Pre-diagnostic Plasma Polyunsaturated Fatty Acids and the Risk of Amyotrophic Lateral Sclerosis (S4.003)

Objective: To examine the association between pre-diagnostic plasma polyunsaturated fatty acid levels and amyotrophic lateral sclerosis (ALS) risk.

Background: Potential etiological mechanisms in ALS such as oxidative stress, excitotoxicity, and inflammation are modulated by polyunsaturated fatty acids in brain neural plasma membranes. Individuals with higher dietary intake of n−3 polyunsaturated fatty acids had lower risk of ALS. On the other hand, high dose n−3 intake in an animal model of ALS appeared to accelerate progression.

Design/Methods: We matched 275 individuals who developed ALS while enrolled in five US prospective cohorts to two enrolled controls of the same age, sex and race. Fatty acids, expressed as percentages of total fatty acids, were measured by gas liquid chromatography. Within and between sample coefficients of variation ranged from <1% to 10% across the eleven polyunsaturated fatty acids detected. Gender-specific multivariable-adjusted risk ratios (RR) of ALS incidence or death were estimated by Cox proportional hazards regression and pooled using inverse-variance weighting.

Results: Individuals with higher plasma alpha-linolenic acid had a lower risk of ALS: in age- and matching factor-adjusted analyses, the RR=0.63 (95% CI: [0.41,0.96] p-for-trend=0.018) comparing quartile 4 to quartile 1. Adjustment for BMI, smoking, education attained, plasma urate and other n−3 polyunsaturated fatty acids, did not materially change the findings. Further adjustment for arachidonic acid attenuated findings in women but not men (p-for-trend= 0.002). Individuals with higher plasma arachidonic acid had a higher risk of ALS: in age- and matching factor-adjusted analyses, RR=1.64 (95% CI: [1.06, 2.54] p-for-trend=0.018) comparing quartile 4 to quartile 1. Adjustment for BMI, smoking, education attained, plasma urate, other n−6 and n−3 polyunsaturated fatty acids did not materially change the findings.

Conclusions: Polyunsaturated fatty acid profile may modulate the risk of ALS. Consumption of foods high in alpha-linolenic acid may help prevent or delay the onset of ALS.

Disclosure: Dr. O'Reilly has nothing to disclose. Dr. Bjornevik has nothing to disclose. Dr. McCullough has nothing to disclose. Dr. Kolonel has nothing to disclose. Dr. Le Marchand has nothing to disclose. Dr. Manson has nothing to disclose. Dr. Ascherio has nothing to disclose.