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Featured Study

• The neglected role of Blastocystis sp. and Giardia lamblia in development of irritable bowel syndrome: A systematic review and meta-analysis
  • 29 studies for Blastocystis and 11 studies for Giardia
  • For B. hominis:
    • Individuals with Blastocystis sp. infection were significantly at a higher risk of IBS (OR 1.78)
  • For Giardia:
    • Cohort studies (comparing IBS rates of exposed vs non-exposed) showed increased IBS risk (OR 5.47)
    • Case-control studies (looking at Giardia rates among IBS vs healthy controls) showed NO significant risk
  • Commentary: This meta-analysis did suggest a mild, yet notable effect of parasitic infections on the risk of IBS.

Gastrointestinal Studies

• Effect of wheat bran derived prebiotic supplementation on gastrointestinal transit, gut microbiota, and metabolic health: a randomized controlled trial in healthy adults with a slow gut transit
  • 48 healthy adults w/ constipation, randomized to prebiotic or placebo
  • After 12 weeks:
    • NO difference in transit time
    • Softer stool consistency in prebiotic group
    • Increased Bifidobacterium counts in prebiotic group
  • Commentary: Prebiotics softened stool and increased Bifidobacterium counts WITHOUT improving transit time in this small study.

• Efficacy and safety of fecal transplantation versus targeted therapies in ulcerative colitis: network meta-analysis
  • 19 studies
  • FMT was comparable to other UC pharmacological therapies
  • NO difference in adverse effects between FMT and meds
  • Of the meds, Infliximab was ranked highest in inducing clinical remission
  • Commentary: FMT was comparable to other UC meds in achieving clinical remission.

• The home environment in a nationwide sample of multi-family buildings in Sweden: associations with ocular, nasal, throat and dermal symptoms, headache, and fatigue among adults
  • Cross-sectional study, 5,775 participants in Sweden
  • Of all the participants:
    • 8.3% had ocular symptoms
    • 11.9% nasal symptoms
    • 7.1% throat symptoms
    • 11.9% dermal symptoms
    • 8.5% headache
    • 23.1% fatigue
  • Risk factor for symptoms
    • Buildings constructed from 1961-1985
    • Mold and mold odor
    • Building dampness
    • Lack of mechanical ventilation system
    • Tobacco smoke exposure
  • Commentary: This observational study suggested a link between environmental toxicity and symptoms.

• Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial
  • Multi-center RCT of 2,653 critically-ill patients randomized to L rhamnosus GG probiotic or placebo
  • NO difference in ventilator-associated pneumonia between groups (21.9% probiotics, 21.3% in control)

• Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial
  • 68 patients w/ functional dyspepsia, randomized to soil-based probiotic or placebo
  • After 8 weeks, the probiotic group had:
    • Higher rate of clinical improvement (48% vs 20%)
  • Commentary: A soil-based probiotic improved dyspeptic symptoms in this study. 

• Distinctive Clinical Correlates of Small Intestinal Bacterial Overgrowth with Methanogens
  • Aim: Determine if specific symptoms and conditions are associated with methanogenic SIBO
  • Retrospective study of 1,461 patients who received glucose breath test
  • 33.1% were SIBO positive:
    • 49.8% produced only hydrogen
    • 38.8% produced only methane
    • 11.4% produced both gases
  • Associated conditions for hydrogen-predominant SIBO (but not methane SIBO)
    • Vitamin B12 deficiency (odds ratio 1.44)
    • Roux-en-Y gastric bypass (OR 2.14)
    • Cholecystectomy (OR 1.42)
    • Diabetes (OR 1.59)
  • Commentary: Hydrogen-predominant SIBO is the most common subtype. Make notes of the above risk factors when considering the possibility of SIBO.

• Effect of Bacillus coagulans Unique IS2 with Lactulose on Functional Constipation in Adults: a Double-Blind Placebo Controlled Study
  • 150 patients w/ functional constipation randomized to:
    • Lactulose + soil-based probiotic
    • Lactulose alone
    • Placebo
  • After 4 weeks, the soil-based probiotic + lactulose had significant better improvement in stool frequency compared to lactulose alone in the first few weeks
    • However, this difference was not statistically significant after the end of the trial
  • Commentary: While there was a trend towards better improvement, this study failed to show superiority of probiotic + lactulose over lactulose alone for treating functional constipation. More improvement may have been achieved with using triple probiotic therapy.

• Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial
  • 156 healthy adults randomized to lacto/bifido probiotic or placebo
  • After 8 weeks, the probiotic group had significant improvement in:
    • Depressive symptoms
    • Anxiety
    • Sleep quality
  • Commentary: Probiotics can improve sleep quality and mood balance in otherwise healthy individuals. 

• Is Diet Sufficient as Laryngopharyngeal Reflux Treatment? A Cross-Over Observational Study
  • 50 patients w/ LPR started on low-fat/high-protein diet
  • After 6 weeks, 74% saw significant improvement in symptoms
  • Commentary: Diet can have a significant positive effect on LPR symptoms.

• Influence of adding vitamin D3 to standard clarithromycin-based triple therapy on the eradication rates of Helicobacter pylori infection
  • 150 patients w/ H pylori gastritis treated w/ clarithromycin-based triple therapy and randomized to Vit D x1 month or no additional treatment
  • After 4 weeks post-antibiotics, H pylori eradication was HIGHER in the vitamin D addition group (88% vs 74%)
  • Commentary: Addition of Vit D can possibly improve H pylori eradication when given w/ traditional antibiotic therapy.

• Small intestinal bacterial overgrowth among patients with celiac disease unresponsive to a gluten free diet
  • Case control study of 32 Celiac Disease patients unresponsive to gluten-free diet, 52 healthy age- and sex-matched controls
  • SIBO positive rates per lactulose breath test:
    • 31% of Celiac Disease
    • 15% of healthy controls
  • Commentary: Celiac disease patients unresponsive to gluten-free diets had a x2 higher rate of SIBO compared to healthy controls. SIBO may be a reason for symptoms despite a gluten-free diet.

