Research Briefs for Practitioners – March 2023 - Dr. Michael Ruscio, DC

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Future of Functional Health Review Clinical Newsletter

Research Briefs for Practitioners – March 2023

by the Ruscio Institute for Functional Health 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 89

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Gastrointestinal Studies

Efficacy of Saccharomyces boulardii CNCM I-745 probiotic drug in the prevention and treatment of diarrhea in hospitalized patients with new coronavirus infection COVID-19.

  • Does S. Boulardii reduce diarrhea in hospitalized covid patients?
  • Clinical trial: 120 hospitalized patients w/ covid related pneumonia 
    • Antibiotics alone
    • Antibiotics + S. boulardii
  • Treatment led to:
    • 64% reduced diarrhea
    • Shorter hospital duration 


Probiotics and synbiotics in chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials.

  • Do probiotics and synbiotics improve constipation?
  • Summary: 34 RCTs, ~1200 participants w/ constipation
    • Control 
    • Probiotics (formulas varied, included soil based, lacto, bifido)
    • Synbiotics 
  • Probiotics improved overall stool frequency (medium effect size), but no change in stool consistency
  • Synbiotics had no effects on constipation


Bacillus coagulans TBC169 probiotics for the recovery of intestinal function after gynecological laparoscopic surgery: a randomized, placebo-controlled trial.

  • Do probiotics improve outcomes in those undergoing abdominal surgery? 
  • RCT: Women with recent abdominal surgery were treated with:
    • Placebo
    • Soil based probiotics
  • Probiotics led to reduced surgery side effects (9% probiotics vs 40% control)


The evaluation of different types fecal bacteria products for the treatment of recurrent Clostridium difficile associated diarrhea: A systematic review and network meta-analysis

  • Does FMT work better than antibiotics for recurrent C. Diff infections? 
  • Summary: 10 RCTs, 765 participants with recurrent C. Diff
    • Antibiotics
    • FMT
  • C. Diff cure rates were 7-8x higher with FMT compared to antibiotics


Fecal microbiota transplantation relieves abdominal bloating in children with functional gastrointestinal disorders via modulating the gut microbiome and metabolome

  • Does FMT improve GI symptoms in children?
  • Clinical trial: 12 children with functional GI disorder, treated with FMT
  • After 2 months, FMT led to:
    • Improved GI symptoms (bloating, pain, diarrhea)
  • Shift towards healthier microbiome (similar to healthy controls)


Mindfulness Intervention Decreases Frequency and Severity of Flares in Inactive Ulcerative Colitis Patients: Results of a Phase II, Randomized, Placebo-Controlled Trial

  • Do mindfulness practices reduce flares in UC patients?
  • RCT: 43 inactive UC patients treated with:
    • Placebo
    • Mindfulness practice
  • After 1 year, IBD flares occurred in:
    • 22% in placebo group
    • 0% in mindfulness group

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Thyroid & Hormones Studies

Supplementation with myo-inositol and Selenium improves the clinical conditions and biochemical features of women with or at risk for subclinical hypothyroidism

  • Does myo-inositol + selenium improve subclinical hypothyroidism and thyroid antibodies?
  • 148 women with either:
    • SCH
    • Euthyroid + TPO/Tg
  • All treated with myo-inositol and selenium 
  • Treatment improved: 
    • TSH levels (5.9 → 4.6 mU/l)
    • Tg-ab (-46 IU/L)
    • TPO-ab (-21 IU/L)
  • Other benefits: 
    • More regular menstrual cycles
    • Improved fatigue 
  • Notes: This study didn’t report % SCH converted to euthyroid

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Diet & Lifestyle Studies

The influence of exercise interventions on cognitive functions in patients with amnestic mild cognitive impairment: A systematic review and meta-analysis

  • Does exercise improve cognitive function?
  • Summary: 10 RCTs, 575 participants with mild cognitive impairment
    • Control group
    • Exercise (aerobic, strength, dancing)
  • Various types of exercise led to improved overall cognition function (medium effect size)


Fish oil administration combined with resistance exercise training improves strength, resting metabolic rate, and inflammation in older adults

