We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Dietary ω-3 Polyunsaturated Fatty Acid Intake and Risk for Amyotrophic Lateral Sclerosis

Kathryn C. Fitzgerald, MSc1; Éilis J. O’Reilly, ScD1,7; Guido J. Falcone, MD2,6; Marjorie L. McCullough, ScD3; Yikyung Park, ScD4; Laurence N. Kolonel, MD, PhD5; Alberto Ascherio, MD, DrPH1,6,7
[+] Author Affiliations
1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
2Department of Neurology, Massachusetts General Hospital, Boston
3Epidemiology Research Program, American Cancer Society, Atlanta, Georgia
4Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
5Epidemiology Program, Cancer Center, University of Hawaii, Honolulu
6Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
7Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
JAMA Neurol. 2014;71(9):1102-1110. doi:10.1001/jamaneurol.2014.1214.
Text Size: A A A
Published online

Importance  Amyotrophic lateral sclerosis (ALS) is a severe progressive disease that cannot be prevented or cured. Diet-derived long-chain polyunsaturated fatty acids (PUFAs) are incorporated in brain lipids and modulate oxidative and inflammatory processes and could thus affect ALS risk and progression.

Objective  To examine the association between ω-6 and ω-3 PUFA consumption and ALS risk.

Design, Setting, and Participants  Longitudinal analyses based on 1 002 082 participants (479 114 women and 522 968 men) in 5 prospective cohorts: the National Institutes of Health–AARP 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. Diet was assessed via food frequency questionnaire developed or modified for each cohort. Participants were categorized into cohort-specific quintiles of intake of energy-adjusted dietary variables.

Main Outcomes and Measures  Cohort-specific multivariable-adjusted risk ratios (RRs) of ALS incidence or death estimated by Cox proportional hazards regression and pooled using random-effects methods.

Results  A total of 995 ALS cases were documented during the follow-up. A greater ω-3 PUFA intake was associated with a reduced risk for ALS. The pooled, multivariable-adjusted RR for the highest to the lowest quintile was 0.66 (95% CI, 0.53-0.81; P < .001 for trend). Consumption of both α-linolenic acid (RR, 0.73; 95% CI, 0.59-0.89; P = .003 for trend) and marine ω-3 PUFAs (RR, 0.84; 95% CI, 0.65-1.08; P = .03 for trend) contributed to this inverse association. Intakes of ω-6 PUFA were not associated with ALS risk.

Conclusions and Relevance  Consumption of foods high in ω-3 PUFAs may help prevent or delay the onset of ALS.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Figure 1.
Study-Specific and Pooled Multivariable Relative Risks

Study-specific and pooled multivariable relative risks and 95% CIs of amyotrophic lateral sclerosis for a 1 g/d increase in intake of ω-3 polyunsaturated fatty acid. The squares and horizontal lines correspond to the study-specific multivariable relative risk and 95% CI, respectively. The inverse of the variance is used to calculate study weight and is represented by the area of the square. The diamond displays the pooled multivariable relative risk and 95% CI. We observed no significant effect modification by sex (P = .74). CPS-II Nutrition indicates the Cancer Prevention Study II Nutrition Cohort; HPFS, Health Professionals Follow-up Study; MEC, the Multiethnic Cohort Study; NHS, the Nurses’ Health Study; and NIH-AARP, the National Institutes of Health–AARP Diet and Health Study.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Relationship of ω-3 Fatty Acids With Risk For Amyotrophic Lateral Sclerosis (ALS) Using Restricted Cubic Splines

The solid lines and shaded regions represent the hazard ratios of ALS for changes in intake relative to the median of specified polyunsaturated fatty acid (PUFA) and corresponding 95% CIs, respectively. The dotted vertical lines correspond to the fifth, 25th, 50th, 75th, and 95th percentiles for each fatty acid. To create these estimates, studies were pooled into a single data set and stratified by study, sex, age, and year of questionnaire. Each curve is also adjusted for smoking status, total vitamin E intake, total major carotenoid intake, body mass index, physical activity, education level, and energy intake.

Graphic Jump Location





You need to register in order to view this quiz.
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

3 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles