Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – November 2021

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 28

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Featured Study


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Gastrointestinal Studies

  • Distinctive Clinical Correlates of Small Intestinal Bacterial Overgrowth with Methanogens
    • Aim: Determine if specific symptoms and conditions are associated with methanogenic SIBO
    • Retrospective study of 1,461 patients who received glucose breath test
    • 33.1% were SIBO positive:
      • 49.8% produced only hydrogen
      • 38.8% produced only methane
      • 11.4% produced both gases
    • Associated conditions for hydrogen-predominant SIBO (but not methane SIBO)
      • Vitamin B12 deficiency (odds ratio 1.44)
      • Roux-en-Y gastric bypass (OR 2.14)
      • Cholecystectomy (OR 1.42)
      • Diabetes (OR 1.59)
    • Commentary: Hydrogen-predominant SIBO is the most common subtype. Make notes of the above risk factors when considering the possibility of SIBO.
  • Effect of Bacillus coagulans Unique IS2 with Lactulose on Functional Constipation in Adults: a Double-Blind Placebo Controlled Study
    • 150 patients w/ functional constipation randomized to:
      • Lactulose + soil-based probiotic
      • Lactulose alone
      • Placebo
    • After 4 weeks, the soil-based probiotic + lactulose had significant better improvement in stool frequency compared to lactulose alone in the first few weeks
      • However, this difference was not statistically significant after the end of the trial
    • Commentary: While there was a trend towards better improvement, this study failed to show superiority of probiotic + lactulose over lactulose alone for treating functional constipation. More improvement may have been achieved with using triple probiotic therapy.

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Autoimmunity Studies


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Diet & Lifestyle Studies

  • Do physical interventions improve outcomes following concussion: a systematic review and meta-analysis?
    • 12 studies using exercise as therapy after concussion:
      • 7 on aerobic exercise
      • 1 on vestibular therapy
      • 1 on cervical therapy
      • 3 on multimodal training (cervical, vestibular, oculo-motor training)
    • Benefit for:
      • Aerobic exercise had small-moderate effect in improving symptoms (effect size 0.43) but not time to recovery
      • Multimodal training had moderate effect in improving symptoms (effect size 0.63) and time to recovery
    • No significant improvement w/ cervical or vestibular training
    • Commentary: Isolated neurological rehab tools may not be enough when used in isolation. Instead, using combined cervical, vestibular, and oculomotor training as part of a comprehensive program may play an important role in a post-concussion rehab program.

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Episode 27

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Featured Study

  • Levothyroxine Sodium Oral Solution Normalizes Thyroid Function in a Patient with Hashimoto’s Disease, Gastritis, Diabetic Gastroparesis, and Small Intestinal Bacterial Overgrowth (SIBO)
    • Case study of a 51 year old female w/ long-standing Hashimoto’s with multiple food and medication sensitivities
    • Presented w/ multitude of symptoms: recurrent hives, dry skin, fatigue, weight gain, intermittent constipation and diarrhea, cold intolerance, brain fog
    • Over course of 6 months, TSH was not well controlled on multiple medications (general T4, brand T4, combined T4/T3)
    • Developed projectile vomiting, weight loss,10-20 bowel movements per day
    • Breath test, endoscopy and scintigraphy revealed SIBO, gastritis, gastroparesis, and hiatal hernia
    • Switched to liquid T4
      • TSH decreased from 7.42 to 1.55 after 6 weeks
      • TSH decreased further to 0.56 after being treated w/ Rifaximin
    • Commentary: This case study exemplifies a few things:
      • The gut-thyroid connection: there remains an association between hypothyroidism, SIBO, and gastroparesis symptoms
      • Consider liquid T4 therapy before combined T4/T3: this case study supports the use of our clinical thyroid algorithm of considering oral T4 and working on the gut before combined T4/T3 therapy. 
      • Authors note a meta-analysis of 141 patients that showed that patients with suboptimal TSH on tablet T4 significantly improved TSH by switching to a liquid L-T4 formulation at an unchanged dose

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Gastrointestinal Studies

  • Effects of glutamine supplementation on inflammatory bowel disease: A systematic review of clinical trials
    • 7 studies using glutamine (21-30g or 0.5g per kg of participant’s body weight)
    • Of the 7 studies:
      • 2 of 3 studies showed NO effect on intestinal permeability
      • 2 of 2 studies showed NO effect on body weight or anthropometrics
      • Only 2 of 5 studies showed reduced inflammation and oxidative stress
      • Only 2 of 5 studies showed reduced disease activity
    • Commentary: This systematic review failed to show support the use of glutamine in IBD.

