TITLE An investigation into macular pigment augmentation with all three macular carotenoids and their safety in humans. INTRODUCTION The macula is located at the centre of the retina and is responsible for fine detailed and colour vision. The centre of the macula houses a protective pigment collectively referred to as macular pigment (MP). MP represents the highest concentration of the carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (meso-Z) within the body. MP acts as a filter of short-wave length (blue) light and is a powerful antioxidant. Age-related macular degeneration (AMD) is an eye disease that affects the central part of the retina called the macula and in its late form, results in loss of central vision. Although the pathogenesis of AMD remains poorly understood, it is believed that cumulative exposure to short-wave length (blue) light and reactive oxygen intermediates (ROIs) play an important role in the development of AMD. There is a hypothesis that MP can help protect from this disease by virtue of its protective properties. OBJECTIVES This research study was designed to: 1. Investigate macular and serum response to all three macular carotenoids L, Z and meso-Z in humans. 2. To investigate the response, safety and stability of supplementation with L, Z and meso-Z in combination in humans. METHODS Study One: Augmentation of macular pigment following supplementation with all three macular carotenoids: an exploratory study Ten subjects were included in this study (five normal and five with early AMD). All subjects were instructed to consume a formulation containing 7.3 mg of meso-Z, 3.7 mg of L and 0.8 mg of Z per day over an eight week study period. The spatial profile of MP optical density (i.e. MPOD at 0.25°, 0.5°, 1° and 1.75°) was measured using customised heterochromatic flicker photometry (cHFP) and a blood sample was collected at each study visit in order to analyse serum concentrations of meso-Z, L and Z using high performance liquid chromatography (HPLC). Study Two: Supplementation with all three macular carotenoids: response, stability and safety Forty four healthy subjects were recruited into this randomised, placebo-controlled, clinical trial. Subjects consumed one tablet per day containing 10.6 mg of meso-Z, 5.9 mg of L and 1.2 mg of Z (Intervention, I group) or Placebo (P group). The spatial profile of MPOD was measured using cHFP, and serum concentrations of L and Z were quantified using HPLC. Subjects were assessed at baseline, three and six months. Clinical pathology analysis was performed at baseline and six months. RESULTS Study One There was a significant increase in serum concentrations of meso-Z and L after two weeks of supplementation (p < 0.05). Baseline serum carotenoid analysis (i.e. pre-supplementation) detected a small peak eluting at the same time as meso-Z in all subjects, with a mean ± standard deviation (SD) concentration of 0.02 ± 0.01μmol/L. We also report significant increases in MPOD at 0.25°, 0.5°, 1° and average MPOD across the spatial profile after just two weeks of supplementation with this formulation (p < 0.05, for all). Four subjects (one normal and three AMD) who had an atypical MPOD spatial profile at baseline (i.e. pre-supplementation), had the more typical MPOD spatial profile (i.e. highest MPOD at the centre) after eight weeks of supplementation with the study formulation. Study Two Serum concentrations of L and Z increased significantly in the I group (p = 0.001 and 0.003, respectively) and remained stable in the P group (p > 0.05). There was a significant increase in central MPOD in the I group (0.25°: p = 0.001; 0.5°: p = 0.001), with no significant change in the P group (p > 0.05). Clinical pathology analysis confirmed that all variables remained within the normal reference range, with the exception of total cholesterol and low density lipoprotein (LDL), which exhibited baseline values outside the accepted normal reference range prior to supplementation. CONCLUSION Study One There was a significant increase in serum concentrations of meso-Z and L following supplementation with a formulation containing 7.3 mg meso-Z, 3.7 mg L and 0.8 mg Z and a significant increase in MPOD, including its spatial profile, after just two weeks of supplementation. Also, this study detected the possible presence of meso-Z in human serum pre-supplementation and the ability of this carotenoid formulation to rebuild central MPOD in subjects who have atypical profiles at baseline. Study Two Subjects supplemented with meso-Z, L and Z exhibit significant increases in serum concentrations of these carotenoids, and a subsequent increase in central MPOD. Pathology analysis suggests no adverse clinical implications of consuming these carotenoids.
|Publication status||Unpublished - 2013|
- Macular pigment augmentation