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

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Future of Functional Health Review Clinical Newsletter

Research Briefs for Practitioners – June 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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Episodes 101 & 102

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Multi-Probiotics ameliorate Major depressive disorder and accompanying gastrointestinal syndromes via serotonergic system regulation

  • Can probiotics improve depression?
  • RCT: 28 participants with major depression, randomized to:
    • Placebo
    • Multi-strain probiotics 
      • Bifidobacterium and Pediococcus, 12 billion CFU/day
  • After 1 month, probiotics led to:
    • Improved depression scores (moderate effect) 
    • Decreased GI symptoms
    • NO overall effect on the gut flora


Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

  • Do probiotics favorably impact health markers associated with depression?
  • Meta-analysis: 19 RCTs, 1,461 participants with various mood disorders, randomized to:
    • Control
    • Probiotics
      • Varied by study, included lactobacillus, bifidobacterium, streptococcus thermophilus
  • Probiotics led to:
    • Increased BDNF (small effect)
    • Reduced CRP (small effect)
    • NO effect on other inflammatory markers (IL-10, TNF-α)
    • NO effect on cortisol
  • Note: Greatest effect in clinical depression


Antimicrobial Properties of Bacillus Probiotics as Animal Growth Promoters

  • Do soil-based probiotics have antimicrobial properties?
  • In-Vitro Study: Bacillus strains were evaluated for their antimicrobial effects
  • Bacillus strains showed antimicrobial activity against:
    • Clostridium perfringens
    • Escherichia coli
    • Staphylococcus aureus
    • Pseudomonas aeruginosa
    • Salmonella enterica


Could the Microbiota Be a Predictive Factor for the Clinical Response to Probiotic Supplementation in IBS-D? A Cohort Study

  • Do probiotics improve IBS symptoms and leaky gut? 
  • Clinical trial: 26 adults with IBS-D treated with:
    • Multi-strain probiotics 
      • Bifidobacterium & lactobacillus blend, 20 billion CFU/day
  • After 1 month, probiotics led to improved:
    • Abdominal pain (resolution in 31%)
    • Diarrhea frequency (4.2 → 2.5 days per week)
    • Overall IBS symptoms
    • Intestinal permeability


The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials

  • Can probiotics increase glutathione and reduce inflammation? 
  • Meta-analysis: 32 RCTs, 2,074 participants with prediabetes or type 2 diabetes, randomized to:
    • Control
    • Probiotics +/- prebiotics
      • Probiotics varied by study, included lactobacillus, bifidobacterium, saccharomyces cerevisiae
  • Probiotics +/- prebiotics led to:
    • Reduced inflammatory markers
      • CRP, TNF-α
    • Increased glutathione
    • Improved antioxidant capacity


Bifidobacterium lactis Probio-M8 improves bone metabolism in patients with postmenopausal osteoporosis, possibly by modulating the gut microbiota

  • Can probiotics improve bone health? 
  • RCT: 40 postmenopausal women with osteoporosis, randomized to:
    • Control
      • Calcium + vitamin D 
    • Probiotics + control
      • Bifidobacterium animalis  
  • After 3 months, the addition of probiotics did NOT improve
    • Bone mineral density


The effects of Bacillus coagulans MTCC 5856 on functional gas and bloating in adults: A randomized, double-blind, placebo-controlled study

  • Do soil-based probiotics help with gas and bloating?
  • RCT: 66 adults with functional gas and bloating, randomized to:
    • Placebo
    • Probiotics
      • Bacillus coagulans, 2 billion CFU/day
  • After 1 month, probiotics led to improved:
    • Overall GI symptom 
    • Indigestion 
    • Stool consistency


Postbiotic gel relieves clinical symptoms of bacterial vaginitis by regulating the vaginal microbiota

  • Do probiotics improve bacterial vaginosis?
  • Clinical trial: 50 women with bacterial vaginosis, treated with:
    • Topical probiotic
      • Lactobacillus, 2 million CFU/day
  • Topical probiotics led to:
    • Remission of bacterial vaginosis in 38%
    • Reduced odor & itching
    • Decreased vaginal opportunistic bacteria


Usefulness of Bifidobacterium longum BB536 in Elderly Individuals With Chronic Constipation: A Randomized Controlled Trial

  • Do probiotics improve chronic constipation in the elderly?
  • RCT: 80 older adults with chronic constipation randomly assigned to:
    • Placebo 
    • Probiotics
      • Bifidobacterium longum, 50 billion CFU/day
  • After 1 month, compared to placebo, those taking probiotics experienced improvements in:
    • Constipation 
    • Stool frequency
    • GERD symptoms
  • Note: Constipation score worsened once probiotics stopped, but GERD symptoms kept improving for additional 1 month


Multistrain Probiotics Supplement Alleviates Asthma Symptoms via Increasing Treg Cells Population: A Randomized, Double-Blind, Placebo-Controlled Trial

  • Do multi-strain probiotics improve asthma?
  • RCT: 40 patients with asthma randomized to:
    • Placebo
    • Probiotics
  • After 2 months, the probiotic group experienced:
    • Improved lung function
    • Increased regulatory T-cells
  • Note: No probiotic species or dosing reported in abstract


Probiotics intervention in preventing conversion of impaired glucose tolerance to diabetes: The PPDP follow-on study

  • Do probiotics reduce the risk of developing type 2 diabetes?
  • RCT: 77 patients with impaired glucose tolerance randomized to:
    • Placebo
    • Probiotics
      • Lactobacillus acidophilus, Bifidobacterium, Enterococcus faecalis
  • After 6 years, compared to placebo, probiotics did NOT:
    • Reduce the risk of developing type 2 diabetes
    • Change the gut microbiota


[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 during COVID-19 treatment?
  • Prospective study: 60 patients hospitalized for COVID-19 received:
    • Antibiotics only
    • Antibiotics and probiotics 
      • Saccharomyces boulardii, 10 billion CFU
  • After 10 days, probiotic use was associated with:
    • 65% reduced risk of diarrhea
    • ~2 day shorter duration of diarrhea
    • ~1 day shorter hospital stay


Effects of probiotics on preventing caries in preschool children: a systematic review and meta-analysis

  • Do probiotics reduce the risk of cavities in children? 
  • Meta-analysis: 17 RCTs, preschool children treated with: 
    • Control
    • Probiotics
  • Probiotics, specifically Lactobacillus rhamnosus, led to: 
    • Reduced risk of cavities

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The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials

  • Does melatonin improve IBS outcomes?
  • Meta-analysis: 4 RCTs, 115 participants with IBS randomized to:
    • Placebo
    • Melatonin
      • Varied by study, 3-8 mg/day
  • Melatonin led to improved:
    • Overall IBS severity (medium effect)
    • IBS-related pain 
    • Quality of life
  • NO effect on:
    • Abdominal distention


Coffee and tea intake with long-term risk of irritable bowel syndrome: a large-scale prospective cohort study

  • Do coffee and tea intake reduce the risk of IBS?
  • Observational study: 425,387 participants 
  • After a 12 year follow-up:
    • Coffee consumption was associated with:
      • 19% reduced risk of IBS (≥4 cups/day) 
      • ~8% reduced risk of IBS (1-3 cup/day) 
    • Tea consumption was associated with: 
      • 13% reduced risk of IBS (~1 cup/day) 


Positive psychological well-being and clinical characteristics in IBS: A systematic review

  • How does IBS impact psychological well-being?
  • Systematic review: 22 observational studies with 4,285 IBS patients
  • Compared to healthy populations, IBS was associated with reduced:
    • Psychological well-being
    • Health-related quality of life


Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis

  • Is IBS a risk factor for colon polyps or colon cancer?
  • Meta-analysis: 14 studies, 681,405 participants with IBS, 2,364,998 controls 
  • Those with IBS had:
    • 71% reduced risk for colorectal polyps
    • NO effect on colon cancer incidence


Epidemiology and risk of colorectal cancer in patients with a history of Helicobacter pylori infection: a population-based study

  • Is H. pylori a risk factor for colon cancer?
  • Observational study: 47,714,750 participants with a history of H. pylori infection
  • Increased risk for colorectal cancer was associated with:
    • Type 2 diabetes (2.9x increased risk for colon cancer)
    • Smoking (2.5x)
    • Obesity (2.3x)
    • IBD (2x)
    • H. pylori infection (1.9x)


Evaluation of plasma zonulin level and its relationship with inflammatory cytokines in patients with vitiligo

  • Is autoimmune disease associated with increased intestinal permeability?
  • Observational study: 41 participants with vitiligo, 41 healthy controls
    • Vitiligo = autoimmune skin condition
  • Compared to controls, those with vitiligo had elevated:
    • Zonulin
    • Lipopolysaccharide
  • Note: Did not assess if GI symptoms were worse in those with increased intestinal permeability


One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial

  • Does more dietary restriction lead to better results in those with GI symptoms?
  • Clinical trial: 129 adults with eosinophilic esophagitis, treated with:
    • 1-food elimination diet
      • Dairy
    • 6-food elimination diet 
      • Dairy, wheat, eggs, soy, shellfish, nuts
  • After 1.5 months, similar improvements were noted in both dietary groups for:
    • Histologic remission
    • Symptom severity
    • Quality of life
  • In those who did NOT respond to a 1-food elimination diet, approximately 1/2 of them responded to a 6-food elimination diet.


Is vitamin B12 deficiency a risk factor for gastroparesis in patients with type 2 diabetes?

