Featured Study

• Nasal-spraying Bacillus spores as an effective symptomatic treatment for children with acute respiratory syncytial virus infection
  • 86 children (4 months to 5 years old) hospitalized with RSV infection, randomized to:
    • Placebo nasal spray (saline) 
    • Bacillus probiotic nasal spray 
  • After 6 days of treatment, probiotic nasal spray led to quicker resolution of:
    • Runny nose (4 days probiotics vs 5 days placebo) 
    • Difficulty breathing (2 days vs 3 days) 
    • Chest depression (2 days vs 3 days) 
    • Abnormal lung sounds (4 days vs 5 days) 
  • Probiotic nasal spray also led to: 
    • Reduced RSV nasopharyngeal load by 630x
    • Greater clearance of nasal co-infections like strep pneumoniae and haemophilus influenzae (90% probiotic vs 30% placebo) 
  • Commentary: RSV, an infection in young children, was improved with a spore-based probiotic nasal spray.

Gastrointestinal Studies

• Small Intestinal Bacterial Overgrowth In Various Functional Gastrointestinal Disorders: A Case-Control Study
  • 186 patients with functional GI disorders (FGIDs), 58 healthy controls (HC)
  • All were tested with glucose breath test
  • Compared to HC, SIBO prevalence was: 
    • Greater in IBS-D (24% vs 10% HC) 
    • Similar in functional dyspepsia (14% vs 10% HC)
    • Similar in overall IBS (18% vs 10% HC) 
    • Similar in functional constipation (17% vs 10% HC) 
  • IBS-D was associated with:
    • 2.8x increased risk of SIBO
    • Greater prevalence of elevated H2 (≥20 ppm) gas (18% vs 3% HC)  
  • Chronic constipation patients had  NO difference in methane-positive SIBO compared to healthy controls(9% vs 7%) 
  • Commentary: While SIBO was more prevalent in patients with IBS-D, there was no significant difference in SIBO prevalence when comparing various functional GI disorders and healthy controls.

• Prevalence of Gastrointestinal Symptoms and Irritable Bowel Syndrome Among Individuals With Symptomatic Posttraumatic Stress Disorder
  • 184 patients with PTSD, all assessed for presence of gastrointestinal symptoms
  • 25% were diagnosed with IBS 
  • Most common GI symptoms in those with PTSD include: 
    • Abdominal pain (36%) 
    • Diarrhea (21%)
    • Constipation (18%) 
    • Bloating (17%) 
  • Higher PTSD severity was associated with worse: 
    • Constipation
    • Diarrhea
    • Gas/bloating 
  • Commentary: This study found an association between severity of PTSD and worse GI symptoms. This highlights the gut-brain connection and the effect of trauma on gut symptoms.

• The effect of Bacillus coagulans Unique IS-2 supplementation on plasma amino acid levels and muscle strength in resistance trained males consuming whey protein: a double-blind, placebo-controlled study
  • Healthy controls, randomized to: 
    • Whey protein + placebo
    • Whey protein + Bacillus coagulans 
  • After 2 months, whey +  probiotics led to increased: 
    • Blood amino acids (+16%) 
    • Blood branched-chain amino acid (+33%) 
    • 1-rep max leg press (+17%)  
    • Vertical jump power (+8%) 
  • Commentary: The addition of soil-based probiotics to whey protein led to improved amino acid absorption as well as improved athletic performance.

• Factors Associated with Circulating Zonulin in Inflammatory Bowel Disease
  • 117 IBD patients, 32 healthy controls (HC) 
    • 58% of IBD patients were in remission 
  • There was NO difference in serum zonulin between:
    • IBD patients and healthy controls (95 vs 97 ng/ml) 
    • UC vs CD patients (80 vs 106 ng/ml) 
  • Zonulin did correlate with disease severity in those with UC, but NOT in CD. 
  • Commentary: This study did NOT find a significant difference in zonulin levels in those with IBD compared to healthy controls. However, it’s important to keep in mind that more than half of IBD p
  • Patients were in remission.

• Improvement Effect of Bifidobacterium animalis subsp. lactis MH-02 in Patients Receiving Resection of Colorectal Polyps: A Randomized, Double-Blind, Placebo-Controlled Trial
  • 100 patients undergoing colorectal polyp removal, randomized to one of the following postoperatively:
    • Placebo
    • Probiotics (bifidobacterium) 
  • After 7 days of treatment after surgery, the probiotic group led to:
    • Fewer people with defecation difficulty (8% probiotic vs 23% placebo) 
    • Fewer people requiring laxatives (2% vs 15%) 
    • Shorter time to first bowel movement (2.9 vs 3.6 days) 
    • NO improvement postoperative abdominal pain or bloating
  • Commentary: Probiotics led to improved recovery of bowel function after colorectal surgery.

• Relationship between untreated obstructive sleep apnea and breath hydrogen and methane after glucose load
  • 52 patients with sleep apnea, all tested with a SIBO glucose breath test
  • Compared to healthy controls, patients with sleep apnea had: 
    • NO significant difference in SIBO positivity (31% vs 13% healthy control) 
    • Higher levels of hydrogen (26 ppm vs 6 ppm) 
    • Higher levels of methane (16 ppm vs 6 ppm) 
    • Increased flatulence
  • Commentary: While there was no overall difference in SIBO positivity between groups, those with sleep apnea had worse GI symptoms and higher levels of gas production.

