Age-Related Macular Degeneration and Calcium Supplements: Is There a Reason to Change Clinical Practice?

Charles C. Wykoff, MD, PhD


August 14, 2015

In This Article

Study Limitations

Many inconsistencies within the identified association between AMD and calcium supplementation must be considered. For example, no association between AMD and calcium supplement use was found among participants younger than 68 years of age. Rather, this relationship was only identified in participants older than 68 years of age. Furthermore, no dose-response relationship was identified between quintiles of calcium intake and AMD, a finding that one might anticipate if calcium served a legitimate role in AMD pathogenesis. The authors concluded that the association "suggests a threshold above which susceptible individuals are most vulnerable to the effects of calcium supplementation." This is merely a hypothesis, one that may just as likely be correct as incorrect.

Even with sophisticated statistical analyses that include multivariate logistic regression modeling, application of their results remains fundamentally limited. Most important is that this is an observational analysis and therefore cannot demonstrate causation. Demonstrating that calcium supplements cause a particular outcome would require a longitudinal analysis in which new cases of AMD were identified among participants consuming varying amounts of calcium. This report described an interesting hypothesis-generating observation, which demands substantial further investigation before clinical guidelines are reconsidered.

Beyond this critical limitation, other major limitations are evident. First, NHANES is a questionnaire-based assessment for which participants recall the supplements they ingested within the immediately preceding 30 days. From these data, it is impossible to determine the duration of supplementation. The analysis did not differentiate between participants who consumed calcium supplements for less than 30 days and those who had been consuming calcium supplements for much longer.

Second, dietary calcium from sources other than supplements and antacids was not assessed. Therefore, total calcium intake is unknown and unable to be analyzed. This is particularly relevant in light of the recent analysis of the prospective observational Blue Mountain Eye Study (BMES) involving 2037 adults, with apparently discordant results. Gopinath and colleagues[17] identified an increased risk of developing incident late AMD among participants with lower total dietary calcium intake over 15 years. When considering the relationship between calcium consumption and human diseases such as AMD, total calcium intake, including both dietary and supplemental sources, must be considered.

Finally, there may be limited longitudinal reliability of supplement consumption reporting in NHANES. For example, in NHANES I, 34% of participants who reported consuming daily supplements were no longer daily users at follow-up, and 25% of participants who reported no supplements were taking supplements at follow-up,[18] suggesting that many participants change their supplement consumption behavior over time.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.