  • Is B12 deficiency associated with gastroparesis in type 2 diabetes?
  • Observational study: 100 participants with type 2 diabetes, with or without gastroparesis
  • Vitamin B12 deficiency was associated with:
    • 8.5x higher chance of a gastroparesis diagnosis
    • Gastroparesis symptoms
  • Levels below 189.5 pmol/L were most predictive of gastroparesis 
  • Note: Duration of diabetes and HbA1c levels were more associated with gastroparesis than B12 deficiency


Should we treat Blastocystis sp.? A double-blind placebo-controlled randomized pilot trial

  • Should we treat blastocystis in those with GI symptoms?
  • RCT: 50 participants with persistent GI symptoms and Blastocystis spp infection,  randomized to:
    • Placebo
    • Metronidazole
  • After 10 days, there was NO difference in:
    • Stool consistency
    • Total GI symptoms
  • “Among patients infected with Blastocystis sp, Metronidazole was not better in improving gastrointestinal symptoms, irrespective of subtype or coinfection with other protozoa.”
  • Note: They did not retest to assess eradication rates of blastocystis


Effect of helicobacter pylori infection eradication on serum level of anti-tissue transglutaminase in children with celiac disease

  • Does eradicating H. pylori infections reduce celiac antibodies?
  • Observational study: 88 children with or without celiac disease and H. pylori received:
    • H. pylori eradication therapy
  • Eradication of H. pylori did NOT lead to: 
    • Reduction in celiac antibodies


Association Between Regular Laxative Use and Incident Dementia in UK Biobank Participants

  • Is laxative use associated with the development of dementia?
  • Observational study: 502,229 participants without dementia assessed for laxative use
  • After a 10-year follow-up, laxative use was associated with
    • 51% increased risk for all-cause dementia
    • NO increased risk for Alzheimer’s disease
  • Note: Keep in mind this is observational, so causation cannot be determined. Is it the medications increasing the risk? Or could it be the underlying reason they need the medications (i.e. poor gut health, poor diet, etc) that is contributing to the increased risk?


Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19

  • Is gut dysbiosis associated with worse COVID-19 outcomes?
  • Observational study: 123 participants hospitalized for COVID-19
    • 16S rRNA stool testing performed on all participants
  • Dysbiosis in hospitalized COVID-19 patients was associated with: 
    • 3.7x increased risk of dying
    • Persistent dysbiosis at 3-month follow-up


Improvement of Symptoms in Patients Affected by Chronic Atrophic Gastritis Using L-Cysteine (Acetium®)

  • Does long-term L-Cysteine improve chronic atrophic gastritis?
  • Clinical trial: 330 patients with chronic atrophic gastritis assigned to:
    • No treatment
    • L-cysteine 
      • 300 mg/day
  • After 2 years, those given L-cysteine experienced:
    • Improved gastritis symptoms


​​Antibiotic use as a risk factor for inflammatory bowel disease across the ages: a population-based cohort study

  • Are antibiotics associated with an increased risk of inflammatory bowel disease? 
  • Observational study: 6,104,245 individuals
  • Antibiotic use was associated with: 
    • 41% increased risk for IBD
  • Risk for IBD was highest when antibiotics were used: 
    • More frequently
    • With older age (>40 years old)


Prevalence and Risk Factors Associated With Inflammatory Bowel Disease in Patients Using Proton-Pump Inhibitors: A Population-Based Study

  • Is reflux medication use associated with an increased risk of inflammatory bowel disease?
  • Observational study: 45,586,150 participants with IBD were screened for PPI use
  • PPI use was associated with:
    • 2.8x increased risk for Crohn’s
    • 2x increased risk for ulcerative colitis


Long-term gastrointestinal outcomes of COVID-19

  • Does COVID-19 infection increase the risk of gastrointestinal disorders?
  • Observational study: 154,068 participants with past COVID-19 infections, 5,638795 controls
  • Those with a past COVID-19 infection had an increased risk of: 
    • Constipation (1.6x) 
    • Diarrhea (1.6x) 
    • Peptic ulcers (1.6x) 
    • Irritable bowel syndrome (1.5x)
    • GERD (1.4x) 
    • Dyspepsia (1.4x)
    • Bloating (1.5x)

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Thyroid & Hormones

Impact of fasting on thyrotropin and thyroid status during Ramadan in 292 previously well controlled hypothyroid patients. IFTAR study

  • How does fasting impact thyroid function?
  • Observational study: 292 patients with hypothyroidism taking levothyroxine performed:
    • Ramadan fasting
      • Fasting during daylight hours for 1 month
  • After 1 month, Ramadan fasting led to:
    • Increased TSH levels in 20%
    • No change in TSH in 80%


Correlation Between Vitamin B12 Deficiency and Autoimmune Thyroid Diseases

  • Do those with more significant thyroid autoimmunity have lower B12? 
  • Observational study: 306 patients with and without Hashimoto’s thyroiditis
    • All assessed for B12 deficiency
  • Serum B12 deficiency was associated with:
    • Higher TPO-antibodies (236 IU/mL Hashimoto’s vs 39 IU/mL controls)
  • Note: Around 25% of Hashimoto’s patients have anti-parietal cell antibodies, which is important for B12 absorption.

