Non-Provitamin A and Provitamin A Carotenoids as Immunomodulators: Recommended Dietary Allowance, Therapeutic Index, or Personalized Nutrition?

Abstract

Vegetables and fruits contain non-provitamin A (lycopene, lutein, and zeaxanthin) and provitamin A (β-carotene, β-cryptoxanthin, and α-carotene) carotenoids. Within these compounds, β-carotene has been extensively studied for its health benefits, but its supplementation at doses higher than recommended intakes induces adverse effects. β-Carotene is converted to retinoic acid (RA), a well-known immunomodulatory molecule. Human interventions suggest that β-carotene and lycopene at pharmacological doses affect immune functions after a depletion period of low carotenoid diet. However, these effects appear unrelated to carotenoids and retinol levels in plasma. Local production of RA in the gut-associated lymphoid tissue, as well as the dependency of RA-induced effects on local inflammation, suggests that personalized nutrition/supplementation should be considered in the future. On the other hand, the differential effect of RA and lycopene on transforming growth factor-beta suggests that lycopene supplementation could improve immune functions without increasing risk for cancers. However, such preclinical evidence must be confirmed in human interventions before any recommendations can be made.

Figure 1

Immunomodulatory effects of carotenoids and retinoic acid. α4β7: α4β7 integrin; APO10LA: Apo-10′-lycopenoic acid; ASC: antibody-secreting cells; BCO2: β-carotene 9′,10′ oxygenase-2; CCR9: C-C chemokine receptor 9; CYP26: cytochrome P450 26; DC: dendritic cells; IFN: interferon; Ig: immunoglobulin; IL: interleukin; ILC: innate lymphoid cells; M: macrophages; MLN: mesenteric lymph nodes; NK: natural killer; RA: retinoic acid; TGF: transforming growth factor; Th: T helper; TLR: Toll-like receptor; TNF: tumor necrosis factor; Treg: regulatory T. →: homing and improvement; −•: inhibition.