Research Briefs for Practitioners – December 2021 - Dr. Michael Ruscio, DNM, DC
Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – December 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 32

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Featured Study

  • Strain-specific and outcome-specific efficacy of probiotics for the treatment of irritable bowel syndrome: A systematic review and meta-analysis
    • Aim: To identify if there is a strain-specific outcome bias of certain probiotics
    • 32 RCTs, 3,856 participants
    • Four probiotics demonstrated significant reduction in abdominal pain relief: 
      • B. coagulans MTCC5260 (RR= 4.9)
      • L. plantarum 299v (RR= 4.6)
      • S. boulardii CNCM I-745 (RR= 1.5) 
      • S. cerevisiae CNCM I-3856 (RR= 1.3)
    • However, the multi-strain mixtures had the best improvement in symptoms
    • Commentary: Some may argue that clinicians need to use strains only used in clinical trials for specific conditions. However, this type of thinking is missing the big picture. That is, we have hundreds (if not thousands) of papers suggesting that multiple probiotics species and strains can improve various digestive health complaints. If one is to try to match a specific strain of probiotic with the main health concern of the patient, they may make two mistakes:
      • 1) Make clinical care too theoretical, and thus, too complicated
      • 2) Miss potential benefits of using an empirical trial of triple probiotic therapy given the many studies showing multi-strain/species probiotics may be better than single strain/species (see other FFMR+ research briefs). 
    • Remember, to be evidence-based but not evidence-limited. Stay tuned- Dr Ruscio will be doing a commentary of this study soon on the main podcast feed.

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Gastrointestinal Studies

  • The relation between the diet and the diverticulitis pathophysiology: An integrative review
    • Is there a relationship between diet and the incidence of diverticulitis?
    • 5 prospective cohort studies, 235,206 participants
    • High intake of red med and low intake of fiber was associated w/ higher incidence of diverticulitis
    • Commentary: A few things to note here:
      • 1) This is an observational study and one cannot suggest that low fiber and high red meat CAUSES diverticulitis. Perhaps, poor dietary habits (that are characterized by low fiber/high red meat consumption) are also associated w/ other poor health habits such as smoking, lack of exercise which may be major drivers of diverticulitis.
      • 2) Many individuals w/ diverticulitis may be sensitive to fiber. We should be careful not to shoe-horn all of these patients into eating more fiber given this observational study.
  • Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial
    • Study published in the Lancet
    • Background: Rapid weight loss is a risk factor for cholelithiasis (gallstones)
    • 967 patients w/ an intact gallbladder scheduled for bariatric surgery
    • Randomized to ursodeoxycholic acid (UDCA) (900 mg daily) or placebo x6 months
    • At 24 month followup:
      • UDCA prophylaxis did not significantly reduce the rate of symptomatic gallstone disease 
      • However, in those without gallstones before surgery, UDCA reduced the occurrence of symptomatic gallstone disease
    • Commentary: Bile acid therapy may be an effective strategy to prevent gallstones. UDCA decreases the cholesterol content of bile/bile stones by:
      • Reducing the secretion of cholesterol from the liver 
      • & reducing the reabsorption of cholesterol by the intestines
  • A Biofeedback-Assisted Stress Management Program for Patients with Irritable Bowel Syndrome: a Randomised Controlled Trial
    • 46 IBS patients, randomized to biofeedback stress-management therapy or no treatment
    • After 8 weeks, the stress-management therapy had:
      • Greater reduction in IBS symptoms
      • Reduction in depressive symptoms
      • Better quality of life
    • Commentary: The biofeedback tool used in this study was a portable device used to train the patient to monitor the physical reactions (respiration rate, quality of a single breath, heart rate, and heart rate variability with breathing). The device used in this study can be found here.
  • Bipolar disorder and the gut microbiome: A systematic review
    • 4 of 5 studies showed lower microbiome diversity in those w/ bipolar
    • 3 of 4 studies showed lower butyrate production
    • 2 of 3 studies showed higher Prevotella and Bacteroides species
    • Commentary: Said more generally, dysbiosis is more common in those w/ bipolar. This highlights the gut-brain connection.

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Thyroid & Hormones Studies

  • Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis
    • 4 RCTs, 4,050 patients that investigated the risk of breast cancer (BC) recurrence with the use of HRT in BC survivors
    • Overall, 2,022 patients were randomized to receive HRT (estrogen/progesterone combination) and 2,023 to the control group (placebo or no HRT)
    • HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12-1.91)
      • More effect if hormone-receptor positive BC
      • But, NO effect if hormone-receptor negative BC
    • Commentary: Contrary to popular thought, HRT may not be detrimental in BC survivors if they have hormone-receptor negative BC.

