Short-Term Bixin Supplementation of Healthy Subjects Decreases the Susceptibility of LDL to Cu(2+)-Induced Oxidation Ex Vivo

Lycopene-based medications and supplements have been developed to prevent atherosclerosis, primarily because of their ability to decrease low-density lipoprotein (LDL) oxidation. Bixin and norbixin are carotenoids found in the seeds of annatto (Bixa orellana) and are colorants widely used by the food industry. Some studies have already demonstrated that these compounds have antioxidant and antiatherogenic potential in vitro and in animal models, but there is no evidence supporting the effects of their long-term or short-term consumption by humans. The aim of this study was to evaluate the effects of short-term intake of annatto carotenoids on biochemical and oxidative stress biomarkers as well as on the susceptibility of LDL oxidation in healthy individuals, using lycopene as a positive control. The effect of daily supplementation (0.05 mg/kg of body weight (b.w.)) with bixin, norbixin, lycopene, or placebo for 7 days was evaluated in a randomized, controlled crossover study in 16 healthy volunteers (8 men and 8 women). The susceptibility of LDL to Cu(2+)-induced oxidation ex vivo, biochemical parameters, and oxidative stress biomarkers were evaluated. No treatment affected biochemical parameters or most oxidative stress biomarkers. However, bixin reduced the oxidation rate of the LDL lipid moiety (−275%, p < 0.1) and nitric oxide metabolites (NOx) (−460%, p < 0.1), compared to the placebo group. Moreover, we observed that the changes in these parameters were positively associated, supporting the hypothesis that bixin decreases the susceptibility of LDL to Cu(2+)-induced oxidation by decreasing NOx levels, probably by downregulating the inducible nitric oxide synthase.