British Journal of Nutrition

Full Papers

Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

Laurence S. Harbigea1a2 c1 and Mohammad K. Shariefa3

a1 Centre for Bioscience Research, School of Science, University of Greenwich at Medway, United Kingdom

a2 Medway School of Pharmacy, University of Kent and University of Greenwich, United Kingdom

a3 Department of Neurology, King's, Guy's and St Thomas' Hospital, London, United Kingdom

Abstract

Epidemiological, biochemical, animal model and clinical trial data described in this overview strongly suggest that polyunsaturated fatty acids, particularly n-6 fatty acids, have a role in the pathogenesis and treatment of multiple sclerosis (MS). Data presented provides further evidence for a disturbance in n-6 fatty acid metabolism in MS. Disturbance of n-6 fatty acid metabolism and dysregulation of cytokines are shown to be linked and a “proof of concept clinical trial” further supports such a hypothesis. In a randomised double-blind, placebo controlled trial of a high dose and low dose selected GLA (18 : 3n-6)-rich oil and placebo control, the high dose had a marked clinical effect in relapsing-remitting MS, significantly decreasing the relapse rate and the progression of disease. Laboratory findings paralleled clinical changes in the placebo group in that production of mononuclear cell pro-inflammatory cytokines (TNF-α, IL-1β) was increased and anti-inflammatory TGF-β markedly decreased with loss of membrane n-6 fatty acids linoleic (18 : 2n-6) and arachidonic acids (20 : 4n-6). In contrast there were no such changes in the high dose group. The improvement in disability (Expanded Disability Status Scale) in the high dose suggests there maybe a beneficial effect on neuronal lipids and neural function in MS. Thus disturbed n-6 fatty acid metabolism in MS gives rise to loss of membrane long chain n-6 fatty acids and loss of the anti-inflammatory regulatory cytokine TGF-β, particularly during the relapse phase, as well as loss of these important neural fatty acids for CNS structure and function and consequent long term neurological deficit in MS.

Correspondence:

c1 Corresponding author: Dr Laurence Harbige, fax 0044 (0)1813319805, email L.Harbige@gre.ac.uk