Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial

doi:10.1016/j.clnu.2016.08.015

Clinical Nutrition

Volume 36, Issue 5, October 2017, Pages 1245-1249

https://doi.org/10.1016/j.clnu.2016.08.015 Get rights and content

Summary

Background & aims

This trial was performed to evaluate the effects of probiotic intake on disability, mental health and metabolic condition in subjects with multiple sclerosis (MS).

Methods

This randomized double-blind placebo-controlled clinical trial was conducted among 60 MS patients. Participants were randomly allocated into two groups to receive either a probiotic capsule (n = 30) or placebo containing starch (n = 30) for 12 weeks. Expanded disability status scale (EDSS) scoring and parameters of mental health were recorded at the baseline and 12 weeks after the intervention.

Results

Compared with the placebo, probiotic intake improved EDSS (−0.3 ± 0.6 vs. +0.1 ± 0.3, P = 0.001), beck depression inventory (−5.6 ± 4.9 vs. −1.1 ± 3.4, P < 0.001), general health questionnaire (−9.1 ± 6.2 vs. −2.6 ± 6.4, P < 0.001) and depression anxiety and stress scale (−16.5 ± 12.9 vs. −6.2 ± 11.0, P = 0.001). In addition, changes in high-sensitivity C-reactive protein (−1.3 ± 3.5 vs. +0.4 ± 1.4 μg/mL, P = 0.01), plasma nitric oxide metabolites (+1.0 ± 7.9 vs. −6.0 ± 8.3 μmol/L, P = 0.002) and malondialdehyde (MDA) (+0.009 ± 0.4 vs. +0.3 ± 0.5 μmol/L, P = 0.04) in the probiotic group were significantly different from the changes in these parameters in the placebo group. Additionally, the consumption of probiotic capsule significantly decreased serum insulin (−2.9 ± 3.7 vs. +1.1 ± 4.8 μIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (−0.6 ± 0.8 vs.+0.2 ± 1.0, P = 0.001), Beta cell function (−12.1 ± 15.5 vs. +4.4 ± 17.5, P < 0.001) and total-/HDL-cholesterol (−0.1 ± 0.3 vs.0.1 ± 0.3, P = 0.02), and significantly increased quantitative insulin sensitivity check index (+0.01 ± 0.02 vs. −0.005 ± 0.01, P < 0.001) and HDL-cholesterol levels (2.7 ± 3.4 vs. 0.9 ± 2.9 mg/dL, P = 0.02) compared with the placebo.

Conclusions

Our study demonstrated that the use of probiotic capsule for 12 weeks among subjects with MS had favorable effects on EDSS, parameters of mental health, inflammatory factors, markers of insulin resistance, HDL-, total-/HDL-cholesterol and MDA levels.

Introduction

Multiple sclerosis (MS) is an inflammatory disease affecting mostly young adult females with multifactorial etiology [1]. It is reported that 2.5 million persons endure from MS [2]. Regarding the high prevalence of MS in Isfahan province/Iran (43.8 per 100,000), this province could be considered as the area with the maximum prevalence of MS in the Asia and Oceania [3]. Prior studies have demonstrated that activated inflammatory and oxidative pathways play a substantial function in MS pathophysiology [4], [5]. Increased inflammation would result in hyperinsulinemia and dyslipidemia [6]. In addition, insulin resistance compensated by hyperinsulinemia has been suggested to be related with neurodegenerative diseases like Alzheimer disease (AD) [7].

Probiotics are reported that have the beneficial effects on chronic diseases [8]. Few studies have also indicated that the gut flora may influence the immune system [9], [10]. Fleming et al. [11] was found that probiotic administration resulted in suitable trends in findings of MRI and few immunological determinations after 3 months. Our previous study among subjects with major depressive disorder (MDD) has demonstrated that probiotic supplementation after 8 weeks had useful effects on depression and metabolic parameters [12]. In addition, improved mental health parameters were seen following the use of probiotic among petrochemical workers after 6 weeks [13]. However, any significant alteration in psychiatric symptoms was not seen after intake of Lactobacillus rhamnosus and Bifidobacterium animalis for 14 weeks in schizophrenia patients [10].

Probiotics intake may result in improved disability, symptoms of mental health and metabolic indicators by their effect on neuronal circuits and through the effect on gene expression [14]. This study was, thus, conducted to evaluate the effects of probiotic intake on disability, parameters of mental health and metabolic indicators in MS subjects.

Section snippets

Trial design

This intervention (done between December 2015 through February 2016) was designed as a 12-week randomized, double-blind and placebo-controlled clinical trial.

Participants

Peoples were entered in the study if they were at ages between 18 and 55 with clinically definite RRMS diagnosed according to McDonald criteria and an expanded disability status scale (EDSS) score ≤4.5 referred to the Shahid Beheshti Hospital in Kashan (located in Esfahan province), Iran. At first, all participants asked whether we are

Results

Among participants in the probiotic and placebo groups, 3 subjects [withdrawn (n = 3)] were excluded (Fig. 1). In the end, 54 subjects [probiotic (n = 27) and placebo (n = 27)] ended the trial. However, as the analysis was based on the ITT principle, all 60 persons were included in the final analysis. The rate of compliance in our trial was high, such that more than 90% of probiotic capsules were consumed in both groups. No side effects were reported after probiotic intake in MS patients.

The

Discussion

We found that probiotic intake after 12 weeks in MS subjects had favorable effects on EDSS, parameters of mental health, inflammatory factors, markers of insulin resistance, HDL-cholesterol, total-/HDL-cholesterol and MDA concentrations, but unchanged other biomarkers of oxidative stress, FPG and other lipid profiles. It must be kept mind that a clinically significant change of the EDSS is defined as a change of 1.0 point or more at EDSS levels <5.5 or 0.5 point or more at EDSS levels>5.5.

Author contributions

ZA and MS contributed in the conception or design of the work, analysis and drafting of the manuscript. EK, O-RT, MS, FB, RD, EA, MT-E and PJ. contributed in conception and manuscript drafting.

Conflicts of interest

No conflicts are declared.

Acknowledgements

The present study was supported by a grant from the Vice-chancellor for Research, KUMS, and Iran (grant no. 94081).

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Randomized Control TrialsClinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial

Summary

Background & aims

Methods

Results

Conclusions

Introduction

Section snippets

Trial design

Participants

Results

Discussion

Author contributions

Conflicts of interest

Acknowledgements

J Neuroimmunol

J Neurol Sci

Vitam Horm

J Neurol Sci

Med Hypotheses

Nutrition

J Biol Chem

J Psychiatr Res

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

EPMA J

Sharp increase in the incidence and prevalence of multiple sclerosis in Isfahan, Iran

Mult Scler

Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity

Mult Scler

Probiotics and chronic disease

J Clin Gastroenterol

Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial

Prim Care Companion CNS Disord

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study

Mult Scler

The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: a randomized, double-blind, placebo-controlled trial in petrochemical workers

Nutr Neurosci

Randomized Control Trials
Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial