From Bones to Eyes: A Vitamin with Much Broader Functions
Vitamin D has traditionally been associated with skeletal health, intestinal calcium absorption, and the regulation of phosphate-calcium metabolism. Today, however, we know that its biological function is much broader.
Vitamin D acts through the vitamin D receptor (VDR), a nuclear receptor capable of modulating the expression of numerous genes. The vitamin D-VDR system has also been identified in ocular tissues and is being studied for its possible role in regulating inflammation, immune response, oxidative stress, angiogenesis, and vascular function.
These mechanisms are particularly interesting because many of the processes involved in eye aging are the same ones that characterize numerous chronic conditions: low-grade inflammation, metabolic alterations, oxidative stress, and vascular dysfunction.
A systematic review of the literature has identified associations between vitamin D and several eye diseases, especially age-related macular degeneration, diabetic retinopathy, and dry eye syndrome, while the evidence regarding glaucoma remains more limited. The authors nevertheless emphasize that the association observed in epidemiological studies does not necessarily demonstrate a causal relationship.
It is precisely this distinction that becomes fundamental when talking about prevention.
The New Major Prospective Study: A Possible Biological Threshold
An important contribution arrived in 2025 from a major prospective analysis conducted using data from the UK Biobank.
The study examined 322,953 participants, assessing the serum concentration of 25-hydroxyvitamin D [25(OH)D] and the subsequent development of four major eye diseases: cataracts, primary open-angle glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy.
During a median follow-up of approximately 13 years, over 34,000 cases of cataracts, more than 5,000 cases of AMD, over 4,000 cases of open-angle glaucoma, and more than 2,000 cases of diabetic retinopathy were recorded.
The most interesting result was not simply the identification of a linear relationship between vitamin D and disease, but the identification of a possible threshold around 50 nmol/L.
In participants with values below this concentration, every 10 nmol/L increase in 25(OH)D was associated with:
- approximately 3.5% reduction in the risk of cataracts;
- approximately 4.2% reduction in the risk of AMD;
- approximately 6% reduction in the risk of diabetic retinopathy.
Above 50 nmol/L, however, the analysis did not show further statistically significant benefits for these diseases. For primary open-angle glaucoma, no significant association was observed.
This data must be interpreted carefully: these are epidemiological associations, not a demonstration that bringing vitamin D to 50 nmol/L through supplementation prevents these diseases.
However, it is an interesting result because it introduces a fundamental concept: more vitamin D does not necessarily mean more protection.
When Vitamin D Becomes a Matter of Balance
Vitamin D is one of the best examples of how important it is to distinguish between correcting a deficiency and indiscriminate supplementation.
The body does not need increasingly higher concentrations of a micronutrient to achieve a greater benefit. Biological systems are regulated within balance ranges, and when a deficiency is corrected, the physiological benefit may gradually diminish.
In the major prospective study of 2025, the relationship with cataracts and AMD was found to be consistent with a non-linear trend, while for diabetic retinopathy, an L-shaped relationship was observed. In all three cases, the turning point was identified around 50 nmol/L.
This does not mean that 50 nmol/L should be considered a universal value or a valid therapeutic target for everyone. The concentration of 25(OH)D must be interpreted by considering age, nutritional status, sun exposure, clinical conditions, kidney function, calcium metabolism, and other individual factors.
The most accurate message is therefore one of normalizing any deficiencies, avoiding turning vitamin D into a kind of generalized preventive pharmacological intervention.
Inflammation and Metabolism: The Possible Bridge Between Vitamin D and the Retina
But why should a vitamin traditionally associated with bone metabolism have a relationship with the health of the retina and the lens?
One of the possible explanations concerns its ability to interfere with biological processes that participate in eye aging.
Vitamin D and its active metabolite, calcitriol, are involved in the regulation of the immune response and gene expression. Experimental studies have highlighted the ability of the vitamin D-VDR system to modulate mediators of inflammation, angiogenesis, and cellular functions in the ocular environment.
In the new prospective study, part of the association between vitamin D and some eye diseases seemed to be explained precisely by changes in low-grade systemic inflammation and glucose-lipid metabolism.
In particular, mediation analyses identified the so-called low-grade inflammation index and the triglyceride-glucose index (TyG), an indicator linked to insulin resistance, as possible intermediates in the relationship between vitamin D and the risk of cataracts and diabetic retinopathy.
