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Featured Study

• Benefits and Harms of Levothyroxine/liothyronine vs. Levothyroxine Monotherapy for Adult Patients with Hypothyroidism: Systematic Review and Meta-analysis
  • Compare the benefits and harms of combined T4/T3 therapy w/ T4 monotherapy for those w/ hypothyroidism
  • 18 studies
  • Results:
    • No difference in thyroid biomarkers
    • No difference in quality of life
    • No difference in “psychological distress”
    • No difference in depression
    • No difference in fatigue
    • Similar adverse effects
    • Small preference for combined therapy (43% combined, 23% T4 monotherapy, 20% no preference)
  • Commentary: This is aligned w/ our clinic’s hierarchy of starting w/ combined T4 monotherapy for those w/ diagnosed frank hypothyroidism. Even though there was a slight preference for combined therapy, it’s important to note that there was a LACK of CLINICAL OUTCOMES differences between the two groups.

Gastrointestinal Studies

• Gluten-free diet can ameliorate the symptoms of non-celiac autoimmune diseases
  • Does a gluten-free diet (GFD) help reduce symptoms of autoimmune diseases other than celiac disease?
  • Systematic review of 83 studies, 1,408 patients
  • GFD reduced symptoms of other autoimmune diseases in 911 of 1,408 (64.7%)  patients
  • Commentary: A GFD can help reduce symptoms in non-celiac autoimmune diseases.

• Prevalence of Microscopic Colitis in Diarrhea-predominant Irritable Bowel Syndrome Patients: Cohort Study From Upper Egypt
  • Prospective study of 129 IBS-D patients
  • Took biopsies to assess for other diagnosis
  • Results:
    • 86 (71.7%) cases with nonspecific colitis
    • 26 (21.7%) cases with microscopic colitis  
    • 8 (6.7%) cases with ulcerative colitis
  • Commentary: This is a relatively high prevalence of concomitant colitis (especially microscopic colitis) in those w/ IBS-D. 
  • Dr. Ruscio’s comments: It’s important to not get overly caught up in pursuing a diagnosis because this can distract one from working through the GI algorithm (e.g. personalizing therapies to the patient in the most logical sequence). For example here, a patient could have been only diagnosed with microscopic colitis, potentially leading the provider away from the fact that their signs/symptoms were similar to IBS and also overlooking the vast array of therapies we have for IBS and perhaps even forgetting that there is much therapeutic overlap between the more general IBD subtypes; Crohn’s Disease and UC.  

• Comparative study of allicin-containing quadruple therapy vs. bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection: A prospective randomized study
  • Compare allicin-containing quadruple therapy w/ bismuth-containing quadruple therapy
  • 220 H pylori-colonized patients randomized to 14 days of:
    • Allicin-containing quadruple therapy 
    • Bismuth-containing quadruple therapy
  • Eradication was confirmed by urea breath test
  • Results:
    • Eradication rate: 
      • 86% for allicin
      • 92% for bismuth
    • Symptom improvement:
      • 96% for allicin
      • 97% for bismuth
    • Adverse events:
      • 11% for allicin
      • 15% for bismuth
  • Commentary: Allicin-containing quadruple therapy might be regarded as a promising alternative to bismuth-containing quadruple therapy in H. pylori eradication.
  • Dr. Rusico’s reminder: Be evidence-based, but not evidence limited… it’s OK to experiment with treatments if there is not published data, don’t be afraid to think (reasonably) outside the box. 

• Effect of kefir beverage consumption on glycemic control: A systematic review and meta-analysis of randomized controlled clinical trials
  • 6 RCTs, 323 participants
  • Kefir consumption associated with:
    • Reduced fasting blood sugar (-10 mg/dL)
    • Reduced fasting insulin (-2.87)
    • No statistically reduction of A1C
  • Commentary: This study suggests that a common probiotic-containing food product can improve glycemic control. 

• The Clinical Use of Curcumin for the Treatment of Recurrent Aphthous Stomatitis: A Systematic Review of Clinical Trials
  • 9 studies, 469 participants
  • Curcumin significantly REDUCED:
    • Aphthous ulcer size (7 studies)
    • Pain (8 studies)
    • Number of aphthous ulcers (3 studies) 
  • 4 studies showed similar efficacy of curcumin when compared to standard medication (triamcinolone)
  • Commentary: Curcumin can benefit recurrent aphthous ulcers.

• Prevalence and factors associated with poor sleep quality in inflammatory bowel disease outpatients
  • 102 IBD patients
  • 55% also have poor sleep quality
  • Commentary: A high percentage of IBD patients also have poor sleep quality. This highlights a gut-sleep connection.

• Efficacy of probiotic adjuvant therapy for irritable bowel syndrome in children: A systematic review and meta-analysis
  • 9 RCTs of children w/ IBS
  • Probiotics significantly:
    • Reduced abdominal pain (SMD -1.15)
    • Increased treatment success (RR 3.44)
  • Commentary: Probiotics can improve symptoms and treatment success in children w/ IBS.

• 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 positive improvement (48% probiotics vs 20% placebo, RR 1.95)
  • Commentary: More proof-of-concept for the use of soil-based probiotics to remediate GI symptoms. 

Thyroid & Hormones Studies

• Use of Hormone Therapy in Postmenopausal Women with Alzheimer’s Disease: A Systematic Review
  • Does hormone replacement therapy (HRT) improve cognitive function/Alzheimer’s Disease (AD)?
  • 25 studies (14 observational studies, 11 clinical trials)
  • Of the 14 observational studies
    • 8 studies show IMPROVEMENT of cognitive function/AD risk
      • More of a beneficial effect in younger postmenopausal women
    • 5 studies show NO difference in cognitive function/AD risk
  • Of the 11 clinical trials
    • 7 show IMPROVEMENT of cognitive function
    • 4 show NO difference  
  • Commentary: The MAJORITY of the studies show a benefit of HRT for cognitive function/Alzheimer’s Disease risk, especially when started early on in menopause.

