Research Briefs for Practitioners – June 2022 - Dr. Michael Ruscio, DNM, DC
Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – June 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 56

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Featured Study

  • The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality
    • 21,315 participants over 60 years old
    • Randomized to placebo or vitamin D (60,000 IU per month)
    • After 5 years of supplementation and 1,100 recorded deaths, the vitamin D group had:
      • Greater serum vitamin D levels (46 ng/mL vs 30 ng/mL)
      • No difference in overall mortality
      • No difference in cardiovascular disease
      • No difference for cancer
    • Commentary: Administering vitamin D indiscriminately to older individuals did not change the risk of all-cause mortality, cardiovascular disease, or cancer after 5 years of supplementation.

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Gastrointestinal Studies

  • Efficacy of Probiotics for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis
    • 43 RCTs, 5,531 IBS patients treated w/ probiotics
    • Different probiotic strains were evaluated for efficacy 
    • This meta-analysis found that:
      • Bacillus coagulans (soil based probiotic) led to the greatest improvements in IBS symptom scores
      • Length of probiotic therapy (NOT dose) was more influential on clinical outcome in IBS
    • Commentary: This study supports the use of multi-strain/species probiotics in patients with IBS.

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Autoimmunity Study


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Thyroid & Hormones Studies

  • Subclinical hypothyroidism in older individuals
    • Narrative review of subclinical hypothyroidism (SCH)
    • “Studies showed no significantly increased incidence in adverse cardiovascular, musculoskeletal, or cognitive outcomes in individuals aged 65 years or older when serum thyroid-stimulating hormone concentration was 4.5-7.0 mIU/L versus a euthyroid group.”
    • “In older individuals with subclinical hypothyroidism, symptoms of hypothyroidism and cardiac and bone parameters did not improve after levothyroxine treatment.”
    • “Treatment with levothyroxine should be considered for individuals aged 65 years or older with subclinical hypothyroidism when thyroid-stimulating hormone concentration is persistently 7 mIU/L or higher and to not initiate treatment with thyroid-stimulating hormone concentrations of less than 7 mIU/L. Levothyroxine doses should be personalized according to age, comorbidities, and life expectancy.” 
    • Commentary: Take in consideration age and TSH level when deciding to treat SCH or not.

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Diet & Lifestyle Studies


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Episode 55

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Featured Study

  • Pelvic floor biofeedback is an effective treatment for severe bloating in disorders of gut-brain interaction with outlet dysfunction
    • 156 patients with severe bloating
    • All given 2 weeks of diet changes and balloon expulsion test (evaluating patient’s ability to evacuate a stool)
    • 64 were non-responsive – then given pelvic floor electromyography (EMG) and biofeedback 
      • Specifics on biofeedback:
        • First taught to strain more effectively and to coordinate expulsion efforts with their breathing
        • Then taught to relax pelvic floor muscles during straining through EMG imaging 
    • After biofeedback:
      • 54% had major improvement/cure
      • 100% had at least 50% decrease in bloating severity
    • Commentary: Pelvic floor biofeedback can improve non-responsive bloating.

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Gastrointestinal Studies

  • Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies
    • Cross-over study of 19 patients with IBS
    • Participants ingested a test drink containing either:
      • Inulin (20 g) 
      • Psyllium (20 g) 
      • Inulin (20 g) + psyllium (20 g) 
      • Or dextrose (20 g) (placebo)
    • Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours
    • Co-administration of psyllium to inulin significantly reduced the inulin-induced rise in colonic gas levels
    • Commentary: Giving psyllium along with inulin can reduce gas production compared to inulin alone. Adding psyllium to other fiber may increase its tolerability in IBS patients.
  • Small intestinal bacterial overgrowth in patients with inflammatory bowel disease: A case-control study
    • Retrospective study, 86 patients with IBD, 66 healthy controls
    • All participants underwent glucose hydrogen breath tests to assess for SIBO
    • SIBO was more common in: 
      • IBD vs healthy controls (18.6% vs 1.5%)
      • Crohn’s disease vs ulcerative colitis (34.1% vs 4.4%) 
    • Independent risk factors for SIBO in those with IBD included: 
      • Female gender
      • Previous surgery for IBD
    • Commentary: Patients with IBD, specifically Crohn’s disease, had the highest risk of developing SIBO.

