Scurvy Adrenals

Buu Hoi and Ratsimamanga116 found that kojic acid protected the adrenal ascorbic acid in test animals during the reversible period of scurvy, without itself showing vitamin C action. 

Deficiency in vitamin C leads to the disease scurvy due to the role of the vitamin in the post-translational modification of collagens. Scurvy is characterized by easily bruised skin, muscle fatigue, soft swollen gums, decreased wound healing and hemorrhaging, osteoporosis, and anemia. Vitamin C is readily absorbed and so the primary cause of vitamin C deficiency is poor diet and/or an increased requirement. The primary physiological state leading to an ihcreased requirement for vitamin C is severe stress (or trauma). This is due to a rapid depletion in the adrenal stores of the vitamin. The reason for the decrease in adrenal vitamin C levels is unclear but may be due either to redistribution of the vitamin to areas that need it or an overall increased utilization. 

Absorption of vitamin C from the small intestine is a carrier-mediated process that requires sodium at the luminal surface. Transport is most rapid in the ileum and resembles the sodium-dependent transport of sugars and amino acids, but the carrier is distinct for each class of compound. Some ascorbate may also enter by simple diffusion. With dietary intake less than 100 mg/d, efficiency of absorption is 80-90%. With intake equal to the RDA, plasma ascorbate is 0.7-1.2 mg/dL, and the ascorbate pool size is 1500 mg. Scurvy becomes evident when the pool is less than 300 mg, at which point plasma ascorbate is 0.13-0.24 mg/dL. Highest tissue concentrations of ascorbate are in the adrenal gland (cortex > medulla). 

Biochemical changes in scurvy not associated with discrete enzymes have been reported. The ratio of RNA to DNA increased in spleen and adrenals (G6). The DNA content of a fibrosarcoma was decreased by scurvy, and glucoascorbic acid given to lower the tissue ascorbic acid levels in rats decreased the DNA in rat carcinoma (S21). Dinning et al. (D15) expected defects in the reactions where folic acid participates. 

Another method that has been used to measure the excretion of adrenal steroids is the determination of formaldehydogenic steroids in the urine. This is no longer considered a reliable method of chemical assay and bears no certain relation to adrenocortical function (Marrian, 1952) nevertheless, it is worth reviewing the results obtained by this method in human scurvy. When ascorbic acid was administered to three patients with scurvy, instead of the expected increase in the excretion of formalde-hydogenic hormones, there was a fall in their excretion lasting several days (Daughaday et al., 1948). 

Even the most ardent supporters of the belief that ascorbic acid is concerned in the synthesis of cortical hormones would probably hesitate today to suggest that this is the most important function of ascorbic acid in the body, still less its only function there are too many obvious reasons for thinking otherwise. The first is that human patients whose adrenals have been destroyed suffer from Addison s disease but do not develop scurvy. They continue to show normal levels of ascorbic acid in the blood (Jenovese el al., 1940), and there is no evidence that their collagen is affected. Though there were some initial reports (e.g., Wilkinson and Ashford, 1936) that patients with Addison s disease suffered from ascorbic acid deficiency, this idea has faded from the recent literature. Secondly, the amount of ascorbic acid in the adrenal cortices is less than 1 per cent of the total amount in the human body (Section III, 2) it would be against what we know of the economy of the body to think that all the rest of this active metabolite was simply hanging around in the other tissues, waiting for the adrenals to find a use for it. 

It is worth-while nevertheless to consider what may happen in experimental scurvy when the adrenal cortex is (a) relieved of its task of making hormones by directly injecting them, and (b) stimulated to greater hormonal output. This is considered in the following section. Many of the facts have already been reviewed by Morgan (1951). 

It is generally assumed today that cholesterol is the raw material from which the adrenal cortex makes its hormones, despite the theoretical doubts of the chemists (see Sayers, 1950). If ascorbic acid were necessary for this synthesis, it might have been expected that scurvy would result in a piling-up of unused cholesterol in the gland, on the analogy of the accumulation of colloid in the thyroid gland deprived of iodine. In fact,... 

Recently it has been proposed (Eisenstein and Shank, 1951 Pirani, 1952) that scurvy itself is just another nonspecific stress. The changes seen in the adrenals in this disease can then be simply explained on the assumption of cortical stimulation by the anterior pituitary. The dietary deficiency of ascorbic acid is thus no longer necessary to explain the reduction of ascorbic acid in the cortexl A more interesting question than Is scurvy a stress is Does stress precipitate scurvy The answer is certainly, yes. 

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). 

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