Lutein, zeaxanthin, and meso-zeaxanthin supplementation attenuates inflammatory cytokines and markers of oxidative cardiovascular processes in humans

Nutr Metab Cardiovasc Dis. 2024 Aug;34(8):1976-1983. doi: 10.1016/j.numecd.2024.05.009. Epub 2024 May 14.

Abstract

Background and aims: Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the vascular endothelium has been hypothesized to be an initial step in the formation of atherosclerotic plaques, with inflammatory cytokines serving as the signaling mechanism for concomitant macrophage activation. Supplementation with the antioxidative macular xanthophylls (lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]) has been shown to aid in the reduction of inflammatory physiologic responses; therefore, we hypothesized that in our study population, supplementation with these xanthophylls would facilitate a systemic reduction in markers of inflammation and cardiovascular lipid oxidation.

Methods and results: In this double-blind placebo-controlled supplementation study, participants were randomly allocated to receive the active intervention containing L (10 mg) + MZ (10 mg) + Z (2 mg) or placebo (containing sunflower oil). Serum concentrations of carotenoids (assessed by HPLC), inflammatory cytokines (IL-6, IL-1β, TNF-α) and oxidized LDL (OxLDL; by solid-phase sandwich ELISA) were measured at baseline and at 6-months. Results showed that over the supplementation period, compared to placebo, the active group demonstrated statistically significant increases in serum concentrations of L, Z, & MZ (p < 0.05), reductions in inflammatory cytokines IL-1β (p < 0.001) and TNF-α (p = 0.003), as well as a corresponding reduction in serum OxLDL (p = 0.009).

Conclusions: Our data show that L, Z, & MZ supplementation results in decreased serum IL-1β, TNF-α, and OxLDL. This suggests that these carotenoids are acting systemically to attenuate oxidative lipid products and inflammation, thus reducing their contribution to atherosclerotic plaque formation.

Keywords: Atherosclerosis; Carotenoids; IL-1β; Macular xanthophyll; Oxidized LDL; TNF-α.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Antioxidants / administration & dosage
  • Atherosclerosis / blood
  • Atherosclerosis / prevention & control
  • Biomarkers* / blood
  • Cytokines* / blood
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / prevention & control
  • Inflammation Mediators / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Lipoproteins, LDL* / blood
  • Lutein* / administration & dosage
  • Lutein* / blood
  • Male
  • Middle Aged
  • Oxidative Stress* / drug effects
  • Tumor Necrosis Factor-alpha / blood
  • Xanthophylls / administration & dosage
  • Xanthophylls / blood
  • Zeaxanthins* / administration & dosage
  • Zeaxanthins* / blood

Substances

  • Zeaxanthins
  • Biomarkers
  • Lutein
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Cytokines
  • meso-zeaxanthin
  • Inflammation Mediators
  • Antioxidants
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta
  • Anti-Inflammatory Agents
  • Xanthophylls
  • Interleukin-6
  • IL1B protein, human