Etiology
Vitamin C deficiency is always due to inadequate dietary intake of vitamin C. Several factors influencing vitamin C metabolism have been hypothesized, but have not been corroborated with clinical or epidemiologic study. These factors include genetic variability in haptoglobin and conditioned scurvy. Conditioned scurvy, or scurvy with normal vitamin C levels, was hypothesized to occur due to hypermetabolism of vitamin C after cessation of supratherapeutic doses or megadoses of vitamin C.[25] Evidence in humans is limited to case reports, including one of gingival scurvy from 1982 without laboratory data, which was subsequently refuted.[26][27] Conditioned scurvy has not since been substantiated in the medical literature and no known cases have been reported in clinical trials of large doses of vitamin C for various conditions.
Pathophysiology
Scurvy is relatively rare in the animal kingdom. A very small number of animals and humans are known to be susceptible to scurvy; this susceptibility is probably related to differential erythrocyte dehydroascorbate absorption in mammals, including humans, that depend on exogenous vitamin C.[28][29][30][31] In humans, vitamin C enters the body when consumed in various sources including fruits, vegetables, organ meats, or certain animal milks, and is absorbed from the gut by active and passive transport. Nearly all doses up to 100 mg/day of vitamin C are absorbed. Although plasma levels are not used to diagnose scurvy, with recommended doses of vitamin C, levels range from 0.4 to 1.4 mg/dL and urinary excretion begins at approximately 1.4 mg/dL. Human body stores of vitamin C are approximately 20 mg/kg when taking the recommended daily amount of vitamin C.[32] Catabolism of vitamin C occurs at a rate of 2% to 4% per day.[2]
Vitamin C is a powerful reducing agent that remains stable in its crystalline form. Within an aqueous solution, vitamin C is subject to degradation due to oxidation, high pH, high temperature, or metallic ions. This is worth noting because vitamin C intake can be deceptively low in people with diets seemingly replete with fruits and vegetables. For example, frozen peas may have only 17% of the vitamin C available compared with fresh peas, and canned peas may have as little as 6%.[1]
Manifestations of scurvy are related to disruption of vitamin-C-dependent pathways. Most importantly, vitamin C is essential for collagen synthesis as a cofactor for hydroxylation of proline to hydroxyproline in the formation of procollagen. Without this step, the collagen triple helix cannot assemble. As existing collagen breaks down over time with insufficient replacement with new collagen, blood vessel walls lose their integrity, leading to perivascular edema, erythrocyte extravasation, and frank hemorrhage.[1][19] Vitamin C typically increases intestinal iron absorption 2- to 6-fold, and sometimes more, and may explain why iron deficiency is seen as a concomitant illness.[1][20]
Vitamin C is also essential as an electron donor for pathways involving synthesis of norepinephrine, amidation of peptide hormones, and tyrosine metabolism.[20] In vitro, vitamin C acts as a reducing agent and has been proposed to play a role in modifying a host of diseases including malignancies, atherosclerosis, and dementia.[33] Epidemiologic and intervention studies have been contradictory, inconclusive, or shown no benefit. Thus, vitamin C is not recommended as disease modifying therapy for these conditions, though in normal doses it is not thought to be harmful in these diseases.[20][34][35]
Use of this content is subject to our disclaimer