• Comparing probiotic and drug interventions in irritable bowel syndrome: a meta-analysis of randomised controlled trials
  • 32 RCTs on patients with IBS, randomized to:
    • Placebo vs probiotics (e.g. lacto/bifido, saccharomyces boulardii) 
    • Placebo vs medications (e.g.mesalazine, linaclotide, ramosetron, plecanatide, eluxadoline, rifaximin) 
  • Compared to placebo, both medications and probiotics led to:
    • Reduced persistence of IBS symptoms (32% probiotic vs 13% medication) 
    • Improved abdominal pain (small effect size for both) 
  • Only medications led to statistically significant improvements in bloating
  • Commentary: While probiotics led to greater reduction in persistence of IBS symptoms, medications were overall more effective for improving bloating.

• Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • 65 RCTs, 8,483 critically-ill patients 
  • Probiotics led to:
    • 28% reduced risk of ventilator associated pneumonia 
    • 30% reduced risk of health-care associated pneumonia
    • Shorter ICU stay (-1.4 days) 
    • Shorter hospital stay (-2.2 days) 
    • Shorter duration of mechanical ventilation (-2.5 days) 
    • NO impact on mortality 
  • However, when the study eliminated the studies that had a high risk of bias, these benefits were negated
  • Commentary: This large study found probiotics may lead to better health outcomes in critically-ill patients. Because they are very safe and may have significant benefits, it is likely worthwhile for critically-ill patients to take them.

• Positive Association Between Sleep Disturbance and Prevalence of Functional Dyspepsia in Japanese Young People
  • 8,923 young participants
  • Sleep disturbances were associated with an overall 4x increased risk of functional dyspepsia, including:
    • Difficulty falling asleep (3.9x increased risk) 
    • Night-time awakenings (4.3x increased risk) 
    • Early awakenings (4.5x increased risk) 
    • Deep sleep disorders (4.8x increased risk) 
  • Commentary: This study highlights the gut-sleep connection. 

• Effects of probiotic supplementation on glucose metabolism in pregnant women without diabetes: a systematic review and meta-analysis
  • 12 RCTs, 2,213 pregnant women without diabetes
  • Probiotics led to: 
    • 38% lower risk of developing gestational diabetes
    • Lower fasting glucose (-2.5 mg/dl) 
    • Lower insulin (-0.3 uIU/ml) 
    • Lower insulin resistance (HOMA-IR) (-0.3 mmol/L) 
    • NO change in oral glucose tolerance test
  • Commentary: Despite minimal changes in overall glucose and insulin resistance, probiotics still led to a reduced risk of developing gestational diabetes.

• Efficacy of multi-strain probiotic along with dietary and lifestyle modifications on polycystic ovary syndrome: a randomised, double-blind placebo-controlled study
  • 104 PCOS patients, all treated with dietary and exercise modifications, randomized to:
    • Placebo 
    • Synbiotics (lacto/bifido + FOS) 
  • After 6 months, the addition of synbiotics to lifestyle treatment led to: 
    • Increased # participants with menstrual regularity (31% synbiotic vs 12% placebo) 
    • Reduced total testosterone (-9 vs -8 ng/dl)  
    • Improved waist circumference (-4 vs -2 cm) 
    • Better quality of life
  • Commentary: A combination of lacto/bifido probiotics and prebiotics led to additional benefits to diet and exercise for patients with PCOS, highlighting the gut-hormone connection. The most notable benefit was in menstrual regularity.

Thyroid & Hormones Studies

• Suboptimal Thyroid Hormone Replacement Is Associated With Worse Hospital Outcomes
  • 34,605 healthy controls, 8,873 patients with hypothyroidism, categorized by pre-hospitalization TSH status:
    • Low (<0.40 mIU/L) 
    • Normal (0.40-4.5 mIU/L) 
    • Subclinical (4.51-10 mIU/L) 
    • High (>10 mIU/L) 
  • All patients admitted to hospital for various reasons
  • Compared to those with a normal TSH pre-hospitalization, those with a high TSH experienced: 
    • Longer hospital stay (+1.2 days)
    • Higher likelihood of readmission 1 month later (49% vs -54%) 
    • Higher likelihood of readmission 3 months later (43% vs -8%) 
  • Commentary: Higher TSH levels were associated with worse outcomes if one was hospitalized.

• Commercially Available Home Pelvic Training Devices for the Treatment of Pelvic Floor Disorders: A Systematic Review and Meta-analysis
  • 15 studies on patients with pelvic floor disorders
  • Home pelvic muscle training devices led to improvements in: 
    • Number of incontinence episodes (-1.3/day) 
    • Urogenital distress scores (-25 points) 
    • Incontinence scores (-14 points) 
    • Quality of life (+17 points) 
  • Commentary: Home pelvic floor training devices may be an effective option for patients with pelvic floor disorders. Keep in mind this study did not compare the efficacy of home devices versus seeing a physical therapist.

Diet & Lifestyle Studies

• Comorbid insomnia and sleep apnoea is associated with all-cause mortality
  • 5,236 participants, categorized by: 
    • Healthy controls (52%) 
    • Insomnia (3%) 
    • Sleep apnea (42%) 
    • Sleep apnea + insomnia (3%) 
  • Compared to healthy controls, patients with both sleep apnea and insomnia experienced: 
    • 2x increased risk of hypertension
    • 1.7x increased risk of cardiovascular disease
    • 47% increased risk of mortality 
  • Compared to healthy controls, those with just sleep apnea or insomnia had an increased risk of hypertension (but NOT cardiovascular disease)
  • Commentary: The presence of insomnia and sleep apnea may lead to worse cardiovascular outcomes and increased risk of overall mortality.

