DOI: https://doi.org/10.18370/2309-4117.2014.20.98-102

Iron supplements: the quick fix with long-term consequences

Anna E.O. Fisher, Declan P. Naughton

Abstract


Co-supplementation of ferrous salts with vitamin C exacerbates oxidative stress in the gastrointestinal tract leading to ulceration in healthy individuals, exacerbation of chronic gastrointestinal inflammatory diseases and can lead to cancer. Reactive oxygen and nitrogen species (RONS) have been ascribed an important role in oxidative stress. Redox-active metal ions such as Fe (II) and Cu (I) further activate RONS and thus perpetuate their damaging effects. Ascorbic acid can exert a pro-oxidant effect by its interaction with metal ions via a number of established RONS generating systems which are reviewed here. Further studies are required to examine the detrimental effects of nutraceuticals especially in chronic inflammatory conditions which co-present with anaemia


Keywords


iron supplements; ascorbic acid; oxidative stress

References


Griffiths, H.R., Lunec. J. “Ascorbic acid in the 21st century – more than a simple antioxidant.” Environ Toxicol Pharmacol, 10(2001): 173-82.

Kim, S.H., Han, J.H., Keen, C.L. “Vitamin and mineral supplement use by healthy teenagers in Korea: motivating factors and dietary consequences.” Nutrition, 17(2001): 373-380.

Dabbagh, A.J., Lynch, S., Mannion, T., Frei, B. “The effect of iron overload on rat plasma and liver oxidant status in vivo.” Biochem J, 300(1994): 799-803.

Fraga, C.G., Oteiza, P.I. “Iron toxicity and antioxidant nutrients.” Toxicol, 180(2002): 23-32.

Carrier, J., Aghdassi, E., Cullen, J., Allard, J.P. Iron supplementation increases disease activity and vitamin E ameliorates the effect in rats with dextran sulphate sodium-induced colitis. J Nutrit, 132(2002): 3146-3150.

Carrier, J., Aghdassi, E., Platt, I., Cullen, J., Allard, J.P. “Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced coilitis.” Aliment Pharmacol Ther, 15(2001): 1989-1999

Seril, D.N., Liao, J., Ho, K.L., Yang, C.S., Yang, G.Y. “Dietary iron supplementation enhances DSS-induced colitis and associated carcinoma development in mice.” Dig. Dis Sci, 47(2002): 1266-1278.

Naito, Y., Yoshikawa, T., Yoneta, T., Yagi, N., Matsuyama, K., Arai, M., Tanigawa, T., Kondo, M. “A new gastric-ulcer model in rats produced by ferrous iron and ascorbic-acid injection.” Digestion, 56(1995): 472-478.

Troost, F.J., Saris, W.H., Haenen, G.R., Bast, A., Brummer, R.J. “New method to study oxidative damage and antioxidants in thehuman small bowel: effects of iron application.” Am J Physiol Gastrointest Liver Physiol, 285(2003): G354-359.

Erichsen, K., Hausken, T., Ulvik, R.J., Svardal, R.J., Berstad, A., Berge, R.K. “Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease.” Scand J Gastroenterol, 38(2003): 543-548.

Udenfriend, S., Clark, C.T., Axelrod, J., Brodie, B.B. “Ascorbic acid in aromatic hydroxylation. I. A model system for aromatic hydroxylation.” J Biol Chem, 208(1953): 731-739.

Brodie, B.B., Axelrod, J., Shore, P.A., Udenfriend, S. “Ascorbic acid in aromatic hydroxylation. II. Products formed by reaction of substrates with ascorbic acid, ferrous ion and oxygen.” J Biol Chem, 208(1953): 741-750.

Childs, A., Jacobs, C., Kaminski, T., Halliwell, B., Leeuwenburgh, C. “Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.” Free Radic Biol Med, 31(2001): 745-753.

Weissberger, A., LuValle, J.E., Thomas, D.S. Jr. “Oxidation processes. XVI The autoxidation of ascorbic acid.” J Amer Chem Soc, 65(1943): 1934-1939.

