Future of Functional Medicine Review Clinical Newsletter

Research Briefs for Practitioners – August 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
Anchor link

Episode 16

Anchor link

Featured Study

  • Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis
    • 17 observational studies, 1,100 patients (86% women)
    • Tapering regimens included:
      • Discontinuing therapy within 2 weeks:
        • First halving dose at week 1 and discontinuing the remaining dose at week 2
      • Halving dose successively every 4 weeks until a dose ≤12.5 mcg/day was reached and therapy was then discontinued 
      • 25 mcg reductions until discontinuation
    • Results at median 5 year followup:
      • 34.1% remained biochemically euthyroid after discontinuation of medication
      • Subgroup analysis showed that patients with a previous diagnosis of overt hypothyroidism were less likely to remain euthyroid (11.8%)
    • “A deprescribing framework focusing on adequate selection of patients for deprescribing LT4 and a systematic process is warranted to guide clinicians in re-evaluating the need for LT4 in their patients.
    • Commentary: Inappropriate use of thyroid medication is common and more studies are being conducted to bring more understanding to deprescribing unnecessary medication. Once thyroid hormone replacement is started, 90% w/ subclinical hypothyroidism will continue medication indefinitely. This is why it’s so important to correctly identify patients who truly need and don’t need thyroid replacement.

Anchor link

Gastrointestinal Studies

  • The effectiveness of rotating versus single course antibiotics for small intestinal bacterial overgrowth
    • 223 patients w/ diagnosed SIBO (glucose breath test)
    • Randomized to:
      • Single antibiotic (quinolone or azole) 
      • Rotating antibiotics (quinolone and azole, one after the other) for 10 consecutive days/month for 3 months
    • After treatment, measured breath test, IBS score, and quality of life (QoL)
    • After treatment:
      • Remission higher in rotating antibiotic group (70% vs 51%)
      • Remission associated w/ improved QoL and bloating
    • Commentary: Treatment of SIBO using rotating antibiotics was more effective than treatment using a single course of antibiotic

Anchor link

Thyroid & Hormones Studies

  • Relationship between serum total testosterone and prostate volume in aging men
    • Examined relationship between serum testosterone and prostate volume
    • 416 men over 51 yo, w/ NO prostate issues
    • Men w/ low testosterone had significantly:
      • Larger prostate volume
      • Higher BMI 
      • Higher waist circumference
      • Higher insulin
    • Increasing volume of prostate over 4 years was associated w/ low testosterone
      • There was a clear linear trend w/ lower testosterone and increasing prostate size
    • Commentary: This study highlights the common misconception w/ higher testosterone and prostate size
  • The impact of menopausal hormone therapy on overall mortality: A comprehensive review
    • Review, 31 studies, 3 meta-analysis
    • HRT leads to a significant reduction in all-cause mortality
    • Greater benefit for women who: 
      • Initiate HRT soon after menopause
      • Cardiovascular risk factors
    • Commentary: High degree of heterogeneity of individual studies
  • Low testosterone and cardiometabolic risks in a real-world study of US male firefighters
    • Cross-sectional study, 300 firefighters
    • Measured total testosterone (TT), categorized as:
      • Low (< 264 ng/dL)
      • Borderline (264-399 ng/dL)
      • Reference (400-916 ng/dL)
    • Risk factors for low TT:
      • Fatty liver (OR 4.1)
      • A1C >5.7% (OR 2.7)
      • Triglycerides >150 mg/dL (OR 6.6)
    • Commentary: This study highlights a few major points:
      • Consider testosterone screening in those w/ obesity, cardiometabolic risk factors
      • Low TT may be a result of poor glycemic control and insulin resistance

Anchor link

Diet & Lifestyle Studies

  • A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults
    • 24 healthy adults
    • Randomized to:
      • Alternate day fasting (eat regularly x24 hrs, fast 24 hrs)
      • Alternate day fasting w/ energy restriction 
      • Daily caloric restriction (eat a little less each day)
    • Energy restriction groups matched for calories (75% of total calories eaten per day)
    • After 3 weeks:
      • Daily energy restriction lost almost all their weight from fat loss (-1.9 kg)
      • Fasting w/ energy restriction had more lean mass loss than the daily energy restriction group (AKA more of their weight loss came from reduced muscle)
      • No weight loss in fasting without energy restriction group
    • Commentary: In this study, an alternate day fasting protocol lead to suboptimal loss of muscle mass compared to daily energy restriction
  • Effect of the intake of dietary protein on insulin resistance in subjects with obesity: A randomized controlled clinical trial
    • 80 obese participants w/ insulin resistance (HOMA-IR >2.5)
    • Randomized to one of 4 groups:
      • Normal animal protein diet  
      • Normal vegetable protein 
      • High animal protein
      • High vegetable protein
    • After 1 month, both high protein diets had:
      • Better improvement in insulin sensitivity (60-90% improvement)
        • Independent of weight loss
      • Lower fat mass, increased muscle mass
      • Lower triglycerides
      • Lower CRP
    • Commentary: Consider higher protein diets for those with insulin resistance. It can improve insulin sensitivity independent of weight loss.

