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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BMC
2025-05-01
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| 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 |
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| 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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| id | doaj-art-8d5fd8674a1247bfa334a60d0be5b9ca |
| institution | OA Journals |
| issn | 1475-2891 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Nutrition Journal |
| 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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