Scurvy clinical

The first clues to the treatment of scurvy occurred in 1535—1536 when Jacques Cartier, on advice from Newfoundland Indians, fed his crew an extract from spmce tree needles to cure an epidemic. Various physicians were recommending the use of citms fmits to cure scurvy in the mid-sixteenth century. Two hundred years later, in 1753, it was proved by Dr. James Lind, in his famous clinical experiment, that scurvy was associated with diet and caused by lack of fresh vegetables. He also demonstrated that oranges and lemons were the most effective cure against this disease. In 1753, inM Treatise on the Scurvy[ Lind pubhshed his results and recommendations (7). Eorty-two years later, in 1795, the British Navy included lemon juice in seamen s diets, resulting in the familiar nickname "limeys" for British seamen. Evidence has shown that even with undefined scorbutic symptoms, vitamin C levels can be low, and can cause marked diminution in resistance to infections and slow healing of wounds. 

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. 

While this idea of a comparative trial was known in the time of Elijah in the ninth century BC, it took 2500 years for physicians to learn this biblical lesson. In 1774, James Lind did his famous trial comparing several different recommended treatments of scurvy and showing that one worked while all of the others were worthless. It is important to recognize that each of these treatments was recommended by recognized authorities of the day. One must assume that these intelligent physicians had reasons why they thought the remedies they recommended worked. It was just that they were wrong. But it took the comparative trial, not clinical observations to prove that citrus juice cured scurvy and the other treatments were worthless. 

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... 

Most of the other clinical signs of scurvy can be accounted for by effects of deficiency on collagen synthesis as a result of impaired proUne and lysine hydroxylase activity (Section 13.3.3). 

In general, the effects on collagen synthesis are more marked and more important than those of decreased formation of carnitine (as a result of impaired activity of trimethyllysine and y-butyrobetaine hydroxylases Section 14.1.1), impaired xenobiotic metabolism, or hypercholesterolemia (Section 13.3.8). However, depletion of muscle carititine may account for the lassitude and fatigue that precede clinical signs of scurvy. 

The plasma concentration of vitamin C falls relatively rapidly during depletion studies, to undetectably low levels within 4 weeks of initiating a vitamin C-free diet, although clinical signs of scurvy may not develop for a further 3 to... 

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. 

The minimum requirement for vitamin C was established in the Sheffield study (Medical Research Council, 1948), which showed that an intake of marginally less than 10 mg per day was adequate to prevent the development of scurvy or to cure the clinical signs. Results from the Iowa study (Baker et al., 1969,... 

A priori, the best means of determining vitamin C requirement would seem to be determination of the total body pool and its fractional rate of loss or catabolism. An appropriate intake would then be that to replace losses and maintain the body pool. Clinical signs of scurvy are seen when the total body pool of ascorbate is below 1.7 mmol (300 mg). The pool increases with intake, reaching a maximum of about 8.5 mmol (1,500 mg) in adults -114 /rmol (20 mg) per kg of body weight. The fractional turnover rate of ascorbate is 3% to 4% daily, suggesting a need for 45 to 60 mg per day for replacement. The basis for the 1989 U.S. Recommended Daily Allowance (RDA) of 60 mg (National Research Council, 1989) was the observed mean fractional turnover rate of 3.2% of a body pool of 20 mg per kg of body weight per day, with allowances for incomplete absorption of dietary ascorbate and individual variation. 

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. 

His Treatise of the Scurvy published in 1753 is the first example of a controlled clinical trial experiment. In his treatise, Lind gave a thorough review of other authors who had written on scurvy along with a careful clinical description of the condition. It was not until the end of the eighteenth century that the British navy finally had its sailors drink a daily portion of lime or lemon juice to prevent scurvy. 

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