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Featured Study

Effect of APOE Genotype on Plasma Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid, Arachidonic Acid, and Hippocampal Volume in the Alzheimer’s Disease Cooperative Study-Sponsored DHA Clinical Trial

• Previous knowledge:
  • APOE 4/4 carriers have faster clearance of lipoproteins in blood
  • Lower hippocampal volume predicts incidence of Alzheimer’s disease
• 275 participants, randomized to 2 g/d DHA
• After 18 months of supplementation, APOE 4/4 carriers had:
  • Less increase in plasma DHA levels
  • More reduction in hippocampus volume
• Commentary: It may be worth measuring fatty acids in patients and foregoing genotype testing given high intra-individual variability found in study.

Gastrointestinal Studies

• Low FODMAP Diet for Functional Gastrointestinal Symptoms in Quiescent Inflammatory Bowel Disease: A Systematic Review of Randomized Controlled Trials
  • 4 RCTs using low FODMAP x 3-6 weeks in IBD patients
  • Low FODMAP group
    • Improved quality of life: 2 studies
    • Reduced abdominal pain: 2 studies
  • Commentary: High degree of variability in studies

• An elemental diet is effective in the management of diversion colitis
  • Diversion colitis = inflammation of a section of bowel that has been isolated from functioning bowel after surgery
  • Case report of 29 yo female w/ Crohn’s and diversion colitis
  • Given exclusive elemental diet followed by LOFFLEX diet
  • Improvements:
    • Bowel movement frequency
    • Taken off biologic medication

• The effect of Lactiplantibacillus plantarum 299v together with a low dose of iron on iron status in healthy pregnant women: A randomized clinical trial
  • Probiotics given to healthy pregnant women:
    • Attenuated the decrease in serum ferritin throughout pregnancy
    • Reduced rates of iron deficiency (59% vs 78%)
    • Reduced rates of iron deficiency anemia (7.4% vs 21%)

• Effectiveness of fecal microbiota transplant for the treatment of Clostridioides difficile diarrhea: A systematic review and meta-analysis
  • FMT had 82% response rate
  • More adverse effects w/ colonoscopy (72%) compared to enema (40%) or capsule (35%)
  • Capsule had best success rate

• Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity
  • Multi-center study of 86 patients, with non-celiac gluten sensitivity (NCGS)
    • 59 also had IBS-D
    • 15 had celiac disease
    • 25 controls
  • Serum zonulin positively associated with NCGS
    • Reduced with 6-months of wheat avoidance in those with HLA-DQ2/8
  • Accuracy of serum zonulin to distinguish NCGS vs IBS-D= 81%

• Clinical Characteristics and Management of 50 Patients with Anti-GAD Ataxia: Gluten-Free Diet Has a Major Impact
  • 50 patients with cerebellar ataxia and anti-GAD antibodies
  • Among the 70% who had gluten sensitivity, after gluten-free diet:
    • 51% improved
    • 37% stabilized

• The effects of flaxseed supplementation on metabolic syndrome parameters, insulin resistance and inflammation in ulcerative colitis patients: An open-labeled randomized controlled trial
  • 70 patients with ulcerative colitis, randomized to 30 g/day ground flaxseed or placebo
  • After 12 weeks, flaxseed group had improved:
    • Insulin sensitivity
    • Triglycerides
    • Total cholesterol
    • HDL-C
    • CRP

• Relationship between pathological menstrual symptoms and the development of extragenital forms of local inflammation
  • 52% of those with menstrual irregularity had IBS

• Digestive symptoms in daily life of chronic adrenal insufficiency patients are similar to irritable bowel syndrome symptoms
  • 30% of patients with chronic adrenal insufficiency have symptoms consistent with IBS

• Association of small intestinal bacterial overgrowth with Parkinson’s disease: a systematic review and meta-analysis
  • 11 studies, 1,000 participants
  • Prevalence of SIBO in Parkinson’s:
    • 51% if lactulose breath test
    • 35% if glucose breath test
  • Odds ratio of 5.2 for SIBO in PD patients
  • Commentary: This is a chicken or the egg scenario? Does SIBO contribute to Parkinson’s or does poor motility in Parkinson’s lead to SIBO?

• Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results
  • Calprotectin significantly elevated (in a concentration-dependent manner) that correlated with the number of active inflammation sites on biopsy
    • Better marker than CRP or leukocytes

• An algorithm for differentiating food antigen-related gastrointestinal symptoms
  • 150 IBS patients went on gluten and low FODMAP diet
  • After 6 weeks
    • 70% improved
    • 53% became asymptomatic

• The frequency of HLA-DQ2/DQ8 haplotypes and celiac disease among the first-degree relatives of patients with celiac disease
  • 100 first degree relatives (FDR) of those with Celiac disease, 150 healthy controls
  • No difference in HLA-DQ2/DQ8 alleles in FDR and controls
  • Commentary: Other methods such as serological tests have a higher priority compared with HLA-DQ typing.

• The gut microbiota is associated with clinical response to statin treatment in patients with coronary artery disease
  • Gut microbiota structure is associated with the response to statin therapy

Thyroid & Hormone Studies

• Thyroid Dysfunction and Dysmetabolic Syndrome: The Need for Enhanced Thyrovigilance Strategies
  • What’s the connection between PCOS and thyroid dysfunction?
    • Autoimmune thyroid disease in up to 40% of those with PCOS
    • Prolactin and TSH levels increased in hypothyroidism
      • Increase DHEA
      • Change ratio of LH/FSH
      • Inhibit ovulation
      • Collagen deposits in ovaries
    • Women are more likely to be overweight and insulin-resistant if have both PCOS and autoimmune thyroid disease

• Therapeutic Effect of Curcumin in Women with Polycystic Ovary Syndrome Receiving Metformin: A Randomized Controlled Trial
  • 100 women w/ PCOS
    • 50 received Metformin, 50 received Metformin + Curcumin
  • After 3 months, Metformin + Curcumin group had:
    • Improved insulin resistance
    • Lower testosterone
    • Lower LDL-C
    • Higher HDL-C
    • Lower triglycerides
  • Commentary: Curcumin has synergistic effect w/ Metformin for treatment of PCOS

• The Effect of Curcumin Phytosome on the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial
  • 80 fatty liver patients randomized to 250 mg curcumin or placebo
  • After 2 months, curcumin group had improved:
    • HDL-C
    • Liver enzymes
    • Hepatic fat mass

• Insulin resistance: still an underestimated factor in polycystic ovary syndrome?
  • Prevalence of insulin resistance in lean patients with PCOS was 57%
    • Only 15% in lean controls
  • Commentary: PCOS is associated with insulin resistance independent of weight

• Non-alcoholic fatty liver disease in premenopausal women with polycystic ovary syndrome: A systematic review and meta-analysis
  • 23 studies, 7,200 participants
  • Women with PCOS had a 5-fold increase in the risk of non-alcoholic fatty liver compared to controls

• Improvement of Insulin Sensitivity Increases Pregnancy Rate in Infertile PCOS Women: A Systemic Review
  • 10 RCTs
  • Pregnancy rate increased in infertile PCOS women after improvement of insulin sensitivity
  • Effect seen regardless of the various interventions
  • Commentary: insulin resistance→ androgen excess→ more insulin resistance…

• SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction
  • Sex hormone-binding globulin (SHBG) <33.4 nmol/l independently associated with worse metabolic markers and increased risk of fatty liver
    • sensitivity= 74%
    • specificity= 70%