• Whether a Gluten-Free Diet Should Be Recommended in Chronic Autoimmune Thyroiditis or Not?: A 12-Month Follow-Up
  • 62 women w/ autoimmune thyroid disease randomized to gluten-free diet (GFD) or control
  • After 12 months:
    • NO differences in TPO or Tg antibodies
    • NO differences in fT3 or fT4
    • GFD lead to significant reduction in TSH
  • Commentary: 
    • A GFD is worth a reasonable and prudent trial for those w/ autoimmune thyroid disease.
    • Dr. Rusico’s note: Remember not to be dogmatic with GF diet in AIT

Diet & Lifestyle Studies

• Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: A meta-analysis
  • Compared a very-low carb ketogenic (VLCK) diet (carbohydrate intake < 50 g/d or < 10% of total energy) with standard recommended diet for type 2 diabetes 
  • 8 RCTs, 648 participants
  • Compared to standard diet, the VLCK diet resulted in:
    • Greater decrease in A1C (-0.61% difference at 3 months, -0.58% at 6 months)
    • Greater weight loss (-2.9 kg at 3 months, -2.8 kg at 6 months)
    • Greater reduction in triglycerides
    • Greater reduction in use of antidiabetic medications
  • However, there were NO DIFFERENCES after 12 months follow up
  • Commentary: A VLCK diet may lead to short-term improvements WITHOUT long-term gains. I suspect this may be because of a lack of substantial body composition improvements made with these diets, or compliance.

• Impact of Metabolic Syndrome and Its Components on Prognosis in Patients With Cardiovascular Diseases: A Meta-Analysis
  • What is the impact of metabolic syndrome (MetS) w/ cardiovascular disease?
    • Reminder: Metabolic Syndrome = 3 of the 5 following parameters:
      • Triglycerides >150
      • HDL <40 (men), <50 (women)
      • Hypertension
      • High blood sugar
      • High waist circumference
  • 55 studies, 16,245 participants
  • Compared to patients without MetS, those w/ MetS had higher:
    • All-cause death (RR 1.22)
    • Cardiovascular death (RR 1.36)
    • Myocardial infarction (RR 1.46)
    • Stroke (RR 1.43)

• ​​Effect of intermittent versus continuous calorie restriction on body weight and cardiometabolic risk markers in subjects with overweight or obesity and mild-to-moderate hypertriglyceridemia: A randomized trial
  • 88 participants w/ obesity and high triglycerides
  • Randomized to:
    • Continuous calorie restriction (CCR) 
    • Or intermittent fasting (IF)
      • Very low-calorie diet x3 days/week
  • After 8 weeks:
    • Similar body weight reutions (4.1 kg in CCR, 4.6 kg in IF)
    • No differences in fat mass reduction, fat-free mass, waist circumference
    • Similar reductions in triglycerides
    • Greater reduction in insulin resistance scores (HOMA-IR) in IF compared to CCR group
  • Commentary: 3-days a week of IF is comparable to CCR for improving metabolic markers in overweight/obese adults w/ high triglycerides

• Effects of Sodium Bicarbonate Supplementation on Muscular Strength and Endurance: A Systematic Review and Meta-analysis
  • 13 studies
  • Sodium bicarbonate supplementation associated w/:
    • Better muscular endurance (effect size 0.37)
    • No effect for muscular strength
  • Commentary: Supplemental bicarbonate may act as an ergogenic/performance aid. 

• Vitamin D supplementation among Bangladeshi children under-five years of age hospitalised for severe pneumonia: A randomized placebo controlled trial
  • 197 kids <5 yo hospitalized w/ severe pneumonia randomized to:
    • Vit D 
      • Mega-dose on first day (20,000 IU-100,000 IU per day depending on age)
      • Then maintenance dose of 10,000 IU/d x4 days or until discharged
    • Placebo
  • NO differences in clinical outcomes
  • Commentary: This study failed to show benefit of high-dose vitamin D for young kids w/ pneumonia.

• Perspective: Does Glycemic Index Matter for Weight Loss and Obesity Prevention? Examination of the Evidence on “Fast” Compared with “Slow” Carbs
  • 43 cohorts, 1.9 MILLION participants
  • NO DIFFERENCES in BMI and body weight reduction when comparing low vs high glycemic index (GI) interventions
    • Results of 30 meta-analyses of RCTs showed that low-GI diets were generally no better than high-GI diets for reducing body weight or body fat
  • Commentary: If food quality and/or processing wasn’t incorporated it may be difficult to show any association. 

• Effects of mindfulness meditation interventions on depression in older adults: A meta-analysis
  • 19 studies, 1,076 participants
  • Mindfulness meditation showed significant improvement in depression (effect size 0.65)

• Revision of serum ALT upper limits of normal facilitates assessment of mild liver injury in obese children with non-alcoholic fatty liver disease
  • 1,638 children
  • Higher BMI was associated w/ higher ALT
  • Prevalence of fatty liver:
    • 82-94% (depending on sex) for ALT >50
    • 68-76% for ALT 25-50
    • 21-38% for ALT <25
  • Commentary: BMI is associated w/ fatty liver. A significant percentage of those w/ normal ALT have fatty liver.

