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Featured Study

• The Effect of Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) Meals on Transient Lower Esophageal Relaxations (TLESR) in Gastroesophageal Reflux Disease (GERD) Patients with Overlapping Irritable Bowel Syndrome (IBS)
  • Cross-over study of 8 patients with overlapping GERD-IBS (non-constipation)
  • Randomized to either breakfast and lunch that contained either:
    • Control (rice noodle)
    • Low FODMAP (wheat noodle)
  • Measured the following after ingestion of the meals:
    • Postprandial transient lower esophageal sphincter relaxation (TLESR)
    • Intestinal gas production
    • GERD/GI symptoms
  • FODMAP ingestion was associated with:
    • Higher H2 and CH4 levels
    • More TLESR
      • Higher H2 gas production correlated with TLESR
    • More postprandial regurgitation (2.9 vs. 0.4)
    • More bloating (7.0 vs. 3.1)
    • Satiety (7.7 vs. 3.5)
    • Belching (3.8 vs. 1.1) 
  • Commentary: FODMAP ingestion was related to greater gas production, esophageal sphincter relaxation, and GI/GERD symptoms.

Gastrointestinal Studies

• Depression and Inflammatory Bowel Disease: A Bidirectional Two-sample Mendelian Randomization Study
  • Mendelian randomization study of 693,000 participants (36,500 with IBD)
  • Genetically predicted depression was associated with a higher risk of:
    • IBD (20% increase)
    • Crohn’s disease (29% increase)
    • Ulcerative colitis (22% increase)
  • Commentary: Depression may have a causal role in IBD; highlighting the gut-brain axis.
• A multi-center, randomized controlled study on the effect of Saccharomyces boulardii combined with triple therapy for the initial eradication of Helicobacter pylori infection
  • 497 patients with H. pylori infection, randomized to:
    • Bismuth quadruple eradication therapy (BQT)
    • Triple eradication therapy (TT)
    • Triple therapy + S. boulardii (TT+S)
  • All patients received urea breath test after treatment
  • After 6 weeks, the eradication rates were:
    • 65% TT
    • 78% TT+S
    • 80% BQT
  • Compared to TT and BQT, TT+S led to: 
    • Fewer patients dropping out of the study
    • Less abdominal distension
    • Less belching
    • Less diarrhea 
  • Commentary: The addition of S. boulardii led to similar eradication rates as BQT and less GI symptoms. Fewer patients dropped out with the addition of S. Boulardii, possibly indicating greater tolerability of treatment.

• Prolonged use of proton pump inhibitors and risk of type 2 diabetes: Results from a large population-based nested case-control study
  • 777,000 participants who used PPIs
    • 50,500 who also had diabetes
  • Compared with patients who used PPIs for < 8 weeks, those who used PPIs longer than 8 weeks had higher odds of diabetes:
    • 8 weeks – 6 months (19% increased risk)
    • 6 months – 2 years (43% increased risk)
    • >2 years (56% increased risk) 
  • Commentary: Long-term PPI use was associated with increased diabetes risk in a dose-dependent fashion.

• Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment
  • Open label study, 45 patients with hepatic encephalopathy (HE), randomized to: 
    • Lactulose
    • Rifaximin
    • Probiotic (E. coli Nissle 1917)
  • After 1 month, compared to lactulose, probiotic and rifaximin led to improved:
    • Serum ammonia
    • Inflammatory cytokines
    • Cognitive function
  • Probiotics led to the greatest improvement in gut microbiota
  • Commentary: Probiotics and rifaximin were both effective in improving HE.

• Do Probiotics in Pregnancy Reduce Allergies and Asthma in Infancy and Childhood? A Systematic Review
  • 6 studies 
  • Probiotics taken during pregnancy led to: 
    • NO change in atopic conditions in children in 2/6 studies
    • Less atopic conditions in children in 2/6 studies 
    • Less atopic conditions ONLY in children at high hereditary risk in 1/6 studies
  • Commentary: Inconsistent results were found for the effect of probiotics during pregnancy on incidence of atopic conditions in children.

• Golden bifid might improve diarrhea-predominant irritable bowel syndrome via microbiota modulation
  • 21 IBS-D patients, all treated with probiotics 
    • 16/21 also diagnosed with SIBO 
  • After 1 month, probiotics led to improved IBS symptom scores, including: 
    • Abdominal pain (-1)
    • Abdominal distension (-0.7)
    • Diarrhea (-1.4)
    • Stool urgency (-1.1)
    • Incomplete evacuation (-1)
    • Depression (-2.9)
  • SIBO was eradicated in 25% 
  • Commentary: Probiotics led to improvements in IBS symptoms while also eradicating SIBO in a small proportion of patients.

• Can Lactose Intolerance Be a Cause of Constipation? A Narrative Review
  • Narrative review
  • Constipation may occur in approximately 30% of lactose intolerance patients
  • Commentary: Don’t rule out lactose intolerance in patients presenting with constipation.

• Postinfection Irritable Bowel Syndrome
  • Narrative review
  • Post-infectious (PI) IBS develops in approximately 11.5% of acute gastroenteritis (AGE) cases
  • Infections most commonly associated with developing PI-IBS include:
    • Shigella
    • Vibrio cholerae
    • Giardia lamblia 
  • Commentary: A significant percentage of IBS diagnoses may be due to a history of GI infection.

• Intestinal Dysbiosis in Patients with Histamine Intolerance
  • 12 histamine intolerant (HIT) patients, 14 healthy controls
  • Stool samples were collected on all participants
  • Compared to healthy controls, HIT patients had greater:
    • Diamine oxidase (DAO) deficiency (83% of HIT patients) 
    • Histamine-secreting bacteria (staphylococcus, proteus, clostridium perfringens, enterococcus faecalis, enterobacteriaceae)
  • Commentary: This small study showed patients with HIT have greater dysbiosis and lower DAO. This supports the hypothesis that HIT begins in the gut.

• Effects of Lactobacillus gasseri CP2305 on Mild Menopausal Symptoms in Middle-Aged Women
  • 80 women (40-60 y/o) with mild menopausal symptoms, randomized to: 
    • Placebo
    • Probiotic 
  • After 6 months, the probiotic group had improved:
    • Overall symptom relief (75% probiotic vs 55% placebo) 
    • Global menopausal symptom score
    • Vasomotor score
    • Psychological score
  • Commentary: Probiotics may improve menopausal symptoms. Note the high placebo response.

• The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies
  • 43 studies, 3,936 participants with depression
  • PRObiotics and synbiotics led to improvements in depressive symptoms, whereas PREbiotics had NO effect
  • Commentary: Another study showing the benefit of probiotics for depression. This highlights the gut-brain connection.

• A Starch- and Sucrose-Reduced Diet in Irritable Bowel Syndrome Leads to Lower Circulating Levels of PAI-1 and Visfatin: A Randomized Controlled Study
  • 105 IBS patients randomized to:
    • No dietary change (control)
    • Starch and sucrose reduced diet (SSRD)
  • After 1 month, compared to control group, SSRD led to greater improvements in:
    • IBS symptom score (–150 SSRD vs -10 control)
    • Abdominal pain (-28 vs +1) 
    • Diarrhea (-43 vs -23) 
    • Gas and bloating (-50 vs -9)
    • Psychological well-being (-14 vs +1) 
    • Complete resolution of symptoms (19% vs 0%) 
  • Commentary: SSRD was effective in improving IBS symptoms within a very short period of time.

• Probiotic sepsis in preterm neonates-a systematic review
  • 1,569 studies on probiotics in preterm infants (<32 weeks old)
  • Sepsis caused by probiotics was confirmed in 25 cases
  • Commentary: This study showed a very small number of preterm infants developed sepsis from probiotics. Keep in mind that many other studies show significant benefit from probiotics for preterm infants in preventing necrotising enterocolitis, all-cause mortality and even sepsis.

• The association between Fusobacterium nucleatum and cancer colorectal: A systematic review and meta-analysis
  • 57 studies
  • Fusobacterium nucleatum is found at higher rates in colorectal cancer tumor tissue samples in comparison to control samples of healthy tissue (OR 4.6)
  • Commentary: Points to possibility of microbial changes associated with colon cancer.

• Gender differences in Barrett’s esophagus and progression of disease: a systematic review and meta-analysis
  • 10 studies, 19,337 patients with Barrett’s esophagus
  • Men had higher rates of BE (4.7% vs 1.3%)
  • Men also had higher rates of annual progression of Barrett’s to high-grade dysplasia or adenocarcinoma (1.54% vs 0.62%) 
  • Commentary: This study demonstrates a 70% lower rate of prevalence and a 60% lower rate of neoplastic progression of Barrett’s in women.

Thyroid & Hormones Studies

• Changes in serum heavy metals in polycystic ovary syndrome and their association with endocrine, lipid-metabolism, inflammatory characteristics and pregnancy outcomes
  • 40 PCOS patients, 40 healthy controls
  • Measured serum heavy metal concentration
  • PCOS patients had higher serum chromium (Cr), mercury (Hg) and copper (Cu) 
    • Hg was associated with higher androgens (e.g. testosterone)

• A Systematic Review and Meta-Analysis of the Association Between Polycystic Ovary Syndrome and Coronary Artery Calcification
  • 7 observational studies, 2,341 participants with PCOS
  • PCOS was associated with an increased risk of having a coronary artery calcium score >0 (OR 1.8 to 2.5) 
  • Commentary: PCOS is associated with approximately double the risk of having cardiovascular disease, possibly due to underlying metabolic dysfunction. Keep in mind this is an observational study.

• Appropriate duration of antithyroid drug treatment as a predictor for relapse of Graves’ disease: a systematic scoping review
  • Aim: Identify optimal duration of antithyroid drug (ATD) treatment for preventing Graves’ disease relapse
  • Treatment with methimazole for > 5 years led to: 
    • Persistent normalization of TSH-receptor antibodies
    • 4-year remission rate of 85% (compared to 50% remission after conventional length of treatment 12-18 months) 
  • Commentary: Long-term ATD treatment should be considered in patients with Graves’ disease.

Diet & Lifestyle Studies

• Effects of exercise training on the cognitive function of older adults with different types of dementia: a systematic review and meta-analysis
  • 28 RCTs, 2,158 participants with dementia
  • Exercise improved cognitive function (small effect size)

• Intermittent Fasting versus Continuous Calorie Restriction: Which Is Better for Weight Loss?
  • Meta-analysis
  • Intermittent fasting led to greater weight loss compared to continuous calorie restriction (small effect size) 
  • NO effect on BMI between groups
  • Commentary: Intermittent fasting may be more effective for weight loss compared to caloric restriction.

