- The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial
- Open-label study (patients knew what they were getting) of 44 patients w/ mild-to-moderate Crohn’s disease w/ elevated inflammatory markers
- Randomized to:
- Crohn’s disease exclusion diet (CDED)
- Or CDED + partial enteral nutrition (e.g. elemental diet)
- After 12 weeks, the CDED + elemental diet group had higher clinical remission (68% vs 57%)
- Both groups had sustained remission of 35% at 6 month followup
- Both groups had reduced CRP levels
- Commentary: This study suggests that diet alone can induce remission in Crohn’s disease and an elemental diet can have synergistic effects. CDED is broken up into 3 phases and emphasizes lower fiber foods similar to SCD or Paleo low FODMAP diet. More info can be found here.
- Dietary strategies for chronic spontaneous urticaria: an evidence-based review
- Review of nonpharmacologic strategies for chronic spontaneous urticaria
- Grade A recommendations:
- Elimination diet
- Vitamin D
- DAO supplementation
- Probiotics
- Grade B recommendation:
- Low-histamine diet
- Grade C recommendation:
- Gluten elimination
- Non-Lactulose Medication Therapies for the Management of Hepatic Encephalopathy: A Literature Review
- Suggests that probiotics may be efficacious in the use of treating hepatic encephalopathy
- Effects of Resistant Starch on Symptoms, Fecal Markers and Gut Microbiota in Parkinson’s Disease – the RESISTA-PD Trial
- 87 participants:
- 32 Parkinson’s Disease (PD) patients received resistant starch (RS)
- 30 control subjects received RS
- 25 PD patients received solely diet recommendations
- After 8 weeks, only the PD who received RS had:
- Increased fecal butyrate
- Reduced fecal calprotectin
- Reduced non-motor symptoms
- 87 participants:
- Association Between the Sulfur Microbial Diet and Risk of Colorectal Cancer
- Combination of 3 larger prospective cohorts, including 214,797 participants
- Higher intakes of french fries, red meats, and processed meats and low intakes of fruits, vegetables, whole grains, and legumes was associated with a higher risk of colorectal cancer.
- Commentary: In other words, a processed foods rich diet is associated w/ a higher colorectal cancer risk.
- Soluble and Insoluble Dietary Fiber Consumption and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis
- Both soluble and insoluble fiber intake was associated with reduced colorectal cancer risk
- The reduction of risk was equal in both types of fiber (effect size 0.77-0.78)
- Long-term risk of upper gastrointestinal bleeding after Helicobacter pylori eradication: a population-based cohort study
- Does H. pylori increase the risk of upper GI bleeding (UGIB) even after eradication?
- 62,000 H. pylori eradicated participants, 62,000 matched H. pylori negative controls
- Followed over 8 years
- Compared to controls, H. pylori-eradicated patients had a significantly higher risk of UGIB (HR 1.65)
- Commentary: H. pylori increases the risk of UGIB, even after eradication.
- A positive diagnostic strategy is safe and saves endoscopies in patients with irritable bowel syndrome: A five-year follow-up of a randomized controlled trial
- 352 IBS patients randomized to limited lab strategy (limited blood tests) or extensive lab strategy (extensive blood tests, fecal samples, sigmoidoscopy w/ biopsy)
- At 5 year followup:
- No cases of celiac disease, and GI cancers
- Comparable numbers were diagnosed with IBD, benign gynecologic cancer, and upper GI conditions
- Commentary: A limited lab approach is an efficacious way of treating IBS patients and can save on financial resources and burden on the patient. Consider reserving extensive lab workup.
- Treatment of psoriasis vulgaris using Bacteroides fragilis BF839: a single-arm, open preliminary clinical study
- 27 psoriasis patients all given Bacteroides fragilis probiotic
- After 12 weeks:
- Symptom severity reduced (9.1 to 5.8)
- High response rate:
- 65% had at least 30% reduction in symptoms
- 42% had at least 50% reduction in symptoms
- 19% had at least 75% reduction in symptoms
- Commentary: This study suggests that probiotics can be an effective strategy for psoriasis. Note: This study was not placebo controlled, though.
- Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway
- 8 patients w/ constipation, received FMT x3
- 6 of the 8 patients (75%) achieved clinical remission of symptoms
- Improved quality of life
- High FODMAP diet causes barrier loss via lipopolysaccharide-mediated mast cell activation
- Mice fed a high FODMAP diet had mast cell activation
- Intestinal permeability was dependent on this mast cell activation
- A low FODMAP diet was able to resolve the mast cell activation
- Commentary: Although this is an animal study (which we rarely showcase), it suggested a possible connection between dietary mismatch and mast cell activation.
- Microinflammation in the intestinal mucosa and symptoms of irritable bowel syndrome
- Biopsies taken from IBS and healthy controls
- Concentration of mast cells and lymphocytes in the duodenum was significantly higher in IBS patients than in controls
- Commentary: This study hints to the immune system derangement that may contribute to IBS.
- Association of small intestinal bacterial overgrowth with nonalcoholic fatty liver disease in children: A meta-analysis
- 3 studies, 205 children
- Children with SIBO were more likely to have fatty liver (odds ratio = 5.27)
- Commentary: This highlights the gut-metabolic connection. However, only an association (not causation) can be inferred from this study.
