Serum Vitamin D Levels Differentially Associated with AMD Stages in Older Adults

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Higher serum 25(OH)D level was related to an increased risk of early AMD in those aged 60 years or younger, and decreased risk of late AMD in individuals older than 60 years.

A new analysis revealed serum 25-hydroxyvitamin D (25[OH]D) had a differential association with early and late age-related macular degeneration (AMD) in adults in the United States.1

The research indicates a higher level of serum 25(OH)D was related to an increased risk of early AMD in patients aged 60 years or younger, but a decreased risk of late AMD in individuals older than 60 years, showing a non-linear L-shaped pattern.

“These results indicated that maintaining serum 25 (OH)D within certain levels may have the benefit of reducing the risk of early or late AMD for at-risk individuals,” investigators wrote. “Our unique findings add to the body of literature exploring the association between 25 (OH)D level and AMD risks.”

Investigators, led by Yihang Fu and Xiaoyun Chen, Zhongshan Ophthalmic Center, Sun Yat-sen University, cited the pathogenesis of AMD as multifactorial, comprising a complex interaction between aging, genetic susceptibility, and behavioral, and environmental risk factors. Discrepancies in understanding the relationship between serum vitamin D levels and AMD risk are generally caused by heterogeneity in study procedures. Thus, pooling existing data have drawn no definitive association on said risk.

Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007-2008 cycles allowed investigators to examine the relationship between 25(OH)D levels and the odds of different subtypes of AMD, with a focus on exploring their non-linear relationship. In each cycle, retinal photographs were taken and graded for the AMD stage.

To estimate the odds ratios (ORs) of AMD according to serum 25(OH)D level, investigators used logistic regression models adjusted for demographic variables, lifestyle variables, and medical history variables. Regression analysis was stratified by age (≥60 years versus <60 years subgroup). To investigate non-linear relations, the team used restricted cubic spline (RCS) logistic regression analysis to model the association between the AMD subtype and serum 25(OH)D level.

Ultimately, a total of 5041 eligible participants from NHANES data were included in the analysis. There were 405 participants (8.0%) with any AMD, including 354 with early stage (7.0%) and 51 with the late stage (1.0%). Participants with AMD were indicated to be older, of non-Hispanic White race, and had a higher prevalence of cardiovascular disease.

Upon analysis, investigators found the rate of early AMD increased with the increasing level of the serum 25(OH)D. Data showed the rate of early AMD in the deficiency group (<30 nmol/L) was 4.20%, while the sufficiency group (>50 nmol/L) increased to 7.92%. On the other hand, the rate of late AMD in the sufficiency group was lower than that of the deficiency group (1.06% versus 1.62%), and this trend was more apparent among patients over 60 years (2.06% versus 3.82%).

After adjustments for covariates, investigators found participants with higher levels of serum 25(OH)D had significantly greater odds of early AMD (OR, 1.65; 95% CI, 1.08 – 2.51) and decreased risk of late AMD (OR, 0.29; 95% CI, 0.09 – 0.88). When stratified by age, a positive association between the level of serum 25(OH)D and early AMD was observed in the 60 years and younger group (OR, 2.79; 95% CI, 1.08 – 7.29).

However, a negative relationship between the level of serum 25(OH)D and late AMD was detected in the 60 years and older group (OR, 0.24; 95% CI, 0.08 – 0.76). Meanwhile, the spline analysis indicated the risk of early AMD was positively associated with the level of serum 25(OH)D in an approximately linear pattern but revealed an L-shaped association between serum 25(OH)D and the risk of late AMD.

“Further prospective studies and randomized trials with long-term follow-up are needed to better evaluate the effectiveness of 25(OH)D on late AMD,” investigators wrote.


  1. Fu Y, Chen X, Luo S, Jiang S, Mao Y, Xiao W. Serum 25-Hydroxyvitamin D Is Differentially Associated with Early and Late Age-Related Macular Degeneration in the United States Population. Nutrients. 2023; 15(5):1216.