3.2.2. Vitamins
High-altitude hypoxia may alter the endogenous bioactivity of vitamins. Pu et al. assessed the differential metabolites in the whey of buffaloes reared at different altitudes and found that vitamin B6 levels were elevated in the high-altitude group (Pu et al., 2021). Vitamin B supplementation attenuates hypoxic injury (Yu et al., 2016). Similarly, vitamins C and E, which are important antioxidants, can ameliorate the hypoxic response by blocking the immune response, oxidative stress, and loss of mitochondrial integrity and function caused by hypoxia (Goswami et al., 2014; Wang et al., 2009). Vitamin D plays important roles in bone metabolism and mineral homeostasis. Notably, children living at high altitudes have a high prevalence of vitamin D deficiency (Kapil et al., 2017), and a study by Śliwicka et al. further found that plateau environments lead to a substantial decrease in 25-hydroxyvitamin D levels (Śliwicka et al., 2017; Yu et al., 2020), suggesting that hypoxia decreases vitamin D levels, which in turn affects bone development. Furthermore, vitamin D has important noncalcific effects on the cardiovascular, reproductive, immune, and neuronal systems in hypoxic environments (Mata-Greenwood et al., 2023; Pelham et al., 2016). Other vitamins, such as vitamins A and K, also influence the state of the body under hypoxia (Al-Qassab et al., 2018).
How vitamins are involved in pathophysiological processes under hypoxia needs to be further explored. However, the expression of vitamins under hypoxia is inextricably linked to changes in the associated CYP. Goyal et al. found that the circulating levels of 25-OH-D, 1,25-(OH)2D, and vitamin D were higher in hypoxic sheep than in normoxic sheep. Increased biological activity of vitamin D is then associated with increased expression of CYP27B1, and renal CYP27B1 is increased under hypoxia (Goyal et al., 2016), which may account for the increased expression of vitamin D in hypoxic sheep. Chen et al. found that serum 25(OH)D3 levels in plateau pikas decreased substantially with increasing altitude, and further measurements revealed substantial decreases in the mRNA and protein levels of hepatic CYP2R1 and renal CYP27B1, suggesting that hypoxia inhibits the conversion of vitamin D3 to 25(OH)D3 and 1,25(OH)2D3in plateau pikas by downregulating CYP2R1 and CYP27B1 expression (Chen et al., 2022). In addition, a variety of CYPs are involved in the regulation of vitamin metabolism; CYP26 is involved in the metabolism and elimination of vitamin A. CYP2C11, CYP27A1, CYP2D25, CYP2R1, and CYP2J3 have vitamin D 25-hydroxylation activity, CYP27B1 and CYP24 are 1α-hydroxylases and 24-hydroxylases, respectively, and CYP4F2 and CYP4F11 are both vitamin K1 and K2 ω-hydroxylases, but whether these enzymes are equally involved in the regulation of vitamins under hypoxia has rarely been investigated.