Handbook of Vitamin C Research

viiiHubert Kucharski and Julek Zajacattempted to elucidate methods aimed at attenuating such a stress. One such method that hasreceived considerable attention during the past several years is the use of supplementalvitamin C (either alone or in combination with other antioxidant nutrients). Although someinvestigators have reported a reduction in oxidative stress following vitamin C intake, resultsare mixed, and controversy exists as to whether such attenuation is really desirable. That is,the consumption of additional vitamin C or other exogenous antioxidants, within otherwisehealthy populations, may actually blunt the adaptive improvement in antioxidant defensescommonly observed with regular exercise training. This phenomenon is based on theprinciple of hormesis and suggests that exercise-induced free radical production may serve asthe necessary ―signal‖ for the induction/regulation of a wide variety of favorable adaptations.At the present time, it would appear that vitamin C supplementation likely possesses noadditional benefits related to improved performance in otherwise healthy individuals engagedin regular exercise training who consume a quality diet containing adequate amount of fruits,vegetables, whole grains, and antioxidant-rich oils (fish, flax, olive). However, conditionswhereby an individual is continuously exposed to a currently undefined critical level ofexcessive exercise (i.e., overtraining) may warrant supplementation with vitamin C. Clearly,more research is needed in order to further elucidate the point at which the detrimental effectsof exercise begin to outweigh the positive benefits, and at which time intake of supplementalvitamin C may be recommended.Chapter II - The biomedical significance of human vitamin C (VC) metabolism isreviewed in the light of polymorphisms in xenobiotic enzymes deduced from genetic,biochemical, and epidemiological results to estimate optimal nutrition. VC comprises bothascorbic acid (AsA) and dehydroascorbic acid (DAsA). AsA is oxidized to DAsA via shortlivedmonodehydroascorbate radicals in a series of xenobiotic reactions and by reactiveoxygen species (ROS). DAsA is reversibly reduced by glutaredoxin, but is also irreversiblyhydrolyzed into 2,3-diketo-L-gulonate by dehydroascorbatase [EC 3.1.1.17] and nonenzymaticreactions. VC is a cofactor in reactions catalyzed by Cu + -dependentmonooxygenases [EC 1.13.12.-] and Fe 2+ -dependent dioxygenases [EC 1.13.11.-]. VC playsa protective role against oxidative stress by ROS and xenobiotics, via monodehydroascorbateradicals. The Vitamin Society of Japan has re-evaluated old data because of the developmentof life science. The recommended dietary allowance (RDA) of VC is 100 mg/day for adultsin Japan to prevent scurvy. RDA is defined as EAR+2SD, i.e. estimated average requirement(EAR) and the standard deviation (SD) obtained by short-term depletion-repletion studies.However, based on VC synthetic rates in rat, Pauling proposed that the optimum intake is 2.3g/day. This is the problem of RDA vs. optimal nutrition. Optimal nutrition is wider in scopethan RDA that covers genetic polymorphisms, long-term health outcome during the lifespan,and xenobiotics. Humans (VC auxotrophs) have relatively low plasma AsA levels and highserum uric acid levels compared to most VC-synthesizing mammals (VC autotrophs) due togene defects in L-gulonolactone oxidase (GLO [EC 1.1.3.8]) and uricase (urate oxidase) [EC1.7.3.3], respectively. Extrapolation of metabolic data of VC autotrophs to estimate humanoptimal nutrition is limited because of the compensatory mechanism for the GLO defect inVC auxotrophs, including DAsA transport by GLUT1, and specific mutations in uricase anddehydroascorbatase. Beneficial effects of long-term VC supplementation remaincontroversial, perhaps because of 1. genetic heterogeneity in study populations, and 2. the