Correlates of Metabolic Syndrome Are Associated with Low Macular Pigment Despite Moderate to High Intakes of Macular Carotenoids

Abstract

Purpose: Variable macular response to dietary lutein and zeaxanthin (LZ) has been reported and may explain inconsistent benefit of LZ from observational studies and clinical trials for AMD. We evaluated phenotypic and genotypic measures of metabolic syndrome, including measures of abdominal adiposity, hypertension, diabetes, elevated triglycerides, and dyslipidemia, for associations with macular response to diets containing moderate to high intakes of LZ (>1.7mg/day) in the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study to the Women’s Health Initiative.

Methods: Macular pigment optical density (MPOD) was assessed using customized heterochromatic flicker photometry in 2001-2004. LZ intake was estimated from food frequency and supplement questionnaires. Visits also included anthropometric measurements and queries for chronic diseases. WHI visits (1994-1998) included blood collection for analysis of triglycerides and genotyping of variants related to carotenoid and HDL status. Among women with intake of LZ >1.7mg/day (N=867), we compared dietary, lifestyle, health status, and genotypic characteristics of women who had MPOD ranking two or more quintiles below their quintile rank for LZ intake (low responders) with characteristics of women who had MPOD which equaled or exceeded their quintile ranking for LZ intake (responders).

Results: Low responders (n=377), relative to women with MPOD which ranked similarly to their LZ intake (n=490), were more likely to have waist circumference in high quartiles (30 vs. 17%), diabetes (8 vs. 4%), hypertension (68 vs. 58%), elevated triglycerides (10 vs. 7%), and use statins (28 vs. 23%). Low responders were also more likely to have genotypes associated with low MPOD in genes which have been related to HDL: GG for BCMO1 rs11645428 (54% vs. 41%), AG/GG for SCARB1 rs838879 (60% vs. 43%), and CC for ABCA1 rs1929841 (8% vs. 3%). Considered jointly, increasing number of factors related to metabolic syndrome was associated with lower MPOD, adjusted for LZ intake (mean MPOD = 0.55, 0.45, 0.41, 0.36, 0.32, 0.34. 0.17 and 0.05 for scores of 0 to 7, respectively (P-trend<0.0001)).

Conclusions: The number of metabolic syndrome components may be a crude marker for identifying persons less likely to respond to supplements in clinical trials, or for use in comparing results within and across studies of LZ supplements.

Keywords: 587 macular pigment • 412 age-related macular degeneration • 618 nutritional factors