Low-fat diet reduces fatigue and alters serum metabolomic pathways in people with multiple sclerosis: a sub-study of a randomized controlled trial
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Vijayshree Yadav1, Laurel Kelley2, Emma Young3
1Department of Neurology, Oregon Health & Science University (OHSU), 3181 S.W. Sam Jackson Park Rd, Portland, OR, 97239, United States; Department of Veterans Affairs MS Center of Excellence-West, 3710 Southwest US Veterans Hospital Road, Portland, OR, 97239-2964, United States.
Background:
Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS). Dietary interventions have shown promise for fatigue reduction, but the metabolic mechanisms remain unclear. We investigated the effects of a low-fat diet on fatigue and serum metabolomic pathways in people with MS, focusing on lipid and amino-acid metabolism.
Methods:
This exploratory analysis used data from a 16-week, two-arm, randomized controlled trial in people with MS comparing a low-fat diet (intervention) with a waitlist (control) group that continued their usual diet. Serum metabolites and fatigue (Modified Fatigue Impact Scale, MFIS) were measured at baseline and week 16. Additional outcomes included dietary composition, adherence, body composition, and cardiometabolic biomarkers. Spearman rank correlations were used to examine associations between MFIS scores and individual metabolites. Metabolites were then grouped into biochemical super-pathways and sub-pathways for pathway-level summary. Group-level percentage changes in metabolites were also calculated.
Results:
Twenty-seven participants (16 intervention, 11 control) with complete data were included. Of the 986 metabolites detected, changes in MFIS scores were correlated to shifts in fatty acid (e.g., octadecenedioylcarnitine, cis-4-decenoate) and amino acid (e.g., phenol sulfate, phenylpyruvate) pathways. Over the 16-week study, several lipids decreased in the intervention group but increased in controls, consistent with modulation of mitochondrial fatty acid β-oxidation.
Conclusions:
To our knowledge, this is the first study to explore the impact of a low-fat diet on serum metabolomic pathways in people with MS. These preliminary exploratory findings suggest that diet-induced modulation of lipid and amino acid metabolism may contribute to fatigue changes. The small sample size and inter-individual variability warrant cautious interpretation; replication in larger, adequately powered trials is needed.
Trial Registration:
ClinicalTrials.gov identifier: NCT03322982.
