- Strain-specific and outcome-specific efficacy of probiotics for the treatment of irritable bowel syndrome: A systematic review and meta-analysis
- Aim: To identify if there is a strain-specific outcome bias of certain probiotics
- 32 RCTs, 3,856 participants
- Four probiotics demonstrated significant reduction in abdominal pain relief:
- B. coagulans MTCC5260 (RR= 4.9)
- L. plantarum 299v (RR= 4.6)
- S. boulardii CNCM I-745 (RR= 1.5)
- S. cerevisiae CNCM I-3856 (RR= 1.3)
- However, the multi-strain mixtures had the best improvement in symptoms
- Commentary: Some may argue that clinicians need to use strains only used in clinical trials for specific conditions. However, this type of thinking is missing the big picture. That is, we have hundreds (if not thousands) of papers suggesting that multiple probiotics species and strains can improve various digestive health complaints. If one is to try to match a specific strain of probiotic with the main health concern of the patient, they may make two mistakes:
- 1) Make clinical care too theoretical, and thus, too complicated
- 2) Miss potential benefits of using an empirical trial of triple probiotic therapy given the many studies showing multi-strain/species probiotics may be better than single strain/species (see other FFMR+ research briefs).
- Remember, to be evidence-based but not evidence-limited. Stay tuned- Dr Ruscio will be doing a commentary of this study soon on the main podcast feed.
- The relation between the diet and the diverticulitis pathophysiology: An integrative review
- Is there a relationship between diet and the incidence of diverticulitis?
- 5 prospective cohort studies, 235,206 participants
- High intake of red med and low intake of fiber was associated w/ higher incidence of diverticulitis
- Commentary: A few things to note here:
- 1) This is an observational study and one cannot suggest that low fiber and high red meat CAUSES diverticulitis. Perhaps, poor dietary habits (that are characterized by low fiber/high red meat consumption) are also associated w/ other poor health habits such as smoking, lack of exercise which may be major drivers of diverticulitis.
- 2) Many individuals w/ diverticulitis may be sensitive to fiber. We should be careful not to shoe-horn all of these patients into eating more fiber given this observational study.
- Effect of Gluten Ingestion and FODMAP Restriction on Intestinal Epithelial Integrity in Patients with Irritable Bowel Syndrome and Self-Reported Non-Coeliac Gluten Sensitivity
- 33 IBS patients, measured markers of intestinal permeability
- Participants were on gluten-free diet instructed to adopt low FODMAP diet and then challenge themselves w/ either gluten or placebo
- Results:
- Gluten ingestion had NO effect on intestinal permeability markers or symptoms
- A low FODMAP diet reduced a marker of intestinal permeability (by 3,335%) and reduced symptoms
- Commentary: Reducing FODMAP intake may have more efficacy than reducing gluten in those w/ IBS.
- Helicobacter pylori infection and autoimmune diseases; Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study
- 43 studies, 5,052 patients
- Infection with more virulent strains of H. pylori (e.g. cagA positive) can increase the risk of autoimmune diseases
- Commentary: This study supports the gut-immune connection.
- Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial
- Study published in the Lancet
- Background: Rapid weight loss is a risk factor for cholelithiasis (gallstones)
- 967 patients w/ an intact gallbladder scheduled for bariatric surgery
- Randomized to ursodeoxycholic acid (UDCA) (900 mg daily) or placebo x6 months
- At 24 month followup:
- UDCA prophylaxis did not significantly reduce the rate of symptomatic gallstone disease
- However, in those without gallstones before surgery, UDCA reduced the occurrence of symptomatic gallstone disease
- Commentary: Bile acid therapy may be an effective strategy to prevent gallstones. UDCA decreases the cholesterol content of bile/bile stones by:
- Reducing the secretion of cholesterol from the liver
- & reducing the reabsorption of cholesterol by the intestines
- Enhanced Clostridioides difficile Infection Prevention With a Pharmacy-Controlled Policy That Adds a 3-Strain Lactobacillus Probiotic Concomitantly to Antibiotic Therapy
- Prospective study, 8,266 in-hospital patients w/ signs of possible C. diff infection who received antibiotics plus either 3-strain Lactobacillus probiotic or no additional treatment
- C. difficile infection rate decreased by about half in those who took the probiotics (0.9% vs 1.5%)
- Sex differences in zonulin in affective disorders and associations with current mood symptoms
- 55 depressed participants, 37 euthymic participants, measured serum zonulin
- NO correlation between serum zonulin levels and depression severity.
- Commentary: This highlights serum zonulin’s relatively poor accuracy.
- Lactobacillus plantarum CCFM1143 Alleviates Chronic Diarrhea via Inflammation Regulation and Gut Microbiota Modulation: A Double-Blind, Randomized, Placebo-Controlled Study
- 55 patients w/ chronic diarrhea randomized to lactobacillus probiotic or placebo
- After 4 weeks, the probiotic group trended towards better improvement of symptoms but results were not statistically significant.
- A Biofeedback-Assisted Stress Management Program for Patients with Irritable Bowel Syndrome: a Randomised Controlled Trial
- 46 IBS patients, randomized to biofeedback stress-management therapy or no treatment
- After 8 weeks, the stress-management therapy had:
- Greater reduction in IBS symptoms
- Reduction in depressive symptoms
- Better quality of life
- Commentary: The biofeedback tool used in this study was a portable device used to train the patient to monitor the physical reactions (respiration rate, quality of a single breath, heart rate, and heart rate variability with breathing). The device used in this study can be found here.