• Markers of vitamin D metabolism and premenstrual symptoms in healthy women with regular cycles
  • Vitamin D insufficiency was associated with increased risk of breast fullness/tenderness and generalized aches and pains

• Does subclinical hypothyroidism add on any symptoms? evidence from a Danish population-based study
  • 400 subclinical hypothyroid patients, 7,500 controls
  • Subclinical hypothyroid patients did not report higher hypothyroidism score compared to euthyroid controls
  • TSH level had no impact on symptom score

• The Relationship Between Thyroid Function and Metabolic Syndrome and Its Components: A Cross-Sectional Study in a Chinese Population
  • What is the association between thyroid status and metabolic syndrome?
  • 63,000 participants
  • For men and women, subclinical hypothyroid group had higher:
    • BMI
    • Waist circumference
    • Systolic blood pressure
    • Triglycerides
  • Commentary: Subclinical hypothyroidism may be the “canary in the coalmine” of some other issue in the body (e.g. poor gut health, stress, toxins, dysglycemia)

• Relation of kidney function and homocysteine in patients with hypothyroidism
  • 450 participants w/ hypothyroidism
  • Patients with hypothyroidism had:
    • Higher serum homocysteine
    • Higher creatinine levels
    • Lower eGFR levels
  • Levothyroxine treatment resulted in significantly decreased Hcy and increased eGFR
  • Commentary: Hypothyroidism is associated with high homocysteine and lower kidney function

Diet & Lifestyle Studies

• Underweight rather than adiposity is an important predictor of death in rural Chinese adults: A cohort study
  • Retrospective study, 30,000 participants
  • A J-shaped association was observed between BMI and all-cause mortality in men
  • Underweight also had an increased risk of cardiovascular disease and cancer mortalities in men
  • Commentary: A confounding variable could be lean body mass

• Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study
  • 18,000 participants in rural China
  • Low BMI was associated with increased risk of all-cause mortality regardless of hypertension status
  • High BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.
  • Commentary: I suspect this is because BMI is positively correlated with lean body mass which is protective.

• Vitamin B6 efficacy in the treatment of nonalcoholic fatty liver disease: An open-label, single-arm, single-center trial
  • 22 patients w/ fatty liver, 90 mg/d Vitamin B6
  • After 12 weeks:
    • No changes in liver function tests
    • Reduced hepatic lipid accumulation

• Impact of Ramadan Intermittent Fasting on the Heart Rate Variability and Cardiovascular Parameters of Patients with Controlled Hypertension
  • 58 patients w/ hypertension
  • Fasting increased heart rate variability only during the afternoon (not morning or evening)
  • Commentary: Fasting may be able to reduce cardiac stress among those with hypertension.

• Vitamin D Supplementation during Winter: Effects on Stress Resilience in a Randomized Control Trial
  • RCT of 86 participants with normal vitamin D levels before winter
  • Given Vitamin D throughout winter
  • After the winter, Vitamin D group showed better response to stress

• Beneficial effect of Mediterranean diet on disease activity and cardiovascular risk in systemic lupus erythematosus patients: A cross-sectional study
  • 280 patients with lupus
  • Greater adherence to Mediterranean diet associated with:
    • Lower disease activity
    • Less cardiovascular risk factors

• Persistent Cigarette Smoking Attenuates Plaque Stabilization in Response to Lipid-Lowering Therapy: A Serial Optical Coherence Tomography Study
  • Persistent smoking is associated with an attenuated effect of statin therapy on plaque stabilization in acute coronary syndrome patients
  • Commentary: Smoking is in the top 2 risk factors for cardiovascular disease.

• 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/ moderate-severe sleep apnea randomized to CPAP or control
  • After 12 weeks, CPAP group did NOT have improved glycemic control as measured by A1C, fasting glucose, continuous glucose monitor
  • Commentary: For those with both sleep apnea and diabetes, blood sugar control should be managed in addition to CPAP therapy.

• Vitamin D Status is Independently Associated with Insulin Resistance in Patients with Type 2 Diabetes Mellitus
  • 172 diabetic adults
  • Vitamin D status is INDEPENDENTLY inversely associated with insulin resistance
  • Commentary: This relationship is dose-dependant (the lower the vitamin D, the higher the insulin resistance)

• Maternal and perinatal risk factors for pediatric non-alcoholic fatty liver disease: A systematic review
  • 33 studies
  • Maternal pre-pregnancy overweight/obesity was associated with an increased risk of pediatric fatty liver
  • Breastfeeding is protective for fatty liver if >6 months

• The effect of heat therapy on blood pressure and peripheral vascular function: A systematic review and meta-analysis
  • 15 studies
  • Sauna therapy reduced:
    • Mean arterial pressure (-5.86 mmHg)
    • Systolic blood pressure SBP (-3.94 mmHg)
    • Diastolic blood pressure (-3.88 mmHg)
  • No change in heart rate
  • May improve arterial stiffness

• Is the effect of atorvastatin 60 mg on stabilization of lipid-rich plaque equivalent to that of rosuvastatin 10 mg? A serial optical coherence tomography combined with intravascular ultrasound imaging
  • 50 patients with hyperlipidemia
  • After 6 months:
    • 10 mg Rosuvastatin is comparable to 60 mg Atorvastatin in stabilizing atherosclerotic plaques in group

• Effects of continuous positive airway pressure treatment in obstructive sleep apnea patients with atrial fibrillation: A meta-analysis
  • Sleep apnea is associated with atrial fibrillation (AF)
  • 9 studies, 15,000 participants
  • Among those with sleep apnea, CPAP therapy reduced the risk of AF recurrence or progression by 63%

• Burden of osteoporosis and costs associated with human biomonitored cadmium exposure in three European countries: France, Spain, and Belgium
  • 23% of osteoporosis is attributable to cadmium exposure from environment

• Severity of Nonalcoholic Fatty Liver Disease and Risk of Future Ischemic Stroke Events
  • 80,000 participants followed for 10 years
  • 31% had non-alcoholic fatty liver disease (NAFLD)
  • The severity of NAFLD is associated with a higher risk of future ischemic stroke events

• Does exercise training improve the function of vascular smooth muscle? A systematic review and meta-analysis
  • 35 studies
  • Vigorous aerobic exercise and mixture training modality were the best ways to promote the dilation response of vascular smooth muscle cells

• Impact of Long-Term Supplementation with Fish Oil in Individuals with Non-Alcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial
  • 24 participants w/ fatty liver, 600 mg combined EPA + DHA or placebo
  • After 12 months of supplementation, fish oil group had:
    • Reduced alkaline phosphatase (ALP)
    • Reduced hepatic fat

• Serum metabolic signatures of subclinical atherosclerosis in patients with type 2 diabetes mellitus: a preliminary study
  • 450 type 2 diabetics, some with abnormal carotid intima thickness (CIMT) scores
  • Measured serum bile acids
  • Patients with high CIMT had significantly:
    • Higher deoxycholic acid (DCA) levels
    • Higher taurodeoxycholic acid (TDCA) levels
    • Lower levels of taurocholic acid (TCA)
  • Commentary: Serum bile acids may serve as early predictors of atherosclerosis.

• The association between homocysteine levels and cardiovascular disease risk among middle-aged and elderly adults in Taiwan
  • 400 participants
  • Higher homocysteine levels independently associated with higher cardiovascular disease risk as measured by Framingham Risk Score

Podcast Summary

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Featured Study

Incidence of thyroid diseases: Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

• 10,000 euthyroid participants followed over 4 years
• Incidence of thyroid disease at 4-year mark
  • Overall thyroid disease: 7%
  • Overt HYPERthyroidism: 0.2%
  • Subclinical HYPERthyroidism: 0.5%
  • Overt HYPOthyroid: 2%
  • Subclinical HYPOthyroid: 4%
• Higher incidence in women
• Presence of TPO antibodies at baseline was associated with higher incidence of overt thyroid diseases
• Commentary: The prevalence and incidence of thyroid disease is much less than what some would have you believe.

