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Featured Study

• Feasibility of a low FODMAPs diet without initial dietician intervention in the management of patients with irritable bowel syndrome: a prospective study
  • 35 IBS patients, all given low FODMAP diet handout
  • After 6 weeks: 
    • 52% followed LFD regularly
    • 28% sometimes followed
    • 20% barely/did not follow
  • All symptoms (except constipation) decreased significantly
  • 77% reported symptom satisfaction
  • Commentary: This study showed a large response rate despite a lack of full diet adherence. This is why we at the clinic do not push our patients into 100% compliance with diets – this can often lead to anxiety and unwarranted fear around food.

Gastrointestinal Studies

• Exploring the Link between Leaky-Gut-Related Markers and Metabolic Health in a Large Dutch Adult Population
  • 500 participants, measured levels of intestinal permeability and metabolic health
  • Zonulin and lipopolysaccharide-binding protein levels were associated with higher:
    • CRP levels 
    • Worse metabolic health
  • Commentary: Increased gut permeability is associated w/ markers of inflammation and poor metabolic health.

• Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial
  • Cross-over study of 101 adolescents with obesity
  • Randomized to probiotic or placebo w/ 4 week wash-out period
  • Probiotic supplementation resulted in improved insulin sensitivity
  • Commentary: Another study showcasing the gut-metabolic connection. 

• Lack of association of the esophageal microbiome in adults with eosinophilic esophagitis compared with non-EoE controls
  • 24 eosinophilic esophagitis (EoE) patients, 25 healthy controls
  • All had esophageal biopsy w/ microbiome analysis
  • No significant differences in the esophageal microbiome between EoE cases and healthy controls
  • No association between microbiome and EoE severity
  • Commentary: Another data point where the lab findings don’t always match clinical presentation.

• A meta-analysis reveals the effectiveness of probiotics and prebiotics against respiratory viral infection
  • Pre-clinical studies: Probiotics reduced mortality rate (HR 0.7)
  • Human clinical studies: Probiotics reduced symptom scores and infection rate (RR 0.8)
  • Commentary: Probiotics may have favorable effects against respiratory viral infections.

• The Yield of Endoscopy and Histology in the Evaluation of Esophageal Dysphagia: Two  Centers’ Experiences
  • Retrospective multicenter study of 209 patients w/ dysphagia referred for endoscopy + biopsy 
  • Most common endoscopic findings:
    • 36.4% normal endoscopy
    • 35.9% erosive esophagitis
    • 5.3% Barrett’s esophagus 
    • 0.95% malignancy
    • 0.5% eosinophilic esophagitis
  • Commentary: Endoscopic findings were fairly prevalent in a group of patients w/ dysphagia. Malignancy and eosinophilic esophagitis were rare.

• Pilot Trial of Vitamin D3 and Calcifediol in Healthy Vitamin D Deficient Adults: Does It Change the Fecal Microbiome?
  • 18 adults with vitamin D deficiency (<20 ng/mL) received either Vit D3 or 25-hydroxyvitamin D3
  • Measured microbiome w/ 16S rRNA gene sequencing
  • After 8 weeks:
    • Average 25(OH)D levels increased significantly (16.7 to 50.6 ng/mL)
    • Fecal microbial α-diversity and β-diversity did not change with D3 or 25D3 supplementation
  • Commentary: Repleting those w/ Vit D deficiency did not lead to significant changes in the microbial diversity. 

• The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors
  • 18 IBS-D patients w/ anxiety and depression, allocated (non-randomized) to FMT or control (no treatment)
  • The FMT had:
    • Improved anxiety and depression
    • Improved IBS symptom severity
  • Better quality of life
  • Commentary: FMT can improve quality of life, IBS symptoms, and mood imbalances. This is another data point for the gut-brain connection.

Autoimmunity Studies

• The Effectiveness and Safety of Probiotic Supplements for Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Preclinical Trials
  • 3 RCTs, 164 participants
  • 2 studies: probiotics reduced psoriasis severity
  • 1 study: probiotics lowered levels of inflammation
  • Commentary: Probiotics can improve psoriasis.

• Oral Administration of Live and Dead Cells of Lactobacillus sakei proBio65 Alleviated Atopic Dermatitis in Children and Adolescents: a Randomized, Double-Blind, and Placebo-Controlled Study
  • 90 kids w/ atopic dermatitis, randomized to:
    • Placebo
    • Non-viable/dead probiotics
    • Viable/live probiotics
  • After 12 weeks of supplementation, both live AND dead probiotics had improved symptoms
  • Commentary: Both live and dead probiotics can exert beneficial effects.

• Therapeutic Benefits of Balneotherapy on Quality of Life of Patients with Rheumatoid Arthritis: A Systematic Review
  • 7 studies examining the effect of balneotherapy (bathing in warm mineral water) for those w/ rheumatoid arthritis (RA)
  • All studies showed a significant improvement in quality of life
  • Authors suggest “Sessions should be approximately 20 min long and use natural mineral waters enriched with elements, or mud, at a water temperature between 35-38 °C.”
  • Commentary: Balneotherapy may be a viable option for those w/ rheumatic joint pain like RA.

Thyroid & Hormones Studies

• Subclinical hypothyroidism in older individuals
  • Narrative review of subclinical hypothyroidism (SCH) in those >65 yo
  • Studies showed no increased risk of poor outcomes (e.g. cardiovascular, cognitive) if TSH between 4.5-7 
  • In older individuals with SCH, symptoms of hypothyroidism, and cardiac and bone health did not improve after levothyroxine treatment. 
  • “This data suggest that treatment with levothyroxine should be considered for TSH concentration is persistently 7 mIU/L or higher and to not initiate treatment with TSH concentrations of less than 7 mIU/L.”
  • Commentary: Consider age and the degree of TSH elevation when managing SCH.

• Cardiovascular Outcomes in Thyroid Cancer Patients Treated With Thyroidectomy: A Meta-analysis
  • 18 studies, 193,320 thyroid cancer patients treated w/ thyroidectomy or thyroid hormone suppression, and 225,575 healthy controls
  • Thyroid cancer was associated with:
    • Atrial fibrillation (RR 1.55)
    • Coronary artery disease (RR 1.1)
    • Cerebrovascular accidents (RR  1.15)
  • Commentary: Patients treated for thyroid cancer are at a slight increased risk of a-fib, CAD, and CVA.

• Weekly Versus Daily Levothyroxine Tablet Replacement in Adults with Hypothyroidism: A Meta-Analysis
  • 2 RCTs, 109 participants comparing weekly vs daily levothyroxine
  • After 12 weeks:
    • The weekly levothyroxine group had a 1.78 mIU/mL higher TSH
    • No difference in symptoms
    • No difference in adverse events
  • Commentary: Weekly levothyroxine led to slightly higher TSH with no difference in symptoms or side effects.

Diet & Lifestyle Studies

• Blood lead concentrations among pediatric patients with abdominal pain: a prospective cross-sectional study
  • 187 children w/ abdominal pain
  • 20% had elevated blood lead levels (≥ 5 µg/dL)
  • Risk factors:
    • Playing with both plastic and cotton toys (OR 2.8)
    • Height and weight
    • Age

• Hair cortisol levels in women with medically unexplained symptoms
  • 4 groups of women::
    • 33 w/ functional somatic syndrome (chronic fatigue, fibromyalgia, IBS)
    • 23 w/ somatic symptom disorder (excessive thoughts and feelings about their symptoms)
    • 27 w/ depression
    • 30 healthy controls
  • Hair cortisol levels measured in all groups
  • No differences in hair cortisol were found between groups. 
  • Neither childhood trauma nor chronic stress was correlated with hair cortisol levels.
  • Commentary: This study challenges the concept of “adrenal fatigue.”

• Treatment of Chinese Patients with Hypertriglyceridemia with a Pharmaceutical-Grade Preparation of Highly Purified Omega-3 Polyunsaturated Fatty Acid Ethyl Esters: Main Results of a Randomized, Double-Blind, Controlled Trial
  • 728 patients w/ high triglycerides randomized to placebo or high-dose fish oil (2 g/day for 4 weeks, then 4 g/day for 8 weeks)
  • The interventional group had reduced triglycerides (-29.5%)
  • Commentary: High-dose fish oil at 2-4 g/d can substantially reduce triglycerides.

• Omega-3 in The Treatment of Mood and Sleep Disorders Induced by Hormone Therapy in Women with Breast Cancer: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial 
  • 60 women treated for breast cancer, randomized to placebo or omega-3 (2g/d)
  • After 4 weeks, the omega-3 group had:
    • Improved depressive symptoms and mood
    • Better sleep quality
  • Commentary: Omega-3 supplementation can improve mood and sleep quality.

• The Effect of L-arginine Supplementation On Blood Pressure in Adults: A Systematic Review and Dose-response Meta-analysis of Randomized Clinical Trials
  • 22 RCTs
  • L-arginine supplementation resulted in significant reduction in systolic (-6.4 mmHg) and diastolic blood pressure (-2.6 mmHg)
  • Effective dose is ≥4 g/day 
  • Commentary: This meta-analysis suggested efficacy of arginine on reducing blood pressure.

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Featured Study

• Vitamin D and Marine n-3 Fatty Acid Supplementation and Prevention of Autoimmune Disease in the VITAL Randomized Controlled Trial
  • 25,871 healthy men and women over 55 years old
  • Randomized to:
    • Placebo
    • Vit D (2,000 IU/d) 
    • Omega-3 fatty acids (1 g/d)
    • Combined Vit D + omega-3
  • After 5.3 year follow-up, the autoimmune disease incidence rate was LOWER in the supplementation group:
    • Vit D (HR 0.61)
    • Omega-3 (HR 0.85)
  • Overall, supplementation lowered autoimmune disease risk by 25-30%
  • Commentary: This high quality randomized controlled trial showed a benefit of Vit D and omega-3 fatty acids for reducing autoimmune disease risk.

Gastrointestinal Studies

• Assessment of Markers of Gut Integrity and Inflammation in Non-Celiac Gluten Sensitivity After a Gluten Free-Diet
  • Biomarkers analyzed in:
    • 20 non-celiac gluten sensitivity (NCGS) on gluten-free diet
    • 20 IBS patients
    • 20 healthy controls
  • IBS symptom score was higher in those w/ NCGS and IBS compared to healthy controls
  • NO difference in gut permeability markers, inflammatory markers, or antigliadin IgG antibodies between the three groups
  • However, gut permeability markers correlated with antigliadin antibodies
  • Commentary: There was no difference in intestinal permeability markers in the 3 groups. Labs do NOT always correlate with symptoms.

• Helicobacter Pylori CagA Virulence Gene and Severe Esophagastroduodenal Diseases: Is there an association?
  • Gastric biopsies from 117 patients w/ various esogastroduodenal diseases
  • H. pylori detected in 66% of patients, 80.5% had cagA virulence gene
  • The cagA gene was NOT associated w/ severity of disease
  • Commentary: Contrary to conventional thinking, the cagA virulence gene was not associated with upper GI disease severity in this study.

