Handbook of Vitamin C Research

76Yasuo Kagawa, Shizu Higasa, Masaru Tsujimura et al.similar to V max of the human sodium-dependent VC tissue transporter (SVCT2) [16, 30].VC concentrations were determined at steady state over the dose range in neutrophils,monocytes, lymphocytes, and platelets [63]. As for plasma, most cells saturated between 200and 400 mg/day [68].There are three important questions raised against the uniform RDA based on the averageshort-term EAR [28, 29] as follows: (1) the genetic polymorphisms of VC-related enzymesmay cause marked interindividual difference in VC metabolism as shown by Tables 1-3 andFigure 3 [4, 5]; (2) the long-term optimal intake of VC may be different from RDA; and (3)the increase of VC requirement by ROS produced by exercise and xenobiotics has alreadybeen described on smokers [42, 81], coke oven workers [79] and chronic intoxication [80].For example, Genetic analysis of polymorphisms especially on xenobiotic enzymes (Tables 2and 3) [4, 5, 8] will partly answer the question (1) as described in this review. Detailed wellcontrolled interventional [10, 33] and epidemiological studies [9, 10] will partly answer thequestion (2). Besides RDA, tentative dietary goal for preventing life-style related diseases(DG) is determined for many nutrients. However, DG for VC has not been announced [28,29].Pauling recommended to ingest 2.3g or more VC/day for optimal nutrition and health foran adult with energy requirement 2500 kcal/day, based on synthetic rates in rat (VC58mg/day/kg body weight), proportionality of VC requirement for guinea pig (VC 1.8-4.1g/day/70kg) , and the green foodstuffs eaten by gorilla (VC intake 4.5 g/day) [30].However, the comparison with rat, guinea pig and monkeys is not pertinent because the ratelimiting step in VC catabolism, dehydroascorbatase activity per liver protein is about 34-, 14-and 2 fold, respectively, higher than that of humans [3]. The tolerable upper intake level (UL)of VC is not determined officially but stated as around 40 g/day [28], because the intravenousadministration of 30 g VC/ 80 min for therapeutic purpose are still tolerated [75]. Johnsonsgroup suggest that both mutations in GLO and uricase during human evolution may haveprovided a survival advantage to early primates by helping maintain blood pressure duringperiods of dietary change and environmental stress [25]. In fact, in a randomised, doubleblind,placebo-controlled study, treatment of hypertensive patients with ascorbic acid (500mg/day) lowered mean blood pressure (110 to 100 mmHg, p