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Future of Functional Health Review Clinical Newsletter

Research Briefs for Practitioners – July 2021

by Dr. Ruscio, DC, Gavin Guard, PA-C, MPAS, CISSN, Pn1, and the Ruscio Institute for Functional Medicine Clinical Team

Medically reviewed & fact checked by a
board-certified doctor
Dr. Ruscio and his team are committed to delivering content that is accurate and objective. Every new article is thoroughly fact-checked by a board certified doctor from our network.
Medically reviewed & fact checked by a
board-certified doctor
Dr. Ruscio, DC and his team are committed to delivering content that is accurate and objective. Every new article is thoroughly fact-checked by a board certified doctor from our network.
Published on July 1, 2021 by

Sections

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Episode 12

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Featured Study

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Gastrointestinal Studies

  • Elevated Faecal Calprotectin in Patients with a Normal Colonoscopy: Does It Matter in Clinical Practice? A Retrospective Observational Study
    • 1,200 patients referred for colonoscopy, measured fecal calprotectin day before, followed for 3 years
    • Of the 600 who had normal colonoscopy
      • 34% had elevated calprotectin (>50 μg/g)
      • 66% had normal calprotectin
    • Association of elevated calprotectin and UPPER GI diseases (e.g. gastritis)
      • BUT, this association was not seen after adjusting for NSAID, PPI, age, and gender
    • No increased risk of LOWER GI disease in those w/ elevated calprotectin but had NORMAL colonoscopy
    • Commentary: An elevated calprotectin does NOT indicate increased future risk of GI disease in those with NORMAL colonoscopy.
  • Histamine Intolerance: The Current State of the Art
    • Review of histamine intolerance
    • In study of 27 headache patients, DAO deficiency in 85%
      • After patients followed low histamine diet x4 weeks:
        • Significant increase in DAO activity
        • remission or reduction in frequency of headaches in 90%
      • In another study of 137 migraine patients, 87% had DAO deficiency
      • In a pediatric population under 15 years of age, DAO deficiency in 88% of patients with abdominal pain, diarrhea and vomiting
      • Efficacy of low histamine diet ranges from 33-100%
        • Majority of studies (10 of the 13) reviewed found an improvement in symptoms in >50% of patients
      • Efficacy of DAO supplementation of 93% in one small study of 14 participants
      • Commentary: Histamine may play a role in headaches/migraines/functional GI disorders. Most importantly, a low histamine diet can lead to clinical improvements.
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Autoimmunity Studies

  • Intestinal permeability in spondyloarthritis and rheumatoid arthritis: A systematic review of the literature
    • Is intestinal permeability part of the pathogenesis of spondyloarthritis (SA) and rheumatoid arthritis (RA)
    • Systematic review of 23 studies
    • Increased permeability in:
      • large majority of studies for SA regardless of the method used
        • Effect seen independent of NSAID use
      • only ½ of studies looking at RA
    • Commentary: Increased intestinal permeability may play a role in the pathogenesis of some autoimmune disease, some more than others.
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Diet & Lifestyle Studies