• The relationship between Helicobacter pylori infection and reflux esophagitis and the long-term effects of eradication of Helicobacter pylori on reflux esophagitis 
  • Retrospective study of 185 w/ successful H. pylori eradication, w/ at least a 3 year followup
  • Reflux incidence increased after eradication therapy (from 1.6% to 7%)
  • Prevalence of reflux was NOT related to gastric atrophy. 
  • Commentary: This study observed an INCREASED rate of reflux after eradication therapy w/ a long-term followup. Furthermore, gastric atrophy was not associated w/ reflux symptoms and suggested a dissociation between symptoms and lab findings.

• Helicobacter pylori eradication prevents secondary gastric cancer in patients with mild-to-moderate atrophic gastritis
  • Multi-center retrospective study of 483 patients who had endoscopic resection for early gastric cancer
  • Split into 2 groups:
    • Undergone successful H. pylori eradication in the past year
    • Failed or not attempted H. pylori eradication
  • After 5.2 year follow-up, cancer recurrence rates occurred at similar rates between 2 groups (17.7% vs 18.5%)
  • However, in those w/ mild-to-moderate atrophic gastritis
    • Incidence of cancer recurrence was significantly lower in the eradicated group than in the non-eradicated group
  • However, NO difference in the severe atrophic gastritis group
  • Commentary: Overall, this study suggested very little effect of H. pylori treatment on gastric cancer recurrence rates.

• Esophageal Eosinophilia and Eosinophilic Esophagitis in Celiac Children: A Ten Year Prospective Observational Study
  • 370 children w/ celiac disease who had endoscopy
  • Prevalence of eosinophilic esophagitis (EoE) was 0.3% 
    • NO difference in EoE rates compared to healthy controls
  • Commentary: Kids w/ celiac disease are not at higher risk of EoE compared to healthy controls.

• A Specifically Tailored Multistrain Probiotic and Micronutrient Mixture Affects Nonalcoholic Fatty Liver Disease-Related Markers in Patients with Obesity after Mini Gastric Bypass Surgery
  • 48 obese patients after gastric bypass surgery randomized to:
    • Multi-strain probiotics + customized micronutrient blend
    • Basic micronutrient blend only
  • After 3 months of supplementation, the probiotic + micronutrient group had:
    • Lower AST (-8.0 U/L)
    • Reduced fibrosis scores
    • Reduced triglycerides (-22.8 mg/dL)
    • Reduced visceral adiposity 
  • Commentary: This highlights the gut-liver connection.

• Effect of continuous positive airway pressure on gastroesophageal reflux in patients with obstructive sleep apnea: a meta-analysis
  • 10 studies, 272 patients w/ sleep apnea
  • CPAP therapy reduced reflux symptoms
    • More reduction w/ longer use of CPAP
  • Commentary: Given that reflux is common in those w/ sleep apnea, treating sleep disordered breathing may be an important part of getting optimal GI health improvement.

• Clinical efficacy of fecal microbial transplantation treatment in adults with moderate-to-severe atopic dermatitis
  • 9 patients w/ moderate-severe atopic dermatitis
  • All patients received 2 placebo transplantations followed by 4 FMTs, each 2 weeks apart
  • Atopic dermatitis severity decreased after FMT
    • 50% reduction in 77%
  • Reduced steroid use
  • Commentary: Treating the gut can alleviate atopic disease.

• Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet in patients with diarrhea-predominant irritable bowel syndrome: A prospective, randomized trial
  • 166 IBS-D patients randomized to low FODMAP diet (LFD) or traditional IBS diet 
  • After 16 weeks:
    • Greater reduction in IBS symptoms for LFD (53% vs 30.6% response rate)
  • However, compliance to the LFD was only 64% at 16 weeks
  • Commentary: This study shows that even a modified LFD for long-term use can lead to improvement in those w/ IBS.

• Circulating Levels of Inflammatory and Metabolic Biomarkers and Risk of Esophageal Adenocarcinoma and Barrett Esophagus: Systematic Review and Meta-analysis
  • 19 studies
  • The following was associated w/ a higher risk of Barrett Esophagus or esophageal adenocarcinoma:
    • Higher fasting glucose (OR 1.1)
    • Higher insulin (OR 1.47)
    • Higher CRP (OR 2.1)
    • IL-6 (OR 1.5)
  • Commentary: Inflammation and worse glycemic control is associated w/ esophageal cancer and Barrett esophagus.

• The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis
  • 62 studies
  • Probiotics, prebiotics, and synbiotics had significant benefit for depressive symptoms 
  • NO effect of FMT
  • Commentary: Another data point for the gut-brain connection.

Thyroid & Hormones Study

• The Effects of 6 Weeks of Tribulus terrestris L. Supplementation on Body Composition, Hormonal Response, Perceived Exertion, and CrossFit ® Performance: A Randomized, Single-Blind, Placebo-Controlled Study
  • 30 healthy males who train in CrossFit
  • Randomized to tribulus (750 mg) or placebo
  • After 6 weeks of supplementation:
    • No difference in most performance metrics (except increase in bench press +11 kg)
    • No difference in body composition/fat mass
    • No difference in cortisol levels
    • No change in total testosterone (where the control group had decrease in testosterone)
  • Commentary: Tribulus supplementation had very minor effects on performance and testosterone.

