Research Briefs for Practitioners – January 2023 - Dr. Michael Ruscio, DC

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Future of Functional Health Review Clinical Newsletter

Research Briefs for Practitioners – January 2023

by the Ruscio Institute for Functional Healthcare 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 81

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Podcast Summary


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Featured Study

  • Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials
    • 34 RCTs on 8 types of inflammatory arthritis treated with probiotics (e.g. lacto/bifido, soiled based, Strep spp, Enterococcus spp)
    • Probiotic supplementation led to improvements in:
      • Rheumatoid arthritis (10 RCTS, 632 participants) 
        • Reduced CRP (large effect size) 
        • NO change in joint pain, joint swelling or ESR
      • Psoriasis (4 RCTs, 214 participants)
        • Improved objective psoriasis severity (large effect size) 
      • Gout (4 RCTs, 157 participants)
        • Reduced uric acid (moderate effect size) 
      • Osteoporosis/osteopenia (10 RCTS, 1,156 participants)
        • Improved bone mineral density (small effect size) 
      • Osteoarthritis (1 RCT, 215 participants)
        • Improved joint pain
        • Reduced hsCRP
      • IBD arthritis (1 RCT, 120 participants) 
    • Probiotics did NOT lead to improvements in: 
      • Spondyloarthritis
      • Juvenile arthritis
    • Commentary: Probiotics led to improvements in some facets of various autoimmune conditions, with the most notable improvements in psoriasis, gout and osteoarthritis. It’s important to note that many of the studies found improved objective findings (e.g. lab results) without symptomatic improvements.

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Gastrointestinal Studies

 

  • Meta-analysis of the efficacy of probiotics to treat diarrhea
    • 16 RCTs, 1,585 participants with diarrhea from various causes (IBS-D, acute diarrhea, C. diff infection, etc), randomized to: 
      • Control (placebo, low FODMAP diet, antibiotics)
      • Probiotics (soil based, lacto/bifido, synbiotics) 
    • Compared to control groups, probiotics led to improved:
      • IBS symptom score (large effect size) 
      • Stool frequency (small effect size) 
    • Probiotics did NOT lead to greater improvements in: 
      • Bristol stool scale
      • IBS quality of life
    • Commentary: While probiotics led to greater improvements in IBS symptoms and stool frequency, they did NOT lead to better outcomes in IBS quality of life or stool form. It’s important to keep in mind the control group did include both antibiotics and a low FODMAP diet, which are also effective for diarrhea.

 

  • Comparison of two probiotics in follow-on formula: Bifidobacterium animalis subsp. lactis HN019 reduced upper respiratory tract infections in Chinese infants
    • 192 healthy infants (6-12 months old), randomized to:
      • Formula (control)
      • Formula + Bifidobacterium animalis (10 million CFU) (bifido)
      • Formula + Lacticaseibacillus rhamnosus (10 million CFU) (lacto)
    • After 3 months, compared to formula alone, the addition of probiotics led to reduced: 
      • Physician confirmed upper respiratory tract infections (URTI) (9% control vs 3% lacto vs 0% bifido)
      • Parent reported URTI (25% vs 14% vs 9%) 
      • Antibiotic/antiviral prescriptions (11% vs 5% vs 0%
    • Commentary: Probioitcs led to less URTIs and antibiotics/antivirals prescribed to infants, with bifidobacterium probiotics leading to the best outcomes.

 

 

  • The Effect of Fiber Supplementation on Chronic Constipation in Adults: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
    • 16 RCTs, 1,251 participants with chronic constipation, randomized to:
      • Control (maltodextrin, yogurt, milk, apple juice) 
      • Fiber (psyllium, pectin, inulin, guar gum, galacto-oligosaccharide, wheat bran) 
    • Compared to control, fiber supplementation led to: 
      • Greater response rate (66% vs 41%)
      • Increased stool frequency (moderate effect size) 
      • Worse flatulence (due to inulin and wheat bran) (moderate effect size) 
      • Improved stool consistency (small effect size) 
    • Constipation was most improved with: 
      • Psyllium and pectin 
      • Fiber doses >10 g/day
      • ≥4 weeks of treatment 
    • Commentary: Fiber, specifically psyllium and pectin, were most effective for improving constipation. Note the importance of the dose and length of treatment for improving constipation. 

