Research Briefs for Practitioners – September 2022 - Dr. Michael Ruscio, DNM, DC

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Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – September 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 68

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Podcast Summary


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Featured Study


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Gastrointestinal Studies

  • Gut microbiota–derived metabolite trimethylamine-N-oxide and multiple health outcomes: an umbrella review and updated meta-analysis
    • Aim: Assess the association between elevated plasma TMAO and various health outcomes
    • Higher TMAO was associated with: 
      • 60% increased risk of all-cause mortality 
        • 37 studies, 38,862 participants
      • 74% increased risk major adverse cardiovascular events 
        • 36 studies, 39,314 participants 
      • 39% increased risk of hypertension
        • 15 studies, 18,854 participants 
      • 75% increased risk of diabetes 
        • 18 studies, 22,999 participants
      • Reduced kidney function (large effect size) 
        • 20 studies, 29,497 participants
    • Commentary: Elevations in TMAO are associated with multiple negative health outcomes. This highlights the connection between the gut microbiome and various cardiovascular and metabolic outcomes.

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Thyroid & Hormones Studies


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Diet & Lifestyle Study


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Episode 67

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Podcast Summary


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Featured Study

  • Levothyroxine treatment and gastric juice pH in humans: the proof of concept 
    • 61 Hashimoto’s thyroiditis patients with upper GI symptoms on LT4, categorized by:
      • Normal stomach acidity (pH ≤ 2) 
      • Low stomach acidity (pH > 2) 
    • Compared to normal stomach acidity, patients with low stomach acidity were associated with: 
      • 23% higher doses of LT4 required
      • Higher prevalence of H. pylori infections (92%) 
    • H. Pylori infections were associated with higher: 
      • Serum gastrin (357 + H. pylori vs 39 pg/ml – H. pylori)
      • Positive anti-parietal cell antibodies (83% vs 22%)  
      • 20% higher LT4 dose required
    • Commentary: This study highlights the importance of improving gut health when treating thyroid disease. Improving the gut may allow patients to reduce their LT4 dose due to enhanced absorption.

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Gastrointestinal Studies

  • Physical activity for treatment of irritable bowel syndrome
    • 11 RCTs, 622 participants 
    • This meta-analysis found physical activity, such as yoga or treadmill, led to:
      • Improved IBS symptoms
      • NO improvement in quality of life
      • NO improvement in abdominal pain  
    • Commentary: This study found exercise provides benefit for patients with IBS, which reinforces the use of lifestyle as foundational for treating IBS.
  • Dysbiosis in the Gut Microbiota in Patients with Inflammatory Bowel Disease during Remission
    • 98 IBD patients in remission, 97 healthy controls
    • Stool samples were collected on all participants
    • Compared to healthy controls, IBD patients had:
      • Lower microbiome alpha diversity 
      • Less beneficial bacteria (Akkermansia, Coprococcus, Oscillibacter
      • More pathogenic bacteria (Enterobacteriaceae family)
    • Commentary: Even in remission, IBD patients have more dysbiosis than healthy controls. Dr. Ruscio wanted me to add this is why we don’t treat numbers only; a patient in remission is the win and there is not need to make dysbiosis ‘perfect’.
  • Beneficial Effects of Repeated Washed Microbiota Transplantation in Children With Autism
    • 42 autistic children treated with 2-6 fecal microbiota transplants (FMT) 
    • FMT led to improvements in:  
      • Autism behavior scores
      • Sleep disturbances
      • Constipation 
    • Children that had more FMTs saw greater improvement in symptoms
    • Commentary: FMT led to improvements in autism and associated symptoms. This highlights the gut-brain connection. Keep in mind that there was no control group. 
  • The impact of treatment with bile acid sequestrants on quality of life in patients with bile acid diarrhoea
    • 47 patients with chronic diarrhea and positive for bile acid malabsorption (BAM)
      • 51% with bile acid diarrhea alone (BAD)
      • 23% with Crohn’s disease with ileal resection (CD) 
      • 26% with post-cholecystectomy (PC) 
    • Treatment with WelChol led to positive responses in: 
      • 82% with CD
      • 58% with PC
      • 42% with BAD
    • Those with CD had the most severe BAM based on a SeHCAT test
    • Commentary: Those with Crohn’s Disease and no terminal ileum (where bile is reabsorbed) experienced the greatest response to treatment and also had the worse degree of bile acid malabsorption. This highlights the importance of terminal ileum function health and improving BAM.
  • A No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: Can It Be Real?
    • Retrospective study, 269 patients with confirmed Celiac disease (CD)
    • The sensitivity and specificity of utilizing tissue transglutaminase antibodies (tTG-IgA) for diagnosing CD were tested by using the following cutoffs: 
      • ≥ 100 U/mL (sensitivity 72%, specificity 100%)
      • ≥ 52.7 U/mL (sensitivity 90%, specificity 100%) 
      • ≥ 29.4 U/mL (sensitivity 100%, specificity 99.5%)
    • Commentary: Using various cutoffs for tTG-IgA can help determine likelihood of CD.