Diet & Lifestyle Studies

• Benefits to Performance and Well-Being of Nature-Based Exercise: A Critical Systematic Review and Meta-Analysis
  • 49 studies comparing outdoor vs indoor exercise
  • Compared to indoor exercise, outdoor training associated with:
    • Better cognitive performance 
    • Lower ratings of perceived exhaustion
    • Higher levels of “vigor”
  • Commentary: You may suggest combining time in nature with exercise for your patients.

• Examining the Efficacy of a Very-Low-Carbohydrate Ketogenic Diet on Cardiovascular Health in Adults with Mildly Elevated Low-Density Lipoprotein Cholesterol in an Open-Label Pilot Study
  • 14 participants with slightly elevated LDL-C (100-160 mg/dL) put on ketogenic diet
  • After 140 days (~4 months):
    • Reduced body fat (-4.4%)
    • Increased muscle mass
    • Increased total cholesterol, LDL-C, and HDL-C
    • Decreased A1C (-0.22%)
    • Decreased systolic blood pressure
  • Commentary: It’s important to note that the change in diet was NOT isocaloric as the patients reduced their total calorie intake by roughly 600 calories, which could explain some of the beneficial results.

• Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials
  • Review in JAMA of 11 meta-analysis, 130 RCTs, median follow-up of 3 months
  • Intermittent fasting was associated with an improvement of:
    • BMI, fat mass
    • Cholesterol (LDL-C, total cholesterol)
    • Fasting insulin and glucose
    • Blood pressure
  • Commentary: This high-quality study showed a benefit of intermittent fasting to improve cardiometabolic markers. 

• The Role of Iron and Zinc in the Treatment of ADHD among Children and Adolescents: A Systematic Review of Randomized Clinical Trials
  • Zinc and iron supplementation may improve ADHD symptoms
  • However, the effect size was low in most clinical trials

• Effects of Coffee Consumption on Insulin Resistance and Sensitivity: A Meta-Analysis
  • 4 RCTs, 268 participants
  • Coffee consumption decreased insulin resistance 
  • However, the effect size was small (effect size -0.13)

• Comparative assessment of changes in pharyngeal airway space in cases of obstructive sleep apnoea with a customized mandibular repositioning appliance – a clinical study
  • 10 sleep apnea patients given customized mandibular advancement device (MAD)
  • After 2 years:
    • Improved daytime fatigue
    • Decreased sleep apnea severity
    • Reduced snoring
    • Improvement of airway patency
  • Commentary: This study suggested an improvement in sleep apnea related symptoms and anatomic findings w/ long-term use of a MAD.

• Effect of continuous positive airway pressure on symptoms of anxiety and depression in patients with obstructive sleep apnea
  • 468 sleep apnea patients who received CPAP therapy
  • After an average of 5 weeks, anxiety and depression scores decreased (small effect size)
  • Commentary: Treating sleep disordered breathing may improve mood imbalances.

• Quality of life in upper airway resistance syndrome
  • Retrospective study of 888 sleep PSG studies
    • 10.5% had upper airway resistance syndrome (UARS)
    • 90.5% had sleep apnea
  • Compared to 641 healthy controls
  • UARS had 5.5x and OSA patients had 6.2x greater probability of having a low quality of life score (compared to the healthy controls)
  • Commentary: Those w/ sleep disordered breathing are more likely to suffer from lower quality of life.

• Impact of CPAP treatment for obstructive sleep apnea on visceral adipose tissue: a meta-analysis of randomized controlled trials
  • 5 studies, 160 sleep apnea patients
  • CPAP therapy led to NO reduction in visceral fat content

• Oral appliance-generated malocclusion traits during the long-term management of obstructive sleep apnea in adults
  • 12 studies using oral devices for sleep apnea for at least 5 years
  • Oral devices are associated with dental malocclusion 
  • Commentary: This is why we at the clinic often use myofunctional therapy before oral devices for those w/ sleep disordered breathing.

• Efficacy of the New Generation of Devices for Positional Therapy for Patients With Positional Obstructive Sleep Apnea: A Systematic Review of the Literature and Meta-Analysis
  • 3 prospective cohorts, 4 RCTs of patients w/ positional sleep apnea (apnea that is worse in a supine or prone position).
  • Positional sleep devices:
    • Reduced time slept in supine position by 84%
    • Reduced AHI by 54% (-11.3 events/hour)
  • Commentary: Given that 56-75% of OSA is influenced by body position, this remains as a very practical first-line therapy. Examples of positional sleep devices can be found here and here.

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Featured Study

• Comparative Effectiveness of Persistent Use of a Name-Brand Levothyroxine (Synthroid®) vs. Persistent Use of Generic Levothyroxine on TSH Goal Achievement: A Retrospective Study Among Patients with Hypothyroidism in a Managed Care Setting
  • Aim: Is brand name Synthroid better than generic levothyroxine for those w/ hypothyroidism?
  • Retrospective study of 36,764 patients w/ hypothyroidism 
    • 18,382 on Synthroid 
    • 18,382 on generic levothyroxine
  • At the 12 month follow-up, significantly more patients receiving Synthroid were in the TSH reference range vs. general levothyroxine (78.5% vs. 77.2%, p=0.002)
  • Both groups had similar healthcare costs and provider visits
  • Commentary: Even though these results are statistically significant, they are not clinically significant (only a 1.3% difference). We argue that it doesn’t matter if you use Synthroid or generic levothyroxine. Just get a hypothyroid patient’s TSH level in the normal range and optimize their GI health.