- Thyroid Function and the Risk of Alzheimer’s Disease: A Mendelian Randomization Study
- Mendelian randomization study of 119,715 participants including 71,880 Alzheimer’s Disease (AD) cases
- Higher levels of genetically predicted TSH within the normal range was associated w/ a decrease of AD risk in younger individuals
- No relationship between fT4 or hypothyroidism and AD risk
- Commentary: This study did not find an association between low thyroid function and AD risk.
- Testosterone Therapy for Late-Onset Hypogonadism Improves Erectile Function: A Systematic Review and Meta-Analysis
- 18 studies, 1,458 participants
- Testosterone therapy improved erectile function compared to placebo
- Especially for those using testosterone gel, used >30 weeks, without diabetes
- Commentary: Testosterone replacement therapy can improve erectile dysfunction.
- Efficacy of flavonoids on biomarkers of type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
- 28 RCTs
- Flavonoids lead to significant reduction in:
- Fasting glucose
- A1C
- Insulin resistance
- Triglycerides
- Total cholesterol
- LDL-C
- Trace elements in children with autism spectrum disorder: A meta-analysis based on case-control studies
- 22 studies,1,014 children with autism and 999 healthy controls
- Children w/ autism had higher levels of barium, mercury, lithium, lead, and copper
- Commentary: Heavy metal toxicity may play a role in neuropsychological disorders.
- The effects of vitamin D supplementation on prognosis in patients with mild obstructive sleep apnea syndrome
- 19 adults w/ obstructive sleep apnea (OSA)
- Given 50,000 IU Vit D per week
- After 8 weeks, there was less obstructive apneas and hypopneas
- Commentary: Vit D may have a favorable effect on OSA. Dr. Ruscio also wanted to mention: This showcases our foundations-first approach can also help sleep.
- Reducing cost and time to diagnosis and treatment of obstructive sleep apnea using ambulatory sleep study: a Singapore sleep centre experience
- Retrospective study of 1,898 patients who had sleep study
- 88% had in-lab PSG, 22% had home sleep study (WatchPat)
- Patients in the home sleep test group had:
- Shorter time to diagnosis (21 days versus 79.8 days)
- Shorter time to treatment (46.3 days versus 118.4 days)
- More cost-savings ($1,117)
- Commentary: A home sleep test is a viable alternative to in-lab PSG.
- Impact of insufficient sleep on dysregulated blood glucose control under standardised meal conditions
- 953 healthy adults (41% twins) consumed isoenergetic standardized meals over 2 weeks
- Measured sleep variables and continuous glucose monitoring
- Poor sleep efficiency and later bedtime routines are associated with higher postprandial glycaemic responses to breakfast the following morning
- Deviation from usual sleep pattern associated with worse postprandial glycaemic control
- Commentary: Optimal sleep is a vital part of glycemic control.
- Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease-A randomized controlled trial
- 30 type 2 diabetic patients w/ kidney disease randomized to:
- Very low carb (<20g carbs/d)
- Or low protein, low salt diet
- After 12 weeks, the low carb group had:
- No change in serum creatinine
- More decrease in A1C (-1.3% vs -0.7%)
- More reduction in insulin dose (-39 IU vs +0 IU)
- Reduction in LDL-C
- Reduction in inflammatory markers (IL-6)
- More weight loss (-4.0 kg vs +0.2 kg)
- Commentary: This study demonstrated that a very low carb (e.g. ketogenic) and higher protein diet is both safe and can ameliorate glycemic abnormalities in those w/ kidney disease.
- 30 type 2 diabetic patients w/ kidney disease randomized to:
- Effects of respiratory training on obstructive sleep apnea: systematic review and meta-analysis
- 6 studies
- Breathing exercises (e.g. expiratory exercises) can reduce the apnea-hypopnea index and decrease levels of daytime fatigue
- Commentary: Another non-CPAP therapy for sleep apnea. An example of an expiratory training device can be found here.
- The diagnostic accuracy of HbA 1c , compared to the oral glucose tolerance test, for screening for type 2 diabetes mellitus in Africa-a systematic review and meta-analysis
- 11 studies, 12,925 participants
- An A1C >6.5% missed a type 2 diabetes diagnosis 42.3% of the time when compared to oral glucose tolerance test
- Commentary: Consider a continuous glucose monitor to get more data of glycemic control instead of relying solely on A1C.
- Blastocystis in the faeces of children from six distant countries: prevalence, quantity, subtypes and the relation to the gut bacteriome
- 244 asymptomatic/healthy children, analyzed for Blastocystis prevalence using PCR (very sensitive method)
- Blasto was found in 36% of children
- Coinfection of other parasites was found in 12% of individuals
- The most frequent subtype was ST3 (49%), ST1 (36%) and ST2 (25%)
- Commentary: This study showed a notable prevalence of Blasto in a cohort of asymptomatic children. This may suggest that Blasto is more of a commensal than a pathogen. Be on the lookout for a large review of Blasto we will be publishing here soon.
- The Association between Free Sugars Consumption and Laryngopharyngeal Reflux: A Cross-Sectional Study among Chinese Adolescents
- Cross-sectional study of 1,517 participants
- Laryngopharyngeal reflux (LPR) was found in 8.1% of participants
- Higher sugar intake was associated w/ the presence of LPR (OR 1.7)
- Commentary: Poor diet may be a contributing factor to LPR.
