Inhibition of Iron Absorption

Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim.

29. Gillooly, M. 1983. The effect of organic acids, phytates and polyphenols on absorption of iron from vegetables. Br. J. Nutr., 49: 331-342. 

30. Hallberg, L., Brune, M. & Rossander, L. 1989. Iron absorption in man: ascorbic acidand dose-dependent inhibition by phytate. Am. J. Clin. Nutr., 49: 140-144.

Phytates are found in all kinds of grains, seeds, nuts, vegetables, roots (e.g., potatoes), and fruits. Chemically, phytates are inositol hexaphosphate salts and are a storage form of phosphates and minerals. Other phosphates have not been shown to inhibit non-heme iron absorption. In North American and European diets, about 90 percent of phytates originate from cereals. Phytates strongly inhibit iron absorption in a dose-dependent fashion and even small amounts of phytates have a marked effect (29, 30).

31. Hallberg, L., Rossander, L. & Skånberg, A-B. 1987. Phytates and the inhibitory effect of bran on iron absorption in man. Am. J. Clin. Nutr., 45: 988-996.

32. Brune, M. 1992. Iron absorption from bread in Humans: Inhibiting effects of cereal fiber, phytate and inositol phosphates with different numbers of phosphate groups. J. Nutr., 122:442-449.

Bran has a high content of phytate and strongly inhibits iron absorption. Whole-wheat flour, therefore, has a much higher content of phytates than does white wheat flour (31). In bread some of the phytates in bran are degraded during the fermentation of the dough. Fermentation for a couple of days (sourdough fermentation) can therefore almost completely degrade the phytate and increase the bio-availability of iron in bread made from whole-wheat flour (32).

33. Rossander-Hulthén, L., Gleerup, A. & Hallberg, L. 1990. Inhibitory effect of oat products on non-haem iron absorption in man. Eur. J. Clin. Nutr., 44: 783-791.

34. Siegenberg, D. 1991. Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption. Am. J. Clin. Nutr., 53: 537-41.

Oats strongly inhibit iron absorption because of their high phytate content, that results from native phytase in oats being destroyed by the normal heat process used to avoid rancidity (33). Sufficient amounts of ascorbic acid can counteract this inhibition (34).

35. Brune, M., Rossander, L. & Hallberg, L. 1989. Iron absorption and phenolic compounds: importance of different phenolic structures. Eur. J. Clin. Nutr., 43: 547-558. 

By contrast, non-phytate-containing dietary fibre components have almost no influence on iron absorption. Almost all plants contain phenolic compounds as part of their defence system against insects, animals, and humans. Only some of the phenolic compounds (mainly those containing galloyl groups) seem to be responsible for the inhibition of iron absorption (35).

36. Disler, P.B. 1975. The effect of tea on iron absorption. Gut, 16: 193-200.

39. Hallberg, L. & Rossander, L. 1982. Effect of different drinks on the absorption of nonheme iron from composite meals. Hum. Nutr: Appl. Nutr., 36: 116-123.

Tea, coffee, and cocoa are common plant products that contain iron-binding polyphenols (36-39). Many vegetables, especially green leafy vegetables (e.g., spinach), and herbs and spices (e.g., oregano) contain appreciable amounts of galloyl groups, that strongly inhibit iron absorption. Consumption of betel leaves, common in areas of Asia, also has a marked negative effect on iron absorption.

40. Hallberg, L. 1991. Calcium: effect of different amounts on nonheme-and heme-iron absorption in Humans. Am. J. Clin. Nutr., 53: 112-119.

41. Hallberg, L. 1992. Calcium and iron absorption: mechanism of action and nutritional importance. Eur. J. Clin. Nutr., 46: 317-327.

42. Gleerup, A., Rossander-Hultén, L. & Hallberg, L. 1993. Duration of the inhibitory effect of calcium on non-haem iron absorption in man. Eur. J. Clin. Nutr., 47: 875-879.

Calcium, consumed as a salt or in dairy products interferes significantly with the absorption of both heme and non-heme iron (40-42). Because calcium and iron are both essential nutrients, calcium cannot be considered to be an inhibitor in the same way as phytates or phenolic compounds. The practical solution for this competition is to increase iron intake, increase its bio-availability, or avoid the intake of foods rich in calcium and foods rich in iron at the same meal (43).

The mechanism of action for absorption inhibition is unknown, but the balance of evidence strongly suggest that the inhibition is located within the mucosal cell itself at the common final transfer step for heme and non-heme iron. Recent analyses of the dose-effect relationship show that no inhibition is seen from the first 40 mg of calcium in a meal. A sigmoid relationship is then seen, reaching a 60 percent maximal inhibition of iron absorption by 300–600 mg calcium. The form of this curve suggests a one-site competitive binding of iron and calcium (Figure 24).

44. Hallberg, L. 1998. Does calcium interfere with iron absorption? Am. J. Clin. Nutr., 68:

3-4. 

45. Cook, J.D., Morck,T.A. & Lynch, S.R. 1981. The inhibitory effects of soy products on nonheme iron absorption in man. Am. J. Clin. Nutr., 34: 2622-9.

46. Hallberg, L. & Hultén, L. 1982. Effect of soy protein on nonheme iron absorption in man. Am. J. Clin. Nutr., 36: 514-520.

47. Hallberg, L. & Rossander, L. 1984. Improvment of iron nutrition in developing countries: comparison of adding meat, soy protein, ascorbic acid, citric acid, and ferrous sulphate on iron absorption from a simple Latin American-type of meal. Am. J. Clin. Nutr., 39: 577-583.

48. Hurrell, R.F. 1992. Soy protein, phytate, and iron absorption in Humans. Am. J. Clin. Nutr., 56: 573-578.

This relationship explains some of the seemingly conflicting results obtained in studies on the interaction between calcium and iron (44). For unknown reasons, the addition of soy protein to a meal reduces the fraction of iron absorbed (45-48). This inhibition is not solely explained by the high phytate content of soy protein. However, because of the high iron content of soy proteins, the net effect on iron absorption of an addition of soy products to a meal is usually positive.

49. Baynes, R.D. 1990. The promotive effect of soy sauce on iron absorption in Human subjects. Eur. J. Clin. Nutr., 44: 419-24.

50. Macfarlane, B.J. 1990. The effect of traditional oriental soy products on iron absorption. Am. J. Clin. Nutr., 51: 873-80.

In infant foods containing soy proteins, the inhibiting effect can be overcome by the addition of sufficient amounts of ascorbic acid. Some fermented soy sauces, however, have been found to enhance iron absorption (49, 50).