Gastrointestinal Studies

• Long-Term Effects of a Web-Based Low-FODMAP Diet Versus Probiotic Treatment for Irritable Bowel Syndrome, Including Shotgun Analyses of Microbiota: Randomized, Double-Crossover Clinical Trial
  • Cross-over study of 34 IBS patients, 6 healthy controls
  • Randomized to probiotic (VSL#3) or low FODMAP diet x4 weeks, then cross-over to the other intervention
  • Results:
    • 55% response rate for LFD
    • 62% response rate for probiotics
    • No difference in IBS symptom reduction between two groups (-127 LFD, -130 probiotics)
    • Response to treatment was NOT able to be predicted using metagenomic microbiome sequencing
  • Commentary: This study (although small) shows the efficacy of both probiotics and a LFD for IBS. It also suggests that changes in the microbiota are not predictive of treatment success.

• Administration of dietary antioxidants for patients with inflammatory bowel disease: A systematic review and meta-analysis of randomized controlled clinical trials
  • 12 studies
  • In those w/ IBD, curcumin supplementation resulted in significant improvement of:
    • Clinical remission (large effect size, 0.86)
    • Endoscopic remission (medium effect size, 0.51)
    • Quality of life (large effect size 1.23)
  • Commentary: Curcumin is helpful in those w/ IBD.

• Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial
  • 171 kids (ages 3-10 yo) randomized to probiotic + Vit C (50 mg) or placebo
  • After 6 months of supplementation, the probiotic + Vit C group had:
    • Less coughing
    • Less severe upper respiratory tract symptoms
    • Fewer missed days of school
    • Less use of antibiotics
  • Commentary: Probiotics + Vit C may have beneficial effects on upper respiratory tract health in kids.

• Efficacy and safety of probiotics in the induction and maintenance of inflammatory bowel disease remission: a systematic review and meta-analysis
  • 20 RCTs, 777 IBD patients
  • Probiotics can induce remission in active UC
  • But had no effect on maintaining UC or CD remission

• Effectiveness of Crohn’s Disease Exclusion Diet for Induction of Remission in Crohn’s Disease Adult Patients
  • 32 Crohn’s Disease patients put on Crohn’s Disease Exclusion Diet (50% of calories) and elemental diet (50% of calories)
  • After 3 months:
    • Clinical remission in 82% of participants 
    • Lower calprotectin
  • Commentary: A CDED + partial elemental dieting has a very notable positive effect on those w/ Crohn’s Disease.

• Psychological Interventions for Irritable Bowel Syndrome: A Meta-Analysis of Iranian Randomized Trials
  • 20 RCTs
  • Psychological interventions (e.g. meditation, relaxation) had a large effect size at improving:
    • IBS symptom severity (effect size -1.2)
    • Anxiety (-0.97)
    • Depression (-0.86)
    • Quality of life (-0.64)
  • Commentary: Addressing limbic imbalances can be a very impactful line of therapy for improving IBS.

• Hypnotherapy for Irritable Bowel Syndrome-Type Symptoms in Patients with Quiescent Inflammatory Bowel Disease: A Randomized, Controlled Trial
  • 70 patients w/ IBD in remission and IBS, randomized to hypnotherapy or standard therapy
  • After 6 months, hypnotherapy was NOT superior to standard treatment
  • Commentary: Following more foundational GI therapies (e.g. low FODMAP, probiotics, elemental dieting) has more merit and evidence that a more exotic therapy such as hypnotherapy.

• Genetically predicted circulating B vitamins in relation to digestive system cancers
  • Mendelian randomization of 367,561 individuals
  • Genetically predicted higher serum B12 levels were associated with a higher rate of:
    • GI cancer (OR 1.12)
    • Colorectal cancer (OR 1.16)
  • No association w/ B6 or folate levels
  • Commentary: High B12 levels may be associated w/ GI malignancy.

• Effect of nonsteroidal anti-inflammatory drugs on Barrett’s esophagus risk: a systematic review and meta-analysis
  • 7 studies
  • NSAIDs could reduce Barrett’s esophagus risk (OR: 0.84)
  • Association was only seen for females (not males)
  • Commentary: NSAID use was associated with a lower risk of Barrett’s esophagus in women.

• Randomized Controlled Trial of Probiotic PS128 in Children with Tourette Syndrome
  • 58 children w/ Tourette syndrome, randomized to probiotics or placebo
  • After 2 months of supplementation:
    • No differences in tic severity
    • Probiotic group had better attention

• The effect of daily probiotics on the incidence and severity of necrotizing enterocolitis in infants with very low birth weight
  • Retrospective study of 665 infants w/ very low birth rate
  • Those who received probiotics had:
    • Similar rates of necrotizing enterocolitis
    • Similar rates of mortality and hospital stay
    • Reduced infection rate (27% vs 34%)
  • Commentary: Probiotics may reduce overall infection rates despite the null difference in necrotizing enterocolitis rates.

• Efficacy of Bifidobacterium animalis subsp. lactis, BB-12 ® on infant colic – a randomised, double-blinded, placebo-controlled study
  • 192 neonates w/ infant colic, randomized to probiotic or placebo
  • After 3 weeks of supplementation, the probiotic group had:
    • Greater reduction of crying/fussing
    • More sleep
    • Better quality of life for parents
  • Commentary: Probiotics can help alleviate infant colic.

