Gastrointestinal Studies

• Effect of probiotics combined with metformin on improvement of menstrual and metabolic patterns in women with polycystic ovary syndrome: a randomized clinical trial
  • 60 women with PCOS and irregular menstrual cycles, randomized to:
    • Probiotics alone
    • Metformin (1.5 g/day) alone
    • Probiotics + metformin 
  • After 3 months, regulation of menstrual cycle occured in: 
    • 80% in probiotic + metformin group 
    • 55% metformin group 
    • 40% probiotic group
  • Commentary: Combination of probiotics and metformin led to the greatest improvement in menstrual cycle regularity in women with PCOS. Important to note this study was open label and had no placebo group.

• A randomized trial of probiotic supplementation in nurses to reduce stress and viral illness
  • 484 healthy nurses during Covid-19 pandemic, randomized to: 
    • Placebo
    • Probiotics (lactobacillus rhamnosus) 
  • After 3 months, there was NO difference between groups for:
    • Perceived stress
    • Anxiety 
    • Wellbeing 
    • Number of days sick 
  • Commentary: This study did NOT find probiotics led to improved resilience to stress.
• The Global Incidence of Adverse Events Associated with Fecal Microbiota Transplantation in Children over the Past 20 Years: A Systematic Review and Meta-Analysis
  • 18 studies, 681 children
  • FMT led to:
    • 86% overall efficacy in children with GI symptoms
    • 91% efficacy in children with C. diff infections
    • 27.7% mild to moderate side effects (abdominal pain, diarrhea, bloating, etc) 
    • 0.9% severe side effects
  • Commentary: While FMT may be effective, there are some side effects that can occur, with a majority being mild to moderate.
• Patients with breath test positive are necessary to be identified from irritable bowel syndrome: a clinical trial based on microbiomics and rifaximin sensitivity
  • 127 IBS-D patients, 49 healthy controls, all performed lactulose SIBO breath testing (BT) 
  • 40% of IBS-D patients tested positive for SIBO 
  • Both SIBO negative and positive IBS-D patients were treated with Rifaximin (400 mg BID) 
  • Compared to IBS-D negative BT, IBS-D positive BT patients treated with Rifaximin led to greater improvements in: 
    • Abdominal pain (-42 vs -36 points) 
    • BM satisfaction (-29 vs -25 points) 
    • Diarrhea (-5 vs -1.9 points)
    • Bristol stool form
  •  Commentary: Rifaximin, an FDA approved medication for IBS-D, led to better outcomes in those IBS-D + SIBO compared to those without SIBO. Note the 40% prevalence rate of SIBO in this cohort of patients.  
  • Dr. R’s comment: still not sure this data necessitates a test because the responses rates don’t appear that different (you could test, not sure this data suggest  you MUST test).

• Use of a proline-specific endopeptidase to reintroduce gluten in patients with non-coeliac gluten sensitivity: A randomized trial
  • 23 patients with non-celiac gluten sensitivity (NCGS) currently avoiding gluten, randomized to:
    • Placebo
    • Endopeptidase (gluten-digesting enzyme) 
  • After 3 weeks of introducing gluten in both groups, both groups experienced:
    • Worsen abdominal pain 
    • Worse stool consistency
    • NO change in quality of life
  • Commentary: Gluten-digesting enzymes were NOT found to be effective in reducing GI symptoms upon gluten reintroduction in NCGS patients. 

• Fecal calprotectin predicts endoscopic activity and mucosal healing of small bowel Crohn’s disease evaluated by double-balloon endoscopy
  • 254 Crohn’s disease (CD) patients, all underwent endoscopy and tested for fecal calprotectin (FC) 
  • Endoscopic remission was correlated with:
    • FC <156 ug/g in all patients
    • FC <211.5 ug/g in small bowel CD patients (91% specificity, 74% sensitivity)  
  • Mucosal healing was correlated with FC <77 ug/g
  • Commentary: Fecal calprotectin was highly correlated with endoscopic remission and mucosal healing in Crohn’s disease patients.
• Effects of Washed Microbiota Transplantation on Serum Uric Acid Levels, Symptoms, and Intestinal Barrier Function in Patients with Acute and Recurrent Gout: A Pilot Study
  • 11 patients with gout, treated with washed fecal microbiota transplantation (FMT) 
  • FMT led to reductions in:
    • Frequency and duration of gout flares
    • Uric acid
    • Serum endotoxins
  • Commentary: This study highlights the connection between the gut and gout.
    

