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J Nutr. 2018 Aug 1;148(8):1380-1386. doi: 10.1093/jn/nxy116.

High-dose ω-3 Fatty Acid Plus Vitamin D3 Supplementation Affects Clinical Symptoms and Metabolic Status of Patients with Multiple Sclerosis: A Randomized Controlled Clinical Trial.

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Department of Neurology, School of Medicine.
Physiology Research Center; and.
Pure North S'Energy Foundation, Calgary, Alberta, Canada.
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R. Iran.



Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation.


This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS.


This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables.


Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (β -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (β -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (β +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (β +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (β -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations.


Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website ( for registration of clinical trials as IRCT2017090133941N20.

[Indexed for MEDLINE]

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