• Evidence of Lactobacillus reuteri to reduce colic in breastfed babies: Systematic review and meta-analysis
  • 10 RCTs, 477 infants w/ colic
  • Probiotics led to significant reduction in crying

• Probiotics for preventing and treating infant regurgitation: A systematic review and meta-analysis
  • 6 RCTs
  • Probiotics led to reduction in regurgitation (-1.79 episodes/day)

• Effect of infant formula supplemented with prebiotics and probiotics on incidence of respiratory tract infections: A systematic review and meta-analysis of randomized clinical trials
  • 15 RCTs, 3,805 participants
  • Probiotic supplemented formula had a protective effect against respiratory tract infections (RR 0.89)
  • Commentary: According to the last 5 studies, probiotics can help with infant colic, regurgitation, general infection rate, and respiratory tract infections.

Autoimmunity Studies

• Associations of Yersinia Enterocolitica Infection with Autoimmune Thyroid Diseases: A Systematic Review and Meta-Analysis
  • 8 studies, 1,490 participants
  • Yersinia enterocolitica infection is associated with a higher risk of autoimmune thyroid disease (OR 4.3)
    • Graves’ disease (OR 6.1)
    • Hashimoto’s (OR 2.8)
  • Commentary: This highlights the gut-thyroid connection.

• Efficacy of Whole-Body Vibration Training on Brain-Derived Neurotrophic Factor, Clinical and Functional Outcomes, and Quality of Life in Women with Fibromyalgia Syndrome: A Randomized Controlled Trial
  • 32 women w/ fibromyalgia, randomized to whole-body vibration training (WBVT) or no treatment
  • After 6 weeks, the WBVT group had:
    • Improved symptoms
    • Increased blood BDNF levels
    • Less depressive symptoms
    • Better quality of life

• The effect of Helicobacter pylori seropositivity and activity on disease outcome in patients with rheumatoid arthritis, systemic lupus erythematosus and ankylosing spondylitis
  • Cross-sectional study of 100 patients w/ autoimmunity, 50 healthy controls
  • A positive H. pylori stool antigen test was found at a higher rate in those w/ autoimmunity compared to controls
    • 30% for lupus
    • 70% rheumatoid arthritis
    • 20% ankylosing spondylitis
    • 10% healthy controls
  • Patients with active lupus and rheumatoid arthritis had a higher rate of positive H. pylori stool tests than patients in remission (66.7% lupus, 83.3% RA)
  • Commentary: H. pylori was found at higher rates in those w/ autoimmunity and is associated w/ severity of disease activity.

Thyroid & Hormones Studies

• Effect of an ashwagandha (Withania Somnifera) root extract on climacteric symptoms in women during perimenopause: A randomized, double-blind, placebo-controlled study
  • 91 perimenopausal women, randomized to placebo or ashwagandha (300 mg BID)
  • The ashwagandha group had:
    • Less menopausal symptoms
    • Increased estradiol levels
  • Commentary: Ashwaghanda is a promising therapy for menopausal women.

• Metabolic syndrome is associated with prostate enlargement: a systematic review, meta-analysis, and meta-regression on patients with lower urinary tract symptom factors
  • 70 studies, 90,206 participants
  • Metabolic syndrome was associated with:
    • Higher severity of nocturia 
    • More overactive bladder symptoms
    • Greater prostate volume
  • Commentary: Metabolic syndrome may contribute to health concerns related to the prostate.

• Iron Deficiency, a Risk Factor of Thyroid Disorders in Reproductive-Age and Pregnant Women: A Systematic Review and Meta-Analysis
  • 8 studies
  • Iron deficiency increased the risk of:
    • Positive TPO Ab (OR 1.89)
  • In pregnant women, iron deficiency increased the risk of:
    • Overt hypothyroidism (OR 1.6)
    • Subclinical hypothyroidism (OR 1.37)
  • Commentary: Iron deficiency (i.e. low ferritin) may be an important risk factor for thyroid dysfunction. That is why we address this along with gut health in our thyroid algorithm.

Diet & Lifestyle Studies

• Targeting dyslipidemia with antioxidative vitamins C, D, and E; a systematic review of meta-analysis studies: Dyslipidemia and antioxidative vitamins
  • Review of 25 meta-analysis, 32,177 participants 
  • Vitamin D
    • 400 IU/day to 50,000 IU/week for at least 8 weeks improved total cholesterol, LDL-C, and triglycerides
  • Vitamin C
    • 500-2,000 mg/d for at least 3 weeks improved LDL-C and triglycerides
  • Vitamin E
    • No effect
  • Combo of omega-3s (400-1,800 mg/d) and Vit E (400 IU/d)
    • Reduced LDL-C and triglycerides
  • Commentary: This very large review of other meta-analysis gives some support for common antioxidants to improve lipids. Unfortunately, the effect size was unavailable.

• Effect of omega-3 and vitamin D co-supplementation on psychological distress in reproductive-aged women with pre-diabetes and hypovitaminosis D: A randomized controlled trial
  • 168 women w/ low Vit D and pre-diabetes, randomized to 4 groups:
    • Placebo
    • Omega-3 (1 g/d)
    • Vit D (50,000 IU every 2 weeks)
    • Omega-3 + Vit D
  • After 8 weeks of supplementation, the omega-3 + Vit D group had:
    • Improved anxiety
    • Improved depression
    • Improved sleep quality
  • Commentary: Omega-3 + Vit D supplementation improved depression, anxiety, and sleep in those w/ low baseline Vit D.