Anchor link

Episode 15

Anchor link

Featured Study

  • Comparative effectiveness of levothyroxine, desiccated thyroid extract, and levothyroxine+Liothyronine in hypothyroidism
    • Comparing the use of levothyroxine, desiccated thyroid hormone, and combined T4 + T3 therapy
    • Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients 
      • 61% had autoimmune thyroiditis
    • Randomized to one of 3 groups and treated for 22 weeks in each group, then moved to other group for another 22 weeks:
      • Levothyroxine (LT4)
      • LT4+LT3 (combined)
      • Desiccated thyroid extract (DTE)
    • Measured thyroid symptom questionnaire, quality of life, memory, depression scores, treatment preference
    • Results:
      • TSH remained within reference range across all treatment arms
      • NO differences for outcomes
        • Except for a minor increase in heart rate caused by DTE
      • NO treatment preference
      • Of the 25 who were most symptomatic, combined therapy was preferred, had better thyroid symptom score, quality of life, and memory score
    • Commentary: Overall, there wasn’t a big difference between the 3 groups. Those that remain symptomatic may benefit from combined therapy ONLY AFTER you have worked through the thyroid algorithm.

Anchor link

Gastrointestinal Studies


Anchor link

Autoimmunity Studies


Anchor link

Thyroid & Hormones Studies


Anchor link

Diet & Lifestyle Studies


Anchor link

Episode 14

Anchor link

Featured Study

  • Systematic review with meta-analysis of partial enteral nutrition for the maintenance of remission in Crohn’s disease
    • Can a partial elemental diet (part liquid elemental diet, part regular diet) help w/ Crohn’s disease (CD)?
    • 8 prospective controlled studies, 429 CD patients
    • Those receiving partial elemental diet had:
      • Lower relapse at 2 year followup (RR 0.67, NNT=5)
      • Higher frequency of remission (67% vs 48%)
      • No increased side effect profile
    • Commentary: This high quality review suggests that a partial elemental diet can be effective for those w/ CD and has a very low number needed to treat (NNT).

Anchor link

Gastrointestinal Studies

  • Small Intestinal Bacterial Overgrowth in Functional Dyspepsia: A Systematic Review and Meta-Analysis
    • Does SIBO play a role in functional dyspepsia?
    • 7 studies, 260 patients w/ functional dyspepsia, 84 controls
    • Patients w/ functional dyspepsia were 4.3x more likely to have SIBO compared to controls
      • This finding was w/ high degree of heterogeneity (some studied were 4x more likely, some 8x more likely)
    • SIBO prevalence in those w/ functional dyspepsia depended on type of test
      • Lactulose: 53%
      • Glucose: 17%
    • Commentary: This meta-analysis suggests a modest association between SIBO and dyspepsia although the evidence is generally weak and largely depends on the type of SIBO breath test used to identify the prevalence rate.
  • Dietary Practices of Women with Endometriosis: A Cross-Sectional Survey
    • 480 women w/ endometriosis
    • 44% used dietary management for symptoms
    • Most common dietary strategies:
      • Eliminate gluten
      • Eliminate dairy
      • Low FODMAP template
    • Participants reported a 6.4/10 effectiveness score for reduction in pelvic pain with dietary changes
      • NO difference in pain reduction between the various diets used
    • Commentary: Dietary management of endometriosis seems to be an (moderately) effective strategy.
  • Low FODMAP diet significantly improves IBS symptoms: An Irish retrospective cohort study
    • 164 IBS patients, started on low FODMAP diet
    • Baseline symptoms
      • lethargy (92%)
      • bloating (91%)
      • flatulence (91%)
      • abdominal pain (89%)
    • At followup:
      • Only 25% had continued low FODMAP diet at 12 months
      • ALL symptoms improved to some degree at 3 months
      • 66% satisfied w/ symptom control at 12 months
      • After re-introduction of the high FODMAP foods, ALL patients maintained their symptomatic response
      • The best symptom improvement was seen in those who were fully adherent to the FODMAP diet
  • Effects of probiotics or broccoli supplementation on Helicobacter pylori eradication with standard clarithromycin-based triple therapy
    • 183 patients w/ chronic gastritis from H pylori infection
    • Randomized to one of 3 groups:
      • Triple therapy (Proton Pump Inhibitor or PPI, clarithromycin, amoxicillin) alone
      • Triple therapy + probiotics 
      • Triple therapy + sulforaphane
    • Assessed H pylori eradication w/ urea breath test 4 weeks after completion
    • Eradication rates similar between groups (all around 85%)
    • Commentary: The triple therapy + probiotics group trended toward a slightly higher eradication rate (89%) but this did NOT reach statistical significance. This may be due to low sample size. Don’t avoid antibiotic treatment when indicated. 