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Diet & Lifestyle

The effect of cold water immersion on the recovery of physical performance revisited: A systematic review with meta-analysis

  • Does cold water immersion improve physical performance and recovery post-exercise?
  • Meta-analysis: 68 studies, 513 participants underwent cold water immersion post-exercise
  • Cold-water immersion led to improved:
    • Endurance performance
    • Muscle soreness
    • Long-term strength
    • Muscle damage
      • Lower creatine kinase


The impact of time restricted eating on appetite and disordered eating in adults: A mixed methods systematic review

  • Does time-restricted eating impact disordered eating behaviors?
  • Systematic review: 16 studies, participants with disordered eating underwent time-restricted eating 
    • Eating window ≤ 16 hours
  • Time-restricted eating led to: 
    • NO effect on disordered eating scores

Effects of Omega-3 Fatty Acids Supplementation on Serum Lipid Profile and Blood Pressure in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

  • Do omega-3s fatty acids improve cardiometabolic health?
  • Meta-analysis: 8 RCTs, 387 participants with metabolic syndrome, randomized to:
    • Control
    • Omega-3 fatty acids
      • Dosing varied, ranged between ~1-3 grams/day
  • Compared to control, omega-3 fatty acids led to:
    • Decreased blood pressure (medium effect)
    • Decreased triglycerides (small effect)
    • NO effect on other lipid levels


The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis

  • Does fish oil improve physical fitness? 
  • Meta-analysis: 14 RCTs, 1,443 healthy participants received:
    • Placebo
    • Omega 3 fatty acids
  • Omega 3 fatty acids had NO effect on:
    • Physical fitness 
      • Muscle strength, mass or function


Timing of physical activity across adulthood on later-life cognition: 30 years follow-up in the 1946 British birth cohort

  • Does physical activity during adulthood improve cognitive function later in life?
  • Observational study: 1,417 adults were categorized by physical activity level: 
    • Not active 
    • Moderately active (1-4x/month)
    • Highly active (≥5x/month)
  • After a 30-year follow up, those with moderate-to-high activity levels experienced:
    • Better cognitive function later in life
  • While beginning physical activity at any time in life is helpful for cognition, it is even better to encourage people to start as early as possible. 
    • “Being physically active at any time in adulthood is linked with higher later-life cognitive state, but lifelong maintenance of physical activity was most optimal.”


The effect of cognitive behavioural therapy for insomnia in people with comorbid insomnia and sleep apnoea: A systematic review and meta-analysis

  • Does cognitive behavioral therapy improve insomnia?
  • Meta-analysis: 9 studies, participants with insomnia, treated with either:
    • Control
    • CBT-Insomnia (CBT-I)
  • Compared to control, CBT-I led to improved:
    • Insomnia severity (large effect)
    • Insomnia in untreated sleep apnea (large effect)
    • Insomnia in treated sleep apnea (medium effect)
  • Note: CBT-I can improve insomnia even in those with untreated sleep apnea


The effect of caffeine on subsequent sleep: A systematic review and meta-analysis

  • When should you stop consuming caffeine to avoid sleep disruptions? 
  • Meta-analysis: 24 studies 
  • To avoid reductions in sleep quality and duration: 
    • Coffee should be consumed at least 9 hours prior to bedtime
    • Pre-workout supplement should be consumed at least 13 hours prior to bedtime
      • Based on typical caffeine amount (217 mg) in pre-workout


Exercise sustains motor function in Parkinson’s disease: Evidence from 109 randomized controlled trials on over 4,600 patients

  • Does long-term exercise improve Parkinson’s disease outcomes?
  • Meta-analysis: 109 RCTs, 4,631 participants with Parkinson’s disease randomized to:
    • Control
    • Exercise 
      • Regimens varied, included yoga, Qi Going, Nordic walking, aquatics, dancing
  • Long-term exercise delayed the progression of:
    • Motor symptoms
    • Mobility & balance decline


Health effects of the time-restricted eating in adults with obesity: A systematic review and meta-analysis

  • Does intermittent fasting improve obesity?
  • Meta-analysis: 9 RCTs, 665 obese individuals randomized to:
    • Control
      • No diet restriction or 12 hour eating window
    • Time-restricted feeding (TRF)
      • 8-12 hour eating window
  • Compared to control, the TRF-group experienced greater reductions in:
    • Weight (-2.8 lbs)
    • Body fat (-1.5 lbs)
  • However, these benefits were ONLY noted for: 
    • 8 hour eating windows (not > 8 hours) 
    • ≥3 month interventions (not < 3 months)
    • Caloric restriction alongside fasting (not ad libitum)
  • Fasting did NOT lead to significant difference in:
    • Blood pressure
    • Fasting glucose
    • Fasting insulin
    • Lipids (Total cholesterol, HDL-C, LDL-C, Triglycerides)


Effects of Creatine Monohydrate on Endurance Performance in a Trained Population: A Systematic Review and Meta-analysis

  • Is creatine effective for improving endurance performance?
  • Meta-analysis: 13 RCTs, trained individuals were randomized to:
    • Placebo
    • Creatine 
  • Compared to placebo, creatine did NOT improve:
    • Endurance 


Association of sleep apnea and depressive symptoms among US adults: a cross-sectional study