Autoimmunity Studies

• Antibiotic treatment during early childhood and risk of type 1 diabetes in children: A national birth cohort study
  • Cross-sectional study, 75,615 mother-child dyads
  • NO association between antibiotic exposure and risk of type 1 diabetes
    • NO association seen w/ 1, 2, or 3 or more courses of antibiotics
  • Commentary: This study failed to show an association between antibiotic exposure and T1D.

• Effect of omega-3 fatty acids supplementation during childhood in preventing allergic disease: a systematic review and Meta-Analysis
  • 5 RCTs, 2 prospective studies
  • Omega-3 fatty acids during childhood did NOT reduce risk of atopy (allergic disease) 

Diet & Lifestyle Studies

• Systolic Blood Pressure Time in Target Range and Cardiovascular Outcomes in Patients With Hypertension
  • Post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial)
  • Each 1-standard deviation increase in time in target range (110-140 mmHg) was significantly associated with a decreased risk of first major adverse cardiovascular event 
  • Commentary: Controlling blood pressure is an important aspect of cardiovascular disease reduction

• Do physical interventions improve outcomes following concussion: a systematic review and meta-analysis?
  • 12 studies using exercise as therapy after concussion:
    • 7 on aerobic exercise
    • 1 on vestibular therapy
    • 1 on cervical therapy
    • 3 on multimodal training (cervical, vestibular, oculo-motor training)
  • Benefit for:
    • Aerobic exercise had small-moderate effect in improving symptoms (effect size 0.43) but not time to recovery
    • Multimodal training had moderate effect in improving symptoms (effect size 0.63) and time to recovery
  • No significant improvement w/ cervical or vestibular training
  • Commentary: Isolated neurological rehab tools may not be enough when used in isolation. Instead, using combined cervical, vestibular, and oculomotor training as part of a comprehensive program may play an important role in a post-concussion rehab program.

• Supplementation with oil rich in eicosapentaenoic acid, but not in docosahexaenoic acid, improves global cognitive function in healthy, young adults: results from randomized controlled trials
  • 310 healthy adults randomized to 
    • DHA rich oil (900 mg DHA + 270 mg EPA)
    • EPA rich oil (360 mg DHA + 900 mg EPA)
    • Placebo (olive oil)
  • EPA rich oil group had:
    • Better cognitive speed and accuracy
    • Better memory
  • Commentary: This study suggests the superiority of EPA in promoting cognitive health in healthy adults, and counters the hypothesis that DHA is superior for brain health.

• Diagnostic accuracy of level IV portable sleep monitors versus polysomnography for pediatric obstructive sleep apnea: a systematic review and meta-analysis
  • 20 studies, 7,062 pediatric participants
  • Portable sleep monitors (e.g home sleep test) had a sensitivity of 74% and specificity of 90% in detecting sleep apnea
  • Commentary: Portable sleep monitors have fairly good accuracy in diagnosing sleep apnea in a pediatric cohort.

• Changes in headache characteristics with oral appliance treatment for obstructive sleep apnea
  • Thirteen obstructive sleep apnea (OSA) patients with headaches treated with a mandibular advancement device
  • 8 patients (62%) had at least >30% reduction in headache frequency
  • Commentary: Oral appliances may be an effective strategy to reduce OSA-related symptoms.

• Prevalence and Assessment of Sleep-Disordered Breathing in Patients with Atrial Fibrillation:A Systematic Review and Meta-Analysis
  • 33 studies, 23,894 patients w/ afib
  • Prevalence of sleep-disordered breathing was 78%
    • Mod-severe SDB; 40% prevalence
  • Commentary: There was a high rate of SDB among those w/ afib.

• Effect of position therapy and oral devices on sleep parameters in patients with obstructive sleep apnea
  • 160 patients w/ obstructive sleep apnea (OSA) randomized to position therapy device (PTD) or oral appliance (OA)
  • After 8 weeks, 
    • Apnea-hypopnea index decreased in both groups (-8/h for PTD, -10/hr for OA)
    • Snoring decreased in both groups (-14% for PTD, -10% for OA)
  • Commentary: Both side-sleeping devices and oral appliances are effective therapies for OSA.

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Featured Study

• Levothyroxine Sodium Oral Solution Normalizes Thyroid Function in a Patient with Hashimoto’s Disease, Gastritis, Diabetic Gastroparesis, and Small Intestinal Bacterial Overgrowth (SIBO)
  • Case study of a 51 year old female w/ long-standing Hashimoto’s with multiple food and medication sensitivities
  • Presented w/ multitude of symptoms: recurrent hives, dry skin, fatigue, weight gain, intermittent constipation and diarrhea, cold intolerance, brain fog
  • Over course of 6 months, TSH was not well controlled on multiple medications (general T4, brand T4, combined T4/T3)
  • Developed projectile vomiting, weight loss,10-20 bowel movements per day
  • Breath test, endoscopy and scintigraphy revealed SIBO, gastritis, gastroparesis, and hiatal hernia
  • Switched to liquid T4
    • TSH decreased from 7.42 to 1.55 after 6 weeks
    • TSH decreased further to 0.56 after being treated w/ Rifaximin
  • Commentary: This case study exemplifies a few things:
    • The gut-thyroid connection: there remains an association between hypothyroidism, SIBO, and gastroparesis symptoms
    • Consider liquid T4 therapy before combined T4/T3: this case study supports the use of our clinical thyroid algorithm of considering oral T4 and working on the gut before combined T4/T3 therapy. 
    • Authors note a meta-analysis of 141 patients that showed that patients with suboptimal TSH on tablet T4 significantly improved TSH by switching to a liquid L-T4 formulation at an unchanged dose

Gastrointestinal Studies

• Immunogloboulin E-Mediated Food Sensitization in Children with Celiac Disease: A Single-Center Experience
  • 59 children w/ Celiac Disease assessed for Ig-E sensitivity (food allergy)
  • 20.3% of CD patients also had food allergies
    • Only 41.7% of these patients reported symptoms associated w/ the consumption of these foods
  • Commentary: A notable portion of CD patients also had diagnosed IgE food sensitivity. The most significant finding was that less than half reported symptoms despite positive lab findings. 

