Iron: Background and Relevant Pharmacokinetics

2010

Iron is an essential mineral found in the body in haem or non-haem form. The average human body contains 2-4 g of iron. Although the metal exists in several oxidation states in nature, only the ferrous (Fe2+) and ferric (Fe3+) forms are stable in the aqueous environment of the body.

Iron is found in the body in: haemoglobin (65%); myoglobin (10%); enzymes (1-5%); the transport form, transferrin (0.05%); and the storage forms ferritin (4-9%) and haemosiderin (1-4%).

The haem form of iron is more soluble than the non-haem form and is absorbed 2-3 times more readily. It is absorbed via mucosal cells in the small intestine. Non-haem iron is bound to other substances in food, and must first be liberated by gastric secretions such as hydrochloric acid and pepsin. As such, absorption is best in the acidic environment of the stomach.

Clinical note— Factors affecting the absorption of iron

If the dietary intake of iron is adequate, it is often assumed that a patient’s iron levels will be within the normal range. In practice, this is not always the case as absorption is significantly affected by a number of factors, thereby increasing or decreasing the amount of ingested dietary iron that reaches the systemic circulation.

Here is a brief summary of the main influences on absorption.

SOLUBILITY ENHANCERS OF NON-HAEM IRON

• Acids (including ascorbic acid) aid solubility of non-haem iron, thus improving absorption; the addition of 20 mg ascorbic acid has been shown to increase non-haem iron absorption by 39%.

• Sugars (e.g. fructose) aid absorption.

• Meat stimulates digestive secretions, and breakdown products such as cysteine-containing peptides aid absorption. The addition of red meat increases non-haem iron absorption by 85%. This appears to be dose-dependent, as a recent study found that the addition of 60 g Danish pork meat three times daily improved the absorption of non-haem iron from 5.3% to 7.9% although addition of smaller amounts were not as effective.

• Alcohol appears to improve iron uptake. The consumption of up to two alcoholic drinks per day is associated with reduced risk of iron deficiency and more than two can increase the risk of iron overload.

SOLUBILITY INHIBITORS OF NON-HAEM IRON

• Polyphenols, including tannin derivatives of gallic acid (tea has been reported to reduce iron absorption by 60%, coffee by 40%). A number of studies have shown that tea catechins can inhibit intestinal non-haem iron absorption; however, polyphenols do not have chelating effects on cooked haem iron. Recent studies suggest that impaired absorption is unlikely to be significant in people with normal iron stores. The addition of milk to tea may reduce the chelating effects.

• Phytic acid (whole grains).

• Oxalic acid (spinach, chard, chocolate, berries).

Calcium — single-meal studies have established that calcium (including calcium phosphate and foods such as milk) reduces iron absorption by up to 70%; however, the effect may not be as pronounced when calcium is served as part of a whole diet. For instance, the consumption of a glass of milk or the equivalent amount of calcium from fortified food does not appear to decrease non-haem iron absorption. Although it remains to be shown in iron-deficient persons, long-term iron status does not seem to be compromised by high calcium intake.

Zinc competes with iron for absorption — inorganic zinc supplements may reduce iron absorption by 66-80%, and supplements containing both iron and zinc may not be as efficacious as the same doses given in isolation, but nutrients consumed in a meal may not be as affected.

• Manganese may reduce absorption by 22-40%.

• Rapid intestinal transit time.

• Malabsorption syndromes.

Helicobacter pylori infection.

• Gastrointestinal blood loss.

• Insufficient digestive secretions (including achlorhydria).

Antacids and PPI.