  • Is sleep apnea associated with depression?
  • Observational study: 9,817 individuals
  • Compared to those without sleep apnea, sleep apnea was associated with a:
    • ~1.4x greater likelihood of depressive symptoms


Effects of lifestyle intervention on adults with metabolic associated fatty liver disease: A systematic review and meta-analysis

  • What are the most effective lifestyle interventions for fatty liver disease?
  • Meta-analysis: 34 RCTs, 2,652 overweight participants with fatty liver disease
  • Lifestyle interventions that reduce liver fat content the most were:
    • Low carbohydrate diet
      • More effective than low fat diet
    • Resistance exercise
      • More effective than aerobic exercise


Evidence for the carbohydrate-insulin model in a reanalysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial

  • Does glycemic load affect weight loss?
  • Secondary analysis of the DIETFITS trial: 609 overweight adults, randomized to:
    • Low-carb diet
    • Low-fat diet
  • After 1 year, the results showed:
    • BOTH groups experienced similar weight loss
    • Lower glycemic load was a strong predictor of weight loss 
    • Fat intake was not associated with weight loss
  • As predicted by the carbohydrate-insulin model of obesity, weight loss in both diet groups of DIETFITS seems to have been driven by the reduction of glycemic load more so than dietary fat or calories.


Pelvic floor physical therapy and mindfulness: approaches for chronic pelvic pain in women-a systematic review and meta-analysis

  • Does mindfulness and pelvic floor physical therapy improve pelvic pain in women?
  • Meta-analysis: 7 clinical trials, 279 women treated with: 
    • Mindfulness and pelvic floor physical therapy
  • Mindfulness and pelvic floor physical therapy improved:
    • Pain catastrophizing
    • Sexual function


The Effects of Mindfulness Interventions on Older Adults’ Cognition: A Meta-Analysis

  • Does mindfulness improve cognition in the elderly?
  • Meta-analysis: 30 RCTs of 1,682 older adults randomized to:
    • Control
    • Mindfulness
  • Mindfulness led to improvements in:
    • Attention (small effect size)
    • Long-term memory (small effect size)


Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status

  • Does vitamin D supplementation reduce dementia risk?
  • Observational study: 12,388 dementia-free subjects
  • Over 10 years, vitamin D supplementation was associated with:
    •  40% lower incidence of dementia
  • Benefits of vitamin D were greater in those without APOE ε4


Effect of Vitamin D Supplementation on Depression in Adults: A Systematic Review of Randomized Controlled Trials (RCTs)

  • Does vitamin D supplementation improve depression?
  • Systematic review: 8 RCTs, 513 participants with depression, randomized to:
    • Control 
    • Vitamin D
      • Dose varied by study, ranged from 1500-14,000 IU/day
  • Vitamin D led to mixed results for depression:
    • Depression symptoms improved (63% of studies) 
    • NO effect on depression (37% of studies)


Efficacy and acceptability of vitamin D supplements for depressed patients: A systematic review and meta-analysis of randomized controlled trials

  • Are vitamin D supplements effective for depression?
  • Meta-analysis: 18 RCTs, 1,980 participants with depression, randomized to:
    • Placebo
    • Vitamin D
  • Vitamin D supplementation led to improvements in depression
    • Adults (moderate effect size)
    • Children (small effect size)
  • Single high doses of vitamin D were more effective than regular daily doses

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Episodes 103 & 104

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Comparison of multiple treatment regimens in children with Helicobacter pylori infection: A network meta-analysis

  • What are the most effective treatments for H. pylori infections?
  • Meta-analysis: 163 RCTs with 18,257 children with H. pylori
    • 10 different interventions were analyzed
  • The most effective treatments for H. pylori were:
    • 1. Sequential antibiotic therapy with probiotics (93% eradication rate) 
    • 2. Bismuth-containing quadruple antibiotic therapy (87%)
    • 3. Triple antibiotic therapy with probiotics (73%)


Lactobacillus ruteri compared with placebo as an adjuvant in quadruple therapy for Helicobacter pylori eradication: A randomized, double-blind, controlled trial

  • Are probiotics effective for H. pylori eradication?
  • RCT: 450 patients with H. pylori infections randomized to:
    • Placebo + quadruple antibiotic therapy
    • Probiotics + quadruple antibiotic therapy
      • Lactobacillus reuteri 
  • After 2 months, compared to placebo, the addition of probiotics led to:
    • Similar eradication rates (79% probiotics vs 72% placebo)
    • ~30% fewer side effects


Effects of Microecological Regulators on Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials

  • Are gut-directed therapies effective for rheumatoid arthritis?
  • Meta-analysis: 11 RCTs involving 762 rheumatoid arthritis patients randomized to:
    • Placebo
    • Prebiotics
    • Probiotics +/- prebiotics
      • Varied by study, included lactobacillus, bifidobacterium, bacillus coagulans
  • Compared to placebo, probiotics, prebiotics and synbiotics led to improved:
    • Rheumatoid arthritis symptom severity
    • Inflammatory markers
      • CRP, IL-1β