Gastrointestinal Studies

• Screening and eradication of Helicobacter pylori for gastric cancer prevention: The Taipei global consensus
  • Consensus of 28 experts in 11 countries
  • Worldwide fraction for H. pylori in gastric cancer is >85%
  • Eradication of H. pylori reduces the risk of gastric cancer in asymptomatic subjects (backed by 10 RCTs ) and is recommended unless there are competing considerations
  • Young individuals would benefit most from H. pylori eradication
  • If 1st-degree relative w/ gastric cancer, screen and treat H. pylori
  • Confirmation test after H. pylori eradication therapy is recommended for symptomatic H. pylori infected

• PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression: A Randomized Controlled Trial
  • 83 depressed patients in hospital randomly assigned to either:
    • multistrain probiotic + biotin
      • or
    • biotin + placebo
  • After 1 month:
    • Both groups improved w/ psychiatric symptoms
      • No more improvement in probiotic group
    • Better diversity score in probiotic group

• Actionable biomarkers: The key to resolving disorders of gastrointestinal function
  • Up to 33% of those w/ functional diarrhea had bile acid malabsorption
    • Best diagnostic tests:
      • SeCHAT test= gold standard
      • 48 hr fecal bile acids
        • >2337 μmol
        • Or primary bile acids >10%
        • Or primary bile acids >4% + total BA >1000 μmol
      • Best treatment:
        • Empiric trial of binders (e.g. cholestyramine)

• Rapid gastric emptying in diabetes mellitus: Pathophysiology and clinical importance
  • Rapid gastric emptying is common in T2 Diabetics
  • What comes first: Hyperglycemia or rapid gastric emptying?
    • Hyperglycemia may be the main driver for fast gastric emptying
  • Whey protein 15 minutes before meals can:
    • Reduce postprandial glucose excursions
    • And slow down gastric emptying rates
  • Commentary: Consider pre-loading meals w/ whey protein to reduce rapid gastric emptying and glucose excursions.

• Non-responsive celiac disease in children on a gluten-free diet
  • Why do some children w/ Celiac disease remain symptomatic despite a GF diet?
  • Retrospective study of 600 children
  • Causes of non-responsiveness to GFD:
    • Inadvertent gluten exposure: 30%
    • Constipation: 20%
    • Lactose intolerance: 9%
    • Reflux: 8%

• A combination of three probiotic strains for treatment of acute diarrhea in hospitalized children: An open-label, randomized controlled trial
  • Probiotic group had a 22.5 h shorter mean duration of diarrhea and 1.2 day shorter hospital stays

• The prevalence of celiac disease in women with infertility-A systematic review with meta-analysis
  • Celiac disease is not more common in infertile women than in the general population

• Riboflavin Supplementation in Patients with Crohn’s Disease [the RISE-UP study]
  • 70 patients w/ Crohn’s Disease, given 100 mg riboflavin
  • After 3 weeks:
    • Reduced CRP levels (only if high baseline calprotectin)
    • Reduced disease activity

• Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives
  • Probiotics can reduce chemotherapy toxicity (e.g. colitis, oral mucositis)

• The Impact of Sham Feeding with Chewing Gum on Postoperative Ileus Following Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials
  • 16 RCT, 970 patients
  • Chewing gum after colorectal surgery is a safe and effective to reduce postoperative ileus
  • Commentary: adequate chewing of food may stimulate healthy gut motility.

• Fecal microbiota transplantation in hepatic encephalopathy: a systematic review
  • 8 studies including 2 RCTs
  • FMT lead to:
    • Improved neurocognitive test results in 4 human studies
    • Lowered hospital readmission rates
  • Commentary: Treating the gut is a promising strategy to improve liver health.

• Serum Zonulin Measured by Commercial Kit Fails to Correlate with Physiologic Measures of Altered Gut Permeability in First Degree Relatives of Crohn’s Disease Patients
  • Measured serum zonulin and lactulose-mannitol test in 39 healthy relatives of patients with Crohn’s disease
  • No correlation between lactulose-mannitol test and serum zonulin
  • Commentary: These tests lack consistency, specificity, and validity in the use of clinical practice. This is another example of how we can’t “hang our hat” on some of these popular functional medicine tests and must rather rely on a good history, physical exam, and more validated tests.

• A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma
  • 77 chemotherapy patients received probiotic (Lactobacillus) x7 weeks
  • Probiotics significantly reduce rates of oral mucositis

• Epigastric symptom response to low FODMAP dietary advice compared with standard dietetic advice in individuals with functional dyspepsia
  • 60 patients with dyspepsia, 40 received low FODMAP and 20 standard dietary advice
  • 81% of those with functional dyspepsia had IBS
  • low FODMAP group had greater symptom reduction

• Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study
  • Xylitol resulted in:
    • Dose-dependent stimulation of glucagon-like peptide-1 (GLP-1)
    • Slower gastric emptying
    • Increased uric acid
  • Commentary: Increased GLP-1 may lead to increased insulin sensitivity and decreased glucagon secretion. Xylitol and artificial sweetener consumption may contribute to hypoglycemia.

• The relationship between calcium oxalate lithiasis and chronic proinflammatory intestinal dysbiosis pattern: A prospective study
  • Patients with calcium oxalate kidney stones have chronic pro-inflammatory intestinal dysbiosis
  • Commentary: Consider addressing dysbiosis and less restrictive diets (e.g. partial elemental, low FODMAP) before using something like a low oxalate diet.

• Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review
  • 17 studies
  • Potential link between Celiac Disease and Autism Spectrum
  • However, this is supported by low-quality studies

• Gluten-Free Foods Cooked in Shared Fryers With Wheat: A Pilot Study Assessing Gluten Cross Contact
  • 20 orders of gluten-free fries were purchased from 10 different restaurants
    • All restaurants confirmed that their fryers were used to cook wheat-containing foods.
  • Gluten found in 9 of the 20 orders
  • Commentary: Gluten cross-contact can occur frequently when eating out.

• Overlap of Rome IV Irritable Bowel Syndrome and Functional Dyspepsia and Effect on Natural History: A Longitudinal Follow-up Study
  • 807 w/ IBS
  • 55% had functional dyspepsia
  • Those with functional dyspepsia had worse IBS symptoms and more likely to have anxiety and depression compared to IBS alone

• Gut microbiota profiles and characterization of cultivable fungal isolates in IBS patients
  • Different fungal gut mycobiota in those with IBS compared to healthy controls

Thyroid & Hormone Studies

• Traumatic Brain Injury as Frequent Cause of Hypopituitarism and Growth Hormone Deficiency: Epidemiology, Diagnosis, and Treatment
  • Hormonal disruption can last decades after traumatic brain injury
    • Epidemiology of hormone deficiencies after TBI:
      • Growth hormone: 22%
      • FSH/LH: 13%
      • ACTH: 10%
      • TSH: 6%
    • Commentary: Consider asking about history of TBIs on intake form.

• Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights
  • Oxidative stress may lead to the following in those with PCOS:
    • Worse insulin resistance
    • Adipocyte proliferation
    • High androgens
    • Infertility

• LC-MS/MS determination of thyroid hormones in dietary supplements
  • 11 of 19 glandular thyroid supplements had quantifiable amounts of thyroid hormone
    • Max amount per serving of supplement serving
      • T4: 210 microgram
      • T3: 32 micrograms
      • rT3: 7.6 micrograms

• Lithium carbonate as add-on therapy to radioiodine in the treatment on hyperthyroidism: A systematic review and meta-analysis
  • 9 RCTs, 500 participants w/ hyperthyroid
  • Lithium adjunct to radioactive iodine did not show significant differences compared with radioactive iodine alone in terms of cure rate or decreasing T4

• Subcutaneous administration of levothyroxine: a novel approach to refractory hypothyroidism – A review and a case report
  • 28-year-old woman with intestinal drug malabsorption successfully treated by subcutaneous LT4 administration.
  • Blood hormone levels returned to normal within a few days and remained stable over an 8-month follow-up period.
  • Commentary: Great example of how poor gut health (malabsorption) can contribute to poor thyroid health and the need for increased doses.

• The effect of ketogenic diet on thyroid functions in children with drug-resistant epilepsy
  • 66 children on keto diet 12+ months
  • Median serum FT4 and TSH concentrations, and the frequencies of patients with low FT4 and high TSH concentrations did not change significantly
  • Commentary: This contradicts some papers (1) regarding a ketogenic/low carb diet and its effect on thyroid.
    • Some individuals may need more carbohydrates to match energy levels (especially females); “GnRH neuron activity and LH pulsatility are actually regulated by brain glucose availability. The adult female human brain oxidizes about 80g of glucose each day at a continuous rate. This must be provided daily by dietary carb, because the brain’s rate of energy expenditure can deplete liver glycogen stores in less than a day.” –Loucks 2013

Autoimmunity Studies

• Oxidative Stress and Lipid Mediators Modulate Immune Cell Functions in Autoimmune Diseases
  • Oxidative stress involved in development of lupus, rheumatoid arthritis, and other autoimmune disease
    • In Lupus, oxidative stress causes DNA damage, leads to the production of anti-dsDNA antibodies
  • 2 studies: NAC and metformin have a positive impact on lupus
  • Commentary: oxidative may be a major part of autoimmune disease development.

• Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome
  • 18 PCOS women, 8-hour time-restricted feeding
  • After 5 weeks:
    • 73% had improved menstrual cycle regularity
    • Improved BMI, BF%, insulin sensitivity, CRP, testosterone

• Metabolic syndrome and adipokine levels in systemic lupus erythematosus and systemic sclerosis
  • 50 SLE patients, 85 systemic sclerosis patients
  • Results:
    • Prevalence of MetS was higher in SLE patients than systemic sclerosis patients (36% vs 11%)
    • Worse symptoms in those with MetS

Diet & Lifestyle Studies

• Inverse associations of bisphenol A and phthalate metabolites with serum bilirubin levels in Korean population
  • Phthalate levels were inversely associated with serum bilirubin levels
  • No association between phthalates and GGT or uric acid
  • Commentary: LOW bilirubin may be an indicator of lipid oxidative stress.

• Microbiota, Fiber, and NAFLD: Is There Any Connection?
  • Benefit of fiber for non-alcoholic fatty liver disease:
    • 5 RCT
    • 1 cross-sectional study

• The interpretation and effect of a low-carbohydrate diet in the management of type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials
  • 18 studies, 2200 participants
  • Statistical significance in favor of the low carb group for:
    • A1C (-0.28%)
    • HDL-C (+2.3 mg/dL)
    • Triglycerides (-21 mg/dL)
    • Blood pressure (-2.75 mmHg)
    • Reduced requirement for diabetes medication
  • No difference for:
    • weight change
    • LDL-C
  • Commentary: 15 of 18 studies were high-risk for bias. Dietary adherence was an issue if <50g/day. <130 g/day was achievable for most.

• Vitamin D Effect on Ultrasonography and Laboratory Indices and Biochemical Indicators in the Blood: An Interventional Study on 12 to 18-Year-Old Children with Fatty Liver
  • 100 overweight children w/ fatty liver
  • Randomized to receive 50,000 IU/week of Vit. D
  • At 12 weeks, Vit D. group had improved:
    • Fatty liver grade
    • Insulin
    • LDL-C
    • HDL-C
    • Insulin sensitivity (average decrease insulin of 5 points)
    • Uric Acid

• Aflatoxins as a risk factor for liver cirrhosis: a systematic review and meta-analysis
  • 5 studies
  • Significant increase in the risk of liver cirrhosis is associated with aflatoxin exposure (odds ratio = 3.35)

• Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults
  • Blood flow to nucleus accumbens (limbic part of brain) was 40% higher in high carb diet group compared to low carb diet
  • Associated with insulin secretion

• An Exploratory Analysis of Changes in Mental Wellbeing Following Curcumin and Fish Oil Supplementation in Middle-Aged and Older Adults
  • 16-week double-blind placebo-controlled trial
    • Non-depressed adults given curcumin, fish oil, or both
  • Results
    • Curcumin improved memory and “vigor”
    • Fish oil improved vigor and mood only in non APOE4 carriers
    • Combining curcumin with fish oil did not result in additive effects.

• Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19
  • 287 patients
  • Those >65 years, Vit D sufficiency (>30 ng/mL) is independently associated with decreased odds of:
    • death (adjusted OR 0.33)
    • acute respiratory distress syndrome (adjusted OR 0.22)
    • severe sepsis/septic shock (adjusted OR 0.26)
  • This association was not present if BMI >30 or <65 yo
  • Commentary: A significant association between Vit D and COVID mortality exists in non-obese elderly.

• Impact of high-intensity interval training on cardiorespiratory fitness, body composition, physical fitness, and metabolic parameters in older adults: A meta-analysis of randomized controlled trials
  • More effective training to improve VO2 Max (cardiorespiratory fitness)
    • Training periods >12 weeks
    • Training frequencies of 2+ sessions/week
    • Session lengths of 40 min
    • 6 sets,
    • Rest <90 seconds
  • HIIT induces favorable adaptations in cardiorespiratory fitness, physical fitness, muscle power, cardiac contractile function, mitochondrial citrate synthase activity, and reduced blood triglyceride and glucose levels in older individuals
  • Commentary: Older age should not hinder a recommendation to engage in higher-intensity exercise.

• Effect of exercise training on subjective parameters in patients with obstructive sleep apnea: A systematic review and meta-analysis
  • 8 studies, 230 patients
  • Exercise improves:
    • Quality of life
    • Sleep quality
    • Daytime sleepiness
    • OSA severity (average of 11 less events per hour)
  • Commentary: Exercise may be beneficial for those with sleep apnea independent of weight loss.

• Endocrine-disrupting chemicals and breast cancer: a systematic review of epidemiological studies
  • 131 studies
  • EDCs =
    • Mycotoxins (e.g. zearalenone)
    • Phytoestrogens (e.g. resveratrol)
    • BPA
    • DDT
    • PCB
  • “We identified certain EDC exposures could potentially elevate the risk of breast cancer”

• Environmental exposures to endocrine-disrupting chemicals (EDCs) and their role in endometriosis: a systematic literature review
  • 29 studies
  • 71% of studies revealed a significant association between EDCs and prevalence of endometriosis
  • Commentary: Consider a detoxification strategy in those with persistent female hormone burden after you have addressed gut health, blood sugar balance, and other “low hanging fruit”.

• Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression
  • 35 studies, ~12 million patients
  • Statins did not lead to worse outcomes in those with COVID
  • Commentary: those with dyslipidemia should continue taking statins regardless of COVID infection status

• Glycemic Control and Cardiovascular Risk Factor Management in Adults with Type 2 Diabetes With and Without Chronic Kidney Disease Before Sodium-Glucose Cotransporter Protein 2 Inhibitors: Insights From the Diabetes Mellitus Status in Canada Survey
  • Retrospective study of 5,200 Type 2 Diabetics
  • Only ⅛ of T2D patients achieve optimal blood sugar, blood pressure, and cholesterol goals
  • Commentary: do not forget about cardiometabolic risk factors after you have addressed a patient’s short-term goals (e.g. IBS, thyroid, fatigue)

• Effects of supplementation with main coffee components including caffeine and/or chlorogenic acid on hepatic, metabolic, and inflammatory indices in patients with non-alcoholic fatty liver disease and type 2 diabetes: A randomized, double-blind, placebo-controlled, clinical trial
  • Non-alcoholic fatty liver disease patients given chlorogenic acid and/or caffeine for 6 months
  • No difference compared to placebo in:
    • Hepatic fat
    • Liver enzyme tests
  • Caffeine group had lower total cholesterol

• Association between autonomic function and obstructive sleep apnea: A systematic review
  • 71 studies
  • Sleep apnea associated with:
    • Increased sympathetic activity
    • Reduced parasympathetic activity
    • Reduced heart rate variability
  • Commentary: Consider limbic retraining in those who have a history of childhood trauma, severe anxiety (especially around their health), or who have poor coping/stress management skills. Limbic activation may contribute to sleep apnea.

• The effect of intermittent energy restriction on weight loss and diabetes risk markers in women with a history of gestational diabetes: A 12-month randomized control trial
  • 121 overweight females
  • Randomized to intermittent fasting or continuous calorie restriction
  • After 12 months, no difference in
    • A1C
    • Fasting glucose
    • Fasting insulin
  • Similar weight loss

Podcast Summary

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Featured Study

Association between statin use and cognitive function: A systematic review of randomized clinical trials and observational studies

• 24 studies with 1.4 million participants
• 21 observational studies, 3 RCTs
  • All 3 RCTs, which ranged from 3-6 years of follow-up, showed no significant association between statin use and adverse cognitive effects
  • The follow-up for observational studies ranged from 3-15 years
    • 10 studies: Reduced incidence of dementia
    • 7 studies: No association with incident dementia
    • 3 studies: Decline in cognition was similar to no statin
    • 1 study: Cognitive decline with statin use
  • There was no evidence of adverse cognitive effects, including incidence of dementia, decrease global cognition or specific cognitive domains associated with statin use in individuals aged ≥60 years
  • Commentary: Some experts argue that statin use may actually be associated with a reduced rate of Alzheimer’s

Gastrointestinal Studies

• Diet supporting therapy for inflammatory bowel diseases
  • 50% improvement in IBD in 1 week after 5g/day of serum bovine immunoglobulin
    • Corroborated in 5 other studies
  • Mesalazine works better when given with curcumin
  • Other beneficial therapies
    • Essential fatty acids
    • Vitamin D
    • Phosphatidylcholine
    • Nettle

• Atherosclerotic Cardiovascular Disease Prevalence Among Patients With Celiac Disease in the United States: An Observational Study
  • 370 million people
  • Young women (<40 years old) with celiac disease had a higher prevalence of ASCVD

• The Relationship between Low Serum Vitamin D Levels and Altered Intestinal Barrier Function in Patients with IBS Diarrhoea Undergoing a Long-Term Low-FODMAP Diet: Novel Observations from a Clinical Trial
  • 36 IBS-D patient evaluated for markers of intestinal permeability, dysbiosis, vitamin D levels before and after 12 wks Low FODMAP diet
  • At baseline, patients w/ low vitamin D (<20) showed worse symptoms and altered small intestinal permeability
  • After LFD, a significant increase in the circulating Vit. D levels and a significant improvement of intestinal permeability

• Therapeutic Implications of Diet in Inflammatory Bowel Disease and Related Immune-Mediated Inflammatory Diseases
  • Gluten-free diet
    • 1 study: Improvement
    • 1 study: No effect
  • Calorie restriction/fasting
    • 1 study: Improvement
  • Specific Carbohydrate Diet
    • 4 studies: Improvement
  • Low FODMAP
    • 5 studies: Improvement

• The Effect of Multiprobiotics on Memory and Attention in Fibromyalgia: A Pilot Randomized Controlled Trial
  • 31 pts w/ fibromyalgia using multi-species probiotics (24 million CFU bifido/lacto per day) x8 wks
  • Probiotics improved attention, but it had no effect on memory

• Premature Atherosclerotic Cardiovascular Disease Risk Among Patients with Inflammatory Bowel Disease
  • 160,000 patients w/ premature atherosclerotic cardiovascular disease
  • Higher prevalence of inflammatory bowel disease among premature CVD
  • Association especially for those age ≤40 years
  • Commentary: Highlights the gut-cardiovascular axis.

• Evaluation of the Efficacy of Probiotics (MCP® BCMC® Strains) Treating Constipation in Elderly Patients with Multiple Chronic Co-Morbidities: A Randomized Control Trial
  • 72 pts >60 yo w/ constipation
  • 30 billion CFU of bifido/lacto probiotic or placebo BID
  • Results: improved stool frequency, stool consistency, straining, sensation of incomplete evacuation

• Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology
  • 16 studies, 2,000 patients
  • Long-term PPI therapy:
    • Average gastrin levels rose to 1-3x upper limit of the normal range (~100 pg/mL)
    • Increased prevalence (8-50%) of cell hyperplasia
  • But, not a single case of gastric adenocarcinoma was found
  • Commentary: PPI use may increase gastrin levels and hyperplasia but not cancer rates.

• Gut microbiota dysbiosis in a cohort of patients with psoriasis
  • Microbiome sequencing on 19 patients with psoriasis, 20 healthy controls
  • Psoriasis patients displayed a lower diversity score

• Distribution and molecular analysis of Blastocystis subtypes from gastrointestinal symptomatic and asymptomatic patients in Iran
  • 900 patients admitted to hospital in Iran
  • 8% of population infected w/ Blastocystis hominis
  • GI symptoms in only 61%
  • Commentary: Parasitic infections are 1) Not always a problem. Use clinical judgment. 2) Not always associated with GI symptoms.

• Celiac disease antibody levels reflect duodenal mucosal damage but not clinical symptoms
  • 96 celiac patients categorized to having either high (>70) or low tTG-IgA levels
  • Duodenal mucosa was more severely damaged in the high antibody group than in the low antibody group at baseline AND after gluten-free diet
  • At baseline: Ironically, the high tTG-ab group had fewer GI symptoms (43% vs. 68%) but lower vitamin D levels and higher rate of microcytosis. After a gluten-free diet, these differences were no longer detected.
  • Commentary: Symptoms are not always associated with physical damage.

• Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial
  • 66 pts w/ relapsing MS not on disease-modifying treatment
  • Randomized to receive hookworm treatment or placebo x9 mo
  • Results:
    • No significant difference in MRI results between the groups
    • Treatment with hookworm was safe and well-tolerated
    • Increase in regulatory T cell activity
    • Fewer relapses in the hookworm group (14 vs 30%)
  • Commentary: MRI change results did not reach significance because of a low level of baseline disease activity.