• Effects of Intermittent Fasting in Human Compared to a Non-intervention Diet and Caloric Restriction: A Meta-Analysis of Randomized Controlled Trials
  • 43 RCTs with 2,483 participants
  • Compared to continuous calorie restriction, intermittent fasting led to:
    • Lower weight (large effect size)
    • Lower BMI (medium effect size)
    • Higher fat-free mass (medium effect size)
    • Better insulin sensitivity (small effect size)
    • Lower triglycerides and cholesterol (small effect size)

• The Effects of Omega-3 Supplementation on Depression in Adults with Cardiometabolic Disease: A Systematic Review of Randomised Control Trials
  • 7 RCTs, 2,575 participants with depression, randomized to placebo or omega-3 supplementation 
  • Compared to placebo, omega-3 supplementation did NOT improve depression scores in 6/7 studies
  • However, omega 3-supplementation did improve depression in participants with:
    • Severe depression
    • Current antidepressant medication use
  • Commentary: While omega-3 supplementation overall does NOT improve depression, some may benefit with more severe depression. 

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Featured Study

• Systematic review and meta-analysis of the efficacy and pregnancy outcomes of levothyroxine sodium tablet administration in pregnant women complicated with hypothyroidism
  • 9 studies, 2,873 pregnant women w/ subclinical hypothyroidism 
  • Compared to control, treatment with levothyroxine lowered the risk of: 
    • Preterm birth (OR 0.4)
    • Abortion (OR 0.3)
    • Postpartum hemorrhage (OR 0.4)
    • Low birth weight infants (OR 0.1)
  • Commentary: This study illustrates an important patient population that significantly benefits from treating subclinical hypothyroidism.

Gastrointestinal Studies

• The effects of probiotics plus dietary fiber on antipsychotic induced weight gain: a randomized clinical trial
  • 113 schizophrenic and bipolar patients taking antipsychotics, randomized to: 
    • Placebo
    • Probiotics
    • Fiber
    • Probiotics + fiber
  • After 3 months, compared to placebo, probiotics + fiber led to the greatest improvements in: 
    • Weight loss (-5.2 lb probiotic/fiber vs +5.7 lbs placebo) 
    • BMI (-0.9 vs +1.0)
    • Insulin (-1.9 vs +4.6 µIU/mL) 
    • Insulin resistance (-0.4 vs +1.1) 
  • Commentary: Probiotics + fiber prevented weight gain and metabolic imbalances in those taking antipsychotics, which are known side effects. This highlights the gut-metabolism connection.

• The efficacy of vitamin D supplementation for irritable bowel syndrome: a systematic review with meta-analysis
  • 4 RCTs, 335 participants with IBS randomized to placebo or vitamin D
  • Vitamin D led to improvements in:
    • IBS symptom score (-84 vitamin D vs -28 placebo)
    • Quality of life (+15 vs +6.5)
  • Commentary: Vitamin D may be an effective therapy for improving IBS symptoms and quality of life.

• Systematic review and meta-analysis of probiotics in the treatment of allergic rhinitis
  • 30 RCTs, 2,708 patients with allergic rhinitis randomized to placebo or probiotics 
  • Probiotics led to improvements in: 
    • Quality of life score (-9.4)
    • Allergic rhinitis symptom score (-1.9)
  • NO change in blood eosinophils, allergic eye symptoms or antigen-specific IgE levels between groups
  • Commentary: Probiotics improved allergic rhinitis symptoms and quality of life.

• Probiotic as an adjuvant therapy in chronic urticaria: a blinded randomized controlled clinical trial
  • 42 patients with chronic urticaria, randomized to: 
    • Antihistamines alone (control)
    • Antihistamines + probiotics (intervention)
  • After 2 months, antihistamines + probiotics led to greater improvements in:
    • Urticaria scores (-21 intervention vs -18.4 control)
    • Quality of life (+66% vs +44%) 
  • Commentary: Addition of probiotics to antihistamine medication led to better clinical outcomes in patients with urticaria.

• Restoration of the Original Inhabitants: A Systematic Review on Fecal Microbiota Transplantation for Graft-Versus-Host Disease
  • 6 studies, 79 patients with graft-versus-host disease (GVHD), treated with FMT
  • FMT led to complete remission in 56% and partial remission in 26.5% of patients with GVHD 
  • Commentary: This study highlights the connection between our gut microbiota and immune tolerance.

• Improvement of Psoriasis Using Oral Probiotic Streptococcus salivarius K-12: a Case-Control 24-Month Longitudinal Study
  • Retrospective study, 198 adults and children with psoriasis randomized to: 
    • Topical emollient
    • Topical emollient + probiotics
  • After 6 months, the probiotic group experienced greater rates of: 
    • Complete remission (55% probiotics vs 21% control)
    • 90% remission (75% vs 30.6%)
    • 75% remission (84% vs 42.8%) 
  • Commentary: Probiotics may be an effective therapy for treating psoriasis. This highlights the gut-skin connection.

• Effect of Probiotic-Assisted Eradication of cagA+/ vacA s1m1 Helicobacter pylori on Intestinal Flora
  • 168 patients with cagA+/vacA H. pylori, randomized to:
    • Bismuth quadruple therapy (BQT)
    • BQT + S. boulardii
  • After 2 weeks, the probiotic group experienced: 
    • Greater eradication rates (82% vs 77%)
    • Fewer adverse events (8% vs 25%) 
    • Quicker resolution of symptoms
  • Commentary: Another study showing the synergistic effect of adding probiotics to antimicrobial therapy in treating H. pylori, especially in reducing side effects.

• Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study
  • 55 COVID-19 hospital patients randomized to:
    • Standard treatments (control) 
    • Standard treatment + synbiotics
  • After 1 month, treatment with synbiotics led to: 
    • Greater antibody response (88% synbiotic vs 63% control) 
    • Reduced inflammatory markers 
    • Lower nasopharyngeal viral load 
  • Commentary: Synbiotics can improve the immune response to a viral infection.