  • Does fish oil improve strength training outcomes? 
  • RCT: 28 healthy participants
    • Strength training 
    • Strength training + fish oil
  • Fish oil + exercise did NOT lead to greater strength gains than strength training alone


Effect of Benson’s relaxation therapy alone or combined with aerobic exercise on cortisol, sleeping quality, estrogen, and severity of dyspeptic symptoms in perimenopausal women with functional dyspepsia

  • Does stress reduction and exercise improve GI symptoms, sleep and mood? 
  • RCT: 60 perimenopausal women with dyspepsia
    • Stress reduction (breathing and muscle relaxation)
    • Aerobic exercise + stress reduction
  • After 2 months, BOTH groups had improved:
    • GI symptoms
    • Sleep
    • Mood
  • Trend in greater symptomatic improvements with addition of exercise 
  • Note: Exercise group saw significant improvement in estrogen levels


Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis

  • Does berberine improve blood sugar in diabetics?
  • Summary: 37 RCTs, ~3,000 participants with type 2 diabetes
    • Medication 
    • Berberine +/- medication 
  • Berberine led to greater reductions in:
    • Fasting glucose (-15 mg/dL) 
    • HbA1c (-0.6%)
  • Medication side effects (-27%)

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Episode 90

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Gastrointestinal Studies

Health Effects of Infant Formula Supplemented with Probiotics or Synbiotics in Infants and Toddlers: Systematic Review with Network Meta-Analysis

  • Do healthy infants/toddlers benefit from supplementation with probiotics?
  • Summary: 26 RCTs, 3,495 healthy infants and children
    • Placebo
    • Probiotics (formulas highly varied across studies, included strep thermophilus, lacto/bifido +/- prebiotics) 
  • Probiotics led to reduced: 
    • Colic (large effect size)
    • Regurgitation (large effect size)
    • Need for antibiotics (large effect size) 
    • Respiratory infections (small effect size) 

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Multi-Strain Synbiotic in Patients with Functional Diarrhea and High Fecal Calprotectin Levels: A Pilot Study

  • Do synbiotics improve functional diarrhea? 
  • RCT: 39 participants with functional diarrhea and elevated calprotectin
    • Placebo
    • Synbiotics (lacto/bifido + FOS)
  • After 2 months, synbiotics led to improved:
    • Stool consistency
    • Bowel movement satisfaction
  • There was NO difference in:
    • Stool frequency
    • Fecal calprotectin


Shift work is significantly and positively associated with possible gastro-esophageal reflux disease: A meta-analysis study

  • Does shift work increase risk of GERD?
  • Summary: 26,940 shift workers
  • Shift work was associated with a 53% increased risk for GERD


Therapeutic Effects of Butyrate on Pediatric Obesity: A Randomized Clinical Trial

  • Does butyrate improve obesity in children?
  • RCT: 48 obese children
    • Diet and exercise 
    • Butyrate + diet and exercise
  • After 6 months, the addition of butyrate led to greater improvements in:
    • BMI (-3 butyrate vs -0.8) 
    • Waist circumference (-5 vs -0.3 cm)
    • Insulin (-7.7 vs -2.4 μU/mL)
  • NO effect on lipid or fasting glucose levels

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Diet & Lifestyle Studies

Association between vitamin D supplementation and mortality: systematic review and meta-analysis

  • Does vitamin D supplementation reduce risk of dying from any cause?
  • Summary: 50 RCTs, 74,655 participants
    • Control 
    • Vitamin D
  • No effect on:
    • All cause mortality
    • Cardiovascular-related death
  • 15% reduced risk of cancer


The Effect of Aerobic Exercise on Cognitive Function in People with Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

  • Does aerobic exercise improve cognitive function in those with Alzheimer’s disease?
  • Summary: 15 RCTs, 909 participants with Alzheimer’s disease
    • Control
    • Aerobic exercise
  • Cognitive function was improved with just 30 minutes of aerobic exercise, 3x/week
  • Note: Those with the worst baseline cognitive function saw the greatest improvement


Gradual Strength Training Improves Sleep Quality, Physical Function and Pain in Women with Fibromyalgia

  • Does strength training improve fibromyalgia-related concerns?
  • 41 women with fibromyalgia treated with strength training (60 min 2x/week)
  • After 6 months, strength training led to improved:
    • Pain
    • Physical performance
    • Sleep quality
  • NO effect on anxiety or fatigue
  • Note: Consistent finding in literature that strength training doesn’t improve energy for ME/CFS either, but aerobic training does. Supports the use of both strength and aerobic training for comprehensive symptomatic improvement.

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Episode 91

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Gastrointestinal Studies 

Microbiome-Targeted Therapies as an Adjunct to Traditional Weight Loss Interventions: A Systematic Review and Meta-Analysis

  • Do probiotics help with weight loss?
  • Summary: 21 studies, ~1,200 overweight adults
    • Diet and exercise
    • Diet and exercise + probiotics (varied by study, included lacto/bifido, streptococcus) +/- prebiotics
  • Compared to diet and exercise alone, probiotics/prebiotics led to an additional 1.6 lbs of weight loss


The effect of probiotic and synbiotic supplementation on appetite-regulating hormones and desire to eat: a systematic review and meta-analysis of clinical trials

  • Do probiotics affect hormones associated with hunger?
  • Summary: 26 RCTs, 1,536 participants (healthy and metabolically unhealthy) 
    • Placebo
    • Probiotics (lacto/bifido) +/- prebiotics
  • Probiotics +/- prebiotics led to:
    • Reduced leptin (small effect size)
    • Increased desire to eat (small effect size)
    • NO effect on weight


A randomized controlled trial of an oral probiotic to reduce antepartum group B Streptococcus colonization and gastrointestinal symptoms

  • Do pregnant women benefit from taking probiotics? 
  • RCT: 83 healthy pregnant women
    • Placebo
    • Probiotics (lacto/bifido)
  • Probiotic supplementation during pregnancy led to: 
    • Reduced pregnancy-associated GI symptoms (moderate effect size) 
    • NO reduction in strep B colonization (common issue during pregnancy)


Impact of Synbiotic Therapy on the Quality of Life in Patients with Mild-to-Moderately Active Ulcerative Colitis

  • Do synbiotics improve ulcerative colitis outcomes? 
  • RCT: 40 participants with mild-to-moderate ulcerative colitis
    • Placebo
    • Synbiotics (lacto/bifido, Enterococcus, Streptococcus + prebiotics) 
  • After 2 months, synbiotics had NO effect on:
    • Remission rates (56% synbiotics vs 33% controls)
    • Quality of life
  • Note: Trend in high remission rate for synbiotics, but not statistically significant likely due to small sample size


Candida species detection in patients with chronic periodontitis: A systematic review and meta-analysis

  • Is candida associated with increased risk of gum disease?
  • Summary: 26 studies assessing the oral microbiome
  • Compared to healthy people, the presence of Candida spp in the mouth was associated with a 76% increased risk of developing gum disease

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Thyroid & Hormones Studies

Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody-Positive Women

  • What percentage of euthyroid, TPO positive women will progress to hypothyroidism?
  • Observational study: 940 euthyroid women with TPO antibodies
    • Placebo
    • Levothyroxine
  • 7% progressed to either SCH or over hypothyroidism, with no significant difference between treatment groups


A comparison of the effects of cinnamon, ginger, and metformin consumption on metabolic health, anthropometric indices, and sexual hormone levels in women with poly cystic ovary syndrome: A randomized double-blinded placebo-controlled clinical trial

  • What effect do ginger, cinnamon and metformin have on women with PCOS?
  • RCT: 83 women with PCOS
    • Placebo
    • Ginger
    • Cinnamon
    • Metformin
  • After 2 months, metformin and cinnamon led to similar improvements in:
    • Testosterone 
    • Insulin
    • Weight loss
  • Note: Cinnamon was as effective as a medication for improving some aspects of PCOS

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Diet & Lifestyle Studies

Effects of Cold-Water Immersion Compared with Other Recovery Modalities on Athletic Performance Following Acute Strenuous Exercise in Physically Active Participants: A Systematic Review, Meta-Analysis, and Meta-Regression

  • What effect does cold water immersion have on acute exercise recovery?
  • Summary: 28 studies on adults after exercise
    • Control (active recovery, cryotherapy, etc)
    • Cold-water immersion (<59℉)
  • Cold water immersion was the most effective for reducing muscle soreness


Effects of exercise on obsessive-compulsive disorder symptoms: a systematic review and meta-analysis

  • Can exercise improve obsessive/compulsive thinking?
  • Summary: 6 studies, 137 participants with obsessive-compulsive disorder (OCD)
    • All Treated with physical activity (aerobic exercise, yoga, etc)
  • Regular exercise led to reduced:
    • OCD symptom scores (large effect size)
    • Depression (medium effect size)
    • Anxiety (medium effect size)
  • Interesting thought: How does OCD compare with those who are obsessed/overly focused on their health condition? 


The effect of aerobic exercise on metabolic parameters of patients with non-alcoholic fatty liver disease: systematic review and meta-analysis

  • Does aerobic exercise improve metabolic health?
  • Summary: 16 studies, 710 participants with fatty liver disease
    • Control
    • Aerobic exercise
  • Aerobic exercise led to improved:
    • Blood sugar balance (glucose, insulin, A1c)
    • Lipids (triglycerides, LDL-C)


Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial

  • What effect does stress reduction and exercise have on cognitive function? 
  • RCT: 585 older adults with subjective cognitive concerns
    • Exercise (aerobic + strength)
    • Mindfulness based stress reduction
    • Exercise + mindfulness
  • After 6 months, NO groups saw improved cognitive function  


Daytime Sleepiness and Quality of Life in Obstructive Sleep Apnoea Patients before and after Long-Term Mandibular Advancement Device Treatment

  • What effect does a mandibular advancement device have on sleep apnea? 
  • 27 participants with sleep apnea, 32 healthy controls
    • All treated with mandibular advancement device
  • Long-term treatment (~1 to 2 years) led to: 
    • Reduced daytime sleepiness (large effect size
    • Improved energy levels (moderate effect size


The effects of oral magnesium supplementation on glycaemic control in patients with type 2 diabetes: a systematic review and dose-response meta-analysis of controlled clinical trials

  • Does magnesium improve blood sugar control? 
  • Summary: 18 RCTs on participants with type 2 diabetes
    • Control
    • Magnesium (~500 mg/day)
  • After 6 months, magnesium led to improved:
    • HbA1c (-0.48%)
    • Fasting blood glucose (-15.58 mg/dl)

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Episode 92

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Gastrointestinal Studies

Efficacy and Safety of Fecal Microbiota Transplantation in Treatment of Clostridioides difficile Infection among Pediatric Patients: A Systematic Review and Meta-Analysis

  • Is FMT safe and effective for treating children with C. diff?
  • Summary: 14 studies, ~ 900 children with acute or recurrent C. Diff infection
    • All treated with FMT
  • FMT led to resolution of C. diff infection in 86% of participants
  • 15% had side effects


Efficacy of Oral Psyllium in Pediatric Irritable Bowel Syndrome: A Double-Blind Randomized Control Trial

  • Does psyllium improve IBS in children?
  • RCT: 81 children with IBS received
    • Placebo
    • Psyllium
  • After 1 month, psyllium led resolution of IBS symptoms in 44% (vs 10% in placebo)


Interactions between symptoms and psychological status in irritable bowel syndrome: An exploratory study of the impact of a probiotic combination

  • Do probiotics improve anxiety and depression associated with IBS?
  • Interventional trial: 40 IBS participants with anxiety/depression
    • All treated with probiotics (bifidobacterium only)
  • Pobiotics led to improved:
    • IBS symptoms in 82% 
    • Anxiety in 61%
    • Depression in 61%
    • Sleep quality 
    • Cortisol levels (cortisol awakening response) 
  • Note: IBS scores and cortisol returned to baseline 2 months after d/c probiotics, but anxiety/depression still improved


Orally Ingested Probiotics, Prebiotics, and Synbiotics as Countermeasures for Respiratory Tract Infections in Nonelderly Adults: A Systematic Review and Meta-Analysis

  • Do probiotics and/or prebiotics improve upper respiratory tract infection outcomes?
  • Summary: 42 studies, ~9,000 healthy adults received:
    • Placebo
    • Probiotics (formulas varied, included: lacto/bifido, Enterococcus, Lactococcus)
    • Prebiotics
    • Synbiotics
  • Probiotics led to:
    • 9% lower risk of getting URI
    • Reduced duration and severity (small effect size)
  • Unclear benefit of prebiotics/synbiotics (only 3 studies)


The Prevalence of Small Intestinal Bacterial Overgrowth in Patients with Non-Alcoholic Liver Diseases: NAFLD, NASH, Fibrosis, Cirrhosis-A Systematic Review, Meta-Analysis and Meta-Regression

  • What’s the prevalence of SIBO in fatty liver disease?
  • Summary: 18 studies, ~1,200 participants with liver disease
  • SIBO detected in about 35% of those with fatty liver disease


Gut microbiome signatures reflect different subtypes of irritable bowel syndrome

  • Are certain microbiome profiles associated with different IBS subtypes?
  • 942 participants with IBS, 942 controls
    • All underwent PCR stool testing
  • Compared to controls, ALL IBS subtypes had:
    • Increased Escherichia/Shigella bacteria
    • Reduced bacterial diversity
  • IBS-D, but NOT IBS-C, had reduced bacterial richness (# of bacterial species)
  • Authors conclusion: “These findings highlight the importance of personalized gut microbiome modulation approaches in different subtypes for optimal therapeutic effects.”

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Thyroid & Hormones Studies

Environmental exposure to perchlorate, nitrate and thiocyanate, and thyroid function in Chinese adults: A community-based cross-sectional study

  • Does environmental exposure to toxins affect thyroid function?
  • ~2500 euthyroid participants tested for perchlorates (common in drinking water) 
  • Higher levels of perchlorates was associated with: 
    • Lower fT4 and fT3
    • Higher TSH
  • Note: Did not look at conversion rate to hypothyroid


Benefits of physical therapy in improving quality of life and pain associated with endometriosis: Systematic Review and Meta-analysis

  • Does physical therapy improve endometriosis symptoms?
  • Summary: 6 RCTs, women with endometriosis received
    • Placebo
    • Physical therapy
  • Physical therapy led to significant improvements in:
    • Physical function (large effect size)
  • Pain (moderate effect size)

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Diet & Lifestyle Studies

Effect of resistance training on heart rate variability of anxious female college students

  • Does resistance training improve anxiety?
  • RCT: 27 sedentary women with anxiety
    • Control
    • Strength training (2x/week)
  • 2 months of strength training led to reduced anxiety (large effect) 


Effects of inspiratory muscle training on blood pressure- and sleep-related outcomes in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials

  • Does respiratory muscle training improve sleep apnea?
  • Summary: 7 RCTs, 160 participants with sleep apnea
    • Control
    • Inspiratory muscle training
  • Improved sleep quality and fatigue
    • NO change in sleep apnea severity
  • Note: Symptom improvement, no lab improvement


Intermittent fasting and protein pacing are superior to caloric restriction for weight and visceral ifat loss

  • Does intermittent fasting + increased protein intake lead to more weight loss?
    • RCT: 41 obese participants
    • Calorie restriction (~70 g protein/day)
    • Fasting + higher protein (~135 g/day)
  • Caloric intake and exercise equal between groups
  • After 2 months, both groups had similar reductions in:
    • Weight (-18 lbs IF vs -11 lbs calorie restriction)
    • Visceral fat mass (-33% vs -14%)
    • Desire to eat (-17% vs -1%)
  • Note: Small sample size, hence not statistically significant difference


Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Biomarkers of Systemic Inflammation: 4-Year Findings from the VITAL Randomized Trial

  • Do vitamin D or omega-3s fatty acids lower inflammation?
  • RCT: ~2,700 participants received:
    • Placebo
    • Vitamin D
    • Omega-3 fatty acid
    • Vitamin D + omega-3s
  • Only Vitamin D led to a reduction in hsCRP (-19%), but this effect was not found after long-term follow up (4 years)


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