Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

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-a, IL-1b) was increased and anti-inflammatory TGF-b 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-b, 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.

Gas Chromatography Results Interpretation: Absolute Amounts Versus Relative Percentages

“…Altered lipid metabolism in the cell membrane is believed to contribute to central nervous system injury (Adibhatla & Hatcher, 2007) and influences the function of immune cells (Calder, 2007). Fatty acids have been implicated in the pathogenesis and treatment of multiple sclerosis (Zamaria, 2004;Harbige & Sharief, 2007). However, although some studies reported an improvement in symptoms during fatty acid supplementation (Bates et al 1978;Nordvik et al 2000;Weinstock-Guttman et al 2005;Harbige & Sharief, 2007) others found no improvement in the disease progression of patients (Paty et al 1978;Farinotti et al 2007).…”

“…Fatty acids have been implicated in the pathogenesis and treatment of multiple sclerosis (Zamaria, 2004;Harbige & Sharief, 2007). However, although some studies reported an improvement in symptoms during fatty acid supplementation (Bates et al 1978;Nordvik et al 2000;Weinstock-Guttman et al 2005;Harbige & Sharief, 2007) others found no improvement in the disease progression of patients (Paty et al 1978;Farinotti et al 2007). Therefore, it is important to investigate fatty acid metabolic abnormalities and possible treatment with fatty acid supplements in a disease such as multiple sclerosis carefully and comprehensively.…”

“…The long-chain n-6 and n-3 polyunsaturated fatty acids are also required in large amounts in the brain, which requires four times the amount of C20:4n-6 than C22:6n-3 4 times the amount of C20:4n-6 than C22:6n-3 on a daily basis (Harbige & Sharief, 2007;Rapoport et al, 2007). Furthermore, the composition of membrane phospholipids and their fatty acids determines the degree of membrane fluidity and the degree of fatty acid unsaturation plays an important role in maintaining required physiological levels of fluidity (Mouritsen & Jorgensen, 1998;Zamaria, 2004).…”

“…Reports on fatty acid composition in blood and brain tissue from patients with multiple sclerosis may vary substantially (Harbige & Sharief, 2007;Hon et al, 2009aHon et al, , 2009b. Cultural and ethnic differences as well as dietary variability have been implicated in these differences (Harbige & Sharief, 2007).…”

Circulating plasma cytokines, zinc, copper, vitamins A and E in multiple sclerosis patients and healthy controls

“…Moreover, vitamin E is an important membrane lipid antioxidant and given the importance of PUFA in MS (9) it should be further investigated in patients with MS both in remission and relapse phases of the disease and in relation to membrane PUFA.…”