Scurvy experimental

In 1907, Holst and Frolich, of Norway, produced scurvy experimentally in guinea pigs by feeding them a diet deficient in foods containing ascorbic acid. 

Research lea ding to the discovery of vitamin C began in 1907 when it was observed by Axel Holst and Theodor Ern hlich that guinea pigs were as susceptible to scurvy as humans and that the disease could be produced experimentally in these animals (8). These findings led to the development of an assay for the biological deterrnination of antiscorbutic activity of food products (9). 

Vitamin C occurs as L-ascorbic acid and dihydroascorbic acid in fruits, vegetables and potatoes, as well as in processed foods to which it has been added as an antioxidant. The only wholly undisputed function of vitamin C is the prevention of scurvy. Although this is the physiological rationale for the currently recommended intake levels, there is growing evidence that vitamin C may provide additional protective effects against other diseases including cancer, and the recommended dietary allowance (RDA) may be increased in the near future. Scurvy develops in adults whose habitual intake of vitamin C falls below 1 mg/d, and under experimental conditions 10 mg/d is sufficient to prevent or alleviate symptoms (Bartley et al., 1953). The RDA is 60 mg per day in the USA, but plasma levels of ascorbate do not achieve saturation until daily intakes reach around 100 mg (Bates et al., 1979). Most of the ascorbate in human diets is derived from natural sources, and consumers who eat five portions, or about 400-500 g, of fruits and vegetables per day could obtain as much as 200 mg of ascorbate. 

Between mid-1792 and late 1793 Beddoes published a number of works, which set out the theoretical basis for his plans to develop pneumatic medicine. That basis lay primarily in the notion of regulating the atmosphere, that is, adjusting (in experimental and clinical situations) the amount of oxygen that the breathed atmosphere contained, or at least the amount of oxygen taken in by patients. See, in particular, T. Beddoes, Observations on the Nature and Cure of Calculus, Sea Scurvy, Consumption, Catarrh and Fever Together with Conjectures upon Several other subjects of Physiology... 

Baker EM, Hodges RE, Hood J, Sauberlich HE, and March SC (1969) Metabolism of ascorbic-1- C acid in experimental human scurvy. American Journal of Clinical Nutrition 22, 549-58. 

Roy and Guha (R24) induced experimental scurvy in a bird, the red-vented bulbul Pycrorotus cafer). The birds lost weight and feathers and died after 16 to 45 days on a scorbutigenic ration. The scorbutic birds recovered with administration of ascorbic acid. The susceptibility to scurvy correlated well with the lack of activity in this species of the specific liver enzyme which is indispensable for ascorbic acid biosynthesis (L-gulonolactone oxidase). This enzyme was present in the liver of bank-myna Acridotheres ginginmanus) which was not susceptible to scurvy. 

Adult scurvy develops exactly like that observed in the experimental human cases. Its effects are often more severe because they are more prolonged, and because the patients are debilitated by age, other diseases, and associated deficiencies. Purpura and ecchymoses develop at the sites of minor trauma on the lower extremities, and there are hemorrhages into muscles and joints. The gums become swollen, blue-red, and bleed easily, but only around teeth whose looseness provides the mechanical strain needed to initiate the lesion. Old ulcers break down, recent scars of apparently healed wounds become red and hemorrhagic and new wounds fail to heal. Death often occurs suddenly from minor precipitating reasons. The prompt administration of ascorbic acid in curative amounts can be lifesaving. 

There is only uncertainty as to the cause of the hemorrhages. Numerous investigations of capillaries and of the bleeding time in sciurvy have been prompted by the hemorrhages. The results are remarkable only for the lack of any significant alterations uniformly observed. The possibility exists, as Wolbach (W8) assumed, that intercellular substances of the vascular endothelium are not formed. It is clear from the nature of the hemorrhages in human and experimental scurvy that a failure of support either from within or nearby the vascular tissues would permit them to occur. 

Anemia has frequently, but not consistently, been reported in association with scurvy in clinical cases, both in adults and infants, and in experimental scurvy in guinea pigs and monkeys. The extensive literature has been cited (M18, L19, V2). The anemias were not constant in type or severity, although all were reheved when ascorbic acid was reintroduced to tbe diet. In contrast, no anemia or abnormality of the blood picture was ever seen in experimental human scurvy. The therapeutic effect of ascorbic acid on the anemia cannot be accepted as proof of its etiology, since associated deficiencies would also be made good with the return of normal appetite. It is well recognized that the clinical cases of scurvy usually have associated deficiencies. Often, there is iron deficiency in the milk-fed infants, and folic acid or vitamin B12 deficiency in the malnourished adult. ... 

G8. Gould, B. S., and Shwachman, H., Bone and tissue phosphatase in experimental scurvy and studies on the source of serum phosphatase. Am. J. Physiol. 136, 485-491 (1942). 

H16. Holst, A., and Frolich, T., Experimental studies relating to ship beri-beri and scurvy. II. On etiology of scurvy.. Hyg. 7, 634-671 (1907). 

WIO. Wolbach, S. B., Experimental scurvy. Its employment for the study of intercellular substances. In Lind Bicentenary Symposium. Proc. Nutrition Soc. (Engl, and Scot.) 12, 247-255 (1953). 

A recent paper (Reppert et al., 1951) has drawn attention to the remarkable speed with which ascorbic acid corrects the increased capillary fragility in scurvy. It is argued that this could hardly allow time for the repair of intercellular cement substance and suggests rather a direct chemical or enzymic response. Some experiments, reported in the barest outline, claim to show that ascorbic acid in large doses inhibits the hyaluronidase-hyaluronic reaction in rabbits and, to a small extent, in vitro. It is suggested that this inhibition of the spreading factor may account for the rapid improvement in capillary fragility. Obviously more experimental evidence is needed before this supposition can be seriously considered. 

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). 

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