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Plasma caffeine level as a protective factor against age-related eye diseases: a two-sample Mendelian randomisation study

Published online by Cambridge University Press:  17 November 2025

Xinni Zheng ,
Yuze Mi ,
Yien Cao ,
Luyao Tong  and
Minghui Wan Open the ORCID record for Minghui Wan [Opens in a new window]
Xinni Zheng
Affiliation:
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China
Yuze Mi
Affiliation:
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China
Yien Cao
Affiliation:
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China
Luyao Tong
Affiliation:
The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China
Minghui Wan*
Affiliation:
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China
*
Corresponding author: Minghui Wan; Email: wanmh@eye.ac.cn
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Abstract

Traditional studies examining caffeine intake and age-related eye diseases (ARED) have shown inconsistent results, potentially related to variations in caffeine assessment methods. This two-sample Mendelian randomisation study investigated associations between plasma caffeine and four ARED: senile cataract, diabetic retinopathy (DR) and glaucoma and age-related macular degeneration (AMD). Summary data on genetically predicted plasma caffeine came from a genome-wide association study of 9876 European-ancestry participants across six population-based studies. ARED data were extracted from FinnGen Consortium clinical records. We further examined causal effects on glaucoma subtypes: primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) and assessed intraocular pressure (IOP) as a potential mediator. Higher genetically predicted plasma caffeine levels were associated with reduced risk of senile cataract (OR 0·84, 95 % CI 0·78, 0·90, P < 0·001), DR (OR 0·81, 95 % CI 0·74, 0·88, P < 0·001), glaucoma (OR 0·83, 95 % CI 0·73, 0·95, P = 0·008) and PACG (OR 0·74, 95 % CI 0·54, 0·99, P = 0·046). No associations were observed with AMD or POAG. Mediation analysis suggested that 41 % (95 % CI −0·14, −0·01) of caffeine’s effect on glaucoma was mediated by IOP. Our findings indicate that elevated plasma caffeine may protect against senile cataract, DR and glaucoma, but not AMD. Effects differed by glaucoma subtype, with IOP partially explaining the overall association. This study provides genetic evidence supporting caffeine’s role in mitigating ARED risk, highlighting its potential therapeutic implications.

Keywords

Plasma caffeineAge-related eye diseasesSenile cataractDiabetic retinopathyGlaucomaAge-related macular degenerationMendelian randomisation

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Type
Research Article
Information
British Journal of Nutrition , First View , pp. 1 - 7
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Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society

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