 

  • Probiotics and rifaximin for the prevention of travelers’ diarrhea: A systematic review and network meta-analysis
    • 17 RCTs, healthy participants traveling to other countries, prophylactically randomized to:
      • Controls (no treatment or placebo)
      • Rifaxamin
      • Probiotics/prebiotics (e.g. lacto/bifido, Strep thermophilus, galacto-oligosaccharides (GOS), S. boulardii, sodium butyrate) 
    • Compared to placebo, both interventions reduced the risk for traveler’s diarrhea (TD):
      • Rifaxamin (-53%) 
      • Probiotics/prebiotics (-15%) 
    • Of the probiotic/prebiotic therapies, the following provided the greatest risk reduction for TD:
      • Sodium butyrate (-89%) 
      • Lacto/bifido + Strep thermophilus (-39%) 
      • GOS (-36%) 
      • S. boulardii (-17%) 
    • Commentary: Both probiotics and rifaximin are effective for preventing TD, with antibiotic treatment showing the greatest risk reduction. Of the probiotics/prebiotics, sub-analysis reveals that sodium butyrate and lacto/bifido + strep thermophilus offer the most protective benefit against TD.

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Thyroid & Hormones Studies

 

  • Perceived stress and hair cortisol concentration in a study of Mexican and Icelandic women
    • 1,279 women, hair cortisol and self-perceived stress were assessed
    • Compared to women with the low stress, higher stress was associated with increased hair cortisol levels (1.8 vs 1.6)
    • Commentary: While hair cortisol levels increased as perceived stress increased, the absolute difference between these groups was very small. This supports why we at the clinic do not use hair cortisol testing, as it doesn’t inform our treatment approach.

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Diet & Lifestyle Studies

 

  • Association of step counts over time with the risk of chronic disease in the All of Us Research Program
    • 6,042 overweight participants wearing a Fitbit step-tracking device, followed over 4 years  
    • Every 1,000 step increase above 8,200 steps was associated with a reduced risk of:
      • Type 2 diabetes (-31%)
      • Sleep apnea (-12%) 
      • Obesity (-11%) 
      • GERD (-8%) 
      • Hypertension (-8%) 
      • Major depression (-8%) 
    • Aside from hypertension, the incidence of all conditions approached zero at very high step counts (16,000-20,000)
    • Commentary: At least 8,000-9,000 steps per day is linked to a reduced risk of several chronic conditions, with a very low incidence of disease seen at higher steps levels.

 

  • Association between adherence to three healthy dietary patterns and risk of cognitive disorders:Meta-analysis
    • 15 observational studies, 124,977 participants, categorized by diet:
      • Mediterranean (MED)
      • Dietary approaches to stop hypertension (DASH)
      • MED + DASH (MIND)
    • Compared to lower dietary compliance, high dietary compliance reduced the risk for general cognitive disorders and mild cognitive impairment by:
      • MIND (-52% and N/A)
      • DASH (-21% and -37%)
      • MED (-16% and -24%)
    • There was no association between a MED or DASH diet on dementia risk.
    • Commentary: Both a Mediterranean-style and DASH diet reduce the risk of cognitive dysfunction (especially when used together) and mild cognitive impairment, but not dementia.

 

 

  • Health effects of voluntary exposure to cold water – a continuing subject of debate
    • 104 studies assessing the effects of cold water exposure and various health outcomes 
    • Cold water exposure led to: 
      • Reduced ApoB/A1 ratio (reduced CVD risk) 
      • Reduced oxidative stress markers 
      • Improved Insulin sensitivity 
      • Increased fat metabolism 
      • Reduced cortisol 
      • Increased norepinephrine
    • Commentary: Cold water exposure can lead to numerous beneficial effects on an individual’s health.

