Ascorbate depletion, scurvy

The elasticity and structural integrity of the vascular matrix is dependent on ascorbate as an essential cofactor for molecular cross-linking of collagen, hence, the connective tissue-related defects found in scurvy. Even moderate ascorbate depletion, short of scurvy, has been shown to result in increased tendency of the gingiva to bleed or become inflamed (Leggott et al., 1986). Evidence suggests that ascorbic acid has beneficial effects on the human cardiovascular system beyond collagen formation and the antioxidant protection of lipids and LDL mentioned previously. 

Mobilization and Metabolism. The total ascorbic acid body pool in healthy adults has been estimated to be approximately 1.5 g, which increases to 2.3—2.8 g with intakes of 200 mg/d (151—158). Depletion of the body pool to 600 mg initiates physiological changes, and signs of clinical scurvy are reported when the body pool falls below 300 mg (149). Approximately 3—4% of the body pool turns over daily, representing 40—60 mg/d of metabolized, or consumed, vitamin C. Smokers have a higher metaboHc turnover rate of vitamin C (approximately 100 mg/d) and a lower body pool than nonsmokers, unless compensated through increased daily intakes of vitamin C (159). The metaboHsm of ascorbic acid varies among different species. 

The concentration of ascorbate in leukocytes is well correlated with the concentrations in other tissues and falls more slowly than plasma concentration in depletion studies. The reference range of leukocyte ascorbate is 1.1 to 2.8 pmol per 10 cells a significant loss of leukocyte ascorbate coincides with the development of clear clinical signs of scurvy. Predictably, at high levels of ascorbate intake, although the plasma concentration continues to increase with intake, the leukocyte content does not, because the cells, like othertissues, are saturated. 

Efficiency in vitamin C, unlike the case with most vitamins, is associated with a specific disease. This disease is scurvy. The symptoms of scurvy include swollen or bleeding gums and hemorrhages under the skin. These symptoms occur when the body s ascorbate is depleted to the point where plasma ascorbate levels are under 0.2 mg/100 mi. Controlled studies with human subjects revealed that symptoms of the disease may develop within 4 weeks with the consumption of an ascorbate-free diet. Scurvy is rarely encountered in developed countries, though it may occur in chronic alcoholism. The disease in humans may be prevented by consuming 10 to 15 mg ascorbic acid per day. 

This information indicates that depletion of the ascorbate pools to a level causing scurvy takes 2-4 months, but some people may survive... 

There is a quahtative difference between the action of compounds against part of the picture of scurvy, and the action against all symptoms of scurvy but with reduced potency. The small antiscorbutic activity of isoascorbic acid, which has been observed in the past, was not found when guinea pigs were first seriously depleted of ascorbic acid (R8). These authors interpreted the small antiscorbutic action of isoascorbic acid, previously observed, to its protection of residual stores of L-ascorbic acid in the body, an effect which they demonstrated. Similar protective effects by n-ascorbic acid and 3-methylcholanthrene appeared to have been eliminated in the experiments cited above. The several other compounds known to have low antiscorbutic potency deserve reinvestigation in the light of this work. 

It is interesting therefore to review what evidence there is of deranged carbohydrate metabolism under conditions of AA and DHA depletion. The reviewer has not been able to find any reference to deranged carbohydrate in human scurvy. Crandon s glucose tolerance was unaffected by scurvy (Crandon et al., 1940). There is some indecisive literature on the alleged effect of diets low in ascorbic acid on the human glucose tolerance test, but Owens et al. (1941) were unable to show that clinical diabetes was affected in any way by the state of ascorbic acid nutrition. 

Because wounds fail to heal in scurvy, ascorbic acid has been administered routinely to surgical cases, usually in the absence of any evidence that the tissues of the patients were depleted of the vitamin. Yet the observations of Crandon et al. (1940) make it clear that it requires a really severe dietary deficiency of the vitamin to produce any impmrment in the healing of wounds. If any measurable amount of ascorbic acid is present in the plasma, it is most unlikely that doses of ascorbic acid wUl make any difference to the rate of healing or the strength of the scar. The present writer disagrees, in this matter only, with the views of Hunt (1941). 

Ascorbate and Hormone Balance. The highest concentrations of ascorbate are found in the adrenal and pituitary glands, and the terminal stages of scurvy are just preceded by complete depletion of adrenal ascorbate, leading, it has been frequently stated, to scurvy death from adrenocortical failure. This has caused many to suggest that the ascorbic acid-dehydroascorbic acid system plays an important role in the synthesis and release of hormones of the adrenopituitary axis. The evidence for this is both conflicting and confusing (13, 72, 73,102, 277, 278). 

The last section of this review discusses the possible roles of ascorbic acid in the disease states of the nervous system. Mental depression is the first symptom of scurvy, although the half-life of ascorbic acid during depletion in the brain is the longest of all tissues (Pelletier, 1969 Hodges et al., 1971). The appearance of this symptom may be relevant to the interactions of ascorbic acid with dopamine and/or other monoamine neurotransmitter systems (Section 4). 

The concentration of ascorbic acid in the white cell-platelet layer of blood is a much better index of tissue concentration and body stores of vitamin C then the level in plasma. In normal subjects whose tissues are nearly saturated, the white cell-platelet concentration is 25 to 30 mg. per 100 ml. The concentration falls gradually during depletion and reaches zero shortly before signs of scurvy make their appearance. Peters and associates228c suggest that a white cell-platelet concentration of less than 2 mg. per 100 g., on repeated analyses, supports the diagnosis of scurvy. 

Most of the other clinical signs of scurvy can be accounted for by the effects of ascorbate deficiency on collagen synthesis, as a result of impaired proline and lysine hydroxylase activity. Depletion of muscle carnitine (section 5.5.1), as a result of impaired activity of trimethyllysine and y-butyrobetaine hydroxylases, may account for the lassitude and fatigue that precede clinical signs of scurvy. 

---