Research Briefs for Practitioners – March 2022 - Dr. Michael Ruscio, DNM, DC
Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – March 2022

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 44

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Featured Studies

  • The effectiveness of rotating versus single course antibiotics for small intestinal bacterial overgrowth
    • 223 patients w/ SIBO (by glucose breath test)
    • Patients were treated either with a single antibiotic (quinolone or azole) or rotating antibiotics (quinolone and azole, one after the other) for 10 consecutive days per month for 3 months. 
    • The rotating antibiotic group had higher rate of clinical remission (70% vs 50.8%)
    • Clinical remission was associated with an improvement in quality of life and bloating
    • Commentary: Rotating antimicrobials may be superior for treating SIBO. This study showed an association between the eradication of SIBO and the improvement of quality of life and bloating.

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Gastrointestinal Studies

  • Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome
    • Aim: Investigate predictors of symptom improvement after dietary change in those w/ IBS
    • 67 IBS patients, randomized to low FODMAP diet or traditional diet x4 weeks
    • Factors associated w/ more symptom improvement:
      • Less severe dysbiosis (per GA-map Dysbiosis test)
      • Higher energy intake at baseline (less food restriction)
    • More psychological distress associated with LESS symptom improvement
    • Commentary: Those who may respond better to a low FODMAP (or another IBS diet) include: those w/ less dysbiosis, less anxiety, and who are able to tolerate more foods at baseline.
  • The Effects of One Anastomosis Gastric Bypass Surgery on the Gastrointestinal Tract
    • Prospective study of 32 patients who all had one anastomosis gastric bypass (OAGB) bariatric surgery
    • 6 months after surgery:
      • Increase in SIBO positive (0% to 37%)
        • SIBO was associated w/ lower fiber intake and higher vitamin A deficiency 
      • Increase in exocrine pancreatic insufficiency (0% to 26%)
      • Decrease in microbial diversity
    • Commentary: Relatively high rates of SIBO and exocrine pancreatic insufficiency were found after bariatric surgery at a 6 month follow up.
  • Additive effect of probiotics on 5-aminosalicylic acid therapy in patient with ulcerative colitis
    • 118 patients w/ mild-to-moderate ulcerative colitis (UC)
    • Randomized to E. coli Nissle 1917 probiotic or placebo
    • After 8 weeks of supplementation, the probiotic group had:
      • NO difference in IBD symptom score
      • HIGHER clinical response (39.7% vs 21.7%)
      • HIGHER endoscopic remission (46.4% vs 27.1%)
    • Commentary: This study found that the probiotic, E. coli Nissle 1917 was effective in improving UC.
  • Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial
    • 35 patients w/ active ulcerative colitis (UC) all had 2 weeks of antibiotics (amoxicillin, metronidazole, and doxycycline)
    • Then randomized to placebo or FMT capsules x8 weeks
    • After 8 weeks, those who responded to the FMT were randomized to withdrawal or continuation of FMT for another 48 weeks
    • After 8 weeks of supplementation, the FMT group had:
      • Higher rate of clinical and endoscopic remission (53% vs 15%)
      • No difference in adverse event rate (67% vs 85%)
    • Those who continued FMT x48 weeks had higher rate of remission (100% vs 0%)
    • Commentary: FMT capsules are beneficial for those w/ UC. However, it looks as though the benefit may be only transitory while the patient is taking FMT.

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Thyroid & Hormones Studies


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Diet & Lifestyle Studies

  • An Open-Label, Pilot Trial of HRG80™ Red Ginseng in Chronic Fatigue Syndrome, Fibromyalgia, and Post-Viral Fatigue
    • Open-label prospective study of 188 w/ chronic fatigue/fibromyalgia
    • All took red ginseng supplementation
    • After 30 days of supplementation:
      • 67% increase in energy
      • 48% increase in mental clarity
      • 46% improvement in sleep
      • 72% increase in physical stamina
      • 33% decrease in pain
    • Commentary: This study showed that red ginseng supplementation led to a significant improvement in chronic fatigue/fibromyalgia. Note that there was no testing performed before supplementation w/ this adaptogen.