Khan, M.M., Martell, A.E. “Metal ion and metal chelate catalyzed oxidation of ascorbic acid by molecular oxygen. I. Cupric and ferric ion catalyzed oxidation.” J Amer Chem Soc, 89(1967): 4176-4185.

Hamilton, G.A. “Mechanisms of two- and four-electron oxidations catalyzed by some metalloenzymes.” Adv Enzymol Rel Areas Molec Biol, 32(1969): 55-96.

Khan, M.M., Martell, A.E. “Metal ion and metal chelate catalyzed oxidation of ascorbic acid by molecular oxygen. II. Cupric and ferric chelate catalyzed oxidation.” J Amer Chem Soc, 89(1967): 7104-7111.

Kasai, H., Nishimura, S. “Hydroxylation of deoxy guanosine at the C-8 position by polyphenols and aminophenols in the presence of hydrogen peroxide and ferric ion.” Nucleic Acids Res, 75(1984): 565-566.

Martell, A.E., Taqui Khan, M.M. “Metal ion catalysis of reactions of molecular oxygen.” In: Inorganic Biochemistry Edited by: Eichhorn G.L. Amsterdam, Elsevier Scientific Publishing Company; 1973:654-688.

Parkes, H.G., Allen, R.E., Furst, A., Blake, D.R., Grootveld, M.C. “Speciation of non-transferrin-bound iron ions in synovial fluid from patients with rheumatoid arthritis by proton nuclear magnetic resonance spectroscopy.” J Pharm Biomed Anal, 9(1991): 29-32.

Halliwell, B., Gutteridge, J.M. Free radicals in biology and medicine Oxford University Press (1999).

Spiro, T.G. Metal activation of dioxygen New York: Wiley (1980).

Rehman, A., Collis, C.S., Yang, M., Kelly, M., Diplock, A.T., Halliwell, B., Rice-Evans, C. “The effects of iron and vitamin c co-supplementation on oxidative damage to DNA in healthy volunteers.” Biochem Biophys Res Commun, 246(1998): 293-298.

Food, U.K. Standards Agency Report: Expert Group on Vitamins and Minerals (2003).

Morgan, E.H., Oates, P.S. “Mechanisms and regulation of intestinal iron absorption.” Blood Cells Mol Dis, 29(2002): 384-399.


GOST Style Citations


1. Griffiths, H.R., Lunec. J. “Ascorbic acid in the 21st century – more than a simple antioxidant.” Environ Toxicol Pharmacol, 10(2001): 173-82.

2. Kim, S.H., Han, J.H., Keen, C.L. “Vitamin and mineral supplement use by healthy teenagers in Korea: motivating factors and dietary consequences.” Nutrition, 17(2001): 373-380.

3. Dabbagh, A.J., Lynch, S., Mannion, T., Frei, B. “The effect of iron overload on rat plasma and liver oxidant status in vivo.” Biochem J, 300(1994): 799-803.

4. Fraga, C.G., Oteiza, P.I. “Iron toxicity and antioxidant nutrients.” Toxicol, 180(2002): 23-32.

5. Carrier, J., Aghdassi, E., Cullen, J., Allard, J.P. Iron supplementation increases disease activity and vitamin E ameliorates the effect in rats with dextran sulphate sodium-induced colitis. J Nutrit, 132(2002): 3146-3150.

6. Carrier, J., Aghdassi, E., Platt, I., Cullen, J., Allard, J.P. “Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced coilitis.” Aliment Pharmacol Ther, 15(2001): 1989-1999 

7. Seril, D.N., Liao, J., Ho, K.L., Yang, C.S., Yang, G.Y. “Dietary iron supplementation enhances DSS-induced colitis and associated carcinoma development in mice.” Dig. Dis Sci, 47(2002): 1266-1278.