This is an important result because it links eye health to overall metabolic health.
The eye, in fact, is not an organ isolated from the rest of the body. The retina is one of the most metabolically active tissues and has an extremely delicate vascular network. Persistent alterations in blood sugar, insulin resistance, lipid balance, oxidative stress, and inflammation can compromise the integrity of the retinal microcirculation over time.
Vitamin D and Diabetic Retinopathy: A Biologically Plausible Relationship
Diabetic retinopathy represents one of the most evident examples of the link between systemic metabolism and eye health.
Chronic hyperglycemia promotes oxidative stress, advanced glycation end products, endothelial alterations, inflammation, and damage to the blood-retinal barrier. The resulting microangiopathy can progressively compromise the retina.
Vitamin D has been studied precisely in relation to these mechanisms. A review of pathophysiological and clinical aspects has highlighted potential effects on endothelial function, oxidative stress, inflammation, and the vascular systems involved in diabetic retinopathy. However, the same literature emphasizes that intervention evidence is still insufficient to establish that vitamin D supplementation modifies the natural history of the disease.
More recent intervention data also call for caution. In 2026, an exploratory uncontrolled study assessed the correction of vitamin D deficiency in people with type 2 diabetes without retinopathy or with mild-to-moderate non-proliferative forms. After correcting the deficiency, no significant changes were observed in most macular perfusion parameters measured by OCT angiography, nor a significant relationship between the increase in 25(OH)D and the improvement of visual function.
Biological plausibility, therefore, does not yet equate to therapeutic proof.
Macular Degeneration: Epidemiological Association
Age-related macular degeneration is a complex disease in which age, genetics, smoking, metabolism, inflammation, oxidative stress, and vascular factors interact.
Numerous observational studies have highlighted a possible relationship between higher concentrations of vitamin D and a lower probability of AMD. The systematic review of the literature has gathered several studies that support this association.
But when moving from observational studies to randomized studies, the picture becomes more cautious.
In the major VITAL-AMD study, 25,871 adults were followed for a median of 5.3 years. Participants received 2,000 IU per day of vitamin D3 or placebo, as part of a randomized trial. Supplementation did not produce a significant reduction in the overall incidence or progression of AMD.
This result is fundamental for correctly interpreting the new 2025 study.
Having lower levels of vitamin D can be associated with a higher risk of AMD, but it has not yet been demonstrated that pharmacologically increasing vitamin D in non-deficient people reduces the risk of developing it.
The Story for Cataracts Is Also More Complex
Cataracts are characterized by the progressive loss of lens transparency and represent one of the main causes of visual impairment in old age.
Oxidative stress, protein alterations, cellular metabolism, age, and metabolic conditions contribute to its formation. It is therefore plausible that nutritional and metabolic factors can influence its risk.
The major prospective study of 2025 found a relationship between lower concentrations of 25(OH)D and a higher risk of cataracts, especially below the threshold of approximately 50 nmol/L.
But even in this case, randomized studies downsize the interpretation.
An analysis of the D-Health trial followed 19,925 older adults randomized to 60,000 IU of vitamin D3 per month or placebo for up to five years. The incidence of cataract surgery was substantially identical in the two groups: the hazard ratio was 1.02, with no significant reduction associated with supplementation.
Therefore, correcting a vitamin D deficiency remains physiologically important, but it cannot be presented as a proven strategy to avoid cataracts.
And Glaucoma?
In the relationship between vitamin D and glaucoma, the evidence is even more uncertain.
The major prospective study did not find a significant association between serum concentration of 25(OH)D and primary open-angle glaucoma.
Several biological mechanisms have been hypothesized through which vitamin D could theoretically influence intraocular pressure, inflammation, and neurovascular function, but the available evidence does not allow vitamin D to be attributed a consolidated preventive or therapeutic role in glaucoma.
This is another example of the importance of not generalizing the concept of “vitamin D and eye health” to all eye diseases.
The Retina as a Mirror of Metabolic Health
One of the most interesting aspects emerging from research is the need to consider eye health within a systemic model.
The retina is characterized by extremely high energy consumption. Its functionality depends on mitochondrial efficiency, oxygen supply, microcirculation stability, and the ability to keep free radicals under control.
With advancing age, oxidative stress, inflammation, and metabolic alterations may increase. Diabetes, obesity, insulin resistance, hypertension, and dyslipidemia can add further stress conditions.