Anchor link

Thyroid & Hormone Studies

  • Seasonal Variations in Sex Steroids in a Young Male Population and Their Relationship with Plasma Levels of Vitamin D
    • Are there seasonal variations in sex steroids and Vit D in a healthy male population?
    • 29 healthy males, median age 34 yo
    • Seasonal variation was noted between winter and summer:
      • Lower Vit D in winter (18 vs 38 ng/mL)
      • Higher total testosterone in winter (500 vs 400 ng/dL)
    • Lower Vit D associated w/ higher total testosterone (r= -0.27)
    • Commentary: Make sure to standardize sex hormone testing as much as possible. This applies to men too (e.g. get first 8 am levels x2 before coming to any conclusions).

Anchor link

Diet & Lifestyle Studies

  • Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial
    • 80 diabetic patients on oral anti-diabetic drug (e.g. Metformin), randomized to one of following groups:
      • Add-on folic acid (5 mg/day)
      • Add-on methylcobalamin (500 mcg/day)
      • Add-on Folic acid (5 mg/day) + Methylcobalamin (500 mcg/day) 
      • No add on (control)
    • After 8 weeks:
      • A1C significantly improved in B12 (-1.2%) and folate + B12 groups (-1.5%)
      • B12 and folate + B12 groups also had improvements in insulin, adiponectin, and insulin resistance
      • No improvement in lipids
      • Homocysteine lowered in all B vitamin supplementation groups
    • Commentary: Add on supplementation of select B vitamins may improve blood glucose when added on to conventional diabetic medications. 
  • Effect of exercise intervention on primary insomnia: A meta-analysis
    • 23 trials, 1,200 participants
    • Exercise intervention had a significant effect on the treatment of primary insomnia
      • Effects were greater for:
        • Older individuals (>60 years old)
        • Exercise for at least 8 weeks
        • Exercise <60 minutes
        • Exercise <4x/wk
    • Commentary: Exercise regimen of 60 min/day 4-5 times a week for 8-12 weeks can improve sleep quality and treat the symptoms of primary insomnia.
  • Effect of wearables on sleep in healthy individuals: A randomized crossover trial and validation study
    • 32 healthy adults, randomized to one of the following then crossed over to other group
      • 1 week sleep log alone
      • 1 week sleep log + WHOOP strap (sleep tracker wearable)
    • Sleep wearable improved nighttime sleep quality
    • When compared to simultaneous polysomnography, low amount of errors for measuring:
      • Sleep duration 
      • Deep sleep
      • Respiratory rate
      • Heart rate
    • Commentary: In healthy people, wearables can improve sleep quality and accurately measure sleep and cardiorespiratory variables.
  • Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease
    • 26 patients w/ Alzheimer’s
    • Randomized to ketogenic diet (KD) or low fat standard diet (SD) for 12 weeks→ 10 week wash out period→ switched to different group
    • 21 (81%) finished KD diet
    • For those on KD:
      • Patients achieved ketosis 
      • Improved quality of life
      • Improved daily function
    • Commentary: This is the first RCT of a ketogenic diet in those w/ Alzheimer’s disease that shows mostly positive results.

Anchor link

Episode 13

Anchor link

Featured Study

  • Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines
    • Consensus statement for managing pancreatic exocrine insufficiency (EPI)
    • Symptoms of EPI:
      • Steatorrhea
      • Weight Loss
      • Diarrhea
      • Abdominal Pain
      • Bloating 
    • Consensus summary points:
      • Associated conditions
        • Diabetes (20% prevalence)
        • Elderly (20% prevalence)
        • Celiac (30% prevalence)
        • IBS-D (9% prevalence)
        • IBD (30% prevalence)
        • Alcohol-related liver disease (20% prevalence)
      • Fecal pancreatic elastase-1 can be 1st line test for EPI
        • <200 µg/g = moderate EPI
        • <100 µg/g = severe EPI
        • A repeat test should be considered when a watery sample is reported by the laboratory
      • Markers of malnutrition (clinical history, anthropometric measurements or serum micronutrient levels) can be used to support diagnosis of EPI: 
        • Magnesium (<2 mg/dL)
        • Vitamin E 
        • Retinol-binding protein/vitamin A
        • Vitamin D
      • An abdominal CT scan should also be performed when EPI is diagnosed, especially to exclude a neoplastic cause
        • Commentary: you may not need to do this if no known risk factors given low prevalence of malignant causes.
      • Pancreatic enzyme replacement therapy (PERT) associated w/ improved survival, weight loss, quality of life, and nutritional status
        • PERT should be started at a dose of at least 50,000 units lipase with meals and 25,000 units lipase with snacks 
        • patients should be encouraged to adjust their dose if this is ineffective
        • No max dose but may have more side effects >100,000 units per meal (may even be safe in pregnancy)
      • Consumption of pancreatic enzymes should be spread out throughout a meal 
        • A study examining the timing of PERT in 24 patients with chronic pancreatitis suggested that spreading the dose throughout the meal supported optimal absorption
      • In those who cannot swallow pills
        • Capsules can be opened and the contents taken on a spoonful of cold acidic food (fruit puree, apple sauce, jam or fruit yogurt) and swallowed immediately.
      • Diet
        • Avoid low-fat diets 
          • Can exacerbate malnutrition
        • Low fiber diets are better (e.g. low FODMAP)
        • Consider elemental diet
          • Can use less PERT when taking elemental diet
      • Differential Diagnosis
        • Consider bile acid diarrhea in those non-responsive to PERT