Clinical, microbiological and immunological short, medium and long-term effects of different strains of probiotics as an adjunct to non-surgical periodontal therapy in patients with periodontitis. Systematic review with meta-analysis

  • Are probiotics effective for gum disease?
  • Meta-analysis: 25 studies, 894 patients with gum disease assigned to:
    • Dental therapy alone
    • Dental therapy + probiotics
  • The addition of probiotics led to greater improvements in:
    • Gum inflammation
  • Note: Lactobacillus reuteri lozenges were most clinically beneficial 


A clinical trial about effects of prebiotic and probiotic supplementation on weight loss, psychological profile and metabolic parameters in obese subjects

  • Can gut-directed therapies support weight loss? 
  • Prospective study: 45 obese patients were randomized to:
    • Diet 
    • Diet plus prebiotics
      • Carob beans
    • Diet plus probiotics
      • Lactobacillus/Bifidobacterium blend, 10 billion CFU/day
  • After 1 month, compared to diet alone, the addition of probiotics or prebiotics led to:
    • NO difference in weight loss
    • Improved blood sugar regulation 
      • Insulin, fasting glucose
    • Improved sleep quality


Lacticaseibacillus paracasei GM-080 Ameliorates Allergic Airway Inflammation in Children with Allergic Rhinitis: From an Animal Model to a Double-Blind, Randomized, Placebo-Controlled Trial

  • Can probiotics treat allergies?
  • RCT: 122 children with allergic rhinitis randomized to:
    • Placebo
    • Probiotics
      • Lacticaseibacillus paracasei, up to 1 billion CFU/day
  • After 3 months, compared to placebo, probiotics improved:
    • Overall allergy severity
    • Sneezing
  • Probiotics did NOT improve:
    • Serum IgE levels


Benefits of Probiotic Pretreatment on the Gut Microbiota and Minor Complications after Bowel Preparation for Colonoscopy: A Randomized Double-Blind, Placebo-Controlled Pilot Trial

  • Do probiotics help the gut microbiota recover from colonoscopy?
  • RCT: 51 subjects undergoing colonoscopy randomized to:
    • Placebo
    • Probiotics
      • Lactobacillus/Bifidobacterium, 1 billion CFU/day
  • After 1 month, compared to placebo, probiotics:
    • Reduced duration of colonoscopy side effects 
    • Prevented disruptions in the gut microbiome


Clinical trials targeting the gut-microbiome to effect ocular health: a systematic review

  • Do probiotics improve eye health?
  • Systematic review: 29 studies 
  • Various eye conditions were: 
    • Associated with gut dysbiosis
    • Improved with probiotics


Safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) in pregnant women at high-risk of preterm birth

  • Can probiotics reduce the risk of worse pregnancy outcomes? 
  • Clinical trial: 61 women with a high-risk of preterm birth, treated with: 
    • Vaginal probiotics 
      • Lactobacillus crispatus
  • The use of probiotics led to: 
    • Lower incidence of preterm births
    • Side effects in 19% (discharge, odor, itching, etc)
  • Compliance was 93%


Investigating the effect of oral synbiotic on enteral feeding tolerance in critically ill patients: A double-blinded controlled clinical trial of gut microbiota

  • Do probiotics improve outcomes in critically ill patients? 
  • RCT: 105 critically ill patients needing a feeding tube, randomized to:
    • Control 
    • Synbiotics
  • After 1 week, the use of synbiotics led to: 
    • Improved GI motility 
      • Less need to motility drugs
    • Overall better tolerance to enteral nutrition


Benefits and harm of probiotics and synbiotics in adult critically ill patients. A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis

  • Are probiotics safe for critically ill patients?
  • Meta-analysis: 75 studies, 8,551 critically ill patients assigned to:
    • Control (placebo or usual care) 
    • Probiotics +/- prebiotics
  • Compared to control groups, probiotics +/- prebiotics led to: 
    • NO effect on ventilator-associated pneumonia
    • 1% increased risk of adverse events
  • Note: While lower quality studies showed reduced risk of ventilator associated pneumonia, higher quality studies found no benefit. 


Use of Streptococcus salivarius K12 in supporting the mucosal immune function of active young subjects: A randomised double-blind study

  • Do probiotics improve immune function?
  • RCT: 20 healthy subjects were randomized to:
    • Placebo
    • Probiotics
      • Streptococcus salivarius, 5 billion CFU
  • After 1 month, compared to placebo, probiotics led to:
    • Increased secretory IgA levels
    • NO difference in upper respiratory tract infection


Probiotic supplementation improved cognitive function in cognitively impaired and healthy older adults: a systematic review of recent trials

  • Do probiotics improve cognitive function?
  • Systematic review: 10 RCTs, older adults categorized by cognitive function:
    • Normal cognition 
    • Mild cognitive impairment
    • Alzheimer’s disease
  • All participants randomized to: 
    • Control
    • Probiotics 
      • Lactobacillus, bifidobacterium
  • Compared to control, probiotic supplementation led to:
    • Improved cognitive function in all participants
  • Most improvement was noted with ~3-6 months of treatment


Effect of Bacillus coagulans Unique IS2 with Lactulose on Functional Constipation in Adults: a Double-Blind Placebo Controlled Study

  • Do soil-based probiotics improve constipation?
  • RCT: 150 adults with functional constipation, randomized to:
    • Placebo
    • Prebiotics
      • Lactulose, 10 g/day
    • Probiotics + prebiotics
      • Bacillus coagulans, 2 billion CFU/day
  • After 1 month, compared to prebiotics alone, the addition of probiotics led to:
    • Improved constipation symptoms
    • Quicker improvements in stool frequency

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The causal role of gastroesophageal reflux disease in anxiety disorders and depression: A bidirectional Mendelian randomization study

  • Can GERD cause anxiety and depression?
  • Mendelian randomization: 129,080 GERD patients, 473,524 healthy controls
  • The analysis showed that GERD increased the risk of:
    • Anxiety by 35%
    • Depression by 32%
  • This study supports a causal association between GERD and an increased risk of anxiety disorders and depression.”


The role of psychological factors in functional gastrointestinal disorders: a systematic review and meta-analysis

  • Is poor digestive health associated with worse mental health?
  • Meta-analysis: 22 studies, 2,430 patients with functional GI disorders,12,397 healthy controls
  • Compared to healthy controls, patients with functional GI disorders had an increased risk of:
    • Anxiety (moderate effect size)
    • Depression (moderate effect size)
    • Sleep disorders (moderate effect) 


COVID-19 susceptibility and clinical outcomes in inflammatory bowel disease: An updated systematic review and meta-analysis

  • Does inflammatory bowel disease affect clinical outcomes of COVID-19?
  • Meta-analysis: 35 observational studies involving IBD patients and non-IBD controls
  • Compared to non-IBD controls, having IBD did NOT increase risk of:
    • Hospitalization
    • ICU admission
    • Death


Anti-vinculin antibodies in systemic sclerosis: associations with slow gastric transit and extra-intestinal clinical phenotype

  • Do anti-vinculin antibodies correlate with slow gastric motility?
  • Observational study: 88 patients with systemic scleroderma and GI symptoms
    • All assessed for anti-vinculin antibodies 
  • Anti-vinculin antibodies were positive in 23% of individuals, and associated with: 
    • Slower gastric emptying (large effect size)
    • Thyroid disease (4x increased risk)


Efficacies of prokinetics and rifaximin on the positivity of a glucose breath test in patients with functional dyspepsia: a randomized trial

  • Do prokinetics increase SIBO eradication rates?
  • RCT: 83 patients with SIBO randomized to:
    • Prokinetic
      • Mosapride
    • Rifaximin
    • Prokinetic + Rifaximin
  • Compared to rifaximin alone, the addition of a prokinetic:
    • Did NOT improve eradication rates
      • 17% prokinetic vs 32% rifaximin vs 35% combo


Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care

  • Does acid-reflux medication promote SIBO?
  • Observational study: 125 GERD patients on proton pump inhibitors for ≥ 6 months
    • All underwent lactulose breath testing
  • Compared to controls, use of PPIs was associated with:
    • Increased SIBO prevalence (30% vs 27%)
    • Higher methane levels (62% vs 21%)


Acid Suppression and Antibiotics Administered during Infancy Are Associated with Celiac Disease

  • Do certain medications increase celiac disease risk in children?
  • Observational study: 968,524 children
    • Medication use assessed during first 6 months of life  
  • An increased risk of celiac disease was associated with use of:
    • Proton pump inhibitors (2.2x increased risk) 
    • Histamine-2 Receptor blockers (1.9x)
    • Antibiotics (1.1x)


Helicobacter pylori infection increase the risk of subclinical hyperthyroidism in middle-aged and elderly women independent of dietary factors: Results from the Tianjin chronic low-grade systemic inflammation and health cohort study in China

  • Does H. pylori increase the risk of thyroid disease?
  • Observational study: N = 2,050 participants 
  • H. pylori infection was associated with: 
    • 2.5x increased risk of developing subclinical hyper-thyroidism
      • Especially in those ≥ 40 years old (2.8x increased risk)


Lifestyle factors associated with inflammatory bowel disease: data from the Swiss IBD cohort study

  • What early lifestyle factors are associated with an increased risk for IBD?
  • Observational study: 1,111 IBD patients, 365 controls
  • Early lifestyle factors associated with increased IBD risk included:
    • Less physically active
    • Not being breastfed
    • Being overweight or underweight
    • High meat consumption

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Thyroid & Hormones

Vitamin B12 levels in thyroid disorders: A systematic review and meta-analysis

  • Is vitamin B12 deficiency associated with various thyroid conditions?
  • Meta-analysis: 64 observational studies, 28,597 participants categorized by:
    • Various thyroid conditions
      • Hypothyroidism, subclinical hypothyroidism, hyperthyroidism, Hashimoto’s thyroiditis
    • Healthy controls
  • Compared to healthy controls, only hypothyroid patients had lower levels of B12 
    • -61 pg/mL
  • Anti-parietal cell antibodies were: 
    • Present in 27% of autoimmune thyroid participants