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Thyroid & Hormones Studies

• Association of Hashimoto’s thyroiditis and anti-thyroid antibodies with oral lichen planus: A cross-sectional study 
  • 247 patients with oral lichen planus (OLP) (inflammatory oral condition that affects mucous membranes)
  • Hashimoto’s thyroiditis was positive in 40% of those with OLP
    • 34% had positive TPO-ab
    • 20% had positive Tg-ab
  • The degree of antibody elevation was NOT associated with OLP severity
  • Commentary: Hashimmoto’s thyroiditis may be associated with oral lichen planus.
• Association of longitudinal changes in serum lipids with the natural history of subclinical hypothyroidism: A retrospective cohort study using data from the REACTION study
  • 412 subclinical hypothyroid (SCH) patients 
  • After 3 years, this study found: 
    • 46.5% became euthyroid
    • 46% remained SCH
    • 4.6% progressed to overt hypothyroidism 
  • After controlling for confounding variables (e.g. BMI, TSH, fT4, TPO-ab status, and baseline total cholesterol), the following associations were found: 
    • Increased total cholesterol by ≥ 25% led to a 5.4x increased risk of developing overt hypothyroidism 
    • Reduced total cholesterol by ≥ 25% led to a 3.5x increased chance of becoming euthyroid
  • Commentary: This study found increased total cholesterol was associated with an increased risk of developing overt hypothyroidism. Keep in mind this was an observational study, so we cannot conclude that high cholesterol causes hypothyroidism.
• Behavioral interventions for improving sleep outcomes in menopausal women: a systematic review and meta-analysis
  • 16 RCTs, 2,108 peri/post menopausal women 
  • Sleep quality was improved with: 
    • Mindfulness/relaxation (large effect size) 
    • Low intensity exercise (large effect size)
    • Moderate intensity exercise (small effect size) 
    • Cognitive behavioral therapy (small effect size) 
  • Commentary: Multiple lifestyle interventions, specifically mindfulness/relaxation and low intensity exercise, were found to improve sleep quality in peri/post menopausal women.
    

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Diet & Lifestyle Studies

• A systematic literature review of randomized controlled trials evaluating prognosis following treatment for adults with chronic fatigue syndrome
  • 15 studies, 1,990 participants with chronic fatigue syndrome
  • Aim: Assess the effects of graded exercise and cognitive behavioral therapy on fatigue
  • Graded exercise (gradual increase in exercise) led to:
    • Improved energy in 43% of studies
    • Worse energy in 14% of studies
  • Cognitive behavioral therapy (CBT) led to:
    • Improved energy in 44% of studies
    • Worse energy in 11% of studies 
  • Commentary: An overall positive trend in the data suggests graded exercise and CBT are beneficial for patients with chronic fatigue.
    

• Effects of a 6-Month Multifaceted Diet and Exercise Intervention on Cognition in Older Adults at Risk of Cognitive Decline: The PONDER Double-Blind, Placebo-Controlled Randomized Trial
  • 147 older participants (70 years old) with memory impairment, randomized to: 
    • Control group (flexibility training + placebo) 
    • Lifestyle interventions:
      • Exercise (resistance and aerobic training) 
      • Omega-3 supplementation (900 mg EPA, 600 mg DHA) 
      • Vitamin D (1,000 IU/day) 
      • Protein supplementation (20 g/day) 
  • After 1 year, compared to the control group, the lifestyle group experienced:
    • NO difference in cognition
    • Increased lean mass (+1.5 lbs) 
  • Commentary: This study did not find improvement in cognition with a comprehensive lifestyle intervention. Keep in mind this study did not modulate nutrition.
    

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Featured Study

• Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial
  • 100 pediatric patients with eczema, randomized to:
    • Placebo
    • Probiotics (lactobacillus rhamnosus GG) 
  • After 3 months, compared to placebo, probiotics led to:
    • Higher response rate for reduced eczema severity (60% probiotic vs 20% placebo) 
    • NO difference in gut microbiome based on stool test
  • Improvements in eczema were maintained 1 month after stopping probiotics 
  • Commentary: Probiotics led to improved eczema despite NO improvement in gut microbiome. This highlights 1) the gut-skin connection and 2) lab findings do NOT always correlate with symptomatic improvements.
    

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Gastrointestinal Studies

• Irritable bowel syndrome patients who are not likely to respond to fecal microbiota transplantation
  • 109 IBS patients treated with fecal microbiota transplant (FMT) 
  • 83% of patients were responders to FMT (reduction in IBS symptom score)
  • NO connection was found between FMT responders vs non-responders with:
    • IBS Duration
    • IBS Subtype
    • IBS Symptoms
    • Dysbiosis index
  • Commentary: Most IBS patients in this study responded well to FMT regardless of various IBS factors or degree of dysbiosis.
• Molecular detection of pathogenic bacteria in the colonic biopsies from patients with Ulcerative Colitis
  • 40 ulcerative colitis (UC) patients, 20 healthy controls (HC)
  • All underwent colonic biopsies to assess for various pathogens
  • Compared to healthy controls, UC patients had:
    • Increased pathogenic E. coli (28% vs 0%) 
    • Increased H. pylori (7.5% vs 0%)  
    • No C. diff (0% UC vs 0% HC) 
  • Commentary: Compared to HC, patients with UC had a higher prevalence of pathogenic E. coli. This is an observational study, so correlation does not imply causation. 
  • Dr. R: does not tell us best way to treat 
    • Could be due to immunosuppressive drug use?
• Effects of oligosaccharides on the markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials
  • 46 RCTs on the effect of oligosaccharides (prebiotics) on glucose regulation
  • Oligosaccharides led to improvements in:
    • Fasting glucose (-5 mg/dl) 
    • Fasting insulin (small effect size) 
    • Insulin resistance (-0.8) 
    • A1c (-0.4%) 
  • The positive effects of oligosaccharides were more notable in patients with:
    • Obesity
    • Diabetes
  • Commentary: Oligosaccharides, a category of prebiotics, slightly improve blood sugar regulation.
• Supplementing Dietary Fibers With a Low FODMAP Diet in Irritable Bowel Syndrome: A Randomized Controlled Crossover Trial
  • 26 IBS patients were placed on a low FODMAP diet, randomized to each of the following fiber amounts for 2 weeks with a 3 week washout between: 
    • 23 g/day (control group)  
    • 33 g/day of added sugarcane fiber 
    • 45 g/day of added sugarcane fiber + resistant starch
  • While all groups experienced similar improvements in IBS symptom scores, the addition of sugarcane fiber increased stool volume
  • Commentary: Added fiber to a low FODMAP diet did NOT lead to better or worse symptoms, but did lead to increased stool volume.
• Factors Determining Effective Probiotic Activity: Evaluation of Survival and Antibacterial Activity
  • In vitro study comparing 4 types of store-bought probiotics
  • This study found “The best antimicrobial activity against most common human gastrointestinal pathogens such as Eschericha coli, Shigella, Salmonella spp., Clostridium difficile are shown by probiotic products with the greatest diversity of bacterial strains
  • Commentary: This preclinical study supports the use of using a multi-strain probiotic formula vs specific individual strains.
• Association of Barrett’s esophagus with Helicobacter pylori infection: a meta-analysis
  • 24 studies, 1.3 million participants 
  • Patients with Barrett’s esophagus (BE) had a 47% lower prevalence of H. pylori 
  • Specifically, CagA-positive H. pylori was associated with a 75% reduced risk of BE
  • Commentary: This large study found a lower risk of BE in participants positive for H. pylori.
• Helicobacter pylori Infection- A Risk Factor for Irritable Bowel Syndrome? An Updated Systematic Review and Meta-Analysis
  • 13 studies, 13,173 participants
  • H. pylori infections were associated with a 1.5x increased risk of having IBS-D, but NOT for IBS in general 
  • Commentary: H. pylori infections were only associated with IBS-D, but not IBS in general.
• Examining the cognitive benefits of probiotic supplementation in physically active older adults: A randomized clinical trial
  • 127 physically active healthy adults, treated with probiotics (Lactobacillus rhamnosus GG) 
  • Probiotics did NOT lead to improved cognition in healthy adults who were physically active
• Intestinal Flora Balance Therapy Based on Probiotic Support Improves Cognitive Function and Symptoms in Patients with Alzheimer’s Disease: A Systematic Review and Meta-analysis
  • 5 RCTs, 386 Alzheimer’s patients
  • Probiotics led to improvements in:
    • Cognitive function 
    • Acute memory 
    • Ability to perform activities of daily living
  • Commentary: Probiotics may be clinically useful for patients with Alzheimer’s disease, highlighting the gut-brain connection.
• Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial
  • 72 pediatric patients with IBD, randomized to:
    • Standard medications + placebo
    • Standard medications + sodium butyrate (300 mg/day) 
  • Compared to placebo group, sodium butyrate led to NO difference with: 
    • Clinical remission (62% butyrate vs 72% placebo) 
    • Fecal calprotectin (-640 vs -537 ug/g) 
  • Commentary: Butyrate supplementation did NOT lead to additional benefit for IBD pediatric patients alongside conventional treatment.
    

