Dietary intervention studies on the phosphoglyceride fatty acids and electrophoretic mobility of erythrocytes in multiple sclerosis

Harbige, Lauerence S.; Crawford, Michael; Jones, R.; Preece, AW; Forti, Alec

doi:10.1016/0163-7827(86)90051-2

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Taken together the above indicate that nervonic and lignoceric acids could be useful pathogenic biomarkers of myelin damage and/or biomarkers for monitoring fatty acid treatments. We also found that the atypical erythrocyte electrophoretic response of MS patients was positively correlated with membrane linoleic acid and could be corrected by a diet rich in polyunsaturated fatty acids particularly linoleic acid 67 . This is in agreement with Field and Joyce 71 who found an increase in erythrocyte electrophoretic response in MS patients supplemented with evening primrose oil (EPO).…”

Section: Biochemical and Metabolic Studies Of Fatty Acids In Multiplementioning

confidence: 54%

“…Previously we proposed nervonic acid as a marker of CNS myelin damage in MS 66 and found that MS patients consuming a diet rich in polyunsaturated fatty acids particularly linoleic acid had an inverse relationship between erythrocyte membrane linoleic acid and nervonic acid (24 : 1) 67 . A similar finding was described by Homa et al 68 , showing a decrease in erythrocyte lignoceric acid (24 : 0) in sunflower oil (rich in linoleic acid) supplemented MS patients.…”

Section: Biochemical and Metabolic Studies Of Fatty Acids In Multiplementioning

confidence: 99%

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Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

Harbige

Sharief

2007

Br J Nutr

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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.

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Section: Biochemical and Metabolic Studies Of Fatty Acids In Multiplementioning

confidence: 54%

Section: Biochemical and Metabolic Studies Of Fatty Acids In Multiplementioning

confidence: 99%

Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

Harbige

Sharief

2007

Br J Nutr

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“…However, these effects are (135), or are likely to be, dependent on the vitamin E level. It is possible that LA may act in a proinflammatory capacity when it is in excess of requirements as a membrane structural fatty acid and there is an associated vitamin E insufficiency (135)(136)(137)(138). Several human disorders involving an autoimmune-inflammatory pathogenesis appear to be clinically responsive to certain n-6 fatty acids.…”

Section: Autoimmunity Immune Functions and N-6 Pufamentioning

confidence: 99%

Fatty acids, the immune response, and autoimmunity: A question of n−6 essentiality and the balance between n−6 and n−3

Harbige

2003

Lipids

278

171

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The essentiality of n-6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20:4n-6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (1 8:2n-6, LA) for membrane phospholipids. Low n-6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2-like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer-chain n-6 PUFA produced by gamma-linolenic acid (18:3n-6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n-6 PUFA, GLA, dihomo-gamma-linolenic acid (20:3n-6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (TGF)-beta-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha production. Low intakes of long-chain n-3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and Th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long-chain n-3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n-3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n-3 PUFA augment disease, whereas n-6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n-6 and n-3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n-6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.

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“…The conclusions drawn from this work were that the suppressive effects of n-6 essential fatty acids on EAE are derived from prostaglandins produced in the spleen. Moreover, patients with the demyelinating condition multiple sclerosis show abnormalities in the metabolism of n-6 essential fatty acids (Baker et al 1964;Sanders et al 1968;Tsang et al 1976;Neu, 1983;Cherayil, 1984;Harbige et al 1986;Fisher et al 1987;Navarro & Segura, 1989), and oral treatment with linoleic-acid-rich oil has been found to have a beneficial influence on the disease course @workin et al. 1984).…”

mentioning

confidence: 99%

Prevention of experimental autoimmune encephalomyelitis in Lewis rats by a novel fungal source of γ-linolenic acid

et al. 1995

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The effects of oral administration of linoleic- and γ-inolenic-acid-rich oils on the clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE) were investigated in Lewis rats 7 d post-inoculation. γ-Linolenic-acid-rich fungal (Mucor javanicus) oil at 500 mg/kg body weight abrogated clinical and histological signs of EAE although at doses of 200 and 1000 mg/kg body weight it was only effective in delaying the onset of clinical disease. Linoleic-acid-rich safflower-seed (Carthamus tinctorius) oil at 500, 750 and 1000 mg/kg body weight decreased the severity of clinical EAE. disease in a dose-dependent manner. The effects in healthy animals of orally administered γ-linolenic-acid-rich fungal oil (500 mg/kg body weight) and linoleic-acid-rich safflower-seed oil (1000 mg/kg body weight) on splenic lymphocyte proliferative responses to the T-cell mitogen concanavalin-A (Con A), membrane fatty acid composition and lymphocyte sub-sets were also studied. Both treatments enhanced the T-cell proliferative response to Con A. There was no significant effect on the proportion of splenic CD8+ or CD4+ lymphocytes. Compositional studies on splenic phosphoglyceride fatty acids of oil-treated animals suggest the above responses were associated with increases in spleen dihomo-γ-linolenic and arachidonic acids.

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Dietary intervention studies on the phosphoglyceride fatty acids and electrophoretic mobility of erythrocytes in multiple sclerosis

Cited by 7 publications

References 22 publications

Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis

Fatty acids, the immune response, and autoimmunity: A question of n−6 essentiality and the balance between n−6 and n−3

Prevention of experimental autoimmune encephalomyelitis in Lewis rats by a novel fungal source of γ-linolenic acid

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