More on vitamin C deficiency in mice and humans

Abstract

I read with great interest the article by Park etal.,1 who found that a vitamin C deficiency ameliorated liver fibrosis via the up-regulated expression of peroxisome proliferator-activated receptor gamma in senescence marker protein 30 (SMP30) knockout mice. The results are interesting and shed light on the possible mechanisms underlying the attenuated liver fibrosis of SMP30 knockout mice. Here I propose that if these results in SMP30 knockout mice are to be extended to humans, we will need more comprehensive studies based on the new and significant finding that humans employ a unique strategy for adapting to vitamin C deficiency. As we know, humans and some other mammals such as guinea pigs and fruit bats have an inborn metabolic error, that is, an inability to synthesize vitamin C from glucose due to a defective form of the gene for the L-gulonolactone oxidase enzyme required in the last step of vitamin C synthesis.2 Montel-Hagen etal.3 recently demonstrated that human erythrocytes from the vitamin C auxotrophs can dramatically enhance their vitamin C–transporting ability by switching the preference of glucose transporter 1 (Glut1) from glucose to the oxidized form of ascorbic acid [L-dehydroascorbic acid (DHA)]. The membrane protein stomatin has been shown to regulate the substrate preference switch. More interestingly, erythrocyte Glut1 and its associated DHA uptake are specific to species unable to produce vitamin C from glucose. Mice can synthesize vitamin C, and further experimentation has indicated that their mature erythrocytes do not harbor Glut1 or transport DHA. Therefore, in comparison with mice, humans possess a compensatory mechanism to adapt to a vitamin C deficiency, and this may lead us to reevaluate the human vitamin C deficiency status and potentially result in more complicated reflections on vitamin C deficiency in human liver tissues. I do not mean to question the rationality and significance of the findings of Park etal.,1 but Isubmit that this unique compensatory mechanism should be considered in future studies on the relationships between vitamin C deficiency and liver fibrosis in humans. Liang Shen Ph.D.*, * Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo, People's Republic of China.