- Irritable Bowel Syndrome on Inflammatory Bowel Disease in Deep Remission: No Relation with Remission Deepening and Inflammation
- 43 ulcerative colitis (UC) patients, 38 Crohn’s disease (CD) patients in remission for >6 months
- Had colonoscopy, biopsy, fecal calprotectin, inflammatory markers, and IBS evaluation
- IBS frequency was:
- 20.9% in UC cases
- 28.9% in CD cases
- Inflammatory markers were NOT associated w/ remission on colonoscopy
- Commentary: Two things to note:
- 1) The rate of IBS is notable in those w/ IBD
- 2) Inflammatory markers did NOT correlate well w/ histological remission
- Effect of amino acid-based formula added to four-food elimination in adult eosinophilic esophagitis patients: A randomized clinical trial
- 41 patients w/ eosinophilic esophagitis (EoE)
- Randomized to:
- Elimination diet
- Or elimination diet + elemental diet
- After 6 weeks, the elimination + elemental diet had:
- Better remission rate (48% vs 25%)
- Improvement of quality of life (elimination diet alone had NO improvement)
- Commentary: An elemental diet can improve EoE and increase quality of life.
- Therapeutic Potential of Escherichia coli Nissle 1917 in Clinically Remission-attained Ulcerative Colitis Patients: A Hospital-based Cohort Study
- 94 UC patients who received E coli Nissle 1917 probiotic after being in clinical remission for more than 3 months
- After 3 months of supplementation:
- NO change in fecal calprotectin
- Increased bodyweight
- Reduced disease activity
- Commentary: Probiotics improved ulcerative colitis disease activity independent of changes in fecal calprotectin.
- Oral Health Status in Patients with Inflammatory Bowel Diseases: A Systematic Review
- 6 studies
- Crohn’s disease and ulcerative colitis patients had a 2-3x increased odds of periodontitis compared to controls
- The influence of probiotics on gastrointestinal tract infections among children attending childcare : A systematic review and meta-analysis
- 18 RCTs, 779 children
- Probiotics may reduce the risk of GI infections by 26% in kids attending daycare
- Commentary: Another large study supporting the efficacy of probiotics reducing infection rates.
- Use of a probiotic mixture containing Bifidobacterium animalis subsp. lactis BB-12 and Enterococcus faecium L3 as prophylaxis to reduce the incidence of acute gastroenteritis and upper respiratory tract infections in children
- 203 healthy children randomized to probiotic or no treatment
- The probiotic group had:
- Reduced acute gastroenteritis (82% reduction in incidence, 45% reduction in duration)
- Reduced upper respiratory tract infection (84% reduction in incidence, 50% reduction in duration)
- x3 increased salivary sIgA levels
- Commentary: Probiotics can reduce both GI and respiratory tract infections by bolstering the immune system.
- Fecal calprotectin levels used as a noninvasive method for screening for chronic gastritis in pediatric patients. A descriptive study
- 67 gastritis pediatric patients, measured fecal calprotectin levels
- The mean calprotectin levels were higher in the gastritis vs healthy control group (153.4 μg/g vs 43.8 μg/g) but lower than IBD patients
- Among gastritis patients, levels were higher in the H. pylori + group compared to the H. pylori – group
- Commentary: This study suggests a higher calprotectin level in those with gastritis, especially for those who are positive for H. pylori.
- Small intestinal bacterial overgrowth in Alzheimer’s disease
- 45 Alzheimer’s Disease (AD) patients and 27 healthy controls given lactulose breath test
- SIBO was found in 49% in AD patients, 22% in controls
- Among those w/ AD, SIBO positivity was NOT associated w/ cognitive impairment
- Zonulin levels were higher in the AD patients compared to controls (73.5 vs 49.0 ng/ml)
- Commentary: SIBO and increased zonulin levels are found at higher rates in those w/ AD.
- Gluten intake and risk of digestive system cancers in three large prospective cohort studies
- 3 prospective cohorts including 146,206 participants
- Gluten intake was NOT associated w/ an increased risk of GI cancer
- Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet
- 41 IBS patients, 41 healthy controls
- Measured microbiota before and after 4 weeks of low FODMAP diet
- 50% of IBS cases had a “pathogenic microbial composition”
- A low FODMAP diet shifted this to a healthier profile
- Commentary: In other words, a low FODMAP diet can rectify dysbiosis.
- Efficacy of probiotic adjuvant therapy for irritable bowel syndrome in children: A systematic review and meta-analysis
- 9 RCTs of children w/ IBS
- Probiotics significantly reduced abdominal pain and improved GI symptom score
- Commentary: High-quality study validating probiotics for IBS in kids.
- Efficacy of a probiotic supplement in patients with atopic dermatitis: a randomized, double-blind, placebo-controlled clinical trial
- 80 patients w/ mild-severe atopic dermatitis, randomized to to placebo or probiotic
- After 60 days, the probiotic group had:
- Improved skin smoothness
- Decreased atopic dermatitis symptom score
- Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies
- 9 studies, 756 FMTs
- Pooled adverse event rate was 39.3%
- Most common: Abdominal pain and diarrhea
- Serious adverse event was 5.3%
- Most common: C. diff infection
- Commentary: FMT has a notable adverse event probability. Ironically, the most common serious adverse event from FMT is C. diff infection which is something FMT is used for.
- Dr. Ruscio wanted me to point out this is exactly why we use a foundations up approach for digestive health and do not jump to new/novel.
- Cognitive Impairment in Adult Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
- 12 studies, 687 participants
- Compared to controls, those w/ IBD had deficits in:
- Attention
- Executive function
- And memory
- Commentary: This study suggests that those w/ IBD are more likely to have cognitive impairment, hinting at the gut-brain connection.
