Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: The LUNA study

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Abstract

Macular pigment (MP), consisting of lutein (L) and zeaxanthin (Z), is believed to protect the retina from photo-oxidative damage. The current study investigates, in terms of MP optical density (MPOD) and serum concentrations of its constituent carotenoids, response to supplemental L and Z, and co-antioxidants. An intervention (I) group, consisting of 108 subjects (mean [±SD] age: 71.5 [±7.1] years), of which 92.6% exhibited features of age-related macular degeneration (AMD), received a daily supplement consisting of 12 mg L and 1 mg Z, both provided as ester 120 mg vitamin C, 17.6 mg vitamin E, 10 mg zinc, 40 μg selenium (Ocuvite Lutein™) for a period of 6 months. MPOD was measured, by 2-wavelength autofluorescence (AF), on five occasions during the period of supplementation, and once again 3 months following discontinuation of the supplement. A control (C) group of 28 subjects (mean [±SD] age: 71.0 [±8.1] years), who received no dietary supplementation or modification, was examined at baseline and once again after a mean of 29.4 (±9.3) weeks. At baseline, mean (±SD) MPOD (at 0.5°) was 0.504 (±0.197) and 0.525 (±0.189) in the I and C groups, respectively. There was a statistically significant increase in MPOD (at 0.5°) for the I group (0.1 [±0.009]; p < 0.0008), whereas no significant increase was seen in the C group (0.03 [±0.02]; p > 0.05), over the period of supplementation. In order to classify supplemented subjects into quartiles, in terms of MPOD response, we calculated the difference between MPOD (at 0.5°) at visit 6 and at baseline (visit 1). Quartile 1 (the “non-responder” quartile) displayed no increase in MPOD (at 0.5°), in spite of rises seen in serum concentrations of L and Z. The three “responder” quartiles reached similar final plateaus of MPOD (at 0.5°), reflected in final mean (±SEM) values of 0.59 (±0.04) optical density unit (ODU), 0.64 (±0.03) ODU and 0.64 (±0.03) ODU for quartiles 2, 3 and 4, respectively. Subjects with low baseline MPOD were more likely to exhibit a dramatic rise in MPOD, or to exhibit no rise in MPOD, in response to supplements than subjects with medium to high baseline MPOD values. Supplementation with 12 mg L and 1 mg Z, combined with co-antioxidants, resulted in an increase of MPOD at 0.5° eccentricity in a majority of subjects, including those afflicted with AMD. However, there remains a substantial proportion of subjects for whom, in spite of rises in serum concentrations of L and Z in these subjects, MPOD augmentation in response to supplemental L, Z and co-antioxidants could not be detected over the study period, thus indicating that intestinal malabsorption of these carotenoids is not responsible for the lack of a macular response to such supplements. Further, our results suggest that saturable mechanisms play a role in the retinal capture and/or stabilisation of the macular carotenoids.

Introduction

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world (Klaver et al., 1998). Oxidative stress, which refers to tissue damage caused by reactive oxygen intermediates (Beatty et al., 2000), and retinal damage by short-wavelength (blue) light, has been implicated in the aetiopathogenesis of AMD.

A pigment composed of three carotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (meso-Z), accumulates at the macula, where it is known as macular pigment (MP) (Beatty et al., 2001, Bone et al., 1992, Bone et al., 1988, Sommerburg et al., 1999). In humans, L and Z cannot be synthesised de novo and are derived entirely from diet (Malinow et al., 1980), whereas meso-Z is largely derived from retinal L (Neuringer et al., 2004). Due to its short-wavelength light screening and antioxidant properties, it is believed that MP may afford protection against the development of AMD.

Several studies have investigated the relationship between dietary and serum concentrations of L (and Z) and MPOD in humans, and all have demonstrated a positive relationship between these variables (Bone et al., 2000, Brady et al., 1996, Ciulla et al., 2001, Hammond et al., 2002, Hammond et al., 1996a, Rock et al., 2002).

Non-dietary variables suspected of acting as determinants of serum concentrations of L (and Z) and/or MP optical density include: age (Beatty et al., 2001, Gellermann et al., 2002); sex (Hammond et al., 1996a); iris colour (Hammond et al., 1996b); race (Rock et al., 2002, Gruber et al., 2004); body fat (Gruber et al., 2004, Hammond et al., 2002, Nolan et al., 2004); ultraviolet light exposure (Rock et al., 2002); tobacco and drinking habits (Gruber et al., 2004, Hammond et al., 1996c, Rock et al., 2002); and genetic background (Hammond et al., 1995, Liew et al., 2005). However, the exclusively dietary origins of L and Z would suggest that dietary intake of these carotenoids represents one of the most important determinants of serum L (and Z) and MPOD. This notion is consistent with most cross-sectional and supplementation studies (Bone et al., 2000, Broekmans et al., 2002, Hammond et al., 1997).

The LUNA (LUtein Nutrition effects measured by Autofluorescence [AF]) study was designed to investigate changes in MPOD, and in serum concentrations of L and Z, in response to supplements consisting of the macular carotenoids and co-antioxidants.

Section snippets

Subjects

We recruited 136 subjects into the LUNA study. None of the subjects had taken supplemental L, Z, or co-antioxidants prior to recruitment. This study was conducted according to best clinical practice, approved by the local medical ethics committee, and adhered to the tenets of the Declaration of Helsinki. Informed consent was given by each subject prior to his/her involvement.

Inclusion criteria for this study was as follows: age 50 years or greater; no or minimal lens opacity, thereby allowing

Baseline findings

The baseline characteristics in the I group are shown in Table 1. The I and C groups were similar in terms of age [mean age (±SD): I group = 71.5 (±7.1); C group = 71.0 (±8.1) years; p = 0.77] and sex (male:female ratio = 40:68 [37:63%] for the I group; male:female ratio = 12:16 [43:57%] for the C group; p = 0.6). Mean (±SD) MPOD at 0.5° eccentricity for the I group was 0.504 (±0.197) ODU and was statistically comparable to the mean (±SD) MPOD at 0.5° eccentricity for the C group, which was 0.525 (±0.189)

Baseline findings

The LUNA (LUtein Nutrition effects measured by Autofluorescence) study was designed to report on the effects of dietary supplementation with macular carotenoids, and co-antioxidants, on serum concentrations of L and Z and on MPOD.

Consistent with other studies (Berendschot et al., 2000, Bone et al., 2000, Burke et al., 2005, Curran-Celentano et al., 2001, Hammond et al., 1996a, Johnson et al., 2000), we found a significant and positive relationship between baseline serum concentrations of L (and

Conclusion and summary

The Age-Related Eye Disease Study (AREDS) has furnished the ophthalmic community with convincing evidence that antioxidant supplements are beneficial to patients with at least intermediate AMD (AREDS, 2001). Low dietary intake and/or serum levels of L and Z were associated with subtypes of AMD in some, (Gale et al., 2003, Mares-Perlman et al., 2001, Seddon et al., 1994, Snellen et al., 2002), but not all (Cardinault et al., 2005, Dasch et al., 2005, Mares-Perlman et al., 1995, VandenLangenberg

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