- Bipolar disorder and the gut microbiome: A systematic review
- 4 of 5 studies showed lower microbiome diversity in those w/ bipolar
- 3 of 4 studies showed lower butyrate production
- 2 of 3 studies showed higher Prevotella and Bacteroides species
- Commentary: Said more generally, dysbiosis is more common in those w/ bipolar. This highlights the gut-brain connection.
- Quantitative sequencing clarifies the role of disruptor taxa, oral microbiota, and strict anaerobes in the human small-intestine microbiome
- 250 duodenal-aspirate samples and 21 paired duodenum-saliva samples from participants in the REIMAGINE study
- Results suggest that there is transmission of oral microbiota into the duodenum
- Commentary: This study gives support to the top-down approach of SIBO pathogenesis.
- Helicobacter pylori in gastric cancer: Features of infection and their correlations with long-term results of treatment
- 109 patients w/ gastric cancer
- H. pylori detected in 84.5% of cases
- In cases of moderate-high concentrations of H. pylori, the 10-year remission rate and overall survival was significantly decreased (from 55.6% to 26.3%)
- Commentary: H. pylori may be associated with a more aggressive gastric cancer or may contribute to its progression. However, note that this study was observational in nature and had a low sample size.
- Routine antibiotics may not be needed to treat uncomplicated right diverticulitis: A retrospective cohort study
- Retrospective study of 197 patients w/ uncomplicated right colonic diverticulitis (138 patients who received antibiotics and 59 who did not)
- There was NO statistically significant difference in the length of hospital stay or initiation of food diet
- Commentary: Antibiotics may not be necessary for uncomplicated cases of right diverticulitis.
- Value of age and alarm features for predicting upper gastrointestinal malignancy in patients with dyspepsia: an endoscopic database review of 4664 patients in Thailand
- Cross-sectional study of 4,664 patients who underwent first-time endoscopy for dyspeptic symptoms
- Alarm symptoms (dysphagia, unintentional weight loss, GI bleeding/anaemia, and persistent vomiting) present in 21.6% of patients
- Patients with alarm features had a higher prevalence of malignancy (OR 22.3)
- Only 1.2% had upper GI malignancy
- And only two patients aged <50 years who did NOT have alarm features had cancer.
- Commentary: The presence of alarm symptoms of patients significantly increases the possibility of upper GI malignancy. Without these alarm symptoms, the possibility of malignancy is negligible.
- Comparison of Thyroid Hormone Levels Between Patients With Major Depressive Disorder and Healthy Individuals in China
- Retrospective study, 535 patients w/ depression and 998 healthy controls
- TSH, fT4, and fT3 were significantly lower in the depressed patients
- However, NO significant difference was found in clinical/subclinical hyperthyroidism or hypothyroidism between the two groups.
- Commentary: NO difference of hypothyroidism was seen between those w/ depression and controls.
- Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis
- 4 RCTs, 4,050 patients that investigated the risk of breast cancer (BC) recurrence with the use of HRT in BC survivors
- Overall, 2,022 patients were randomized to receive HRT (estrogen/progesterone combination) and 2,023 to the control group (placebo or no HRT)
- HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12-1.91)
- More effect if hormone-receptor positive BC
- But, NO effect if hormone-receptor negative BC
- Commentary: Contrary to popular thought, HRT may not be detrimental in BC survivors if they have hormone-receptor negative BC.
- Impact of progesterone on skin and hair in menopause – a comprehensive review
- 2 of 3 studies reported benefit for topical or oral progesterone for skin health.
- Extra virgin olive oil high in polyphenols improves antioxidant status in adults: a double-blind, randomized, controlled, cross-over study (OLIVAUS)
- 43 participants randomized to 4 Tbsp of extra-virgin high polyphenol olive oil (HPOO) or low polyphenol olive oil (LPOO)
- After 3 weeks, the HPOO had more improvement in:
- ox-LDL (-6.5-13.5 mU/mL)
- Total antioxidant capacity
- hs-CRP (-1.9 mg/dL)
- Commentary: High polyphenol olive oil may be superior to regular olive oil for improving cardiometabolic markers.
- Effects of Combined Resistance and Aerobic Training on Arterial Stiffness in Postmenopausal Women: A Systematic Review
- 11 studies
- “The results unequivocally show that combined [resistance and aerobic] training reduces arterial stiffness.”
- 12 weeks of strength training improves fluid cognition in older adults: A nonrandomized pilot trial
- 20 elderly patients
- After 12 weeks of strength training (3 sessions/week), participants had improved:
- Executive function
- Attention
- Working memory
- Processing speed
- Commentary: Resistance training can improve cognitive function.
- The effect of L-carnitine supplementation on insulin resistance, sex hormone-binding globulin and lipid profile in overweight/obese women with polycystic ovary syndrome: a randomized clinical trial
- 62 overweight women w/ PCOS, randomized to L-carnitine (1 g/d) or placebo
- After 12 weeks, the L-carnitine group had:
- Reduction in fasting insulin (-0.7)
- NO difference in triglycerides or lipids
- Commentary: L-carnitine may improve glycemic markers by improving insulin sensitivity.