• Bifidobacteriumlongum subsp. infantis EVC001 Administration Is Associated with a Significant Reduction in the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants
  • Retrospective study, 483 very low birthweight infants in the ICU 
  • Infants treated with probiotics experienced:
    • Lower rates of necrotizing enterocolitis (NEC) (2.7% probiotics vs 11% control)
    • Reduced mortality from NEC (0% vs 2.7%)
  • Commentary: Probiotics led to reduced risk of death from NEC in very high risk infants.

• Effects of Bifidobacterium animalis subspecies lactis supplementation on gastrointestinal symptoms: systematic review with meta-analysis
  • 14 studies on adults GI symptoms
  • Single-strain bifidobacterium animalis lactis probiotic led to:
    • Increased defecation frequency (small effect size) 
    • Faster colon transit time (small effect size) 
    • Improved stool consistency (moderate effect size) 
    • NO change in abdominal pain or bloating

Thyroid & Hormones Study

• Effects of a Cereal Bar with a Combination of Phytoestrogens on the Climacteric Symptoms: A Placebo-Controlled, Randomized Trial
  • 48 women with climacteric symptoms, randomized to: 
    • Placebo bar
    • Phytoestrogen bar (containing soybean and flaxseed phytoestrogens) 
  • After 3 months, the phytoestrogen bar in peri/postmenopausal women led to improvements in: 
    • Hot flashes
    • Sexual complaints
    • Insomnia
    • Sadness
    • Paresthesia
  • Commentary: Phytoestrogens may improve menopausal symptoms.

Diet & Lifestyle Studies

• Positive Airway Pressure and Cognitive Disorders in Adults With Obstructive Sleep Apnea: A Systematic Review of the Literature
  • 11 studies, 60,840 participants w/ sleep apnea, categorized by:
    • No treatment for sleep apnea
    • CPAP therapy 
  • Treatment of sleep apnea with CPAP was associated with:
    • Delayed onset of mild cognitive impairment
    • Reduced incidence of mild cognitive impairment and Alzheimer’s disease
    • Slower cognitive decline
  • Commentary: Treatment of sleep apnea may lead to lower rates of cognitive disorders and cognitive decline.

• Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial: a randomized controlled trial
  • 2,495 participants (≥60-65 y/o) free of heart disease or cancer, randomized to:
    • Placebo
    • Vitamin D 1,600 IU/day
    • Vitamin D 3,200 IU/day
  • After 5 years, vitamin D supplementation did NOT reduce the risk of cardiovascular disease or cancer compared to placebo

• Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease activity in inflammatory rheumatic diseases: a systematic literature review and meta-analysis
  • 30 RCTs, 1,420 patients with inflammatory rheumatic diseases, randomized to: 
    • Control group 
    • Polyunsaturated fatty acids (PUFA) 
  • Compared to control, PUFA supplementation led to improved: 
    • Tender + swollen joints 
    • Morning stiffness duration 
    • Perceived disease activity
    • Perceived overall pain 
    • Erythrocyte sedimentation rate 
  • Greater effects were seen with:
    • Animal derived PUFA
    • Omega 3 PUFA
    • Supplementation between 3-6 months
    • Dose >2 g/day
  • Commentary: Omega 3 PUFA consumption may be clinically useful for patients with inflammatory rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

• Chlamydia pneumoniae and Mycoplasma pneumoniae as Two Emerging Risk Factors in Atherosclerosis: Meta-Analysis Study and Systematic Review
  • 38 studies
  • Atherosclerosis was significantly associated with: 
    • Chlamydia pneumoniae (OR 2.2)
    • Mycoplasma pneumoniae (OR 1.6) 
  • Commentary: Persistent infections may contribute to atherosclerosis.

• A systematic review and meta-analysis of the effects of Hibiscus sabdariffa on blood pressure and cardiometabolic markers
  • 17 studies 
  • Hibiscus is effective at lowering systolic blood pressure compared to: 
    • Medication (-14.9 hibiscus vs -17 mmHg medication)
    • Placebo (-10 vs -1 mmHg placebo)
  • Commentary: Hibiscus lowers blood pressure nearly as effective as medication.

• Meditation-based lifestyle modification in mild to moderate depression-A randomized controlled trial
  • 81 patients with mild to moderate depression, randomized to: 
    • Antidepressant medication (control) 
    • Treatment as usual (TAU) 
      • Includes medication, movement therapy, psychotherapy, relaxation techniques
    • Meditation-based lifestyle modification (MBLM) 
      • Includes whole-food diet, sleep hygiene, yoga, meditation, breathing exercises, mindset etc
    • After 2 months, compared to control and TAU, MBLM led to a greater reduction in depression scores (-13.1 MBLM vs -3.3 TAU vs -1.7 control) 
    • Commentary: A comprehensive lifestyle-based approach was more effective in improving depression than medication.

• Fish intake, n-3 fatty acid body status, and risk of cognitive decline: a systematic review and a dose-response meta-analysis of observational and experimental studies
  • Systematic review and meta-analysis 
  • Fish intake up to 2 portions per week led to:
    • 10% reduction in all-cause dementia
    • 30% reduction in Alzheimer’s disease risk 
  • Commentary: Fish intake is associated with lower risk of cognitive decline.