• Effect of a Mindfulness-Based Intervention for Chronic Migraine and High Frequency Episodic Migraine in Adolescents: A Pilot Single-Arm Open-Label Study
  • Open-label study of 35 migraine patients given group mindfulness and meditation recommendations
  • At 12 month follow up, patients had:
    • Less frequent headaches (21.3 to 9.6 days/month)
    • Less need for medication
    • Less anxiety/depression
  • Commentary: Mindfulness/meditation practices are an effective way to alleviate migraine symptoms.

• Effect of Curcumin on Diabetic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Clinical Trials
  • 5 RCTs, 290 participants diabetic kidney disease
  • Curcumin supplementation associated with:
    • Lower creatinine (-0.16 mg/dL)
    • Lower total cholesterol (-10.1 mg/dL)
    • Lower systolic blood pressure (-3.9 mmHg)
    • Lower fasting glucose (-8.3 mg/dL)
  • Commentary: Curcumin has beneficial effects on kidney function and metabolic markers.

• Comparing the Efficacy and Safety of Low-Carbohydrate Diets with Low-Fat Diets for Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
  • 12 RCTs, 761 participants comparing low carb diets (LCD) and low fat diets (LFD)
  • Compared w/ LFDs, LCDs had better:
    • Reduction in A1C (-0.35%)
    • Reduced weight (-3 kg)
    • Reduced triglycerides (-17 mg/dL)
    • No difference in total cholesterol or LDL-C
  • These differences lasted x1.5-2 years (except weight loss)

Podcast Summary

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Featured Study

• Transient high thyroid stimulating hormone and hypothyroidism incidence during follow up of subclinical hypothyroidism
  • 431 healthy control participants, 225 patients with subclinical hypothyroidism (SCH) 
  • No treatment was given to either groups
  • At a 6 month followup:
    • 12.2% developed frank hypothyroidism
    • 13.4% stayed SCH
    • 73.8% became euthyroid
  • TPO antibodies and a TSH above 6.9 mIU/L was associated with a higher risk of developing overt hypothyroidism.
  • Commentary: The vast majority of those who were SCH became euthyroid WITHOUT treatment. This is an elegant study showing us that many times SCH will correct on its own. Also addressing gut health will most likely improve the rate of those who become euthyroid. There is no need to rush treating SCH in the majority of cases. Dr Ruscio and I encourage you to read the featured study from the FFMR+ two episodes ago which lays out a concise set of recommendations of which SCH patients to treat.

Gastrointestinal Studies

• Gut microbiome composition is predictive of incident type 2 diabetes
  • Stool samples from 5,572 participants, followed x15 years
  • Microbiome changes were predictive of type 2 diabetes onset
  • Commentary: One of the first long-term prospective studies suggesting a causal link between the microbiome and type 2 diabetes.

• Effects of a low-FODMAP enteral formula on diarrhea on patients in the intensive care unit
  • 66 patients in ICU, randomized to high or low FODMAP enteral diet
  • After 7 days, the low FODMAP group had less diarrhea (3% vs 21%)

• Outcomes of Fecal Microbiota Transplantation for C. difficile Infection in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
  • 457 IBD patients who received at least one FMT
  • FMT had a cure rate of 78% for treating C. diff infection (CDI)
  • Commentary: This meta-analysis suggested a high cure rate of FMT for treating recurrent CDI in those w/ IBD.

• Saccharomyces boulardii Combined With Quadruple Therapy for Helicobacter pylori Eradication Decreased the Duration and Severity of Diarrhea: A Multi-Center Prospective Randomized Controlled Trial
  • 360 H. pylori + participants randomized to:
    • Quadruple therapy alone
    • Or quadruple therapy + S. boulardii
  • After 2 weeks, the quadruple therapy + S. boulardii group had:
    • Reduced side effects (27.8% vs 38.5%)
    • Reduced diarrhea (11% vs 21%)
    • NO difference in eradication rate (82.7% vs 95.8%)
  • Commentary: Despite null differences in eradication rate, S. boulardii was shown to significantly decrease antibiotic-related symptoms.

• Impact of Bile Acid Diarrhea in Patients with Diarrhea-Predominant Irritable Bowel Syndrome on Symptoms and Quality of Life
  • Cross-sectional study of 219 IBS-D patients
  • 20% had bile acid diarrhea (BAD)
  • Compared to those without BAD, those w/ BAD had:
    • Worse quality of life
    • More severe diarrhea and symptoms
    • More likely to have depression
  • Commentary: IBS-D caused by BAD indicates worse symptom severity and quality of life.

• Obesity Exacerbates Irritable Bowel Syndrome-Related Sleep and Psychiatric Disorders in Women With Polycystic Ovary Syndrome
  • Cross-sectional study of 431 women with PCOS and 259 healthy controls
  • Compared to healthy controls, women with PCOS were more likely to have: 
    • IBS (10.7% vs 5.8%) 
    • Obesity (29% vs 4%) 
  • Compared to those without IBS, women with PCOS and IBS were more likely to have:
    • Sleep difficulties (67.4% vs 30.9%) 
    • Psychiatric symptoms (21.7% vs 10.1%) 
  • Commentary: Two notes here:
    • 1) PCOS may be an associated condition of IBS
    • 2) IBS is associated with sleep and mood imbalances

• Associations with pancreatic exocrine insufficiency: An United Kingdom single-centre study
  • Retrospective study of 1,027 participants, 182 with exocrine pancreatic insufficiency (EPI)
  • Symptoms that predicted EPI
    • Steatorrhea (OR 2.51)
    • Weight loss (OR 1.5)
  • Associated risk factors:
    • Chronic pancreatitis (OR 8)
    • Pancreatic cancer (OR 6.6)
    • Upper GI surgery (OR 2.6)
    • Type 2 diabetes (OR 1.84)
    • PPI use (OR 1.9)
  • Commentary: This study showed hallmark symptoms and risk factors associated w/ EPI. Keep these in mind when seeing patients.