  • Nutraceuticals in Patients With Heart Failure: A Systematic Review
    • 40 studies over 6 months w/ at least 50 patients
    • Decreased mortality for use of
      • CoQ10
      • Polyunsaturated fatty acids (PUFAs)
    • Underpowered or too small of studies to show benefit:
      • Magnesium
      • Thiamin
      • Vitamin E
      • L-carnitine
      • Beetroot juice
      • L-arginine
      • Vitamin D
    • Commentary: Good evidence exists for using CoQ10 and PUFAs in those w/ heart failure.
  • Snoring and environmental exposure: results from the Swedish GA2LEN study
    • Study published in British Medical Journal
    • Cross-sectional analysis, 25,000 healthy participants in Sweden
    • Of the 4,000 (16%) habitual snorers, there was a higher rate of reported
      • water damage (8.3% vs 7%)
      • floor dampness (4.6% vs 3.8%)
      • And visible mold (5.2% vs 3.8%) in their homes when compared to non-snorers
    • Compared to non-snorers, habitual snorers had higher reports of:
      • Annoyed/irritated by air pollution
        • sometimes 16.2% vs 13.9%
        • daily 4.6% vs 3.1%
      • Annoyed by traffic fumes
        • somewhat 19% vs 18.5%
        • very 5% vs 3.6%
    • Commentary: This study points to the possible CLINICAL EFFECT that mold exposure has on non-specific health outcomes such as snoring/apnea/sleep health. Those who snored, had higher rates of possible mold exposure and chemical sensitivity. However, the percent differences of snorers vs non-snorers is not that different and we should be careful w/ confirmation bias.
  • Aspirin in the primary prevention of cardiovascular disease on diabetic patients: Systematic review and meta-analysis
    • 7 RCT, 28,000 patients
    • Aspirin used in the primary prevention of cardiovascular disease (CVD) in diabetic patients associated with:
      • NO significant reduction in all-cause mortality
      • 8% reduction in major adverse cardiovascular events (MACE)
      • 30% relative increase in major bleeding and 40% relative increase in major GI bleeding
    • Commentary: Aspirin use among diabetic patients in primary prevention appears to be associated with increased risk of major bleeding, a modest decrease of MACE, but lack of mortality benefit.
  • Remnant lipoproteins: are they equal to or more atherogenic than LDL?
    • Review the potential harmful effects of remnant lipoproteins (e.g. remnant VLDL)
    • Main findings:
      • Remnant VLDL particles accumulate significantly in those with high triglycerides and are cleared very slowly
      • Remnant VLDL particles may increase cardiovascular risk
      • In randomized trials involving statin-treated patients with cardiovascular disease, remnant cholesterol levels were associated with atherosclerosis independently of LDL-cholesterol.
    • Commentary: Overall findings from multiple types of studies indicate that remnant lipoproteins are a major contributor to atherosclerosis.
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Episode 11

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Featured Study

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Gastrointestinal Studies

  • Serum Zinc and Selenium in Children with Inflammatory Bowel Disease: A Multicenter Study in Japan
    • Retrospective study of pediatric patients w/ IBD in Japan
      • 98 w/ Crohn’s disease (CD)
      • 118 w/ ulcerative colitis (UC)
      • 43 healthy controls
    • Measured serum zinc and selenium
    • Rates of zinc and selenium deficiency were much more common in CD compared to UC and controls
      • Selenium deficiency:
        • CD: 15%
        • UC: 6%
        • Controls: 0%
      • Zinc deficiency:
        • CD: 60%
        • UC: 52%
        • Controls: 37%
      • Commentary: I suspect that since CD can affect the small bowel, nutrient absorption can be impaired much more compared to UC which solely affects the large bowel.
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Thyroid & Hormone Studies

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Autoimmunity Studies

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Diet & Lifestyle Studies

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Episode 10

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Featured Study

  • Iron deficiency without anaemia: a diagnosis that matters
    • 2 billion people with iron deficiency anaemia (IDA), 2.4 billion people with iron deficiency without anaemia (IDWA)
    • Iron deficiency (ID)= refers to low iron stores, regardless of whether anaemia is present or not
    • Symptoms of anemia such as fatigue can be present without anaemic hemoglobin levels
    • Causes of iron deficiency:
      • inadequate dietary intake
      • increased body needs
      • reduced absorption
      • chronic inflammation
      • chronic blood loss
    • Gut-iron connection
      • gastric acid is required for the reduction of Fe3+ to Fe2+, which is more readily absorbed
      • pylori infection may cause ID due to reduced iron absorption and blood loss
      • Celiac disease and inflammatory bowel disease can lead to ID secondary to chronic inflammation
    • Accurate diagnosis:
      • Ferritin is an indicator of iron stores and is the most sensitive and specific biomarker for assessing ID.
        • Cutoff: <30 μg/L
        • But, cut-off values for ferritin in ID are increased to 100 μg/L in states of chronic inflammation
      • Transferrin saturation (TSAT) levels below 20% are also diagnostic of ID
      • Serum iron levels fluctuate throughout the day and should not be used for diagnosis
      • Other markers
        • Serum transferrin receptor (sTFR) is a valuable indicator of ID
          • it is unaffected by inflammation (unlike ferritin)
          • Would be HIGH in iron deficiency
        • When hemoglobin levels are normal, a low reticulocyte hemoglobin count (RHC) indicates early ID
      • “Clinicians should consider the fact that normal hemoglobin ranges have been set using population data. Essentially, what may be a normal hemoglobin level for one person may be abnormal for another, especially if a patient has a hemoglobin level in the low-normal range but their usual hemoglobin levels are higher.”
    • Treatment of ID
      • “A recent systematic review concluded that iron supplementation in IDWA improves subjective measures of fatigue.”
      • ID (even without anemia) should be treated when identified, with a target ferritin of 100 mg/L
      • Using single doses on alternate days as opposed to multiple doses on consecutive days has been shown to result in higher absorption
        • The recommended oral dose is 28–50 mg iron daily or 100 mg on alternate days for 25 days
      • Once ferritin levels have corrected, patients should be followed up with blood tests every 6–12 months
    • Commentary: Save this algorithm in your notes. Iron deficiency (even without frank anemia) is worth diagnosing accurately and treating when indicated but don’t forget the gut-iron connection.

