Abstract
Vitamin A is a fat-soluble micronutrient essential for growth, immunity, and good vision. The preformed retinol is commonly found in food of animal origin whereas provitamin A is derived from food of plant origin. This review summarises the current evidence from animal, human and cell-culture studies on the effects of vitamin A towards bone health. Animal studies showed that the negative effects of retinol on the skeleton were observed at higher concentrations, especially on the cortical bone. In humans, the direct relationship between vitamin A and poor bone health was more pronounced in individuals with obesity or vitamin D deficiency. Mechanistically, vitamin A differentially influenced the stages of osteogenesis by enhancing early osteoblastic differentiation and inhibiting bone mineralisation via retinoic acid receptor (RAR) signalling and modulation of osteocyte/osteoblast-related bone peptides. However, adequate vitamin A intake through food or supplements was shown to maintain healthy bones. Meanwhile, provitamin A (carotene and β-cryptoxanthin) may also protect bone. In vitro evidence showed that carotene and β-cryptoxanthin may serve as precursors for retinoids, specifically all-trans-retinoic acid, which serve as ligand for RARs to promote osteogenesis and suppressed nuclear factor-kappa B activation to inhibit the differentiation and maturation of osteoclasts. In conclusion, we suggest that both vitamin A and provitamin A may be potential bone-protecting agents, and more studies are warranted to support this hypothesis.
Highlights
Bone health is maintained through normal bone remodelling, which is an active and dynamic process whereby the activities of bone resorption and formation occur in balance to maintain bone microarchitecture, strength, and mineral homeostasis
Upon reaching the targeted cells, retinol and provitamin A undergo the conversion to all-trans-retinoic acid, followed by binding to the retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers to exert their effects [8]
Serum retinol-binding protein 4 (RBP4) [OR = 0.774] and retinol [OR = 0.774] levels was not associated with risk of osteoporosis
Summary
Bone health is maintained through normal bone remodelling, which is an active and dynamic process whereby the activities of bone resorption and formation occur in balance to maintain bone microarchitecture, strength, and mineral homeostasis. Vitamin A can be consumed in two forms, i.e., preformed retinol and provitamin A. Retinol is esterified to retinyl ester, packaged into chylomicrons along with the intact provitamin A, and stored in the liver. Retinyl ester is converted to retinol and bound to retinol-binding protein (RBP) to be released into the circulation. Both retinol and provitamin A reach the peripheral cells (including bone) via signalling receptor and transporter of retinol (STRA6) and delivery by chylomicrons. Upon reaching the targeted cells, retinol and provitamin A undergo the conversion to all-trans-retinoic acid (the biologically active metabolite of vitamin A), followed by binding to the RAR and retinoid X receptor (RXR) heterodimers to exert their effects [8]
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