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Featured Study

• A Systematic Review of the Clinical Use of Curcumin for the Management of Gastrointestinal Diseases
  • 21 studies, 1,478 GI patients
  • Beneficial effects shown in:
    • Peptic ulcer disease: 2 out of 2 (100%) studies
    • IBS: 4 out of 7 (57%) studies
    • Ulcerative colitis: 6 out of 7 (86%) studies
    • H pylori eradication: 2 out of 4 (50%) studies
    • Crohn’s Disease: 2 out of 4 (50%) studies
    • Proctosigmoiditis: 1 of 1 (100%) study
  • No effect:
    • Familial adenomatous polyposis: 1 out of 1 study
  • Commentary: The majority of studies in this review show a BENEFIT of curcumin for GI disorders. This may be due to the thwarting of systemic inflammation stemming from the GI tract. Here at RIFM, we usually prioritize other therapies (diet, lifestyle, probiotics, elemental dieting) BEFORE adding in agents like curcumin. Nonetheless, they can be beneficial in those w/ digestive disorders.

Gastrointestinal Studies

• Sex differences in zonulin in affective disorders and associations with current mood symptoms
  • Aimed to measure possible association between serum zonulin levels and states of depression
  • 55 depressed patients, 37 healthy controls
  • Results:
    • Serum zonulin higher in women than men
    • NO difference in those with and without depression
  • Commentary: Serum zonulin may NOT be the best marker of intestinal permeability. I highlight this study to show that it’s hard to make treatment recommendations based on this common marker used in functional medicine. 

• Infant acid suppression use is associated with the development of eosinophilic esophagitis
  • Does acid suppression therapy (e.g PPI, histamine antagonist) in infancy predispose an individual to develop eosinophilic esophagitis (EoE) later in age?
  • Retrospective study of 526 EoE patients, 2,630 age-matched healthy controls
  • Acid-suppression therapy in infancy was associated with increased likelihood of EoE 
    • PPI (5.7% EoE cases vs. 1.6% controls)
    • H2 antagonists (8.8% EoE cases vs. 4.5% controls)
  • Of the EoE cases, acid suppression during infancy increased the likelihood for the diagnosis with EoE at an EARLIER age
  • Commentary: We should warrant better stewardship of acid-suppression therapy and be familiar with this possible risk factor for EoE.

• Lactobacillus brevis CD2 attenuates traumatic oral lesions induced by fixed orthodontic appliance: A randomized phase 2 trial
  • 20 orthodontic patients, randomized L brevis (4 billion CFU 3x/d) starting on day given fixed orthodontic device
  • After 21 days, the probiotic group had:
    • Less time w/ oral lesions (2.5 days vs 5 days in control group)
    • Less pain
    • No difference in oral health-related quality of life
  • Commentary: Probiotics have shown to have good efficacy in improving oral health. This study shows that they can reduce the time of trauma-induced oral lesions by 50%. 

• Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial
  • IBS patients, randomized to peppermint oil (180 mg 3x/d) or placebo
  • After 6 weeks, BOTH groups had improved symptoms
  • However, there were NO DIFFERENCES BETWEEN groups
  • Commentary: See previous FFMR+ (June 28th) study showing that 27% of participants in placebo arm of IBS trials experienced positive response. 

• The Effect of Continuous Intake of Lactobacillus gasseri OLL2716 on Mild to Moderate Delayed Gastric Emptying: A Randomized Controlled Study
  • 28 participants w/ delayed gastric emptying, randomized to probiotic (lactobacillus strain) or placebo
  • After 12 weeks, the probiotic group had significant improvement in gastric emptying time (OR 4.1 of improvement)

• Systematic review with meta-analysis: Dietary intake in adults with inflammatory bowel disease
  • 19 studies
  • Those w/ IBD consume less:
    • Folate
    • Fiber 
    • Calcium
  • Commentary: Consider possible nutrient insufficiencies in those w/ IBD. Work to expand your patients’ diets without causing a flare in symptoms. 

• Meal Eating Characteristics of Patients with Gastroparesis
  • Cross-sectional analysis of 192 gastroparesis patients
  • Results:
    • 93% had early satiety/ postprandial fullness
    • Quicker eating associated with MORE nausea, loss of appetite, and fullness
  • Commentary: Consider working on meal-hygiene (e.g. take 15 minutes to eat a meal, chew thoroughly) in those w/ GI symptomatology.

• A Comprehensive Review of Transaminitis and Irritable Bowel Syndrome
  • 3 studies
  • Higher levels of ALT in those w/ IBS vs healthy controls (16.9% vs 7.7%)
  • Commentary: Elevated LFTs may be a result of functional GI disorders.

• A Randomized, Double-blind, Placebo-controlled, Parallel Study Evaluating the Efficacy of Bacillus subtilis MB40 to Reduce Abdominal Discomfort, Gas, and Bloating
  • 100 healthy participants, randomized to soil-based probiotics (5 billion CFU/d) or placebo
  • After 4 weeks, NO differences in abdominal discomfort, bloating, or gas
  • However, the probiotic group had improved Quality of Life
  • Commentary: Keep in mind that this is in a group of HEALTHY participants. I’m unsure why the researchers didn’t use a group of participants w/ overt GI symptoms.

• Vitamin D supplementation in people with IBS has no effect on symptom severity and quality of life: Results of a randomised controlled trial
  • 135 IBS patients, given Vit D (3,000 IU/d) or placebo
  • After 12 weeks (3 months):
    • NO difference in symptoms
    • NO difference in quality of life
  • Commentary: It’s important to note trials that do NOT show the effect of common therapies.

