Red blood cell and adipose tissue fatty acids in mild inactive multiple sclerosis

Abstract

The fatty acid profiles of phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) of the red blood cells of 30 patients with mild inactive multiple sclerosis (MS) and 30 healthy controls were studied by gas chromatography. The groups were well matched for factors likely to influence tissue lipid levels, including diet. The MS patients showed a significant reduction in PE eicosapentaenoic acid (p = 0.009) especially in women, and an increase in both PE dihomo‐gamma‐linolenic acid (p = 0.004) and PC stearic acid (p = 0.04). No reduction in linoleic acid was observed in either the PC or PE fractions of the MS subjects. A similar study of the fatty acid profile in adipose tissue in 26 MS and 35 healthy controls found no detectable eicosapentaenoic acid in either group. However, whereas docosahexaenoic acid was not detectable in any MS patient, 40% of the controls had measurable levels varying from to 0.1 to 0.3% of total estimated fatty acid (p = 0.0003). No reduction in linoleic acid in MS subjects was observed. Supplementation with oral fish body oil demonstrated that n ‐ 3 fatty acids were incorporated into red blood cells over 5 weeks and this occurred equally in MS and controls. The effects of oral supplementation on adipose tissue were studied after 1 and 2 years. Whereas many fatty acids such as linoleic acid were raised at 1 year, but did not rise subsequently, eicosapentaenoic acid and docosahexaenoic acid continued to rise through the 2‐year period. Long chain n ‐ 3 fatty acids such as eicosapentaenoic and docosahexaenoic acids may be important in the development of the central nervous system and may be relevant to the pathogenesis and treatment of MS.

Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis

“…Bioinformatics analysis has revealed that metabolism of the PUFA pathway (-3 and -6 metabolism) is down-regulated in the plasma of EAE, which has also been reported in patients with MS (15)(16)(17)(18)(19). We therefore examined the therapeutic potential of resolvin D1 (RvD1; 7S,8R,17S-trihydroxy-docosa-4Z,9E,11E,13Z,15E,19Z-hexaenoic acid) (20), a downstream metabolite of -3 pathways in the EAE disease progression.…”

“…Using KEGG and enrichment pathway analyses, we observed that ␣-linolenic acid and linoleic acid PUFA metabolism (-3 and -6) were altered in both murine EAE models (RR (14) and chronic (supplemental Table S1 and Fig. 5B)), and the levels of its metabolites were found to be low in patients with MS (15)(16)(17)(18)(19), suggesting that this pathway could potentially be a therapeutic target for MS. There are two major sources of -3 fatty acids: ␣-linolenic acid, which is found in plants, and EPA and DHA, which are found in fish.…”

“…Moreover, metabolites of PUFAs were found to be significantly lower in the mouse chronic model of EAE (Fig. 4C and supplemental Table S1) and in patients with MS (15)(16)(17)(18)(19), suggesting the importance of PUFA in MS. ␣-Linolenic acid is the true essential -3 fatty acid found in plants. It is similar to the -3 fatty acids in fish oil, called eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).…”

Gas Chromatography Results Interpretation: Absolute Amounts Versus Relative Percentages

“…The n-6 and n-3 polyunsaturated fatty acids, C18:2n-6, C20:4n-6 and C20:5n-3 have been reported to be decreased in plasma and blood cell membranes from these patients (Baker et al, 1964;Cherayil, 1984;Holman et al, 1989;Nightingale et al, 1990;Hon et al, 2009aHon et al, , 2009b, but other research groups have found no differences compared to control subjects (Cumings et al, 1965;Fisher et al, 1987;Evans & Dodd, 1989;Koch et al, 2006). Disturbed metabolic relationships between C18:2n-6 and C20:3n-6 (Harbige & Sharief, 2007), as well as between C20:3n-6 and C20:4n-6 (Harbige & Sharief, 2007;Hon et al, 2009b) in the peripheral blood mononuclear cell membranes from patients with multiple sclerosis have also been reported.…”

“…Abbreviated chemical formulae and common names of major plasma and blood cell membrane fatty acids. References: Nightingale et al, 1990;Horrobin, 1999;Pereira et al, 2003.…”