Featured Study

• Metagenomic Changes of Gut Microbiota following Treatment of Helicobacter pylori Infection with a Simplified Low-Dose Quadruple Therapy with Bismuth or Lactobacillus reuteri
  • 46 patients with H. pylori infection (+ urea breath test), randomized to
    • Bismuth + triple therapy (PPI, metronidazole and tetracycline)
    • Lactobacillus reuteri + triple therapy 
  • After 1 month, compared to the bismuth group, the probiotic group experienced:
    • Identical eradication rates between groups (18/23 vs 18/23)  
    • NO significant difference in side effects (9.5% probiotic vs 26% bismuth) 
    • NO significant difference in GI symptom improvement (68% vs 53%) 
    • Fewer dropouts (2 vs 4) 
    • NO difference in dysbiosis post antibiotics 
  • After accounting for those that dropped out of the study, the bismuth group ended up being more effective in eradicating H. pylori (18/19 vs 18/21)  
  • Commentary: This study found overall that the addition of bismuth vs probiotics was more effective for eradicating H. pylori. It’s important to note that the amount of patients that dropped out of the study in the bismuth group led to a higher overall eradication rate. When those people are included in the study, the eradication rates are equal in both groups. 

• Saccharomyces boulardii Allows Partial Patients to Avoid Reusing Bismuth Quadruple for Helicobacter pylori Rescue Therapy: A Single-Center Randomized Controlled Study
  • 100 patients with H. pylori infections, randomized to: 
    • S. boulardii monotherapy (20 billion CFU/day) x 2 weeks
    • Control (no treatment) 
  • After 6 weeks, all patients were retested for H. pylori (urea breath test) 
  • Compared to control, S. boulardii monotherapy led to higher eradication of H. pylori (14 negative probiotic vs 1 negative control) 

Commentary: S. boulardii monotherapy led to a 30% eradication in H. pylori infection. This highlights the ability of probiotics to act as antimicrobials.

Gastrointestinal Studies

• Safety of Bifidobacterium breve, Bif195, employing a human exercise-induced intestinal permeability model: a randomised, double-blinded, placebo-controlled, parallel group trial
  • 126 healthy controls, randomized to: 
    • Placebo
    • Probiotic (Bifidobacterium breve 50 billion CFU)
  • All participants assessed for increased intestinal permeability via lactulose/rhamnose pre and post 1 hour treadmill run at week 1, 3 and 5
  • After 6 weeks of treatment, there was NO difference in intestinal permeability between groups
  • Commentary: Probiotics did NOT lead to reduced intestinal permeability as determined by lactulose/rhamnose tests.

• Efficacy of a Restrictive Diet in Irritable Bowel Syndrome: A Systematic Review and Network Meta-analysis
  • 14 RCTs on patients with IBS
  • Compared to usual diet, the following diets were more effective for improving IBS: 
    • Low FODMAP
    • Low starch and sucrose
    • Gluten free 
  • Commentary: Dietary interventions are effective for improving IBS.

• A meta-analysis on randomized controlled trials of treating eosinophilic esophagitis with budesonide
  • 10 studies, 712 patients with eosinophilic esophagitis (EoE), randomized to:
    • Placebo
    • Oral Budesonide 
  • Compared to placebo, oral budesonide led to:
    • 23x higher histological remission
    • Reduced eosinophil count (large effect size) 
    • Improved dysphagia and swallowing symptoms (large effect size)  
    • 3.8x increased side effects (oral candida, nausea, dizziness) 
  • Commentary: Budesonide is an effective treatment for patients with EoE, however the benefits need to be balanced with the increased side effect profile.

• Probiotics Improve Postoperative Adaptive Immunity in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis
  • 6 RCTs, 492 postoperative colorectal cancer patients
  • Probiotics led to improvements in immune function, including increased:
    • IgG (large effect size) 
    • CD4+ T-cells (large effect size)
    • IgA (small effect size) 
    • IgM (small effect size) 
  • Commentary: Probiotics have immune-enhancing effects.

• The effects of synbiotics on indoxyl sulphate level, constipation, and quality of life associated with constipation in chronic haemodialysis patients: a randomized controlled trial
  • 60 patients with chronic kidney disease and constipation, randomized to: 
    • Placebo
    • Synbiotics (lacto/bifido + FOS) 
  • After 2 months, compared to placebo, synbiotics led to: 
    • Improved constipation symptom scores (-7 synbiotic vs -0.5 placebo) 
    • Improved constipation quality of life scores (-7 vs -2) 
  • Commentary: Synbiotics led to improvements in constipation. 

• Probiotics/Synbiotics to Reduce Infectious Complications after Colorectal Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials
  • 21 studies on perioperative colorectal surgical patients, randomized to: 
    • Placebo
    • Synbiotics (lacto/bifido, streptococcus, inulin, FOS, GOS)
    • Probiotics (lacto/bifido, enterococcus, streptococcus, S. boulardii)
  • Probiotics and synbiotics led to: 
    • 41% reduced risk of infectious complications
    • 30% fewer surgical site infections
    • 65% reduced pulmonary infections
    • 59% reduced urinary infections 
  • Overall, there was NO difference between synbiotics or probiotics in reducing postoperative infections (-45% probiotic vs -31% synbiotic)
  • Commentary: This is another large study showing probiotics and synbiotics are effective in reducing infection risk after surgery.

Thyroid & Hormones Studies

• The effect of probiotics on mood and sleep quality in postmenopausal women: A triple-blind randomized controlled trial
  • 66 postmenopausal women randomized to: 
    • Yogurt (control) 
    • Yogurt + probiotics 
  • After 6 weeks, the probiotic group experienced:
    • Less anxiety (moderate effect size) 
    • Reduced stress (moderate effect size) 
    • Improved quality of life (large effect size)
    • NO improvement in sleep or depression
  • Commentary: Probiotics may improve some postmenopausal symptoms, including mood and overall menopause quality of life.

• Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials
  • 2 RCTs, 660 older adults (≥65 years old) with SCH and categorized by TPO antibody positivity (≥34):
    • 29% +TPO-ab (average 170)
    • 71% -TPO-ab
  • All patients were randomized to either placebo or LT4
  • After 1 year, compared to placebo, LT4 led to: 
    • NO improvement in hypothyroid symptom scores (-2 +TPO vs +0.9 -TPO) 
    • NO improvement in fatigue scores (1.7 +TPO vs 1.1 -TPO) 
  • Commentary: This study found older adults with SCH do not gain additional benefits from LT4 based on their TPO antibody status. Also important to note, LT4 did NOT lead to better improvements in hypothyroid symptoms compared to placebo.
• Comparison of reproductive outcomes in subclinical hypothyroidism women with high-normal vs. low-normal thyroid-stimulation hormone levels after treatment with levothyroxine
  • 548 women with SCH on LT4 (euthyroid on LT4), all categorized by TSH status:  
    • Low-normal TSH (0.27-2.5 mIU/L)
    • High-normal TSH (2.5-4.2 mIU/L)
  • All women were attempting to get pregnant via IVF
  • Compared to those with low-normal TSH, those with high-normal TSH experienced NO difference in: 
    • Pregnancy rate
    • Miscarriage rate
    • Live birth rate
  • Commentary: This study found that as long as TSH is within the normal range, there were NO differences in pregnancy outcomes.  However, other research has shown that a TSH <2.5 during the first trimester is important once a woman becomes pregnant.

Diet & Lifestyle Studies

• inflammation, muscle strength, and joint flexibility: A systematic review and dose-response meta-analysis of randomized controlled trials
  • 10 RCTs
  • Curcumin supplementation led to:
    • Reduced delayed onset muscle soreness (moderate effect size) 
    • Reduced creatine kinase (-66 IU/L) 
    • Reduced TNF-α (small effect size)
    • Improved maximal volume contraction (muscle strength) 
    • Improved joint flexibility
  • This study found that duration of supplementation was more important than the dose used
  • Commentary: Curcumin may lead to improved muscle strength and reduced muscle soreness/damage.

• Effect of standardized root extract of ashwagandha ( Withania somnifera) on well-being and sexual performance in adult males: A randomized controlled trial
  • 50 males with low libido were randomized to:
    • Placebo 
    • Ashwagandha extract (600 mg/day) 
  • After 2 months, compared to placebo, men taking ashwagandha experienced: 
    • Increased total testosterone (+60 vs +20 ng/dl)
    • Improved libido scores (+25 vs +13 points) 
  • Commentary: Ashwaghanda led to significant improvement in both libido and total testosterone levels.

• Effects of a palaeolithic diet on obstructive sleep apnoea occurring in females who are overweight after menopause-a randomised controlled trial
  • 70 postmenopausal females with mild sleep apnea, randomized to: 
    • Control low fat diet
    • Paleo diet 
  • After 2 years, compared to control diet, the paleo diet led to:
    • Greater weight loss (16 vs 9 lbs) 
    • Reduction in sleep apnea severity 
    • NO change in sleepiness 
  • Reduced sleep apnea severity correlated with weight loss only in the paleo diet group, NOT the control group
  • Commentary: Paleo diet led to greater reductions in both weight loss and sleep apnea severity.

• Incidence and risk of periodontitis in obstructive sleep apnea: A meta-analysis
  • 9 studies, 43,414 participants
  • Sleep apnea was associated with a 1.5x increased risk of periodontitis
  • Commentary: Sleep apnea may be a risk factor for the development of periodontitis. In those with periodontitis, consider sleep apnea as a differential diagnosis.

• Inositol Nutritional Supplementation for the Prevention of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • 7 RCTs, 1,321 pregnant women, randomized t0: 
    • Control
    • Myo-inositol (MI) (4 g/day) 
  • Compared to control, MI led to:
    • 70% reduction in incidence of gestational diabetes
    • Improved glucose tolerance (large effect size) 
    • Reduced risk of preterm delivery
  • Lower doses of MI, such as 1.1 g/day + 27 mg D-chiro-inositol did NOT lead to any improvements compared to control
  • Commentary: 4 g/day of MI was safe and effective for improving blood sugar control and pregnancy outcomes. 

• Resistance Training and Mortality Risk: A Systematic Review and Meta-Analysis
  • 10 studies
  • Resistance training led to reductions in: 
    • All cause mortality by 15%
    • Cardiovascular disease by 19% 
    • Cancer mortality by 14%
  • 1-hour of resistance training per week led to a 27% reduction in all-cause mortality
  • Commentary: This study found that about 10 minutes per day of resistance training can provide health benefits.

Featured Study

• Effect of Levothyroxine on Older Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis
  • 13 studies, 5,000 older adults (≥60 years old) with subclinical hypothyroidism (SCH), randomized to:
    • Control (placebo, no intervention)
    • Levothyroxine (LT4)
  • Average follow up was about 16 months (6-60 months) 
  • Treatment with LT4 led to NO improvements in: 
    • Fatigue
    • Quality of life
    • Weight loss
    • Cognitive function
    • Depression
    • HDL-C or Apo-A
    • Fasting blood glucose 
    • Blood pressure
    • Bone mass 
  • LT4 did have a positive effect on: 
    • Total cholesterol (large effect size) 
    • Triglycerides (small effect size) 
    • LDL-C (moderate effect size) 
    • Apo-B (small effect size) 
  • LT4 did NOT lead to any adverse events, including: 
    • Cardiovascular events
    • All-cause death 
    • Atrial fibrillation
    • Heart failure 
    • Fracture 
  • Commentary: This large and long-term study found LT4 treatment in older adults with SCH led to 1) NO improvement in numerous hypothyroid symptoms, 2) NO adverse events and 3) improvement in lipids.