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Gastrointestinal Studies

  • Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study
    • 160 adults w/ morbid obesity
    • Tracked serum zonulin at baseline, 6 months after diet/lifestyle interventions, and 6 months after bariatric surgery
    • Zonulin reduced after the conservative weight loss intervention, and further reduced after bariatric surgery.
    • Reduction in zonulin was associated with improvement of diarrhea, markers of glucose intolerance and liver disease, but not associated with the change in BMI
    • Commentary: Higher quality diet and improved blood sugar control may improve leaky gut independent of weight loss.
  • Gluten-induced Neurocognitive Impairment: Results of a Nationwide Study
    • Survey of 1,400 individuals w/ gluten intolerance (celiac or NCGS)
    • 89% of CD and 95% of NCGS reported some type of neurocognitive impairment
    • Most common symptoms: difficulty concentrating, forgetfulness, and grogginess
    • Commentary: brain fog is a common symptom of gluten intolerance
  • Efficacy of probiotics in multiple sclerosis: a systematic review of preclinical trials and meta-analysis of randomized controlled trials
    • 3 RCT (173 MS patients), 22 preclinical studies
    • Clinical studies
      • significant beneficial effects of probiotic supplementation on mental health
        • BUT, low quality of evidence
      • probiotic intake improved insulin resistance, inflammatory markers, and oxidative stress markers
    • Preclinical studies
      • reduces the incidence and severity of MS
      • delays MS progression (15 studies)
      • improves motor impairment (3 studies)
      • favorable alterations of immune and inflammatory markers (20 studies)
      • Improvement of intestinal microbiome composition (4 studies)
    • Commentary: Probiotics show promise in MS.
  • What is the appropriate cut-off value of CRP to predict endoscopic remission in patients with ulcerative colitis in clinical remission?
    • Conventionally, a CRP <0.3 is the cutoff of clinical remission in those with ulcerative colitis
    • 132 patients w/ ulcerative colitis who underwent endoscopic evaluation, measured CRP values
    • CRP levels significantly lower in those in remission (0.05) vs. those not in remission (0.14)
    • CRP cutoff <0.09 to predict remission
      • Sensitivity: 71%
      • Specificity: 72%
    • Commentary: this study suggests that a much lower CRP level of <0.09 is needed to accurately predict clinical remission in those with ulcerative colitis. In UC patients in remission, it may be helpful to lower the CRP cut-off value that predicts remission other than 0.3 mg/dL, which is usually considered normal.
  • Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review
    • 13 trials
    • limiting or ruling out gluten or FODMAPs in the diet might be beneficial for symptoms such as:
      • depression
      • anxiety (all 7 studies found a positive effect)
      • cognition deficiency (improvements in cognition in 1 trial)
      • schizophrenia and autism spectrum (to a lesser degree)
    • Commentary: this review highlights the gut-brain axis and exemplifies the improvement in symptoms when treating the gut.
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Thyroid & Hormone Studies

  • Risk of All-Cause Mortality in Levothyroxine-Treated Hypothyroid Patients: A Nationwide Korean Cohort Study
    • 500,000 w/ overt hypothyroidism on levothyroxine, 1.5 million healthy controls
    • Followed over 6 years
    • Hypothyroidism was significantly associated with increased all-cause mortality (HR 1.14) even w/ levothyroxine treatment
    • This association was independent of age, sex, and cardiovascular disease
    • Commentary: all-cause mortality was significantly higher in levothyroxine-treated hypothyroid patients than in non-hypothyroid controls.
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Autoimmunity Studies

  • Probiotic baths for atopic dermatitis
    • Randomized, double-blind trial of 22 patients w/ atopic dermatitis
    • Applied 10 minute partial bath in probiotics (4.5 billion CFU/liter) every day
    • After 14 days, probiotic lead to:
      • Significant reduction in atopic dermatitis symptoms (baseline score: 63, day 7: 47, day 14: 35)
      • Reduction in dry skin and itchiness
      • Reduction in aureus gene copy numbers by 83%
    • Commentary: This study shows a few points:
      • Probiotic have an antimicrobial effect
      • Probiotics can be safely given topically and can correct dermal dysbiosis
      • Probiotics should be considered in atopic diseases
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Diet & Lifestyle Studies

