Title: Iron fortification of food
Key words: iron overload, iron deficiency, supplementation, infant milk, cereals, iron complexes, phytate, polyphenols, RNI, haemoglobin, iron deficiency anaemia, retardation, immunity, T-cell, antibody, infection, pregnancy, serum ferritin, iron absorption, SIDS, cancer, heart disease, haemachromatosis, diet,
Date: March 2001
Author: Kate Neil (NS3)
Iron fortification of food
Iron is one of the most plentiful minerals in the earth’s crust1. Iron deficiency is the most common nutritional deficit worldwide and yet it can be successfully prevented on a population basis2. The physiological demand for iron is markedly lower in men than in growing children and in women during their reproductive years, yet iron intake is considerably higher in men than in children or pre-menopausal women1. The amount of iron consumed is many times greater than the amount absorbed1. Excess iron is deleterious, yet excretion is severely limited. Too much is lethal; too little is incompatible with life1.
In recent years there has been growing concern about iron overload in developed countries, which has spurred research in this area2. Emerging findings on the genetic contribution to iron absorption have implications for programmes aimed at the eradication of iron deficiency by supplementation or fortification of the diet3. It is estimated that 10% of adult iron already comes from fortified sources4. Flour is fortified and EC law now says that infant formulas and follow-on milks must either be fortified or the label must indicate that it is not fortified with iron4. Fortifying cereals is currently voluntary4.
Sources of iron used to fortify foods
Fortification of foods with iron can cause rancidity5. Well-absorbed compounds of iron such as ferrous sulfate are usually not suitable as food fortificants because of organoleptic problems, such as colour changes, oxidative rancidity and off flavours. Iron compounds used to fortify foods are not only susceptible to the chemical changes outlined above, but their availability for absorption is reduced by substances that form complexes in the gastro-intestinal tract, such as phytate and polyphenols6. Adding these forms of iron to predominantly cereal-based diets would be of little benefit because much of the fortification iron would also be prevented from being absorbed6. Research aims to identify iron compounds that are not affected by inhibitory ligands present in the diet6.
Iron Deficiency in the UK
Results from surveys reported by MAFF in 1994 indicated that 12% of men and 89% of women aged 19-50 years were below the RNI for iron7 93% of girls in their late teens were below the RNI and 8% below the LRNI. 57% of 4 year olds were below the RNI and 4% below the LRNI7
Iron Deficiency and Performance
In the past 20 years, possible long-term consequences of iron deficiency anaemia on child development have become apparent8. American researchers have found that iron deficiency, as reflected by restricted haemoglobin production, is significantly associated with mild or moderate mental retardation9. The effect of iron deficiency persisted in a low socio-economic population, even after the effects of birth-weight, maternal education, sex, race-ethnicity, age of mother and age of child at entry into the WIC programme for Women, Infants and Children, were controlled for8 The findings indicated that the risk of mild or moderate mental retardation increases with the severity of the anaemia8.
Little question exists that anaemic children display slowed motor and mental development4. However, definitive conclusions from all information currently available regarding the long-term functional consequences of IDA or the irreversibility of the early functional alterations it produces are scientifically unwarranted and should therefore be interpreted with caution4. Jan 99 AMJ.
The work performance is low in adults with IDA4. Supplementing iron correlates with dramatic increase in performance4. Correcting IDA, through food fortification, in adults could positively impact the £13 billion cost to industry each year due to sickness through improved performance and possibly reduced infections.
Iron and Immunity
T-cell and antibody production appear dependent on adequate iron status4. However, the interaction between host and infectious agent is a complex phenomenon, and no theory or experimental model fully explains it10. Tomas Walter. Some investigators favour the contention that mild iron deficiency is beneficial for immunity, whereas others contend that any iron deficit is not good for immunity10.
Infection or inflammation generates anaemia and profound changes in iron metabolism mediated by cytokines, and are important confounders to be considered when individuals or surveys are assessed for iron status10. There is evidence in children that IDA is associated with increased incidence of infection10. High levels of iron are also bad for infection because most bacteria that produce toxins have specific iron receptors that switch on toxin production in response to local iron4. The immune system responds to an infection by removing iron out of the plasma to keep it away from invading pathogenic organisms4. This double-edged sword complicates a case for mass fortification of specific foods with iron.
Iron in Pregnancy
One-third of pregnant women have intakes below the LRNI, and one-third have low iron stores4. Pregnancy poses another area of concern in regard to fortifying foods with iron.
Researchers have shown that plasma volume expansion during pregnancy normally results in decreased serum ferritin levels in the third trimester compared to baseline. Concentrations at 28 weeks which are higher than baseline are associated with increased risk of pre-term deliveries. The failure of ferritin to decrease from its baseline concentration may be indicative of iron deficiency anaemia11. Haemoglobin levels below 8gm% and when ID occurs from early in the pregnancy the risks of low birth weight and pre-term delivery appear to increase12.
However, iron absorption increases up to 9-fold in pregnancy13. The foeto-placental unit is very efficient, so maternal and newborn iron status are poorly correlated except when gross IDA exists4.
