In the news: Antioxidants, Vitamin C Linked to Lower Risk of Diabetic Retinopathy

Antioxidant Vitamins Linked to DR Risk

The development of diabetic retinopathy (DR) is predominantly a metabolically driven process, and vitamins and minerals play an important role in maintaining metabolic homeostasis. However, there is little information guiding clinical practice in the role these micronutrients may play in DR.

A team of Australian and Chinese researchers set out to investigate the associations between circulating vitamins A, C, D, E, and carotenoids and the risk of DR by conducting a cross-sectional study in participants of the U.S. National Health and Nutrition Examination Survey (NHANES) and a meta-analysis of relevant studies published from 1990 through 2020(1) .

In brief, the NHANES study found that a higher serum vitamin C level was associated with a 40% lower risk of DR in the diabetic population. No significant associations were observed between DR and serum levels of vitamins A, D, E or carotenoids.

The meta-analysis confirmed the significantly lower circulating vitamin C levels in DR participants compared with controls. Lower serum levels of vitamins D and E, however, were also significantly associated with a higher DR risk in the meta-analysis.

The NHANES study included 517 diabetics aged 40 years and older. The presence of DR was determined based on non-mydriatic fundus photographs. The meta-analysis included 35 studies, comparing 1,056 participants with DR to 920 controls, diabetics without DR.

Of the 517 included participants in the NHANES analysis, DR was identified in 159 (25.17%). After adjusting for multiple confounders, only serum vitamin C was associated with a lower risk of DR (odds ratio [OR]: 0.60).

In the meta-analysis, the pooled weighted mean difference (WMD) of circulating vitamin C was 11.01. For vitamins D and E, the pooled WMD was 3.06 and -3.03 respectively. No associations were identified between DR and vitamin A or carotenoids, including alpha carotene, beta carotene and lutein/zeaxanthin.

Perhaps the most prominent finding in this study is the inverse association seen between circulating antioxidant vitamin C and DR. That association has been consistently reported in previous studies, and oxidative stress has been implicated as a key underlying mechanism for DR.

A recently published meta-analysis(2) found that across most studies, vitamin C levels are at least 30% lower among people with type 2 diabetes.

That meta-analysis of randomized, controlled trials investigated the efficacy of oral vitamin C supplementation in improving glycemic control, cardiovascular risk factors, and oxidative stress in people with type 2 diabetes. In the 28 included studies, participants took 200-3,000 mg of vitamin C per day for 14 days to 1 year.

The main findings were that vitamin C resulted in statistically significant, clinically meaningful decreases in blood pressure and HbA1c. Based on the GRADE system there was less certainty with HbA1c effect, though the effect size increased in longer and larger studies. HbA1c was lowered by 0.54% (as reference, Metformin lowers HbA1c by a little more than 1%). The results of this systematic review and meta-analysis suggest that vitamin C may benefit type 2 diabetics in general.

References

1. Xiong R, et al. Micronutrients and diabetic retinopathy: Evidence from the National Health and Nutrition Examination Survey and a meta-analysis. Am J Ophthalmol. 238:141-156, 2022.
2. Mason SA, et al. Effects of Vitamin C Supplementation on Glycemic Control and Cardiovascular Risk Factors in People with Type 2 Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis of Randomized Controlled Trials. Diabetes Care. 44:618–630, 2021.