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Episode 82

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Podcast Summary


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Featured Study


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Gastrointestinal Studies

 

  • Allergy-Test-Based Elimination Diets for the Treatment of Eosinophilic Esophagitis: A Systematic Review of Their Efficacy
    • 16 studies, 475 eosinophilic esophagitis (EoE) patients
    • The combined use of skin-prick testing and atopy patch testing led to: 
      • Prediction of problematic foods in 67% 
      • Improved symptoms in 65-88% once identified foods were removed 
    • Commentary: Lab testing to assess for problematic foods in EoE led to improved symptoms in 65-88% of patients. Contrast this to a previous meta-analysis that found EoE improved in: 1) 90% from elemental dieting, 2) 72% from 6-food elimination diet and 3) 46% from allergy-testing directed food elimination. This highlights the importance of treating the person vs treating lab results.

 

 

 

 

 

 

 

  • Association of Probiotic Treatment With Antibiotics in Male Accessory Gland Infections
    • 104 infertile males positive for bacterial infection in semen/prostate secretions, randomized to:
      • Antibiotics alone
      • Antibiotics + S. boulardii, enterococcus and lactobacilli 
    • Eradication of the infection was found in:
      • 76.2% in the probiotic + antibiotic group
      • 50% in the antibiotic alone group 
    • Commentary: Another study showing the beneficial effects of probiotics in addition to antibiotics for eradicating various infections. 

 

  • Clinical outcomes of asymptomatic low-grade esophagitis: results from a multicenter Chinese cohort
    • 248 participants with asymptomatic, low-grade esophagitis +/- PPI therapy
    • After 1 year, PPIs users had NO difference in progression to:
      • GERD (13% PPI vs 9% non-PPI) 
      • Persistent esophagitis (30% vs 20%) 
    • Commentary: PPI therapy did NOT improve the outcomes of patients with asymptomatic esophageal inflammation. This illustrates the importance of treating people (ie their symptoms) instead of just lab results. 

 

 

  • Lactobacillus rhamnosus Used in the Perinatal Period for the Prevention of Atopic Dermatitis in Infants: A Systematic Review and Meta-Analysis of Randomized Trials
    • 11 RCTs on mothers/infants (most with a family history of allergic conditions) randomized to: 
      • Placebo
      • Probiotics (L. rhamnosus alone or lacto/biff combination)
    • Probiotics were taken for an average of: 
      • 1 month prenatal
      • 3 months-2 years postnatal 
    • Probiotics led to a reduction in pediatric eczema by:
      • 40% in those ≤ 2 years old
      • 38% in those 6-7 years old
    • NO reduction in eczema was seen for children 4-5 and 10-11 years old
    • Probiotics were most effective when consumed:
      • Prenatally + in breast milk (mother takes probiotics) (-48% risk of eczema
      • Prenatally + directly given to infant (-34%) 
    • Commentary: The overall trend in the data suggests L. rhamnosus, whether taken alone or with other probiotics, reduces the risk of eczema in children when mothers consume probiotics both prenatally and postnatally.

 


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Diet & Lifestyle Studies

 

  • Protein intake and physical function in older adults: A systematic review and meta-analysis
    • 22 observational studies, 11,332 older adults (~75 years old)
    • Protein intake higher than the RDA was associated with improved: 
      • Physical performance tests (moderate effect size)
      • Lower limb strength (small effect size) 
      • Balance (small effect size) 
      • Walking speed 
    • Commentary: Higher protein intake was associated with better physical performance in older participants.

 

  • Does the Ketogenic Diet Improve the Quality of Ovarian Function in Obese Women?
    • 25 obese young women with PCOS placed on a ketogenic diet
    • After 3 months, the participants had significant improvements in:
      • Weight loss (-40 lbs)
      • Insulin resistance (HOMA-IR) (5.6 to 1.4)
      • Progesterone levels (3.4 to 20 ng/mL)
      • Anti-mullerian hormone (2.1 to 7.8 ng/mL)
    • Commentary: A ketogenic diet significantly improved metabolic health and markers of ovarian reserve and function in overweight women with PCOS. This highlights the ability of dietary interventions to improve female hormone balance.