- Association between dietary antioxidant vitamins intake and homocysteine levels in middle-aged and older adults with hypertension: a cross-sectional study
- Cross-sectional study of 1,465 middle-aged and older adults with hypertension
- Higher intakes of dietary vitamin C was associated with lower rates of high homocysteine (≥15 µmol/L)
- NO effect was seen for vitamin E, carotenes, retinol, or lutein
- Clinical and Nutritional Impact of a Semi-Elemental Hydrolyzed Whey Protein Diet in Patients with Active Crohn’s Disease: A Prospective Observational Study
- 144 Crohn’s disease patients, given exclusive semi-elemental diet as sole source of nutrition
- After 12 weeks:
- Average number of stools per day decreased (from 4.6 stools/day to 1.7 stools/day)
- Reduction of malnourishment (91.4% to 23.9%)
- Reduced disease activity (10.2 to 3.7)
- Significant increase in remission (5.6% to 71.8% of participants)
- Commentary: This study suggests out a few points:
- A semi-elemental diet can be as effective as a fully-elemental diet
- A moderate-term exclusive semi-elemental dieting does not result in malnutrition. In fact, a significant reduction in malnourishment occurred in this study.
- Elemental dieting results in a significant reduction in disease activity in those w/ IBD.
- Association of Small Intestinal Bacterial Overgrowth With Heart Failure and Its Prediction for Short-Term Outcomes
- Cross-sectional study of 287 heart failure patients
- Given lactulose breath test
- 45% SIBO+ (using North American Consensus)
- SIBO was an independent risk factor for cardiovascular death and rehospitalization (HR 2.13)
- Association only for CH4 predominant SIBO (not hydrogen SIBO)
- Commentary: This study highlights the gut-cardiovascular connection. There is a higher prevalence of SIBO in those w/ heart failure. However, a weakness of this study was that it used a lactulose breath test (instead of glucose). Dr. Rusico wanted to point out that the newer guidelines restrict the test interpretation window to the first 90 min, thus reducing likelihood of false positives (remember, older guidelines and some labs, would use 120 interpretation window).
- Prevalence of fibromyalgia 10 years after infection with Giardia lamblia: a controlled prospective cohort study
- 572 Giardia exposed individuals (had history of acute infection), 673 controls
- Fibromyalgia rates:
- 8.6% in Giardia exposed
- 3.1% in controls
- Commentary: An acute Giardia infection can increase the odds of fibromyalgia. However, the overall rate still remains low. We cannot establish causality from this study especially since those w/ fibromyalgia also had higher rates of IBS.
- Evaluation of serum zonulin level in prediabetic patients
- 45 diabetics, 56 prediabetics, 40 healthy controls
- Measured serum zonulin levels at baseline and after glucose tolerance test
- Baseline serum zonulin was higher in the diabetic group
- No difference in prediabetic and control group
- After glucose tolerance test, zonulin was higher in the prediabetic and diabetic groups compared to controls
- Commentary: Poor glycemic control may be one reason for increased intestinal permeability.
- Vitamin D in Children With Inflammatory Bowel Disease: A Randomized Controlled Clinical Trial
- 120 children w/ IBD and low Vit D levels
- Randomized to Vit D (2,000 IU/day) or placebo
- After 6 months, the Vit D group had:
- Decreased IBD activity score
- Better quality of life
- Decreased inflammatory markers (ESR, CRP, TNF-alpha)
- Commentary: Vit D supplementation has beneficial effects on children w/ IBD.
- Novel Bioenhanced Curcumin With Mesalamine for Induction of Clinical and Endoscopic Remission in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-controlled Pilot Study
- 69 patients w/ mild-to-moderate ulcerative colitis (UC) on max dose mesalamine
- Randomized to curcumin or placebo
- After 6 weeks, the curcumin group had:
- More beneficial response (53% vs 14%)
- More clinical remission (44.1% vs 35.3%)
- The curcumin group also had better clinical remission at 12 months (84% vs 0%)
- Commentary: Curcumin was capable of inducing sustained clinical remission in patients with mild-to-moderately UC on maximal dose of mesalamine.
- Changes in the Crohn’s Disease Activity Index and Safety of Administering Saccharomyces Boulardii in Patients with Crohn’s Disease in Clinical Remission: A Single Hospital-based Retrospective Cohort Study
- Retrospective cohort study of 92 Crohn’s Disease patients who had received S. boulardii for more than 6 months, and 64 controls
- S boulardii was associated with:
- Improved disease activity scores
- Increased hemoglobin
- NO change in fecal calprotein, CRP, ferritin, B12, folate, or albumin
- Commentary: S boulardii is associated w/ improved disease activity scores independent of inflammatory markers in Crohn’s Disease patients.
- A Systematic Review With Meta-Analysis of the Efficacy of Cannabis and Cannabinoids for Inflammatory Bowel Disease: What Can We Learn From Randomized and Nonrandomized Studies?
- 15 nonrandomized studies and 5 randomized controlled trials
- Cannabinoids associated with:
- NO improvement in remission
- NO effect on inflammatory markers
- Some improvement in symptoms
- Commentary: Cannabinoids do not induce clinical remission or affect inflammation in IBD patients.
- Synbiotics Supplements Lower the Risk of Hand, Foot, and Mouth Disease in Children, Potentially by Providing Resistance to Gut Microbiota Dysbiosis
- 749 children ages 2-7 yo
- Children who took synbiotics had a lower risk of hand-foot-and-mouth disease (viral)
- Dysbiosis was found in those w/ hand-foot-and-mouth disease
- Effectiveness and safety of Bifidobacterium in preventing dental caries: a systematic review and meta-analysis
- Probiotics had NO effect on:
- Streptococcus mutans and Lactobacilli counts in saliva
- Dental caries rates
- Probiotics had NO effect on:
- Impact of menopausal hormone therapy on colorectal cancer risk-A systematic review
- 57 studies, 9 meta-analysis
- HRT was associated with:
- Neutral or protective effect for colorectal cancer (CRC) and adenoma risk
- Neutral effect for colorectal cancer mortality
- Commentary: Overall, HRT has a neutral (possibly beneficial) effect on CRC risk and mortality.
