Augmentation of Macular Pigment Following Supplementation with All Three Macular Carotenoids: An Exploratory Study

Abstract

Purpose: At the macula, the carotenoids meso-zeaxanthin (MZ), lutein (L), and zeaxanthin (Z) are collectively referred to as macular pigment (MP). This study was designed to measure serum and macular responses to a macular carotenoid formulation. Materials and Methods: Ten subjects were recruited into this study (five normal and five with early age-related macular degeneration [AMD]). Subjects were instructed to consume a formulation containing 7.3 mg of MZ, 3.7 mg of L, and 0.8 mg of Z everyday over an eight-week period. The spatial profile of MP optical density (i.e., MPOD at 0.25°, 0.5°, 1°, and 1.75°) was measured using customized heterochromatic flicker photometry, and a blood sample was collected at each study visit in order to analyze serum concentrations of MZ, L, and Z. Results: There was a significant increase in serum concentrations of MZ and L after two weeks of supplementation (p < 0.05). Baseline serum carotenoid analysis detected a small peak eluting at the same time as MZ in all subjects, with a mean ± SD of 0.02 ± 0.01 μmol/L. We report significant increases in MPOD at 0.25°, 0.5°, 1°, and average MPOD across its spatial profile after just two weeks of supplementation (p < 0.05, for all). Four subjects (one normal and three AMD) who had an atypical MPOD spatial profile (i.e., central dip) at baseline had the more typical MPOD spatial profile (i.e., highest MPOD at the center) after eight weeks of supplementation. Conclusion: We report significant increases in serum concentrations of MZ and L following supplementation with MZ, L, and Z and a significant increase in MPOD, including its spatial profile, after two weeks of supplementation. Also, this study has detected the possible presence of MZ in human serum pre-supplementation and the ability of the study carotenoid formulation to rebuild central MPOD in subjects who have atypical profiles at baseline. 1,2 It is estimated that the number of people suffering from AMD will continue to increase, primarily due to increasing longevity. 3,4 It is now believed that both oxidative stress and cumulative exposure to short-wavelength (blue) light are involved in the aetiopathogenesis of AMD. KEYWORDS: 5-7The center of the retina has a distinct yellow color attributable to the presence of a pigment known as macular pigment (MP), and this coloration contributed to the original eponymous description of this retinal region as the macula lutea (or yellow spot).8,9 MP comprises three dietary carotenoids meso-zeaxanthin (MZ), lutein (L), and zeaxanthin (Z). [8][9][10] There is now a biologically plausible rationale, supported by a growing body of evidence, in support of the view that MP protects against AMD.7 For example, MP has been shown to significantly reduce the amount of blue light incident on the macula.11-14 Furthermore, the antioxidant properties of MP′s constituent carotenoids within the retina and elsewhere have been demonstrated in vitro. 15,16 L and Z are found in a typical western diet, in fruit and vegetables (e.g., spinach, corn, orange p...

Retinal light toxicity

“…142,143 Owing to the ability of macular pigments to serve as both effective absorbers of high-energy, short-wavelength light, as well as antioxidants, many investigators have started to measure macular pigment optical density. In fact, several groups of investigators have shown an increase in macular pigment density [144][145][146] Additionally, the lutein antioxidant supplementation trial (LAST) and the LUNA study both support the association between dietary supplementation and macular pigment density. 147,148 Others have noted great variability in macular pigment optical density depending on factors such as gender, body fat composition, and smoking.…”

What is meso-zeaxanthin, and where does it come from?

“…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. 30,40 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. 41 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.…”

“…41 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. 28,30,40 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. 30 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.…”

Response to Bernstein et al

“…Meso-zeaxanthin in lutein supplements. 4. Additional evidence supporting lutein as the precursor of meso-zeaxanthin.…”

“…We are very familiar with this method, as we have used it in several of our recently published studies. [3][4][5][6] In our review article, we point out the limitations of the standard 'two-step method' commonly used by many laboratories to quantify MZ. These limitations include the following: its labour intensive nature due to manual collection; operator dependency and potential for human error; and a very long sample run time, rendering it difficult to perform bulk analysis (eg, for clinical trials).…”