Safety

MZ is now available in commercially available preparations (eg, MacuShield (Macuvision Europe Ltd, Solihull, UK), MacuHealth with LMZ3 (MacuHealth LLC, Birmingham, MI, USA), and Lutein Plus (Holland & Barrett, Nuneaton, UK)), and many have been consuming MZ in supplement form since the 1990s, and there are no published accounts of adverse events or safety issues arising from its use. Recently published trials have found that subjects supplemented with all the three macular carotenoids (MZ, L, and Z) exhibit significant increases in serum concentrations of these carotenoids and an associated augmentation in MP. Indeed, a recent publication reports that the typical central peak of MP can be realised in subjects with atypical MP spatial profiles at baseline when supplemented with a preparation containing all the three macular carotenoids, but not with a supplement lacking MZ. MZ in such supplements is derived from natural L, which has been extracted from the Aztec Marigold flower, and has been used to date in many clinical trials and subjected to toxicity studies. A recent study of supplemental MZ in human subjects has reported that renal and liver function, as well as lipid profile, haematological parameters, and markers of inflammation, are unaffected following supplementation with a formulation containing MZ, L, and Z. MZ is also a component of a typical diet in countries and states where it is commonly used in hen feed to enhance the colouration of the egg yolk by the poultry industry (eg, Mexico), and no associated adverse events have ever been reported.

Moreover, the safety of MZ has been further evaluated in a recent toxicity trial using an animal model (Wister rats). The results of this trial demonstrated that the NOAEL (‘No Observed-Adverse-Effect Level’) was in excess of 200 mg/kg/day, far greater than doses used in dietary supplements, which are typically o0.5 mg/kg/day. Absence of mutagenicity was confirmed in the same study, using the Ames test. In 2011, the GRAS (‘Generally Regarded As Safe’) status of MZ was acknowledged by the FDA in a reply to a proposal from a US company on the status of MZ (plus L and Z). Finally, a recent safety evaluation of MZ by Xu et al concluded that MZ has no acute toxicity and no genotoxicity and the use of MZ is safe at dose of 300 mg/kg body weight per day in rats from a 90 day feeding study. The authors then applied a 100 fold safety factor, and reported an ADI (acceptable daily intake) of 3 mg/kg body weight per day for MZ.