- Polyphenols for improvement of inflammation and symptoms in rheumatic diseases: systematic review
- 17 articles examining polyphenols for rheumatoid arthritis
- Intake of polyphenols had:
- Benefit on clinical outcomes in 94% of the studies
- Improved pain in 65% of studies
- Reduced inflammation in 59% of studies
- Commentary: Polyphenols may be a useful tool to manage rheumatoid disorders.
- A Modified MCT-Based Ketogenic Diet Increases Plasma β-Hydroxybutyrate but Has Less Effect on Fatigue and Quality of Life in People with Multiple Sclerosis Compared to a Modified Paleolithic Diet: A Waitlist-Controlled, Randomized Pilot Study
- 15 multiple sclerosis (MS) patients randomized to:
- Modified Paleo diet
- MCT-based ketogenic diet (coconut as main fuel source)
- Usual diet
- After 12 weeks:
- The keto group achieved nutritional ketosis
- The Paleo group had significant reduction in fatigue levels
- The Keto group had significant reductions in fasting glucose and insulin
- However, no clinical outcomes significantly changed.
- Commentary: Both a Paleo and ketogenic diet may be used in those w/ MS. The former (Paleo) may be more practical for patients resistant to dietary shifts.
- 15 multiple sclerosis (MS) patients randomized to:
- Low-Dose Naltrexone Use for Patients with Chronic Regional Pain Syndrome: A Systematic Literature Review
- 29 studies
- Low-dose Naltrexone was associated with lower symptoms and better sleep in patients w/ chronic pain
- The effect of obstructive sleep apnea on the increased risk of cardiovascular disease: a systematic review and meta-analysis
- 12 studies
- Obstructive sleep apnea is associated w/ a higher risk of:
- Cardiovascular disease (OR 1.71)
- Stroke (OR 1.86)
- Mortality (1.77)
- Commentary: Sleep apnea is associated w/ poor cardiometabolic outcomes.
- Causal Effect of Obstructive Sleep Apnea on Atrial Fibrillation: A Mendelian Randomization Study
- Genetic data from 217,955 participants
- Genetic OSA was associated with an increased risk of atrial fibrillation (odds ratio 1.21)
- Commentary: Sleep apnea may be a contributing factor to atrial fibrillation.
- Randomized trial of vitamin D versus placebo supplementation on markers of systemic inflammation in hypertensive patients
- 187 participants w/ hypertension and low Vit D levels (<30 ng/mL)
- Randomized to placebo or Vit D (2,800 IU/d)
- After 8 weeks, Vit D supplementation had no significant reduction in inflammatory markers
- Association between obstructive sleep apnea syndrome and nocturia: a meta-analysis
- 13 studies, 406 OSA patients and 9,518 controls
- OSA was associated with a higher rate of nocturia (RR 1.5)
- Commentary: Nocturia may be an associated symptom of sleep apnea.
- Impact of dietary nitrate supplementation on exercise capacity and cardiovascular parameters in chronic respiratory disease: a systematic review and meta-analysis
- 11 studies, 282 participants
- Dietary nitrate supplementation (e.g. beetroot juice) reduced systolic blood pressure (-3.4 mmHg)
- NO association with exercise capacity
- Treating hypothyroidism is not always easy: When to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy
- Narrative review of treating the nuances of subclinical hypothyroidism (SCH)
- Treating SCH is fairly common but the majority of cases do not see benefits
- “Some of this dissatisfaction is unintentionally caused by well-meaning practitioners who enthusiastically begin patients on levothyroxine for minimal hypothyroidism, with the promise that it will address their symptoms. Unfortunately, the evidence suggests that few such patients will experience long-term benefit in their symptoms. And in the elderly, aggressive treatment may possibly cause harm.”
- Many patients are put on unnecessary thyroid medication
- “A 2018 study using a United States insurance claims database linked to laboratory data found that 65.7% of patients started on levothyroxine had subclinical hypothyroidism, and the mean TSH level at the initiation of treatment was 5.3 mIU/L.”
- TSH is highly variable. Get a repeat TSH before rushing to treat SCH
- “Before diagnosing and treating subclinical hypothyroidism, one must ascertain whether steady-state conditions exist, and whether hypothyroidism is transient.”
- “Additionally, TSH is released in pulses, which becomes more frequent in the evening; TSH sampled at the time of a pulse might transiently be just above the upper limit of normal, especially in a patient whose baseline TSH levels are in the upper portion of the normal range.”
- “Among over 422,000 patients, none of these patients were on thyroid medications, 3% had an elevated TSH; when lab tests were repeated, 62% became normal spontaneously. The European Thyroid Association guideline for management of subclinical hypothyroidism recommends a repeat TSH measurement preferably after a 2–3-month interval.”
- The upper limit of TSH is age-dependent
- “While it is true that the 97.5 percentile for TSH is 3.6 mIU/L in adult subjects under age 40, the normal range is shifted to higher values with aging, and the 97.5 percentile increases to 7.5 mIU/L in subjects over age 80 with no evidence of thyroid disease (negative thyroid peroxidase [TPO] antibodies, no thyroid history, and no drugs that affect thyroid function).”
- Most patients w/ a TSH >10 should be treated
- “…there is general agreement that patients with TSH levels that exceed 10 mIU/L should be treated.”