• Effects of glutamine supplementation on inflammatory bowel disease: A systematic review of clinical trials
  • 7 studies using glutamine (21-30g or 0.5g per kg of participant’s body weight)
  • Of the 7 studies:
    • 2 of 3 studies showed NO effect on intestinal permeability
    • 2 of 2 studies showed NO effect on body weight or anthropometrics
    • Only 2 of 5 studies showed reduced inflammation and oxidative stress
    • Only 2 of 5 studies showed reduced disease activity
  • Commentary: This systematic review failed to show support the use of glutamine in IBD.

• The effect of acute consumption of resistant starch on appetite in healthy adults; a systematic review and meta-analysis of the controlled clinical trials
  • Resistant starch interventions associated w/ reduced appetite
    • Especially when use >25 g

• Head of bed elevation to relieve gastroesophageal reflux symptoms: a systematic review
  • 5 trials, 228 patients
  • Head elevation at bedtime was associated w/ an improvement of GERD symptoms
  • Commentary: This study validates the common lifestyle measure of bedtime head elevation for those w/ reflux and GERD.

• The effects of Bacillus coagulans supplementation in patients with non-alcoholic fatty liver disease: A randomized, placebo-controlled, clinical trial
  • 53 patients w/ fatty liver randomized to probiotics or placebo
  • After 12 weeks, the probiotic group had a greater reduction in:
    • Serum liver function tests
    • Inflammatory markers
    • Liver steatosis

• Effect of Saccharomyces boulardii CNCM-I 3799 and Bacillus subtilis CU-1 on Acute Watery Diarrhea: A Randomized Double-Blind Placebo-Controlled Study in Indian Children
  • 180 children (<5 yo) w/ acute mild-moderate diarrhea, randomized to standard care plus either S boulardii + soil-based probiotic or placebo
  • The probiotic group had:
    • Reduced time of diarrhea (54 hrs vs 59.5 hrs)
      • Greater improvement if given probiotics within 24 hrs of diarrhea onset (25 hr difference)
    • Less diarrhea at 3 month followup (15% vs 18.5% of participants)
  • Commentary: More evidence for probiotics for acute diarrhea in kids.

• Correlation of clinical symptoms, endoscopic features and density of oesophageal eosinophilia in children with newly-diagnosed eosinophilic esophagitis
  • Retrospective study of 47 children w/ newly diagnosed eosinophilic esophagitis 
  • 70% of the children had a history of an allergy disease
  • Most common clinical symptoms were abdominal pain (53%) and GERD-like symptoms (26%)
  • NO significant differences were found between the density of eosinophil infiltration and clinical symptoms or endoscopic features
  • Commentary: Reminder that symptoms do NOT always correlate w/ mechanisms/histopathologic findings.

• A comparison of the inhibitory activities of Lactobacillus and Bifidobacterium against Penicillium expansum and an analysis of potential antifungal metabolites
  • Mechanistic study aimed to examine probiotic’s effect on mycotoxin production
  • Bifidobacterium was found to reduce multiple mycotoxins produced by ​​Penicillium expansum mold species

• Effect of Probiotic Supplementation on Glycemic Outcomes in Patients with Abnormal Glucose Metabolism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • 31 studies, 1,948 participants w/ prediabetes or diabetes
  • Compared to controls, probiotics had reduced:
    • Fasting blood glucose (-5.8 mg/dL)
    • A1C (-0.3%)
    • Insulin (-2.95 µIU/mL)
  • Commentary: Probiotics have a modest favorable effect on glycemic control in those with abnormal glucose metabolism.

• Impact of 24-h high and low fermentable oligo-, di-, monosaccharide, and polyol diets on markers of exercise-induced gastrointestinal syndrome in response to exertional heat stress
  • Cross-over study of 18 endurance runners ate either low or high FODMAP diet 24 hours before completing 2 hours of running in the heat
  • The low FODMAP diet had less severity of GI symptoms compared to high FODMAP diet
  • Commentary: Consider a low FODMAP diet in endurance athletes given the high prevalence of digestive symptoms.

• Effects of Automatic Abdominal Massage Device in Treatment of Chronic Constipation Patients: A Prospective Study
  • 37 patients w/ functional constipation
  • All patients received device-assisted automatic abdominal massage for 15 min twice daily
  • After 14 days, colon transit time improved from 54 to 29 hours
  • ALL patients were alleviated of symptoms after treatment

• Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: a double blind placebo controlled randomized clinical trial
  • 44 patients w/ coronary artery disease (CAD), given calorie-restricted diet and randomized to probiotics or placebo
  • After 12 weeks, the probiotic group had:
    • Lower IL-1 (-1.9 vs +0.5)
    • Lower LPS (-5.9 vs +3)
  • Commentary: A calorie-restricted diet and probiotics may reduce inflammatory markers. 

• Incidence of Saccharomyces cerevisiae Fungemia in Hospitalized Patients Administered Saccharomyces boulardii Probiotic
  • Retrospective study of 46,729 patients hospitalized
  • S. boulardii supplementation given in 16,404 of these patients
  • Observed incidence of fungemia attributable to S. boulardii administration is 1.70 cases per 10,000 patient-days
    • This was similar to hospital-acquired infection rates
  • Commentary: Risk of bloodstream infection as a result of S. boulardii probiotic use appears rare.