Anchor link

Gastrointestinal Studies

  • A Randomized Open-Label Study of Two Methods of Proton Pump Inhibitors Discontinuation
    • Is tapering better than abrupt discontinuation of PPI use?
    • 38 patients w/ reflux randomized to abrupt discontinuation or slow taper
    • NO difference between two groups at 12-month followup
    • BUT taper group had less symptoms at 14, 18, 22, and 30 weeks after discontinuation
    • Commentary: Gradual taper lead to less symptoms in the short-term and may be a better strategy to PPI discontinuation 
  • Utility of Routine Esophageal Biopsies in Patients With Refractory Reflux Symptoms
    • 300 patients referred for endoscopy
    • Only 4.7% met diagnostic criteria for eosinophilic esophagitis (EoE)
    • Strongest risk factors for EoE:
      • Dysphagia (trouble swallowing)
      • Food bolus impaction
      • Atopic disease history
    • If patient does NOT have these symptoms, then risk of EoE diagnosis is 0%
    • Commentary: It may not be necessary to receive endoscopy to diagnose EoE in the absence of these symptoms.
  • Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
    • 28 RCT, 2,000 participants
    • Compared to placebo, probiotics:
      • Reduced fasting blood glucose (-13 mg/dL short-term, -3 mg/dL long-term)
        • Greater effect if baseline blood glucose >130 mg/dL
      • Reduced A1C (-0.2% short term, -0.14% long-term)
        • But did NOT reach statistical significance
      • Reduced cholesterol in both short and long term
    • Commentary: Optimizing gut health can impact metabolic markers. But, don’t forget to also address diet/lifestyle factors that may play a larger role in heart disease and metabolic management. 
  • Elemental diet therapy for eosinophilic gastroenteritis and dietary habits
    • Retrospective study of 4 children w/ INTRACTABLE eosinophilic esophagitis (EoE) not responsive to traditional therapy
    • Given elemental diet x2 weeks
    • ALL 4 patients had RESOLUTION of symptoms after 2 weeks
    • 3 patients reintroduced food and returned to normal life
    • No adverse effects
    • Commentary: An elemental diet can be a game-changer for some patients. Consider the use of it especially in those w/ reflux and EoE.

Anchor link

Thyroid & Hormones Studies

  • Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape
    • Review of subclinical hypothyroidism (SCH)
    • “It is important to remember that a considerable proportion of SCH cases are transient and reversible in nature”
    • “Despite significant evidence documenting the health impacts of SCH, the effects of levothyroxine treatment in patients with SCH remains controversial, especially [in older adults]”
    • Commentary: Current evidence lacks for routinely treating SCH to get thyroid tests into “optimal ranges”

Anchor link

Diet & Lifestyle Studies

  • Effect of Protein and Carbohydrate Combined with Resistance Training on Muscular Adaptation
    • Does protein + carbohydrate supplementation increase effects of resistance training compared to protein supplementation alone?
    • 17 untrained young men, given resistance training protocol (leg press, leg extensions) 3x/wk for 8 weeks
    • Randomized to 
      • PRO (0.25g/kg whey protein) supplementation 
      • or PRO + CHO supplementation (0.25g/kg whey protein + 50g maltodextrin)
    • Measured muscle strength and muscle mass before and after protocol
    • After 8 weeks:
      • NO differences in muscle strength or muscle mass
    • Commentary: Added CHO to PRO supplementation may not yield additional benefits of resistance training in untrained individuals. Hitting an adequate protein threshold per day may be enough to stimulate muscle protein synthesis. However, a possible benefit may be seen in more trained individuals.

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!