Pre-diagnostic plasma carotenoids, tocopherols and retinol levels, and risk of amyotrophic lateral sclerosis
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Date
2026-05-04
Authors
O'Reilly, Éilis J.
Bjornevik, Kjetil
Furtado, Jeremy D.
Patel, Alpa V.
Wang, Ying
Kolonel, Laurence N.
Le Marchand, Loïc
Ascherio, Alberto
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Abstract
Objective: Our goal was to examine whether pre-diagnostic plasma carotenoids and tocopherols are associated with amyotrophic lateral sclerosis (ALS). Methods: A nested case–control study within 4 United States cohorts, where 154 participants with pre-diagnostic blood-draw, were diagnosed during follow-up with amyotrophic lateral sclerosis (ALS). Controls were randomly selected from participants alive on the date a case was diagnosed, matched 2:1 by cohort, sex, age, race/ethnicity, fasting-status, time of blood-draw. Carotenoid and tocopherol levels were quantified by high-performance liquid-chromatography with diode array-detector. ALS incidence or death rate ratios (RR) were estimated using conditional logistic regression adjusting for body mass index, smoking status, physical activity, cholesterol, and urate levels. Results: The association between beta-carotene and ALS varied by sex (p-for-interaction = 0.007). After matched- and multivariable-adjustment, women with higher cis-, trans- and total beta-carotene had lower incidence of ALS (RR for 1-standard deviation [SD] increase in total beta-carotene: 0.68; 95% CI: 0.48–0.98; p = 0.038), whereas a positive association was seen in men (1-SD increase: RR = 1.44; 95% CI: 1.03–2.01; p = 0.033). However, after further adjustment for other correlated carotenoids, the association in men was attenuated, whereas it remained significant in women. Women with higher beta-cryptoxanthin, but not men, had a lower risk of ALS (1-SD increase: RR = 0.67; 95% CI: 0.48–0.94; p = 0.02; p-for-interaction = 0.12). Alpha-carotene, lutein-zeaxanthin, lycopene, retinol, and tocopherols were not associated with ALS, except for a borderline inverse association of gamma-tocopherol in men (RR = 0.74; 95% CI: 0.54–1.01; p = 0.059). Interpretation: Higher pre-diagnostic plasma levels of beta-carotene and beta-cryptoxanthin in women and gamma-tocopherol in men were suggestively associated with lower ALS risk. Other carotenoids or tocopherols were not clearly associated with ALS. ANN NEUROL 2026.
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© 2026 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Keywords
Pre-diagnostic plasma carotenoids , [PublicHealth] , and tocoAmyotrophic lateral sclerosis (ALS)
Citation
O'Reilly, É J, Bjornevik, K, Furtado, J D, Patel, A V, Wang, Y, Kolonel, L N, Le Marchand, L & Ascherio, A 2026, 'Pre-diagnostic plasma carotenoids, tocopherols and retinol levels, and risk of amyotrophic lateral sclerosis', Annals of Neurology, vol. 100, no. 2, pp. 1-10. https://doi.org/10.1002/ana.78240
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