Slower ALS Progression Is Linked To Omega-3 Fatty Acids
Observational data demonstrated that individuals with amyotrophic lateral sclerosis (ALS) had slower disease progression when their plasma levels of omega-3 fatty acids, particularly alpha-linolenic acid (ALA), were high.
Kjetil Bjornevik, MD, PhD, of the Harvard T.H. Chan School of Public Health in Boston and his co-authors found that ALS patients with the highest levels of ALA had a 50% lower risk of death over an 18-month study period than those with the lowest levels (HR 0.50, 95% CI 0.29-0.86, P=0.041 for trend).
Higher ALA levels were associated with slower functional decline in a joint-rank test of survival at 12 months (difference in score according to one standard deviation increase: 10.7, 95% CI 0.2-21.1, P=0.045) in Neurology, which opens in a new window or tab.
During follow-up, lower mortality risk was also associated with eicosapentaenoic acid (EPA) and linoleic acid (LA), two additional polyunsaturated fatty acids.
The findings build on previous research that suggested eating more omega-3s, particularly ALA, in the diet may lower the risk of ALS. “This fatty acid may have neuroprotective effects that could benefit people with ALS, according to these findings and our previous research,” Bjornevik said in a statement.
Plasma samples from 449 ALS patients who participated in the EMPOWER clinical trial of dexpramipexole were collected at random in the study. At the time of screening, participants’ upright slow vital capacity was at least 65% of the predicted value for their age, and symptom onset occurred within 24 months of baseline. 65.3% of the participants were male, with a mean baseline age of 57.5.
Plasma fatty acid levels were assessed using two endpoints in the post-hoc analysis: death for up to 18 months, and a joint-rank test that took into account both survival for up to 12 months and functional decline, which is measured by a change in the ALS Functional Rating Scale-Revised (ALSFRS-Ropens in a new tab or window). Time to death was used to rank participants who died during follow-up (a shorter time to death was ranked lower); The survivors were ranked according to the change in their ALSFRS-R score (a greater decline was ranked lower).
During the course of the study, 28.1% of participants died in total. Compared to participants in quartiles 1 (32.7%), 2 (27.4%), and 3, 18.9% of those in the top quartile of plasma ALA died during follow-up.
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) were also associated with lower mortality risk during follow-up when comparing the top and bottom quartiles.
Participants in quartile 4 of the ALA had a least-squares mean joint-rank test score that was 24.3 points higher than the score in quartile 1 (95% CI, -5.0 to 53.5), but the difference was not significant.
Age and gender were removed from the results. When adjusted for BMI, race and ethnicity, symptom duration, site of onset, use of riluzole, family history of ALS, predicted upright slow vital capacity, and trial treatment arm, estimates remained the same.
The researchers noted that plasma fatty acid concentrations may not always reflect dietary intake. They acknowledged that the EMPOWER trial participants may not be representative of the general ALS population.
Alberto Ascherio, MD, DrPH, a co-author from the Harvard T.H. Chan School of Public Health, stated, “We are now reaching out to clinical investigators to promote a randomized trial to determine whether ALA is beneficial in people with ALS.” Since ALA is not a drug that can be patented, getting funding will be difficult, but we hope to complete the project.
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