• Helicobacter pylori infection is associated with reduced risk of Barrett’s esophagus: a meta-analysis and systematic review
  • 46 studies
  • H. pylori was associated with a LOWER risk of Barrett’s esophagus (OR 0.7)
  • Especially if the CagA gene was present (OR 0.3)
  • NO association between H. pylori and GERD
  • Commentary: Contrary to current thinking, H. pylori was associated with a LOWER risk of Barrett’s esophagus.

Thyroid & Hormones Studies

• Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis
  • 8 studies, 196 participants
  • Diversity and abundance of certain gut microbiota were changed in patients with autoimmune thyroid disease (AITD) compared to controls
    • E.g. Bifidobacterium and Lactobacillus decreased in the AITD group
  • Commentary: A high-quality study pointing to the gut-thyroid connection.

• Is Hashimoto thyroiditis associated with increasing risk of thyroid malignancies? A systematic review and meta-analysis
  • 50 studies
  • Hashimoto’s was associated with a higher risk of:
    • Papillary thyroid cancer (OR 1.65)
    • Medullary thyroid cancer (OR 2.7)
    • Lymphoma (OR 12.9)
    • Thyroid malignancy (OR 1.36)
  • NO association w/ anaplastic thyroid cancer
  • NO association with follicular thyroid cancer
  • Commentary: With a high level of heterogeneity, this study suggested an association between Hashimoto’s and some (but not all) thyroid cancers, perhaps driven by immune system disruption.

• Effects of vitamin D on thyroid autoimmunity markers in Hashimoto’s thyroiditis: systematic review and meta-analysis
  • 8 RCTs, 652 participants
  • Vitamin D supplementation associated with:
    • Reduced TPO antibodies (effect size -1.1)
    • Reduced Tg antibodies (effect size -1.1)
  • Treatment needs to be at least 3 months to see notable effect
  • Commentary: This high-quality study showed a large beneficial effect of vitamin D reducing thyroid autoantibodies.

• The Influence of Treated and Untreated Subclinical Hypothyroidism on Metabolic Profile in Women with Polycystic Ovary Syndrome
  • Cross-sectional study of 190 women w/ PCOS divided into 3 groups
    • 38 women with PCOS and subclinical hypothyroidism (SCH)
    • 76 women with PCOS and SCH w/ thyroid replacement therapy
    • 76 women with PCOS and normal thyroid function 
  • Measured metabolic markers
  • NO statistical difference of metabolic health between groups
  • BMI was the main determinant of metabolic outcomes
  • Commentary: In a group of women at risk for metabolic dysfunction (PCOS), those who treated their SCH did not have better metabolic outcomes.

• Reduced Plasma Estradiol Levels are Associated with Sleep Apnea in Depressed Peri- and Post-Menopausal Women
  • Retrospective study of 84 peri- and post-menopausal women diagnosed w/ depression
  • 45% had obstructive sleep apnea (OSA) on an in-lab sleep test
  • Lower estradiol levels were associated with a higher risk of OSA (OR 0.86)
  • Commentary: This study suggests that the drop in estrogen levels around menopause is associated w/ OSA.

Diet & Lifestyle Studies

• Sarcopenia Is Associated With a Risk of Mortality in People With Type 2 Diabetes Mellitus
  • 396 older individuals (mean 71 years) with type 2 diabetes, followed x3.5 years
  • 14.6% had sarcopenia
  • Sarcopenia was associated with all-cause mortality (HR 6.1)

• The effect of long chain omega-3 polyunsaturated fatty acids on muscle mass and function in sarcopenia: A scoping systematic review and meta-analysis
  • 123 studies
  • Omega-3 fatty acids associated with:
    • Higher lean body mass
    • Higher muscle mass
    • Higher muscle strength
  • Commentary: This study suggests a beneficial effect of omega-3 fatty acids on muscle quality.

• Neuroadrenergic activation in obstructive sleep apnoea syndrome: a new selected meta-analysis – revisited
  • 14 studies
  • Sympathetic nervous system activity is directly related to the apnea-hypopnea index (AHI)
  • Commentary: This study suggests an association between SNS activity and sleep apnea severity.

• Effect of β-alanine and sodium bicarbonate co-supplementation on the body’s buffering capacity and sports performance: A systematic review
  • 9 studies, 221 athletes
  • 5 of the 9 studies showed that co-supplementation w/ sodium bicarbonate and beta-alanine was superior at improving performance as compared to just one in isolation

• Effects of Pre-, Post- and Intra-Exercise Hyperbaric Oxygen Therapy on Performance and Recovery: A Systematic Review and Meta-Analysis
  • 10 studies, 166 participants
  • Hyperbaric oxygen therapy before or after exercise had no significant effect on performance and recovery

• Vitamin D is directly associated with favorable glycemic, lipid, and inflammatory profiles in individuals with at least one component of metabolic syndrome irrespective of total adiposity: Pró-Saúde Study, Brazil
  • Cross-sectional study of 511 participants
  • 56% had vitamin D deficiency (<20 ng/mL)
  • Lower vitamin D levels was associated with:
    • Higher visceral fat
    • Higher insulin and insulin resistance
    • Higher TNF-α
  • Commentary: Inflammation and adiposity is associated w/ lower vitamin D levels.