The instability of vitamin C in air, and especially in neutral or alkaline aqueous solution, is attributable to the fact that in the presence of oxygen or other oxidizing agents it readily undergoes two successive one-electron oxidation steps to produce dehydro-ascorbate. Since the oxidation products are also unstable and undergo an irreversible lactone ring opening to diketogulonic acid, the vitamin is very easily destroyed, both in foods and (to a lesser extent because of efficient recycling mechanisms) in the body. Diketogulonic acid is one of several degradation products of vitamin C that cannot be reconverted to the vitamin and are further degraded to stable excretory products, such as oxalic acid, by oxidative metabolism. Of all the micronutrients that are essential for human health and survival, vitamin C is the most easily destroyed during drying and other traditional methods of preserving food. Citrus fruits contain other organic acids that inhibit this process of oxidation by lowering the pH of the fruit juice. This enables them, and extracts of them, to preserve at least some of their vitamin content for several weeks and even months of storage and thereby helps them to prevent and cure scurvy.
It remains largely a mystery why some people succumb to classical scurvy after a short period of virtually zero intake, whereas others survive for much longer. It has been speculated that some people may be able to produce all of the enzymes of the vitamin C synthetic pathway, including gulo-nolactone oxidase, which is normally absent from humans. However, this now seems unlikely, and it is more probable that the retention and recycling mechanisms for the vitamin are more efficient in some people than in others. We now know, for example, that smokers have a higher turnover of endogenous vitamin C than non-smokers, presumably because of the free-radical oxidant species in cigarette smoke. People with infections also have increased vitamin C turnover, which is associated with the liberation of pro-oxidant substances (such as hypochlorous acid) that are used by the body to kill bacteria. Some people have isoforms of certain blood proteins such as haptoglobins that are associated with relatively low levels of vitamin C in the blood. Very occasionally, there arise non-lethal mutations of vitamin C-dependent pathways whose abnormalities can be treated with high vitamin C intakes. A well-characterized example is Ehlers-Danlos syndrome, type VI, which is associated with impaired collagen lysyl hydroxylation and presents with a variety of clinical and biochemical connective-tissue (collagen-related) defects. However, much more research is needed to determine which of many possible genetic and environmental factors modulate the turnover of vitamin C in the body and to determine individual requirements and hence relative resistance to scurvy. Although 100-200 mg of the vitamin per day is needed to approach saturation of the tissues of humans, the amount needed to prevent or cure scurvy is less than 10mgday_1, as was shown by experiments involving prolonged periods of feeding with depleted diets in the middle of the twentieth century (Table 1). Today, overt clinical scurvy is rare. It is occasionally seen in refugee camps or in elderly people with poor diets that are devoid of the usual sources of the vitamin. The latter high-risk group contains many individuals who are unable to chew fresh fruit and vegetables because of bad dentures or poor gastric tolerance of acidic or fibrous foods (see below).
An essential dietary requirement for vitamin C (l-ascorbic acid) is shared with humans by only a small number of other vertebrates, including primates, guinea pigs and agoutis, and some birds and fishes. Most mammals synthesize the vitamin in their livers from hexose sugars; birds synthesize it in their kidneys. The final enzyme in the pathway, l-gulono-lactone oxidase, has been lost in several unrelated species, suggesting a vulnerable and easily mutated locus on the genome. Presumably this mutation was neutral or advantageous during the natural selection of man's ancestors, when human and related-primate diets were rich in plant-derived sources of the vitamin.
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