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Autoimmunity Studies


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Thyroid & Hormones Studies


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Diet & Lifestyle Studies

  • Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study
    • Retrospective study on 146 patients w/ histamine intolerance (HIT) symptoms 
    • Serum diamine oxide (DAO) levels were measured and categorized by:
      • Low (< 3 U/mL)
      • Moderate (3-10 U/mL)
      • High (> 10 U/mL) 
    • Compared to the high DAO group, those with low DAO experienced:
      • More frequent HIT symptoms (87% vs 29%) 
      • More severe HIT symptoms
    • After 6-8 months of treatment w/ low histamine diet and/or DAO supplementation, patients with moderate DAO levels showed the greatest response to treatment 
    • Commentary: DAO levels correlated with HIT symptom frequency and severity, however response to treatment was greatest in those with moderate levels of DAO.

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Episode 54

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Featured Study

  • Low FODMAP Diet and Probiotics in Irritable Bowel Syndrome: A Systematic Review With Network Meta-analysis
    • 76 RCTs, 8,058 participants
    • Both lactobacillus/bifidobacterium and soil-based probiotics were effective in reducing IBS symptoms:
      • Bacillus species (RR 5.67)
      • Lactobacillus (RR 1.74)
      • Bifidobacterium (RR 1.76) 
    • The combination of Bifidobacterium, Lactobacillus, and Streptococcus (RR 1.50) was the most effective among all the treatment combinations
    • Commentary: This high-quality meta-analysis showed benefit of both lactobacillus/bifidobacterium and soil-based probiotics in improving IBS. It also highlights the superiority of multi-species probiotics.

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Gastrointestinal Studies

  • Probiotics for treatment of chronic constipation in children
    • 14 RCTs, 1,127 pediatric patients w/ constipation
    • Compared to placebo, probiotics alone or in combination with other constipation therapies (e.g magnesium oxide or laxatives) did NOT lead to improved constipation 
    • Constipation was improved with the use of synbiotics (RR  2.3) 
    • Commentary: Synbiotics, not probiotics, were effective in improving constipation.
  • A Randomized Pilot Study to Compare the Effectiveness of a Low FODMAP Diet vs Psyllium in Patients With Fecal Incontinence and Loose Stools
    • 37 patients w/ fecal incontinence and loose stool, randomized to:
      • Low FODMAP diet (LFD) 
      • Psyllium (6 g/d) 
    • After 1 month the LFD group had:
      • More improvement of fecal incontinence severity score (-6.8 LFD vs -3.3 psyllium)
      • NO significant difference in proportion of patients who experienced >50% reduction in fecal incontinence episodes (38.9% LFD vs 50% psyllium)
    • Both groups experienced similar improvements in quality of life 
    • Commentary: Both LFD and psyllium led to improvements in quality of life and fecal incontinence frequency, while LFD led to greater improvements in severity of fecal incontinence.
  • A systematic review and meta-analysis on the efficacy of probiotics for bacterial vaginosis
    • 18 studies, 1,651 patients w/ bacterial vaginosis (BV)
    • Compared to antibiotics alone, antibiotics + probiotic led to: 
      • Lower recurrence rate (RR 0.4) 
      • Greater cure rate (1.2)
    • Compared to placebo, probiotics led to: 
      • Lower recurrence rate (RR 0.3)
      • Greater cure rate (RR 10) 
    • Compared to antibiotics, probiotics led to: 
      • Lower recurrence rate (RR 0.3)
      • Greater cure rate (RR 1.3) 
    • Probiotic treatment for 1-3 months led to greater clinical outcomes compared to <1 month
    • Commentary: Probiotic supplementation for 1-3 months improved clinical outcomes in patients with BV. Note the lower recurrence rate and greater cure rates when comparing probiotics alone vs antibiotics + probiotics