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Episode 43

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Featured Study

  • Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis 
    • 17 studies, 1,103 patients
    • About 1/3 of patients undergoing thyroid hormone discontinuation remained euthyroid at follow-up (37.2%)
    • Patients with a previous diagnosis of overt hypothyroidism were less likely to remain euthyroid (11.8%) than patients with a prior diagnosis of subclinical hypothyroidism (35.6%)
    • Commentary: A substantial amount of patients on thyroid hormone remain euthyroid after discontinuing thyroid replacement therapy.

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Gastrointestinal Studies

  • A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn’s Disease
    • 194 Crohn’s Disease (CD) patients randomized to mediterranean diet (MD) or specific carbohydrate diet (SCD)
    • After week 6, the SCD group had, NO difference in:
      • Clinical remission rate (46.5% vs 43.5%)
      • Fecal calprotectin remission (34.8% vs 30.8%)
      • CRP remission rate (5.4% vs 3.6%)
    • Commentary: This study showed NO difference between the MD and SCD for improving Crohn’s Disease. This is why we at the clinic follow a step-wise approach for dietary interventions (e.g. first start with a paleo diet before moving to a SCD).
  • A Single Fasting Exhaled Methane Level Correlates With Fecal Methanogen Load, Clinical Symptoms and Accurately Detects Intestinal Methanogen Overgrowth
    • Assessed the viability of using a single fasting breath methane level to diagnose intestinal methanogen overgrowth (IMO)
    • Using the cutoff of ≥10 ppm, a single methane measurement had a:
      • Sensitivity of 86.4% 
      • Specificity of 100% for diagnosing IMO
      • And was associated with constipation
    • Antibiotics led to a decrease of the fasting single methane measurement
    • Single methane measurement was associated with higher stool M. smithii levels
    • Commentary: A single methane breath level may be an accurate predictor of IMO, and correlates w/ M. smithii levels in the stool. 
    • Dr. Ruscio has been critical of some of Rao’s work on probiotics, however this study deserves praise as it has much clinical relevance.
  • Frequency of Celiac Disease in Patients With Chronic Diarrhea
    • Cross-sectional study of 188 patients w/ chronic diarrhea (>3 months)
    • Celiac disease was found in 12.2% of the individuals
    • 21% of those w/ a family history of celiac disease developed the disease
    • Commentary: A small (but notable) portion of those w/ chronic diarrhea may have diarrhea, especially if there is a family history of the disease.

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Thyroid & Hormones Studies

  • Vitamin D and thyroid disorders: a systematic review and Meta-analysis of observational studies
    • Examine the relationship between vitamin D levels and thyroid disorders
    • Serum vit D levels were significantly lower in those with:
      • Autoimmune thyroid disease (-3.1 ng/dL)
      • Hashimoto’s (-6.1 ng/dL)
      • Hypothyroidism (-13.4 ng/dL)
    • No difference in those w/ Graves’ disease
    • Commentary: This study showed lower Vit D levels in those w/ thyroid dysfunction, except for Graves’ disease.

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Diet & Lifestyle Studies

  • Sleep disordered breathing as a risk factor for unnecessary pacemaker implantation
    • 207 patients w/ cardiovascular disease at high risk for sleep disordered breathing (SDB)
    • SDB confirmed in 84.5% (36% had severe SDB)
    • Severe SDB was a predictor of the following during sleep:
      • Third-degree AV block (OR 11.6)
      • Second-degree AV block type 2 (Mobitz) (OR 4.5)
      • Sinus bradycardia below 40 bpm (OR 3)
    • Commentary: SDB may be a risk factor for heart arrhythmias. 
  • Effects of Periodization on Strength and Muscle Hypertrophy in Volume-Equated Resistance Training Programs: A Systematic Review and Meta-analysis
    • 35 studies comparing periodized vs non-periodized strength training
    • Periodized strength training had:
      • Better 1-rep max strength (effect size 0.31) in trained participants
      • NO difference in muscle hypertrophy
    • Commentary: Following a periodized (change in volume and intensity over time) strength training program may be better, as compared to non-periodized training. However, this may not make a big difference in an untrained population. 
    • Dr. Ruscio wanted to make the connection that periodization might make exercise unnecessarily complicated, much like some practices in GI and FM care.