8. Naito, Y., Yoshikawa, T., Yoneta, T., Yagi, N., Matsuyama, K., Arai, M., Tanigawa, T., Kondo, M. “A new gastric-ulcer model in rats produced by ferrous iron and ascorbic-acid injection.” Digestion, 56(1995): 472-478.

9. Troost, F.J., Saris, W.H., Haenen, G.R., Bast, A., Brummer, R.J. “New method to study oxidative damage and antioxidants in thehuman small bowel: effects of iron application.” Am J Physiol Gastrointest Liver Physiol, 285(2003): G354-359.

10. Erichsen, K., Hausken, T., Ulvik, R.J., Svardal, R.J., Berstad, A., Berge, R.K. “Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease.” Scand J Gastroenterol, 38(2003): 543-548.

11. Udenfriend, S., Clark, C.T., Axelrod, J., Brodie, B.B. “Ascorbic acid in aromatic hydroxylation. I. A model system for aromatic hydroxylation.” J Biol Chem, 208(1953): 731-739.

12. Brodie, B.B., Axelrod, J., Shore, P.A., Udenfriend, S. “Ascorbic acid in aromatic hydroxylation. II. Products formed by reaction of substrates with ascorbic acid, ferrous ion and oxygen.” J Biol Chem, 208(1953): 741-750.

13. Childs, A., Jacobs, C., Kaminski, T., Halliwell, B., Leeuwenburgh, C. “Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.” Free Radic Biol Med, 31(2001): 745-753.

14. Weissberger, A., LuValle, J.E., Thomas, D.S. Jr. “Oxidation processes. XVI The autoxidation of ascorbic acid.” J Amer Chem Soc, 65(1943): 1934-1939.

15. Khan, M.M., Martell, A.E. “Metal ion and metal chelate catalyzed oxidation of ascorbic acid by molecular oxygen. I. Cupric and ferric ion catalyzed oxidation.” J Amer Chem Soc, 89(1967): 4176-4185.

16. Hamilton, G.A. “Mechanisms of two- and four-electron oxidations catalyzed by some metalloenzymes.” Adv Enzymol Rel Areas Molec Biol, 32(1969): 55-96.

17. Khan, M.M., Martell, A.E. “Metal ion and metal chelate catalyzed oxidation of ascorbic acid by molecular oxygen. II. Cupric and ferric chelate catalyzed oxidation.” J Amer Chem Soc, 89(1967): 7104-7111.

18. Kasai, H., Nishimura, S. “Hydroxylation of deoxy guanosine at the C-8 position by polyphenols and aminophenols in the presence of hydrogen peroxide and ferric ion.” Nucleic Acids Res, 75(1984): 565-566.

19. Martell, A.E., Taqui Khan, M.M. “Metal ion catalysis of reactions of molecular oxygen.” In: Inorganic Biochemistry Edited by: Eichhorn G.L. Amsterdam, Elsevier Scientific Publishing Company; 1973:654-688.

20. Parkes, H.G., Allen, R.E., Furst, A., Blake, D.R., Grootveld, M.C. “Speciation of non-transferrin-bound iron ions in synovial fluid from patients with rheumatoid arthritis by proton nuclear magnetic resonance spectroscopy.” J Pharm Biomed Anal, 9(1991): 29-32.

21. Halliwell, B., Gutteridge, J.M. Free radicals in biology and medicine Oxford University Press (1999).

22. Spiro, T.G. Metal activation of dioxygen New York: Wiley (1980). 

23. Rehman, A., Collis, C.S., Yang, M., Kelly, M., Diplock, A.T., Halliwell, B., Rice-Evans, C. “The effects of iron and vitamin c co-supplementation on oxidative damage to DNA in healthy volunteers.” Biochem Biophys Res Commun, 246(1998): 293-298.

24. Food, U.K. Standards Agency Report: Expert Group on Vitamins and Minerals (2003).

25. Morgan, E.H., Oates, P.S. “Mechanisms and regulation of intestinal iron absorption.” Blood Cells Mol Dis, 29(2002): 384-399.





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