Heart-Healthy Fatty Acids May Stave Off ALS

The benefit to cardiovascular health offers one reason to chow down on foods loaded with omega-3 fatty acids. A paper in the July 14 JAMA Neurology online adds another: The same chemicals pare down a person’s risk of developing amyotrophic lateral sclerosis. Researchers at the Harvard School of Public Health determined that among a massive sample of one million people, those who ate the most omega-3-rich foods—such as salmon, flaxseed, and walnuts—had two-thirds the risk of developing ALS later on than those who ate the least. This retrospective, observational study cannot determine cause and effect, cautioned first author Kathryn Fitzgerald. She suspects that these unsaturated fatty acids, which form part of cell membranes in the brain, could protect neurons against oxidative stress or inflammation.

“The result is persuasive and consistent with earlier studies,” commented Michael Swash of the Royal London Hospital in an editorial accompanying the publication (Veldink et al., 2007; Okamoto et al., 2007). Unlike that previous work, which examined people’s diets after they were diagnosed with ALS, the current study analyzed data collected before any subject came down with the disease.

Despite finding that diet helps, eating more omega-3s would be unlikely to make much difference for people at high risk for ALS due to familial mutations, said Joseph Quinn of the Oregon Health and Science University in Portland, who was not involved in the study. Anne-Marie Wills of Massachusetts General Hospital in Boston suggested that since the incidence of ALS is so low compared with cardiovascular disease, healthy people should focus more on eating a heart-healthy diet.

Alzheimer’s researchers have been researching these fats for a long time. In a randomized, placebo-controlled clinical trial, introducing omega-3 fatty acids after diagnosis failed to improve symptoms in people Alzheimer’s disease (see Nov 2010 news story), and this “should make us skeptical about using omega-3 fatty acids to treat ALS,” Wills said. Quinn said the picture for AD prevention remains incomplete. One study found people who dined on fish weekly were less likely to develop Alzheimer’s (see Jul 2003 news story).

Because inflammation and oxidative stress have been implicated in ALS, Fitzgerald, senior author Alberto Ascherio, and colleagues suspected that omega-3s might do some good. Fortunately, the data to answer their question was available. They obtained dietary and disease information from five longitudinal, prospective studies: the National Institutes of Health-American Association of Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Health Professionals Follow-Up Study, the Multiethnic Cohort Study, and the Nurses’ Health Study. Together, these cohorts included more than one million participants. Of those, nearly 1,000 developed ALS over the data collection periods of eight to 24 years, depending on the cohort.

The studies provided Fitzgerald with data on omega-3 fatty acid intake, based on food questionnaires the subjects filled out. She divided the participants into five quintiles, from those who savored the most omega-3s to those who ate the least. Those in the highest quintile had a 34 percent lower risk of developing ALS than those in the lowest. Intake of other kinds of fats did not influence ALS risk. While a thin physique has been associated with ALS (see May 2011 news story and O’Reilly et al., 2013), Fitzgerald found the omega-3 benefit held true even if she controlled for body mass index.

Mouse studies would be the obvious next step, Quinn said, and in fact one such experiment has already been done. Researchers attempted to treat ALS model mice with omega-3 fatty acids and found the disease course sped up, instead of slowing down (Yip et al., 2013). That might be because the researchers used seafood-derived fatty acids, while Fitzgerald observed plant-made versions were most beneficial, Wills speculated.

“This big-data study suggests that at least 20 percent of the U.S. population may be at risk for ALS due to inadequate omega-3 intake … It seems doubtful that any protection involves an ALS-specific mechanism, but more likely a general neuroprotective or anti-inflammatory mechanism,” Greg Cole of the University of California, Los Angeles, commented in an email to Alzforum. Cole was not part of the study group, but he has studied the role of such fatty acids in AD. “The study lacks measurement of blood levels of omega-3 but dietary questionnaires are reasonably well-validated,” he said. Fitzgerald said she hopes to examine how blood biomarkers for fatty acids correlate to ALS incidence in a follow-up study. Wills said that proving the fatty acid benefit experimentally would be difficult. “Unfortunately, deciding whether it would be helpful to increase [omega-3 fatty acid] intake if you carry an ALS mutation would require a very large and long clinical trial,” she wrote.—Amber Dance.


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