To the Editor:
Dr. Richard Bone and colleagues recently published an article  [Targeting AMD with a Critical Carotenoid, March 2011] that claims benefits of meso-zeaxanthin, the non-dietary component of the macular pigment. Bone and Landrum discovered that meso-zeaxanthin was a constituent of the macular pigment in 1993. Meso-zeaxanthin (MZ) is not found in substances consumed in a typical diet. In a study published in 1986, Maoka et al. identified MZ in turtle fat, shrimp carapace and fish skin and did not detect MZ in foods that contain high concentrations of zeaxanthin such as corn and egg yolks.4 However, the extraction procedure used in this study may have in fact generated MZ as subsequent studies have failed to reproduce the Maoka results (EJ Johnson, Tufts/USDA, personal communication).

Currently, there are only three published human clinical trials and one conference abstract in which subjects were supplemented with MZ.^1-3,5 These trials also included lutein and zeaxanthin in the treatment regimen as the synthesis of MZ produces a mixture of the three xanthophylls. The source, amount and ratio of these three xanthophylls varied in each of the four studies. Bone et al. state that “the L to MZ conversion can be augmented by supplementing the diet directly with MZ.” There is no published evidence that supports this statement. Three of the four trials evaluated macular pigment optical density (MPOD) as an endpoint, but any increase in MPOD cannot be attributed to MZ as any potential beneficial effect of MZ cannot be isolated from those conferred by lutein or dietary zeaxanthin. Additionally, as MPOD is a measurement of the total level of xanthophylls in the macula, there is no way to determine whether increases in MPOD were due to an increase in the conversion of lutein to MZ or enhanced deposition of MZ in the macula.

Finally, the available evidence suggests supplementation with MZ may actually hinder the uptake of lutein and zeaxanthin. All three published studies showed a decreased absorption rate of lutein and zeaxanthin into the blood stream, compared with results from other studies that supplemented subjects with lutein and/or zeaxanthin alone at comparable levels, suggesting that MZ might actually impair the body’s ability to absorb lutein and zeaxanthin. For example, one study showed that MZ was less bioavailable than dietary zeaxanthin since dietary zeaxanthin was 2.6 times better absorbed than MZ.5 Epidemiology studies from 1993 on have supported a role for lutein and dietary zeaxanthin in eye health. This led to the NEI launching the AREDS-2 trial with just these two pigments. The safety of lutein and dietary zeaxanthin has been reviewed numerous times by the FDA in response to, e.g., New Dietary Ingredient notifications and Generally Recognized as Safe notifications from various manufacturers seeking to use these ingredients in dietary supplements and conventional foods. In contrast, the public record reflects no such safety submissions and FDA response for meso-zeaxanthin.

Eye-care professionals should proceed with caution when considering whether to recommend a supplement containing meso-zeaxanthin. As MZ is not consumed in the diet and is the result of a biotransformation of lutein in the macula, there is no evidence that the body either needs or deposits exogenous sources of MZ. The human clinical literature is limited and does not provide competent and reliable scientific evidence that supports a benefit of MZ for eye health.