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Diet & Lifestyle Studies


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Episode 31

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Featured Study

  • Clinical and Nutritional Impact of a Semi-Elemental Hydrolyzed Whey Protein Diet in Patients with Active Crohn’s Disease: A Prospective Observational Study
    • 144 Crohn’s disease patients, given exclusive semi-elemental diet as sole source of nutrition
    • After 12 weeks:
      • Average number of stools per day decreased (from 4.6 stools/day to 1.7 stools/day)
      • Reduction of malnourishment (91.4% to 23.9%)
      • Reduced disease activity (10.2 to 3.7)
      • Significant increase in remission (5.6% to 71.8% of participants)
    • Commentary: This study suggests out a few points:
      • A semi-elemental diet can be as effective as a fully-elemental diet
      • A moderate-term exclusive semi-elemental dieting does not result in malnutrition. In fact, a significant reduction in malnourishment occurred in this study. 
      • Elemental dieting results in a significant reduction in disease activity in those w/ IBD.

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Gastrointestinal Studies

  • Association of Small Intestinal Bacterial Overgrowth With Heart Failure and Its Prediction for Short-Term Outcomes
    • Cross-sectional study of 287 heart failure patients
    • Given lactulose breath test
    • 45% SIBO+ (using North American Consensus)
    • SIBO was an independent risk factor for cardiovascular death and rehospitalization (HR 2.13)
      • Association only for CH4 predominant SIBO (not hydrogen SIBO)
    • Commentary: This study highlights the gut-cardiovascular connection. There is a higher prevalence of SIBO in those w/ heart failure. However, a weakness of this study was that it used a lactulose breath test (instead of glucose). Dr. Rusico wanted to point out that the newer guidelines restrict the test interpretation window to the first 90 min, thus reducing likelihood of false positives (remember, older guidelines and some labs, would use 120 interpretation window).
  • Evaluation of serum zonulin level in prediabetic patients
    • 45 diabetics, 56 prediabetics, 40 healthy controls 
    • Measured serum zonulin levels at baseline and after glucose tolerance test
    • Baseline serum zonulin was higher in the diabetic group 
      • No difference in prediabetic and control group
    • After glucose tolerance test, zonulin was higher in the prediabetic and diabetic groups compared to controls
    • Commentary: Poor glycemic control may be one reason for increased intestinal permeability.

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Diet & Lifestyle Studies

  • Is resistance training alone an antihypertensive therapy? A meta-analysis
    • 13 studies, 417 participants (207 assigned to resistance training and 210 controls) w/ hypertension
    • Resistance training was associated w/ a significant reduction in systolic blood pressure (-6.16 mmHg)
    • Commentary: Resistance training alone has the potential to significantly reduce blood pressure.

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Episode 30

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Featured Study

  • Age-specific thyrotropin references decrease over-diagnosis of hypothyroidism in elderly patients in iodine-excessive areas
    • Cross-sectional study of 2,559 participants from iodine-excessive areas and no previous history of thyroid disorders
    • Diagnosed subclinical hypothyroidism (SCH) and overt hypothyroidism (OH) by using both lab reference ranges (TSH >4.2) and age-appropriate reference ranges (TSH >11.5 for those >70, as determined by >97% of population studied)
    • Iodine excess was a novel risk factor for hypothyroidism
      • Especially urinary iodine concentrations  ≥ 700 µg/L (OR = 2.5) 
    • Prevalence of hypothyroidism for those >70:
      • OH:
        • Lab reference ranges: 2.37%
        • Age-appropriate reference ranges: 1.78%
      • SCH:
        • Lab reference ranges: 29.6%
        • Age-appropriate reference ranges: 2.96%
    • Commentary: 
      • Iodine excess is a risk factor for hypothyroidism
      • TSH naturally rises with age. This is a great illustration of how SCH may be OVER-diagnosed in an older population. The prevalence of SCH decreased to 10% of the original rate when using an age-appropriate TSH reference range. For those >70 yo, TSH up to 6-8 may NOT need treatment. 
      • One endocrine society “recommends that clinicians derive the upper limit of normal for people over 60 years by dividing the patient’s age by 10 (e.g., TSH ≤ 8 mIU/L for an 80-year-old individual).

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Gastrointestinal Studies

  • Association between bacteria other than Helicobacter pylori and the risk of gastric cancer 
    • 268 gastric cancer (GC) cases and 288 healthy controls
    • 16S rRNA gene sequencing performed from gastric biopsy samples
    • The microbiota was different between the GC and healthy control groups
    • Participants with higher levels of Actinobacteria species showed a significantly increased risk of GC (OR: 3.16)
    • Commentary: Dysbiosis may be a contributing factor to GC and/or GC may alter the microbiota composition. 
  • Probiotics as the live microscopic fighters against Helicobacter pylori gastric infections
    • “Administration of standard antibiotic therapy combined with probiotics plays an important role in the effective treatment of H. pylori infection.
    • “According to the literature, Lactobacillus casei, Lactobacillus reuteri, Lactobacillus rhamnosus GG, and Saccharomyces boulardii can effectively eradicate H. pylori infection.”
    • “Our results showed that in addition to decrease gastrointestinal symptoms, probiotics can reduce the side effects of antibiotics (especially diarrhea) by altering the intestinal microbiome.”

