Scurvy

The best clinical description of scurvy is that given by Lind (1753) he had greater experience of the disease than perhaps any other physician before or since and knew how to record his observations. In his study of the natural history and pathology of the disease he advanced knowledge about as far as it was possible to go without the aid of a microscope. Even so, he described the peculiar laxness of the tissues at autopsy—a change now known to be due to lack of collagen in the connective tissue. 

A clinical account of scurvy as it still occurs sporadically in Edinburgh has been given by McMillan and Inglis (1944) and in the United States by Vilter et al. (1946). 

The application of Lind s teaching to the prevention of scurvy had made it a rare disease in civilized communities long before ascorbic acid was isolated, identified, and synthesized in 1928-1933. The historian of the future, looking back on this time, might well conclude that the discovery of vitamin C was important not so much for the inunediate nutritional benefits that it brought to mankind as for the stimulus it gave to the study of metabolic processes involving the vitamin. 

The distribution of ascorbic acid in animal tissues has been reviewed by Giroud (1939). Cellular tissues contain a greater concentration of the 

When the human body is saturated with the vitamin the blood plasma contains 1.0 to 1.4 mg./lOO ml. Attempts to produce higher blood levels, by means of massive doses, merely result in a rapid loss of the excess vitamin in the urine (Van Eekelen, 1936 Faulkner and Taylor, 1938 Ralli et ah, 1939). The above figures, however, do not represent a true renal threshold because small amounts of the vitamin appear in the urine when the plasma level is much lower. 

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M.p. 190-192 C. The enolic form of 3-oxo-L-gulofuranolactone. It can be prepared by synthesis from glucose, or extracted from plant sources such as rose hips, blackcurrants or citrus fruits. Easily oxidized. It is essential for the formation of collagen and intercellular material, bone and teeth, and for the healing of wounds. It is used in the treatment of scurvy. Man is one of the few mammals unable to manufacture ascorbic acid in his liver. Used as a photographic developing agent in alkaline solution. 

Our word vitamin was coined m 1912 m the belief that the substances present m the diet that prevented scurvy pellagra beriberi rickets and other diseases were vital amines In many cases that belief was confirmed certain vitamins did prove to be amines In many other cases however vitamins were not amines Nevertheless the name vitamin entered our language and stands as a reminder that early chemists recognized the crucial place occupied by amines m biological processes... 

In this period, the empirical healing of certain diseases by foods was estabUshed. Examples (3) were the treatment of night blindness (vitamin A deficiency) with hver ia many cultures over centuries, of beriberi (vitamin deficiency) by use of unpoHshed rice by the Japanese navy, of scurvy (vitamin C deficiency) by citms fmits ia the British navy or piae needle extracts by North American natives, and pellagra (niacia deficiency) by a dietary shift away from corn-based foods ia many countries. Other, nondietary empirical treatments iavolved, eg, exposure of children ia northern latitudes to sunlight to cute tickets (vitamin D deficiency) (4). 

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. 

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). 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

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. 

The half-life of ascorbic acid is inversely related to the daily intake and is 13—40 d in humans and 3 d in guinea pigs, which is consistent with the longer time for humans to develop scurvy. 

J. Lind,H Treatise on the Scurvy, London, 1753 (repubhshed by Edinburgh University Press, Edinburgh, Scodand, 1953). 

Scurvy results from a dietary vitamin C deficiency and involves the inability to form collagen fibrils properly. This is the result of reduced activity of prolyl hydroxylase, which is vitamin C-dependent, as previously noted. Scurvy leads to lesions in the skin and blood vessels, and, in its advanced stages, it can lead to grotesque disfiguration and eventual death. Although rare in the modern world, it was a disease well known to sea-faring explorers in earlier times who did not appreciate the importance of fresh fruits and vegetables in the diet. 

In addition to its role in preventing scurvy (see Human Biochemistry box Ascorbic Acid and Scurvy and also Chapter 6), ascorbic acid also plays important roles in the brain and nervous system. It also mobilizes iron in the body, prevents anemia, ameliorates allergic responses, and stimulates the immune system. 

Coclilearia or apoonwort oil is distilled frr-m the freah-Howering plant Cuchl iriji (scurvy grass which yielda a very small quanlily of... 

Ibffelfonnig, a. spoon-shaped, spatular. LSffelkraut, n. scurvy grass (Cochlearia offiei-nalia). 

In addition to the hazards of weather, participants in early polar expeditions often suffered from scurvy, caused by a dietary vitamin C deficiency. 

Schiffbase, 1147 Scurvy vitamin C and, 772 sec-Butyl group, 84 Second-order reaction, 363 Secondary alcohol, 600 Secondary amine, 917 Secondary carbon, 84 Secondary hydrogen. 85 Secondary structure (protein), 1038-1039... 

Vitamin C, industrial synthesis of, 773 molecular model of, 772 scurvy and. 772 uses of. 772... 

The complex series of events in collagen maturation provide a model that illustrates the biologic consequences of incomplete polypeptide maturation. The best-known defect in collagen biosynthesis is scurvy, a result of a dietary deficiency of vitamin C required by... 

Silk fibroin and collagen illustrate the close linkage of protein stmcture and biologic function. Diseases of collagen mamration include Ehlers-Danlos syndrome and the vitamin C deficiency disease scurvy. 

Peptidyl hydroxyprohne and hydroxylysine are formed by hydroxylation of peptidyl proline or lysine in reactions catalyzed by mixed-function oxidases that require vitamin C as cofactor. The nutritional disease scurvy reflects impaired hydroxylation due to a deficiency of vitamin C. 

The water-soluble vitamins comprise the B complex and vitamin C and function as enzyme cofactors. Fofic acid acts as a carrier of one-carbon units. Deficiency of a single vitamin of the B complex is rare, since poor diets are most often associated with multiple deficiency states. Nevertheless, specific syndromes are characteristic of deficiencies of individual vitamins, eg, beriberi (thiamin) cheilosis, glossitis, seborrhea (riboflavin) pellagra (niacin) peripheral neuritis (pyridoxine) megaloblastic anemia, methyhnalonic aciduria, and pernicious anemia (vitamin Bjj) and megaloblastic anemia (folic acid). Vitamin C deficiency leads to scurvy. 

C Ascorbic acid Coenzyme in hydroxylation of proline and lysine in collagen synthesis antioxidant enhances absorption of iron Scurvy—impaired wound healing, loss of dental cement, subcutaneous hemorrhage... 

Signs of vitamin C deficiency in scurvy include skin changes, fragifity of blood capillaries, gum decay, tooth loss, and bone fracmre, many of which can be attributed to deficient collagen synthesis. 

Scurvy affects the structure of collagen. However, it is due to a deficiency of ascorbic acid (Chapter 45) and is not a genetic disease. Its major signs are bleeding... 

Diseases associated with impaired synthesis of collagen include scurvy, osteogenesis imperfecta, Ehlers-Danlos syndrome (many types), and Menkes disease. 

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. 

This of course goes a long way to explaining the association of scurvy with vitamin C deficiency, and the successful utilization by the British navy of lime juice as a means of prevention of the disease - hence the expression limey for British sailors. 

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