Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study

Abstract Background Investigations into the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of age-related ocular diseases have yielded inconsistent results. Thus, we aimed to provide robust longitudinal evidence, identify optimal serum thresholds, and explore the underly...

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Main Authors: Zhiqian Huang, Shuyu Liu, Chao Chen, Keke Zhang, Yu Du, Xiangjia Zhu
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Nutrition Journal
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Online Access:https://doi.org/10.1186/s12937-025-01156-y
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author Zhiqian Huang
Shuyu Liu
Chao Chen
Keke Zhang
Yu Du
Xiangjia Zhu
author_facet Zhiqian Huang
Shuyu Liu
Chao Chen
Keke Zhang
Yu Du
Xiangjia Zhu
author_sort Zhiqian Huang
collection DOAJ
description Abstract Background Investigations into the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of age-related ocular diseases have yielded inconsistent results. Thus, we aimed to provide robust longitudinal evidence, identify optimal serum thresholds, and explore the underlying mechanisms. Methods We analyzed data of 322,953 participants from the UK Biobank. The serum 25(OH)D levels were assessed using chemiluminescent immunoassay. Outcomes were incidences of cataract, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. Nonlinear relationships were explored using restricted cubic splines, and mediation analyses were performed to delineate potential mechanistic pathways. Results Our findings revealed U-shaped associations for cataract and AMD, and L-shaped associations for DR (all P < 0.05), with an optimal threshold of approximately 50 nmol/L, while no association with POAG was observed. Below this threshold, each 10 nmol/L increase in serum 25(OH)D concentration was linked to a 3.5%, 4.2%, and 6.0% reduction in the risk of cataract, AMD, and DR, respectively (HR 0.965 [95% CI 0.951–0.980]; HR 0.958 [95% CI 0.921–0.997]; HR 0.940 [95% CI 0.894–0.989], respectively), while above 50 nmol/L, no significant protective effects were observed. Mediation analyses revealed that the low-grade inflammation score and triglyceride-glucose index may mediate the effects of serum 25(OH)D on cataract and DR. Conclusions This study identified 50 nmol/L as the optimal serum 25(OH)D threshold for reducing risks of cataract, AMD and DR, with no benefits beyond this level. The protective effects may be mediated through modulation of inflammation and glucolipid metabolism pathways. The threshold effects highlight the importance of targeted vitamin D supplementation under careful monitoring of serum levels to optimize ocular health outcomes.
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spelling doaj-art-8d5fd8674a1247bfa334a60d0be5b9ca2025-08-20T02:00:06ZengBMCNutrition Journal1475-28912025-05-0124111210.1186/s12937-025-01156-yOptimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort studyZhiqian Huang0Shuyu Liu1Chao Chen2Keke Zhang3Yu Du4Xiangjia Zhu5Eye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityEye Institute, Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityAbstract Background Investigations into the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of age-related ocular diseases have yielded inconsistent results. Thus, we aimed to provide robust longitudinal evidence, identify optimal serum thresholds, and explore the underlying mechanisms. Methods We analyzed data of 322,953 participants from the UK Biobank. The serum 25(OH)D levels were assessed using chemiluminescent immunoassay. Outcomes were incidences of cataract, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. Nonlinear relationships were explored using restricted cubic splines, and mediation analyses were performed to delineate potential mechanistic pathways. Results Our findings revealed U-shaped associations for cataract and AMD, and L-shaped associations for DR (all P < 0.05), with an optimal threshold of approximately 50 nmol/L, while no association with POAG was observed. Below this threshold, each 10 nmol/L increase in serum 25(OH)D concentration was linked to a 3.5%, 4.2%, and 6.0% reduction in the risk of cataract, AMD, and DR, respectively (HR 0.965 [95% CI 0.951–0.980]; HR 0.958 [95% CI 0.921–0.997]; HR 0.940 [95% CI 0.894–0.989], respectively), while above 50 nmol/L, no significant protective effects were observed. Mediation analyses revealed that the low-grade inflammation score and triglyceride-glucose index may mediate the effects of serum 25(OH)D on cataract and DR. Conclusions This study identified 50 nmol/L as the optimal serum 25(OH)D threshold for reducing risks of cataract, AMD and DR, with no benefits beyond this level. The protective effects may be mediated through modulation of inflammation and glucolipid metabolism pathways. The threshold effects highlight the importance of targeted vitamin D supplementation under careful monitoring of serum levels to optimize ocular health outcomes.https://doi.org/10.1186/s12937-025-01156-ySerum 25(OH)DAge-related ocular diseaseNonlinear associationInflammatory statusTyG index
spellingShingle Zhiqian Huang
Shuyu Liu
Chao Chen
Keke Zhang
Yu Du
Xiangjia Zhu
Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study
Nutrition Journal
Serum 25(OH)D
Age-related ocular disease
Nonlinear association
Inflammatory status
TyG index
title Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study
title_full Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study
title_fullStr Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study
title_full_unstemmed Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study
title_short Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study
title_sort optimizing serum 25 oh d levels to mitigate the risk of age related ocular diseases insights from a large scale prospective cohort study
topic Serum 25(OH)D
Age-related ocular disease
Nonlinear association
Inflammatory status
TyG index
url https://doi.org/10.1186/s12937-025-01156-y
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