Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – October 2021

by Dr. Ruscio, DNM, 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
Medically reviewed & fact checked by a
board-certified doctor
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Episode 24

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Featured Study

  • Diagnosing Small Intestinal Bacterial Overgrowth: A Comparison of Lactulose Breath Tests to Small Bowel Aspirates
    • Retrospective study of 106 patients who underwent both a lactulose breath test (NA Consensus- positive if increase H2 20+ ppm within 90 minutes or methane 10+ ppm anytime) and duodenal aspirate
    • Results:
      • 16.5% SIBO+ on aspiration
      • 31.1% SIBO+ on LBT
    • Risk factors for SIBO:
      • PPI (62% vs 29%)
      • Diabetes (94% vs 71%)
    • Aspiration and LBT results agreed in only 63.5% of the time
    • Commentary: The agreement of aspiration and LBT for the evaluation of SIBO was poor. GBT is more sensitive and specific to assess SIBO.

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Gastrointestinal Studies

  • Impact of Different Helicobacter Pylori Eradication Therapies on Gastrointestinal Symptoms
    • 140 patients w/ H pylori colonization
    • Randomized to:
      • Concomitant therapy (PPI, amoxicillin, clarithromycin, Flagyl x14 days) 
      • Hybrid therapy (PPI, amoxicillin for 14 days, with added Flagyl and Clarithromycin in last 7 days)
    • Results:
      • Both groups had reduced GI symptoms
      • Slightly better improvement w/ hybrid therapy
    • Commentary: H pylori eradication therapy could alleviate GI symptoms regardless of treatment used, but small favorable effect for hybrid therapy. 
  • Association between serum zonulin level and severity of house dust mite allergic asthma
    • 48 w/ house dust mite allergic asthma, 48 healthy controls
    • Measured serum zonulin as proxy for intestinal permeability
    • The mean serum zonulin was 258.3 ng/ml in the asthmatic group and 80 ng/mL in the control group
    • Higher serum zonulin associated with increased asthma severity
    • Commentary: Increased intestinal permeability contributes to pathogenesis of allergic asthma
  • Seronegative autoimmune atrophic gastritis is more common in elderly patients
    • To assess the occurrence and clinical features of seronegative (absence of parietal cell antibodies (PCA)) compared to seropositive autoimmune gastritis (AAG)
    • Cross-sectional study of 516 adults (mean age 60 yo) w/ biopsy proven AAG in last 10 years
    • 21% were seronegative (had NO antibodies)
    • Older AAG patients had lower rates of being seropositive (having PCA)
      • 70-79 yo= 5% positive
      • 80+ yo= 21% positive
    • Patients over 50 yo had 2.4x increased risk of being seronegative
    • Commentary: Roughly 21% of patients in this study had no PCA despite biopsy-proven AAG diagnosis. Keep AAG in your differential even if seronegative, especially in the elderly. 
  • ​​Prevalence and impact of Rome IV versus Rome III irritable bowel syndrome in patients with inflammatory bowel disease
    • Cross-sectional study of 973 IBD patients
    • Prevalence of IBS:
      • 31% per ROME III criteria
      • 18% per ROME IV criteria
    • Co-presence of IBS associated w/ mood imbalances and lower quality of life
    • Compared to ROME III criteria, those w/ ROME IV IBS had higher rates of anxiety, depression, and lower quality of life
    • Commentary: This study exemplifies 2 major points:
      • There is a substantial concomitant presence of IBS in those w/ IBD
      • Presence of IBS is associated with mood imbalances and worse quality of life

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Diet & Lifestyle Studies

  • Interaction between APOE ε4 and dietary protein intake on cognitive decline: A longitudinal cohort study
    • Prospective study of 3,029 Chinese participants (mean age 77 yo)
    • Those carrying the APOE ε4 allele had faster cognitive decline (OR 1.19)
    • Regular fish intake reduced cognitive decline in those carrying APOE ε4 allele (OR 0.43)
    • Commentary: APOE ε4 allele is associated w/ a small but notable increased risk of cognitive decline (but be careful not to cast fear/worry to patients). Regular fish intake can reduce this risk. 