- Plasma TMAO increase after healthy diets: results from 2 randomized controlled trials with dietary fish, polyphenols, and whole-grain cereals
- Aim: Evaluate the effects on plasma TMAO of healthy diets
- Post hoc analysis of 2 RCTs
- Higher TMAO levels associated with higher intake of fish, vegetables and whole-grain products
- But not meat, processed meat and dairy products
- Commentary: Higher TMAO levels were associated with healthier dietary patterns, thus questioning that popular thought that higher TMAO is inherently bad.
- Blood Lead Levels and Cardiovascular Disease Risk: Results from the Korean National Health and Nutrition Examination Survey
- Cross-sectional study of 1,929 Korean participants
- Higher serum lead levels were associated with higher:
- Cardiovascular risk (per the Framingham risk score)
- Total cholesterol
- Systolic blood pressure
- Commentary: This study hints at heavy metals’ relationship w/ cardiovascular risk. However, this only suggests association, not causation.
- Effects of resistance training on endothelial function: A systematic review and meta-analysis
- 23 studies, 785 participants
- Resistance training lead to improvement in endothelial function (as measured by flow-mediated dilatation) regardless of health status (healthy or have disease)
- Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer’s Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial
- 101 patients w/ stable Alzheimer’s Disease randomized to B vitamins (folic acid 1.2 mg/d + vitamin B12 50 μg/d) or placebo
- After 6 months, folic acid plus vitamin B12 supplementation had:
- Improved cognitive scores
- Decreased homocysteine
- Is resistance training alone an antihypertensive therapy? A meta-analysis
- 13 studies, 417 participants (207 assigned to resistance training and 210 controls) w/ hypertension
- Resistance training was associated w/ a significant reduction in systolic blood pressure (-6.16 mmHg)
- Commentary: Resistance training alone has the potential to significantly reduce blood pressure.
- Effects of Exercise Therapy on Anxiety and Depression in Patients With Coronary Heart Disease: A Meta-Analysis of a Randomized Controlled Study
- 11 RCTs, 771 participants
- Compared with the control group, the exercise group showed a significant improvement in anxiety (effect size, 0.61) and depression (effect size 0.48)
- Commentary: This meta-analysis suggests that exercise is a powerful non-pharmacologic therapy for anxiety and depression.
- Sarcopenia predicts adverse outcomes in an elderly population with coronary artery disease: a systematic review and meta-analysis
- 10 studies, 3,707 patients followed x0.6-4.5 years
- Sarcopenia was associated with higher rates of major cardiovascular events in those w/ existing coronary disease (HR 2.86)
- Commentary: Sarcopenia is a risk factor for poor metabolic health.
- The Effect of Oral Simvastatin on the Clinical Outcome of Patients with Severe Traumatic Brain Injury: A Randomized Clinical Trial
- 98 patients w/ severe TBI, randomized to placebo or oral simvastatin (40 mg, daily) x10 days
- 1 month after discharge, the simvastatin group had:
- Higher rates of conscious patients (64.9 % versus 28.1%)
- Greater GCS scores
- Commentary: This study suggests some promise for statin therapy for TBI therapy.
- Age-specific thyrotropin references decrease over-diagnosis of hypothyroidism in elderly patients in iodine-excessive areas
- Cross-sectional study of 2,559 participants from iodine-excessive areas and no previous history of thyroid disorders
- Diagnosed subclinical hypothyroidism (SCH) and overt hypothyroidism (OH) by using both lab reference ranges (TSH >4.2) and age-appropriate reference ranges (TSH >11.5 for those >70, as determined by >97% of population studied)
- Iodine excess was a novel risk factor for hypothyroidism
- Especially urinary iodine concentrations ≥ 700 µg/L (OR = 2.5)
- Prevalence of hypothyroidism for those >70:
- OH:
- Lab reference ranges: 2.37%
- Age-appropriate reference ranges: 1.78%
- SCH:
- Lab reference ranges: 29.6%
- Age-appropriate reference ranges: 2.96%
- OH:
- Commentary:
- Iodine excess is a risk factor for hypothyroidism
- TSH naturally rises with age. This is a great illustration of how SCH may be OVER-diagnosed in an older population. The prevalence of SCH decreased to 10% of the original rate when using an age-appropriate TSH reference range. For those >70 yo, TSH up to 6-8 may NOT need treatment.
- One endocrine society “recommends that clinicians derive the upper limit of normal for people over 60 years by dividing the patient’s age by 10 (e.g., TSH ≤ 8 mIU/L for an 80-year-old individual).”
- Examination of plasma zonulin levels in bipolar I disorder: a case-control study with follow-up
- Serum zonulin levels measured in 30 patients with bipolar disease type I and 29 healthy controls
- NO difference in serum zonulin levels
- NO association between zonulin levels and disease symptoms
- Commentary: This study failed to show an association between serum zonulin and bipolar disease. Perhaps this is due to the poor reliability of this marker.
- Effect of long-term acid suppression therapy with proton pump inhibitors or H 2 receptor blockers on serum vitamin B 12 levels in elderly population
- 70 patients >60 yo on long-term PPI or H2-blocker use (>6 months)
- ~50% of the patients were either “deficient” (less than 200 pg/ml) or “insufficient” (200 to 300 pg/ml) in serum vitamin B12 levels
- Commentary: Nearly half of long-term PPI or H2-blocker users had insufficient B12 levels.
