ArticleAnnals of neurology2026
Pre-Diagnostic Plasma Carotenoids, Tocopherols and Retinol Levels, and Risk of Amyotrophic Lateral Sclerosis.
Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveOur goal was to examine whether pre-diagnostic plasma carotenoids and tocopherols are associated with amyotrophic lateral sclerosis (ALS).
methodsA 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.
resultsThe 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).
interpretationHigher 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;100:426-435.
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