Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strong clinical and experimental evidence suggests that chronic latent vitamin C deficiency leads to hypercholesterolaemia and the accumulation of cholesterol in certain tissues. Ascorbic acid supplementation of the diet of hypercholesterolaemic humans and animals generally results in a significant reduction in plasma cholesterol concentration. While most studies relating ascorbic acid to atherosclerosis have used the rabbit as a model, those concerned with elucidating the role of ascorbic acid in the regulation of cholesterol metabolism have generally used the guinea pig. Comparatively little use has been made of the non-human primates. A significant advance in recent years has been the development of a model of chronic latent scurvy in the guinea pig. Chronic dietary inadequacy of vitamin C may influence the pathogenesis of atherosclerosis as it affects not only plasma cholesterol and triglyceride concentrations but also the integrity of the vascular wall. Ascorbic acid is involved in the regulation of cholesterol metabolism in several ways. Dietary inadequacy of vitamin C is associated indirectly with a lowering of cholesterol absorption, this effect resulting from a reduction in the availability of bile acids, monoglycerides and fatty acids. The excretion of cholesterol as neutral steroids, however, appears not to be affected by ascorbic acid. Although much of the evidence for the involvement of ascorbic acid in cholesterol synthesis is equivocal, it seems likely that cholesterol synthesis is decreased in vitamin C deficiency. A series of studies using guinea pigs with chronic latent vitamin C deficiency has provided clear evidence that bile acid synthesis is reduced in this condition. Indirect evidence strongly suggests that this results from a decrease in the activity of the microsomal enzyme cholesterol 7 alpha-hydroxylase. However, some evidence suggests that the mitochondrial reactions of bile acid synthesis require ascorbic acid. The role of ascorbic acid in the regulation of steroidogenesis appears to involve selective inhibitory and stimulatory effects on the desmolase, hydroxylase and dehydrogenase reactions which lead to the formation of pregnenolone and its subsequent conversion to steroid hormones.
Atherosclerosis
PMID:The role of ascorbic acid in the regulation of cholesterol metabolism and in the pathogenesis of artherosclerosis. 94 15

Pharmacologic doses of folate, in the absence of clinical folate deficiency, can reduce plasma levels of the putatively atherothrombotic amino acid, homocysteine (H(e)). Data suggesting that H(e) may accumulate in experimental scurvy prompted us to explore the efficacy of high dose ascorbate supplementation as a H(e)-lowering treatment, in the absence of clinical ascorbate deficiency. A randomized, placebo-controlled trial of 12 weeks of high dose (4.5 g/day) ascorbate supplementation was completed by 44 patients with established coronary heart disease. No significant change in mean fasting total plasma H(e) levels was demonstrable despite a marked increase in mean fasting plasma ascorbate levels amongst those patients randomized to active treatment. Ascorbate supplementation to prevent the development of fasting hyperhomocysteinemia may only be relevant at scorbutic levels of plasma ascorbate.
Atherosclerosis 1994 Dec
PMID:High dose ascorbate supplementation fails to affect plasma homocyst(e)ine levels in patients with coronary heart disease. 771 29

Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease. Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity. We suggest that in latent scurvy, large blood vessels use modified LDL--in particular lipoprotein(a)--in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange. The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.
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PMID:Hyperglycemia-induced latent scurvy and atherosclerosis: the scorbutic-metaplasia hypothesis. 869 35

Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype-related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis between Hp phenotypes is attributable to variation in LDL oxidation. The classical view of vitamin C and scurvy being a pure nutritional condition needs to be updated. These findings should foster research investigating the role of Hp polymorphism in human disease, and in vitamin C deficiency and atherosclerosis in particular.
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PMID:Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. 1764 91

