title: Serum and retinal responses to three different doses of macular carotenoids over 12 weeks of supplementation.
abstract: The macular carotenoids lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) have been shown to have neuroprotective and visual performance benefits once deposited in retinal tissues. The purpose of this 12-week trial was to determine biweekly the absorption kinetics, efficiency of retinal deposition, and effects on the spatial profile of macular pigment for three levels of L + Z + MZ supplement. This study was a double-blind, placebo-controlled 12-week trial. Twenty-eight healthy subjects, aged 18-25 yrs participated. Subjects were randomly assigned to one of four daily supplementation groups: placebo (safflower oil; n = 5), 7.44 mg total macular carotenoid (n = 7), 13.13 mg total macular carotenoid (n = 8), and 27.03 (n = 8) mg total macular carotenoid. Ratios of the three carotenoids were virtually identical for the three levels of supplement (83% L, 10% Z, 7% MZ). At baseline and every two weeks thereafter over the 12-week study period, a fasting blood draw was conducted and, via heterochromatic flicker photometry, spatial profiles of macular pigment optical density (MPOD) were determined. Compared to placebo, serum concentrations of both L and total Z, for each of the supplement levels, were found to increase significantly from baseline after two weeks of daily ingestion (p < 0.001). Likewise, MPOD increased significantly in all treatment groups (p < 0.001) compared to placebo. Serum responses (L, Z, and L + Z) were linearly related to dose (p < 0.001 for all), but not to retinal response. L: Z serum response ratios decreased exponentially with increases in dose (p = 0.008). The ratio of MPOD change: total serum response was found to be highest for the 13.13 mg level of supplement (p = 0.021), followed by 27.03- and 7.44-mg doses. The very center of the spatial profile of MPOD increased in a fashion commensurate with dose level. Although L serum responses increased with dose, the slope of increase was shallower than for Z. Given the higher levels of L in the supplements, this is suggestive of a compressed response with relatively high doses of L. Although all three doses significantly augmented MPOD, the 13.13 mg/day L + Z supplement level was the most efficient in doing so. The data regarding efficiency may inform recommendations regarding macular carotenoid supplementation for age-related macular degeneration. Lastly (although not statistically significant), the shift toward a more pronounced central peak in the spatial profile of MPOD in all treatment groups suggests that central retinal deposition of Z and MZ was efficient and can be seen after a short period of supplementation, especially with higher (e.g. 27.03 mg) daily doses of macular carotenoids. ISRCTN trial registration number: ISRCTN54990825.
authors.affiliation: Nutritional Neuroscience Laboratory, Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA. Electronic address: psychjim@uga.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Stringham
authors.affiliation: Interdisciplinary Neuroscience Program, Biomedical Health Sciences Institute, University of Georgia, Athens, GA 30602, USA. Electronic address: ntwood@uga.edu.
authors.forename: Nicole T
authors.initials: NT
authors.lastname: Stringham
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D064368:Healthy Volunteers; D006801:Humans; D014975:Lutein / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008266:Macula Lutea / Q000000981:diagnostic imaging / Q000378:metabolism*; D008268:Macular Degeneration / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D065348:Macular Pigment / Q000378:metabolism*; D008297:Male; D010783:Photometry; D013997:Time Factors; D014792:Visual Acuity; D055815:Young Adult; D065146:Zeaxanthins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D015415:Biomarkers; D065348:Macular Pigment; D065146:Zeaxanthins; D014975:Lutein
keywords: Age-related macular degeneration; Lutein; Macular carotenoids; Macular pigment; Mesozeaxanthin; Zeaxanthin