• Preventive Effect of High-Dose Digestive Enzyme Management on Development of Nonalcoholic Fatty Liver Disease after Pancreaticoduodenectomy: A Randomized Controlled Clinical Trial
  • Multicenter study, 84 patients undergoing elective pancreaticoduodenectomy (PD)
  • Randomized to normal or high-dose digestive enzymes after surgery
  • High-dose digestive enzymes reduced the onset of NAFLD after PD compared with normal-dose administration
  • Commentary: Consider the diagnosis of exocrine pancreatic insufficiency and the use of enzymatic therapy for those with history of abdominal surgery (especially small bowel resection).

• Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet-Results of a Randomized, Placebo-Controlled, Pilot Trial
  • 34 children w/ celiac who were on strict GF diet, given 10g inulin
  • Overall, no change of intestinal permeability but:
    • Improvement in calprotectin if elevated baseline levels

• Pleiotropic Effects of Modified Citrus Pectin
  • Citrus pectin is modified to allow for systemic absorption
  • Average dose 10-15g/d
  • Prostate Cancer
    • Decrease PSA levels, possible prolongation of life, benefit in pain, QOL
  • Detox
    • 4 clinical studies
      • increased urinary excretion of lead, arsenic, and cadmium
      • 74% reduction in lead or mercury
      • “Dramatically decreased” the levels of lead in blood and increased the levels of lead in urine in children hospitalized with lead toxicity- this is good!
      • Increased fecal uranium excretion in a family with low-level chronic exposure from their environment
    • Commentary: Overall, pectin has greatest potential use for detox (especially of heavy metals). Use 10-15 g dose.

Thyroid & Hormone Studies

• The Influence of Reducing Diets on Changes in Thyroid Parameters in Women Suffering from Obesity and Hashimoto’s Disease
  • RCT of 100 obese women with Hashimoto’s
  • Treatment group received antibody (IgG) and instructed to follow hypocaloric custom elimination diet. Control group followed hypocaloric diet w/o elimination.
  • After 6 months
    • Elimination group had greater reduction of TSH levels (48 vs 25%)
    • Improvement in fT4 and fT3 in both groups
    • Greater reduction in TPO-Ab in elimination group
    • Greater reduction in BMI in elimination group
      • But NOT clinically significant (average of 5# more at 6 mo)
    • Commentary: A basic or extended elimination diet may be performed without IgG testing.

• Levothyroxine Interactions with Food and Dietary Supplements-A Systematic Review
  • 31 pts w/ hypothyroid and gastritis given 500 mg of vitamin C x6 mo
    • TSH decreased significantly in ALL patients
    • TSH normalized in 55%
  • Commentary: Make sure that your patient is taking their thyroid medication properly (i.e. timing, void of interactions) before changing dose. Follow the algorithm!

• Iodine Absorption in Celiac Children: A Longitudinal Pilot Study
  • Measure iodine absorption in 36 children/adolescents with newly diagnosed celiac disease before starting GF diet
  • Iodine absorption in celiac children is impaired compared to the general population
  • Absorption increases slightly, but not significantly, during the GFD

• Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge
  • Up to 30% of premature ovarian failure (menopause <40 yo) are autoimmune in nature

• What Is the Quality of Life in Patients Treated with Levothyroxine for Hypothyroidism and How Are We Measuring It? A Critical, Narrative Review
  • Review of 58 studies
  • Improved QOL after 3-6 months with thyroid hormone replacement
  • “Combination treatment with LT4 and liothyronine was not generally associated with better QoL.”
    • 6 of 8 studies: No difference in QOL
      • This was true even in a thyroid-specific QOL questionnaire
      • When benefits were found, found in some but not all QOL domains
      • Patients preferred T4/T3 combo 50-70% of the time
    • TSH in the high-normal range (>2.5 but not out of range) is NOT associated with poor QOL in most (but not all) studies.
    • Commentary: Despite T4/T3 combo therapy being preferred by a good portion of patients, this cannot be explained by improvement of QOL.

• The Role of Chronic Inflammation in Polycystic Ovarian Syndrome-A Systematic Review and Meta-Analysis
  • 63 studies
  • Significantly higher circulating C-reactive protein in PCOS women than controls
  • Association seen even in non-obese PCOS patients

• The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine
  • Narrative review
  • “An altered intestinal absorption of L-T4 (caused by gastrointestinal disorders, some nutrients, or drugs) is considered the principal cause of refractory hypothyroidism.”
  • 40%–48% of patients receiving L-T4 are under- or over-treated
  • Increased need of thyroid medication in those with:
    • Less gastric acid production (H pylori or atrophic gastritis) leads to need of up to 34% more medication
    • Lactose Intolerance
    • Presence of parietal cell antibodies
      • Case series of 5 patients with autoimmune gastritis + hypothyroidism
        • Patients receiving T4 tablets switched to the same dosage of liquid L-T4→ circulating TSH normalized in all patients
        • Four patients were switched back to T4 tablets at the same dosage, and TSH worsened again.
      • Meta-analysis suggested that subjects receiving T4 tablets with suboptimal TSH values can achieve the desirable TSH following the switch to liquid L-T4 using the same dose
      • In one study, hypothyroid subjects with no confirmed malabsorption
        • TSH level was in the normal range in 11/18 patients receiving T4 tablets
        • After switching to liquid T4, 16/18 had TSH in normal range
      • Commentary: This review supports our philosophy of a gut-first approach before moving to thyroid hormone alternatives. Again, follow the algorithm and don’t rush improvements.

• Iron Deficiency, a Risk Factor of Thyroid Disorders in Reproductive-Age and Pregnant Women: A Systematic Review and Meta-Analysis
  • For women of reproductive age, iron deficiency could significantly:
    • Increase the risk of positive TPO antibodies
    • Increased TSH
    • Decreased fT4
    • Increased prevalence of overt and subclinical hypothyroidism
  • Commentary: A possible mechanism is that iron deficiency can negatively impact thyroid function by interfering with oxygen transport or affecting TPO activity (iron-dependent enzyme).

• Exploring the Effect of Metformin to Lower Thyroid-Stimulating Hormone in Euthyroid and Hypothyroid Type-2 Diabetic Patients
  • 160 T2DM split into two groups: hypothyroid on T4 or euthyroid
  • After 6 months of Metformin therapy
    • Improved TSH levels in hypothyroid patients
    • No TSH changes in the euthyroid patients
    • No significant difference in the fT4 levels in either of the groups
  • Commentary: Improving metabolic health may improve thyroid levels independent of weight loss

• Cognitive Impairment and Associated Factors Among Adult Hypothyroid Patients in Referral Hospitals, Amhara Region, Ethiopia: Multicenter Cross-Sectional Study
  • Prevalence of cognitive impairment was 27% in 216 hypothyroid patients
    • Associated with:
      • Increased age
      • Increased duration of illness
      • High TSH levels
    • Commentary: Highlights the gut-thyroid-brain axis.

• Risk of Cancer in Long-Term Levothyroxine Users: Retrospective Population-based Study
  • 600,000 on Levothyroxine, 2.4 million controls
  • Levothyroxine users showed a 50% higher risk of any cancer (adjusted odds ratio: 1.5) compared with controls
  • Increase in:
    • Brain cancer (AOR: 1.9)
    • Skin cancer (AOR: 1.4)
    • Pancreatic cancer (AOR: 1.3)
    • Female breast cancer (AOR: 1.2)
  • Commentary: Remember, this is an observational study and does not prove causation.