Gastrointestinal Studies

• Association between menstrual pain and functional dyspepsia in a Japanese young population
  • 4,693 female participants
  • Menstrual pain was associated with: 
    • 3x increased risk of functional dyspepsia 
    • 2.9x increased risk of postprandial distress syndrome 
  • Commentary: This study highlights the connection between the gut and menstrual symptoms.

• An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis
  • 16 studies on patients with ulcerative colitis
  • Compared to placebo, fecal microbiota transplantation led to:
    • 2.7x increased rate of complete remission (clinical and endoscopic remission)
    • 3.6x increased rate of steroid-free remission (remission without the use of steroids) 
    • NO difference in adverse events`
  • Commentary: FMT is an effective treatment for patients with ulcerative colitis.

• Diet or medication in primary care patients with IBS: the DOMINO study – a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute 
  • 459 IBS (IBS-C, IBS-D, IBS-M) patients randomized to:
    • Spasmolytic drug (Otilonium Bromide)
    • Low FODMAP diet-based app (LFD) 
  • After 2 months, LFD led to greater improvements in: 
    • Response rate (≥50 point on IBS-SSS) (71% vs 61%) 
    • Compliance to treatment (94% vs 73%) 
    • IBS symptom score (-97 points vs -77 points) 
  • NO significant difference between quality of life between groups 
  • Commentary: LFD led to greater improvement in IBS symptoms compared to an IBS medication.

• The effects of co-administration of probiotics and prebiotics on chronic inflammation, and depression symptoms in patients with coronary artery diseases: a randomized clinical trial
  • 96 patients with coronary artery disease and depression, randomized to:
    • Placebo
    • Probiotics (lactobacillus GG) alone
    • Inulin alone
    • Probiotics + inulin
  • After 2 months, compared to placebo, probiotics + inulin led to greater improvements in: 
    • Depression scores (-11.5 vs +3 points) 
    • Anxiety scores (-17.6 vs -0.6 points) 
    • hs-CRP (-1.7 vs +0.4 mg/dl) 
    • Lipopolysaccharide (-22 vs +0.3 EU/l) 
    • TNF-α (-25 vs +0.7 ng/l) 
  • Commentary: Probiotics + inulin led to significant improvements in emotional wellbeing and inflammatory markers.

• Efficacy and Safety of Vitamin D Adjuvant Therapy for Ulcerative Colitis: A Meta-Analysis
  • 10 studies, 1,077 ulcerative colitis patients randomized to:
    • Mesalazine alone
    • Mesalazine + vitamin D 
  • Compared to mesalazine alone, mesalazine + Vitamin D supplementation led to: 
    • 4x increased clinical efficacy
    • Reduced disease activity (small effect size) 
    • Improved intestinal barrier function (moderate to large effect size) 
    • Reduced inflammatory markers ( IL-6, TNF-α, and CRP) (large effect size) 
    • NO difference in adverse events 
  • Commentary: Vitamin D may enhance the effects of other ulcerative colitis treatments by further reducing inflammation, improving leaky gut and reducing symptoms.  

• Abdominal Massage in Functional Chronic Constipation: A Randomized Placebo-Controlled Trial
  • 74 patients with functional constipation, randomized to:
    • Placebo abdominal ultrasound + lifestyle advice 
    • Abdominal massage + lifestyle advice
  • After 1 month, compared to placebo group, abdominal massage led to:
    • Reduced constipation severity (70% massage vs 28% placebo) 
    • Improved quality of life (56% vs 38%) 
    • Increased stool frequency (70% vs 43%)
  • Commentary: Abdominal massage is a cheap and effective therapy for improving functional constipation. Consider using this as a first-line therapy in those with constipation. 

• Antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis
  • 160 observational studies, 22 million children
  • Antibiotic exposure, especially in the first 2 years of life, was associated with an increased risk of: 
    • Asthma (2x) 
    • Allergies (1.9x) 
    • Wheezing (1.8x) 
    • Psoriasis (1.7x) 
    • Arthritis (1.7x) 
    • Atopic dermatitis (1.4x) 
    • Food allergies (1.3x)
    • Neurodevelopmental disorders (1.3x) 
    • Obesity (1.2x) 
    • Autism (1.1x) 
  • NO association was found between antibiotics and IBD, celiac disease, type 1 diabetes or ADHD. 
  • Commentary: Antibiotics were associated with a near two-fold increased risk of developing asthma, allergies and wheezing in children, among other negative health outcomes. Keep in mind this is an observational study, so causation can’t be determined.

Thyroid & Hormones Studies

• Obstructive sleep apnea and serum total testosterone: a system review and meta-analysis
  • 24 studies, 1,389 sleep apnea patients, 845 healthy controls
  • Compared to healthy controls, sleep apnea was associated with lower serum testosterone levels (large effect size) 
  • This effect was ONLY seen in men, not women 
  • Commentary: This study found an association between sleep apnea and low testosterone. Keep in mind this is an observational study, so causation cannot be determined.

