Alpha-linolenic acid associations with disability and brain volume in multiple sclerosis: a brief replication report

Objective To replicate and extend recent findings, suggesting that higher serum alpha-linolenic acid (ALA) levels are associated with reduced disease activity and progression in multiple sclerosis (MS). Methods We reanalysed clinical trial data from 85 people with MS who had serum ALA using magnetic resonance imaging (MRI) and clinical (EDSS, PASAT) assessments, collected for 2 years, with additional follow-up at 12-years. Linear and mixed models were used to assess the relationship between ALA and clinical and MRI outcomes. Mediation analyses tested whether ALA mediated associations between brain volume or T2 lesion load and disability. Results ALA measures were consistent over time ( κ = 0.83). Higher ALA predicted lower EDSS ( β = −0.41, 95% CI [−0.73, −0.08]) and larger brain volume ( β = 0.22, 95% CI [0.09, 0.36]). ALA was a non-significant mediator of brain volume or lesion effects on EDSS and did not predict long-term clinical or cognitive changes. Discussion We replicate prior associations between higher serum ALA levels and reduced disability in MS and extend these by showing a beneficial association of serum ALA with brain volume. However, ALA did not predict long-term progression, limiting its prognostic value.