• Exocrine pancreatic function and dynamic of digestion after restrictive and malabsorptive bariatric surgery: A prospective, cross-sectional, and comparative study
  • Compare the effect of common bariatric surgeries on exocrine pancreatic function
  • Of 105 patients who underwent bariatric surgery, exocrine pancreatic insufficiency (EPI) found in:
    • 75% of patients after biliopancreatic diversion with duodenal switch ( BPD/DS)
    • 8.3% of patients after Roux-en-Y gastric bypass (RYGB)
    • 4.3% of patients after sleeve gastrectomy (SG)
  • Commentary: Bariatric surgery is a risk factor for EPI- especially BPD/DS. Consider adding this as part of your intake forms.

Thyroid & Hormones Studies

• It’s All Due to the Thyroid: Lessons Learnt From a Patient’s Perspective
  • Case report of 79 yo, w/ past medical history of Hashimoto’s
  • Patient had symptoms of fatigue, dysphagia, and proximal muscle weakness
  • Attributed these symptoms to hypothyroidism
  • However, the patient already had an existing diagnosis of dermatomyositis and Zenker’s diverticulum which could explain her above symptoms
  • Commentary: Here are my take home points from this case report:
    • This corroborates our findings at the clinic of patients mistakenly attributing their symptoms to their thyroid function
    • GI disturbances can mimic hypothyroid symptoms 
      • Given that GI disorders are more likely (functional GI disorders 40% vs 5% hypothyroid), work to address the GI first
    • Remember to revisit and expand your differential even in patients w/ confirmed past diagnosis

• Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: A US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study
  • Aim is to redefine cutoff points for iron deficiency
  • 2,569 children and 7,498 non-pregnant women, measured ferritin, hemoglobin (Hgb) and soluble transferrin receptor (sTfR)
  • Iron deficiency cutoff=
    • Children: ferritin <20 μg/L 
    • Non-pregnant women <25 μg/L
  • Commentary: Iron deficiency can be diagnosed as <20 for children and <25 for non-pregnant women. Review prior FFMR+ episode (episode #10) for a more expansive review of iron deficiency assessment and management. 
  • Dr. Rusico agrees with the 25 and has found Soppi’s proposal of <100 to not correlate well clinically.

• The influence of thyroid autoimmunity on pregnancy outcome in infertile women: A prospective study
  • 590 infertile women on levothyroxine
  • Results:
    • Fertility was NOT affected by TPOAb levels or other thyroid metrics
    • However, miscarriages were HIGHER in those w/ higher TPOAb levels (46 IU/mL miscarriage vs. 19 IU/mL non-miscarriage)
  • Commentary: Higher TPOAb titer should be considered as one of the risk factors for miscarriage in infertile women, even if they have been treated with Levothyroxine for hypothyroidism. Reducing TPOAbs titer levels may be indicated in a subset of women w/ a history of miscarriages

Diet & Lifestyle Studies

• Sleep disordered breathing symptoms are associated with depressive symptoms: A longitudinal study of Chinese adolescents
  • Cross-sectional analysis of 7,072 adolescents
  • Sleep-disordered breathing (loud snoring, breathing pauses, and snorting/gasping) associated w/ more depressive symptoms independent of other variables (OR 2.23)
  • Commentary: Sleep-disordered breathing is an INDEPENDENT risk factor for affective disorders/ mood imbalances.

• Obstructive sleep apnea increases the risk of cardiovascular damage: A systematic review and meta-analysis of imaging studies
  • 80 studies on the association between sleep apnea and cardiovascular disease
  • Sleep apnea patients had:  
    • HIGHER RATE of coronary atherosclerosis 
    • MORE cardiac structure abnormalities (e.g. increased left ventricular mass)
    • DECREASED left ventricular ejection fraction
  • Commentary: Sleep apnea increases cardiovascular disease and atherosclerosis.

• Changes in cortisol levels by continuous positive airway pressure in patients with obstructive sleep apnoea: Meta-analysis of 637 individuals
  • 22 studies, 637 participants w/ obstructive sleep apnea (OSA)
  • CPAP therapy associated w/:
    • A reduction in cortisol levels
    • Improved systolic  (-5.4 mmHg) and diastolic (-3.3 mmHg) blood pressure 
  • Commentary: CPAP therapy in those w/ OSA can improve important neuro-endocrine-hormonal axis and blood pressure metrics.

• Effects of 6 Months of Soy-Enriched High Protein Compared to Eucaloric Low Protein Snack Replacement on Appetite, Dietary Intake, and Body Composition in Normal-Weight Obese Women: A Randomized Controlled Trial
  • 107 overweight women
  • Randomized to high-protein (50 g) or low-protein (<2 g) snacks, interventions matched for calories
  • After 6 months, high-protein group:
    • Ate less calories (-166 Cals/d)
    • Ate less carbs (-58 g/d)
    • Had less appetite
    • Reduced waist circumference more (-4.3 cm vs -0.9 cm)
    • Lost more body fat percentage (-3.7% vs -0.9%) 
  • Commentary: This corroborates other studies suggesting higher-protein diets lead to less appetite and a subsequent subconscious reduction in overall caloric intake- See below.

• Is protein the forgotten ingredient: Effects of higher compared to lower protein diets on cardiometabolic risk factors. A systematic review and meta-analysis of randomised controlled trials
  • Comparing low-protein (LP) and high-protein (HP) diets
  • 54 RCTs, 4,344 participants, average duration 18 wks of interventions
  • Compared to LP diets (10-23% of calories), HP diets (20-45% of calories) led to greater reductions in: 
    • Fat mass (-0.55kg more than LP)
    • Systolic BP (1.16 mmHg)
    • Total cholesterol (-3.1 mg/dL)
    • Triglycerides (-10.6 mg/dL)
    • Insulin and insulin resistance
  • Commentary: An ancestral/Paleo template can make a small win for patients and set a necessary foundation to layer on more therapies.