- Association between bacteria other than Helicobacter pylori and the risk of gastric cancer
- 268 gastric cancer (GC) cases and 288 healthy controls
- 16S rRNA gene sequencing performed from gastric biopsy samples
- The microbiota was different between the GC and healthy control groups
- Participants with higher levels of Actinobacteria species showed a significantly increased risk of GC (OR: 3.16)
- Commentary: Dysbiosis may be a contributing factor to GC and/or GC may alter the microbiota composition.
- Adult celiac disease with persistent IBS-type symptoms: a pilot study of an adjuvant FODMAP diet
- 15 patients w/ Celiac Disease (CD) w/ concurrent IBS put on a low FODMAP diet
- After 4 weeks, 53% had relief of symptoms
- Commentary: This study supports the use of a low FODMAP diet for those w/ IBS symptoms despite a gluten-free diet.
- Effects of probiotic Bifidobacterium bifidum G9-1 on the gastrointestinal symptoms of patients with type 2 diabetes mellitus treated with metformin: an open-label, single-arm, exploratory research trial
- 40 diabetic patients taking Metformin, given lacto/biff probiotic
- After 10 weeks:
- Improved GI symptoms in all domains (e.g. diarrhea, constipation, etc)
- No change in A1C
- Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn’s Disease: A Post Hoc Analysis From the CALM Study
- Aim: Examine association between biomarker cutoff concentrations and endoscopic end points in Crohn’s disease patients. .
- Biomarker accuracy for predicting mucosal healing on endoscopy:
- Fecal calprotectin <250 µg/g
- Sensitivity: 72%
- Specificity: 63%
- CRP <5 mg/L
- Sensitivity: 86%
- Specificity: 42%
- Fecal calprotectin <250 µg/g
- Commentary: A cutoff of fecal calprotectin <250 µg/g and CRP <5 mg/L are useful markers to predict mucosal healing in Crohn’s disease.
- Associations of atrophic gastritis and proton-pump inhibitor drug use with vitamin B-12 status, and the impact of fortified foods, in older adults
- Cross-sectional study of 3,299 participants >60 yo not using vitamin B-12 supplements
- Atrophic gastritis (AG) was identified in 15% of participants
- Associated with significantly lower serum total vitamin B-12 and higher prevalence of vitamin B-12 deficiency (38%)
- Lower B12 levels found only in those taking higher PPI doses over 6 months
- Commentary: Older adults who have AG and/or use higher doses of PPIs are more likely to have vitamin B-12 deficiency.
- Probiotics for the treatment of depression and anxiety: A systematic review and meta-analysis of randomized controlled trials
- 16 RCTs including 1,125 patients
- Probiotics associated w/ a significant improvement in:
- Depression scores (w/ moderate certainty)
- Anxiety scores (w/ low certainty)
- Commentary: Probiotics have favorable effects on mood balance.
- Efficacy of Probiotics as Prophylaxis for Urinary Tract Infections in Premenopausal Women: A Systematic Review and Meta-Analysis
- 3 RCTs, 284 participants
- Probiotics did not have a significant effect in the prophylaxis of UTIs (w/ high degree of heterogeneity)
- Probiotics as the live microscopic fighters against Helicobacter pylori gastric infections
- “Administration of standard antibiotic therapy combined with probiotics plays an important role in the effective treatment of H. pylori infection.”
- “According to the literature, Lactobacillus casei, Lactobacillus reuteri, Lactobacillus rhamnosus GG, and Saccharomyces boulardii can effectively eradicate H. pylori infection.”
- “Our results showed that in addition to decrease gastrointestinal symptoms, probiotics can reduce the side effects of antibiotics (especially diarrhea) by altering the intestinal microbiome.”
- Adverse events in trials of licensed drugs for irritable bowel syndrome with constipation or diarrhea: Systematic review and meta-analysis
- 21 RCTs for in IBS-C (5,953 patients in placebo group) and 17 in IBS-D (3,854 patients in placebo group)
- In the placebo groups:
- 34.9% in the IBS-C trials reported adverse events
- 46.9% in the IBS-D trials reported adverse events
- Commentary: Just like the placebo effect, there is a strong nocebo effect in IBS literature. About 35-50% of IBS participants in the placebo group reported adverse events that they attributed to the placebo pill. This highlights the strong mind-body connection in those w/ IBS (and functional GI disorders more broadly).
- Dosage of resistance exercises in fibromyalgia: evidence synthesis for a systematic literature review up-date and meta-analysis
- 9 RCTs
- Compared to the control groups, resistance exercise had a significant reduction on pain when performed at:
- Moderate-to-high intensity
- 1-2 sets of 4-20 reps, 2x per week
- For total of 8-12 weeks
- Commentary: Paradoxically, higher intensity resistance exercises can improve fibromyalgia pain levels.
- Dietary factors and risk of islet autoimmunity and type 1 diabetes: a systematic review and meta-analysis
- 96 studies
- Following factors associated w/ lower risk of T1D (w/ moderate/high certainty):
- Longer duration of breastfeeding (>6-12 months)
- Later introduction of gluten (3-6 months), cow’s milk (>2-3 months), and fruit (4-6 months)
- Commentary: This study gives us some interesting associated risk factors for type 1 diabetes. Be cautious with this information as we can only conclude correlation (not causation).
- Impact of dehydroepiandrosterone on thyroid autoimmunity and function in men with autoimmune hypothyroidism
- Aim: To examine the effect of DHEA supplementation on thyroid autoimmunity
- 32 elderly men with autoimmune hypothyroidism and low serum DHEA-S levels
- Randomized to DHEA (50 mg daily) or no treatment
- After 6 months, DHEA therapy lead to:
- Reduced TPO antibody levels (-226 IU/mL)
- Reduced Tg antibody levels (-237 IU/mL)
- Reduced TSH (-1.3)
- Increased DHEA-S levels (+0.8 µmol/L)
- NO change in estradiol levels
- Commentary: This small study showed support of oral DHEA supplementation on thyroid autoimmunity. Given the fact that this study was for 6 months, DHEA may need to be supplemented for a sufficient amount of time to exert beneficial effects. These findings are clinically significant but more research is needed.