- Treating SCH w/ TSH <10 usually does NOT result in symptom improvement
- “…A large RCT of 737 patients over age 65 with TSH values 4.6–19.99 mIU/L, average TSH 6.4 mIU/L, found no change in cognitive function or improvement in symptoms compared to placebo when the mean TSH was reduced to 3.63 with levothyroxine treatment.”
- “Finally, a meta-analysis of 21 RCTs showed no change in quality of life, thyroid-related symptoms, fatigue, or depressive symptoms with levothyroxine treatment”.
- “These data suggest that few, if any, patients have improvement in fatigue, depression, or “brain fog” when mild thyroid dysfunction is treated with levothyroxine.”
- SCH is associated w/ higher cardiovascular disease risk
- “Another study of subjects over age 65 found the HR for cardiovascular mortality in subjects with subclinical hypothyroidism to be 1.7 if TSH exceeded 6.38 mIU/L. And a third study of 115,746 subjects where 1841 had subclinical hypothyroidism (TSH 5.00–19.96) found a relative risk of 1.30 for all-cause mortality and 1.68 for cardiovascular mortality.”
- Treating SCH w/ TSH between 7-10 who are younger and at higher risk for cardiovascular disease could be beneficial
- “While the evidence is far from conclusive, it strongly suggests that younger patients have an overall cardiovascular benefit if subclinical hypothyroidism is treated, whereas older patients may experience no benefit but possibly demonstrate harm.”
- These are the groups of patients the author recommends treating SCH:
- Younger (<70 yo), TSH between 7-10
- Older (>70 yo), TSH between 7-10 with significant symptoms
- TSH >10 regardless of age
- Commentary: This is a really comprehensive and fair review of the SCH literature. Well worth a read.
- The efficacy of Lactobacillus acidophilus and rhamnosus in the reduction of bacterial load of Helicobacter pylori and modification of gut microbiota-a double-blind, placebo-controlled, randomized trial
- 40 adults w/ moderate-high H. pylori counts
- Randomized to probiotic (L acidophilus/ L rhamnosus) or placebo
- After 4 weeks, H. pylori counts were significantly lower in the probiotic group
- However, the eradication rate for H. pylori was 0% in both groups
- There was no change in bacterial diversity between the two groups
- Commentary: Despite some null findings, probiotics were able to reduce H. pylori counts.
- Effects of non-viable Lactobacillus reuteri combining with 14-day standard triple therapy on Helicobacter pylori eradication: A randomized double-blind placebo-controlled trial
- 200 H. pylori colonized participants, randomized to non-viable L. reuteri probiotic or placebo x4 weeks
- Also received triple eradication therapy x2 weeks
- After 4 weeks:
- No difference in eradication rate (86.2% probiotic, 87.2% placebo)
- Less abdominal distension in the probiotic group (5.1% vs 16.3%)
- Less diarrhea in the probiotic group (11.1% vs 23.5%)
- Commentary: This study suggests that probiotics are an important part of managing H. pylori colonization.
- The impact of Helicobacter pylori infection, eradication therapy, and probiotics intervention on gastric microbiota in young adults
- 95 H. pylori colonized participants, 56 healthy controls
- H. pylori colonized participants randomized to:
- Probiotics alone
- Quadruple therapy alone
- Probiotics + Quadruple therapy
- After 4 weeks:
- The probiotic + quadruple therapy had a microbiome more closely resembling the healthy controls compared to quadruple therapy alone
- Commentary: This study highlights probiotics’ effect on correcting dysbiosis.
- Efficacy of rifaximin in treating with small intestine bacterial overgrowth: a systematic review and meta-analysis
- 21 observational studies, 5 RCTs, 874 patients
- Rifaximin’s overall eradication rate of SIBO was 59-63%
- Higher efficacy for higher doses
- However, in the RCTs, there was no difference between Rifaximin and placebo (although there was a small sample size)
- Impact of Probiotics on the Performance of Endurance Athletes: A Systematic Review
- 9 studies
- 3 studies reported improvement of sports performance
- 6 studies reported improvements in oxidative stress, increased immune system function, and decreased upper respiratory tract infection
- Prucalopride in diabetic and connective tissue disease-related gastroparesis: Randomized placebo-controlled crossover pilot trial
- Crossover study of 15 gastroparesis patients (13 from diabetes, 2 from connective tissue disease), randomized to 2 weeks of prucalopride or placebo, then switched to different group w/ 2 week washout
- The prucalopride group had:
- Faster gastric emptying time
- Higher weekly bowel movements (10.5 vs 7.5)
- NO difference in gastroparesis symptoms
- Commentary: This study showed that prucalopride (a 5-HT4 serotonin agonist prokinetic) had favorable effects on gastric motility but NO significantly better improvement in symptoms when compared to placebo.
- Non-antibiotic interventions for prevention of urinary tract infections in children: a systematic review and meta-analysis of randomized controlled trials
- 16 RCTs, 1,426 participants
- Probiotic therapy was more effective in reducing UTI recurrence (RR 0.52) and lowered antibiotic resistance when compared with placebo.
- Commentary: This meta-analysis suggests that probiotics may be a useful strategy for those w/ recurrent UTIs and should be used alongside conventional antibiotics.
- Prevalence of migraine in adults with celiac disease: A case control cross-sectional study
- Cross-sectional study of 1,000 celiac disease patients compared to healthy controls
- Those w/ Celiac disease had a higher prevalence of both headache (34% vs 27% in controls) and migraines (20.7% vs 11.9% in controls) when compared to controls
- Efficacy and Outcomes of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease
- Multicenter retrospective review of 396 pediatric patients, including 148 with IBD
- Children with IBD had the same success rate for FMT to treat recurrent C. diff infections when compared to those without IBD (76% vs 81%)
- Commentary: According to this multicenter review, the efficacy of FMT for treating rCDI was the same for kids w/ and without IBD.
