Taking vitamin C with Iron: A Dangerous Concoction?

Written by Daniel Roytas, MHSc (Nutrition), BHSc (Naturopathy), Dip. RM, MANTA

Taking vitamin C with iron is commonly recommended by clinicians to enhance the bioavailability and metabolism of iron. Vitamin C has been shown to stimulate a number of physiological mechanisms involved in the intestinal absorption, cellular uptake and metabolism of iron including;

1. Up-regulation of the intestinal iron transporter (ferroportin)¹.
2. Maintaining iron in its ferrous state (Fe2⁺), which is required for incorporation in to haeme².
3. Acting as an enzyme co-factor to facilitate the interaction between transferrin and iron³.
4. Stimulating hepatic ferritin synthesis³.
5. Stimulating the release of iron from ferritin stores within reticuloendothelial cells, making iron available for haemoglobin synthesis³.
6. Protecting iron against oxidation and subsequent sequestration within hepatocytes and macrophages⁴, via the up-regulation of antioxidants like glutathione and superoxide dismutase⁵.
7. Reducing iron loss through the inhibition of lysosomal ferritin degradation³.

Despite these beneficial interactions, it has been reported that there may be unfavourable interactions between iron and vitamin C. In a study of 40 healthy volunteers supplemented with 14 mg/d of ferrous sulphate and either 60 mg/d or 260 mg/d of ascorbic acid for 12 weeks, a transient rise in white blood cell oxidative DNA damage was observed after 6 weeks of supplementation. By 12 weeks, the levels of oxidative DNA damage had resolved, which is thought to be due to an adaptive response within the cell to increase repair enzymes or by enhancing iron sequestration into ferritin⁶. Could it be that the observed increase in cellular repair enzyme activity and ferritin concentrations in patients taking iron and vitamin C, is actually a sign of the body going in to “damage control”?

It is also well known that supra-physiological doses of vitamin C or iron taken alone, generates reactive oxygen and nitrogen species, lipid peroxidation and oxidative stress⁷. When taken together, is it possible that these two nutrients could create a potent oxidative cocktail? Animal studies seem to confirm this hypothesis. For example, in one study when rats were injected with a solution of iron and vitamin C in to their gastro-intestinal tracts, they developed gastric ulcers. Interestingly, the rats did not develop ulceration when vitamin C or iron were injected separately⁸.

Vitamin C is known to reduce ferric iron (Fe3⁺) in to ferrous state (Fe2⁺), which is required for incorporation in to haeme². In other words, without the presence of vitamin C, sufficient iron may not be made available for erythropoiesis. But do these nutrients really need to be given at the same time? It has been proposed that when given together in a bolus, this reducing effect can induce the Fenton reaction, resulting in the activation of peroxides, hydrogen peroxide (H₂0₂) and hydroxyl radical generation. When ingested together, iron and vitamin C may generate substantial concentrations of pro-oxidants, which are purported to cause tissue damage in the gastro-intestinal tract, leading to the formation of gastric ulcers⁷.

The combination therapy of vitamin C and iron is something that many clinicians prescribe patient’s with iron deficiency in clinical practice, without a second thought. Given the potential harms associated with this practice, is it time for us to re-evaluate the co-prescription of iron and vitamin C?

References

1. Scheers N, Sandberg A-S. Iron Transport through Ferroportin Is Induced by Intracellular Ascorbate and Involves IRP2 and HIF2α. Nutrients. 2014;6(1):249-260. doi:10.3390/nu6010249
2. Hallberg L, Brune M, Rossander L. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-108. http://www.ncbi.nlm.nih.gov/pubmed/2507689.
3. Lane DJR, Richardson DR. The active role of vitamin C in mammalian iron metabolism: Much more than just enhanced iron absorption! Free Radic Biol Med. 2014;75:69-83. doi:10.1016/j.freeradbiomed.2014.07.007
4. Sehbai AS, Asif N. De Novo Anemia and Relationship with Vitamin C Deficiency and Zinc Deficiency in a Southern Delaware Population, a Retrospective Analysis. Blood. 2015;126(23):4547-4547. doi:10.1182/blood.V126.23.4547.4547
5. Choi J, Kim D-Y, Choue R, Lim H. Effects of Vitamin C Supplementation on Plasma and Urinary Vitamin C Concentration in Korean Women. Clin Nutr Res. 2017;6(3):198. doi:10.7762/cnr.2017.6.3.198
6. Rehman A, Collis CS, Yang M, et al. The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochem Biophys Res Commun. 1998;246(1):293-298. doi:10.1006/bbrc.1998.8592
7. Fisher AEO, Naughton DP. Iron supplements: The quick fix with long-term consequences. Nutr J. 2004;3:1-5. doi:10.1186/1475-2891-3-1
8. Naito Y, Yoshikawa T, Yoneta T, et al. A New Gastric Ulcer Model in Rats Produced by Ferrous Iron and Ascorbic Acid Injection. Digestion. 1995;56(6):472-478. doi:10.1159/000201278