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Episode 23

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Featured Studies

  • Diagnostic yield of endoscopy in irritable bowel syndrome: A nationwide prevalence study 1987-2016
    • Compared 21,944 IBS patients vs 81,000 without IBS who had colonoscopy + biopsy
    • Also compared 10,000 IBS patients vs 46,000 without IBS who had endoscopy + biopsy
    • For those receiving colonoscopy
      • IBD higher in CONTROLS (1.6% IBS vs. in 5.9% controls) 
      • Precancerous polyps higher in CONTROLS (4.1% vs  13%)
      • Colon cancer higher in CONTROLS (0.8% vs 6.3%)
    • For those receiving endoscopy
      • Celiac disease higher in CONTROLS (1.9% vs 3.4%)
      • Microscopic colitis higher in IBS (2.9% vs 1.7%)
        • Especially for older patients
    • Commentary: The diagnostic yield of colonoscopy and endoscopy for those w/ IBS remains low, but increases with age. 

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Gastrointestinal Studies

  • Probiotics and synbiotics show clinical efficacy in treating gestational diabetes mellitus: A meta-analysis
    • 12 RCTs, 894 participants
    • Compared to the placebo, patients administered probiotics/synbiotics supplements benefited more with regards to: 
      • Glucose 
      • Insulin
      • Lipid metabolism (VLDL -5 mg/dL)
      • Inflammation (hsCRP -1.23)
    • Probiotics also reduced risk of:
      • Fetal hyperbilirubinemia (RR 0.26)
      • Fetal macrosomia (RR 0.47)
      • Newborn weight (effect size -0.29)
    • Commentary: Probiotics given to mothers w/ gestational diabetes not only affect the mother but lowered the risk of fetal adverse events. 
  • Small Intestinal Bacterial Overgrowth In Various Functional Gastrointestinal Disorders: A Case-Control Study
    • 244 participants, 186 w/ functional GI disorders (FGID), 58 healthy controls
    • All had glucose breath test
    • FGIDs had a higher prevalence of SIBO compared to controls (16% FGIDs vs. 10% controls)
      • Even higher rate of SIBO in IBS-D (24%)
    • NO difference for prevalence of methane-positive SIBO between chronic constipation compared to controls (9% vs. 7%)
    • Commentary: Higher rates of SIBO are found in those w/ FGID, especially in those w/ IBS-D. This study surprisingly found NO association between methane-positive SIBO and constipation.
  • Placebo Response Rates in Trials of Licensed Drugs for Irritable Bowel Syndrome with Constipation or Diarrhea: Meta-Analysis
    • 17 RCTs of drugs used for IBS-C (4,600 participants), 17 RCTs of drugs used for IBS-D (3,900 participants) 
    • For IBS-C trials, placebo response rate:
      • Abdominal pain: 35%
      • Stool improvement: 30%
    • For IBS-D trials, placebo response rate:
      • Abdominal pain: 40%
      • Stool improvement: 16%
    • Commentary: There is a strong placebo effect in IBS literature. This corroborates a prior FFMR+ meta-analysis of 73 RCTs suggesting a positive response in 27% of those in the placebo arm. This also highlights the role of limbic retraining/distress tolerance in patients w/ IBS. 

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Autoimmunity Studies


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Thyroid & Hormones Studies

  • Elevated thyroid-stimulating hormone levels are associated with poor sleep: A cross-sectional and longitudinal study
    • 168 subclinical hypothyroid patients, 119 healthy controls
    • Those w/ SCH had higher rates of poor sleep (70% vs 50%)
    • Of those w/ SCH at baseline, TSH normalization was significantly higher in those who slept better than in those w/ poor sleep (85.42% vs. 6.45%)
    • Commentary: Poor sleep is associated w/ SCH. Furthermore, TSH can normalize w/ improvement of sleep
    • Dr. R added: If they did not control for age, we could be seeing the association between age and sleep deterioration

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Diet & Lifestyle Studies

  • A 1-week diet break improves muscle endurance during an intermittent dieting regime in adult athletes: A pre-specified secondary analysis of the ICECAP trial
    • 26 resistance-trained athletes went on 12 weeks of time-restricted feeding, then did 1 week of maintenance calories (by increasing carbs)
    • The 1-week diet break:
      • Had NO significant effect on fat mass
      • Led to small but significant increases in mean body weight (0.6 kg) and fat-free mass (0.7 kg)
      • Small increase in resting energy expenditure (+200 Cals/d)
      • Improved muscle endurance in the legs (but not arms)
      • No change in muscle strength 
      • Lower sensation of hunger and irritability
      • Better mental alertness
    • Commentary: A 1-week diet break to maintenance calories can be a powerful physical and psychological “reset” button to use for patients who are dieting.