• Update on subclinical thyroid dysfunction
  • 2022 Review in Endocrinology on Subclinical Hypothyroidism
  • “Prior to confirming a diagnosis of SCH, serum FT4 and TSH levels should be reassessed 1–3 months later in order to rule out a transient increase of serum TSH levels”
  • “LT4 supplementation is NOT recommended if TSH levels are less than 10 mIU/L AND no symptoms of hypothyroidism are present, including fatigue, constipation, dry skin, edema, weight gain, and hoarseness”
  • “LT4 supplementation may be considered in those less than 70 years old with a TSH between 7-10 mIU/L if the patient has:
    • Cardiovascular risk factors such as high cholesterol, atherosclerosis, angina, a medical history of ischemic heart disease
    • Positive TPO antibodies “
  • “Overall, there is no evidence that long-term LT4 supplementation against SCH can ameliorate the symptoms of hypothyroidism, such as:
    • General fatigue
    • Depression
    • Improved quality of the life
    • Lowering BMI
    • Reduction of cardiovascular events”

• Effects of exercise on vasomotor symptoms in menopausal women: a systematic review and meta-analysis
  • 21 RCTs, 2,884 menopausal women, randomized to:
    • No treatment
    • Exercise (aerobic training)
  • Compared to no treatment, exercise led to:
    • Reduced severity of hot flashes (small effect size) 
    • NO change in frequency of hot flashes 
  • Commentary: This study found aerobic exercise led to a small improvement in hot flash severity, but not frequency.

• Cancer Risk in Hashimoto’s Thyroiditis: a Systematic Review and Meta-Analysis
  • 23 studies, 73,426 participants
  • Compared to healthy controls, those with Hashimoto’s thyroiditis (HT) had an increased risk of developing:
    • Thyroid cancer (1.7x) 
    • Breast cancer (1.7x) 
    • Digestive cancers (2.8x) 
    • Urogenital cancers (1.5x) 
    • Blood cancers (4x) 
  • Commentary: This study found associations between HT and various forms of cancer. Keep in mind this is an observational study, so causation cannot be determined.

• The effects of magnesium supplementation on abnormal uterine bleeding, alopecia, quality of life, and acne in women with polycystic ovary syndrome: a randomized clinical trial
  • 64 women with PCOS, randomized to:
    • Placebo
    • Magnesium oxide (250 mg/d)
  • Compared to placebo, magnesium led to improvements in the following quality of life scores:
    • Energy (+10 vs -1.7 points) 
    • Emotional wellbeing (+8 vs -2.8 points) 
    • Limitations due to physical health (+16 vs +4 points) 
    • Limitations due to emotional problems (+53 vs +6.7 points)
    • Quality of life (+9.4 vs -2.2 points)
  • NO differences in abnormal uterine bleeding, alopecia or acne between groups
  • Commentary: Magnesium led to improvements in overall quality of life, but no improvement in hormonal-related symptoms

• Exposure to multiple toxic metals and polycystic ovary syndrome risk: Endocrine disrupting effect from As, Pb and Ba
  • 369 women with PCOS, 441 healthy controls
  • All were assessed for blood heavy metals, including lead, mercury, arsenic, barium and cadmium
  • Compared to healthy controls, the following metals were associated with an increased risk of PCOS
    • Lead (1.8x)
    • Arsenic (2.5x) 
    • Barium (1.2x)  
  • Commentary: Heavy metal exposure may increase the risk of PCOS.

• Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS)
  • 270 SCH participants, categorized by TSH level: 
    • TSH (5.06-10 mU/L)
    • TSH (≥10 mU/L) 
  • After a 10-year follow up: 
    • 40% became euthyroid 
    • 44% remained subclinical hypothyroid 
    • 16% developed overt hypothyroidism
  • Risk factors for developing overt hypothyroidism include:
    • Positive TPO antibody (2.3x increased risk) 
    • TSH ≥10 mU/L (5x increased risk) 
  • Positive TPO antibody was associated with an increased risk of developing overt hypothyroidism only in those with:
    • TSH of 5.06-10 mU/L (2.4x increased risk)
    • NOT ≥10 mU/L

Commentary: This 10 year follow-up study found 16% of participants with subclinical hypothyroidism developed overt hypothyroidism, which was associated with positive TPO antibodies and a TSH ≥10 mU/L.

Diet & Lifestyle Studies

• Effects of continuous positive airway pressure on depression, anxiety and quality of life in obstructive sleep apnea hypopnea syndrome patients
  • 33 patients with moderate-severe sleep apnea, treated with CPAP
  • After 3 months, CPAP therapy led to: 
    • Reduced prevalence of depression (46% pre-CPAP vs 18% post-CPAP)
    • Reduced prevalence of anxiety (21% vs 6%) 
    • Improved quality of life 
  • Commentary: Treating sleep apnea may lead to improvements in mood. Consider this diagnosis in patients with depression and anxiety.

• Effects of omega-3 fatty acid on major cardiovascular outcomes: A systematic review and meta-analysis
  • 28 RCTs, 136,965 participants 
  • Compared to control, omega 3 fatty acids led to: 
    • 6% reduced risk of major cardiovascular events
    • 8% reduced risk of cardiac death
    • NO difference in all-cause mortality, heart attacks and strokes
  • Commentary: While omega 3 fatty acids slightly reduced the risk of cardiovascular events and cardiac death, there were no reductions in other important outcomes like all-cause mortality, heart attacks and strokes.

