Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis.
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-alpha, IL-1beta) was increased and anti-inflammatory TGF-beta 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-beta, 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.
Harbige
Laurence S
LS
Centre for Bioscience Research, School of Science, University of Greenwich at Medway, United Kingdom. L.Harbige@gre.ac.uk
Sharief
Mohammad K
MK
D000818:Animals; D002986:Clinical Trials as Topic; D004032:Diet / Q000706:statistics & numerical data; D004195:Disease Models, Animal; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D009103:Multiple Sclerosis / Q000178:diet therapy / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism
D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated