Congestive Cardiomyopathy and Haemochromatosis- Rapid Progression Possibly Accelerated by Excessive Ingestion of Ascorbic Acid

McLaran, Christopher J.; Bett, J. H. N.; Nye, Jonathan A.; Halliday, June W.

doi:10.1111/j.1445-5994.1982.tb02457.x

Cited by 70 publications

(32 citation statements)

References 8 publications

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“…This seems to be so in patients with idiopathic haemochromatosis and dietary iron overload ; indeed, supplementation of their diet with AA was reported to cause serious complications resulting from additional oxidative damage [38]. As final note, an in-hospital depletion-repletion study performed in human volunteers has revealed that AA supplementation promotes a prompt increase in the vitamin content of white blood cells [39].…”

Section: Resultsmentioning

confidence: 99%

Intracellular ascorbic acid enhances the DNA single-strand breakage and toxicity induced by peroxynitrite in U937 cells

et al. 2001

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A well-established protocol to increase the intracellular content of ascorbic acid was used to investigate the effects of the vitamin on DNA single-strand breakage and toxicity mediated by authentic peroxynitrite (ONOO-) in U937 cells. This protocol involved exposure for 60 min to 100 muM dehydroascorbic acid, which was taken up by the cells and converted into ascorbic acid via a GSH-independent mechanism. At the time of exposure to ONOO-, which was performed in fresh saline immediately after loading with dehydroascorbic acid, the vitamin present in the cells was all in its reduced form. It was found that, in cells that are otherwise ascorbate-deficient, an increase in their ascorbic acid content does not prevent, but rather enhances, the DNA-damaging and lethal responses mediated by exogenous ONOO-. These results therefore suggest that acute supplementation of ascorbic acid can be detrimental for individuals with pathologies associated with a decrease in ascorbic acid and in which ONOO- is known to promote deleterious effects

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Section: Resultsmentioning

confidence: 99%

Intracellular ascorbic acid enhances the DNA single-strand breakage and toxicity induced by peroxynitrite in U937 cells

et al. 2001

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“…Although AA-mediated Fenton reactions may be controlled in the plasma and lymph of healthy individuals by efficient iron sequestration in transferrin [21,22], the redox-active NTBI found in the serum of individuals with iron overload may catalyse free radical formation in the presence of AA. AA supplements were reported to enhance cell and organ damage, and eventually cause cardiac failure, in patients with iron overload [23][24][25]. Additionally, the formation of hydroxyl radicals from H 2 O 2 may occur intracellularly due to the presence of a pool of labile iron.…”

Section: Introductionmentioning

confidence: 99%

Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

Duarte

Jones

2007

Free Radical Biology and Medicine

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Vitamin C (ascorbic acid, AA) is an important antioxidant in human plasma. It is clear, however, that AA has other important, non-antioxidant roles in cells. Of particular interest is its involvement in iron metabolism, since AA enhances dietary iron absorption, increases the activity of Fe 2+ -dependent cellular enzymes, promotes Fenton reactions in vitro and was reported to have deleterious effects in individuals with iron overload. Nevertheless, the ability of AA to modulate iron metabolism and enhance iron-dependent damage in cells, tissues and organisms has not been fully elucidated. Here we investigated the effect of AA on iron-mediated oxidative stress in normal human fibroblasts. Incubation with physiologically relevant concentrations of AA was not harmful but sensitised cells towards H 2 O 2 -induced, iron-dependent DNA strand breakage and cell death. We also report that AA increased the levels of intracellular catalytic iron and concomitantly modulated the expression of two wellestablished iron-regulated genes, ferritin and transferrin receptor. In summary, we present evidence of a novel, non-antioxidant role of AA in human cells, where it increases iron availability and enhances ROS-mediated, iron-dependent damage. We suggest that AA may exacerbate the deleterious effects of metals in vivo and promote normal tissue injury in situations associated with elevated ROS production.

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“…However, in humans, antioxidant therapy has not been shown to slow the progression of atherosclerotic coronary artery disease (7)(8)(9). On the contrary, several prospective angiographic studies have demonstrated that antioxidant therapy may be associated with a more rapid progression of atherosclerosis, potentially due to a deleterious effect on the lipid profile (8,10,11) or perhaps the ability of these antioxidants to become pro-oxidants under certain conditions (12)(13)(14)(15)(16)(17)(18).…”

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confidence: 99%

The Effect of Vitamin Therapy on the Progression of Coronary Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women

et al. 2004

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OBJECTIVE -Antioxidant trials have not demonstrated efficacy in slowing cardiovascular disease but could not rule out benefit for specific patient subgroups. Antioxidant therapy reduces LDL oxidizability in haptoglobin 1 allele homozygotes (Hp 1-1), but not in individuals with the haptoglobin 2 allele (Hp 2-1 or Hp 2-2). We therefore hypothesized that haptoglobin type would be predictive of the effect of vitamin therapy on coronary atherosclerosis as assessed by angiography. RESEARCH DESIGN AND METHODS -We tested this hypothesis in the Women'sAngiographic Vitamin and Estrogen (WAVE) trial, a prospective angiographic study of vitamins C and E with or without hormone replacement therapy (HRT) in postmenopausal women. Haptoglobin type was determined in 299 women who underwent baseline and follow-up angiography. The annualized change in the minimum luminal diameter (MLD) was examined in analyses stratified by vitamin use, haptoglobin type, and diabetes status.RESULTS -We found a significant benefit on the change in MLD with vitamin therapy as compared with placebo in Hp 1-1 subjects (0.079 Ϯ 0.040 mm, P ϭ 0.049). This benefit was more marked in diabetic subjects (0.149 Ϯ 0.064 mm, P ϭ 0.021). On the other hand, there was a trend toward a more rapid decrease in MLD with vitamin therapy in Hp 2-2 subjects, which was more marked in diabetic subjects (0.128 Ϯ 0.057 mm, P ϭ 0.027). HRT had no effect on these outcomes.CONCLUSIONS -The relative benefit or harm of vitamin therapy on the progression of coronary artery stenoses in women in the WAVE study was dependent on haptoglobin type. This influence of haptoglobin type seemed to be stronger in women with diabetes.

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Congestive Cardiomyopathy and Haemochromatosis- Rapid Progression Possibly Accelerated by Excessive Ingestion of Ascorbic Acid

Cited by 70 publications

References 8 publications

Intracellular ascorbic acid enhances the DNA single-strand breakage and toxicity induced by peroxynitrite in U937 cells

Intracellular ascorbic acid enhances the DNA single-strand breakage and toxicity induced by peroxynitrite in U937 cells

Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

The Effect of Vitamin Therapy on the Progression of Coronary Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women

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