Omega-3 Fatty Acids Linked to Slowed ALS Progression

Polyunsaturated fatty acids (PUFAs) may have a favorable effect on disease progression and survival for patients with amyotrophic lateral sclerosis (ALS). Among more than 400 ALS patients who were followed for over 18 months, higher levels of the omega-3 fatty acid alpha-linolenic acid (ALA) were associated with longer survival and slower functional decline.

Higher levels of the n-3 fatty acid eicosapentaenoic acid (EPA) and the n-6 fatty acid linoleic acid (LA) were also associated with a lower risk of dying during follow-up. The results suggest that specific PUFAs, ALA in particular, “may have neuroprotective properties that could benefit people with ALS,” Kjetil Bjornevik, MD, PhD, of Harvard University in Boston, Massachusetts, told Medscape Medical News. The study was published online June 21 in Neurology.

Novel Data

Previous studies have shown that a diet high in ALA and increased blood levels of this fatty acid may decrease the risk of ALS, but less is known about how PUFAs affect disease progression. To investigate, Bjornevik and colleagues studied 449 adults with ALS (mean age, 58; 65% men) who were enrolled in the EMPOWER study.  Plasma samples were collected from the participants at the time of randomization and were available for fatty acid analyses.

The endpoints included death within 18 months and a joint-rank test that reflected both functional decline as change from baseline to month 12 in ALS Functional Rating Scale–Revised (ALSFRS-R) score and survival up to 12 months.

During the 18-month follow-up period, 126 (28%) patients died. Fewer patients in the top quartile of ALA (n = 21, 19%) died during follow-up than did peers in quartile 1 (n = 37, 33%), quartile 2 (n = 31, 27%), and quartile 3 (n = 37, 33%). After adjusting for age and sex, higher plasma levels of ALA were associated with a lower risk of death (hazard ratio [HR], 0.50 for highest vs lowest quartile; 95% CI, 0.29 – 0.86; P = .041), as well as a higher joint-rank test score consistent with slower functional decline (difference in score according to 1 SD increase: 10.7; 95% CI, 0.2 – 21.1; P = .045).

The results were similar when adjusted for body mass index, race/ethnicity, symptom duration, site of onset, use of riluzole, family history of ALS, predicted upright slow vital capacity, and treatment group.

Higher levels of EPA and LA were also associated with a lower risk of death during follow-up. For EPA, the multivariable-adjusted HR comparing top and bottom quartile was 0.45 (95% CI, 0.26 – 0.79; P = .008); for LA, it was 0.54 (95% CI, 0.31 – 0.93; P = .048). The results suggest that specific PUFAs may have a beneficial effect for ALS patients, but more study is needed, said Bjornevik.

“There are no immediate clinical implications. We need to conduct a randomized trial testing whether ALA is beneficial in people with ALS before we can recommend supplements to patients,” he added.

Potentially Beneficial

Commenting on this research for Medscape Medical News, Stephen Scelsa, MD, director of the ALS Center, Mount Sinai Downtown Union Square, New York, said when it comes to nutrition in ALS, “we don’t have great data. “The only thing we know historically for ALS is there’s good evidence that weight loss is detrimental, but we don’t know what an optimal diet is,” said Scelsa, professor of neurology at the Icahn School of Medicine at Mount Sinai.

“We need more nutritional information, so anything in this realm I think is important, and I think the paper makes a good case that alpha-linolenic acid might be beneficial,” he noted. Scelsa also noted that data on statins in ALS are also needed. Some studies suggest that higher cholesterol or triglyceride levels are associated with a better disease course.

“Whether statin drugs, which lower your cholesterol and triglycerides, are detrimental in ALS patients, we don’t really know the answer to that,” Scelsa said.

The study was funded by a grant from the ALS Association, Neurology.

Published online June 21, 2023.