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Abstract
Background and Objectives Polyunsaturated fatty acids (PUFAs) have neuroprotective and anti-inflammatory effects and could be beneficial in amyotrophic lateral sclerosis (ALS). Higher dietary intake and plasma levels of PUFAs, in particular alpha-linolenic acid (ALA), have been associated with a lower risk of ALS in large epidemiologic cohort studies, but data on disease progression in patients with ALS are sparse. We examined whether plasma levels of ALA and other PUFAs contributed to predicting survival time and functional decline in patients with ALS.
Methods We conducted a study among participants in the EMPOWER clinical trial who had plasma samples collected at the time of randomization that were available for fatty acid analyses. Plasma fatty acids were measured using gas chromatography. We used Cox proportional hazards models and linear regression to evaluate the association of individual fatty acids with risk of death and joint rank test score of functional decline and survival.
Results Fatty acid analyses were conducted in 449 participants. The mean (SD) age of these participants at baseline was 57.5 (10.7) years, and 293 (65.3%) were men; 126 (28.1%) died during follow-up. Higher ALA levels were associated with lower risk of death (age-adjusted and sex-adjusted hazard ratio comparing highest vs lowest quartile 0.50, 95% CI 0.29–0.86, p-trend = 0.041) and higher joint rank test score (difference in score according to 1 SD increase 10.7, 95% CI 0.2–21.1, p = 0.045), consistent with a slower functional decline. The estimates remained similar in analyses adjusted for body mass index, race/ethnicity, symptom duration, site of onset, riluzole use, family history of ALS, predicted upright slow vital capacity, and treatment group. Higher levels of the n-3 fatty acid eicosapentaenoic acid and the n-6 fatty acid linoleic acid were associated with a lower risk of death during follow-up.
Discussion Higher levels of ALA were associated with longer survival and slower functional decline in patients with ALS. These results suggest that ALA may have a favorable effect on disease progression in patients with ALS.
Glossary
- ALA=
- alpha-linolenic acid;
- ALS=
- amyotrophic lateral sclerosis;
- ALSFRS-R=
- ALS Functional Rating Scale–Revised;
- BMI=
- body mass index;
- DHA=
- docosahexaenoic acid;
- EPA=
- eicosapentaenoic acid;
- FVC=
- forced vital capacity;
- HR=
- hazard ratio;
- IL=
- interleukin;
- LA=
- linoleic acid;
- PUFA=
- polyunsaturated fatty acid
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Associate Editor Anthony Amato, MD, FAAN.
- Received November 21, 2022.
- Accepted in final form April 18, 2023.
- © 2023 American Academy of Neurology
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- Reader Response: Association of Polyunsaturated Fatty Acids and Clinical Progression in Patients With ALS: Post Hoc Analysis of the EMPOWER Trial
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