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Review: Lutein & Zeaxanthin Metabolism

Metabolism is Key to Lutein’s Protective Role

Growing evidence suggests lutein and zeaxanthin play an important role in protection against AMD by filtering out blue light or quenching free radicals. While much remains to be learned, researchers from Waterford Institute and Regional Hospital in Ireland and the University of Utah’s Moran Eye Center have reviewed mechanisms involved in absorption and transport of these carotenoids, their uptake by the retina and how they are stabilized (1). Below are highlights of these findings, along with editorial comment on implications for diet, lifestyle and supplement use.

Absorption of Lutein and Zeaxanthin

Dietary fat is important for the absorption of xanthophyll carotenoids like lutein and zeaxanthin. Fat stimulates bile flow from the gall bladder to emulsify fat-soluble vitamins into lipid micelles – microscopic fat droplets – so they can be absorbed in the small intestine. Inadequate fat intake can result in reduced absorption of carotenoids, even if the diet is carotenoid-rich. Experimental data suggest absorption of lutein is mediated by a non-specific transporter protein (this protein, scavenger receptor class B type I, appears to play a primary role in intestinal absorption, but other proteins or passive diffusion may also be involved). Of note, some competition for absorption is seen when similarly structured carotenoids like beta-carotene and lutein are consumed together.

Comments: Though different carotenoids compete for absorption, some evidence suggests that balanced amounts of various carotenoids consumed together over time don’t interfere with each other in terms of bioavailability (2). Importantly, doses of lutein (10 mg) and zeaxanthin (2 mg) now being used in the AREDS 2 trial, did not reduce serum levels of other important carotenoids in a dosing study (3).

Transport of Lutein and Zeaxanthin

Dietary lutein and zeaxanthin are delivered to the retina via plasma lipoproteins, chiefly LDL and HDL cholesterol. While LDL is the primary carrier for most carotenoids, LDL and HDL carry about equal amounts of lutein and zeaxanthin. Several studies suggest relatively low HDL levels could hinder transport and capture of these carotenoids. Lower HDL levels have been found in overweight and obese individuals, for example, and higher body fat percentage is linked to risk of AMD progression as well as to lower macular pigment density. Lipoproteins also include protein components known as apolipoproteins. Researchers are investigating whether a person’s apolipoprotein profile might influence transport and delivery of these carotenoids to the retina. Of many apolipoproteins types, ApoE has the strongest link with AMD.

Comments: Lower levels of HDL have been found in overweight individuals, consistent with the possibility that a relative lack of HDL may impair transport and/or retinal capture of the carotenoids. Obesity has been identified as a risk factor for AMD. Take home message? Aerobic exercise, which aids weight loss and increases HDL, may prove useful in lowering AMD risk.

Retinal Uptake of the Xanthophyll Carotenoids

The mechanisms governing retinal capture and accumulation of lutein and zeaxanthin to the exclusion of other carotenoids are still poorly understood. However, retinal capture of xanthophyll carotenoids is performed by xanthophyll-binding proteins (XBP). XBPs may also be involved in: a) stabilizing xanthophylls in cell membranes, the cytosol or the cytoskeleton, b) mediating inter-conversion of lutein, zeaxanthin and various metabolites within the retina, and c) facilitating antioxidant activity of macular carotenoids. Importantly, it has been found that XBPs can become saturated, with implications for xanthophyll carotenoid supplementation.

Comments: Macular pigment density often increases dramatically in the first 4 weeks of supplementation, and then levels off. In a number of studies testing 10-12 mg of lutein, macular pigment density reached a plateau after the first month. This may be due to saturation of binding proteins, and suggests higher doses may not further enhance macular pigment over time.

References

1. Loane E, et al. Transport and retinal capture of lutein and zeaxanthin with reference to age-related macular Degeneration. Surv Ophthalmol 53:68-81, 2008.
2. Tyssandier V, et al. Vegetable-borne lutein, lycopene, and beta-carotene compete for incorporation into chylomicrons, with no adverse effect on the medium-term (3-wk) plasma status of carotenoids in humans. Am J Clin Nutr 75:526–34 2002.
3. Rosenthal JM, et al. Dose-ranging study of lutein supplementation in persons aged 60 years or older.Invest Ophthalmol Vis Sci 47:5227–233, 2006.