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Prediagnostic plasma polyunsaturated fatty acids and the risk of amyotrophic lateral sclerosis
Éilis J O'Reilly1, Kjetil Bjornevik2, Jeremy D Furtado2
1From the Departments of Nutrition (É.J.O., K.B., J.D.F., A.A.) and Epidemiology (J.E.M., A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; School of Public Health (É.J.O.), College of Medicine, University College Cork, Ireland; Epidemiology Program (L.N.K., L.L.M.), University of Hawaii Cancer Center, Honolulu; Behavioral and Epidemiology Research Group (M.L.M., V.L.S.), American Cancer Society, Atlanta, GA; Family Medicine and Public Health (A.H.S.), School of Medicine, University of California San Diego; Department of Epidemiology (L.S.), College of Public Health, University of Iowa, Iowa City; and Department of Medicine (J.E.M.) and Channing Division of Network Medicine (J.E.M., A.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. poeor@channing.harvard.edu.
Objective:
To examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS).
Methods:
We identified 275 individuals who developed ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS.
Results:
There was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartile: RR = 0.21 [95% CI 0.07, 0.58], p for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartile: RR = 1.65 [95% CI 0.99, 2.76], p for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartile: RR = 1.56 [95% CI 1.01, 2.41], p for trend = 0.054), but in multivariable models the association was only evident in men.
Conclusions:
The majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies.
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