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Episode 83

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Podcast Summary


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Featured Study


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Gastrointestinal Studies

  • Effects of Quadruple Therapy Combined with Probiotics on Helicobacter Pylori-Related Peptic Ulcer
    • 180 participants with H. Pylori, randomized to:
      • Control (quadruple therapy)
      • Quadruple therapy + probiotics (lacto/biff, enterococcus)
    • After 2 weeks, compared to controls, the addition of probiotics led to:
      • Greater H. pylori eradication (88% vs 79%)
      • Reduced recurrence rates 3 months after treatment (7% vs 13%)
      • Reduced serum gastrin (92.2 vs 114.4 pg/mL)
    • There was NO difference in side effects between groups
    • Commentary: The addition of probiotics to quadruple therapy led to greater H. pylori eradication and reduced recurrence rates up to 3 months after treatment.

 

  • Assessment of Selected Intestinal Permeability Markers in Children with Food Allergy Depending on the Type and Severity of Clinical Symptoms
    • 103 children, categorized by those with:
      • Symptomatic food allergies (IgE and non-IgE) 
      • Functional GI symptoms (Control group) 
    • Compared to the control group, children with food allergies had higher levels of intestinal permeability markers, including:
      • Zonulin (35 vs 23 ng/ml) 
      • Lipopolysaccharide (904 vs 675 ng/ml) 
    • However, there was NO relationship between elevated intestinal permeability markers and presence of:
      • Gastrointestinal symptoms 
      • Respiratory symptoms
      • Skin symptoms
    • Commentary: While children with food allergies have higher leaky gut markers, they did NOT correlate with the presence of symptoms, especially GI symptoms. 

 


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Thyroid & Hormones Studies

  • Autoimmune Thyroid Disorders Are More Prevalent in Patients with Celiac Disease: A Retrospective Case-Control Study
    • 623 participants with celiac disease (CD), 7,866 healthy controls
    • Compared to controls, those with CD had more:
      • Thyroid disease in general (26% vs 13%)
      • Autoimmune thyroid disease (Hashimoto’s and Graves’) (15.4% vs 7.5%)
      • Non-autoimmune thyroid disease (e.g. nodules, goiter, iatrogenic hypo- and hyperthyroidism, thyroid cancer) (2.7% vs 1.1%)
    • Commentary: Those with celiac disease have a greater risk for thyroid-related conditions, with a two-fold increased risk for autoimmune thyroid diseases. This may highlight the gut-thyroid connection.

 

 


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Diet & Lifestyle Studies

  • Comparison of the Effectiveness of Low Carbohydrate Versus Low Fat Diets, in Type 2 Diabetes: Systematic Review and Meta-Analysis of Randomized Controlled Trials
    • 22 RCTs, 1,391 obese participants with type 2 diabetes, randomized to:
      • Low-carbohydrate diet
      • Low-fat diet 
    • After 3 months, a low carb diet led to greater improvements in:
      • Triglycerides 
      • Fasting insulin
      • A1c
      • Body weight 
      • BMI
      • Blood pressure 
    • However, after 1 year, both low carb and low fat diets led to similar improvements in:
      • Fasting glucose 
      • Fasting insulin
      • A1c
      • Body weight 
      • BMI
      • Waist circumference
      • Blood pressure 
      • LDL-C
      • C-reactive protein 
      • Triglycerides
    • Commentary: This large meta analysis found when comparing longer-term compared to shorter term studies, there was NO difference in metabolic health between dietary interventions.