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Autoimmunity Studies


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Thyroid & Hormones Studies

  • Impact of dehydroepiandrosterone on thyroid autoimmunity and function in men with autoimmune hypothyroidism
    • Aim: To examine the effect of DHEA supplementation on thyroid autoimmunity
    • 32 elderly men with autoimmune hypothyroidism and low serum DHEA-S levels
    • Randomized to DHEA (50 mg daily) or no treatment
    • After 6 months, DHEA therapy lead to:
      • Reduced TPO antibody levels (-226 IU/mL)
      • Reduced Tg antibody levels (-237 IU/mL)
      • Reduced TSH (-1.3)
      • Increased DHEA-S levels (+0.8 µmol/L)
      • NO change in estradiol levels
    • Commentary: This small study showed support of oral DHEA supplementation on thyroid autoimmunity. Given the fact that this study was for 6 months, DHEA may need to be supplemented for a sufficient amount of time to exert beneficial effects. These findings are clinically significant but more research is needed.

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Diet & Lifestyle Studies


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Episode 29

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Featured Study

  • Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS-Results from an Open Label Study
    • 73 female IBS-M patients randomized to:
      • Low FODMAP diet
      • IgG based elimination diet (eliminated foods that had high IgG levels)
      • Control diet recommended by gastroenterologist
    • After 8 weeks:
      • IgG elimination diet saw more symptom improvement compared to low FODMAP diet
      • NO improvement in control diet
    • Commentary: At first glance this study suggests superiority of IgG based elimination diets. However, after further investigation, we see some methodologic issues with this study:
      • The diets did not control for fiber content: during periods of diarrhea, patients in each treatment group were told to reduce insoluble fiber and fat. Conversely, during periods of constipation, patients were told to increase dietary fiber intake (to 30-50 g/day). So, in practice, these diets had a high fluctuation of fiber intake
        • The low FODMAP diet was NOT truly low FODMAP for the course of the 8 weeks
        • And the IgG based diet had elements of the low FODMAP diet (during periods of diarrhea)
      • The IgG test examined over 269 foods: This would add a considerable cost to the patient. Rather, an empiric trial of an ancestral template +/- further reduction of possible food sensitivities (e.g. low histamine, low nightshade) diets could save the patient financial resources and be more practical in a clinical setting. 
      • Overall, this was a low powered study that had a few methodological errors to show superiority of an IgG based elimination diet.

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Gastrointestinal Studies

  • Impact of timing of PERT on gastrointestinal symptoms in Danish children and adolescents with CF
    • Cross-over trial of 30 cystic fibrosis (CF) patients taking pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (common in CF)
    • Randomized to taking PERT either before or after meals, then switched to other treatment arm 
    • After 4 weeks of each intervention, there was NO significant difference regarding abdominal pain, bowel habits or QOL related to GI symptoms 
    • Commentary: It does NOT make a big difference if PERT is taken before or after a meal.
  • Self-reported Wheat Sensitivity in Irritable Bowel Syndrome and Healthy Subjects: Prevalence of Celiac Markers and Response to Wheat-free Diet
    • 204 IBS patients and 400 healthy persons evaluated for self-reported wheat sensitivity 
    • tTG and HLA allele genotyping performed on those who reported wheat sensitivity
    • Self-reported wheat sensitivity (symptoms with wheat consumption):
      • 11.3% IBS patients
      • 0% healthy controls
    • Of the 11% of IBS patients who reported wheat sensitivity:
      • 0% had tTG Ab positivity
      • 61% positive for HLA DQ2 or DQ8
      • After 6 week wheat-free diet, ALL patients reported improved bloating/diarrhea/constipation
    • Commentary: True wheat sensitivity remains relatively rare in IBS patients. However, in those w/ self-reported wheat sensitivity, a wheat-free diet can improve symptoms. 
  • Systematic review with meta-analysis: association of Helicobacter pylori infection with gastro-oesophageal reflux and its complications
    • Aim: To examine association between H pylori infection and GERD symptoms and erosive esophagitis
    • 11 observational studies of H pylori and GERD
      • 7 studies: H pylori associated w/ LOWER rates (OR 0.74) 
      • 4 studies: NO association 
    • 26 studies of patients w/ GERD symptoms:
      • H pylori associated w/ LOWER rates (OR 0.7)
    • 9 studies showed NO association between H pylori and Barrett’s esophagus
    • Commentary: H pylori infection/colonization appears to be associated w/ decreased odds of GERD symptoms and erosive esophagitis, as well as lower rates of Barrett’s esophagus (contrary to popular thought). 

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Thyroid & Hormones Studies

  • Is there a role for Natural Desiccated Thyroid in the treatment of levothyroxine unresponsive hypothyroidism? Results from a Consecutive Case Series
    • 28 women and 3 men who switched from levothyroxine (due to continued symptoms) to natural desiccated thyroid
    • Adverse effects:
      • 1 discontinued due to lack of response
      • 2 had cardiac events
    • On average:
      • Quality of life increased 
      • Symptoms decreased
    • Commentary: Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism treated with NDT. However, a recent meta-analysis of 18 studies failed to show a benefit of combined thyroid therapy when compared to levothyroxine. Reminder: As per our thyroid algorithm, desiccated and/or combination therapy is an option, but is reserved for end phase. 

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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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