Caroline Helwick

November 20, 2012

CHICAGO — High intake of total calcium and iron appear to be associated with greater odds of self-reported glaucoma, researchers from the University of California, San Francisco, determined from an analysis of the National Health and Nutrition Examination Survey (NHANES).

The findings were reported here at the American Academy of Ophthalmology (AAO) 2012 Annual Meeting by Sophia Y. Wang, a medical student at the university. The senior author was Shan C. Lin, MD.

"But greater dietary intake of calcium and iron, however, was associated with a decreased odds of glaucoma in this study," Dr. Wang added. "We think dietary rather than supplementary intake of iron and calcium may be absorbed differently, in different forms, or act in biologically different ways."

Dr. Wang and colleagues concluded, therefore, that the increased odds for glaucoma may be driven by higher use of supplements.

The researchers examined dietary surveys (24-hour recalls) from NHANES participants for the years 2005 to 2008, which included 6316 persons aged 40 years and older. They estimated usual intake of calcium and iron on the basis of multiple measures of 24-hour recall, and these were put into quintiles. Age, sex, race, and comorbidities (including osteoporosis and anemia) were entered into the multivariate logistic regression model to produce an adjusted odds ratio for self-reported glaucoma.

Of these participants, 422 developed glaucoma. An examination of total calcium and iron intake (including dietary and supplement intake) showed that higher total intakes of each nutrient were associated with increased risks, Dr. Wang reported.

For total iron intake, odds ratios were 2.95 (2.52 - 3.45) for the 4th quintile and 1.58 (1.36 - 1.83) for the 5th, compared with 1.13 (0.94 - 1.36) for the 2nd and 0.95 (0.72 - 1.26) for the 3rd quintiles.

For total calcium intake, odds ratios were 1.58 (1.32 - 1.89) for the 4th quintile and 1.26 (0.96 - 1.64) for the 5th, compared with 1.14 (0.99 - 1.31) for the 2nd and 1.21 (1.03 - 1.43) for the 3rd quintiles.

Dietary Intake Had Opposite Effect on Risk

But the picture was different when they analyzed the nutrients in foods.

For dietary iron, odds ratios progressively diminished as intake lessened, from 0.82 (0.32 - 2.09) for the 2nd quintile to 0.70 (0.32 - 1.54) for the 3rd, 0.60 (0.18 - 1.93) for the 4th, and 0.39 (0.13 - 1.22) for the 5th.

For dietary calcium, the odds ratios were 0.82 (0.32 - 2.09) for the 2nd quintile, 0.70 (0.32 - 1.54) for the 3rd, 0.60 (0.18 - 1.93) for the 4th, and 0.39 (0.13 - 1.22) for the 5th.

The researchers were not able to accurately determine intake of supplements alone, she said.

"Those with higher levels of total calcium and iron tended to have higher odds ratios, although for dietary nutrients, the trend was in the opposite direction. We think that supplement use is driving the difference, but because of limitations in this methodology, we could not isolate supplement use," Dr. Wang said. She added that a previous study with a different approach to data collection did, in fact, find that greater use of supplements was associated with greater odds ratios.

Dr. Wang offered an explanation as to how these nutrients may affect glaucoma risk. "Based on these results and previous studies, we can hypothesize that high total intakes of calcium or iron, driven by supplement use, may serve as potential environmental stressors," she said. "And this, combined with a background of already impaired calcium or iron homeostasis due to aging or other factors, may lead to damage of the trabecular meshwork or ganglion cell death, thus ultimately increasing the risk of glaucoma."

She emphasized that the findings are hypothesis-generating, and it is premature to make a recommendation. "We need a prospective study to tease out the differences," she said.

Joel Schuman, MD, the Eye & Ear Foundation professor and chairman of ophthalmology at the University of Pittsburgh, Pennsylvania, and the director of the Eye Center there, commented on the findings.

"The study by Wang et al suggests that supplemental calcium and iron are associated with a higher risk of glaucoma; however, dietary calcium and iron are associated with a lower risk of glaucoma. This is certainly a confusing result and highlights a problem with large-scale self-reporting databases. Glaucoma was self-reported, as was intake," he noted.

"The hypothesis that high consumption of certain elements, in particular, elements associated with oxidative damage, would result in glaucoma is attractive, but the proof of that hypothesis will require further study with more definitive results," Dr. Schuman concluded.

Dr. Wang and Dr. Schuman have disclosed no relevant financial relationships.

American Academy of Ophthalmology (AAO) 2012 Annual Meeting. Abstract 126. Presented November 11, 2012.