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Thyroid & Hormones Studies

• Level of non-conventional lipid parameters and its comparative analysis with TSH in subclinical hypothyroidism
  • 40 subclinical hypothyroid (SCH) patients, 40 healthy controls
  • Compared to healthy controls, SCH patients had higher levels of:
    • Oxidized LDL-C
    • Small-density LDL
    • Lp (a) 
    • Apo-B and Apo-A1
  • Commentary: This small study found patients with SCH may have higher levels of atherogenic lab markers.
• Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials
  • 9 studies on both healthy and hypogonadal men
  • Compared to placebo, Longjack (eurycoma longifolia) led to an increase in total testosterone (+51 ng/dl vs -6.9 ng/dl)
  • 2/9 studies found dosages of 200-600 mg increased total testosterone by +121 ng/dl 
  • Commentary: Longjack may be an effective herb to increase total testosterone levels.
• The impact of levothyroxine therapy on the pregnancy, neonatal and childhood outcomes of subclinical hypothyroidism during pregnancy: An updated systematic review, meta-analysis and trial sequential analysis 
  • 9 RCTs, 11,273 pregnant women with subclinical hypothyroidism (SCH), randomized to:
    • Control
    • LT4
  • Compared to control, LT4 led to no difference in:
    • Preterm delivery
    • Miscarriages
    • Preeclampsia
    • Gestational hypertension or diabetes
  • Commentary: This study found treating SCH with LT4 did NOT improve pregnancy outcomes.

Diet & Lifestyle Studies

• Effects of hypohydration and fluid balance in athletes’ cognitive performance: a systematic review
  • 24 studies, 493 athletic participants
  • Dehydration of up to 3-5% body fluid loss was associated with:
    • Worse cognitive performance 
    • Mood imbalance
    • Fatigue 
  • Commentary: This study illustrates the importance of proper hydration for patients experiencing fatigue and brain fog.
• Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Randomized Dose-Finding Clinical Trial
  • 45 participants with major depression and high hs-CRP were randomized to:
    • Placebo
    • Low dose EPA (1 g/day) 
    • Moderate dose EPA (2 g/day) 
    • High dose EPA (4 g/day) 
  • After 3 months, high dose EPA led to the greatest response rate (≥50% reduced depression scores) compared to placebo, low dose and moderate dose EPA (64% vs 40% vs 38% vs 36%, respectively)  
  • Commentary: High dose EPA led to significant improvements in depression in patients with increased inflammation.
• Exercise training for cognitive and physical function in patients with mild cognitive impairment: A PRISMA-compliant systematic review and meta-analysis
  • 10 RCTs, 635 patients with mild cognitive impairment
  • Physical exercise led to improvements in cognitive function (moderate effect size)
  • Commentary: Exercise is likely an important therapy to include for patients with mild cognitive impairment.

Featured Study

• Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials
  • 31 RCTs on 10 types of autoimmune diseases treated with curcumin
  • Curcumin supplementation led to improvements in multiple autoimmune diseases, including:
    • Ulcerative colitis (UC) (9 studies) 
      • Reduced disease activity (moderate effect size) 
      • Reduced inflammation markers (moderate effect size) 
    • Rheumatoid arthritis (RA) (5 studies)
      • Reduced disease activity (large effect size) 
      • Reduced inflammation markers (large effect size) 
    • Psoriasis (2 studies)
      • 1.6x greater chance of 50% reduction in symptoms
    • Lupus (2 studies) 
      • Reduced disease activity and inflammation markers 
    • Multiple sclerosis (2 studies)
      • Reduced disability and inflammatory markers 
    • Ankylosing spondylitis (1 study) 
      • Reduced inflammatory markers only
  • Curcumin had NO effect on: 
    • Oral lichen planus (6 studies) 
    • Crohn’s disease (2 studies) 
  • Commentary: The best researched applications of curcumin were for UC, RA and  lichen planus, with curcumin demonstrating the most benefit for UC and RA. Curcumin may be clinically useful for psoriasis, lupus and multiple sclerosis, however more studies are needed to draw better conclusions.
    

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Gastrointestinal Studies

• Rotavirus immunisation status affects the efficacy of Lacticaseibacillus rhamnosus GG for the treatment of children with acute diarrhoea: a meta-analysis
  • 15 RCTs, 3,465 children
  • In children infected with Rotavirus, lactobacillus rhamnosus GG (LGG) treatment led to: 
    • 27% reduced risk of diarrhea in children not immunized
    • Reduced duration of diarrhea by 1 day in children not immunized
    • NO reduction in diarrhea in children immunized 
  • Commentary: While LGG led to reduced diarrhea in unimmunised children infected with Rotavirus, no additional benefits were seen for LGG when given to those immunized.

