KEAP1 and osteoporosis: Additionally, β-carotene can be cleaved to form vitamin A, which acts through its metabolite, all-trans-retinoic acid (ATRA), a highly potent transcriptional regulator which can affect the transcription of genes that are critical to mediate the indirect antioxidant effects of vitamin A. Therefore, vitamin A can activate the NRF2/KEAP1 or NF-κB signaling pathways to inhibit oxidative stress as an indirect antioxidant [29, 30], and β-carotene and its metabolite can increase BMD and reduce the risk of osteoporosis via both direct and indirect antioxidant effects.