Pre-diagnostic plasma carotenoids, tocopherols and retinol levels, and risk of amyotrophic lateral sclerosis

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dc.contributor.authorO'Reilly, Éilis J.
dc.contributor.authorBjornevik, Kjetil
dc.contributor.authorFurtado, Jeremy D.
dc.contributor.authorPatel, Alpa V.
dc.contributor.authorWang, Ying
dc.contributor.authorKolonel, Laurence N.
dc.contributor.authorLe Marchand, Loïc
dc.contributor.authorAscherio, Alberto
dc.contributor.funderNational Institute of Neurological Diseases and Stroke
dc.contributor.funderNational Institutes of Health
dc.date.accessioned2026-05-26T09:50:07Z
dc.date.available2026-05-26T09:50:07Z
dc.date.issued2026-05-04
dc.description.abstractObjective: 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.en
dc.description.sponsorshipThis work was supported by a grant from the National Institute of Neurological Diseases and Stroke (R01 NS045893) awarded to A.A. The NHS is funded by the National Institutes of Health through grants UM1 CA186107 and R01 CA49449. The HPFS cohort is funded by the National Institutes of Health through grant U01 CA167552. The MEC cohort is funded by the National Institutes of Health through U01 CA164973. The American Cancer Society supports the maintenance and follow-up of the Cancer Prevention Studies.
dc.description.versionPublished Version
dc.format.extent10
dc.format.mimetypeapplication/pdfen
dc.identifier.authororcidO'Reilly, Éilis J.§0000-0002-6802-9956
dc.identifier.authororcidBjornevik, Kjetil
dc.identifier.authororcidFurtado, Jeremy D.
dc.identifier.authororcidPatel, Alpa V.
dc.identifier.authororcidWang, Ying
dc.identifier.authororcidKolonel, Laurence N.
dc.identifier.authororcidLe Marchand, Loïc
dc.identifier.authororcidAscherio, Alberto
dc.identifier.citationO'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
dc.identifier.doi10.1002/ana.78240
dc.identifier.endpage10
dc.identifier.issn0364-5134
dc.identifier.issued2
dc.identifier.journaltitleAnnals of Neurology
dc.identifier.otherORCID: /0000-0002-6802-9956/work/214627200
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/18882
dc.identifier.volume100
dc.language.isoen
dc.publisherJohn Wiley & Sons Inc.
dc.relation.urihttps://www.scopus.com/pages/publications/105038001911
dc.rights© 2026 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.statusPeer reviewed
dc.subjectPre-diagnostic plasma carotenoids
dc.subject[PublicHealth]
dc.subjectand tocoAmyotrophic lateral sclerosis (ALS)
dc.titlePre-diagnostic plasma carotenoids, tocopherols and retinol levels, and risk of amyotrophic lateral sclerosisen
dc.typeArticle (peer-reviewed)
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