• Exploring the Causality Between Hypothyroidism and Non-alcoholic Fatty Liver: A Mendelian Randomization Study
  • 10,000 hypothyroidism, 10,000 controls analyzed for SNPs
  • NAFLD increases significantly in patients with hypothyroidism
  • Commentary: Possible mechanism- Low thyroid→ low insulin secretion→ reduced lipolysis inhibition→ more fatty acids to liver→ NAFLD

• Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document
  • Consensus statement from American, British, and European Thyroid Associations
  • 14 RCT examining T4/T3 combo
    • 2 trials: Better mood/QOL
    • 1 trial (33 patients): better cognition
  • Meta-analysis referenced in study
    • 27% of patients preferred monotherapy
    • 25% had no preference
    • 48% preferred combination therapy
  • Monitoring T3 levels in those on combo therapy
    • Measuring T3 is problematic due to 24 hr variability
  • Commentary: The majority of studies do NOT show that the average hypothyroid patient benefits from combination therapy.

Diet & Lifestyle Studies

• Posterior-Chain Resistance Training Compared to General Exercise and Walking Programs for the Treatment of Chronic Low Back Pain in the General Population: A Systematic Review and Meta-Analysis
  • 8 studies
  • Posterior chain exercise= hinge movements, squats, deadlifts, hamstring strengthening
  • 12-16 weeks of posterior chain training greater effect than general exercise on
    • Pain
    • Level of disability
  • No difference in adverse events

• Animal Protein versus Plant Protein in Supporting Lean Mass and Muscle Strength: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • 16 studies
  • Animal protein tends to be more beneficial for lean mass than plant protein, especially in younger adults.
  • But, not clinically significant (0.5% mean difference increase in percent lean mass)
  • Commentary: Be sure not to confuse statistical significance with clinical significance.

• Visit-to-visit blood pressure variability is common in primary care patients: Retrospective cohort study of 221,803 adults
  • Assessed blood pressure variability (>13 mmHg) over course of multiple healthcare provider visits
  • High visit-to-visit BPV is present in 1/6 of non-hypertensive adults and 1/3 of hypertensive individuals and more common if have comorbidities
  • Commentary: make sure to get multiple BP readings before deciding upon BP medication regimen

• Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults
  • Randomized trial of hypocaloric diets x 6 weeks:
    • Low fat
    • Keto
    • Keto + ketone supplements
  • Weight loss was similar between groups
  • Liver fat assessed by MRI decreased in all groups with no group differences

• Moderating effects of plastic-packaged food on association of urinary phthalate metabolites with emotional symptoms in Chinese adolescents
  • 890 patients
  • Measured urinary phthalate levels
  • Plastic packaged food consumption associated with higher phthalate levels and emotional symptoms (depressive, anxiety and stress)
    • This relationship was dose-dependent between plastic-packaged food consumption and phthalate levels
  • Diet was the most important source of phthalate exposure

• The use of ketogenic diets in cancer patients: a systematic review
  • 39 studies, 770 patients
  • Most studies had a low quality, high risk of bias and were highly heterogeneous
  • No conclusive evidence for anti-tumor effects or improved survival
  • Mild to moderate side effects
  • Low adherence rates
  • Commentary: Consider the potential risks of popular diets (e.g. social isolation, stress, side effects)

• Effects of a single dose of vitamin D in septic children: a randomized, double-blinded, controlled trial
  • 109 children w/ vitamin D deficiency and sepsis
  • Randomized to one dose 150,000 IU Vit D or placebo
  • Vitamin D group showed:
    • Reduced inflammatory cytokines
    • Reduced sepsis score
    • Lower incidence of septic shock (7% vs. 20%)
    • No difference in the duration of ventilation or mortality rates

• Effect of Monthly High-Dose Vitamin D Supplementation on Acute Respiratory Infections in Older Adults: A Randomized Controlled Trial
  • 5,000 adults 50-84 yo
  • Randomized to an initial dose of 200,000 IU Vit. D followed by 100,000 IU monthly or placebo for 18 months
  • D does not prevent acute respiratory infections in older adults

• A Fad too Far? Dietary Strategies for the Prevention and Treatment of NAFLD
  • Increasing dietary protein can improve in those with NAFLD independent of BMI/body fat change
    • Lipids
    • Glucose balance
    • Liver enzymes

• Effect of Chromium Supplementation on Blood Glucose and Lipid Levels in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis
  • 10 RCT, 509 patients
  • Chromium only improved A1C
  • Did not change lipids or fasting glucose

• Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): A case-control study
  • 15,000 cases (new acute MI), 15,000 controls
  • Current smoking and raised ApoB/ApoA1 ratio were the two strongest risk factors for MI
    • Smoking Odds Ratio: 2.9
    • High ApoB/ApoA (>2) OR: 3.25
    • HTN OR: 1.9
    • T2DM OR: 2.4
  • Nine modifiable risk factors account for over 90% of the risk
    • “Effect of these risk factors is consistent in men and women, across different geographic regions, and by ethnic group, making the study applicable worldwide.”
  • Smoking and abnormal lipids account for ⅔ of risk
  • Commentary: Although family history is important, more time should be spent measuring and managing modifiable risk factors.

Podcast Summary

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Featured Study

The association between anti-thyroid antibodies and quality of life in patients with Hashimoto’s thyroiditis: A systematic review and meta-analysis

• Of the 13 studies examining euthyroid Hashimoto patients
  • Negative association between quality of life and antibodies: 5 studies
  • Positive association between symptoms and antibodies: 3 studies
  • Negative association between executive function and antibodies: 2 studies
  • Negative association between mental health and antibodies: 12 studies
• However, this study showed:
  • Significant correlation between TSH and TPO Abs observed only in patients with antibody levels >500 IU/mL
  • But even if Abs >500, only a 0.5 increase in TSH at 10-year mark

Commentary: This new study suggests that we cannot completely ignore TPO antibody levels. However, we should be cautious not to create unwarranted fear around mildly elevated levels (<500). Nonetheless, antibody levels may be associated with decreased quality of life and mental health despite minimal risk of significantly altering TSH levels and increased risk of overt hypothyroidism.

Gastrointestinal Studies

• Low isolated ferritin levels without anemia: is gastrointestinal tract endoscopy sufficient to explain the cause?
  • Of the pediatric patients who had low ferritin without anemia
    • 24% had H pylori
    • 6% had celiac disease
  • Commentary: low ferritin/iron-deficiency may be indicator of either of these conditions

• Is There an Exercise-Intensity Threshold Capable of Avoiding the Leaky Gut?
  • Vigorous endurance training (70% of the maximum work capacity) led to the characteristic responses of leaky gut
  • Commentary: reminder that both undertraining AND overtraining can have deleterious effects on gut health

• Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet compared with traditional dietary advice for diarrhea-predominant irritable bowel syndrome: a parallel-group, randomized controlled trial with analysis of clinical and microbiological factors associated with patient outcomes
  • 100 IBS-D patients randomly assigned low FODMAP or traditional diet
  • Patients in the LFD group achieved earlier improvement in stool frequency and excessive gas than those following traditional diet

• Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson’s disease: A randomized controlled trial
  • At 8 weeks, probiotic group had better:
    • Bowel frequency
    • Gut transit

• Long-term symptom severity in people with irritable bowel syndrome following dietetic treatment in primary care: A service evaluation
  • Prospective; Over 150 patients went on low FODMAP diet for 13 months
  • Satisfactory relief of gut symptoms in 55% at long-term

• Oxidative stress and inflammatory markers in type 2 diabetic patients
  • About 60% of T2DM tested positive for SIBO using GBT

• Fecal microbiota transplantation for Crohn’s disease: a systematic review and meta-analysis
  • After fecal microbiome transplant:
    • 79% had clinical response
    • 62% achieved clinical remission
  • Further analysis: rate of clinical remission with fresh stool FMT was higher (73%) than with frozen stool FMT (43%)