• Temporal and mediation relations of weight loss, and changes in insulin resistance and blood pressure in response to 2-year weight-loss diet interventions: The POUNDS Lost trial
  • 742 overweight/obese adults, randomized different low-calorie diets
  • At 24 months, weight loss preceded improvements in insulin sensitivity
  • Commentary: Weight loss should be a main goal for overweight/obese patients who seek improvements in glycemic control/insulin resistance. This study shows that weight loss comes BEFORE improvements in insulin sensitivity.

• Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL)
  • 771 adults 50+ years old, randomized to Vit D (2,000 IU/d) or placebo
  • Supplemental Vit D had NO effect on 2-year changes in bone mineral density (BMD) at the spine, femoral neck, and hip.
  • Commentary: In this study, a medium dose of Vit D did NOT improve BMD. I wonder if there may be a benefit if this study only looked at possible benefits for post-menopausal women. 

• Effect of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis
  • 6 studies, 417 patients w/ fatty liver
  • Intermittent fasting associated w/ IMPROVEMENT in:
    • Body weight (-2.45 kg)
    • BMI (-0.5)
    • AST (-11.3) 
    • ALT (-10.5)
  • NO differences in triglycerides, total cholesterol, and other cardiometabolic markers
  • Commentary: Intermittent fasting associated w/ improvements in anthropometric parameters and liver function in those w/ fatty liver. Other studies suggest that just 5% weight loss (e.g. from 200 lbs to 190 lbs) is associated w/ significant reductions in hepatic steatosis. 

• Is Physical Activity Associated with Less Depression and Anxiety During the COVID-19 Pandemic? A Rapid Systematic Review
  • 21 observational studies, 42,293 participants from 5 continents
  • Those who performed more physical activity (PA) showed LESS symptoms of depression and anxiety (32% less for depression, 34% less for anxiety)

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Featured Study

• Small intestinal bacterial overgrowth and evaluation of intestinal barrier function in patients with ulcerative colitis
  • 96 ulcerative colitis (UC) patients, 40 healthy controls underwent lactulose breath testing
  • SIBO positive patients randomized to:
    • Mesalazine (x6 wks)
    • Mesalazine (x6 wks) + Rifaximin (x2 wks)
  • Results:
    • UC patients had higher rates of SIBO compared to controls (56% vs 25%)
    • Mesalazine + Rifaximin group had:
      • Higher rates of positive symptom improvement (93% vs 64%)
      • Higher rates of complete remission (57% vs 27%)
      • Lower inflammatory markers (ESR, CRP) than mesalazine alone
  • Commentary: Rifaximin (and other antimicrobials) can play a crucial role in IBD cases as this trial presents, and is superior to mesalazine alone.

Gastrointestinal Studies

• Functional Gastrointestinal Disorders and Associated Health Impairment in Individuals with Celiac Disease
  • What is the rate of functional GI disorders (FGID) in Celiac Disease (CD) patients w/ persistent GI symptoms despite gluten-free diet?
  • 863 CD patients on gluten-free diet (GFD) for 1+ year
  • 61% were adherent to GF diet 
  • Of the CD patients, FGID found in:
    • 51% of adherent patients
    • 75% to non-adherent patients
  • GFD-adherent subjects with FGIDs were more likely to have high level of anxiety (5% vs. 2%, OR 2.8)
  • Commentary: 
    • One in two people with CD, will have ongoing GI symptoms despite a GFD for a long period of time (1+ years). 
    • Those w/ FGID and CD are 3x more likely to experience anxiety as those without FGID. 

• Comparison of safety, effectiveness and serum inflammatory factor indexes of Saccharomyces boulardii versus Bifidobacterium triple viable in treating children with chronic diarrhea: A randomized trial
  • 161 children 2-8 yo hospitalized for chronic diarrhea
  • Randomized to:
    • S. boulardii
    • Multi-strain Bifidobacterium/Lactobacillus
    • Placebo
  • After 14 days:
    • Effective rate of both probiotics was BETTER than placebo
      • Bifidobacterium had faster recovery rate compared to S. boulardii
    • Inflammatory markers in both probiotic groups were LOWER than placebo
  • Commentary: 
    • Both multi-strain Bifidobacterium/Lactobacillus probiotics AND S. boulardii lead to IMPROVEMENTS in diarrhea recovery in children.
    • Multi-strain probiotics may be a little better than single-strain probiotics.

• Guidance on the interpretation of faecal calprotectin levels in children
  • Fecal calprotectin (FC) measurements from 3,000 children
  • Of those with FC > 50 μg/g WITHOUT typical IBD symptoms (bloody diarrhea, nocturnal abdominal pain, weight loss), 76% did NOT have IBD
  • Commentary: 
    • An elevated FC level WITHOUT typical IBD symptoms may NOT constitute IBD.
    • Remember that other conditions (e.g. IBS) can also increase FC levels. 

• Randomized clinical trial: Effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome
  • 160 IBS patients, randomized to aloe or control (inulin)
  • After 4 weeks: NO differences in IBS symptom score
  • Commentary: Aloe was NOT superior to a control in alleviating IBS symptoms in this trial

• Cytomegalovirus colitis induced segmental colonic hypoganglionosis in an immunocompetent patient: A case report
  • Case report 
  • 48 yo women with NO past medical history, admitted to hospital for abdominal pain and constipation
  • PCR test showed cytomegalovirus (CMV) infection
  • Treated w/ ganciclovir and PCR levels dropped
  • Returned 8 months later for severe abdominal pain 
  • Surgical removal of colon revealed reduced ganglionic cells (nerve cells that allow the bowel to relax)
  • Commentary: CMV infection can:
    • Occur in patients with no underlying disease
    • Contribute to colitis 
    • Associated w/ reduced ganglion cells→ poor motility

• Food-symptom diaries can generate personalized lifestyle advice for managing gastrointestinal symptoms: A pilot study
  • 209 diaries from patients w/ GI symptoms 
  • Meta-analysis showed that late-night eating was associated w/ more GI symptoms, especially bloating
  • Commentary: A simple intervention to help w/ GI symptoms is to push the last meal 2+ hours before bed time.

