Practitioner Research Review – February 2017

Interesting Notes:

• “Chronic autoimmune (AIT) or Hashimoto’s thyroiditis affects 1–2% of the population with increasing prevalence with age and a female preponderance.”
• “In communities replete in iodine intake, it is the predominant cause of hypothyroidism.”
• “In a recent narrative review it was suggested that selenomethionine might be more effective than selenite in lowering thyroid autoantibody levels. However, no such trends were observed for any of the clinical outcomes assessed in our study”

Clinical Takeaways:

• Selenium may not be the thyroid panacea it has been suggested to be, however it may help with thyroid gland health and with quality of life. The effect of selenium appears limited to the short term, 3-6 months.

Dr. Ruscio’s Comments

A previous meta-analysis based upon 4 trials did show benefit, however these studies only looked at a 3 month window https://www.ncbi.nlm.nih.gov/pubmed/27702392.  A key insight provided by this paper was looking at the level of impact of selenium in studies that were 3 months, compared to 6 months, compared to 12 months.  Looking at this data it’s clear that the effect at 3 months is present however by 12 months no benefit is show and the placebo was actually shown to be more powerful.

So what does this mean?  It means selenium may have its highest utility when used in the short term.  This is good news because this means we should use a more conservative treatment duration with our patients.  Also recall from a previous issue that you may not need to keep administering selenium until antibodies or “normal”.  Achieving TPO less than 500 may be adequate

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A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/26400188

Study purpose:

• To assess berberine’s utility in the treatment of diarrheal type IBS

Intervention:

• 132 patients randomized to receive 400mg of berberine hydrochloride daily, (delivered twice daily at 200mg) or placebo for 8 weeks – double blinded.
• Patients were followed for an additional 4 weeks post treatment

Main Results:

• A reduction of diarrhea frequency, abdominal pain frequency, and urgent need for defecation frequency were significantly more pronounced in the berberine group than the placebo group.
• A trend of improvement was observed with berberine hydrochloride for IBS symptom score, depression score, and anxiety score and IBS quality of life, compared with placebo.

Additional Results:

• After being off berberine for 4 weeks the treatment’s group’s symptoms approximated that of the control – meaning the effect of berberine was not long lasting.

Authors’ Conclusion:

• “berberine hydrochloride, conveniently delivered, is well tolerated and reduces diarrhea frequency, abdominal pain frequency, and overall IBS-D symptoms score as well as anxiety and depression scores; consequently, berberine improves the quality of life of IBS-D patients.”

Interesting Notes:

• Prevalence of IBS diagnosed by the Rome III criteria in the general population is 1.1–29.2%.
• The placebo response rate in randomized clinical trials conducted in Europe may vary from 0 to 91.7%, with a mean value of 43%.
• Studies have shown that berberine has antidepressant-like effect & has inhibitory action on monoamine oxidase enzyme

Clinical Takeaways:

• Berberine appears to be an effective treatment for diarrheal type IBS and may also benefit mood and quality of life. A lower dose, 400mg/day, may be effective. The effect however, may not be long term.

Dr. Ruscio’s Comments

Both the placebo group and the berberine group improved, remember, placebo can account for sizable improvements in IBS (43% on average). However, the treatment group experienced significantly better improvements than the placebo group. After being off berberine for 4 weeks the treatment’s group’s symptoms approximated that of the control – meaning the effect of berberine was not long lasting.

What does this mean? Perhaps a higher dose or longer duration of treatment would lead to longer lasting results? Perhaps if a healthy diet was implemented at the same time the results would have been more prolonged? It essentially tells us that management/treatment of IBS is likely not a mono-therapeutic endeavor.

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The Intestinal Microbiota And The Role Of Probiotics In Irritable Bowel Syndrome: A Review

https://www.ncbi.nlm.nih.gov/pubmed/26840477

Study purpose:

• To review the available data so as to determine if probiotics are a viable treatment for IBS.

Intervention:

• This was an informal review, meaning it was not a systematic review or meta-analysis. Roughly 15-20 clinical studies were reviewed. And the paper cited 74 references total.

Main Results:

• Probiotics are helpful for global symptoms, pain, bloating and flatulence.

Additional Results:

• N/A

Authors’ Conclusion:

• “… probiotics, which are generally regarded as safe and may act on the global symptoms, bloating and flatulence, which have considerable appeal. Furthermore, a rather impressive scientific rationale has emerged for the use of probiotics in gastrointestinal conditions, including IBS.”
• “However, recommendations regarding individual species or strains continue to be limited by a lack of data and the poor quality of much of the available data.”

Interesting Notes:

• “A number of reviews as well as a recent well conducted systematic review and meta-analysis have demonstrated that probiotics have a therapeutic benefit in the IBS and may improve global symptoms, abdominal pain, bloating and flatulence.” https://www.ncbi.nlm.nih.gov/pubmed/25070051
• ‘IBS is a disorder is defined by the coexistence of abdominal discomfort or pain associated with an alteration in bowel habits.’
• “Irritable bowel syndrome is a common, chronic relapsing gastrointestinal disorder that affects 7%–22% of the population worldwide.”
• “The cardinal symptom in IBS is abdominal pain occurring in association with an alteration in bowel habit; diarrhea and/or constipation.”
• “It should be remembered that although dysbiosis has been recognized in various intestinal diseases, in most cases a definitive cause-and-effect relationship remains to be established.” Dr. R’s note: I think this point is most salient with regards to the changes we see in the microbiota (not including SIBO, SIFO, or infection) – we are unclear if the altered microbiota in IBS is a cause or a result of the disease.
• This paper lists the four main classes of probiotics as
  • – Lactic bacteria that include Lactobacillus, Lactococcus, Bifidobacterium and Streptococcus
  • – Saccharomyces (S. Boulardi)
  • – Escherichia
  • – Bacillus
• It is known that Lactobacillus and Bifidobacterium species have anti-inflammatory effects in the intestine and their depletion could contribute to lowgrade inflammation. Proinflammatory cytokine levels (e.g. interleukin (IL)-6, IL-8, tumor necrosis factor-α, and IL-1β) are elevated in the systemic circulation of patients with IBS.”

Clinical Takeaways:

• Probiotics are a viable treatment for IBS.

Dr. Ruscio Comments

The ‘best’ probiotic type or dose has yet to be defined so determine this empirically – perform a therapeutic trial with one of the major probiotic classes at a time and evaluate the response. Use what works. If nothing works, use nothing. Treat based upon symptoms, not labs, as we do not know if ‘microbiota lab changes’ are causal.

Remember that probiotics have been noted to improve GI barrier health, modulate the immune system (especially small intestinal immunity – GALT/MALT), reduce inflammation, have antibacterial actions and shown to be an efficacious treatment in SIBO. It is likely because of all these reasons that we see improvements in IBS with probiotics.

Does this mean EVERYONE will improve? No. The most common reaction I have seen is bloating. If someone bloats then either use less probiotics, another probiotic, or no probiotic at all.

I’d like to hear your thoughts or questions regarding any of the above information. Please leave comments or questions below – it might become our next practitioner question of the month.