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Episode 42

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Featured Study

  • Small Intestinal Bacterial Overgrowth in Subclinical Hypothyroidism of Pregnant Women
    • 224 pregnant women w/ subclinical hypothyroidism (SCH), 196 euthyroid pregnant women
    • Lactulose breath test and thyroid function tests performed in all women
    • Pregnant women w/ SCH had:
      • HIGHER rate of SIBO (57% vs 32%)
      • Higher CRP (7.8 vs 4.7)
      • More GI symptoms
      • Higher TPO antibodies (32 vs 11)
      • Higher TSH (5.9 vs 5.3) and lower fT4 (13.5 vs 14.1)
    • Commentary: SIBO is associated w/ SCH.

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Gastrointestinal Studies

  • Monocytosis Is a Biomarker of Severity in Inflammatory Bowel Disease: Analysis of a 6-Year Prospective Natural History Registry
    • Prospective study of 1,290 patients with IBD (64.1% with Crohn’s disease; 35.9% with ulcerative colitis)
    • Followed over 6 years
    • Monocytosis (high monocytes on CBC) was found in 399 (30.9%) of patients with IBD 
      • 29.3% with Crohn’s disease
      • 33.9% with ulcerative colitis
    • Monocytosis was associated with:
      • Elevated CRP and ESR levels
      • Anemia
      • Worse quality of life
      • Longer time on biologic medications
      • Higher financial costs
      • Increased risk of hospitalization
    • Commentary: High monocytes can be an indicator of higher disease activity in those w/ IBD. 
  • Proton pump inhibitors and risk of gastric cancer: population-based cohort study
    • Prospective study of 973,281 new PPI users, and 193,306 new H2 blocker users
    • Followed ~5 years
    • The use of PPIs was associated with a 45% increased risk of gastric cancer compared with the use of H2 blockers (HR 1.45)
    • The number needed to harm was:
      • 2,121 for 5 years after starting treatment
      • 1,191 for 10 years after starting treatment
    • Commentary: Compared to H2 blockers (e.g. Pepcid), PPI use was associated w/ a higher risk of gastric cancer, although the absolute risk is low.
  • Chronic Intestinal Pseudo-Obstruction Is Associated with Intestinal Methanogen Overgrowth
    • Retrospective study of 494 patients, all had glucose breath test
    • 7.7% had intestinal pseudo-obstruction (rare motility disorder of dilated small bowel in the absence of mechanical obstruction)
    • Prevalence of methane-positive SIBO was much higher in those w/ intestinal pseudo-obstruction (53% vs 12%)
    • No difference in hydrogen SIBO between the 2 groups
    • Commentary: Methane-positive SIBO can contribute to reduced GI motility.
  • Diagnostic yield of esophagogastroduodenoscopy in France
    • Survey of 342 gastroenterologists, including 2,735 endoscopies
    • Most common findings on endoscopy:
      • 32.8% normal
      • 20.9% gastritis
      • 18.1% hiatal hernia
      • 13.7% esophagitis
      • 4% Barrett’s esophagus
      • 2.9% peptic ulcer
      • 0.7% malignancy
    • Commentary: The majority of endoscopies are normal. Only a small fraction find malignancy.
  • Probiotic Supplementation for Promotion of Growth in Children: A Systematic Review and Meta-Analysis
    • 79 RCTs of probiotics used in kids 0-5 years old 
    • Probiotics had a small effect on increasing weight (effect size 0.26) and height (effect size 0.16)
    • This beneficial effect was only seen in low-middle income countries (not in high-income countries)
    • Commentary: Probiotics may be able to improve weight and height in kids who may be predisposed to malnutrition (e.g. kids who live in low-middle income countries).

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Thyroid & Hormones Study

  • Hyperthyroidism in Graves’ disease causes sleep disorders related to sympathetic hypertonia
    • Prospective study of :
      • 22 newly diagnosed Graves’ Disease (GD) with untreated hyperthyroidism
      • 20 previously diagnosed with GD with normal thyroid function
      • And 30 healthy controls
    • Newly diagnosed GD patients started treatment and all followed x12 months
    • At 12 month follow-up:
      • Sleep quality was worse in untreated GD group
      • Higher fT4 levels were associated with worse sleep quality
      • Sleep quality improved by treating the GD group
    • Commentary: Sleep quality can be impaired by hyperthyroidism and improved by treating it.

