Clinical manifestations of ascorbic acid deficiency in man

Hodges, Robert E.; Hood, James; Canham, John E.; Sauberlich, Howerde E.; Baker, Eugene M.

doi:10.1093/ajcn/24.4.432

Cited by 339 publications

(163 citation statements)

References 16 publications

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“…Thus, activated neutrophils participating in inflammatory reactions may provide other cell types with increased antioxidant protection. Using phorbol 12-myristate 13-acetate (PMA) 1 -activated cells (HL-60 neutrophils and normal human neutrophils), we validated the concept that superoxide produced by activated cells does oxidize extracellular ascorbic acid to dehydroascorbic acid. We used co-culture assays to demonstrate that human cells can acquire vitamin C by a "bystander effect," taking up dehydroascorbic acid generated by superoxide anions produced by activated neighboring cells and subsequently accumulating ascorbic acid.…”

mentioning

confidence: 85%

Recycling of Vitamin C by a Bystander Effect

Nualart

Rivas

Montecinos

et al. 2003

Journal of Biological Chemistry

140

130

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Human cells transport dehydroascorbic acid through facilitative glucose transporters, in apparent contradiction with evidence indicating that vitamin C is present in human blood only as ascorbic acid. On the other hand, activated host defense cells undergoing the oxidative burst show increased vitamin C accumulation. We analyzed the role of the oxidative burst and the glucose transporters on vitamin C recycling in an in vitro system consisting of activated host-defense cells co-cultured with human cell lines and primary cells. We asked whether human cells can acquire vitamin C by a "bystander effect" by taking up dehydroascorbic acid generated from extracellular ascorbic acid by neighboring cells undergoing the oxidative burst. As activated cells, we used HL-60 neutrophils and normal human neutrophils activated with phorbol 12 myristate 13-acetate. As bystander cells, we used immortalized cell lines and primary cultures of human epithelial and endothelial cells. Activated cells produced superoxide anions that oxidized extracellular ascorbic acid to dehydroascorbic acid. At the same time, there was a marked increase in vitamin C uptake by the bystander cells that was blocked by superoxide dismutase but not by catalase and was inhibited by the glucose transporter inhibitor cytochalasin B. Only ascorbic acid was accumulated intracellularly by the bystander cells. Glucose partially blocked vitamin C uptake by the bystander cells, although it increased superoxide production by the activated cells. We conclude that the local production of superoxide anions by activated cells causes the oxidation of extracellular ascorbic acid to dehydroascorbic acid, which is then transported by neighboring cells through the glucose transporters and immediately reduced to ascorbic acid intracellularly. In addition to causing increased intracellular concentrations of ascorbic acid with likely associated enhanced antioxidant defense mechanisms, the bystander effect may allow the recycling of vitamin C in vivo, which may contribute to the low daily requirements of the vitamin in humans.

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mentioning

confidence: 85%

Recycling of Vitamin C by a Bystander Effect

Nualart

Rivas

Montecinos

et al. 2003

Journal of Biological Chemistry

140

130

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“…In most studies, upper and lower tertiles, quartiles or quintiles are compared, making it difficult to compare groups between studies. Consequently, the category of marginal vitamin C deficiency can rarely be singled out from vitamin C deficiency or hypovitaminosis C. With respect to scurvy, clinical cases among individuals with marginal vitamin C deficiency are rare, but do occur (39,40) . Probably more important though, considerable epidemiological evidence suggests that there may be other clinical consequences of marginal vitamin C deficiency.…”

Section: Marginal Vitamin C Deficiencymentioning

confidence: 99%

Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials

2009

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In contrast to the promised 'antioxidant miracle' of the 1980s, several randomised controlled trials have shown no effect of antioxidant supplements on hard endpoints such as morbidity and mortality. The former over-optimistic attitude has clearly called for a more realistic assessment of the benefit:harm ratio of antioxidant supplements. We have examined the literature on vitamin C intervention with the intention of drawing a conclusion on its possible beneficial or deleterious effect on health and the result is discouraging. One of several important issues is that vitamin C uptake is tightly controlled, resulting in a wide-ranging bioavailability depending on the current vitamin C status. Lack of proper selection criteria dominates the currently available literature. Thus, while supplementation with vitamin C is likely to be without effect for the majority of the Western population due to saturation through their normal diet, there could be a large subpopulation with a potential health problem that remains uninvestigated. The present review discusses the relevance of the available literature on vitamin C supplementation and proposes guidelines for future randomised intervention trials.

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“…This is probably because gingivitis and periodontitis are of multifactorial aetiology. Patients with severe scurvy can have healthy gingivae, but a deficiency of vitamin C can exacerbate an existing gingivitis (Hodges et al 1971). Therapeutic trials of vitamin C in the treatment of periodontal disease have shown mixed results.…”

Section: T H E R E L a T I O N S H I P Between D I E T A N D N U T R mentioning

confidence: 99%