Deficiency ascorbate

In a recent study, serum ascorbate concentrations were significantly reduced in a group of elderly diabetic patients (w = 40, mean age 69 years) in comparison with an age-matched group of non-diabetic controls ( = 22, mean age 71 years), and this reduction was more pronounced in those patients with microangiopathy (Sinclair et al., 1991). Diabetic patients were shown to have a high serum dehydroascorbate/ascorbate ratio indicative of increased oxidative stress. Ascorbate deficiency was partially corrected by vitamin C supplementation, 1 g daily by mouth, but the obvious disturbance in ascorbate metabolism in the diabetic patients was accentuated, since serum ascorbate concentrations fell (after the initial rise) despite continued vitamin C supplementation (Fig. 12.3). 

Scurvy Deficient hydroxylation secondary to ascorbate deficiency Petechiae, ecchymoses Loose teeth, bleeding gums Poor woimd healing Poor bone development... 

Lenton KJ, Sane AT, Therriault H, et al. Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency. Am J Clin Nutr 2003 77 189-195. 

Ascorbate is synthesized in large amounts in plants, it can reach 20 to 300 mmol per L in chloroplasts, where its function is mainly to remove hydrogen peroxide formed during photosynthesis. Ascorbate-deficient mutant plants are especially sensitive to ozone- and ultraviolet-induced stress (Smirnoff, 2000). 

L-Ascorbic acid was also analyzed in tissues from hornworms fed a vitamin-deficient diet. Without L-ascorbic acid neonate larvae grew into the third instar, but died before the next molt. These larvae retained little or no vitamin in tissues (Table II). A similar result was characteristic of fifth instar larvae reared on an ascorbate-deficient diet beginning at the mid fourth instar. These larvae failed to complete pupation. Apparently, the diet was the sole source of L-ascorbic acid and when tissues became depleted, major pathological consequences ensued. 

Hornworm reared on ascorbate deficient diet from middle of fourth larval instar. Hornworm reared on ascorbate deficient diet from neonate stage. 

A large documentation on scurvy has been accumulated during the centuries. Some relevant reports, which contain kinetic information on the development of ascorbate deficiency, will be reviewed briefly. The first well-known, detailed, and comprehensive report on this disease, Treatise on Scurvy, was published in 1757 by the Scottish naval physician James Lind (2). Some case reports are cited here. Thus, during the journey of H.M.S. Salisbury from August 10 to October 28, 1746 (i.e., 75 d), only one sailor was reported ill with the disease. In a report of four ships bound for the East Indies, 105 out of 424 sailors were reported dead from scurvy within 4 months. Other fragmentary notes are oflBcial reports by the Danish and Dutch East India Companies of regular outbreaks of the disease after 5-6 months at sea. This was in the seventeenth century. 

Table VII. Hepatic Epoxide Hydrase and Glutathione Transferase in Normal and Ascorbate Deficient Guinea Pigs...

Ascorbic Acid Deficiency. Scurvy is the classical disease associated with ascorbate deficiency. It is a disease of the connective tissue and probably is caused by inadequate crosslinking attributed to a lack of hydroxy-lated proline and lysine. Many consider scurvy to be an advanced stage of ascorbate deficiency. Chronic deficiencies may also (l)in-crease risk for malignancies, as evidenced by oxidized DNA markers and increased concentrations of reactive oxygen species (2) decreased immune function, as evidenced by less vitamin in neutrophils and lymphocytes (3) cardiovascular disease caused by the inflammatory response on the blood vessel walls and (4) cataract formation caused by decreased concentrations of ascorbate in the ocular tissues. 

Ascorbic acid deficiency in guinea pigs has been shown to decrease microsomal cytochrome P-450 activity to about 50% of its normal value (96, 97,192, 203, 268) cytochrome bs (96,97, 174,192, 302, 358), NADPH-linked cytochrome c reductase (174, 358), and O- and A/-demethylase activities (174, 185, 192, 358). Conflicting data by Kato et al. (170) in which the above-mentioned enzyme activities were not affected by ascorbate deficiency seem to be the result of a shorter depletion period (12 days). Zannoni and Sato (Ref. 174, p. 119) have shown that microsomal enzyme activities are not decreased significantly in a 10-day depletion experiment but are significantly decreased after 21 days. Repletion experiments with scorbutic guinea pigs have shown that supplementation with ascorbic acid returned cytochrome P-450 and demethylation activities to normal within 48 hr (97,192, 203). 

Ascorbate and Energy Production. Cytochromes P-450 and bs are decreased by ascorbate deprivation in the guinea pig, and because cytochromes are intimately associated with electron transport, and therefore oxidative phosphorylation, it is possible that cell respiratory impairment could result from relative ascorbate deficiency and, of course, an... 

We have recently presented ascorbate deficiency as the primary cause of human CVD. We proposed that the most frequent pathome-chanism leading to the development of atherosclerotic plaques is the deposition of Lp(a) and fibrinogen/fibrin in the ascorbate-deficient vascular wall. - In the course of this work we discovered that virtually every patho-mechanism for human CVD known today can be induced by ascorbate deficiency. Beside the deposition of Lp(a) this includes such seemingly unrelated processes as foam cell formation and decreased reverse-cholesterol... 

The morphologic changes in the vascular wall induced by ascorbate deficiency are well characterized the loosening of the connective tissue and the loss of the endothelial barrier function. The extraordinary pressure by fatal blood loss through the scorbutic vascular wall favored genetic and metabolic countermeasures attenuating increased vascular permeability. 

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