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Featured Studies

• The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms
  • 164 IBS patients randomized to placebo or FMT
    • 58.5% had severe IBS
    • 41.5% had moderate IBS
  • After 3 months, compared to placebo, FMT led to greater improvements in IBS symptom score in both: 
    • Severe IBS (-160 FMT vs -40 placebo)
    • Moderate IBS (-80 vs -20) 
  • Severe IBS treated with FMT had greater response rates compared moderate IBS (80% vs 60%) 
  • Commentary: FMT was effective in improving IBS symptoms, especially in those with severe IBS.

• Efficacy and safety of fecal microbiota transplant for recurrent Clostridium difficile infection in inflammatory bowel disease patients: a systematic review and meta-analysis
  • 11 studies on IBD patients with recurrent C. Diff infections (CDI)
  • Fecal microbiota transplants (FMT) led to: 
    • 80% cure rate of CDI after initial treatment
    • 90% cure rate after 2 or more treatments  
    • Higher cure rates in ulcerative colitis compared to Crohn’s disease (85% vs 79%) 
  • Recurrence rate after FMT was 25%
  • NO adverse events occurred after treatment with FMT 
  • Commentary: FMT is highly effective and safe for curing CDI in IBD patients.

Gastrointestinal Studies

• Emotional stress responsivity of patients with IBS – a systematic review
  • 37 studies on patients with IBS 
  • Patients with IBS were more likely to experience:
    • Worse GI symptoms from increased stress
    • Hyperresponsiveness to stress
  • Commentary: Improving stress response is important for patients with IBS.

• Comparison of synbiotics combined with enteral nutrition and prophylactic antibiotics as supportive care in patients with esophageal cancer undergoing neoadjuvant chemotherapy: A multicenter randomized study
  • 81 patients with esophageal cancer treated with chemotherapy, randomized to: 
    • Antibiotics 
    • Synbiotics + enteral nutrition (EN) 
  • Synbiotics + EN led to:
    • Lower rates of neutropenia (side effect of chemotherapy) 
    • Less severe diarrhea
    • Ability to tolerate higher chemotherapy doses 
    • Increased microbiota alpha diversity 
  • Commentary: Synbiotics + EN were safe and improved tolerability of chemotherapy.

• Effectiveness of Partially Hydrolyzed Guar Gum in Reducing Constipation in Long Term Care Facility Residents: A Randomized Single-Blinded Placebo-Controlled Trial
  • 52 elderly adults with chronic constipation using laxatives, randomized to: 
    • Control group (water)
    • Partially hydrolyzed guar gum (PHGG) (5 g/day)
  • After 1 month, PHGG led to:
    • NO improvements in bowel frequency or consistency
    • Fewer laxative medications needed 
  • Commentary: PHGG may help lead to less laxative dependence in patients with constipation.

• Probiotic in the prevention of ventilator-associated pneumonia in critically ill patients: evidence from meta-analysis and trial sequential analysis of randomized clinical trials
  • 23 studies, 5,543 critically ill ventilated patients
  • Probiotics led to a reduced risk of ventilator-associated pneumonia in adults (RR 0.7) and neonates/children (RR 0.5) 
  • Probiotics did NOT have an effect on: 
    • Time in ICU or hospital
    • 90-day mortality rate
    • Bacteremia
    • Diarrhea 
  • Commentary: Another study showing the benefits of probiotics on improving patient outcomes in the ICU, especially neonates/children.

• Characterization of Specific Signatures of the Oral Cavity, Sputum, and Ileum Microbiota in Patients With Crohn’s Disease
  • 43 patients with Crohn’s disease, 18 healthy controls 
  • Microbial composition was sampled in oral cavity, sputum and ileum in all participants
  • Crohn’s disease patients had reduced microbial diversity in the oral cavity and sputum compared to healthy controls 
  • Commentary: Oral dysbiosis was more common in this small group of Crohn’s disease patients.

• Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women
  • 15 women with recurrent UTIs, 16 healthy controls 
  • Women with recurrent UTIs had less gut microbiota diversity compared to healthy controls
  • NO difference was found in E. Coli colonization in the gut or bladder between groups
  • Commentary: Lack of gut microbiota diversity and NOT E. Coli colonization was associated with more frequent UTIs, suggesting a gut-bladder connection.

Thyroid & Hormones Studies

• Green tea promotes weight loss in women with polycystic ovary syndrome: Systematic review and meta-analysis
  • 4 RCTs, 169 women with PCOS, randomized to placebo or green tea 
  • Green tea led to greater weight loss than placebo (-6 lbs) 
  • Commentary: Green tea may be a simple and cost-effective option for weight loss in PCOS patients.

• Different regimens of menopausal hormone therapy for improving sleep quality: a systematic review and meta-analysis
  • 15 studies, 27,715 menopausal women randomized to placebo or hormone therapy
  • Sleep quality was improved to a greater extent with: 
    • Hormone therapy in general vs placebo (small effect size) 
    • Estradiol vs conjugated equine estrogen (small effect size) 
    • Transdermal vs oral estrogen (small effect size)
    • Combined estrogen/progesterone vs estrogen alone (small effect size) 
  • Commentary: While hormone therapy does provide some benefit for sleep quality, the effect size is small.

Diet & Lifestyle Studies

• Clinical information predicting severe obstructive sleep apnea: A cross-sectional study of patients waiting for sleep diagnostics
  • 3,646 patients, all underwent a sleep study
  • 15.7% were diagnosed with severe sleep apnea
  • Risk factors associated with severe sleep apnea included:
    • ≥50 years old
    • Snoring
    • Breathing cessation
    • BMI ≥ 30
    • History of hypertension
  • The presence of ≥2 of these risk factors had a sensitivity of 96% and negative predictive value of 97% for the diagnosis of severe sleep apnea
  • Commentary: The presence of the above risk factors may be a simple screening tool to increase suspicion of severe sleep apnea.

• Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis
  • 115 studies, 199,055 participants
  • The following nutrients were associated with lower risk of respiratory tract infections (RTIs):
    • Zinc (RR 0.8)
    • Vitamin D (RR 0.9)
  • NO effect on RTIs was seen for:
    • Vitamin C 
    • Vitamin A 
    • Vitamin E
    • Beta-carotene
  • Commentary: Zinc and vitamin D provided slight protection against RTI. Note commonly recommended vitamin C did NOT protect against RTIs.

• Effectiveness of Physical Activity and Exercise on Ambulatory Blood Pressure in Adults with Resistant Hypertension: A Systematic Review and Meta-Analysis
  • 4 studies, 178 individuals with resistant hypertension
  • Compared to control groups, 24-hour systolic blood pressure was improved significantly with:
    • Aerobic exercise (-12 mm Hg)
    • General physical activity (-9.8 mm Hg) 
  • Commentary: Exercise is a cost-effective strategy to reduce blood pressure.

• Comparison of a home sleep test with in-laboratory polysomnography in the diagnosis of obstructive sleep apnea syndrome
  • Retrospective study, 67 patients with suspected sleep apnea
  • All patients received home sleep test (HST) and in-laboratory polysomnography (PSG) 
  • Compared to the gold standard PSG, the HST was able to diagnose: 
    • Sleep apnea in general (sensitivity and specificity of 95% and 62.5%, respectively)
    • Moderate to severe sleep apnea (sensitivity and specificity of 80% and 74%, respectively)
  • Commentary: HST has fair accuracy for diagnosing sleep apnea.

• The effect of ketogenic diet on body composition and anthropometric measures: A systematic review and meta-analysis of randomized controlled trials
  • 18 RCTs
  • Ketogenic diet led to improvements in:
    • Body weight (-6.3 lbs)
    • BMI (-1.4)
    • Fat mass (-3 lbs)
    • Percent body fat (-6 lb) 
    • Waist circumference (-3.2 cm) 
    • Visceral adipose tissue (-29 grams) 
  • Lean body mass was reduced by 1.4 lb 
  • Commentary: Ketogenic diet is an effective way to improve body composition.

• The Effects of Cold Exposure Training and a Breathing Exercise on the Inflammatory Response in Humans: A Pilot Study
  • 48 healthy males randomized to:
    • Control (no training)
    • Cold exposure 
    • Breathing exercise (Wim Hof breathing exercise)  
    • Cold exposure + breathing exercise 
  • All participants trained for 1 week before they were injected with lipopolysaccharide (LPS) to induce inflammation
  • Breathing exercise alone and combined with cold exposure led a reduction in proinflammatory cytokines, including: 
    • TNF-α (-32%)
    • IL-6  (-35%)
    • IL-8: (-30%)
  • Commentary: This is the second study to show the combination of breathing exercise + cold exposure can reduce inflammatory cytokines.

• Red meat consumption and risk factors for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
  • 21 RCTs
  • Red meat consumption did NOT worsen risk factors associated with type 2 diabetes, including: 
    • Insulin sensitivity 
    • Insulin resistance
    • Fasting insulin
    • Fasting glucose
    • A1c
  • Read meat intake led to a reduction in postprandial glucose (small effect size) 
  • Commentary: Contrary to observational studies, red meat intake was NOT associated with increased risk of type 2 diabetes.

• Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial
  • 193 healthy adults (20-80 years old) were randomized to: 
    • Placebo
    • Omega-3 fatty acids (2.5 g/day) 
  • After 6 months, cognitive performance was NOT different between groups 
  • However, omega-3 fatty acids did improve memory scores in those who began the study with low memory scores
  • Commentary: Omega 3 fatty acids may be more helpful in those experiencing memory issues, and not healthy individuals.

Podcast Summary

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Featured Studies

• Combined T4+T3 Therapy Versus T4 Monotherapy Effect on Psychological Health in Hypothyroidism: A Systematic Review and Meta-analysis
  • 18 prospective studies, 883 patients comparing T4+T3 combo therapy vs T4 monotherapy for those with overt hypothyroidism
  • T4+T3 therapy led to NO difference in:
    • Depression 
    • Fatigue 
    • Pain 
    • Anxiety
    • Anger
  • However, patients preferred combination therapy significantly.
  • Commentary: Despite no difference in symptom improvement, patients prefer combo therapy. This could be from:
    • Improvements in subjective health not measured in this study
    • Growing market forces

• Effect of Liothyronine Treatment on Quality of Life in Female Hypothyroid Patients With Residual Symptoms on Levothyroxine Therapy: A Randomized Crossover Study
  • 59 female patients with residual hypothyroid symptoms despite adequate levothyroxine (T4) or combined T4/T3 combo therapy
  • Randomized (non-blinded) to: 
    • T4 x 3 months, then T3 x 3 months
    • T3 x 3 months, then T4 x 3 months 
  • Patients initially on T4/T3 had to take 1 month of T4 alone prior to randomization
  • After 3 months, T3 treatment led to greater improvements in: 
    • Hypothyroid symptom (-12 T3 vs -2 T4)
    • Physical fatigue (-4 vs -0.5) 
    • Mental fatigue (-1.8 vs -0.4)
    • Cognitive complaints (-20 vs -9)
    • Quality of life (+11 vs +1) 
    • Depression (-10 vs +1) 
  • TSH levels remained within range in both groups
  • Commentary: Compared to the study above, this smaller study shows symptomatic hypothyroid patients may benefit from treatment with T3. Keep in mind these patients knew which medication they were getting as the study was unblinded.