Autoimmunity Studies

• Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity
  • 126 MS patients and healthy controls measured for markers of intestinal permeability (e.g. LPS, serum zonulin, tight junction proteins)
  • Higher serum zonulin was associated with 1-year disease progression in progressive MS 
  • Commentary: Intestinal permeability could be part of the pathogenesis of MS and other autoimmune diseases.

• Is Fibromyalgia Associated with Borrelia Specific T Lymphocytes?
  • Enzyme-linked immunospot used to detect T-lymphocyte reactivity to Borrelia burgdorferi from 27 fibromyalgia patients and 26 healthy controls
  • NO difference in T-cell reactivity between the two groups
  • Commentary: Work through GI algorithm before considering more rare issues like stealth infections (e.g. spirochetes).

Thyroid & Hormones Studies

• Randomized Study of the Effects of Zinc, Vitamin A, and Magnesium Co-supplementation on Thyroid Function, Oxidative Stress, and hs-CRP in Patients with Hypothyroidism
  • 86 hypothyroid patients randomized to:
    • Zinc (30 mg/d) + Magnesium oxide (250 mg/d) + Vitamin A (25,000 IU 2x/week)
    • Or placebo
  • After 10 weeks, the micronutrient group had a:
    • Significant increase in fT4
    • Lower CRP
    • NO difference in TSH

• Role of selenium and myo-inositol supplementation on autoimmune thyroiditis progression
  • Retrospective study of Hashimoto’s patients divided into 3 groups:
    • Untreated
    • Treated w/ selenium (83 mcg/d)
    • Treated w/ selenium (83 mcg/d) + myo-inositol (600 mg/d)
  • Selenium and selenium + myo-inositol associated w/ reduced TSH (31% and 38%, respectively)
  • Selenium + myo-inositol had EARLIER reduction in TSH

• Role of Selenium Deficiency in Pediatrics with Acquired Hypothyroidism
  • Case-control study of 60 hypothyroid children and 60 healthy children
  • Serum selenium levels were NOT different between the two groups (94 mcg/dL vs 86 mcg/dL)
  • Commentary: This is not to say selenium is not an effective treatment strategy. Also note that selenium is typically used in Hashimoto’s patients to reduce TPO Abs (this study was looking at congenital hypothyro).

• Association between intake of soft drinks and testicular function in young men
  • Observational study of 2,936 young men 
  • Those w/ the highest consumption of sugar-sweetened beverages had the lowest sperm concentration and count
  • Commentary: A standard American diet may have deleterious effects on fertility markers.

Diet & Lifestyle Studies

• Cold Water Immersion Offers No Functional or Perceptual Benefit Compared to a Sham Intervention During a Resistance Training Program
  • 13 trained men randomized to cold water bath (10 minutes at 50℉) or sham immediately following workout session
  • After 4 weeks, NO differences in muscle strength or peak force
  • Commentary: Despite these null findings, it does not negate the other possible beneficial effects of cold-water exposure. Furthermore, this was a small and short study.

• One-month of a low-energy diet, with no additional effect of high-protein, reduces Obstructive Sleep Apnea severity and improve metabolic parameters in obese males
  • 45 men w/ obstructive sleep apnea (OSA) put on 30% reduced calorie diet and randomized to high or low protein group
  • After 1 month, AHI reduced in both groups (-38% in low protein, -46% in high protein group)
  • Commentary: A hypocaloric diet can improve OSA regardless of macronutrient profile.

• Phthalate exposure and risk of diabetes mellitus: Implications from a systematic review and meta-analysis
  • 7 studies, 12,139 participants
  • Higher urinary concentrations of phthalates were associated with higher risk of type 2 diabetes (T2D) 
    • Odd ratio range of 1.27-3.1 depending on type of phthalate
  • Commentary: Phthalate exposure and impaired detoxification may be implicated in the pathogenesis of type 2 diabetes.

• Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis
  • 13 trials, 633 participants
  • Extra virgin olive oil was NOT associated with any improvement of glycemic control (fasting blood sugar, insulin)

Podcast Summary

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Featured Study

• Triiodothyronine alongside levothyroxine in the management of hypothyroidism?
  • Narrative review of T4 +T3 combo therapy for managing hypothyroidism
  • Important point: Of endogenous thyroid production; 80% T4, 20% T3
  • Why do some individuals have hypothyroid symptoms despite normal thyroid levels?
    • Different individual “set points” for thyroid hormones
    • Genetic SNPs of deiodinase enzymes
    • Varying degree of TSH and thyroid sensitivity
    • Poor T4-T3 conversion
    • TSH measurement variations due to body weight, meds (e.g. metformin), diurnal variations, gender, and age
    • Commentary: Gut imbalance can be another cause of hypothyroid symptoms
  • What can we take away from randomized trials?
    • “Overall, these [randomized] trials did not demonstrate a clear or consistent benefit from adding T3 to LT4 therapy, for example based on evaluations of cognition, mood, or QoL. Moreover, no particular ratio of LT4:T3 was more or less successful. Although patients preferred the combination in some studies, this was not explained necessarily by improvements in symptoms related to hypothyroidism.”
  • What about meta-analysis?
    • “Recent (2018 and 2021) systematic review/meta-analyses concluded that the addition of T3 to LT4 therapy had little benefit in terms of objective improvements in such outcomes (the more recent review also concluded that LT4 + T3 and LT4 monotherapy were tolerated similarly). However, these trials were conducted in relatively broad populations of patients with hypothyroidism, did not consistently use disease-specific instruments for measuring patient-reported outcomes, and therefore cannot exclude a potential benefit in subgroups of patients with hypothyroidism.”
  • Is combo T4 + T3 therapy safe for those who need it?
    • The largest and longest observational study of LT4 + T3 combination therapy was conducted in Tayside, UK. Here, patients who had received thyroid hormone replacement were divided into those who had only ever received LT4 (n = 33,955) and those who had received at least one additional prescription of T3 (n = 400) and were followed retrospectively for a total of 17 years. There was no excess risk of side effects associated with over-treatment of hypothyroidism, i.e. cardiovascular disease (hazard ratio [HR] 1.0 [0.7, 1.5]), atrial fibrillation (HR 0.9: [0.5, 1.8]), or fractures (HR 0.8: [0.5, 1.3]), and no increased use of medications for cardiovascular disease or osteoporosis (statins, bisphosphonates). 
  • Helpful T4 to combo conversion (assuming a 4x more activity of T3)
    • 100 mcg LT4 → 87.5 mcg/5 mcg T4/T3 combo
    • 150 mcg LT4 → 125 mcg/7.5 mcg T4/T3 combo
    • 200 mcg LT4 to 175 mcg/10 mcg T4/T3 combo
  • Commentary: Combo therapy CAN be helpful in a subset of hypothyroid patients but it may not be the best first choice in most individuals. Work through the thyroid algorithm to find the best solution for your patient.