The recognition of vitamin C is associated with a history of an unrelenting search for the cause of the ancient haemorrhagic disease scurvy. Isolated in 1928, vitamin C is essential for the development and maintenance of connective tissues. It plays an important role in bone formation, wound healing and the maintenance of healthy gums. Vitamin C plays an important role in a number of metabolic functions including the activation of the B vitamin, folic acid, the conversion of cholesterol to bile acids and the conversion of the amino acid, tryptophan, to the neurotransmitter, serotonin. It is an antioxidant that protects body from free radical damage. It is used as therapeutic agent in many diseases and disorders. Vitamin C protects the immune system, reduces the severity of allergic reactions and helps to fight off infections. However the significance and beneficial effect of vitamin C in respect to human disease such as cancer, atherosclerosis, diabetes, neurodegenerative disease and metal toxicity however remains equivocal. Thus further continuous uninterrupted efforts may open new vistas to understand its significance in disease management.
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PMID:Vitamin C in disease prevention and cure: an overview. 2442 32

Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals. Better understanding of the evolutionary advantage of this molecule should elucidate its physiological role. We developed a new mouse model with two characteristics of human metabolism: the expression of Lp(a) and the lack of endogenous ascorbate (vitamin C) production. We show that dietary deficiency of ascorbate increases serum levels of Lp(a). Moreover, chronic hypoascorbemia and complete depletion of ascorbate (scurvy) leads to Lp(a) accumulation in the vascular wall and parallels atherosclerotic lesion development. The results suggest that dietary ascorbate deficiency is a risk factor for atherosclerosis independent of dietary lipids. We provide support for the concept that Lp(a) functions as a mobile repair molecule compensating for the structural impairment of the vascular wall, a morphological hallmark of hypoascorbemia and scurvy.
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PMID:Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice. 2606 92

Vitamin C is a powerful dietary antioxidant that has received considerable attention in the literature related to its possible role in heart health. Although classical vitamin C deficiency, marked by scurvy, is rare in most parts of the world, some research has shown variable heart disease risks depending on plasma vitamin C concentration, even within the normal range. Furthermore, other studies have suggested possible heart-related benefits to vitamin C taken in doses beyond the minimal amounts required to prevent classically defined deficiency. The objective of this review is to systematically review the findings of existing epidemiologic research on vitamin C and its potential role in cardiovascular disease (CVD). It is well established that vitamin C inhibits oxidation of LDL-protein, thereby reducing atherosclerosis, but the cardiovascular outcomes related to this action and other actions of vitamin C are not fully understood. Randomized controlled trials as well as observational cohort studies have investigated this topic with varying results. Vitamin C has been linked in some work to improvements in lipid profiles, arterial stiffness, and endothelial function. However, other studies have failed to confirm these results, and observational cohort studies are varied in their findings on the vitamin's effect on CVD risk and mortality. Overall, current research suggests that vitamin C deficiency is associated with a higher risk of mortality from CVD and that vitamin C may slightly improve endothelial function and lipid profiles in some groups, especially those with low plasma vitamin C levels. However, the current literature provides little support for the widespread use of vitamin C supplementation to reduce CVD risk or mortality.
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PMID:Vitamin C and Heart Health: A Review Based on Findings from Epidemiologic Studies. 2752 39

Garcinia dulcis (Roxb.) Kurz is a tropical fruit tree native to Southeast Asia where it has a long history of use as a traditional medicine for the treatment of ailments such as lymphatitis, parotitis, struma, scurvy, cough, and sore throat. Despite its medicinal values, this plant is not well known and rarely found nowadays. Research on the phytochemical constituents and biological activities of G. dulcis have demonstrated that various parts of the plant contain an. abundance of bioactive compounds mainly xanthones and flavonoids, with significant pharmacological properties such as anti-atherosclerosis, anti-bacterial, anti-cancer, anti-hypertension, and anti-malarial. In the present review, current knowledge of the phytochemistry of G. dulcis and biological activities of its active constituents based on the available literature are summarized in order to explore application potentials and prospective research works on this plant.
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PMID:Phytoconstituents and Biological Activities of Garcinia dulcis (Clusiaceae): A Review. 3054 9