- Non-inferiority of liquid thyroxine in comparison to tablets formulation in the treatment of children with congenital hypothyroidism
- 36 children w/ congenital hypothyroidism randomized to tablet or liquid levothyroxine
- After 6 months, the liquid T4 group had:
- LOWER TSH
- LESS dose adjustments
- NO increased adverse effects
- Commentary: Liquid T4 is non-inferior to tablet form and can lead to less dose adjustments perhaps by bypassing any underlying GI dysfunction.
- Does Hormone Supplementation With Levothyroxine Improve Hypothyroid Impaired Cognitive Dysfunction?
- 6 studies examining levothyroxine’s effect on cognitive impairment and dementia in those w/ overt hypothyroidism
- 5 of 6 studies show a positive impact of levothyroxine on dementia
- Commentary: The majority of studies support levothyroxine’s beneficial effect on cognitive function in those w/ established overt hypothyroidism.
- Frequency of Subclinical Hypothyroidism in Women With Polycystic Ovary Syndrome
- 200 PCOS females, 200 healthy female controls
- SCH was found to be more prevalent in those with PCOS compared to healthy controls (43.5% vs. 20.5%)
- Commentary: Consider hypothyroidism in those w/ PCOS.
- The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial
- 66 women w/ PCOS randomized to myo-inositol (4g/d) or metformin (1,500 mg/d)
- After 6 months: NO difference in improvement in BMI, fat mass, testosterone, or fasting glucose levels between two treatment arms
- Commentary: 4g/d of myoinositol is comparable to gold standard treatment (Metformin) for PCOS.
- Serum cadmium positively correlates with inflammatory cytokines in patients with chronic obstructive pulmonary disease
- 940 COPD patients
- Higher serum cadmium levels was associated with:
- LOWER pulmonary function
- Higher inflammatory cytokine levels
- Commentary: Toxic burden and inflammation may be contributing factors to COPD and poor pulmonary function.
- The effects of coenzyme Q10 supplementation on metabolic profiles and parameters of mental health in women with polycystic ovary syndrome
- 55 women w/ PCOS, randomized to CoQ10 (100 mg/d) or placebo
- After 12 weeks, the CoQ10 group had:
- Reduced depression scores
- Reduced hs-CRP
- Reduced testosterone, DHEA-S, and hirsutism
- Increased antioxidant capacity
- Commentary: This small study shows some promise for CoQ10 to improve mood, reduce inflammation, and female hormone health.
- Effect of 12-week continuous positive airway pressure therapy on glucose levels assessed by continuous glucose monitoring in people with type 2 diabetes and obstructive sleep apnoea; a randomized controlled trial
- 72 diabetic patients w/ mod-severe OSA randomized to CPAP therapy or control
- After 12 weeks, NO difference in glucose markers between the two groups.
- However, there was a slight trend toward improvement in the CPAP group.
- Commentary: CPAP therapy has no-to-minor positive effect on glycemic variables in T2D patients.
- Effect of Curcumin on Glycaemic and Lipid Parameters in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- 5 RCTs using curcumin for those w/ PCOS
- Curcumin therapy associated with:
- Reduced fasting glucose (-3.68 mg/dL)
- Reduced insulin levels (-1.72 µUI/mL)
- NO change in lipids
- Commentary: Curucmin led to a statistically significant (but not clinically significant) improvement in cardiometabolic markers in a PCOS cohort.
- Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS-Results from an Open Label Study
- 73 female IBS-M patients randomized to:
- Low FODMAP diet
- IgG based elimination diet (eliminated foods that had high IgG levels)
- Control diet recommended by gastroenterologist
- After 8 weeks:
- IgG elimination diet saw more symptom improvement compared to low FODMAP diet
- NO improvement in control diet
- Commentary: At first glance this study suggests superiority of IgG based elimination diets. However, after further investigation, we see some methodologic issues with this study:
- The diets did not control for fiber content: during periods of diarrhea, patients in each treatment group were told to reduce insoluble fiber and fat. Conversely, during periods of constipation, patients were told to increase dietary fiber intake (to 30-50 g/day). So, in practice, these diets had a high fluctuation of fiber intake.
- The low FODMAP diet was NOT truly low FODMAP for the course of the 8 weeks
- And the IgG based diet had elements of the low FODMAP diet (during periods of diarrhea)
- The IgG test examined over 269 foods: This would add a considerable cost to the patient. Rather, an empiric trial of an ancestral template +/- further reduction of possible food sensitivities (e.g. low histamine, low nightshade) diets could save the patient financial resources and be more practical in a clinical setting.
- Overall, this was a low powered study that had a few methodological errors to show superiority of an IgG based elimination diet.
- The diets did not control for fiber content: during periods of diarrhea, patients in each treatment group were told to reduce insoluble fiber and fat. Conversely, during periods of constipation, patients were told to increase dietary fiber intake (to 30-50 g/day). So, in practice, these diets had a high fluctuation of fiber intake.
- 73 female IBS-M patients randomized to:
- FODMAPs, but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial
- Aim: To see if high intake of FODMAP, gluten, or placebo increased IBS symptoms
- Cross-over study of 103 mod-severe IBS patients randomized to high FODMAP, high gluten, or placebo diet x1 week → separated by one week washout→ switched to another intervention
- At end of the study, FODMAPs caused the greatest increase in IBS symptom severity
- NO difference between gluten or placebo
- Commentary: FODMAPs can be problematic for IBS symptoms.
- Prevalence of disordered eating in adults with gastrointestinal disorders: A systematic review
- 17 studies
- Prevalence of disordered eating ranged from 13-55%
- Higher for those w/ gut-brain GI disorder (e.g. IBS) than organic disease (e.g. IBD)
- Commentary: There is a high prevalence of eating disorders in those w/ GI disorders
- Clinical effectiveness of adding probiotics to a low FODMAP diet: Randomized double-blind placebo-controlled study
- 100 IBS patients put on low FODMAP diet and randomized to probiotic (from food) or placebo
- After 21 days, NO differences in IBS symptoms
- Commentary: This study failed to show an additional benefit of adding a probiotic to a low FODMAP diet. However, this study used a low dose probiotic in food form. Dr. Ruscio wanted to point out our comparison article here.
- Systemic inflammation in the pathogenesis of irritable bowel syndrome associated with obesity
- 97 IBS patients w/ obesity, 21 healthy controls measured for inflammatory markers
- IBS patients had higher CRP, fibrinogen, and TNFα compared to healthy controls
- Commentary: Both obesity and IBS are associated w/ higher levels of inflammation.
- Effects of an elemental diet to reduce adverse events in patients with esophageal cancer receiving docetaxel/cisplatin/5-fluorouracil: a phase III randomized controlled trial-EPOC 2 (JFMC49-1601-C5)
- 113 patients w/ esophageal cancer on chemotherapy randomized to elemental diet (ED) or no therapy
- ED group had:
- Reduced oral mucositis rates (15% vs 34%)
- Lower CRP
- Commentary: Elemental dieting can improve oral mucositis rates and lower inflammation in those taking chemotherapy.
- Impact of timing of PERT on gastrointestinal symptoms in Danish children and adolescents with CF
- Cross-over trial of 30 cystic fibrosis (CF) patients taking pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (common in CF)
- Randomized to taking PERT either before or after meals, then switched to other treatment arm
- After 4 weeks of each intervention, there was NO significant difference regarding abdominal pain, bowel habits or QOL related to GI symptoms
- Commentary: It does NOT make a big difference if PERT is taken before or after a meal.
- Self-reported Wheat Sensitivity in Irritable Bowel Syndrome and Healthy Subjects: Prevalence of Celiac Markers and Response to Wheat-free Diet
- 204 IBS patients and 400 healthy persons evaluated for self-reported wheat sensitivity
- tTG and HLA allele genotyping performed on those who reported wheat sensitivity
- Self-reported wheat sensitivity (symptoms with wheat consumption):
- 11.3% IBS patients
- 0% healthy controls
- Of the 11% of IBS patients who reported wheat sensitivity:
- 0% had tTG Ab positivity
- 61% positive for HLA DQ2 or DQ8
- After 6 week wheat-free diet, ALL patients reported improved bloating/diarrhea/constipation
- Commentary: True wheat sensitivity remains relatively rare in IBS patients. However, in those w/ self-reported wheat sensitivity, a wheat-free diet can improve symptoms.
- Systematic review with meta-analysis: association of Helicobacter pylori infection with gastro-oesophageal reflux and its complications
- Aim: To examine association between H pylori infection and GERD symptoms and erosive esophagitis
- 11 observational studies of H pylori and GERD
- 7 studies: H pylori associated w/ LOWER rates (OR 0.74)
- 4 studies: NO association
- 26 studies of patients w/ GERD symptoms:
- H pylori associated w/ LOWER rates (OR 0.7)
- 9 studies showed NO association between H pylori and Barrett’s esophagus
- Commentary: H pylori infection/colonization appears to be associated w/ decreased odds of GERD symptoms and erosive esophagitis, as well as lower rates of Barrett’s esophagus (contrary to popular thought).
- Aloe barbadensis Mill. extract improves symptoms in IBS patients with diarrhoea: post hoc analysis of two randomized double-blind controlled studies
- 213 IBS patients from two different RCTs combined
- Aloe extract therapy associated w/ improved IBS symptoms only in IBS-D type (not other IBS types)
- Commentary: Aloe may be an effective strategy to improve symptoms in IBS-D. Dr. Ruscio wanted me to mention, don’t be afraid of therapies because they might be ‘high FODMAP’ like aloe or at least as it is sometimes claimed to be.
- Supplementation of dehydroepiandrosterone (DHEA) in pre- and postmenopausal women – position statement of expert panel of Polish Menopause and Andropause Society
- Consensus statement on DHEA supplementation for women
- DHEA supplementation is effective in the following cases:
- Adrenal insufficiency and chronically treated with exogenous glucocorticoids
- Postmenopausal women with low bone mineral density and/or osteoporosis
- Premenopausal women with sexual disorders and low libido
- Vaginal administration in women with vulvovaginal atrophy of menopause
- DHEA supplementation is probably effective in the following cases:
- Postmenopausal women with low libido
- Infertile women with diminished ovarian reserve
- Depression and anxiety
- Obesity and insulin resistance
- Doses used in clinical trials:
- Examining the effects of calorie restriction on testosterone concentrations in men: a systematic review and meta-analysis
- 7 RCTs looking at association between caloric restriction (CR) and testosterone levels
- 3 of 4 studies of overweight/obese men showed CR associated w/ LOWER testosterone
- Commentary: CR can reduce testosterone levels in healthy men but improve levels in overweight/obese men.