- Probiotic Supplementation and Micronutrient Status in Healthy Subjects: A Systematic Review of Clinical Trials
- 14 studies
- With high degree of heterogeneity, intake of probiotics in healthy subjects was associated with a beneficial impact on certain micronutrient levels (vitamin B12, calcium, folate, iron and zinc)
- Commentary: Dr. Ruscio wanted to remind everyone – This is why we at the Ruscio Institute for Functional Medicine (the clinic) address gut health before attempting to optimize micronutrient levels.
- Blood Trace Element Status in Multiple Sclerosis: a Systematic Review and Meta-analysis
- 32 studies, 1,567 Multiple Sclerosis (MS) patients, 1,328 healthy controls
- Levels of zinc (-7.83 mcg/dL) and iron (-13.66 mcg/dL) were lower in the MS patients
- No difference in magnesium, selenium, or copper
- Commentary: This meta-analysis showed lower levels of zinc and iron between MS patients and healthy controls.
- D-Chiro-Inositol improves testosterone levels in older hypogonadal men with low-normal testosterone: a pilot study
- 10 older men w/ low testosterone levels
- All took D-chiro-inositol (600 mg/ BID)
- After 30 days, participants had
- Increased testosterone levels (222 to 262 ng/dL)
- Reduced estrogen levels (42 to 34 pg/mL)
- Improved glycemic markers (fasting glucose 103 to 91 mg/dL)
- Commentary: This small study suggested a beneficial effect of D-chiro-inositol on the male sex hormone profile.
- Association between vitamin D deficiency and hypothyroidism: results from the National Health and Nutrition Examination Survey (NHANES) 2007-2012
- 616 participants from NHANES w/ hypothyroidism, 7,329 controls
- Vitamin D levels were lower in the hypothyroid group compared to healthy controls:
- Insufficient (20-30 ng/mL): 38% hypothyroid, 32.7% controls
- Deficient (<20 ng/mL): 25.6% hypothyroid, 20.6% controls
- Commentary: Low vitamin D levels are associated with hypothyroidism.
- Association of Sleep-Related Hypoxia With Risk of COVID-19 Hospitalizations and Mortality in a Large Integrated Health System
- Cross-sectional study of 5,402 participants, 935 (35.8%) tested positive for SARS-CoV-2
- Sleep disordered breathing was NOT associated w/ SARS-CoV-2
- However, it was an associated risk factor for worse clinical outcomes
- Commentary: This study suggests that sleep disordered breathing is associated w/ worse clinical outcomes related to COVID infections.
- Curcuma longa extract improves serum inflammatory markers and mental health in healthy participants who are overweight: a randomized, double-blind, placebo-controlled trial
- 90 participants ages 50-69 yo, randomized to curcumin or placebo
- After 12 weeks of supplementation, the curcumin group had:
- Lower body weight
- Lower CRP
- No difference in fibrinogen
- Better mental health scores
- Commentary: This study showed that curcumin improved some inflammatory and mental health markers.
- Objective Evidence of Gastro-Esophageal Reflux Disease is Rare in Patients with Autoimmune Gastritis
- 172 patients w/ autoimmune atrophic gastritis (AAG)
- 38 (22%) had reflux symptoms
- But the majority of them (79%) had a normal endoscopy
- Compared to those without reflux symptoms, those w/ reflux symptoms had:
- NO difference in gastrin
- NO difference in pepsinogen
- NO difference in H. pylori colonization
- Of the 87% who received PPI therapy, only 34% reported benefit
- Commentary: This smaller study highlights a few things:
- 1) A minority of those w/ AAG reported reflux symptoms
- 2) Reflux is a symptom that can be seen in AAG cases despite these individuals having LOW stomach acid production (as compared to high acid)
- 3) Gastrin and pepsinogen were relatively poor predictive markers for who did and who did not have symptoms
- 4) PPI therapy was not a great therapeutic option for those w/ AAG (since it’s a condition of LOW HCl production)
- Efficacy of oral magnesium therapy in the treatment of chronic constipation in spastic cerebral palsy children: a randomized controlled trial
- 100 children w/ cerebral palsy and chronic constipation, randomized to placebo or oral magnesium sulfate (1 mL/kg/day)
- After 1 month, the magnesium group had improved:
- Stool frequency
- Stool consistency
- Painful defecation
- Commentary: Oral magnesium is an effective strategy to improve constipation.
- Changes in oral flora of patients with functional dyspepsia
- 21 functional dyspepsia (FD) patients and 12 healthy controls, measured microbiome of saliva and lactulose breath test for SIBO
- FD patients had a higher abundance of Spirochaetes and a lower abundance of Fusobacteria and Proteobacteria than controls
- 71.4% of the FD group was positive for SIBO (vs 8.3% in controls)
- Commentary: Dysbiosis may play a role in the pathogenesis of functional dyspepsia. Higher rates of SIBO were found in the dyspepsia group vs healthy controls.