Gastrointestinal Studies

• Gut fungal dysbiosis and altered bacterial-fungal interaction in patients with diarrhea-predominant irritable bowel syndrome: An explorative study
  • 5 IBS-D patients, 16 healthy controls
  • Fecal samples measured w/ 16s rRNA
  • More fungal dysbiosis in IBS-D compared to healthy controls
  • Commentary: Fungal dysbiosis may play a role in the etiology of IBS. 

• Effects of Probiotics on Diabetic Nephropathy: A Systematic Review
  • 9 studies
  • Probiotics are associated w/ an improvement of:
    • Renal function biomarkers
    • Inflammation
    • Oxidative stress

• Allergy-related diseases in childhood and risk for abdominal pain-related functional gastrointestinal disorders at 16 years-a birth cohort study
  • Prospective study, 2,949 children
  • 12% prevalence of functional GI disorder (GFID), 6% prevalence of IBS
  • History of eczema and asthma increases risk of FGID and IBS
  • Commentary: Allergic-related diseases may play a role in FGID.

• Treatment efficacy of a low FODMAP diet compared to a low lactose diet in IBS patients: A randomized, cross-over designed study
  • 29 IBS patients, randomized to low lactose or low FODMAP diet
  • After 3 weeks:
    • Improved symptoms in BOTH groups
    • Improved quality of life in BOTH groups
    • Low FODMAP diet had more improvement of abdominal pain

• Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
  • 40 patients w/ insomnia randomized to probiotic (lactobacillus) or placebo
  • After 30 days, the probiotic group had:
    • Better depression scores
    • Less fatigue
    • Less awakenings at night
  • Commentary: Probiotics can improve sleep and mood balance.

• Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome
  • 42 participants randomized to Augmentin antibiotic (x7 days) + either probiotic-containing or control yogurt (x14 days)
  • The probiotic group had less reduction in microbiome diversity compared to control group
  • Commentary: Probiotics can maintain microbial diversity when taking antibiotics.

• Systematic review and meta-analysis: Association of a pre-illness Western dietary pattern with the risk of developing inflammatory bowel disease 
  • 9 studies, 1,491 IBD cases and 53,089 controls
  • Western dietary pattern (standard American diet) was associated w/ increased risk of IBD (RR 1.92)

• Irritable bowel syndrome is strongly associated with the primary and idiopathic mast cell disorders
  • Cross-sectional analysis of >53 million patients >20 years old
  • Up to 4% of IBS patients also had a mast cell disorder
    • IBS associated w/ 16.3x increased risk of MCAS
  • Commentary: IBS is associated w/ MCAS.

• Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden
  • Cohort study of 796,492 long-term PPI users
  • Among PPI users, there was a higher risk of pancreatic cancer (standardized incidence rate ratio 2.22)
  • Commentary: A standardized incidence rate ratio compares the disease incidence of a cohort (e.g. PPI users) relative to the general population. 

• Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes
  • 85 type 2 diabetic (T2D) patients, measured fecal elastase levels to assess for exocrine pancreatic insufficiency (EPI)
  • Prevalence of EPI was 18.8%
  • Longer T2D duration was associated with lower fecal elastase levels
  • Commentary: There is a high prevalence (~20%) of EPI in T2D.

• Low FODMAP diet versus traditional dietary advice for functional dyspepsia: a randomized controlled trial
  • Prospective study of 105 functional dyspepsia patients randomized to low FODMAP or traditional therapy
  • After 4 weeks:
    • Both groups had improvement of symptom severity and quality of life
    • NO difference between groups
    • However, those w/ postprandial symptoms or bloating had better response to low FODMAP diet
  • Commentary: Low FODMAP diet is a promising therapy for functional dyspepsia, especially for those w/ postprandial symptoms and/or bloating.

• Meta-Analysis: Randomized Trials of Lactobacillus plantarum on Immune Regulation Over the Last Decades
  • 18 RCTs
  • Lactobacillus plantarum resulted in a reduction in:
    • IL-4
    • IL-10
    • TNF-α
    • IFN-γ
  • Commentary: Probiotics can result in immunologic regulation and have anti-inflammatory effects.

Autoimmunity Study

• Organ-specific autoimmune markers in adult patients with type 1 diabetes mellitus
  • Aim: To discern antibody prevalence in type 1 diabetes
  • Retrospective study of 287 type 1 diabetes
    • Anti-GAD Ig: 72.8%
    • Anti-insulin Ig: 9.1%
    • Anti-islet cell Ig: 25.7%
    • TPO Ig: 34.8%
    • Anti-thyroglobulin Ig: 19.9%
    • Anti-endomysial Ig (celiac): 7.6%
    • Anti-gliadin IgA: 12.2%
    • Tissue transglutaminase IgA: 7.1%
  • About half of the adult T1D patients were positive for at least one non-diabetic antibody
  • Commentary: Given these findings, it may be worth screening for TPO antibodies in T1D patients.

