News Author: Laurie Barclay, MD

May 1, 2006 — A diet high in omega-3 polyunsaturated fatty acids (PUFAs) and vitamin E reduces the risk for amyotrophic lateral sclerosis (ALS), according to the results of a case-control study reported in the April 28 Online First issue of the Journal of Neurology, Neurosurgery, and Psychiatry.

"Despite several studies that investigated environmental exposures in relation to ALS, age, gender and smoking are the only established risk factors," write J. H. Veldink, MD, from the University Medical Center Utrecht in The Netherlands, and colleagues. "Several, not mutually exclusive, pathological processes may contribute to motor neurone death in ALS in a so-called convergence model, including oxidative stress, mitochondrial dysfunction, protein misfolding, axonal strangulation, apoptosis, inflammation, glutamate excitotoxicity and defects in neurotrophin biology. Nutrients are factors that could influence these processes and thereby the risk of developing ALS or its clinical expression."

During 2001-2002, 132 patients referred to the authors' clinic with definite, probable, or possible ALS according to El Escorial criteria, but without a familial history of ALS, were enrolled in a case-control study and matched with 220 healthy controls. All subjects completed a food frequency questionnaire, and multivariate logistic regression analysis was performed with adjustment for confounding factors, including sex, age, level of education, energy intake, body mass index, and smoking.

High PUFA and vitamin E intake was associated with a reduced risk of developing ALS (PUFA: odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2 - 0.7; P = .001; vitamin E: OR, 0.4; 95% CI, 0.2 - 0.7; P = .001). PUFA and vitamin E appeared to act synergistically. In a combined analysis, the trend OR for vitamin E was further reduced from 0.67 to 0.37 (P = .02) and PUFA from 0.60 to 0.26 (P = .005), with a significant interaction term (P = .03). The intake of flavonols, lycopene, vitamin C, vitamin B₂, glutamate, calcium, or phytoestrogens did not affect the risk of developing ALS.

"A high intake of PUFAs and vitamin E is associated with a 50-60% decreased risk of developing ALS, and these nutrients appear to act synergistically," the authors write. "Vitamin E may act directly to reduce the risk of ALS as a known inhibitor of lipid peroxidation, but it could also act indirectly through inhibition of peroxidation of nutritional PUFAs."

Study limitations include the possible influence of overmatching of controls, recall bias, and the non–population-based design.

"Importantly, this case-control study took into account the possible influence of preclinical disease in assessing dietary intake and adjusted for important confounders, including total energy intake, according to the residual method," the authors write. "A population-based case-control study is presently being conducted to generate class I evidence."

ZonMw, The Netherlands Organization for Health Research and Development, supported this study. The authors have disclosed no relevant financial disclosures.