- An Investigational Oral Microbiome Drug, CP101, for the Prevention of Recurrent C. difficile Infection: A Randomized, Placebo-Controlled, Multi-Center Trial (PRISM3)
- 198 recurrent C. diff patients who received standard of care antibiotics and then randomized to placebo or full-spectrum microbiota (fecal microbiota transplant capsule) for one time administration
- At a 8 week follow up, the FMT capsule group had higher clinical cure (73.5% vs 55.4%)
- Commentary: FMT capsules may be a promising strategy to prevent recurrent C. diff. infections.
- Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study
- 30 children w/ autism, given FMT x4 weeks
- At 8 week followup:
- Improved GI symptoms by 35%
- Improved autism symptoms by 6-10%
- Real time micro-organisms PCR in 104 patients with polymorphic signs and symptoms that may be related to a tick bite
- 104 patients w/ fibromyalgia symptoms
- PCR analysis performed on saliva, urine, blood to look for tick-borne pathogens
- 48% of the patients were colonized/infected w/ more than one pathogen
- 25% harboured at least three different microorganisms
- Mycoplasma spp., Rickettsia spp. and Ehrlichia spp. were the most frequent microorganisms observed
- Saliva was the most sensitive marker used
- Commentary: Unfortunately, this was not a controlled study, but did show some interesting results regarding fibro symptoms and tick-borne pathogens.
- The Efficacy and Safety of Fecal Microbiota Transplantation Combined With Biofeedback for Mixed Constipation: A Retrospective Cohort Study
- Retrospective study of 85 patients w/ constipation:
- 40 received biofeedback therapy
- 45 received biofeedback + FMT
- Both therapies had improvement of constipation and bristol stool consistency
- FMT + biofeedback therapy had long-term benefit at 6 and 12 month follow up, and had better improvement of quality of life
- Retrospective study of 85 patients w/ constipation:
- Preoperative Elemental Diet before Laparoscopic Anterior Resection in Patients with Advanced Stenotic Rectal Cancer
- 74 patients w/ rectal cancer scheduled for colectomy
- 42 underwent 10-day elemental diet for prep
- 32 underwent normal bowel prep
- The elemental diet group had lower postoperative complications (OR 6.0)
- Commentary: Elemental dieting may be an effective replacement to conventional bowel prep for those undergoing bowel surgery.
- 74 patients w/ rectal cancer scheduled for colectomy
- Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies
- 58 studies (9 randomized controlled trials, 49 animal studies)
- Human studies
- 6 of 8 studies, 726 patients showed that probiotics was associated w/ reduced respiratory tract infections
- Animal studies
- Beneficial effects against influenza virus infection by:
- Improving survival (20/22 studies)
- Lowering symptoms (21/21 studies)
- Decreasing viral load (23/25 studies)
- Beneficial effects against influenza virus infection by:
- Commentary: This study suggests a beneficial effect of probiotics on respiratory tract infections.
- Dietary vitamin D intake and colorectal cancer risk: a longitudinal approach within the PREDIMED study
- Prospective study of 7,216 participants without colorectal cancer (CRC)
- Followed x6 years, 97 CRC cases
- Higher dietary vitamin D intake was associated with lower CRC incidence (HR 0.44)
- Commentary: Vitamin D may have a protective effect on CRC, but remember that we can only suggest an association (not causation) from this study.
- Study of Antibodies to Cytolethal Distending Toxin B (CdtB) and Antibodies to Vinculin in Patients with Irritable Bowel Syndrome
- Retrospective study of 100 IBS patients
- Anti-vinculin and anti-CdtB levels were higher in patients with IBS (1.58 ng/ml and 2.47 ng/mL) when compared to control subjects (1.13 ng/ml and 2.1 ng/mL)
- Anti-vinculin level was significantly higher in the IBS-D subtype (1.84 ng/mL) than the other subtypes (IBS-C 1.33, Controls 1.13)
- Commentary: Three things to note here:
- 1) This study showed increased antibodies in IBS patients compared to healthy controls but the degree of difference is fairly low
- 2) IBS-D had the highest antibody levels despite evidence suggesting that IBS-C benefits the most from prokinetics
- 3) Even though those w/ IBS had higher levels, according to common antibody labs, the average IBS anti-vinculin level would NOT flag as elevated on many of these tests
- The Effect of Saccharomyces boulardii Primary Prevention on Risk of Hospital-onset Clostridioides difficile Infection in Hospitalized Patients Administered Antibiotics Frequently Associated With C. difficile Infection
- Retrospective study of 8,763 patients administered at least 1 course of antibiotics in the hospital
- Hospital acquired C. diff infection was:
- 0.56% for those who were also given S. boulardii
- 0.82% for those just given antibiotics
- HR for antibiotic + S. boulardii= 0.57
- Commentary: This large study showed a protective effect of S. boulardii reducing C. diff infection rates for at-risk patients. Most benefit was seen when S. boulardii was given within 24 hours of antibiotics.
- Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG
- Prospective study of 50 IBS patients, 25 healthy controls
- IBS patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies
- After 4 weeks of a gluten-free diet:
- IBS symptoms improved in 75% with antigliadin IgG and IgA and in 38% without the antibodies
- The presence of antigliadin IgG was associated with overall reductions in symptoms (OR 129 compared with patients without antibodies)
- No effect on GI symptoms in controls
- Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD
- Commentary: Those w/ antigliadin antibodies may respond better to a GFD but larger studies are needed. Symptoms can be improved even if a patient is not very strict with the diet.
- Mechanistic basis and preliminary practice of butyric acid and butyrate sodium to mitigate gut inflammatory diseases: a comprehensive review
- 197 in vitro and human studies
- “Our review found insufficient evidence to guarantee the safety of clinical practice of [butyrate supplementation], either by anal enema or oral administration of capsule or tablet.”