• Short-course Rifaximin therapy efficacy and lactulose hydrogen breath test in Chinese patients with diarrhea-predominant irritable bowel syndrome
  • Non-randomized clinical trial, 78 IBS-D patients given Rifaximin
  • Those who received Rifaximin:
    • All participants showed significant improvements in GI symptom despite LHBT normalization in only 45%
    • Quality of life scores also improved
  • No GI symptoms were associated with SIBO
  • Commentary: Efficacy of Rifaximin may be independent on resolution of SIBO breath test improvement

• Effect of probiotics on gingival inflammation and oral microbiota: a meta-analysis
  • All comparisons displayed that oral probiotics had no significant improvement in:
    • Gingival health
    • Amount of plaque
    • Gum bleeding
    • Gingivitis

• Hepatic Injury in Nonalcoholic Steatohepatitis Contributes to Altered Intestinal Permeability
  • Meta-analysis of 5 studies measuring intestinal permeability by in Non-Alcoholic Fatty Liver Disease (NAFLD)
  • 39% of NAFLD patients had increased intestinal permeability, compared to 7% of healthy controls

Thyroid & Hormone Studies

• Vitamin D deficiency is associated with thyroid autoimmunity: Results from an epidemiological survey in Tianjin, China
  • Vitamin D deficiency was associated with thyroid autoantibody positivity and involved in the etiology of Hashimoto’s thyroiditis
  • Commentary: Strengthens vitamin D use in AITD disease patients

• Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients with Hashimoto Thyroiditis
  • Of those who have Hashimoto’s thyroiditis
    • No differences in systemic cytokines
    • Increased serum zonulin

• Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society
  • 488 Danish endocrinologists surveyed
    • 94% use LT4 as treatment of choice
    • 58% may prescribe combo T4 + T3 if still symptomatic, despite biochemical euthyroidism
    • Majority will not prescribe hormone therapy if euthyroid unless for infertile women w/ high antibody levels
  • Comment: This is in alignment with our philosophy of first confirming correct hypothyroid diagnosis, and working on the gut before switching thyroid medications. This is also congruent with major endocrine society guidelines regarding the correct administration of thyroid medications.

• Insufficient evidence to support the clinical efficacy of selenium supplementation for patients with chronic autoimmune thyroiditis
  • Systematic review of 23 trials
  • Compared to controls, those who received selenium supplementation experienced:
    • Lower TPO antibody levels at 3 and 6 months (but not at 12 months)
    • No significant change in TSH levels
    • Lower thyroid echogenicity
    • Higher risk of reported adverse effects

• Mediation effects of thyroid function in the associations between phthalate exposure and glucose metabolism in adults
  • Urinary phthalate levels were negatively associated with free T4 and positively associated with HOMA-IR (insulin resistance) scores

• Hashimoto’s thyroiditis worsens ovaries in polycystic ovary syndrome patients compared to Anti-Müllerian hormone levels
  • Quantified ovarian reserve by measuring Anti-Müllerian hormone (AMH) in 46 patients w/ both PCOS and Hashimoto’s
    • AMH: Biomarker of ovarian function. Menopausal women have undetectable levels.
  • Fertility rate significantly lower in those w/ both PCOS and Hashimoto’s
  • AMH values
    • Lower in those with both PCOS and Hashimoto’s
    • Negatively associated with TPO antibodies and duration of Hashimoto’s
  • CONCLUSION: “We recommend evaluating both thyroid autoantibodies and hormone levels in PCOS patients at the first visit”
  • Commentary:
    • Hashimoto’s and PCOS have high prevalence together
    • Low AMH associated with ovarian failure and infertility
    • Negative correlation with TPO Abs and AMH levels
    • We should be cognizant of fertility issues in AITD and PCOS patients and consider further hormonal testing

• The influence of age and body weight on levothyroxine replacement dosage to achieve euthyroidism in patients with primary hypothyroidism
  • Dose of LT4 necessary to achieve euthyroidism is influenced by body weight and the presence of antibodies
  • Age and menopause did not influence the required daily dose of LT4

Autoimmunity Studies

• Anti-Ro/SSA Antibodies May Be Responsible for Cerebellar Degeneration in Sjogren’s Syndrome
  • Anti-Ro/SSA antibodies are responsible for cerebellar degeneration in patients suffering from Sjogren’s

Diet & Lifestyle Studies

• The effect of 4-h versus 6-h time restricted feeding on sleep quality, duration, insomnia severity and obstructive sleep apnea in adults with obesity
  • RCT of 49 obese individuals given either 4h or 6h time restricted feeding x8 wks
  • 4-h nor 6-h TRF did not change sleep quality, duration, or risk of sleep apnea
  • Body weight decreased similarly in both 4-h and 6-h groups (~9 lbs)

• Efficacy of single-dose cholecalciferol in the blood pressure of patients with type 2 diabetes, hypertension and hypovitaminoses D
  • RCT of 43 T2DM pts. w/ low vitamin D
    • Given single dose of 100,000 IU vitamin D
  • At 8 wks, greater decrease in systolic and diastolic BP (-8 mmHg) compared to placebo regardless of normalization of Vit D levels
  • Commentary: Vitamin D may improve high blood pressure independent of increase in vitamin D levels

• New Insights into the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Gut-Derived Lipopolysaccharides and Oxidative Stress
  • Patients with NAFLD had a:
    • 64% additional risk of having fatal or nonfatal cardiovascular events (ie: myocardial infarction, stroke, angina, or coronary artery disease)
    • 40% increase of their LPS serum level
      • Ameliorated by multispecies probiotic supplementation in dose-dependent manner
    • 2x rate of intestinal permeability
    • 3x rate of SIBO
      • Antibiotics can reduce liver function tests in animal models
      • Human study: Rifaximin treatment was associated with reduced liver function tests, NAFLD-liver fat score, and inflammatory cytokines
    • Vitamin E at high daily dosages (~800 IU/d) lead to resolution in 36% of those with non-alcoholic steatohepatitis (NASH)
    • Silymarin
      • Reduces liver function tests in NAFLD patients
      • Long-term treatment may also improve NASH
    • Commentary: reduce sources of inflammation to prevent and manage NAFLD. Often this comes from the gut.

• The beneficial short-term effects of a high-protein/low-carbohydrate diet on glycemic control assessed by continuous glucose monitoring in patients with type 1 diabetes
  • Compared effects of three different but isocaloric dietary patterns on blood sugar controls in 15 T1D:
    • High protein/low carb (20% calories)
    • Mediterranean (40% calories carbs)
    • Control diet (50% calories carbs)
  • No significant difference in time in euglycemic range between diets
  • High protein diet performed better for reducing postprandial glucose excursions and hypoglycemic episodes

• Dietary supplementation for gestational diabetes prevention and management: A meta-analysis of randomized controlled trials
  • 53 RCTs of over 9,000 pregnant women
  • Vitamin D and myoinositol supplementation has the potential in primary prevention and management of gestational diabetes
  • Probiotics did not change gestational diabetes incidence but improved cardiometabolic markers (e.g. lipids, glucose, inflammation)

• Optimal cutoff for the evaluation of insulin resistance through triglyceride-glucose index: A cross-sectional study in a Venezuelan population
  • Measured insulin resistance by calculating “Triglyceride Index” (=natural log (Trigs x fasting glucose)/2)
  • Optimal cutoff point= <4.49
    • sensitivity= 83%
    • specificity= 82%
  • Commentary: This validates a novel and easy calculation of insulin resistance using commonly acquired labs