 

 

  • Resistance training for postmenopausal women: systematic review and meta-analysis
    • 12 RCTs, 452 postmenopausal women, randomized to: 
      • Control (no exercise or aerobic exercise) 
      • Resistance training 
    • Compared to control, resistance training led to: 
      • 13x reduced hot flash frequency 
      • Reduced fat mass (large effect size)
      • Improved bone mineral density (small effect size) 
      • NO difference in waist circumference or BMI
    • Aerobic training led to a greater reduction in hot flashes compared to resistance training
    • Commentary: A combination of aerobic and resistance training is likely an important therapy for postmenopausal women for improving body composition and bothersome symptoms like hot flashes.

 

  • Cardiovascular Mortality, Habitual Exercise, and Particulate Matter 2.5 Exposure: A Longitudinal Cohort Study
    • 384,128 adults assessed for cardiovascular mortality
    • Inactive participants with high particulate matter 2.5 exposure exhibited a 123% higher risk of cardiovascular death than high-exercise-group participants exposed to low levels of particulate matter 2.5”
    • “The beneficial effects of habitual exercise on cardiovascular mortality were NOT modified by chronic exposure to particulate matter 2.5”
    • Commentary: Habitual exercise reduced cardiovascular mortality irrespective of air pollution exposure.

 

 

  • Time-restricted eating with or without low carbohydrate diet reduces visceral fat and improves metabolic syndrome: A randomized trial
    • 162 participants with metabolic syndrome, randomized to: ‘
      • Low carb diet (LCD) 
      • Time restricted eating (TRE) (8 hour window) 
      • LCD + TRE
    • After 3 months, compared to LCD, TRE led to similar or greater reductions in: 
      • Weight (-7 lbs TRE vs -5 lbs LCD) 
      • Visceral fat (-13 vs +6 cm2)
      • Fasting insulin (-3 vs -3 mIU/L) 
      • Fasting glucose (-3 vs +1.3 mg/dl) 
      • Insulin resistance (-1 vs -1.2) 
    • TRE + LCD led to the greatest improvement in: 
      • Fasting insulin (-5.5 mIU/L)
      • Weight (-11 lbs) 
      • Insulin resistance (-2) 
    • Commentary: While the combination of TRE and LCD led to greater improvements in some facets of metabolic health, TRE alone led to similar improvements with a higher rate of compliance. TRE is likely a simpler dietary intervention for patients to follow.

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Episode 84

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Podcast Summary


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Featured Study

  • The effect of probiotics on functional constipation in adults: A randomized, double-blind controlled trial
    • 153 participants with functional constipation (< 3 BM/week), randomized to:
      • Standard fiber treatment (fructo-oligosaccharide) 
      • Low dose probiotics (lacto/bifido, 3 billion CFU) + fiber
      • High dose probiotics (lacto/bifido, 8 billion CFU) + fiber
    • After 1 month, ALL 3 groups experienced:
      • Increased bowel movement frequency (+3/week)
      • Normalized stool consistency
    • There was NO difference in treatment outcomes between groups
    • Commentary: The addition of probiotics to standard fiber treatment did NOT lead to additional improvements in constipation, suggesting probiotics had no added effect.  

 

  • Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial
    • 64 pediatric participants, randomized to:
      • Placebo
      • Synbiotics (Lacto/bifido + prebiotics)
    • Starting BM frequency in both groups were: 
      • 5 BM/week in placebo group
      • 6.8 BM/week in synbiotic group
    • After 3 months, compared to placebo, synbiotics led to an increase of: 
      • +1 BM/week (62% synbiotic group vs 25% placebo group)
      • +3 BM/week (42% vs 10.5%) 
    • Commentary: Synbiotics led to increased bowel movement frequency in children. It’s important to note while this study identifies the children as constipated, they do not fit the standard criteria of <3 BM/week, so we cannot say probiotics improved constipation.
  • Probiotics had 2 different outcomes in these studies. What’s important to consider is the different definitions of constipation used and also the different patient populations. In the first study, probiotics did NOT provide additional benefit over prebiotic fiber to adult patients with true functional constipation. Probiotics given to children with more regular bowel movements led to a greater increase in bowel movements compared to placebo.