• 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 at ≥4 g/day led to reduced systolic blood pressure (-6.4 mm Hg), regardless of: 
    • Duration of use
    • Normotensive or hypertensive 
  • No additional benefits were seen on blood pressure at doses >9 g/day
  • Commentary: Arginine may help reduce blood pressure at a dose of 4-9 g/day

• A double-blinded, randomized, parallel intervention to evaluate biomarker-based nutrition plans for weight loss: The PREVENTOMICS study
  • 82 overweight adults, randomized to:
    • Control diet 
    • Personalized diet
  • Personalized diets were based on lab results (genetics, blood, urine, saliva) to determine their optimal diet
  • After 2.5 months, both groups experienced similar:
    • Fat loss (-4.6 personalized vs -4.4 lbs control)
    • Weight loss (-6.8 vs -7.3 lbs) 
    • Improvements in insulin resistance and lipids
  • Commentary: This double blinded and randomized study found NO difference in weight loss results between a highly personalized and a generic diet. This beautifully illustrates why we at the clinic primarily focus on treating people, not lab results.

Featured Study

• Oral Fluconazole Therapy in Patients With Active Ulcerative Colitis Who Have Detectable Candida in the Stool : A Double-Blind Randomized Placebo-controlled Trial
  • 242 active UC patients assessed for candida via stool culture 
  • 28% of the UC patients were positive for candida, and were randomized to:
    • Placebo
    • Oral fluconazole (200 mg/day) 
  • After 3 weeks, compared to placebo, fluconazole led to:
    • Reduced UC severity score 
    • Higher # patients with reduced fecal calprotectin (84% vs 37%)
    • Higher # patients with reduced histological scores (74% vs 33%) 
    • NO serious side effects
  • Risk factors for the presence of candida included: 
    • Higher UC severity 
    • Steroid use
  • Commentary: This study found around 1/3rd of UC patients were positive for fecal candida, and anti-fungal medication led to significant improvements in symptoms, histology and inflammation.

Gastrointestinal Studies

• Association between irritable bowel syndrome and micronutrients: A systematic review
  • 26 studies on patients with IBS
  • Compared to healthy controls, patients with IBS were more likely to be deficient in:
    • Vitamin B2 (riboflavin) 
    • Vitamin D
    • Calcium
    • Iron 
  • IBS patients on various exclusion diets (SCD, low FODMAP) were associated with lower intake of: 
    • B1 (thiamine) 
    • B2
    • Folate
    • Magnesium
    • Calcium
    • Iron 
    • Zinc
  • Commentary: While diets like low FODMAP may reduce the intake of various vitamins and minerals, it’s important to keep in mind that 1) exclusion diets are designed to be short term and 2) the diets should be used to heal the gut so patients can tolerate more food and expand their diets.

• Safety and tolerance of Lacticaseibacillus paracasei N1115 in caesarean-born young children: a randomised, placebo-controlled trial
  • 101 children (6-24 months) born c-section, randomized to:
    • Placebo
    • Probiotics (Lactobacillus paracasei, 20 billion CFU) 
  • After 3 months, probiotics led to a reduced risk of constipation by 88%
  • NO side effects occurred from probiotics 
  • Commentary: Probiotics may reduce rates of constipation and are safe in children 6 months and older.

• The effect of pro-/synbiotic supplementation on the brain-derived neurotrophic factor: a systematic review and meta-analysis of randomized controlled trials
  • 10 RCTs, 652 participants, randomized to:
    • Placebo
    • Probiotics or synbiotics
  • Compared to placebo, both probiotics and synbiotics led to increased brain derived neurotrophic factor (small effect size) 
  • Commentary: This study shows mechanistically how improving one’s gut health may lead to improved cognitive function. It is more important to keep in mind outcome data is more important than mechanism..

• Beneficial effects of probiotic and synbiotic supplementation on some cardiovascular risk factors among individuals with prediabetes and type 2 diabetes mellitus: A grade-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials
  • 52 RCTs, participants with type 2 diabetes or prediabetes
  • Probiotics and synbiotics led to improved:
    • Triglycerides (-19 mg/dl) 
    • Total cholesterol (-10 mg/dl) 
    • LDL-C (-5 mg/dl) 
    • Systolic blood pressure (-4 mmHg) 
  • Only synbiotics led to weight loss (small effect size) 
  • Commentary: This large study shows probiotics and synbiotics improve lipids, with triglycerides being the most significant in those with metabolic disease.

• Orally Ingested Probiotics, Prebiotics, and Synbiotics as Countermeasures for Respiratory Tract Infections in Non-elderly Adults: A Systematic Review and Meta-analysis
  • 42 studies, 9,179 participants, randomized to: 
    • Placebo vs probiotics (38 studies) 
    • Placebo vs prebiotics (2 studies)
    • Placebo vs synbiotics (1 study) 
  • Compared to placebo, probiotics led to:
    • 9% reduced risk of ≥1 respiratory tract infection (RTI)
    • Reduced duration and severity of RTI (small effect size)
  • Benefits for prebiotics or synbiotics were unclear regarding RTI outcomes
  • Commentary: Probiotics may reduce the risk of developing a RTI, and also slightly reduce the severity and duration if one develops a RTI.

Thyroid & Hormones Studies

• Higher serum thyroid autoantibody value is a risk factor of hypothyroidism in children and young adults with chronic thyroiditis
  • Retrospective study, 133 children (~11 years old) with elevated thyroid antibodies 
  • Children were monitored for 2.5 years, then categorized by thyroid status:
    • Overt hypothyroidism (TSH >10 uIU/mL) 
    • Euthyroid (TSH <10 uIU/mL) 
  • The following levels of thyroid antibodies increased the risk of developing hypothyroidism by 10x: 
    • Tg antibodies >106 IU/mL
    • TPO antibodies >16 IU/mL
  • The sensitivity and specificity for the following antibodies were: 
    • +Tg antibodies (82% sensitivity, 62% specificity) 
    • +TPO antibodies (77% sensitivity, 68% specificity) 
    • TPO >16 and Tg >106 IU/mL (75% sensitivity, 78% specificity)
  • Commentary: This small study found specific cut off values for Tg and TPO antibodies that may predict the progression to hypothyroidism in children.