  • Serum Ferritin Correlates With Liver Fat in Male Adolescents With Obesity
    • Adolescent males; 44 w/ fatty liver, 15 without fatty liver
    • Measured various biomarkers and MRI of liver
    • ferritin was associated with MRI liver fat
    • “Our data indicate that serum ferritin in male adolescents with obesity is mainly determined by liver fat content and inflammation but not by body iron status.”
    • Commentary: remember that ferritin usually is increased in chronic inflammation.
  • Exposure to endocrine disruptors and risk of breast cancer: A systematic review
    • What’s the association between human exposure to endocrine disruptors (EDs) and the risk of breast cancer?
    • 37 studies
    • Most studies reported that exposure to organochlorine pesticides, phthalates, heavy metals, and polycyclic aromatic hydrocarbons was associated with increased breast cancer risk.
    • Commentary: remember that EDs can be found in plastics, cleaning products, personal care products, and some food.
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Episode 9

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Featured Study

Persisting symptoms in patients with Hashimoto’s disease despite normal thyroid hormone levels: Does thyroid autoimmunity play a role? A systematic review

  • 5-10% of Hashimoto patients experience symptoms despite being biochemically euthyroid
  • Review of the relationship between thyroid antibodies and symptoms
  • 30 studies
  • 5 of 7 case cross-sectional studies found an association between thyroid autoimmunity and more symptoms or lower quality of life (QoL)
  • 16 of 23 prospective studies found a comparable association.
    • However, the total number of people studied in the other 7 studies showing no association between symptoms and thyroid autoimmunity was much higher (20,000 in no association studies, 8,000 in association studies)
  • Commentary:
    • In total, the majority of included studies reported an association between thyroid autoimmunity and persisting symptoms or lower QoL in biochemically euthyroid patients.
    • The negative association between antibodies and symptoms was calculated after correcting for TSH and thyroid function
      • In other words, higher antibodies are associated with more symptoms independent of TSH or fT4
    • Thyroid antibodies may affect brain tissue, hence the continuation of low thyroid symptoms.
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Gastrointestinal Studies

  • Long-term Intake of Gluten and Cognitive Function Among US Women
    • Prospective study, 13,500 women without celiac disease
    • NO significant differences in standardized cognitive scores were found across highest and lowest quintiles of gluten intake
    • Commentary: In this study, gluten consumption was not associated with cognitive function in absence of celiac disease.
  • Dietary Therapies and Eosinophilic Esophagitis
    • Expert opinion
    • Endorses elemental diet
    • Elimination diet
      • 6-food elimination diet (milk, wheat, soy, egg, nuts, and seafood): 70-74% effective over 6 weeks
      • 4-food elimination diet (milk, wheat, soy, and egg): 45-60% effective over 6 weeks
      • 2-food elimination diet (milk and wheat): 30-40% effective over 6 weeks
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Diet & Lifestyle Studies

  • Blood Lead Level and Renal Impairment among Adults: A Meta-Analysis
    • 43 studies
    • Lead blood level definitions
      • High= 42 µg/dL
      • Moderate= 22 µg/dL
      • Low= 2.9 µg/dL
    • Mean lead levels of the exposed participants was higher than that of the non-exposed participants
    • Renal markers (BUN, creatinine) were significantly higher in exposed vs non-exposed participants
    • Commentary: This study shows that exposure to lead is associated with higher blood lead levels.
About the author

Dr. Ruscio

Dr. Michael Ruscio is a DC, Naturopathic Practitioner, researcher, and clinician. He serves as an Adjunct Professor at the University of Bridgeport and has published numerous papers in scientific journals as well as the book Healthy Gut, Healthy You. He also founded the Ruscio Institute of Functional Health, where he helps patients with a wide range of GI conditions and serves as the Head of Research.
Dr. Michael Ruscio is a DC, Naturopathic Practitioner, researcher, and clinician. He serves as an Adjunct Professor at the University of Bridgeport and has published numerous papers in scientific journals as well as the book Healthy Gut, Healthy You. He also founded the Ruscio Institute of Functional Health, where he helps patients with a wide range of GI conditions and serves as the Head of Research.

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