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Gastrointestinal Studies

 

 

  • The efficacy of probiotics supplementation for the treatment of atopic dermatitis in adults: a systematic review and meta-analysis
    • 9 RCTs, 208 participants with atopic dermatitis (AD), 194 controls, randomized to:
      • Placebo
      • Probiotics (Lacto/bifido)
    • Compared to placebo, taking probiotics improved:
      • AD severity in the short-term (1 month) (medium effect size)
      • AD severity in the long-term (>2 months) (large effect size)
      • Long-term quality of life (medium effect size)
    • Probiotics led to NO adverse effects
    • Commentary: Probiotics improved atopic dermatitis symptom severity in the short and long-term with no adverse effects, making it a safe and durable treatment for AD.

 

  • Bridge Swallowing Exercise for Gastroesophageal Reflux Disease Symptoms: A Pilot Study
    • 17 participants with symptomatic GERD, treated with “Bridge Swallowing Exercise”
      • Bridge swallowing exercise is performed lying flat and face-up, knees bent with feet flat on the floor, and pelvis lifted up
    • After 1 month of treatment, participants experienced improved:
      • Overall GERD frequency scores
      • Reflux scores
    • 1 of 3 participants who completed pre/post endoscopy had a reversal in esophagitis-induced mucosal damage
    • Commentary: Though the sample size was small, bridge swallowing may be an effective intervention for improving GERD after just 1 month of treatment. The authors state “bridge swallowing increases distal esophageal contractions and lower esophageal sphincter pressure against gravity.

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Diet & Lifestyle Studies

  • Association Between Computer Vision Syndrome, Insomnia, and Migraine Among Lebanese Adults: The Mediating Effect of Stress
    • 749 participants assessed for Computer Vision Syndrome (CVS)
      • CVS refers to a group of ocular and extraocular symptoms due to prolonged digital device screen use
    • 71% of participants experienced CVS, and the most common symptoms were: 
      • Neck pain (43%)
      • Headaches (34%)
      • Back pain (33%) 
      • Eyes burning (11%) 
    • CVS was also associated with: 
      • Increased migraine frequency
      • Worse insomnia
    • Commentary: Excessive digital screen use is associated with migraines and insomnia. The authors also found increased stress seemed to worsen the effects of digital screen use on migraines and insomnia. This highlights the importance of modifying stress and screen time in patients with these symptoms.

 

 

  • The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis
    • 49 RCTs, participants were randomized to:
      • Control (placebo or standard treatment)
      • Berberine (1-5 g/day)
    • Compared to controls, berberine supplementation improved:
      • Triglycerides (-23.70 mg/dl)
      • Total cholesterol (-20.64 mg/dl)
      • LDL-C (-9.63 mg/dl)
      • HDL-C (+1.37 mg/dl)
      • Fasting blood glucose (-7.74 mg/dl)
      • Fasting insulin (-3.27 mg/dl)
      • HbA1c (-0.45%)
      • Systolic blood pressure (-5.46 mmHg)
      • BMI (-0.25 kg/m2)
    • Commentary: Berberine improves cardiometabolic markers, most notably insulin, triglycerides and total cholesterol, with the greatest benefits seen at a dose of 1-5 g/day taken for at least 2 months.

 

  • The effects of probiotic administration on patients with prediabetes: a meta-analysis and systematic review
    • 7 RCTs, 460 participants with prediabetes, randomized to:
      • Placebo
      • Probiotics (lacto/bifido)
    • Compared to placebo, the probiotic groups had improved:
      • HbA1C (-0.7%)
      • LDL cholesterol (-8.94 mg/dl)
      • Total cholesterol (small effect)
      • Triglycerides (small effect)
    • There was NO difference in fasting glucose, HOMA-IR, or HDL-C
    • Commentary: Consistent with other studies, probiotics have a very minor effect on metabolic health in those with blood sugar dysregulation.

Discussion

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