Thyroid & Hormones Studies

• Association of Hypothyroidism and Clinical Depression: A Systematic Review and Meta-analysis
  • 25 studies, 348,000 participants
  • Hypothyroidism was associated w/ depression (OR 1.3)
  • Stronger association w/ overt hypothyroidism (OR 1.77) than subclinical hypothyroidism (OR 1.13)
  • This association was only seen in females (not males)
  • Commentary: Hypothyroidism is weakly associated with depression in females, but not males.

• Association between obstructive sleep apnea and male serum testosterone: A systematic review and meta-analysis
  • 18 studies, 1,823 men
  • Lower testosterone was associated with higher risk of obstructive sleep apnea INDEPENDENT of age and BMI
  • Commentary: OSA may be a contributing factor to hypogonadism.

• Effect of an ashwagandha (Withania Somnifera) root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study
  • 91 women w/ menopausal symptoms randomized to ashwagandha (300 mg BID) or placebo
  • After 8 weeks, the ashwagandha group had:
    • Greater improvement in menopausal symptoms
    • Increased serum estradiol levels
  • Commentary: Ashwagandha root can be a safe and effective tool for menopausal symptoms.

Diet & Lifestyle Studies

• Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial
  • 138 patients w/ mild cognitive impairment (MCI) over 60 yo
  • Randomized to:
    • Folic acid (0.8 mg/day) + DHA (800 mg/day)
    • Folic acid (0.8 mg/day)
    • DHA (800 mg/day)
    • Or placebo
  • After 12 months:
    • Cognitive function improved in ALL treatment groups
    • Amyloid-β peptide levels reduced in the DHA group

• Association of 25-hydroxyvitamin D level with survival outcomes in female breast cancer patients: A meta-analysis
  • 12 studies, 8,574 female breast cancer patients
  • Lower Vit D levels associated w/ higher all-cause mortality (HR 1.57) and breast cancer-specific mortality (HR 1.44)
  • Commentary: Higher vitamin D levels may be protective for cancer. Most studies in this analysis had a cutoff of 20-30 ng/mL to define low vs normal levels. 

• Association between apnea-hypopnea index and coronary artery calcification: a systematic review and meta-analysis
  • 13 studies, 6,620 participants
  • The presence of sleep apnea was associated w/ a higher coronary artery calcium scores compared to healthy controls

• Serum Ferritin and the Risk of Metabolic Syndrome: A Systematic Review and Dose-Response Meta-Analysis of Cross-sectional Studies
  • 14 studies, 74,710 blood samples
  • Higher serum ferritin was associated w/ an increased risk of metabolic syndrome (OR 1.77)
  • Association seen especially in males compared to females
  • Commentary: Higher ferritin is associated with metabolic syndrome. 

• Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial
  • 60 obese patients randomized to 14-hour or 12-hour fast per day (both controlled for calories and macronutrients)
  • After 8 weeks, the 14-hour fast group had:
    • Greater improvement in weight loss (-8.5% vs -7.1%)
    • Greater improvement in fasting glucose (-7.6 vs -3.1)
  • Commentary: A 14-hour fast resulted in greater improvement in metabolic markers than a 12-hour fast.

Podcast Summary

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Featured Study

• Association of Thyroid Dysfunction with Cognitive Function: An Individual Participant Data Analysis
  • Prospective collection of multiple studies published in JAMA, 74,565 total participants
  • Assessing cognitive function: 21 studies, 38,144 participants, followed x1.7-11.3 years
  • Assessing dementia: 8 studies, 44,573 participants, followed x3.8-15.3 years 
  • Results:
    • Rates of thyroid dysfunction:
      • 0.8% overt hyperthyroidism
      • 3.4% subclinical hyperthyroidism
      • 0.9% overt hypothyroidism
      • 5.6% subclinical hypothyroidism
    • Thyroid dysfunction was NOT associated with global cognitive function, executive function, or risk of dementia
  • Commentary: This data suggests that thyroid dysfunction was NOT associated w/ cognitive impairment.

Gastrointestinal Studies

• The Subjective Well-being and Health-Related Quality of Life of Australian Adults with Increased Intestinal Permeability and Associations with Treatment Interventions
  • Cross-sectional study of 589 adults w/ diagnosed or suspected increased intestinal permeability (IP)
  • Adults w/ increased IP had lower quality of life scores compared with the general population

• Ileocolonic Histopathological and Microbial Alterations in the Irritable Bowel Syndrome: A Nested Community Case-Control Study
  • Aim: To examine histological patterns of IBS
  • Retrospective study of 48 IBS patients, 106 controls who received colonoscopy
  • Compared w/ healthy controls, IBS patients had increased intraepithelial lymphocytes
  • Commentary: This study suggests an immunological shift in those w/ IBS.

• Serum Gastrin Predicts Hydrogen-Producing Small Intestinal Bacterial Overgrowth in Patients with Abdominal Surgery: A Prospective Study
  • Aim: Evaluate the prevalence of SIBO and investigate serum gastrin and pepsinogen as predictors of SIBO in patients with abdominal surgery
  • Prospective study of:
    • 30 healthy controls and 146 patients w/ history of hysterectomy/ gastrectomy/ or cholecystectomy 
    • Glucose breath test, gastrin, and pepsinogen levels measured
  • SIBO rates were significantly higher in patients with histories of abdominal surgery than than in controls (37.6% vs 13.3%)
    • Among SIBO+ patients:
      • 36% had hysterectomy 
      • 96% had gastrectomy
      • 11% had cholecystectomy
  • Gastrin levels were higher (>29) in the hydrogen-predominant SIBO group compared with methane-predominant SIBO group
  • Take Home: History of abdominal surgery (especially gastrectomy) and higher gastrin levels were independent predictors of SIBO.

