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The effects of a multispecies probiotic on migraine and markers of intestinal permeability–results of a randomized placebo-controlled study

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Migraine, associated with several gastrointestinal disorders, may result from increased intestinal permeability, allowing endotoxins to enter the bloodstream. We tested whether probiotics could reduce migraine through an effect on intestinal permeability and inflammation.


In total, 63 patients were randomly allocated to the probiotic (n=31) or the placebo group (n=32). Participants ingested a multispecies probiotic (5x109 colony-forming units) or placebo daily for 12 weeks. Migraine was assessed with the Migraine Disability Assessment Scale (MIDAS), the Headache Disability Inventory (HDI) and headache diaries. At baseline and 12 weeks, intestinal permeability was measured with the urinary lactulose/mannitol test and fecal and serum zonulin; inflammation was measured from interleukin (IL) -6, IL-10, tumor necrosis factor-α and C-reactive protein in serum.


The MIDAS migraine intensity score significantly decreased in both groups (P<0.001) and the HDI score significantly decreased in the probiotic group (P=0.032) and borderline in the placebo group (P=0.053). In the probiotics group, patients had a median of 6 migraine days in the first month, 4 in the second month (P=0.002) and 5 in the last month, which was not significantly different from the 5, 4, and 4 days in the placebo group. A 2day reduction in migraine days was seen in 12/31 patients in the probiotics group versus 7/29 in the placebo group (ns). Probiotic use did not significantly affect medication use, intestinal permeability or inflammation compared to placebo.


In this study, we could not confirm significant benefit from a multispecies probiotic compared to a placebo on the outcome parameters of migraine and intestinal integrity.

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This study was financially supported by the Division of Human Nutrition and Epidemiology of Wageningen UR. The probiotic product was provided free of charge by Winclove Probiotics, the Netherlands. We thank the volunteers for taking part in this study; master students Simone van Dorresteijn, Carina Flux, Sara Lookman, Nienke Schipper and Riani Witaningrum for organizing and performing the study or analyzing samples; Ms Nhien Ly for analyzing zonulin and cytokines; Mr Robert Hovenier for performing the L/M tests; and Laura Hettinga for assisting in the data analysis.

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Correspondence to N M de Roos.

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SvH is employee of Winclove Probiotics. SvH has no direct or additional financial interest. The remaining authors declared no conflict of interests.

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