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Episode 22

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Featured Study

  • United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis
    • Consensus of 40 GI experts from 19 European countries
    • Definition of gastroparesis: symptoms associated w/ delayed gastric emptying absent of mechanical blockage
      • Symptoms include: 
        • Postprandial fullness/early satiation
        • Epigastric pain
        • Bloating
        • Belching
        • Vomiting
        • Reflux (in 50%)
        • Nausea (in 95%)
    • Risk factors
      • Diabetes
      • Acute GI infection (post-infectious gastroparesis) 
      • Bariatric surgery
      • Hypothyroidism 
      • Connective tissue disease
      • Opioids
    • Diagnosis
      • Upper GI endoscopy is required (usually before gastric emptying test)
      • Abnormal gastric emptying test (scintigraphy) 
    • Treatment
      • Diet
        • Small meals
      • Symptom control
        • PPI for reflux symptoms
        • Antiemetics (e.g. Zofran) for nausea
      • Prokinetic (e.g. Metoclopramide) most appropriate first-line therapy
        • Not to use for more than 12 weeks secondary to side effects (extrapyramidal side effects, tardive dyskinesia)
    • Commentary: This is a nice review of gastroparesis clinical presentation, diagnosis, and treatment. It was unfortunate that they did not review dietary interventions more. Nonetheless, you can work through the GI algorithm as you normally would to assess response and calibrate therapies.

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Gastrointestinal Studies

  • Fecal elastase levels in children diagnosed with functional abdominal pain-not otherwise specified
    • 110 children (<17 yo) w/ functional abdominal pain of unknown etiology, 80 healthy controls
    • Measured fecal elastase levels
    • The functional abdominal pain group had significantly lower elastase levels
    • Commentary: Consider a trial of pancreatic enzyme supplementation after more foundational therapies (diet, probiotics, elemental dieting) in those who still suffer from bloating, abdominal discomfort, and “IBS-like” symptoms. 
  • Fecal calprotectin levels in Helicobacter pylori gastritis in children
    • 89 children w/ upper GI symptoms who had endoscopy
    • 58% had H pylori colonization
    • Fecal calprotectin levels differed depending on H pylori status
      • 75 μg/g in H pylori + group
      • 53 μg/g in H pylori – group
    • Commentary: Fecal calprotectin levels can be mildly elevated in H pylori colonized individuals. However, they are not at a level indicating an IBD diagnosis.

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Thyroid & Hormones Studies

  • Appropriate dose of levothyroxine replacement therapy for hypothyroid obese patients
    • Retrospective study of 200 hypothyroid patients
    • The recommended daily dose of LT4 is 2.3 mcg/kg of lean body mass that could be applied for all ranges of BMI
    • Commentary: You can use 2.3 mcg/kg of LBM for obese patients whose bodyweight may give inaccurate prediction of required T4 therapy. In order to get LBM, multiply total weight by (100 – body fat percentage).

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Diet & Lifestyle Studies

  • Association of Serum 25-Hydroxyvitamin D Concentrations with All-Cause and Cause-Specific Mortality Among Individuals with Diabetes
    • 6,329 adult diabetics from NHANES analysis
    • Higher serum Vit D levels associated with:
      • Lower blood glucose, insulin, lipids, CRP, and insulin resistance (HOMA-IR)
      • Lower cardiovascular and all-cause mortality
        • Compared to those w/ <25 nmol/L, those w/ Vit D levels >75 nmol/L had 40% reduced risk of all-cause and 50% reduced risk of cardiovascular mortality 
    • Commentary: Those w/ higher Vit D levels had better cardiometabolic markers and reduced risk of cardiovascular and all-cause mortality. However, we cannot tell from this study alone whether this is a correlation or association.

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Episode 21

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Featured Study

  • Effect of Low FODMAPs Diet on Irritable Bowel Syndromes: A Systematic Review and Meta-Analysis of Clinical Trials
    • 22 studies
    • A low FODMAP diet group showed: 
      • Moderate reduction in symptom severity (effect size -0.53)
      • Slight improvement in quality of life (effect size 0.24)
      • Decrease in stool frequency for IBS-D (-5.6 stools/week)
      • Improvement in stool consistency
    • Improvements were consistent across IBS types (e.g. IBS-C, IBS-D)
    • Commentary: This meta-analysis showed that a low FODMAP diet significantly improved symptoms and quality of life in all IBS subtypes.

