difference in gastrin
      • NO difference in pepsinogen
      • NO difference in H. pylori colonization
    • Of the 87% who received PPI therapy, only 34% reported benefit
    • Commentary: This smaller study highlights a few things:
      • 1) A minority of those w/ AAG reported reflux symptoms 
      • 2) Reflux is a symptom that can be seen in AAG cases despite these individuals having LOW stomach acid production (as compared to high acid)
      • 3) Gastrin and pepsinogen were relatively poor predictive markers for who did and who did not have symptoms
      • 4) PPI therapy was not a great therapeutic option for those w/ AAG (since it’s a condition of LOW HCl production)

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Gastrointestinal Studies

  • Changes in oral flora of patients with functional dyspepsia
    • 21 functional dyspepsia (FD) patients and 12 healthy controls, measured microbiome of saliva and lactulose breath test for SIBO
    • FD patients had a higher abundance of Spirochaetes and a lower abundance of Fusobacteria and Proteobacteria than controls
    • 71.4% of the FD group was positive for SIBO (vs 8.3% in controls)
    • Commentary: Dysbiosis may play a role in the pathogenesis of functional dyspepsia. Higher rates of SIBO were found in the dyspepsia group vs healthy controls.
  • Real time micro-organisms PCR in 104 patients with polymorphic signs and symptoms that may be related to a tick bite
    • 104 patients w/ fibromyalgia symptoms
    • PCR analysis performed on saliva, urine, blood to look for tick-borne pathogens
    • 48% of the patients were colonized/infected w/ more than one pathogen
      • 25% harboured at least three different microorganisms
    • Mycoplasma spp., Rickettsia spp. and Ehrlichia spp. were the most frequent microorganisms observed
    • Saliva was the most sensitive marker used
    • Commentary: Unfortunately, this was not a controlled study, but did show some interesting results regarding fibro symptoms and tick-borne pathogens.
  • Study of Antibodies to Cytolethal Distending Toxin B (CdtB) and Antibodies to Vinculin in Patients with Irritable Bowel Syndrome
    • Retrospective study of 100 IBS patients
    • Anti-vinculin and anti-CdtB levels were higher in patients with IBS (1.58 ng/ml and 2.47 ng/mL) when compared to control subjects (1.13 ng/ml and 2.1 ng/mL)
    • Anti-vinculin level was significantly higher in the IBS-D subtype (1.84 ng/mL) than the other subtypes (IBS-C 1.33, Controls 1.13)
    • Commentary: Three things to note here:
      • 1) This study showed increased antibodies in IBS patients compared to healthy controls but the degree of difference is fairly low
      • 2) IBS-D had the highest antibody levels despite evidence suggesting that IBS-C benefits the most from prokinetics
      • 3) Even though those w/ IBS had higher levels, according to common antibody labs, the average IBS anti-vinculin level would NOT flag as elevated on many of these tests
  • Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG
    • Prospective study of 50 IBS patients, 25 healthy controls
    • IBS patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies
    • After 4 weeks of a gluten-free diet:
      • IBS symptoms improved in 75% with antigliadin IgG and IgA and in 38% without the antibodies
      • The presence of antigliadin IgG was associated with overall reductions in symptoms (OR 129 compared with patients without antibodies)
      • No effect on GI symptoms in controls
    • Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD
    • Commentary: Those w/ antigliadin antibodies may respond better to a GFD but larger studies are needed. Symptoms can be improved even if a patient is not very strict with the diet.
  • Impaired Quality of Life in Patients with Autoimmune Atrophic Gastritis
    • Cross-sectional study of 102 autoimmune atrophic gastritis (AAG) patients, 100 w/ a functional GI disorders (FGID), 100 w/ other organic GI disorders, and 100 healthy controls
    • Evaluated quality of life (QOL)
    • Results: 
      • The AAG group had significantly worse QOL compared to other groups
      • Vitamin B12 level was a significant independent predictor of physical functioning
    • Commentary: This study highlights the impaired QOL of those w/ AAG compared to healthy controls and other GI disorders. Repletion of B12 levels may be an important part of managing AAG.

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Thyroid & Hormones Studies


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Diet & Lifestyle Studies

  • A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT
    • 83 individuals w/ mild cognitive impairment, randomized to placebo or “ketone drinks” (ketogenic medium chain triglycerides)
    • After 6 months of supplementation, the ketone group had better cognitive function
      • Some cognitive measures were positively correlated w/ plasma ketone levels
    • Commentary: Ketone supplementation led to improvements in mild cognitive function perhaps due to increased plasma ketone levels.

Discussion

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