Autoimmunity Studies

• Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
  • Compared blood chem results of chronic fatigue patients (149) vs healthy controls (264)
  • Compared to healthy controls, chronic fatigue patients had:
    • HIGHER:
      • Erythrocyte sedimentation rate (mean difference 1.4)
      • Ferritin (MD 28)
    • LOWER:
      • Creatinine (MD 2.6)
      • Creatinine kinase (MD 38)
  • Commentary: Most clinically significant in this study is the increase in ESR and ferritin levels.

Thyroid & Hormones Studies

• Effects of Testosterone Replacement Therapy on Glycolipid Metabolism Among Hypogonadal Men withT2DM: A Meta-Analysis and System Review of Randomized Controlled Trials
  • Does testosterone replacement therapy (TRT) improve insulin resistance?
  • 4 studies
  • TRT did NOT significantly improve insulin resistance 
  • Commentary: TRT still remains to be indicated for symptom improvement of low testosterone (not improvement of cardiometabolic markers).

• Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: A systematic review and meta-analysis
  • What is the effect of exogenous estrogen on bone mineral density (BMD) for premenopausal women with functional hypothalamic amenorrhoea (FHA) due to weight loss, vigorous exercise and/or stress?
  • 9 RCTs, 770 participants
  • Results:
    • 4  trials: INCREASED BMD in premenopausal women with FHA
    • 5 trials:  DECREASED BMD compared with controls.
    • NO difference in BMD between the estrogen and control groups
  • Commentary: Exogenous estrogen therapy does NOT show benefit in PREmenopausal women in regards to improved BMD. 

• Metformin reduces autoimmune antibody levels in patients with Hashimoto’s thyroiditis: A systematic review and meta-analysis
  • 7 studies, 118 Hashimoto’s patients treated w/ metformin
  • Metformin lead to a significant reduction in:
    • TPOAb levels (-178)
    • TSH (-1.25)
  • Commentary: Pharmacological (and diet/lifestyle) interventions that control blood sugar may have a beneficial effect on the thyroid.

Diet & Lifestyle Studies

• Intake of dietary fibre, red and processed meat and risk of late-onset Chronic Inflammatory Diseases: A prospective Danish study on the “diet, cancer and health” cohort
  • What’s the association between intake of fiber, red/processed meat, and chronic inflammatory disease (e.g. psoriasis, rheumatoid arthritis, IBD, multiple sclerosis, psoriatic arthritis)?
  • Cross sectional analysis, 56,000 participants over 50 yo
  • At median followup of 22 years, there was NO association between dietary intake (fiber, red/processed meat) and prevalence of chronic inflammatory disease

• ​​Effects of Time-Restricted Feeding on Supramaximal Exercise Performance and Body Composition: A Randomized and Counterbalanced Crossover Study in Healthy Men
  • 12 healthy young adult males
  • Cross-over study with regular diet vs. time-restricted feeding (TRF) w/ 8-hour feeding window
    • Matched for calories
  • After 4 weeks:
    • Similar increase in muscle mass
    • NO change/difference in cardiorespiratory fitness
  • Commentary: TRF can be paired with resistance training/exercise WITHOUT a decrease of fitness as long as caloric intake is maintained.

• Long-term All-Cause Mortality Risk in Obstructive Sleep Apnea Using Hypopneas Defined by a ≥3 Percent Oxygen Desaturation or Arousal
  • 5,591 participants without cardiovascular disease at baseline analyzed for  obstructive sleep apnea (OSA) diagnosis 
  • At 11 year followup:
    • Higher number of apnea/hypopneas associated w/ all-cause mortality (HR 1.13)
      • Even higher risk in men and those <70 years old
  • Commentary: OSA was associated with all-cause mortality

• Association between Blood Mercury Levels and Non-Alcoholic Fatty Liver Disease in Non-Obese Populations: The Korean National Environmental Health Survey (KoNEHS) 2012-2014
  • Cross-sectional study, 5,919 participants
  • Higher blood mercury levels associated w/ higher rates of NAFLD in both healthy and overweight individuals
  • Commentary: Toxins/heavy metals such as mercury may play a role in fatty liver.

• Tart Cherry Supplementation and Recovery From Strenuous Exercise: A Systematic Review and Meta-Analysis
  • 14 studies
  • Tart cherry supplementation had a:
    • Small beneficial effect in reducing muscle soreness (effect size= -0.44)
    • Moderate beneficial effect for recovery of muscle strength (ES = -0.78) and muscular power (ES = -0.53)
  • Commentary: Tart cherry supplementation may aid in recovery from strenuous exercise.