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Autoimmunity Studies

  • Is Fibromyalgia Associated with Borrelia Specific T Lymphocytes?
    • Enzyme-linked immunospot used to detect T-lymphocyte reactivity to Borrelia burgdorferi from 27 fibromyalgia patients and 26 healthy controls
    • NO difference in T-cell reactivity between the two groups
    • Commentary: Work through GI algorithm before considering more rare issues like stealth infections (e.g. spirochetes).

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Thyroid & Hormones Studies

  • Role of Selenium Deficiency in Pediatrics with Acquired Hypothyroidism
    • Case-control study of 60 hypothyroid children and 60 healthy children
    • Serum selenium levels were NOT different between the two groups (94 mcg/dL vs 86 mcg/dL)
    • Commentary: This is not to say selenium is not an effective treatment strategy. Also note that selenium is typically used in Hashimoto’s patients to reduce TPO Abs (this study was looking at congenital hypothyro).

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Diet & Lifestyle Studies


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Episode 26

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Featured Study

  • Triiodothyronine alongside levothyroxine in the management of hypothyroidism?
    • Narrative review of T4 +T3 combo therapy for managing hypothyroidism
    • Important point: Of endogenous thyroid production; 80% T4, 20% T3
    • Why do some individuals have hypothyroid symptoms despite normal thyroid levels?
      • Different individual “set points” for thyroid hormones
      • Genetic SNPs of deiodinase enzymes
      • Varying degree of TSH and thyroid sensitivity
      • Poor T4-T3 conversion
      • TSH measurement variations due to body weight, meds (e.g. metformin), diurnal variations, gender, and age
      • Commentary: Gut imbalance can be another cause of hypothyroid symptoms
    • What can we take away from randomized trials?
      • Overall, these [randomized] trials did not demonstrate a clear or consistent benefit from adding T3 to LT4 therapy, for example based on evaluations of cognition, mood, or QoL. Moreover, no particular ratio of LT4:T3 was more or less successful. Although patients preferred the combination in some studies, this was not explained necessarily by improvements in symptoms related to hypothyroidism.
    • What about meta-analysis?
      • “Recent (2018 and 2021) systematic review/meta-analyses concluded that the addition of T3 to LT4 therapy had little benefit in terms of objective improvements in such outcomes (the more recent review also concluded that LT4 + T3 and LT4 monotherapy were tolerated similarly). However, these trials were conducted in relatively broad populations of patients with hypothyroidism, did not consistently use disease-specific instruments for measuring patient-reported outcomes, and therefore cannot exclude a potential benefit in subgroups of patients with hypothyroidism.”
    • Is combo T4 + T3 therapy safe for those who need it?
      • The largest and longest observational study of LT4 + T3 combination therapy was conducted in Tayside, UK. Here, patients who had received thyroid hormone replacement were divided into those who had only ever received LT4 (n = 33,955) and those who had received at least one additional prescription of T3 (n = 400) and were followed retrospectively for a total of 17 years. There was no excess risk of side effects associated with over-treatment of hypothyroidism, i.e. cardiovascular disease (hazard ratio [HR] 1.0 [0.7, 1.5]), atrial fibrillation (HR 0.9: [0.5, 1.8]), or fractures (HR 0.8: [0.5, 1.3]), and no increased use of medications for cardiovascular disease or osteoporosis (statins, bisphosphonates). 
    • Helpful T4 to combo conversion (assuming a 4x more activity of T3)
      • 100 mcg LT4 → 87.5 mcg/5 mcg T4/T3 combo
      • 150 mcg LT4 → 125 mcg/7.5 mcg T4/T3 combo
      • 200 mcg LT4 to 175 mcg/10 mcg T4/T3 combo
    • Commentary: Combo therapy CAN be helpful in a subset of hypothyroid patients but it may not be the best first choice in most individuals. Work through the thyroid algorithm to find the best solution for your patient.

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Gastrointestinal Studies

  • Low FODMAP diet versus traditional dietary advice for functional dyspepsia: a randomized controlled trial
    • Prospective study of 105 functional dyspepsia patients randomized to low FODMAP or traditional therapy
    • After 4 weeks:
      • Both groups had improvement of symptom severity and quality of life
      • NO difference between groups
      • However, those w/ postprandial symptoms or bloating had better response to low FODMAP diet
    • Commentary: Low FODMAP diet is a promising therapy for functional dyspepsia, especially for those w/ postprandial symptoms and/or bloating.

