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.