• The effects of dietary nitrate supplementation on endurance exercise performance and cardiorespiratory measures in healthy adults: A systematic review and meta-analysis
  • Nitrate supplementation = beetroot, beets, betaine
  • 73 studies, 1,061 participants
  • Nitrate supplementation improved power output (MD 4.6 watts), time to exhaustion (MD 25.3 s), and distance travelled (MD 163.7 m)
    • BUT, NO significant difference on perceived exertion, time trial performance and work done
  • Commentary: Nitrate supplementation may have a small, but a clinically insignificant effect on endurance performance

• Meta-analysis of the correlation between serum uric acid level and carotid intima-media thickness
  • 15 studies, 11,382 participants 
  • High uric acid (>7 mg/dL for men, >6 mg/dL for women) associated w/ higher carotid intima-media thickness scores in both healthy individuals and those w/ cardiovascular disease
  • Commentary: High uric acid is a risk factor for cardiovascular disease

Podcast Summary

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Featured Study

• Compared with classic Hashimoto’s thyroiditis, chronic autoimmune serum-negative thyroiditis requires a lower substitution dose of L-thyroxine to correct hypothyroidism
  • Cross sectional study
  • 581 w/ autoimmune thyroid disease (AITD) on ultrasound
  • Separated into 2 groups depending on TPO-Ab levels:
    • Seronegative autoimmune thyroiditis (SN-AITD)= hypoechoic ultrasound WITHOUT antibodies
      • 21% of patients
    • Hashimoto’s thyroiditis (HT)= presence of antibodies
      • 79%
  • Findings:
    • HT had higher TSH (7.3 vs 6.9) and higher portion of patients with OVERT hypothyroidism (15% vs 5%)
    • At 9 year follow up, ONLY 16% of SN-AITD patients developed TPO-Ab and/or Tg-Ab
    • Thyroid-volume significantly decreased in HT patients, but NOT in those with SN-AITD
    • Dose of LT4 was smaller in SN-AITD patients as compared with the HT (60 mcg/d vs 71 mcg/d)
  • Commentary: AITD patients without antibodies may not need as high of thyroid medication and only a MINORITY develop antibodies at a 9 year followup.

Gastrointestinal Studies

• The Prevalence of the Celiac Disease in Patients with Dyspepsia: A Systematic Review and Meta-Analysis
  • 21 studies, 10,275 patients w/ dyspepsia
  • Celiac disease diagnosis:
    • 4.8% when measure antibodies
    • 1.5% when confirm w/ biopsy
  • Celiac disease diagnosis in those w/ dyspepsia was NOT statistically different than healthy controls

• Influence of low FODMAP-gluten free diet on gut microbiota alterations and symptom severity in Iranian patients with irritable bowel syndrome
  • 30 IBS patients, given low FODMAP + gluten free diet (LF-GFD)
  • After 6 weeks:
    • Lower symptom severity
    • Altered microbiome (less bacteroidetes)
    • Lower calprotectin
  • Commentary: This study is interesting given their findings of lower calprotectin in a IBS cohort. 

• Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease
  • 54 patients w/ Celiac Disease
  • Randomized to one of groups x94 weeks followed by escalation of gluten consumption:
    • 20 Hookworm (HW20) larvae
    • 40 Hookworm (HW40) larvae
    • Placebo
  • Results:
    • Side effects from gluten consumption significantly reduced in hookworm-treated participants (0 in HW40, 1 in HW20, 4 in placebo)
    • Similar deterioration in duodenal villous health
    • Symptoms were lower in hookworm-positive participants after intermittent gluten challenge (39 vs 46)
  • Commentary: Hookworm infection does NOT restore tolerance to sustained moderate consumption of gluten (2 g/d). But, it was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.

• Hospitalized Older Patients with Clostridioides difficile Infection Refractory to Conventional Antibiotic Therapy Benefit from Fecal Microbiota Transplant
  • 9 older patients (60-96 yo) received FMT for refractory C. diff infection (CDI) not responsive to antibiotic therapy
  • 7 of 9 patients received multiple FMT (average 2.15)
  • Results
    • 5 patients had complete resolution
    • 1 was C. diff negative
    • 1 recurrent CDI
    • 2 deaths
  • Commentary: Overall cure rate of 67%. However, multiple FMT administrations are needed.

• Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial
  • 17 sites, 245 IBS patients
  • Received human milk oligosaccharides (HMO) at 5g/d
  • After 12 weeks:
    • Improvement stool consistency (91% vs 57% at baseline)
    • Improved symptom score (323 vs 144 at baseline)
    • Improved quality of life
  • Similar improvements across all IBS subtypes
  • Most symptoms improve in first 4 weeks

• Pattern of methane levels with lactulose breath testing; can we shorten the test duration?
  • Retrospective study of 745 breath tests
  • SIBO prevalence
    • 33% overall SIBO positive
    • 15% methane positive
    • 3% methane + hydrogen positive
  • Of the methane-positive results:
    • 96.4% had methane levels ≥10 ppm within 90 min 
    • 76% had levels ≥10 ppm at time 0 (baseline)
      • 82% if had constipation
  • In all cases of constipation, methane over 10 ppm in ALL cases
  • Commentary: The vast majority of methane-positive SIBO cases had elevated methane within 90 minutes. Constipation increases the likelihood of high baseline methane. Most guidelines suggest a positive for methane is 10 ppm. Be careful not to use the older thinking of 3 or 4 ppm

• Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial
  • 35 Autism patients ages 3-20 yo
  • Randomized to Oxytocin + probiotics (L. rhamnosus) or Oxytocin + placebo
  • After 28 weeks, the oxytocin + probiotic group had improved symptoms compared to oxytocin + placebo
  • Commentary: Addressing gut health may impact Autism pathogenesis

• Prevalence and predictors of small intestinal bacterial overgrowth in systemic sclerosis: A systematic review and meta-analysis
  • Evaluating the association of systemic sclerosis (SS) and SIBO
  • 14 studies, 700 systemic sclerosis patients, 217 healthy controls
  • Pooled prevalence of SIBO in SSc was 34% (OR 12.51)
    • But, depended on test used
      • Lactulose: 56%
      • Glucose: 27%
      • Aspiration: 35%
  • Higher risk of diarrhea higher in SS patients w/ SIBO, than those without SIBO (OR 8.82)
  • Commentary: Risk of SIBO in SS was increased by nearly thirteenfold compared to the healthy controls