Gastrointestinal Studies

• Diet or medication in primary care patients with IBS: the DOMINO study – a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute
  • 459 IBS patients, randomized to antispasmodic medication or low FODMAP diet
  • After 8 weeks, the low FODMAP diet had:
    • Greater response rate (71% vs 61%)
    • Greater adherence to treatment (94% vs 73%)
  • Commentary: A low FODMAP diet may lead to greater response rate and be easier to follow as compared to taking a medication.

• Adjuvant Probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in Patients With Type 1 Diabetes Mellitus
  • 27 type-1 diabetic patients randomized to:
    • Insulin + placebo 
    • Insulin + probiotics 
  • After 6 months, the addition of probiotics led to improved: 
    • Glucose (-24 mg/dl probiotic vs -1 mg/dl placebo)
    • A1C (-0.8% vs 0%)
    • Inflammatory cytokines 
  • Glucose regulation was superior in the probiotic group even 3 months after discontinuation of probiotics
  • Commentary: Probiotics can help improve glucose regulation.

• A Comparison of the Low-FODMAPs Diet and a Tritordeum-Based Diet on the Gastrointestinal Symptom Profile of Patients Suffering from Irritable Bowel Syndrome-Diarrhea Variant (IBS-D): A Randomized Controlled Trial
  • 42 IBS-D patients randomized to: 
    • Low FODMAP (LFD)
    • Tritordeum-based diet (hybrid wheat/barley product that contains lower gluten)
  • After 3 months, LFD led to greater improvements in IBS symptom scores (-132 vs -75) 
  • Commentary: Another study showing LFD is effective in improving IBS symptoms.

• Probiotics for the Prevention of Ventilator-Associated Pneumonia: An Updated Systematic Review and Meta-Analysis of Randomised Controlled Trials
  • 18 RCTs, 4,893 patients 
  • Probiotics led to a reduction in: 
    • Ventilator-associated pneumonia (RR 0.7)
    • Time in ICU (-2.2 days)
    • Duration of antibiotic use (-1.2 days)
  • Commentary: Probiotics may lead to improved clinical outcomes in ICU patients.

• Synbiotic Supplementation Improves Response to Iron Supplementation in Female Athletes during Training
  • 20 females w/ suboptimal ferritin (~18 ng/ml) were randomized to: 
    • Iron + placebo
    • Iron + synbiotic 
  • After 2 months, the synbiotic group had greater improvements in iron status
  • Commentary: The addition of synbiotics led to greater iron levels, likely by improved gut health.

• Effects of 4G-beta-D-Galactosylsucrose in patients with depression: A randomized, double-blinded, placebo-controlled, parallel-group comparative study
  • 20 patients with depression, randomized to placebo or PREbiotics 
  • After 6 months, NO difference in depression between groups 
  • Commentary: This small study showed no benefit of prebiotics on depression.

• Association between proton pump inhibitor use and risk of pneumonia in children: nationwide self-controlled case series study in Sweden
  • 2,356 pediatric patients w/ history of pneumonia and PPI use 
  • Risk of pneumonia was increased: 
    • Prior to PPI treatment (RR 1.8)
    • During PPI treatment (RR 1.4)
  • Commentary: While there is an association between PPI use and pneumonia, these findings do NOT support a causal relationship. In fact, pneumonia risk was elevated even before PPI use.

• Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
  • 173 preterm infants, randomized to single or multi-strain probiotics
  • Both single and multi-strain probiotics led to:
    • Similar time taken to achieve a full feeding 
    • Reduced dysbiosis 
  • NO adverse effects occurred
  • Commentary: Note that probiotics are safe even in preterm infants.

• Seronegative Celiac Disease in Patients with Isolated Refractory Dyspepsia and Gastroesophageal Reflux Disease
  • 129 patients with refractory dyspepsia or GERD
  • All patients had duodenal biopsy results consistent with celiac disease, despite NORMAL endoscopy
  • 6 months to 2 years on a gluten free (GFD) diet led to improved: 
    • Reflux score (6.3 pre-GFD vs 0.7 post-GFD) 
    • Dyspepsia score (14.3 vs 1.1) 
  • Commentary: A diagnosis of seronegative celiac disease may be considered in patients with persistent GERD or dyspepsia.

• Long-term personalized low FODMAP diet improves symptoms and maintains luminal Bifidobacteria abundance in irritable bowel syndrome
  • 18 IBS patients who had been on low FODMAP diet x12 months
  • After 12 months of a low FODMAP diet:
    • 67% had adequate relief of symptoms (compared to 28% at baseline)
    • IBS symptom severity decreased (from 227 to 154)
    • NO change in Bifidobacteria abundance
    • Lower concentration of total SCFA
  • Commentary: A majority of participants reported symptom relief with a long-term low FODMAP diet despite SCFA levels decreasing.

• Probiotics in the Treatment of Inflammatory Bowel Disease in Adulthood: A Systematic Review
  • 22 studies on patients with IBD
  • Crohn’s disease: 
    • Probiotics alone had NO effect in 6/7 studies
  • Active ulcerative colitis:
    • Probiotics + standard treatment improved active ulcerative colitis compared to standard treatment alone in 5/9 studies
  • Inactive ulcerative colitis:
    • Probiotics were as effective as standard treatment in 3/7 studies
  • Commentary: While the results of this study are mixed, the overall trend suggests probiotics are beneficial especially in combination with other therapies.

