Ascorbate enhances iron uptake into intestinal cells through formation of a FeCl3–ascorbate complex

Thumser, Alfred E.; Rashed, Aswir Abd; Sharp, Paul; Lodge, John K.

doi:10.1016/j.foodchem.2010.04.031

Cited by 16 publications

(12 citation statements)

References 28 publications

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“…However, this complex cannot be compared in efficiency with other chelating molecules responsible for iron transport, primarily DMT1 (divalent metal transporter 1) [81]. In addition to its wellestablished reduction of ferric iron to provide a bioavailable supply of ferrous iron to DMT1, ascorbic acid also directly enhances directly the uptake of ferric iron into Caco-2 cells through the formation of the Fe 3+ -ascorbate complex [82]. Since DMT1 is not involved in the uptake of this complex, further work is required to identify the transporter system (chelating agent) which inhibits Fe 3+ reduction by ascorbate.…”

Section: Discussionmentioning

confidence: 99%

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone

Timoshnikov

Kobzeva

Polyakov

et al. 2020

IJMS

108

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Ascorbic acid (AscH2) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in medical practice especially for increasing iron absorption and as an adjuvant therapeutic in iron chelation therapy, but its mode of action and implications in iron metabolism and toxicity are not yet clear. In this study, we used UV–Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe3+ to Fe2+, followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe3+ ↔ Fe2+ in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron–ascorbate complex compared to the FeL13 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL13 chelate complex resulting in the formation of mixed L12AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4–5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid, iron, and L1.

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Section: Discussionmentioning

confidence: 99%

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone

Timoshnikov

Kobzeva

Polyakov

et al. 2020

IJMS

108

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“…In this context, it was suggested that there are several routes of iron accumulation in cells, including the ascorbate-dependent ferrous iron uptake via the divalent metal transporter (DMT1), plus an independent route for ferric iron uptake [ 39 , 99 ]. For example, it was previously demonstrated that the reduction of ferric iron by ascorbic acid provides bioavailable ferrous iron to DMT1, and also directly enhances the uptake of ferric iron into Caco-2 cells through the formation of an Fe 3+ –ascorbate complex [ 109 ]. The Caco-2 cell line consists of human epithelial colorectal adenocarcinoma cells, which are generally used as an in vitro model of the human small intestinal mucosa to predict the absorption of orally administered drugs [ 109 ].…”

Section: Biological Implications Of the Iron Complexes Of Ascorbicmentioning

confidence: 99%

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

et al. 2020

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Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine.

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“…Beans are also an important source of non-digestible carbohydrates which may impair iron absorption (Luo, Xie, & Cui, 2010. However, controversies remain as some of these foods, such as cabbage (kale) are also good sources of ascorbic acid which improves iron absorption (Thumser, Rashed, Sharp, & Lodge, 2010).…”

Section: Meat a Valuable Iron Sourcementioning

confidence: 99%

Meat nutritional composition and nutritive role in the human diet

2013

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a b s t r a c t a r t i c l e i n f oMeat has exerted a crucial role in human evolution and is an important component of a healthy and well balanced diet due to its nutritional richness. The present review attempts to sum up meats role and importance in human nutrition as well as examine some pejorative beliefs about meat consumption. Meat is a valuable source of high biological value protein, iron, vitamin B12 as well as other B complex vitamins, zinc, selenium and phosphorus. Fat content and fatty acid profile, a constant matter of concern when referring to meat consumption, is highly dependent on species, feeding system as well as the cut used. Pork meat can have the highest fat content but poultry skin is not far behind. It is also crucial to distinguish meat cuts from other meat products especially regarding its association with disease risk. As in other dietary components, moderation is advisable but meat has been shown to be an important component of a balanced diet.

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Ascorbate enhances iron uptake into intestinal cells through formation of a FeCl3–ascorbate complex

Cited by 16 publications

References 28 publications

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone

Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

Meat nutritional composition and nutritive role in the human diet

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