Handbook of Vitamin C Research

Human Specific Vitamin C Metabolism… 63oxidative stress caused by exercise and pathological conditions [14, 15] to prevent oxidativedamage of tissues. However, VC auxotrophs have no VC synthesis in response to xenobioticsand oxidative stress.The recommended dietary allowance (RDA) of VC is 100 mg/day in Japan (RDA 2005,for adults) [28] (Figure 4), and 90 mg/day for men and 75 mg/day for women in U. S. A.(RDA 2000, for detailed recent values, see section (9) of discussion) [29]. However, Paulingpointed out that the RDA is less than the optimum intake, corresponding to the best health[30]. Based on VC synthetic rates in rat, he concluded that the optimum daily intake is about2.3 g or more, for an adult with energy requirement 2500 kcal/day [30]. But in humans themetabolic rate of VC was shown to be in the order of 100mg/day after loading 1 m mole (176mg) of VC [4, 5] (Table 2, 3). Although AsA and DAsA have distinct effects on cell function[69], the utilization of DAsA is nearly equal to that of AsA in humans [4, 5, 61, 70] (Tables 2and 3). However, in GLO knockout mice, the nutritive value of DAsA is only 10% of that ofAsA [71]. In addition, human loading experiments with 1- 14 C-AsA revealed higher metabolicturnover of 140 mg/day and 100 mg/day for smokers and nonsmokers, respectively, to reachsteady-state concentrations [42]. Intakes of VC were in the range of 30 to 180 mg/dayresulting in plasma steady state VC concentrations between 0.25 and 1.57 mg/dL [42],roughly corresponding to the values in Tables 1 and 2.In order to compensate VC auxotrophy with urate as an antioxidant, uricase was lost inhominoids during primate evolution [25]. VC auxotrophs metabolize DAsA slower than VCautotrophs do, owing to very low dehydroascorbatase activity in the former [3]. As will bediscussed in the next section, human and other VC auxotrophs transport DAsA via GLUT1very rapidly to prevent DAsA hydrolysis [26], while VC autotrophs do via GLUT4. Fromabove stated human specific VC metabolism, it is impossible to extrapolate metabolic data ofVC autotrophs to estimate human RDA.The other important aspect is the long-term effect of VC level in humans. RDA of VCestimated by short-term depletion-repletion study may not be enough to test the optimumnutrition to prevent age-related diseases and attain healthy longevity. Thus, long termepidemiologicalstudy of VC intake level is needed. National health and nutrition survey inJapan revealed the very large interindividual difference of daily VC intakes (measured byexact food weighing, not by recall method) during 3 days among Japanese (n=8,762) [65].The highest 1% group ingested 810 mg/day mainly from VC supplements, and the lowest 1%group, 8.4 mg/day, though the average intake was 117 ±157 mg/day [65]. Thus, it wasimpossible to deduce the optimal intake of VC from the average. So, we surveyed 6 Asia-Pacific countries where no supplement is taken, for their blood biochemistry, nutritionalintakes, genetic polymorphisms, daily activity and clinical findings [9, 58-60]. The averageVC intake was the lowest in Mongolians (57.1 mg/day, 48.8 % of Japanese) among thesecountries. Very low blood VC levels (0.35 ±0.25 mg/dL) and high oxidative stress (malondialdehyde 109.5 ±47.7 mg/L, 267 % of Japanese) in Mongolians (Table 1) with the genevariant frequencies in xenobiotic enzymes similar to those in Japanese may explain theirshort life span [9].