Dietary Sources, Sex, and rs5888 (SCARB1) as Modulators of Vitamin A’s Effect on Cardiometabolic Health

Although preclinical studies have attributed vitamin A (VA) cardiometabolic benefits, these effects are still controversial and not always supported in large human studies. Here, the outcomes associated with VA and its relationship with habitual dietary sources, sex, and genetic background have been studied. To do so, the data from an observational study (n = 455) (64% females, mean age of 36 years) showing that suboptimal VA intake (mainly from retinol rather than carotene) is associated with cardiometabolic risk (CMR) were considered. A higher odds ratio (OR) of suffering ≥ 2 simultaneous CMR factors was observed in men in the low consumption tercile of retinol (OR = 2.04; p = 0.019). In women, however, this relationship was not evident. Then, incubation of peripheral blood mononuclear cells (PBMCs) with VA-related compounds (ex vivo functional assay from 81 men and women) induced specific changes in the activity of genes involved in lipid homeostasis and inflammatory status, which were dependent on the type of compound tested and the sex of the person. In addition, the presence of the genetic variant rs5888 in SCARB1 was identified as having a high influence on VA-related metabolic response. The new evidence derived from this study could be relevant for personalized nutritional advice concerning VA and CMR.