- Impaired Quality of Life in Patients with Autoimmune Atrophic Gastritis
- Cross-sectional study of 102 autoimmune atrophic gastritis (AAG) patients, 100 w/ a functional GI disorders (FGID), 100 w/ other organic GI disorders, and 100 healthy controls
- Evaluated quality of life (QOL)
- Results:
- The AAG group had significantly worse QOL compared to other groups
- Vitamin B12 level was a significant independent predictor of physical functioning
- Commentary: This study highlights the impaired QOL of those w/ AAG compared to healthy controls and other GI disorders. Repletion of B12 levels may be an important part of managing AAG.
- Microbiota shaping – the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review
- 23 papers
- Both probiotic supplementation and FMT improved cognitive function
- The effect of hormone replacement therapy on cognitive function in healthy postmenopausal women: a meta-analysis of 23 randomized controlled trials
- 23 RCTs
- HRT had a detrimental effect on global cognition
- This effect was more pronounced in those over 60 years old for more than 6 months duration
- Commentary: HRT may be most beneficial when starting it soon after menopause as compared to waiting until after 60 years old.
- Effectiveness of testosterone replacement in men with obesity: a systematic review and meta-analysis
- 16 trials using testosterone replacement therapy (TRT) in men w/ obesity
- TRT associated with:
- Increase lean body mass (+2 kg)
- Reduced LDL-C
- NO effect on blood pressure
- NO increase in adverse events
- Clinical Observation of Levothyroxine Sodium Combined with Selenium in the Treatment of Patients with Chronic Lymphocytic Thyroiditis and Hypothyroidism and the Effects on Thyroid Function, Mood, and Inflammatory Factors
- 138 Hashimoto’s patients, randomized to levothyroxine or levo + selenium (100 mcg/d)
- After 3 months of treatment:
- Both groups had improved tT3, tT4, TSH, TPO Abs, and depression symptoms
- The combined group had more improvement in:
- Antibody reduction
- Depression
- Efficacy and Safety of a Standardized Soy and Hop Extract on Menopausal Symptoms: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
- 78 women w/ mod-severe menopausal symptoms, randomized to placebo or soy + hop supplement
- After 12 weeks of supplementation, the soy + hop supplement group had:
- More improvement of symptoms (-20 symptom score vs -14 placebo)
- More improvement in fatigue, paresthesia, arthralgia, and myalgia, palpitation and vaginal dryness
- NO difference in hormonal profiles
- Commentary: This study suggests that a combined soy + hop supplementation can improve menopausal symptoms independent of change of the hormonal profile.
- Effect of Epidemic Intermittent Fasting on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- 14 RCTs
- Compared to controls, intermittent fasting lead to reduced:
- Body weight (-1.78 kg)
- Waist circumference (-1.2 cm)
- Fat mass (-1.26 kg)
- Blood pressure (-2.1 mmHg)
- Fasting insulin g (-0.8 mIU/L)
- NO clinical change in triglycerides, fasting glucose, LDL-C, A1C
- Commentary: Intermittent fasting leads to improvement of some but not all cardiometabolic markers compared to controls.
- A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT
- 83 individuals w/ mild cognitive impairment, randomized to placebo or “ketone drinks” (ketogenic medium chain triglycerides)
- After 6 months of supplementation, the ketone group had better cognitive function
- Some cognitive measures were positively correlated w/ plasma ketone levels
- Commentary: Ketone supplementation led to improvements in mild cognitive function perhaps due to increased plasma ketone levels.
- Obstructive Sleep Apnea Risk Is Associated with Cognitive Impairment after Controlling for Mild Traumatic Brain Injury History: A Chronic Effects of Neurotrauma Consortium Study
- 391 veterans (326 w/ history of TBI)
- Those with history of TBI were more likely to be categorized as high risk for obstructive sleep apnea (OSA) (65% vs 51%)
- Presence of OSA was associated w/ worse cognitive function
- Commentary: TBI may be a contributing factor to OSA and presence of OSA may be a cause of mild cognitive impairment.
- Effect of green tea on glycemic control in patients with type 2 diabetes mellitus: A systematic review and meta-analysis
- 14 studies
- Supplementary intake of green tea had NO significant effect on fasting glucose, fasting insulin, A1c and insulin resistance in patients with type 2 diabetes
- Commentary: Supplementary green tea may not be effective for improving cardiometabolic markers.
- Exposure to metals and morbidity at eight years follow-up in women of childbearing age
- Urinary levels of 25 metals analyzed in 111 pregnant women before delivery
- Cancer mostly attributed to the increased levels of cadmium
- Cardiovascular outcomes were linked with lead
- Obesity was found associated with elevated levels of nickel
- Commentary: This study supports an association between heavy metals and adverse health outcomes.
- Continuous positive airway pressure improves blood pressure and serum cardiovascular biomarkers in obstructive sleep apnoea and hypertension
- 92 participants w/ severe obstructive sleep apnea (OSA) and refractory hypertension, randomized to CPAP or no treatment
- After 8 weeks, the CPAP group had:
- Significant reduction in systolic BP (-4.4 mmHg)
- Reduced serum troponin I
- Reduced brain natriuretic peptide
- Commentary: Addressing sleep apnea may help mitigate hypertension. Dr Ruscio wanted me to remind everyone that apnea can be addressed WITHOUT CPAP in many cases.