Omega-3 polyunsaturated fatty acids associated with lower risk of MS activity

In paediatric-onset MS patients, several omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and their metabolites were shown to be associated with various clinical and MRI disease-activity outcomes. These results suggest that ω-3 PUFAs and their derivatives may be associated with a lower risk of MS activity.

Environmental factors, modulated by genetics, contribute to the pathogenesis of MS, which may result in a unique metabolic signature. On the other hand, the acute inflammatory processes that lead to brain tissue damage, may also contribute to this metabolomic signature. Dr Vinicius Schoeps and colleagues (University of California, CA, USA) performed an in-depth analysis of the circulating lipidome profile and its association with disease activity [1]. To this end, they analysed blood samples from a prospective cohort of 435 paediatric-onset MS patients. At sample collection, 285 (66%) patients were women, median age was 16.2 years, 68% were treatment-naïve, median Expanded Disability Status Scale (EDSS) score was 1.5, and median follow-up was 4.12 years (clinical) and 3.89 years (MRI). Dr Schoeps said they used adolescents as study participants because at that age confounding factors that could influence lipid levels are less likely to occur.

A total of 2,104 metabolites were measured; of the 489 that were chemically characterised, 16 were associated with subsequent disease activity. Weighted Correlation Network Analysis (WGCNA) showed that, when clustering all PUFAs to predict outcomes in MS, there was a consistent estimated reduction in multiple outcomes, such as relapse rate (RR 0.89; 95% CI 0.79–1.00; P=0.056). The prespecified threshold in false discovery rate was not reached, however (false discovery rate >0.999).

Dr Schoeps noted that ω-3 PUFAs were consistently associated with protective effects on clinical and MRI outcomes. Examples of ω-3 PUFAs are fish oil, walnuts, and chia seeds. On the other hand, ω-6 PUFAs such as sunflower, corn, and soy-bean oils, were associated with MS worsening.

Focusing on oxylipids, ω-3 PUFA derivatives (8-HETE, 12-HEPE, 9-HETE, 5-HETE, 16,17-DiHDoPE) exerted anti-inflammatory activity, while ω-6 PUFA derivatives, most notably 10-HODE and 12-HODE, exerted mostly pro-inflammatory activity. A notable exception was arachidonic acid, which showed consistent anti-inflammatory effects.

“Structural lipids are a by-product of inflammation,” Dr Schoeps concluded, “while PUFAs modulate immune responses and may be responsible for changing the future risk of disease activity.”

1. Schoeps V, et al. Serum lipidomics and disease activity in pediatric-onset multiple sclerosis: a nation-wide prospective cohort study. O079, MSMilan 2023, 11–13 October, Milan, Italy.

 

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Posted on 4 December, 202325 March, 2024