Retinal Carotenoid Supplementation Increases HDL Cholesterol in Humans and Mice

Carotenoid supplementation may reduce the risk of age-related macular degeneration (AMD). These retinal nutrients are hydrophobic molecules obtained from the diet that are transported to the retina through high-density lipoprotein (HDL) complexes. HDL cholesterol is a recognized biomarker for AMD risk. This study examined the effect of carotenoid supplementation on circulating HDL cholesterol levels. Serum lipid profiles were measured in 20 participants from the Lutein and Zeaxanthin in Pregnancy (L-ZIP) trial, which enrolled 40 pregnant women. In addition to standard prenatal supplements, half received 10 mg of lutein and 2 mg of zeaxanthin daily from the first trimester, and half received a placebo. Carotenoid supplementation significantly increased HDL cholesterol in the third trimester, with no changes in total cholesterol, LDL cholesterol, or triglycerides (TG) across trimesters. To further evaluate individual carotenoids, serum lipids were analyzed in macular pigment transgenic mice fed lutein, zeaxanthin, or β-carotene for one month. All three carotenoids significantly increased HDL cholesterol and reduced TG levels, with the effect ranking as zeaxanthin > lutein > β-carotene. These findings suggest that carotenoid supplementation modulates the serum lipid profile-elevating HDL cholesterol and lowering TG-which may contribute to protection against AMD and other lipid-associated diseases.