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Diet & Lifestyle Studies


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Episode 41

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Featured Studies

  • A Systematic Review and Meta-analysis of Randomized Control Trials: Combination Treatment With Proton Pump Inhibitor Plus Prokinetic for Gastroesophageal Reflux Disease
    • 16 studies, 1,446 participants w/ GERD
      • 727 receiving PPI only
      • 719 receiving PPI + prokinetic
    • The PPI + prokinetic resulted in greater improvement of GERD symptoms regardless of prokinetic type or GERD severity
    • No difference in quality of life or adverse effects
    • Commentary: PPI + prokinetic is superior to PPI alone in those w/ GERD.
      • Dr. Ruscio wanted to add he has mixed emotions about prokinetics. He quickly checked this study and had his hesitancy reinforced by this quote:
        • “In Asia, the most commonly used prokinetics are mosapride, itopride, and domperidone. However, another prokinetic agent, cisapride, has been withdrawn from the market owing to its association with fatal heart arrhythmia.”
      • We aim to treat dysmotility further upstream, although still lacking robust data to support our approach.

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Gastrointestinal Studies

  • Glutamine Supplementation Enhances the Effects of a Low FODMAP Diet in Irritable Bowel Syndrome Management
    • 50 IBS patients, randomized to:
      • Low FODMAP diet + placebo
      • Low FODMAP diet + glutamine (15 g/d)
    • After 6 weeks, the low FODMAP diet + glutamine group had significant improvement in IBS symptoms (58% reduction)
      • Improvement in IBS-severity score of more than 45% was observed in 88% (vs 60% in low FODMAP + placebo)
    • Commentary: Adding glutamine supplementation to a low FODMAP diet is superior to a low FODMAP diet alone. This is one of the mainstays of our clinic model.
  • A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials
    • 42 RCTs examining effect of microbial therapy (probiotics, prebiotics, FMT) for improving metabolic syndrome
    • Microbial therapy resulted in:
      • Reduced waist circumference (effect size -0.26)
      • Reduced fasting glucose (effect size -0.35)
      • Reduced total cholesterol (effect size -0.36)
      • Reduced LDL-C (effect size -0.42)
      • Reduced triglycerides (effect size -0.38)
      • Increased HDL-C (0.28)
      • No change in A1C or systolic blood pressure
    • Commentary: This meta-analysis suggested that GI therapies can improve most metabolic parameters w/ a small effect size. 
  • A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder
    • 20 patients w/ alcohol use disorder and cirrhosis randomized to placebo enema or FMT enema
    • At 2 weeks follow-up:
      • Alcohol cravings reduced significantly in 90% of FMT versus 30% in placebo
      • FMT had reduced serum inflammatory markers
    • At 6 month followup, placebo had HIGHER rates of serious adverse events (8 vs 2)  
    • Commentary: FMT may help improve alcohol cravings and have lower adverse events compared to placebo.

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Thyroid & Hormones Studies

  • Carotid Intima-Media Thickness in Patients with Subclinical Hypothyroidism: A Prospective Controlled Study
    • 54 total participants: 
      • 18 with subclinical hypothyroidism (SCH) 
        •  Median TSH 6.15 µIU/ml
      • 18 with overt hypothyroidism (OH)
      • 18 healthy controls 
    • Carotid Intima-Media thickness (CIMT) measured in all participants
    • Levothyroxine given to those w/ SCH
    • Higher CIMT in SCH compared to healthy controls
    • There was a decreased CIMT after levothyroxine treatment in those w/ SCH
    • Commentary: Even w/ a TSH <10, those w/ SCH had:
      • A higher CIMT
      • Reduced CIMT scores after starting levothyroxine
      • This is why research suggests considering levothyroxine in those w/ SCH who have a TSH between 7-10 and are younger.

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Diet & Lifestyle Studies


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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