• Probiotics for preventing acute upper respiratory tract infections
  • 23 RCTs, 6,950 participants, randomized to:
    • Control (placebo or no treatment) 
    • Probiotics (Lactobacillus) 
  • Probiotics led to:
    • 33% reduced number of people diagnosed with upper respiratory tract infection (URTI) 
    • Reduced duration of URTI (-1.2 days) 
    • 42% less antibiotics required for acute URTI 
  • Commentary: Probiotics may prevent URTI, lower the use of antibiotics and decrease the number of sick days.

• Bacillus clausii UBBC-07 in the symptom management of upper respiratory tract infections in children: a double blind, placebo-controlled randomised study
  • 90 children, randomized to:
    • Placebo
    • Soil-based probiotic (bacillus clausii) 
  • After 6 months, compared to placebo, soil based probiotics reduced upper respiratory tract infection:
    • Frequency
    • Duration
    • Severity
  • Commentary: Soil based probiotics may help improve clinical outcomes of respiratory tract infections.

• Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome
  • 10 RCTs, 1,030 IBS patients randomized to:
    • Placebo
    • Peppermint oil 
  • Compared to placebo, peppermint oil led to:
    • Improved global IBS symptoms
    • Improved abdominal pain
    • 1.5x increased risk of side effects  
  • Commentary: While peppermint oil improved IBS symptoms, it also led to more side effects than placebo.

• Effects of probiotic supplementation on cognitive function in elderly: A systematic review and Meta-analysis
  • 10 studies
  • In elderly participants, probiotics led to:
    • NO improvement in cognitive function
    • NO significant increase in brain-derived neurotrophic factor (BDNF) 
    • Increased glutathione (large effect size) 
  • Commentary: This meta-analysis did NOT find probiotics improved cognitive function in the elderly.

• The Benefit of Probiotics in Pediatric Nonalcoholic Fatty Liver Disease: A Meta-analysis of Randomized Control Trials
  • 4 RCTs, 238 pediatric patients with NAFLD
  • Probiotics (lacto/bifido) led to improvements in: 
    • ALT (-7.5 IU/L) 
    • AST (-6.5 IU/L) 
    • Triglycerides and total cholesterol
    • Fat accumulation in liver based on ultrasound
  • Commentary: Probiotics were safe and clinically beneficial for pediatric patients with NAFLD.

• Long-term exposure to air pollution and risk of incident inflammatory bowel disease among middle and old aged adults
  • 457,947 participants
  • After a 12 year follow up, air pollution was associated with a 1.1x increased risk of developing ulcerative colitis, but NOT Crohn’s disease 
  • Commentary: This study found air pollution led to a slight increased risk of developing ulcerative colitis. Keep in mind this was an observational study, so causation cannot be determined.

• Effect of a multistrain probiotic on leaky gut in patients with diarrhea-predominant irritable bowel syndrome (IBS-D): a pilot study
  • Open label study of 27 patients with IBS-D and leaky gut, treated with multi-strain probiotics (lacto/bifido blend) 
  • Leaky gut determined based on radionuclide tracers and serum zonulin 
  • After 1 month, probiotics led to:
    • 96% experienced satisfactory symptom relief 
    • Improved leaky gut in 82%
    • Normalization of leaky gut in 37%
    • Improved quality of life 
    • Improved abdominal pain and diarrhea
  • While leaky gut was improved based on radionuclide tracers, serum zonulin levels did NOT change 
  • Commentary: Probiotics led to improved IBS symptoms, quality of life and intestinal permeability as measured by radionuclide tracers. This study failed to show an improvement in serum zonulin, despite symptomatic improvement. This is a great example of why lab tests are only 25% of the data used to make clinical decisions.
    

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Thyroid & Hormones Studies

• Increased Incidence of Hashimoto Thyroiditis in Selenium Deficiency: A Prospective 6-Year Cohort Study
  • 1,254 individuals followed over 6 years, categorized by:
    • Low serum selenium (<80 ug/L) 
    • Adequate serum selenium (>80 ug/L) 
  • Compared to adequate selenium status, low selenium levels were associated with higher:
    • Prevalence of hashimoto’s thyroiditis (HT) (0.3% vs 0.1%) 
    • Prevalence of positive TPO-abs (10.2% vs 5.6%) 
    • Risk of developing HT (3.6x) 
  • Commentary: Low serum selenium was associated with an increased risk of developing HT.
    