• Efficacy and Safety of Coenzyme Q10 Supplementation in the Treatment of Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis
  • 9 RCTs, 1,021 PCOS patients, randomized to:
    • Control
    • Coenzyme Q10 (CoQ10
  • CoQ10 supplementation led to improved: 
    • Fasting insulin (large effect size)
    • Fasting glucose (large effect size)
    • Insulin resistance (moderate effect size) 
    • Testosterone (small effect size) 
    • Follicular stimulating hormone (small effect size)
    • Improved lipids (HDL-C, LDL-C, TC, Triglycerides) (small effect size) 
  • Commentary: CoQ10 supplementation led to improved blood sugar control, hormone balance and lipids.

• Effects of Thyroid Dysfunction and the Thyroid-Stimulating Hormone Levels on the Risk of Atrial Fibrillation: A Systematic Review and Dose-Response Meta-Analysis from Cohort Studies
  • 13 studies, 649,293 participants
  • Increased risk of atrial fibrillation was associated with: 
    • Overt hyperthyroidism (2.4x) 
    • Subclinical hyperthyroidism (1.7x) 
    • Subclinical hypothyroidism (1.2x)
  • NO association was found for overt hypothyroidism and atrial fibrillation
  • Commentary: Overt and subclinical hyperthyroidism doubled the risk of developing atrial fibrillation, while subclinical hypothyroidism slightly increased the risk.

• Effects of testosterone therapy in adult males with hypogonadism and T2DM: A meta-analysis and systematic review
  • 13 studies, 1,596 hypogonadal type-2 diabetic patients
  • Testosterone therapy led to improvements in: 
    • Free and total testosterone levels (large effect size) 
    • Insulin resistance (large effect size) 
    • Fasting insulin (large effect size)
    • Fasting glucose (small effect size) 
    • Cholesterol (small effect size) 
    • Triglycerides (small effect size) 
  • Commentary: In patients with low testosterone, testosterone replacement therapy led to significant improvements in metabolic function.

• Subclinical Hypothyroidism and Incident Depression in Adolescents and Young Adults: Results from a Nationwide Representative Prospective Study
  • 4,118 adolescents
  • After 6 years, 2.6% developed subclinical hypothyroidism (SCH) 
  • NO association was found between prevalence of (SCH) and development of major depression
  • Commentary: This study found no association between SCH and depression in adolescents.

Diet & Lifestyle Studies

• The effect of a Mediterranean diet on the symptoms of depression in young males (the “AMMEND: A Mediterranean Diet in MEN with Depression” study): a randomized controlled trial
  • 72 men with moderate to severe depression, randomized to:
    • Control (befriending therapy, aka social support)
    • Mediterranean diet
  • After 3 months, compared to control, the mediterranean diet led to:
    • Reduced depression scores (14 point difference)
    • Improved quality of life scores (13 point difference) 
  • Commentary: This study highlights the importance of improving dietary quality when helping patients with depression.

• Efficacy of CPAP duration and adherence for cognitive improvement in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials
  • 16 RCTs, 1,529 participants with sleep apnea, randomized to:
    • Control
    • CPAP 
  • Compared to control groups, CPAP therapy led to improved:
    • Short term memory (moderate effect size) 
  • When comparing short term (<2 months) vs long term (≥3 months) CPAP therapy, there was NO difference in executive function
  • Commentary: CPAP treatment for sleep apnea may provide some cognitive benefit, but these effects may diminish/plateau with longer-term use.

• Association of Vitamin B12, Vitamin D, and Thyroid-Stimulating Hormone With Fatigue and Neurologic Symptoms in Patients With Fibromyalgia
  • Retrospective study, 2,142 fibromyalgia patients, tested for serum B12, vitamin D and TSH
  • Low serum B12 (<400 ng/L) was present in 42% of patients, and was only associated with fatigue, but NOT: 
    • Neuropathy
    • Memory loss 
    • Brain fog 
  • Vitamin D levels were NOT associated with fibromyalgia symptoms
  • Commentary: Low B12 was associated with fatigue in fibromyalgia patients.

• Ketogenic diet in refractory migraine: possible efficacy and role of ketone bodies-a pilot experience
  • 2 studies, 53 chronic migraine patients, treated with either:
    • Low carb diet 
    • Ketogenic diet 
  • Compared to a low carb diet, the ketogenic diet led to reduced migraine: 
    • Frequency
    • Intensity 
    • Medications needed
  • Commentary: The ketogenic diet may be a useful dietary treatment for refractory migraines.

• Effect of CPAP vs. mandibular advancement device for excessive daytime sleepiness, fatigue, mood, sustained attention, and quality of life in patients with mild OSA
  • 79 patients with sleep apnea, randomized to:
    • Control group
    • CPAP
    • Mandibular advancement device (MAD) 
  • Compared to MAD, CPAP led:
    • Greater improvements in sleep apnea severity (based on polysomnogram) 
    • Higher quality of life
    • Similar improvements in fatigue 
  • Compliance was better in the MAD group compared to CPAP
  • Commentary: Despite CPAP leading to better test results, MAD led to similar improvements in fatigue as well as better compliance. This study illustrates why we at the clinic believe lab results are only 1/4th of the data needed to make a clinical decision.