Researchers at Surrey University have shown that pre-eclamptic women have higher levels of serum iron and ferritin, with transferrin, more highly saturated and with lower levels of unsaturated iron-binding capacity than matched controls14. These findings are relevant to the substantially higher levels of lipid peroxidation and endothelial cell damage occurring in pre-eclamptic women14. Surrey Uni. Pre-eclampsia kills ten women each year in the UK and up to 1,000 babies die each year as a result of pre-eclampsia15. 1 in 10 pregnancies are affected and 1 in 20 to a serious extent15. High haemoglobin levels are also associated with increased risk of adverse pregnancy outcomes14.
Sudden Infant Death Syndrome
The higher concentrations of liver iron shown in SIDS victims appears to be acquired after birth18. Retrospective iron analysis from Guthrie cards indicates that SIDS victims are not born with abnormal concentrations of stored iron compared with controls18. SIDS occurs when tissue iron concentrations are higher than at any other time of life. It is possible that the ready availability of iron enhances free-radical damage, which might be implicated in SIDS19.
Bottle-feeding has been associated with SIDS. Many formula-milks are fortified with iron. Perhaps, there is some correlation to be found in this relationship?
Iron and Cancer
Recent concern that excess iron could be implicated in the high incidence of colon cancer in developed countries has raised questions as to the desirability of fortification practices20. Handout. Most dietary iron remains unabsorbed and hence may be available to participate in Fenton-driven free radical generation in conjunction with the colonic microflora, leading to the production of carcinogens or direct damage to colonocytes. Higher carbohydrate diets were associated with reduced free radical generation in this study10. It has been suggested, notably by Bezkorovainy (1989) that the normal flora has the capacity to accumulate much larger granules of iron than they need, hence making it unavailable to pathogenic organisms22. High fibre diets encourage a normal bowel flora. Iron overload is associated with liver cancer23. Researchers have found an association between body iron stores and overall cancer incidence rates in men23.
Pre-menopausal women have a lower incidence of and lower mortality from coronary heart disease compared with men of similar age or with postmenopausal women, that is not solely accountable to the hormonal differences in pre and post-menopausal women24. Simple hysterectomy without oopherectomy shows an increased risk of CHD indicating that menstrual bleeding may play an important role in risk reduction24.
The Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD), well analysed for confounding factors, showed that men who donated blood regularly had a greatly reduced risk of acute myocardial infarction compared with non-blood donors. The association was strong and statistically significant in spite of the small number of blood donors in the study cohort24. Other studies, e.g. the Rotterdam Study, support this finding24,25. However, there are other studies that failed to observe an association between iron and ischaemic cardiac events, however there are factors that may explain the lack of association24.
Iron, a transition metal with oxidating properties, has the ability to catalyse toxic redox reactions. Some studies have demonstrated a relationship between excessive iron and coronary heart disease, but the results have been inconsistent in human populations26. Researchers have noted that the risk of AMI due to body iron stores may be greater in Finnish men than in Americans, because the use of anti-oxidative vitamins and aspirin is rare in Finland and quite common in America26.
Iron and Haemochromatosis
Haemachromatosis is inherited as an autosomal recessive trait and is manifested by increased absorption of dietary iron, resulting in increased saturation of serum transferrin, elevated serum ferritin concentrations, and excess iron deposition in the parenchymal cells of the liver, heart and certain endocrine organs27. Premature death results from complications of chronic liver disease, hepatocellular carcinoma, or heart failure and can be prevented by early detection and treatment with phlebotomy27. Arthropathy is a common feature with hereditary haemachromatosis28. Pancreatic endocrine and pituitary dysfunction are common in patients with iron overload, as are opportunistic infections.
Haemachromatosis is one of the most common recessive genetic disorders in Northern Europe30. The gene frequency (HFE C282Y mutation) is about 5% with about 10% of the population carrying one copy of the gene and 1 in 400 having the condition30. The degree of penetrance of this genotype is unknown and requires further research31. People with one copy of the gene rarely accumulate enough iron to cause tissue damage but may be less likely to suffer from iron deficiency33.
The common view is that a low iron diet is of little benefit, as treatment needs to be continued, since considerably more iron can be removed in a single venesection than diet alone can prevent32.
However, the Haemachromatosis Society’s advice on diet32:
It is not easy to identify individuals in the early stages of iron accumulation, as measurement of serum transferrin saturation and serum ferritin concentration give many false positive results34.
Given the potential impact of iron overload in genetic haemachromatosis on wide-ranging health conditions that develop over decades it would seem pertinent to be cautious about fortifying foods with iron.
Possible Beneficial Effects of Iron Deficiency
It has been suggested that the infrequency of cardiovascular arteriosclerotic disease in developing communities may result in part at least from a stimulating effect of chronic anaemia on the development of collateral anastomotic vessels in the coronary arterial system. Hypolipidaemia is another aspect of anaemia, which is likely to be interest33.
A single nutrient deficiency is uncommon and it is possible that effects attributed to iron deficiency are caused by concomitant deficiencies of other essential nutrients4. It is important to remember that iron deficiency can be caused by: hookworm, malaria and vitamin A deficiency4 - all relevant issues to UK populations.