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Thyroid & Hormones Study


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Diet & Lifestyle Studies

  • Dose-related meta-analysis for Omega-3 fatty acids supplementation on major adverse cardiovascular events
    • 19 RCTs, 97,709 participants randomized to:
      • Control
      • Omega 3 supplement (doses <1 g/day to ≥3 g/day)
    • Overall, omega-3 supplementation was NOT associated with a reduced rate of:
      • All-cause mortality
      • Cardiac death
      • Myocardial infarction
      • Stroke 
    • However, omega 3 supplementation at 2g/day was associated with reduced cardiac mortality (RR 0.5) 
    • Commentary: Omega 3 supplementation at 2 g/day was associated with lower cardiac mortality, however other doses did NOT show cardiovascular benefit.
  • Sleep apnea and the risk of dementia: A systematic review and meta-analysis
    • 11 studies, 1.3 million participants
    • Sleep apnea was associated with an increased risk of:
      • Neurocognitive disorder (HR 1.4)
      • Alzheimer’s disease (HR 1.2)
      • Parkinson’s disease (HR 1.5)
      • Lewy-body dementia (HR 2.0) 
    • Commentary: This large study shows an association between sleep apnea and dementia. Keep in mind this is an observational study.
  • Myofunctional therapy for OSA: a meta-analysis
    • 15 studies, 237 sleep apnea patients treated with myofunctional therapy 
    • Myofunctional therapy led to improved:
      • Sleep apnea scores (large effect size) 
      • Lowest oxygen saturation (moderate effect size)
      • Sleepiness scores (large effect size) 
    • Commentary: Myofunctional therapy is an effective therapy option for patients with sleep apnea.

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Episode 53

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Featured Studies

Final Commentary: These studies show 1) the benefit of probiotics in those with colon cancer and 2) the safety of probiotics in those with cancer.


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Gastrointestinal Studies

  • Sleep positional therapy for nocturnal gastroesophageal reflux: a double-blind, randomized, sham-controlled trial
    • 100 nocturnal reflux patients, asked to sleep in left lateral decubitus position
    • Randomized to:
      • Sham: wearable device that vibrated during first 20 minutes 
      • Intervention: wearable device that vibrated when patient sleeping on right side
    • The intervention group had:
      • Less time sleeping on right side (2% vs 24%)
      • More time sleeping on left side (61% vs 39%)
      • More patients that had >50% reduction in symptoms (44% vs 20%)
    • Commentary: A wearable device that helps patients sleep on the left side can improve nocturnal reflux.

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Thyroid & Hormones Study

  • Vitamin B12 (Cobalamin) Deficiency in Overt and Subclinical Primary Hypothyroidism
    • 133 patients, categorized by: 
      • Healthy control
      • Subclinical hypothyroid
      • Overt hypothyroid
    • NO difference in prevalence of B12 deficiency between all 3 groups
    • Among hypothyroid patients with B12 deficiency, 7.5% also had intrinsic factor antibodies present 
    • Commentary: Overt or subclinical hypothyroidism is not associated with B12 deficiency.

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Diet & Lifestyle Studies

  • Association between long-term exposure to PM 2.5 and hypertension: A systematic review and meta-analysis of observational studies
    • Examining the association between long-term exposure to particulate matter with a diameter of ≤2.5 μm (PM2.5) and hypertension
    • 27 studies, 42 million participants
    • Each dose increment in PM2.5 was significantly associated with the risks of hypertension incidence (RR = 1.21)
    • Commentary: PM2.5 comes primarily from combustion. Fireplaces, car engines, and coal- or natural gas–fired power plants are all major PM2.5 sources. This meta-analysis strengthens the relationship between air pollution and hypertension.

Discussion

I care about answering your questions and sharing my knowledge with you. Leave a comment or connect with me on social media asking any health question you may have and I just might incorporate it into our next listener questions podcast episode just for you!

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