• Increase in the Lipopolysaccharide Activity and Accumulation of Gram-Negative Bacteria in the Stomach with Low Acidity
  • 158 patients who had endoscopy
  • Lipopolysaccharide (LPS) activity measured in gastric fluid and gram-negative bacteria (GNB) counts measured in saliva and gastric fluid
  • Higher LPS activity found in gastric fluid w/ weak acidity 
  • Compared to the GNB count in the saliva, the GNB count was:
    • The SAME in those In those w/ weak gastric fluid acidity
    • LOWER in those w/ high acidity 
  • Commentary: Low HCl production may be a predisposing factor for dysbiosis and SIBO. This also highlights the possibility that SIBO may have a top-down approach where GNB may migrate to the small bowel in those w/ lower acidic contents.

• Probiotic Bifidobacterium breve in Improving Cognitive Functions of Older Adults with Suspected Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial
  • 80 adults w/ mild cognitive impairment (MCI), randomized to probiotic or placebo
  • After 16 weeks, the probiotic group had better cognitive performance compared to placebo
  • Commentary: Probiotics can enhance cognitive function and be used for symptoms such as “brain fog”.

• Fecal Zonulin as a Noninvasive Biomarker of Intestinal Permeability in Pediatric Patients with Inflammatory Bowel Diseases-Correlation with Disease Activity and Fecal Calprotectin
  • 88 pediatric IBD patients (47 CD, 41 UC) and 6 healthy controls
  • Fecal zonulin levels were higher in the IBD group
    • CD: 113.3 (53.6-593.6) ng/mL
    • UC: 103.6 (50.7-418.3) ng/mL
    • Controls: 46.9 (31.8-123.0) ng/mL
  • NO significant difference between CD and UC
  • Slightly higher fecal zonulin levels during high disease activity in CD, but NOT in UC
  • Higher fecal zonulin correlated w/ higher calprotectin
  • Commentary: Fecal zonulin is associated w/ IBD and tracks w/ disease severity and fecal calprotectin levels.

• The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial
  • 326 pregnant women randomized to probiotic or placebo
  • Probiotic group attenuated the decrease in ferritin through pregnancy and reduced iron deficiency rates (59% vs 78%)
  • Commentary: Probiotics can improve the natural iron level decline in pregnant women. 

• Assessment of a 4-Week Starch- and Sucrose-Reduced Diet and Its Effects on Gastrointestinal Symptoms and Inflammatory Parameters among Patients with Irritable Bowel Syndrome
  • 105 IBS patients, randomized to starch and sucrose reduced diet (SSRD) or control group
  • At 4 weeks, the SSRD had:
    • Less symptoms
    • NO change in CRP levels

• Microbial Diversity and Community Structures Among Those with Moderate to Severe TBI: A United States-Veteran Microbiome Project Study
  • 34 veterans, 79 healthy controls
  • Examined microbiome w/ 16s rRNA gene sequencing
  • NO difference in microbiome diversity between veterans w/ TBIs compared with healthy controls
  • Commentary: This is not to say that TBIs can’t influence the gut through other mechanisms (e.g. altered immune system, cortical imbalance, etc).

• Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: A prospective randomized pilot study
  • 6 patients w/ recurrent ulcerative colitis (UC), randomized to FMT or control
  • After 20 month follow up, NO significant difference between groups

• Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection: Meta-Analysis of Randomized Controlled Trials
  • 7 studies, 238 patients
  • Compared with standard care, FMT did NOT result in significant improvement of C. diff infection (CDI)
  • However, for recurrent CDI, FMT did show significant improvement (RR 2.41)
  • Commentary: FMT should NOT be utilized in every patient w/ CDI but can be considered for recurrent CDI.

• Efficacy and Safety of Ghrelin Agonists in Patients with Diabetic Gastroparesis: A Systematic Review and Meta-Analysis
  • 6 RCT, 557 participants
  • Ghrelin agonist significantly improved gastroparesis symptoms w/ small-medium effect size (-0.34)
  • No adverse effects
  • Commentary: This is an important study since many prescriptive prokinetics like metoclopramide have a poor safety profile for long-term use. 

• Dynamic analysis of human small intestinal microbiota after an ingestion of fermented milk by small-intestinal fluid perfusion using an endoscopic retrograde bowel insertion technique
  • 7 healthy participants, measured terminal ileum microbiome after being given fermented probiotic drink
  • A significant amount of ingested probiotics survived and reached the terminal ileum
  • Commentary: Much of ingested probiotics can survive dramatic pH changes of the gastric fluids and reach the distal end of the small bowel.

• A meta-analysis of the association between Helicobacter pylori infection and risk of atherosclerotic cardiovascular disease
  • 40 studies, 19,691 participants
  • Helicobacter pylori infection increased the risk of adverse cardiovascular events by 51%
  • Presence of CagA virulence factor was associated w/ much higher risk (73% increased risk)
  • Commentary: Supports a gut-cardiovascular connection.

• Improvement in constipation and diarrhea is associated with improved abdominal pain in patients with functional bowel disorders
  • 180 patients w/ functional GI disorders (77% w/ IBS)
  • Improvement of constipation and diarrhea were both INDEPENDENT predictors of abdominal pain improvement
  • Commentary: This suggests addressing bowel regularity should be a central focus of clinical improvement.