• Probiotic mouthwash as an adjunct to mechanical therapy in the treatment of stage II periodontitis: A randomized controlled clinical trial
  • 60 patients w/ periodontitis, randomized to: 
    • Placebo
    • Probiotic mouthwash (lacto/bifido blend + S. boulardii)
  • After 3 months, probiotics led to: 
    • Improved periodontal parameters
    • Increased salivary IgA 
  • Commentary: Probiotics have a positive effect on overall oral health.

• Potential pathobionts in vaginal microbiota are affected by fish oil and/or probiotics intervention in overweight and obese pregnant women
  • Overweight pregnant women were randomized to:
    • Placebo + placebo
    • Placebo + fish oil
    • Placebo + probiotics
    • Probiotics + fish oil
  • Vaginal samples were collected on all participants
  • Compared to placebo, the addition of probiotics and fish oil led to a reduction in vaginal pathogenic bacteria 
  • Commentary: Probiotics and fish oil may have beneficial effects on the vaginal microbiota.

• Randomized, double-blind, placebo-controlled clinical trial on the usefulness of probiotic Lactobacillus reuteri in bismuth-containing quadruple eradication therapy for infection with Helicobacter pylori
  • 80 patients with H pylori
  • Received bismuth quadruple eradication therapy + either probiotic or placebo
  • No difference in eradication rate in the 2 groups
  • However, the probiotic group had:
    • Less abdominal pain (-42% vs -19%)
    • Less abdominal distension (-25% vs -17%)
  • Commentary: While this study showed no change in eradication rate, the probiotic group had less symptoms.

Diet & Lifestyle Studies

• Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial
  • 169 participants w/ sleep apnea and cardiovascular disease, randomized to control or CPAP
  • After 1 year, CPAP led to reduced:
    • 24-hour average blood pressure (-2.7 mm Hg) 
    • Night-time blood pressure (-5.9 mm Hg) 
  • Commentary: Treatment of sleep apnea w/ CPAP led to minor reductions in blood pressure.

• Obesity, Thyroid and OSA: An Intriguing Triangle
  • 65 patients w/ untreated sleep apnea, all underwent thyroid function tests
  • Overt hypothyroidism was diagnosed in 12.3% of patients (as compared to 1% of the general population)
  • Commentary: Hypothyroidism is associated with sleep apnea. Keep in mind this is an observational study.

• Calorie Restriction with or without Time-Restricted Eating in Weight Loss
  • 118 obese participants randomized to: 
    • Calorie restriction (CR) 
    • Time restricted feeding (8:00 AM – 4:00 PM) (TRF) + CR
  • After 1 year, TRF group experienced greater weight loss compared to CR alone (18 lbs vs 14 lbs)
  • Commentary: The addition of TRF to CR may lead to small further improvement in weight loss.

• Respiratory Muscle Training in Patients with Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis
  • 8 studies, 210 sleep apnea patients treated w/ respiratory muscle training
  • Inspiratory muscle training showed improvements in:
    • Sleepiness score (-4.4 points) 
    • Sleep quality score (-2.8 points) 
    • Inspiratory muscle strength 
  • NO change was observed in sleep apnea scores
  • Commentary: Respiratory training improved sleepiness, sleep quality and inspiratory muscle strength.

• Relationship between Egg Consumption and Metabolic Syndrome. A Meta-Analysis of Observational Studies
  • 20 studies, 331,667 participants
  • Consumption of eggs was associated with a lower risk of metabolic syndrome (RR 0.9)
  • Commentary: Keep in mind this is an observational study, so causality cannot be concluded.

• Low-Calorie Ketogenic Diet with Continuous Positive Airway Pressure to Alleviate Severe Obstructive Sleep Apnea Syndrome in Patients with Obesity Scheduled for Bariatric/Metabolic Surgery: a Pilot, Prospective, Randomized Multicenter Comparative Study
  • 70 patients w/ obesity and obstructive sleep apnea (OSA)
  • Randomized to:
    • CPAP therapy
    • Or CPAP + low carb diet (LCD)
  • After 4 weeks, the CPAP + LCD had:
    • Similar improvement in AHI
    • Greater reduction in CRP
    • Greater reduction in body weight
    • Reduction in systolic blood pressure
    • Lower LDL-C and triglycerides
  • Commentary: A LCD may be a good adjunct therapy to CPAP for OSA.

• Omega-3 for the prevention of cardiovascular diseases: meta-analysis and trial-sequential analysis
  • 11 RCTs, 100,609 participants
  • Omega-3 fatty acid supplementation led to a 6% reduction in mortality due to cardiovascular issues (RR=0.94)

• The effects of curcumin on anthropometric and cardiometabolic parameters of patients with metabolic related diseases: a systematic review and dose-effect meta-analysis of randomized controlled trials
  • 31 studies on patients with metabolic-related diseases
  • Curcumin supplementation led to improvements in:
    • Body weight (-2 lbs) 
    • Fasting glucose (-0.5 mg/dl)
    • A1c (-0.4%) 
    • Insulin (-1.7 μIU/mL)
    • Insulin resistance (-0.7)
    • HDL-C (+1.7 mg/dl) 
    • hsCRP (-1.1)
  • Supplementation w/ nanocurcumin showed even greater reductions in:
    • Fasting glucose (-1.7)
    • Total cholesterol (-12.6 mg/dl) 
    • LDL-C (-9 mg/dl)
  • Commentary: Curcumin may improve metabolic health, with notable improvements in hsCRP, cholesterol and insulin.