In this scenario, vitamin D could represent one of the elements that participate in the regulation of the biological environment in which the eye operates.
But it is not the only one.
Diet, blood sugar control, blood pressure, lipid profile, physical activity, smoking cessation, adequate sun exposure, and cardiovascular risk factor control remain much broader components of a visual health protection strategy.
Vitamin D should therefore be considered within this framework and not as an isolated solution.
Deficiency, Insufficiency, and Excess: Why Measuring Can Be More Useful Than Assuming
A common misconception is that if a substance is physiologically useful, taking increasingly larger amounts is automatically beneficial.
This is not the case with vitamin D.
Serum concentration of 25(OH)D is the main parameter used to assess vitamin status. However, the clinical significance of the result must be interpreted by a doctor in light of the individual's situation.
The 2025 data is particularly interesting because it suggests that the benefit associated with increased vitamin D is concentrated mainly in people with low levels and that beyond a certain threshold no additional benefit is observed.
This does not justify establishing a single “perfect” concentration valid for everyone and, above all, does not demonstrate that it is necessary to artificially reach 50 nmol/L to prevent an eye disease.
The most rational approach is another: identify any deficiencies, correct them when necessary, and subsequently avoid unjustified supplementation.
The lesson of vitamin D: prevention is not a race toward excess
Research on vitamin D and the eye offers a lesson that goes beyond this single vitamin.
Physiology does not necessarily follow a linear relationship in which “more is better.” Many biological systems operate according to dose-response curves characterized by thresholds, plateaus, and ranges of effectiveness.
The 2025 study reinforces precisely this perspective.
Bringing an organism from a state of deficiency toward an adequate level may be associated with an improved risk profile. Continuing to increase the concentration beyond that point, however, may not produce further benefits.
For eye health, this concept takes on a particular meaning. The prevention of cataracts, AMD, and diabetic retinopathy cannot be entrusted to a single micronutrient, but must be part of a broader strategy of healthy ageing, in which nutrition, metabolism, physical activity, and control of risk factors proceed together.
An integrated perspective for visual health
Vitamin D therefore deserves attention in the field of ophthalmology as well, but with a balanced approach.
Epidemiological and biological evidence suggests an interesting relationship between low levels of 25(OH)D and certain eye diseases, while the large 2025 prospective study identifies a possible threshold around 50 nmol/L for cataracts, AMD, and diabetic retinopathy.
Randomized studies, however, show that simply administering vitamin D to older people does not guarantee the prevention of cataracts and has not demonstrated an overall effect on the prevention or progression of AMD.
The scientifically soundest message is therefore one of balance.
Vitamin D must be present in sufficient amounts to perform its physiological functions, but it must not be turned into an indiscriminate intervention. In the presence of a possible deficiency, the assessment of 25(OH)D and any supplementation must be personalized and, especially when high doses are used, managed under medical supervision.
Eye health is, in fact, born from the interaction of many factors. Vitamin D can be one of the elements of this balance, but it does not replace ophthalmic prevention, the control of metabolic and cardiovascular diseases, proper nutrition, and lifestyles conducive to longevity.
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Bibliographic references
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- Millen AE, et al. Vitamin D and Ocular Diseases: A Systematic Review. Nutrients. 2022. PMID: 35457041.
- Nebbioso M, Buomprisco G, Pascarella A, Pescosolido N. Modulatory effects of 1,25-dihydroxyvitamin D3 on eye disorders: A critical review. Critical Reviews in Food Science and Nutrition. 2017;57(3):559-565. doi:10.1080/10408398.2014.893504.
- Christen WG, et al. Effect of Vitamin D and ω-3 Fatty Acid Supplementation on Risk of Age-Related Macular Degeneration: An Ancillary Study of the VITAL Randomized Clinical Trial. JAMA Ophthalmology. 2020.
- Neale RE, et al. Vitamin D Supplementation and the Incidence of Cataract Surgery in Older Australian Adults. Ophthalmology. 2023;130(3):313-323. doi:10.1016/j.ophtha.2022.09.015.
- Fekri S, et al. Vitamin D supplementation in diabetic retinopathy: an optical coherence tomography angiography study of changes in macular perfusion. International Journal of Retina and Vitreous. 2026;12:51. doi:10.1186/s40942-026-00822-5.
- Role of vitamin D in diabetic retinopathy: Pathophysiological and clinical aspects. International Journal of Molecular Sciences. 2020.