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Thyroid & Hormones Studies

  • Thyroid Disorders and Dementia Risk: A Nationwide Population-Based Case-Control Study
    • 7,843 adults with dementia, 7,843 healthy controls
    • The risk of developing dementia was:
      • 81% greater if they had a history of hypothyroidism
      • 3x greater if they had a history of hypothyroidism and required thyroid hormone replacement
    • Commentary: This observational study found an increased risk of dementia in those with a history of hypothyroidism. 

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Diet & Lifestyle Studies


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Episode 66

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Featured Study

  • Efficacies of prokinetics and rifaximin on the positivity to glucose breath test in patients with functional dyspepsia: randomized trial
    • 83 patients with SIBO and dyspepsia, randomized to: 
      • Prokinetic (mosapride)
      • Rifaximin 
      • Prokinetic + rifaximin 
    • All patients underwent a glucose breath test after treatment
    • After 2 weeks, there was NO significant difference in SIBO eradication rates: 
      • Prokinetic + rifaximin (35%) 
      • Rifaximin (32%) 
      • Prokinetic  (17%)
    • All treatments led to similar reductions in hydrogen and methane gas
    • Commentary: This study found that 1) there was NO difference in SIBO eradication rates when adding a prokinetic to rifaximin and 2) restoring normal gut motility can be as effective as rifaximin for eradicating SIBO in this study. 

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Gastrointestinal Studies


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Thyroid & Hormones Studies

  • Is thyroid autoimmunity a predisposing factor for fibromyalgia? A systematic review and meta-analysis
    • 5 studies
    • Compared to healthy controls, patients with fibromyalgia were more likely to have positive: 
      • TPO antibodies (3.4x more prevalent)
      • Tg antibodies (2.2x more prevalent)
      • However, there was NO correlation between fibromyalgia severity and degree of thyroid antibody elevation
    • Those with fibromyalgia and thyroid antibodies were 2x more likely to be postmenopausal
    • Commentary: Fibromyalgia may be associated with thyroid autoimmunity and menopausal status.

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Diet & Lifestyle Studies


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Episode 65

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Featured Studies

  • Effects of a low FODMAP diet on the colonic microbiome in irritable bowel syndrome: a systematic review with meta-analysis
    • 9 RCTs, 403 patients with IBS, randomized to:
      • Control diets
      • Low FODMAP diet (LFD)
    • Stool analysis was performed on all patients
    • Compared to control diets, the LFD led to: 
      • NO difference in overall microbiome diversity
      • NO difference in short chain fatty acid production
      • Lower abundance of bifidobacteria
    • Commentary: Despite a reduction in fermentable fiber, a LFD did NOT lead to lower SCFA or microbiome diversity. This puts a hole in the argument that a low FODMAP diet is not optimal because of lower SCFA production.

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Gastrointestinal Studies

  • Efficacy and Safety of High-dose Cholecalciferol in Patients With Inflammatory Bowel Disease Receiving Infliximab
    • 43 patients with IBD and vitamin D deficiency, treated with either: 
      • Low dose vitamin D (50,000 IU every 4-5 weeks)
        • =1,600 IU/d
      • High dose vitamin D (100,000 IU every 6-8 weeks)
        • = 2,000 IU/d
    • In both groups, vitamin D treatment led to:
      • Only 37% of patients achieving vitamin D sufficiency (≥ 30 ng/mL) 
      • NO difference in IBD symptoms 
    • Commentary: Patients with IBD likely require a higher dose of vitamin D, which may be because inflammatory conditions “utilize” more vitamin D.

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Thyroid & Hormones Study

  • The effect of oral vitamin E and omega-3 alone and in combination on menopausal hot flushes: A systematic review and meta-analysis
    • 9 studies, 1100 menopausal participants with hot flashes, randomized to:
      • Placebo
      • Vitamin E alone
      • Omega 3 alone
      • Vitamin E + Omega 3 
    • Compared to placebo: 
      • Combined vitamin E + omega 3 led to a reduction in hot flash intensity (small effect size) 
      • Vitamin E or omega 3 alone did NOT improve hot flashes 
    • Commentary: Vitamin E + omega 3 may slightly improve hot flashes in menopausal women. Consider adding in these nutrients in addition to basic lifestyle support and female hormone adaptogens for improving hot flashes.

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Diet & Lifestyle Studies


Discussion

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