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Gastrointestinal Studies

  • Gut Microbiota Profiles and the Role of Anti-CdtB and Anti-vinculin Antibodies in Patients with FGID
    • 22 healthy controls, 65 patients w/ functional GI disorders (FGID); includes IBS-C, IBS-D, dyspepsia
    • Anti-CdtB or anti-vinculin antibodies positivity:
      • IBS-C: 77%
      • IBS-D: 40%
      • Dyspepsia: 60%
      • Healthy controls: 63%
    • Dysbiosis was more common in those w/ anti-CdtB antibodies
    • No other bacteria markers showed significant differences between FGID subgroups and healthy controls.
    • Commentary: No statistical difference in anti-CdtB and anti-vinculin antibodies between those w/ FGID and healthy controls. However, there was more dysbiosis in those w/ anti-CdtB antibodies.
    • Dr. Ruscio wanted me to mention that his clinical suspicion has been this is not a marker that is highly influential in patient care, which is why he and we at the clinic do not routinely use it.  We will keep an open mind, and an eye on the data, but so far we recommend against it. 
  • Small intestinal bacterial overgrowth in patients with inflammatory bowel disease: A case-control study
    • 86 IBD patients (45 ulcerative colitis [UC] and 41 Crohn’s disease [CD])
    • Measure prevalence of SIBO w/ glucose breath test
    • IBD patients had higher rates of SIBO (18.6%) vs healthy controls (1.5%)
      • SIBO more common in CD than UC (34% vs 4.4%)
    • Commentary: SIBO is more common in those w/ IBD- especially those w/ CD. Refer to FFMR+ episode #15 (July 5th) that showed lower rates of methane SIBO in those w/ IBD. Dr. Ruscio notes that this makes sense given that bowel regularity impacts methane levels and those w/ diarrhea have less hydrogen hanging around in the gut to feed methane. 
  • Are Probiotics and Prebiotics Safe for Use during Pregnancy and Lactation? A Systematic Review and Meta-Analysis
    • 11 studies of probiotics used in pregnancy or lactation
    • Probiotic and prebiotic products are safe for use during pregnancy and lactation
    • One study reported increased risk of vaginal discharge and changes in stool consistency (relative risk 3.67)
    • “Adverse effects associated with probiotic and prebiotic use do not pose any serious health concerns to mother or infant.”
    • Commentary: There’s NO high quality evidence to suggest that probiotics can’t be used in pregnancy or during lactation. 
  • A 12-month pilot study outcomes of vagus nerve stimulation in Crohn’s disease
    • 9 Crohn’s disease (CD) patient, underwent vagal nerve stimulation (electrode on left cervical vagus nerve)
    • After 12 months:
      • 5 patients in clinical remission
      • 6 patients in endoscopic remission
      • 6 patients reduced CRP
      • 5 patients reduced fecal calprotectin
    • Commentary: Vagal nerve stimulation may be a promising (yet invasive) therapy for refractory CD cases after more minimally invasive therapies fail.
  • Homemade Elemental Diet to Treat Intestinal Methanogen Overgrowth: A Case Report
    • Cae report of a 47 yo female w/ methane-predominant SIBO confirmed via multiple lactulose breath test (average of 42 ppm)
    • Refractory to diet/lifestyle/prokinetic therapy
    • Performed a 14-day and 9-day homemade elemental diet 4 months apart.
    • Methane levels reduced to 3 ppm (after 14-day course) and 23 ppm (after 9-day course).
    • Commentary: The authors might have missed on the potential beneficial effects of a partial elemental approach.

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Thyroid & Hormones Studies


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Diet & Lifestyle Studies

  • Association between neuropathy and B-vitamins: A systematic review and meta-analysis
    • 46 observational studies, 7 clinical trials
    • Peripheral neuropathy was associated with lower B12 and higher homocysteine levels
    • B vitamin supplementation associated with a non-significant improvement of peripheral neuropathy
      • Greater benefit for B1 (thiamine)
    • Commentary: The results of these studies are misleading since the clinical trials did NOT assess for B vitamin deficiency prior to treatment.
  • Nutrient Adequacy Is Associated with Reduced Mortality in US Adults
    • Cross-sectional study, 20,602 participants
    • Evaluated for macronutrient and micronutrients
    • Higher intakes of vitamin E, magnesium, iron, dietary fiber, omega-3 fatty acids, and potassium were associated with LOWER all-cause mortality
    • Commentary: Better nutrition quality, and subsequent micronutrient status is associated w/ lower all-cause mortality.

Discussion

I care about answering your questions and sharing my knowledge with you. Leave a comment or connect with me on social media asking any health question you may have and I just might incorporate it into our next listener questions podcast episode just for you!

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