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Diet & Lifestyle Studies

• Effects of regular sauna bathing in conjunction with exercise on cardiovascular function: a multi-arm, randomized controlled trial
  • 47 participants with ≥1 cardiovascular disease risk factor, randomized to:
    • Control group (no exercise) 
    • Exercise alone (Resistance training plus cardio, 3 times per week) 
    • Exercise followed by dry sauna (15 minutes) 
  • Compared to control or exercise alone, the addition of sauna led to:
    • Lower systolic blood pressure (-8 mmHg sauna vs 0 mmHg exercise alone)
    • Reduced fat mass (-4.2 vs -2.9 lb) 
    • Reduced total cholesterol (-12 vs +5 mg/dl) 
    • Improved VO2 max (+5.5 vs +2.6 mL/kg/min) 
  • Commentary: Compared to exercise alone, the addition of sauna therapy to exercise led to greater improvements in weight loss, cholesterol, systolic blood pressure and aerobic capacity. Note these benefits were attained with only 15 minutes per session.

• Effect of vitamin D supplementation on the incidence and prognosis of depression: An updated meta-analysis based on randomized controlled trials
  • 29 studies, 4,504 participants 
  • Vitamin D supplementation led to:
    • Lower incidence of depression (small effect size)
    • Enhanced efficacy of depression treatments (large effect size) 
  • Vitamin D was most effective for treating and preventing depression when: 
    • Patients were deficient (<20 ng/ml) 
    • Dose was >2,800 IU/day
    • Duration of treatment ≥2 months 
  • Commentary: While vitamin D may lower the risk of depression, it has a more notable impact on enhancing the efficacy of other anti-depression treatments.

• Icosapent ethyl for reduction of persistent cardiovascular risk: a critical review of major medical society guidelines and statements
  • Aim of this review: Should icosapent ethyl (IPE) (highly purified EPA) be used for cardiovascular disease (CVD) prevention?
  • This review found IPE (4 g/day) “reduced the risk of major CV events by 25% in high-risk patients with mildly to moderately elevated triglyceride levels despite statin-controlled cholesterol levels.”
  • “Unfortunately, most drugs that lower triglyceride levels, such as niacin, fibrates, and mixed omega-3 fatty acids, have not reduced the risk of cardiovascular events in clinical trials”
  • Commentary: IPE has been shown to effectively lower triglyceride and reduce the
    risk of cardiovascular disease compared to other nutriceuticals such as fish oil.

• High-Intensity Exercise and Geometric Indices of Hip Bone Strength in Postmenopausal Women on or off Bone Medication: The MEDEX-OP Randomised Controlled Trial
  • 102 postmenopausal women with low bone mass, randomized to:
    • High intensity resistance training (HIE) 
    • Low impact Pilates-based exercises (LIE)
  • 22% of women were already taking osteoporosis medication
  • After 8 months, greater improvements in bone mineral density occurred with: 
    • HIE vs LIE
    • HIE + osteoporosis medication vs HIE alone 
  • Commentary: While high intensity strength training was more effective than low intensity training for improving bone mineral density, the addition of osteoporosis medication to HIE led to the greatest improvement in bone mineral density.

• Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder
  • 93 alcoholic participants, randomized to:
    • Psychotherapy (3 months) + diphenhydramine (x 2 sessions) 
    • Psychotherapy (3 months) + psilocybin (x 2 sessions) 
  • After 8 months, compared to the diphenhydramine group, psilocybin led to:
    • Reduced heavy drinking days (56% → 9.7% vs 49% → 24%) 
    • Reduced number of drinks/day (5.2 → 1.1/day vs 4.4 → 2.3/day) 
    • NO difference in adverse events
  • Commentary: Psilocybin was more effective in reducing alcohol consumption than diphenhydramine alongside psychotherapy.
    

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Featured Studies

• Efficacy and safety of fecal microbiota transplantation for the induction of remission in active ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials 
  • 9 RCTs, 425 UC patients, randomized to: 
    • Control group 
    • Fecal microbiota transplant (FMT)
  • Compared to control group, FMT led to higher rates of: 
    • Clinical remission (40% vs 22%) 
    • Endoscopic remission (17% vs 9%) 
    • Serious adverse events (10% vs 5%) 
  • FMT was more effective when:
    • Delivered into the lower GI
    • FMT dose >300 grams
    • Fecal specimen was from multiple donors
  • Commentary: FMT led to higher rates of clinical and endoscopic remission in patients with UC. It is important to weigh the risks and benefits like with any therapy, as FMT did lead to more adverse events.

• Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis
  • 122 patients with active mild-to-moderate UC, treated with:
    • Glucocorticoids (steroids)
    • FMT x 3 days
  • After 3 months, compared to steroids, FMT led to:
    • Similar clinical and endoscopic remission (55% FMT vs 48% GC)
    • Fewer adverse events (23% vs 58%) 
  • Commentary: FMT was as effective as steroids in treating UC with less side effects, making this a clinically useful treatment option.

Both of these studies above provide data suggesting fecal microbiota transplant: 

1) Is a clinically useful therapy for treating ulcerative colitis
2) May be as effective as corticosteroids
3) Does have side effects, but the side effect profile is likely less severe compared to corticosteroids

Gastrointestinal Studies

• Effects of Cannabidiol Chewing Gum on Perceived Pain and Well-Being of Irritable Bowel Syndrome Patients: A Placebo-Controlled Crossover Exploratory Intervention Study with Symptom-Driven Dosing
  • 32 IBS patients randomized to the following as needed for abdominal pain:
    • Placebo chewing gum
    • CBD chewing gum (50 mg CBD)
  • CBD chewing gum did NOT lead to less abdominal pain when compared to placebo chewing gum
  • Commentary: CBD did not reduce abdominal pain in patients with IBS.

• Bidirectional brain-gut axis effects influence mood and prognosis in IBD: a systematic review and meta-analysis
  • 12 studies, 9,192 IBD patients
  • Anxiety or depression was associated with worse IBD outcomes, including:
    • Hospitalization (1.6x)
    • Escalation of IBD therapy (1.6x) 
  • Active IBD was associated with an increased risk of developing:
    • Anxiety (2.2x)
    • Depression (1.5x) 
  • Commentary: IBD increased the risk of anxiety or depression, whereas anxiety and depression increased the risk of worse IBD outcomes. This highlights the gut-brain connection.

• Small intestinal bacterial overgrowth is associated with clinical relapse in patients with quiescent Crohn’s disease: a retrospective cohort study
  • Retrospective study, 73 patients with asymptomatic Crohn’s disease (CD) who underwent lactulose SIBO breath testing 
    • 47% tested positive for SIBO
  • After 18 months, CD patients who relapsed had a higher prevalence of SIBO compared to those who did not relapse (63% vs 37%) 
  • SIBO was associated with a 2.8x increased risk of CD relapse 
  • Commentary: This small study found that 1) SIBO was present in about half of CD patients and 2) SIBO positivity was associated with an increased risk of experiencing a CD relapse.

• Heat-Killed Lactococcus lactis subsp. cremoris H61 Altered the Iron Status of Young Women: A Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group Comparative Study
  • 29 healthy women (18-25 years old) with normal iron status, randomized to:
    • Placebo
    • Killed probiotic  
  • After 1 month, despite no change in iron intake, the killed probiotic group experienced improved:
    • Serum iron (+37 ug/dl vs -2 ug/dl)
    • Ferritin (+5 vs +1) 
    • Transferrin saturation (+7% vs 0%)
  • Commentary: This small study found killed probiotics were able to improve iron status despite no change in dietary or supplemental iron intake.

• Long Term Outcomes of the Six Food Elimination Diet and Food Reintroduction in a Large Cohort of Adults with Eosinophilic Esophagitis
  • Retrospective study, 213 patients with eosinophilic esophagitis (EoE)
  • All completed the 6 food elimination diet (Avoidance of milk, wheat, soy, eggs, tree nuts/peanuts, and fish/shellfish)
  • The elimination diet led to:
    • 58% response rate on endoscopy
    • 42% experiencing symptomatic improvement
  • After reintroduction, 69% of patients only had 1 food trigger, and the most common were:
    • Milk
    • Wheat
    • Soy
  • Commentary: This study found the 6 food elimination diet was helpful for patients with EoE, with most patients reporting only 1 food trigger after reintroduction.

• The role of probiotics in the treatment of adult atopic dermatitis: a meta-analysis of randomized controlled trials
  • 6 RCTs, 241 patients with eczema, randomized to:
    • Control group
    • Probiotics
  • Probiotics led to:
    • Improved objective eczema score (large effect size)
    • Improved quality of life (large effect size) 
    • NO change in subjective symptoms (e.g. itch severity), inflammatory markers or serum IgE
  • Commentary: This meta-analysis found probiotics led to objective improvements in eczema and overall quality of life, but no subjective improvement in symptoms.

