Chronic iron overload and toxicity: Clinical chemistry perspective

Clinical Laboratory Science, Summer 2001 by Kang, Jae O

Acquisition of excess iron from diet

Absorption of iron by the small intestine appears to be regulated by the body's iron needs. However, the quantity of dietary iron and the composition of the diet significantly influence iron absorption. Prolonged intake of high doses of iron can lead to the accumulation of excess iron. This phenomenon has been shown in a number of animal experiments.17,18 In humans, the effect of such high iron doses was well demonstrated in the episode of siderosis among the Bantu tribe in Africa. Tribe members ingested excessive amounts of iron from their diet and beer. Their use of iron pots for cooking and brewing beer increased the iron content. Their traditional beer contained approximately 80 mg/L and alcohol itself enhances iron absorption. Therefore, the beer they consumed may have had a twofold effect on increasing body iron.3,19 Some acquired as much as 100 mg daily.4 Excess hemosiderin-like deposits were observed in 81 % of autopsied subjects over 30 years of age, both male and female.20

Another important factor in iron absorption relates to the form of iron present in a diet. Herne iron and nonheme iron are the two major sources of iron.3 Heme iron, that is found in meat, fish, and poultry, is more effectively absorbed because this iron is associated with the porphyrin ring. This association also allows iron to escape from most of the inhibitors of iron absorption present in a diet. Studies have shown that heme iron absorption is about five to ten times greater than for nonheme iron, and is less sensitive to the amounts of dietary iron and body iron stores.12,21 In addition, heme iron promotes the absorption of nonheme iron which is mainly found in vegetables and grains.22 A recent epidemiological study from Australia showed that normal volunteers have average iron storage of about 1.9 g. This level of iron store is about twice as much as the optimal iron store for normal adults. High meat consumption is believed to be the critical factor.12,23,24

The bioavailability of nonheme iron is significantly influenced by several factors: e.g., the amount of nonheme iron present in the diet, cooking, and manufacturing processes, and the presence of inhibitors and promoters of iron absorption. The inhibitors and promoters of nonheme iron absorption are ubiquitously present in diets. Therefore, the amount of nonheme iron absorbed is markedly dependent on the interplay of these substances. For example, phytates are powerful inhibitors. These are present in nuts, legumes, and many cereals.23 Hallberg reported the dose-dependent inhibitory effect of sodium phytate on iron absorption in humans. Various amounts of phytate, ranging from 2 to 250 mg/serving as phytate phosphorus, and radioactive iron (four mg) were added to phytate-free bread.21 Healthy adults were given the prepared bread on alternate days. Inhibition of iron absorption was dose-dependent, ranging from 18% by two mg to 82% by 250 mg. Ironbinding polyphenols, such as tannins and chlorogenic acid, have about the same inhibitory effect as phytates on iron absorption.12,23 Tea, coffee, vegetables, and legumes contain such polyphenols. Soybeans significantly inhibit nonheme iron absorption since they contain phytic acid and a protein-related moiety that also has an inhibitory effect.26,27 However, soybeans contain high levels of iron, therefore partially compensating for the inhibitory effect.23 A number of studies have shown that milk and cheese inhibit nonheme iron absorption due to the presence of calcium.28-30. Calcium affects the absorption of both nonheme iron and heme iron.