Scurvy human

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). 

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. 

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. 

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. 

With respect to human beings there is some question as to what level of tissue saturation should ideally be maintained. In guinea pigs defects in developing incisors appear when the tissue concentrations are about 40 per cent of the maximum. Scurvy symptoms do not appear until the tissue saturation has reached a much lower level (about 20 per cent saturation). It seems logical to suppose that in different individuals the manifestations of mild vitamin C deficiency would be different and that a high degree of saturation would be safest from the standpoint of all the vulnerable tissues. 19... 

Until the 20th century, it was thought that scurvy was confined to humans. Most plants and animals have the ability to synthesize ascorbic acid, but it was discovered that a limited number of animals, including primates, guinea pigs, the Indian fruit bat, and trout, also lack the ability to produce ascorbic acid. In vertebrates, ascorbic acid is made in the fiver from glucose in a four-step process. Each step requires a specific enzyme and humans lack the enzyme required for the last step, gulonolactone oxidase. 

The nutritional need for accessory food factors was first stated explicitly in 1905-1906, although the influence of diet in preventing or curing some diseases such as scurvy had long been known. The name vitamine was proposed in 1912, but the terminal e was dropped when it was realized that not all these compounds are nitrogenous bases. The vitamins serve as coenzymes in various metabolic processes, and the necessary quantities are usually supplied by an adequate diet or by synthesis by the intestinal flora. Vitamin deficiency can arise from a failure to absorb the compound from the gut. The symptoms of deficiency vary in different animal species, and not all the substances found necessary in other species have been shown to be essential for human nutrition. Vitamins are used for the prevention or cure of deficiency diseases and for some other pathological conditions,... 

Complete lack of vitamin C (ascorbic acid) in the diets of humans and other primates leads to a classic disease, scurvy. This nutritional disease, which was probably the first to be recognized, was widespread in Europe during the fifteenth and sixteenth centuries, but it is rare today. 

The antiscorbutic factor of fresh fruits, which prevents the development of the typical symptoms of scurvy in humans, is a carbohydrate derivative known as vitamin C or ascorbic acid. This substance is not a carboxylic acid, but a lactone, and owes its acidic properties (and ease of oxidation) to the presence of an enediol grouping. It belongs to the l series by the glyceraldehyde convention ... 

Vitamin C is important to all animals, including humans, and is vital in the production of collagen. Collagen is important in the formation of connective tissues that give our body shape and help to support vital organs. Vitamin C prevents the disease scurvy. 

The richest sources of vitamin C are citrus fruits (e.g., lemon, oranges), tomatoes, potatoes, green chilies, and human milk. Severe deficiency causes scurvy and is prevalent in malnourished infants, children, adults, alcoholics, and drug addicts. Symptoms such as bleeding gums, deformed teeth, brittle bones, impaired wound healing, anemia, and growth retardation are observed. 

At this point, it may be useful to the reader to understand some of the background that has led to the contemporary design of human clinical trials. Although the concept of a comparative trial was known in the ninth century bc, it remained for James Lind in 1774 to perform his famous trial. Lind was concerned with comparing several different recommended treatments of the day for scurvy. Lind demonstrated that when all of the proposed treatments were compared in a controlled study in human volunteers, only one proved efficacious—citrus fruit. It is important to realize that each of the treatments tested was recommended by recognized authorities of the day. It took the comparative trial to prove that citrus juice cured scurvy and the other treatments were worthless. In the process of applying this scientific method, Lind did much to destroy the credibility of testimonials. 

Vitamin C cannot be synthesized in the human body and must be obtained from the diet (e.g., citrus fruits, broccoli, turnip greens, sweet peppers, tomatoes) or by taking synthetic vitamin C (e.g., vitamin C tablets, high-C drinks, and other vitamin C-fortified commercial foods). The minimum recommended adult daily requirement of vitamin C to prevent scurvy is 60 mg. Some people, among them the late Linus Pauling, twice Nobel Laureate, suggested that very large daily doses (250 to 10,000 mg) of vitamin C could help prevent the common cold, or at least lessen the symptoms for many individuals. No reliable medical data support this claim. At present, the human quantitative requirement for vitamin C is still controversial and requires further research. 

Ascorbic acid is a vitamin in primates. In most other animals, it can be synthesized by a branch of the glucoronic acid pathway (Chapter 18). It is apparently not changed into any coenzyme in the human being and participates as a vitamin in a reducing capacity in several biochemical reactions. These include the post-translational hydroxylation of proline in collagen biosynthesis (Chapter 8) and in tyrosine metabolism (Chapter 20). Ascorbic acid is oxidized to dehydroascorbic acid, a diketo derivative of ascorbate. Scurvy is a deficiency disease caused by a shortage of dietary ascorbic acid. In children, this results in defective bone formation in adults, extensive bleeding occurs in a number of locations. Scurvy is to be suspected if serum ascorbic acid levels fall below 1 jug/mL. 

An autosomal recessive mutant strain of rat, which lacks gulonolactone oxidase and hence is unable to synthesize ascorbic acid, has been described (Mizushima et al., 1984). The animals have an osteogenic disorder akin to scurvy in human infants, and homozygotes are sterile. The addition of... 

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. 

Pauling began corresponding with Stone and learning about vitamin C. He discovered that although vitamin C was a necessary nutrient—without it people die of scurvy— the human body cannot produce it. It has to be taken in through food. 

AA serves as an important cofactor for enzymes. Lack of AA in food causes scurvy in humans due to inefficient collagen synthesis, caused by the inactivation of the Fe(II)-activating prolyl hydroxylase and lysyl hydroxylase which catalyze the formation of hydroxyproline and hydroxylysine as essential components for collagens. Prolyl hydroxylases can also hydroxylate conserved prolyl residues in the alpha subunit of the hypoxia-inducible transcription factor, which signals for proteasomal degradation of the transcription factor . The proper action of these hydrolases requires dioxygen, thus they can act... 

Efficiency in vitamin C, unlike the case with most vitamins, is associated with a specific disease. This disease is scurvy. The symptoms of scurvy include swollen or bleeding gums and hemorrhages under the skin. These symptoms occur when the body s ascorbate is depleted to the point where plasma ascorbate levels are under 0.2 mg/100 mi. Controlled studies with human subjects revealed that symptoms of the disease may develop within 4 weeks with the consumption of an ascorbate-free diet. Scurvy is rarely encountered in developed countries, though it may occur in chronic alcoholism. The disease in humans may be prevented by consuming 10 to 15 mg ascorbic acid per day. 

The human body cannot make its own vitamin C it must be obtained from external sources. Vitamin C also cannot be stored in the body. The disease scurvy, caused by a lack of vitamin C, has always been a threat to people with a limited diet. In 1747, Dr. James Lind studied the effect of diet on sailors who had scurvy. Those whose diet included citrus fruits recovered. In 1795, long before people knew that citrus fruits were rich in vitamin C, the British navy began to distribute lime juice during long sea voyages. For this reason, British sailors were often called limeys. ... 

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