Glaucoma and Vitamins A, C, and E Supplement Intake and Serum Levels in a Population-Based Sample of the United States
Wang SY, Singh K, Lin SC
Eye. 2013;27:487-494
Study Summary
For this study, Wang, Singh, and Lin took advantage of publicly available data from the 2005-2006 National Health and Nutrition Examination Survey, an annual cross-sectional series of interviews and examinations of the civilian, noninstitutionalized population of the United States. Data on health conditions, participants’ use of dietary supplements, and measurement of serum levels of these supplements were used to assess the relationship between self-reported glaucoma and the intake of vitamin A, C, and E in 2912 participants aged 40 years and older.
The intake of vitamins A, C, and E from dietary supplements and antacids were the primary predictor variables. Vitamins consumed during a 30-day period before the interview were averaged to determine daily intake. The population was divided into quartiles of intake for each of the vitamins, along with a “no intake” group. Serum levels of each vitamin (A, C, and E as alpha-tocopherol and gamma-tocopherol) were divided into quintiles, including undetectable or “zero serum” vitamin levels. Blood samples were collected in the morning and afternoon, and participants were not required to be in a fasting state.
The primary outcome variable was the presence or absence of self-reported glaucoma. Potential confounders before data analysis included age, sex, race, annual income, education, smoking (current and past), alcohol use, body mass index, and self-reported comorbid conditions (kidney disease, cancer, congestive heart failure, myocardial infarction, anemia, ocular conditions, and spherical equivalent on refraction).
The Rao-Scott Pearson-type chi squared and Wald tests were used to compare possible confounding variables (as listed above) between participants with and without self-reported glaucoma. Several multivariate logistic regression models were created and used to examine possible independent associations between supplemental vitamin intake or vitamin serum levels and self-reported glaucoma. Most confounding variables were excluded so that in the final adjusted model, no coexistent systemic medical condition was included, and only 1 visual comorbid conditions (self-reported diabetic retinopathy) was retained.
Study Findings
Of the 2912 participants, 203 reported a history of glaucoma, representing 5.42% of the US population.
Of interest, several demographic characteristics differed significantly between those who did and did not report having glaucoma:
• Mean age (67.4 vs 56.5 years, P = .0001);
• Race (P = .0023);
• Annual household income (P = .0466);
• Smoking status (P = .0006); and
• Daily number of alcoholic drinks consumed over the past year (P = .0228).
Multivariate regression models were constructed to compare the odds of self-reported glaucoma with supplemental vitamin intake. Model A was adjusted only for age, model B for age and other demographic characteristics, and model C for age, demographic characteristics, health-related behaviors, self-reported general health, and comorbid conditions.
Vitamin consumption and glaucoma. Supplemental consumers of vitamin A did not have increased odds of glaucoma, regardless of adjustment for confounders or amount of consumption. Participants who consumed vitamin C (≤ 100 mg/day) had significantly lower odds of glaucoma compared with those who consumed no vitamin C (model C odds ratio [OR], 0.34; 95% confidence interval [CI], 0.13-0.87). This correlation was also significant at the highest quartile dosage of vitamin C (>900 mg/day; model C adjusted OR, 0.47; 95% CI, 0.23-0.97).
Supplemental consumers of vitamin E at the highest quartile level (>400 IU/day) had higher odds of glaucoma compared with nonconsumers in the unadjusted model (OR, 3.40; 95% CI, 1.58-7.33), with persistent statistical significance despite adjustment for age and demographics (OR, 3.15; 95% CI, 1.29-7.72). However, after further adjustment for health-related behaviors and general health condition, this correlation was no longer statistically significant. Higher doses of vitamin E were associated with a higher prevalence of glaucoma (P = .004), and further adjusted models showed borderline significant Pvalues for this association; however, significant dose-response relationships were not observed in any model for the other vitamins.
Serum vitamin levels and glaucoma. Similar multivariate regression models were used to compare odds of self-reported glaucoma among participants on the basis of their serum values of vitamins A, C, and E. Participants with higher serum levels of vitamin A did not have lower odds of having glaucoma; however, there was a greater chance of having glaucoma with increasing quintiles of serum vitamin A in the unadjusted model (P = .002), which persisted after adjusting for age and demographics (P = .032). In model C, this association was borderline significant (P = .052). There was no association between serum vitamin C levels and the odds of glaucoma. Those with the highest quintile of serum alpha-tocopherol (>1720 µg/dL) had higher odds of having glaucoma compared with lower serum levels (OR, 1.59; 95% CI, 1.02-2.47) in the unadjusted model, and there was a trend of increasing odds of glaucoma with increasing quintiles of alpha-tocopherol levels (P = .009). However, these findings did not persist when adjusting for age. Furthermore, participants with serum gamma-tocopherol levels in the second to fourth quintiles (>114 µg/dL to >228 µg/dL) had reduced odds of glaucoma compared with those with the lowest quintile (≤ 114 µg/dL), but only in the unadjusted model.
In conclusion, no compelling evidence suggests a relationship between dietary supplementation with vitamins A or E and glaucomatous disease. Weak evidence suggests that vitamin C intake is associated with lower odds of glaucoma, although these findings should be investigated further before therapeutic recommendations can be established.
Viewpoint
Glaucoma is a chronic, irreversible optic neuropathy that can result in serious visual disability. There is no cure, and treatment is directed at stabilizing or delaying the progression of disease. Therefore, clinicians and scientists have sought ways to prevent the onset or progression of this potentially blinding condition. Although the mechanism of glaucoma is not wholly understood, the optic neuropathy is currently thought to be caused by some combination of neurotrophic, mechanical, and vascular factors. The neurotrophic theory holds that patients with glaucoma have some genetic predisposition to nerve fiber layer cell apoptosis.[1] The mechanical theory is that elevated intraocular pressures directly induce nerve fiber layer death. In the vascular theory, impaired perfusion of the optic nerve leads to nerve fiber layer death.[2]
The mainstay of glaucoma treatment has been targeted at lowering the intraocular pressure through medical or surgical means because this is the only mode of therapy repeatedly shown to delay glaucoma progression. More recently, diet and lifestyle modifications have been studied as potential approaches to treatment. The antioxidant vitamins A, C, and E have gained widespread publicity in recent years, especially in ophthalmology, as a result of their promise in delaying macular degeneration. This study explored a potential association between antioxidants and glaucomatous optic neuropathy.
Unfortunately, the answers remain elusive. Wang, Singh, and Lin did not find enough evidence that supplementation with vitamins A and E was related to the self-reported prevalence of glaucoma. However, it appears that vitamin C supplementation may have a protective effect. No dose-response relationship was demonstrated, and no beneficial association was supported by serum vitamin C levels. This is relatively consistent with previous findings; therefore, these results must be further evaluated before being applied to patient care. No definitive evidence currently supports antioxidant supplementation as a means of preventing glaucoma.[3,4]
The study’s conclusions were further limited by the low reliability of self-reported glaucoma and the lack of classification of type and severity of disease. Participants would need a full ophthalmic evaluation, including analysis of the optic nerve and intraocular pressure measurement, to confirm diagnosis of glaucoma. Moreover, data on vitamin use were limited to a 30-day history. Long-term vs short-term vitamin supplementation might have significantly different effects on glaucoma.
The study was still notable for being a large-scale population-based analysis that included measurements of serum vitamin levels as well as adjustment for multiple confounding factors. It represents a strong initial effort to analyze the potential impact of these popular vitamin supplements on the prevention of glaucoma.