• Meta-analysis and systematic review of the association between adverse childhood events and irritable bowel syndrome
  • 15 studies, 272,686 participants
  • This study did NOT find a clear association between risk of developing IBS and childhood traumatic events
  • When assessed by gender, females with a traumatic childhood were at a 2.2x increased risk of developing IBS, whereas this association was NOT found in males
  • Commentary: The totality of the evidence is unclear whether or not IBS is associated with traumatic events in childhood. There may be a sex difference of how adversity in childhood contributes to IBS.

• Human supplementation with Pediococcus acidilactici GR-1 decreases heavy metals levels through modifying the gut microbiota and metabolome
  • 152 participants with known heavy metal exposure (Cu and Ni), randomized to:
    • Placebo yogurt
    • Probiotic yogurt (Pediococcus acidilactici GR-1)
  • After 3 months, compared to placebo yogurt, the probiotic yogurt led to a greater reduction in blood levels of: 
    • Copper (-429 ug/L probiotic vs -200 ug/L)
    • Nickel (-2.5 ug/L vs -2 ug/L)
  • Commentary: This study highlights the ability of probiotics to act as heavy metal removers. The specific strain Pediococcus acidilactici GR-1 led to better removal of copper and nickel compared to conventional yogurt. Unfortunately, no other heavy metals were tested in this study.

• Multispecies Probiotic for the Prevention of Antibiotic-Associated Diarrhea in Children
  • 350 children recently (within 24 hours) prescribed antibiotics, randomized to: 
    • Placebo
    • Probiotic (Lacto/bifido blend) 
  • Compared to placebo, probiotics reduced the risk of diarrhea by 35%
  • Commentary: Probiotics should be used alongside antibiotics to help reduce side effects.

• Saccharomyces cerevisiae I-3856 in irritable bowel syndrome with predominant constipation
  • 456 participants with IBS-C, randomized to:
    • Placebo
    • Probiotic (Saccharomyces cerevisiae)
  • After 2 months, probiotic supplementation led to: 
    • Improved quality of life
    • Increased number of participants with improved abdominal pain (45% probiotic vs 34% placebo) 
    • NO difference in bowel movement frequency or consistency
  • Commentary: S. cerevisiae probiotic led to reduced abdominal pain and better quality of life, but NO improvement in constipation. Note the high placebo response for improvements in abdominal pain. 

• Fecal microbiota transplantation can improve cognition in patients with cognitive decline and Clostridioides difficile infection
  • 20 patients (≥63 years old) with dementia and severe C. diff infection, randomized to:
    • Antibiotics
    • Fecal microbiota transplant (FMT) 
  • After 1 month, compared to antibiotics, FMT led to improved:
    • Mini-mental status exam scores
    • Dementia scores 
  • Commentary: FMT improved cognitive function in dementia patients with C. diff infections, highlighting the gut-brain connection.

• Probiotic therapy, a novel and efficient adjuvant approach to improve glycemic status: an umbrella meta-analysis
  • Umbrella meta-analysis of 48 RCTs
  • Compared to control groups, probiotics led to improved: 
    • Insulin resistance (-0.5) 
    • Insulin (-1.1 IU/ml) 
    • Fasting glucose (-0.5 mg/dl) 
    • A1c (-0.3%)
  • Commentary: This large study found probiotics most notably improve insulin and insulin resistance, whereas the effects on glucose and A1c are statistically significant but not clinically meaningful.
    

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Diet & Lifestyle Studies

• Effect of Calcium and Vitamin D Supplementation With and Without Collagen Peptides on Volumetric and Areal Bone Mineral Density, Bone Geometry and Bone Turnover in Postmenopausal Women With Osteopenia
  • 51 postmenopausal women with osteopenia, randomized to:
    • Calcium (500 mg/day) and vitamin D (400 IU/day) (C+D alone) 
    • Calcium, vitamin D and collagen peptides (5 g/day) 
  • After 1 year, compared to C+D alone, the addition of collagen peptides led to: 
    • Reduced bone turnover
    • Improved bone mineral density in spine 
  • Commentary: The addition of collagen peptides to vitamin D and calcium led to better clinical outcomes in osteopenic postmenopausal women.

• The Effect of Mindfulness-based Programs on Cognitive Function in Adults: A Systematic Review and Meta-analysis
  • 45 RCTs, 2,238 participants 
  • Compared to control groups, mindfulness-based programs (MBPs) led to an overall improvement in cognitive function (small effect size)
  • The effects of MBPs on cognition were greater in those over 60 years old
  • Commentary: Mindfulness-based practices may be useful for improving cognitive function, especially in older adults.