α-Linolenic acid is associated with MRI activity in a prospective cohort of multiple sclerosis patients

Abstract

Background:

The plant-based ω-3 fatty acid α-linolenic acid (ALA) has been associated with lower MS risk. It is currently unknown whether ALA affects disease activity.

Objective:

To investigate the association between ALA levels and disease activity.

Methods:

We conducted a cohort study including 87 multiple sclerosis (MS)-patients who originally participated in a randomized trial of ω-3 fatty acids (the OFAMS study). We measured serum levels of ALA during follow-up and used random intercept logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association between ALA levels, new magnetic resonance imaging (MRI) lesions, Expanded Disability Status Scale (EDSS) progression and new relapses adjusting for age at inclusion, sex, and use of interferon beta-1a.

Results:

In continuous (per 1-SD increase) multivariable-adjusted analyses, higher ALA levels were significantly associated with lower odds of new T2-lesions (OR: 0.59, 95% CI: 0.37–0.95) during follow-up. The effect estimates were similar for new T1Gd + lesions (OR: 0.73, 95% CI: 0.48–1.11), EDSS-progression (OR: 0.62, 95% CI: 0.34–1.16) and new relapses (OR: 0.49, 95% CI: 0.22–1.10), but these estimates did not reach statistical significance. Further adjustment for vitamin D and tobacco use did not materially change the results.

Conclusion:

We found that higher levels of ALA were associated with lower disease activity in MS-patients.

Keywords

Omega 3 fatty acids alpha linolenic acid disease activity

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References

Mehta

Dworkin

Schwid

SR.

Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis. Nat Clin Pract Neurol 2009; 5: 82–92. DOI: 10.1038/ncpneuro1009.

Wergeland

Torkildsen

et al . Polyunsaturated fatty acids in multiple sclerosis therapy. Acta Neurol Scand Suppl 2012; 126: 70–75.

Bates

Cartlidge

French

et al . A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 1989; 52: 18–22.

Torkildsen

Wergeland

Bakke

et al . Omega-3 fatty acid treatment in multiple sclerosis (OFAMS Study): A randomized, double-blind, placebo-controlled trial. Arch Neurol 2012; 69: 1044–1051.

Weinstock-Guttman

Baier

Park

et al . Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot Essent Fatty Acids 2005; 73: 397–404.

Farinotti

Vacchi

Simi

et al . Dietary interventions for multiple sclerosis. Cochrane Database Syst Rev 2012; 12: CD004192.

Bjornevik

Chitnis

Ascherio

et al . Polyunsaturated fatty acids and the risk of multiple sclerosis. Mult Scler 2017; 23: 1830–1838.

Zhao

Etherton

Martin

et al . Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr 2007; 85: 385–391.

Rallidis

Paschos

Liakos

et al . Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Atherosclerosis 2003; 167: 237–242.

10.

Poisson

Suhail

Singh

et al . Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis. J Biol Chem 2015; 290: 30697–30712.

11.

Lindberg

Midthjell

Bjerve

KS.

Long-term tracking of plasma phospholipid fatty acid concentrations and their correlation with the dietary intake of marine foods in newly diagnosed diabetic patients: Results from a follow-up of the HUNT Study, Norway. Br J Nutr 2013; 109: 1123–1134.

12.

Bjerve

Fischer

Alme

Alpha-linolenic acid deficiency in man: Effect of ethyl linolenate on plasma and erythrocyte fatty acid composition and biosynthesis of prostanoids. Am J Clin Nutr 1987; 46: 570–576.

13.

Kvistad

Myhr

Holmoy

et al . No association of tobacco use and disease activity in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2016; 3: e260.

14.

Loken-Amsrud

Holmoy

Bakke

et al . Vitamin D and disease activity in multiple sclerosis before and during interferon-beta treatment. Neurology 2012; 79: 267–273.

15.

Connor Gorber

Schofield-Hurwitz

Hardt

et al . The accuracy of self-reported smoking: A systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob Res 2009; 11: 12–24.

16.

Fleming

Kris-Etherton

PM.

The evidence for alpha-linolenic acid and cardiovascular disease benefits: Comparisons with eicosapentaenoic acid and docosahexaenoic acid. Adv Nutr 2014; 5: 863S–876S.

17.

Calder

PC.

Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology?

Br J Clin Pharmacol 2013; 75: 645–662.

18.

Burdge

GC.

Metabolism of alpha-linolenic acid in humans. Prostaglandins Leukot Essent Fatty Acids 2006; 75: 161–168.

19.

Giovannucci

Stampfer

Colditz

et al . A comparison of prospective and retrospective assessments of diet in the study of breast cancer. Am J Epidemiol 1993; 137: 502–511.

20.

Dewell

Marvasti

Harris

et al . Low- and high-dose plant and marine (n-3) fatty acids do not affect plasma inflammatory markers in adults with metabolic syndrome. J Nutr 2011; 141: 2166–2171.

21.

Veldhoen

Hocking

Atkins

et al . TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006; 24: 179–189.

22.

Bettelli

Carrier

Gao

et al . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441: 235–238.

23.

Riise

Nortvedt

Ascherio

Smoking is a risk factor for multiple sclerosis. Neurology 2003; 61: 1122–1124.

24.

Fitzgerald

Munger

Kochert

et al . Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA Neurol 2015; 72: 1458–1465.

25.

Hernan

Jick

Logroscino

et al . Cigarette smoking and the progression of multiple sclerosis. Brain 2005; 128: 1461–1465.