Omega-3 Fatty Acids Tied to Slower ALS Progression

Plasma levels of omega-3 fatty acids, especially alpha-linolenic acid (ALA), were tied to slower disease progression in people with amyotrophic lateral sclerosis (ALS), observational data showed.

Over an 18-month study period, ALS patients with the highest levels of ALA had a 50% lower risk of death compared with those with the lowest ALA levels (HR 0.50, 95% CI 0.29-0.86, P=0.041 for trend), reported Kjetil Bjornevik, MD, PhD, of the Harvard T.H. Chan School of Public Health in Boston, and co-authors.

In a joint-rank test of functional decline and survival at 12 months, higher ALA levels were associated with slower functional decline (difference in score according to one standard deviation increase: 10.7, 95% CI 0.2-21.1, P=0.045), the researchers wrote in Neurology.

Two other polyunsaturated fatty acids — eicosapentaenoic acid (EPA) and linoleic acid (LA) — also were associated with lower mortality risk during follow-up.

The findings extend earlier work that suggested increased dietary intake of omega-3s, particularly ALA, may decrease ALS risk. “These findings, along with our previous research, suggest that this fatty acid may have neuroprotective effects that could benefit people with ALS,” Bjornevik said in a statement.

The study evaluated 449 participants with ALS who had plasma samples collected at randomization in the EMPOWER clinical trial of dexpramipexole. Participants had symptom onset within 24 months of baseline and an upright slow vital capacity at screening of at least 65% of the predicted value for their age. Mean baseline age of participants was 57.5, and 65.3% were men.

The post-hoc analysis assessed plasma fatty acid levels on two endpoints: death up to 18 months, and a joint-rank test that considered both functional decline, defined as change in ALS Functional Rating Scale-Revised (ALSFRS-R) score and survival up to 12 months. Participants who died during follow-up were ranked according to time to death (shorter time to death was ranked worse); those who survived were ranked according to ALSFRS-R score change (larger decline was ranked worse).

Overall, 28.1% of participants died during the study period. A lower number of participants in the top quartile of plasma ALA (18.9%) died during follow-up compared to quartile 1 (32.7%), quartile 2 (27.4%), and quartile 3 (33.0%).

Comparing the top versus bottom quartiles, higher plasma levels of the omega-3 fatty acid EPA (P=0.008 for trend) and the omega-6 fatty acid LA (P=0.048 for trend) also were associated with lower mortality risk during follow-up.

The least-squared mean joint-rank test score for participants in quartile 4 of ALA was 24.3 points higher than in quartile 1 (95% CI -5.0 to 53.5), but the difference was not significant.

Findings were adjusted for age and sex. Estimates remained similar when additionally adjusted for BMI, race and ethnicity, symptom duration, site of onset, riluzole use, family history of ALS, predicted upright slow vital capacity, and trial treatment arm.

Plasma fatty acid concentrations may not always reflect dietary intake, the researchers noted. In addition, EMPOWER trial participants may not be representative of the broader ALS population, they acknowledged.

“We are now reaching out to clinical investigators to promote a randomized trial to determine whether ALA is beneficial in people with ALS,” said co-author Alberto Ascherio, MD, DrPH, also of the Harvard T.H. Chan School of Public Health. “Obtaining funding will be challenging, because ALA is not a patentable drug, but we hope to get it done.”