High level of thyroid peroxidase antibodies as a detrimental risk of pregnancy outcomes in euthyroid women undergoing ART: A meta-analysis

  • Does the presence of TPO antibodies lead to worse fertility outcomes?
  • 7 studies, 8,431 euthyroid women, categorized by TPO-antibody levels
    • All undergoing assisted reproductive technology (IVF, etc) 
  • Only TPO-antibodies >100 IU/mL was associated with: 
    • 2x increased risk for miscarriages
    • ~34% lower rates of delivery
  • TPO antibodies <100 did NOT worsen pregnancy outcomes


The impact of levothyroxine therapy on pregnancy and neonatal outcomes in euthyroid pregnant women with thyroid autoimmunity: A systematic review, meta-analysis and trial sequential analysis

  • Do pregnant women with thyroid autoimmunity benefit from levothyroxine?
  • Meta-analysis: 11 studies, 2,901 euthyroid pregnant women with positive TPO or Tg antibodies, randomized to:
    • Control
    • Levothyroxine
  • Compared to control, treatment with levothyroxine had no effect on:
    • Pregnancy and neonatal outcomes
      • Miscarriage
      • Preterm birth
      • Birth weight
      • Preeclampsia
      • Placenta abruption


The Role of Thyroid Dysfunction in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

  • Is hypothyroidism associated with Alzheimer’s disease?
  • Meta-analysis: 7 observational studies, 1,189 Alzheimer’s patients, 72,711 controls
  • Compared to controls, patients with Alzheimer’s had a higher prevalence of:
    • Hypothyroidism (6% vs 2%)
  • Note: This study is observational, so causation cannot be confirmed.

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Diet & Lifestyle

Effect of Vitamin E Supplementation on Chronic Insomnia Disorder in Postmenopausal Women: A Prospective, Double-Blinded Randomized Controlled Trial

  • Does vitamin E improve insomnia?
  • RCT: 160 post-menopausal women with chronic insomnia randomized to:
    • Placebo
    • Vitamin E
      • Mixed tocopherol, 400 IU/day
  • After 1 month, compared to placebo, vitamin E led to:
    • Improved sleep quality
    • 50% reduction in sleep medications 


Meta-Analysis of Exploring the Effect of Curcumin Supplementation with or without Other Advice on Biochemical and Anthropometric Parameters in Patients with Metabolic-Associated Fatty Liver Disease (MAFLD)

  • Does curcumin improve fatty liver disease?
  • Meta-analysis: 14 RCTs, 847 patients with fatty liver disease randomized to:
    • Control
    • Curcumin 
    • Curcumin +  diet & exercise
  • Compared to control, curcumin +/- lifestyle modifications led to improvements in:
    • Liver enzymes (ALT, AST)
    • Insulin resistance
    • Lipids (Total cholesterol, LDL-C, triglycerides)
    • Waist circumference


Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis

  • Does vitamin D deficiency increase the risk of rheumatoid arthritis?
  • Meta-analysis: 7 observational studies, 16,653 participants
  • There was NO association between vitamin D levels and rheumatoid arthritis risk


Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials

  • Does vitamin D reduce risk of type 2 diabetes?
  • Meta-analysis: 3 RCTs, adults with prediabetes randomized to:
    • Placebo
    • Vitamin D
  • Compared to placebo, vitamin D supplementation led to:
    • 15% reduced risk of diabetes


The effects of guar gum supplementation on glycemic control, body mass and blood pressure in adults: a GRADE-assessed systematic review and meta-analysis of randomized clinical trials

  • Do prebiotics improve blood sugar control? 
  • Meta-analysis: 14 RCTs, participants treated with: 
    • Control
    • Guar gum
  • Supplementation with guar gum led to: 
    • Reduced A1c
    • NO effect on: 
      • Fasting blood sugar
      • Systolic blood pressure
      • BMI


Influence of fasting during the night shift on next day eating behavior, hunger, and glucose and insulin levels: a randomized, three-condition, crossover trial

  • Does intermittent fasting improve metabolic health for night-shift workers?
  • Crossover trial: 10 night-shift workers, randomized to the following during their shift:
    • Fasting
    • Eating
    • Sleeping
  • Fasting during shift led to greatest reduction in: 
    • Appetite 
    • Insulin levels
    • Insulin resistance


Substituting meat for mycoprotein reduces genotoxicity and increases the abundance of beneficial microbes in the gut: Mycomeat, a randomised crossover control trial

  • Is plant-based “meat” better than real meat for your gut health?
  • RCT-Crossover: 20 healthy participants, randomized to: 
    • Red and processed meat
    • Mycoprotein
      • Fungal-derived protein concentrate  
  • After 2 weeks, compared to meat, mycoprotein led to: 
    • Reduced stool genotoxicity 
    • Increased beneficial bacteria
      • Lactobacillus, akkermansia
    • Increased short-chain fatty acids


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!