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Autoimmunity Study

  • Organ-specific autoimmune markers in adult patients with type 1 diabetes mellitus
    • Aim: To discern antibody prevalence in type 1 diabetes
    • Retrospective study of 287 type 1 diabetes
      • Anti-GAD Ig: 72.8%
      • Anti-insulin Ig: 9.1%
      • Anti-islet cell Ig: 25.7%
      • TPO Ig: 34.8%
      • Anti-thyroglobulin Ig: 19.9%
      • Anti-endomysial Ig (celiac): 7.6%
      • Anti-gliadin IgA: 12.2%
      • Tissue transglutaminase IgA: 7.1%
    • About half of the adult T1D patients were positive for at least one non-diabetic antibody
    • Commentary: Given these findings, it may be worth screening for TPO antibodies in T1D patients.

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Thyroid & Hormones Studies


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Diet & Lifestyle Studies


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Episode 25

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Featured Study

  • Association of Thyroid Dysfunction with Cognitive Function: An Individual Participant Data Analysis
    • Prospective collection of multiple studies published in JAMA, 74,565 total participants
    • Assessing cognitive function: 21 studies, 38,144 participants, followed x1.7-11.3 years
    • Assessing dementia: 8 studies, 44,573 participants, followed x3.8-15.3 years 
    • Results:
      • Rates of thyroid dysfunction:
        • 0.8% overt hyperthyroidism
        • 3.4% subclinical hyperthyroidism
        • 0.9% overt hypothyroidism
        • 5.6% subclinical hypothyroidism
      • Thyroid dysfunction was NOT associated with global cognitive function, executive function, or risk of dementia
    • Commentary: This data suggests that thyroid dysfunction was NOT associated w/ cognitive impairment.

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Gastrointestinal Studies

  • Serum Gastrin Predicts Hydrogen-Producing Small Intestinal Bacterial Overgrowth in Patients with Abdominal Surgery: A Prospective Study
    • Aim: Evaluate the prevalence of SIBO and investigate serum gastrin and pepsinogen as predictors of SIBO in patients with abdominal surgery
    • Prospective study of:
      • 30 healthy controls and 146 patients w/ history of hysterectomy/ gastrectomy/ or cholecystectomy 
      • Glucose breath test, gastrin, and pepsinogen levels measured
    • SIBO rates were significantly higher in patients with histories of abdominal surgery than than in controls (37.6% vs 13.3%)
      • Among SIBO+ patients:
        • 36% had hysterectomy 
        • 96% had gastrectomy
        • 11% had cholecystectomy
    • Gastrin levels were higher (>29) in the hydrogen-predominant SIBO group compared with methane-predominant SIBO group
    • Take Home: History of abdominal surgery (especially gastrectomy) and higher gastrin levels were independent predictors of SIBO.
  • Increase in the Lipopolysaccharide Activity and Accumulation of Gram-Negative Bacteria in the Stomach with Low Acidity
    • 158 patients who had endoscopy
    • Lipopolysaccharide (LPS) activity measured in gastric fluid and gram-negative bacteria (GNB) counts measured in saliva and gastric fluid
    • Higher LPS activity found in gastric fluid w/ weak acidity 
    • Compared to the GNB count in the saliva, the GNB count was:
      • The SAME in those In those w/ weak gastric fluid acidity
      • LOWER in those w/ high acidity 
    • Commentary: Low HCl production may be a predisposing factor for dysbiosis and SIBO. This also highlights the possibility that SIBO may have a top-down approach where GNB may migrate to the small bowel in those w/ lower acidic contents.

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Thyroid & Hormones Studies


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Diet & Lifestyle Studies

  • Exercise Reduces Medication for Metabolic Syndrome Management: A 5-Year Follow-up Study
    • 51 participants w/ metabolic syndrome (MetS) randomized to exercise intervention (HIT 3x/wk) or control group
    • After 5 years, the exercise group had:
      • Reduced MetS markers (e.g. blood pressure, glucose)
      • Improved cardiorespiratory fitness
      • NO change in medication use whereas the control group had a 2x increase use of meds 
    • Commentary: Just a few sessions a week of exercise can result in significant improvement in metabolic markers.

Discussion

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