Autoimmunity Studies

• Efficacy and safety of weekly vitamin D 3 in patients with fibromyalgia: 12-week, double-blind, randomized, controlled placebo trial
  • 80 female fibromyalgia patients
  • Randomized to Vit D (50,000 IU per week) or placebo
  • After 12 weeks, NO differences in symptom severity
  • Commentary: In this study, Vit D supplementation did NOT lead to improvements in females w/ fibromyalgia

Thyroid & Hormones Studies

• Vitamin B12 and Vitamin D Levels in Patients with Autoimmune Hypothyroidism and Their Correlation with Anti-Thyroid Peroxidase Antibodies
  • 130 autoimmune thyroid disease (AITD) patients
  • Divided into groups depending on B12 and Vit D levels
  • Vit-B12 deficiency(<200 pg/mL) and vit-D deficiency (<20 ng/mL) were associated with autoimmune hypothyroidism
  • The lower the B12 and Vit D, higher the anti-TPO antibodies were 
  • Commentary: Consider nutrient insufficiency in those w/ hypothyroidism

• Association between triglyceride-glucose index and thyroid function in euthyroid adults: The Korea National Health and Nutritional Examination Survey 2015
  • Cross-sectional study, 1,500 participants
  • Measured insulin resistance (triglyceride index) and thyroid metrics
  • Higher insulin resistance scores associated w/ higher TSH and lower fT4
  • Commentary: Poor glycemic control associated w/ thyroid dysfunction.

• The Association between Dietary Inflammatory Index and Sex Hormones among Men in the United States
  • NHANES analysis of 4,151 men
  • Assess 24-hour dietary intake and testosterone levels
  • Increased dietary inflammatory index associated w/ higher likelihood of testosterone deficiency
  • Commentary: Lower testosterone levels can be the “canary in the coalmine” in metabolic syndrome and other inflammatory conditions.

• Dysregulation of the Hypothalamic-Pituitary-Testicular Axis due to Energy Deficit
  • Narrative review of relationship between testosterone and energy intake
  • “Case series and mechanistic studies demonstrate that energy deficit (both acutely over days or chronically over months) either due to inadequate energy intake and/or excessive energy expenditure can lower serum testosterone concentration as a result of hypothalamic-pituitary-testicular axis dysregulation in men.”
  • Commentary: Low testosterone may be a result of insufficient caloric intake

Diet & Lifestyle Studies

• The effects of Ramadan intermittent fasting on liver function in healthy adults: A systematic review, meta-analysis, and meta-regression
  • 20 studies, 600 participants
  • Intermittent fasting associated with:
    • Small improvements in AST and ALT
    • Medium improvement in GGT
  • Commentary: Intermittent fasting may lead to transient improvements in liver health

• The effect of vitamin D supplementation on flow-mediated dilatation, oxidized LDL and intracellular adhesion molecule 1 on type 2 diabetic patients with hypertension: A randomized, placebo-controlled, double-blind trial
  • 44 patients w/ type 2 diabetes (T2D) and hypertension
  • Randomized to Vit D (2,000 IU/d) or placebo
  • After 12 weeks of supplementation, Vit D group had:
    • Average Vit D levels increases from 32 to 40 ng/mL
    • Lower OxLDL 
    • Improved endothelial function (higher flow-mediated dilatation)
  • Commentary: Vit D supplementation can improve oxidation and endothelial function

• Vitamin D can safely reduce asthma exacerbations among corticosteroid-using children and adults with asthma: A systematic review and meta-analysis of randomized controlled trials
  • 12 studies, 1,500 participants
  • Vit D supplementation significantly reduced the risk of asthma exacerbation (RR 0.70)
  • NO difference in pulmonary function or baseline symptom score
  • Commentary: Vit D may lower risk of asthma exacerbation without significant improvement in pulmonary function

• Is caffeine mouth rinsing an effective strategy to improve physical and cognitive performance? A systematic review
  • 18 studies: 15 focused on physical performance, 3 for cognitive function
  • ALL 3 studies found an improvement in cognitive performance with caffeine mouth rinse
  • Four (of 15) studies found positive effects of caffeine mouthwash on physical performance when repeated during exercise
  • Commentary: Fair evidence suggests that caffeine mouth rinse can support cognitive function and physical performance

• Sleep duration and cardiovascular risk factors in children and adolescents: A systematic review
  • 52 reviews/meta-analysis
  • Results:
    • Strong evidence: short sleep duration associated w/ increased adiposity and high blood pressure
    • Moderate evidence: short sleep duration associated w/ insulin resistance
  • Commentary: High-quality evidence to confirm association between sleep debt and poor cardiometabolic health

• The Effect of Combined Vitamin C and Vitamin E Supplementation on Oxidative Stress Markers in Women with Endometriosis: A Randomized, Triple-Blind Placebo-Controlled Clinical Trial
  • 60 reproductive-aged (15-45 years) women with pelvic pain and endometriosis
  • Randomized to:
    • Vitamin C (1,000 mg/day) + vitamin E (800 IU/day)
    • Placebo
  • After 8 weeks:
    • NO significant reduction in total antioxidant capacity
    • Reduced pelvic pain, dysmenorrhea, and dyspareunia (painful sex) in intervention group
  • Commentary: Vit C + E may lead to symptom improvement regardless of improving oxidative stress markers. This may be in part to oxidation being a hard metric to measure.