Thyroid & Hormones Studies

• Safety assessment of compounded non-FDA-approved hormonal therapy versus FDA-approved hormonal therapy in treating postmenopausal women
  • 539 postmenopausal women: 384 on pellet hormonal therapy (PHT) and 155 on normal hormonal therapy (NRT)
  • Side effects were significantly higher in the PHT group (58% vs 15%)
  • Peak estradiol levels were much higher in the PHT group compared to the NRT group (168 vs 93 pg/mL)
  • Commentary: PHT may not be the best HRT option for most women, just like how T3 may not be the best first-line therapy for hypothyroidism.

• Testosterone Replacement Therapy in Hypogonadal Men and Myocardial Infarction Risk: Systematic Review & Meta-Analysis
  • 6 RCTs and 2 observational studies, 55,806 hypogonal men (total testosterone <300 ng/mL)
  • The incidence of myocardial infarction (MI) was similar in the testosterone replacement therapy (TRT) group compared to the control group (2.1% in TRT, 4.3% in control)
  • Commentary: TRT did NOT increase the risk of MI in hypogonadal men in this study. 

• The effects of curcumin as dietary supplement for patients with polycystic ovary syndrome: An updated systematic review and meta-analysis of randomized clinical trials
  • 5 RCTs, 296 patients w/ PCOS
  • The use of curcumin supplementation was associated with an improvement in:
    • Fasting blood glucose (-3.7 mg/dL)
    • Insulin (-1.9)
    • HOMA-IR (-0.6)
    • Total cholesterol (-15.6 mg/dL)
  • Commentary: Curcumin supplementation can result in improved cardiometabolic markers in those w/ PCOS.

• The Association of Overt and Subclinical Hyperthyroidism with the Risk of Cardiovascular Events and Cardiovascular Mortality: Meta-Analysis and Systematic Review of Cohort Studies
  • 37 observational studies
  • OVERT HYPERthyroidism is associated w/ higher risk of:
    • Ischemic heart disease (HR 1.35)
    • Stroke (HR 1.35) 
    • Cardiovascular mortality (HR 1.2)
  • SUBCLINICAL HYPERthyroidism is associated w/ higher risk of:
    • Ischemic heart disease (HR 1.24)
  • Commentary: Even subclinical hyperthyroidism is associated w/ cardiovascular risk.

• Vitamin D and Hashimoto’s Thyroiditis: Observations from CROHT Biobank
  • Cross-sectional study, 461 Hashimoto’s patients and 176 healthy controls
  • NO significant differences in Vit D levels between groups
  • Commentary: This does NOT mean that Vit D can be helpful in those w/ Hashimoto’s.

Diet & Lifestyle Studies

• Efficacy of omega-3 polyunsaturated fatty acids on hormones, oxidative stress, and inflammatory parameters among polycystic ovary syndrome: A systematic review and meta-analysis
  • 10 RCTs, 610 PCOS patients w/ omega-3 supplementation
  • Omega-3 supplementation associated with:
    • Reduced CRP (-9 mg/dL)
    • Reduced oxidative stress (serum malondialdehyde -0.4 mg/dL)
    • Reduced total testosterone
  • Commentary: Omega-3 supplementation can be a powerful anti-inflammatory line of therapy.

• The effect of garlic (Allium sativum) supplementation on the lipid parameters and blood pressure levels in women with polycystic ovary syndrome: A randomized controlled trial
  • 80 PCOS patients, randomized to garlic supplementation (800 mg/d) or placebo
  • After 8 weeks, the garlic supplementation group had:
    • Reduced total cholesterol (-8 mg/dL)
    • Reduced LDL-C (-7.8 mg/dL)
    • NO change in triglycerides
    • NO change in systolic blood pressure
  • Commentary: Garlic supplementation resulted in a very mild improvement in metabolic markers.

• Exercise Reduces Medication for Metabolic Syndrome Management: A 5-Year Follow-up Study
  • 51 participants w/ metabolic syndrome (MetS) randomized to exercise intervention (HIT 3x/wk) or control group
  • After 5 years, the exercise group had:
    • Reduced MetS markers (e.g. blood pressure, glucose)
    • Improved cardiorespiratory fitness
    • NO change in medication use whereas the control group had a 2x increase use of meds 
  • Commentary: Just a few sessions a week of exercise can result in significant improvement in metabolic markers.

• Intake of Fish and Marine n-3 Polyunsaturated Fatty Acids and Risk of Cardiovascular Disease Mortality: A Meta-Analysis of Prospective Cohort Studies
  • 25 cohort studies, 2 Million participants, including 100,000 CVD deaths
  • Higher omega-3 intake was associated with a 13% reduced risk of CVD mortality (RR = 0.87)
  • For every increase of 20g of fish or 80mg of omega-3 intake reduces the risk of CVD mortality by 4%

• Creatine Enhances the Effects of Cluster-Set Resistance Training on Lower-Limb Body Composition and Strength in Resistance-Trained Men: A Pilot Study
  • 23 resistance-trained men randomized to reatine + resistance training, resistance training, or control group
  • After 8 weeks, larger improvements of fat mass reduction and lean body mass increase in the group taking creatine vs resistance training alone
  • Commentary: Creatine is a well-researched ergogenic aid for those looking to increase muscle mass.

• Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors
  • 210 adults 25-60 yo: 105 w/ coronary heart disease (CHD) and 105 age and sex matched healthy controls
  • Mean plasma homocysteine (Hcy) levels:
    • CHD cases: 22 µmol/L 
    • Controls: 12.6 µmol/L 
  • High Hcy levels were an independent predictor of CHD (OR 7.5)

• Does vitamin D improve symptomatic and structural outcomes in knee osteoarthritis? A systematic review and meta-analysis
  • 6 studies, 1,600 participants
  • Vitamin D associated w/ significantly lower pain scores (effect size -0.3) in those w/ osteoarthritis
  • NO effect on structural integrity of the joint (e.g. cartilage volume, joint space)