- Efficacy of Myo-inositol and D-chiro-inositol combination on menstrual cycle regulation and improving insulin resistance in young girls with PCOS: A randomized open-label study
- 70 PCOS girls 15-24 yo w/ delayed cycles randomized to Myo-inositol-D-chiro-inositol combination (550 mg + 150 mg) or combined birth control (CBC)
- Results:
- Spontaneous menses resumed in 84.85% of girls on MI+DCI
- Average cycle length reduced with both MI+DCI (124 to 58 days) and CBC (106 to 31 days)
- Regular menstrual cycles were established in 27% of girls with MI+DCI and 88% with CBC
- Three months after stopping the treatment, 86% on MI+DCI and 74% on CBC continued to have spontaneous cycles
- Commentary: MI+DCI has efficacy for treating PCOS comparable to standard of treatment combined birth control.
- Is there a role for Natural Desiccated Thyroid in the treatment of levothyroxine unresponsive hypothyroidism? Results from a Consecutive Case Series
- 28 women and 3 men who switched from levothyroxine (due to continued symptoms) to natural desiccated thyroid
- Adverse effects:
- 1 discontinued due to lack of response
- 2 had cardiac events
- On average:
- Quality of life increased
- Symptoms decreased
- Commentary: Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism treated with NDT. However, a recent meta-analysis of 18 studies failed to show a benefit of combined thyroid therapy when compared to levothyroxine. Reminder: As per our thyroid algorithm, desiccated and/or combination therapy is an option, but is reserved for end phase.
- Health risk assessment of exposure to organochlorine pesticides in the general population in Seoul, Korea over 12 years: A cross-sectional epidemiological study
- Evaluated the 12-year trends in serum levels of 28 organochlorine pesticides (OCPs) in 880 adults
- Higher levels associated with:
- Higher BMI
- Age
- Hypertension
- Higher creatinine
- Higher uric acid
- Higher TSH
- Lower fT4
- Commentary: Toxins such as OCPs are associated w/ cardiometabolic issues, kidney dysfunction, and thyroid dysfunction.
- Effect of weight loss on erectile function in men with overweight or obesity: A meta-analysis of randomised controlled trials
- 5 studies, 619 overweight/obese participants
- Body weight reduction (mean reduction -18.1 kg) was associated w/ an improvement of erectile dysfunction
- Correlative studies on vitamin D and total, free bioavailable testosterone levels in young, healthy men
- 176 young healthy men
- NO association between vitamin D levels and FSH, LH, total or free testosterone
- No association of cigarette smoking and depressive symptoms with cortisol concentration in adolescents. Results from a population-based Swedish cohort
- Aim: Assess if smokers have higher cortisol levels than non-smokers, and if higher cortisol levels are associated with depressive symptoms
- Salivary samples measured in 409 participants
- Results:
- NO difference in cortisol levels between smokers and non-smokers
- Cortisol levels NOT associated w/ depressive symptoms
- Commentary: This study failed to support HPA axis dysregulation in depressive symptoms.
- A systematic review and meta-analysis of the benefits of a gluten-free diet and/or casein-free diet for children with autism spectrum disorder
- 8 studies using gluten-free or casein-free diet in total of 297 participants w/ autism
- 5 of 8 studies reported significant reduction in autism-related behavior
- 3 studies reported improvement in cognitive function
- Commentary: Gluten-free or casein-free diet may be an effective strategy for those w/ autism.
- Time-Restricted Feeding and Aerobic Performance in Elite Runners: Ramadan Fasting as a Model
- 15 trained male endurance runners
- Completed running test before and after Ramadan fasting
- Results:
- NO difference in body fat, mass, or muscle mass
- NO difference in VO2max
- IMPROVED time to exhaustion and maximal running speed
- Commentary: Prolonged fasting can maintain or even slightly improve endurance performance.
- Wait-there’s evidence for that? Integrative medicine treatments for major depressive disorder
- Highest level of evidence for treating depression:
- St. John’s Wort
- Omega-3 Fatty Acids
- S-adenosyl-L-methionine (SAMe)
- Saffron
- Modest level of evidence:
- Acetyl-l-carnitine
- L-methylfolate
- DHEA
- Lavender
- Highest level of evidence for treating depression:
- Effects of a Short Daytime Nap on the Cognitive Performance: A Systematic Review and Meta-Analysis
- 11 studies, 381 participants w/ mean duration nap of 55 ± 30 min
- Daytime naps were associated with improved overall cognitive performance
- Especially for naps before 1 pm
- Commentary: Daytime napping can improve cognitive performance.
- Dietary fatty acids and risk for Alzheimer’s disease, dementia, and mild cognitive impairment: A prospective cohort meta-analysis
- 14 studies, 54,177 participants total:
- 1,696 patients with Alzheimer’s
- 1,118 patients with dementia
- 2,889 with mild cognitive impairment
- Higher intake of omega-3 fatty acids was associated w/ LOWER odds of mild cognitive impairment (RR 0.86) but NOT for dementia or Alzheimer’s.
- 14 studies, 54,177 participants total:
- Obstructive sleep apnea is common in patients with high-impact chronic pain – an exploratory study from an interdisciplinary pain center
- 90 patients w/ chronic pain underwent home sleep test (sleep apnea confirmed w/ polysomnography)
- 51.3% patients had OSA
- Commentary: There is a high prevalence of sleep apnea in those w/ chronic pain.
- Oral appliance therapy in obstructive sleep apnea and snoring – systematic review and new directions of development
- 15 studies
- 92% of those using mandibular advancement devices improved sleep apnea (per apnea-hypopnea index).