Iron.

KEY POINTS

* Iron is required for the transport of oxygen and numerous metabolic functions, including the production of energy.

* Dietary iron exists in two forms: haem iron is found in foods from animal sources, especially meat; and non-haem iron is found mainly in plant foods. Haem iron is absorbed with much greater efficiency than non-haem iron. Absorption of non-haem iron is enhanced by vitamin C or the presence of meat, poultry or fish; and inhibited by phytate and polyphenols.

* The combination of increased iron requirement for growth, iron loss through bleeding, and poor food selection, increases the risk of iron deficiency, especially in young women and children. Diets that are low in iron, high in inhibitors, with little haem iron intake, are the most common causes of iron deficiency.

* Symptoms of iron deficiency are anaemia, decreased aerobic fitness, and in children, behavioural disturbances, and impairment of both cognitive function and psychomotor development.

* The Recommended Dietary Intake for iron is 18 and 8 mg/day for women and men, respectively. The Dietary Guidelines for Australian Adults, Children and Adolescents identify red meat as the best source of bioavailable iron in the Australian diet.

INTRODUCTION

Adult humans contain approximately 2-4 g of iron, in the ferric ([Fe.sup.3+]) or ferrous ([Fe.sup.2+]) form. The majority (50-70%) of body iron is located in red blood cells in association with haemoglobin, and the remainder is distributed in myoglobin (7-10%), in a range of enzymes (3-5%), stored in the liver (25%), or appears in the plasma (less than 1%). The essentiality of iron relates to its ability to bind oxygen for transport to tissues (haemoglobin) and for short-term storage in muscles (myoglobin). The presence of iron in mitochondrial enzymes (e.g. dehydrogenases or cytochromes) facilitates the flow of electrons that is needed for the production of metabolic energy Other iron-containing enzymes are involved in numerous metabolic pathways, including protein and DNA metabolism, collagen synthesis and metabolism of [beta]-carotene. (1-3)

Dietary iron is absorbed from the small intestine, mainly the duodenum, by a process that requires specific iron transporters. Once absorbed, iron is either bound to ferrtin in the intestinal cell, or transported to tissues by transferrin. Most of the absorbed iron is transported to the bone marrow for the synthesis of haemoglobin and red blood cells. Body iron is tightly conserved, and through recycling of old (senescent) red blood cells, a large percentage of its requirements can be met. Small amounts of iron are excreted through the gastrointestinal tract, skin and kidneys. Significant losses of iron occur when salvage mechanisms are bypassed, primarily by direct loss of intact red blood cells, for example through menstrual blood losses or in people with gastrointestinal infections or ulcers. Iron is stored as ferritin or haemosiderin, with the principal sites of storage being the liver, bone marrow and spleen. (1-3)

In view of the widespread involvement of iron in metabolism, it is not surprising that iron deficiency results in a broad range of adverse effects. Iron deficiency may occur at any stage of the life cycle; however, children, adolescents, pregnant and post-partum women are the most commonly affected individuals because of the high iron requirements of growth, pregnancy and lactation. The most common symptom of iron deficiency is anaemia, which, in its severest form, is associated with weakness and eventually heart failure. Iron deficiency decreases aerobic fitness and work capacity through mechanisms that include impairment of oxygen transport and oxidative phosphorylation within muscles. In children, symptoms of iron deficiency include weakness, behavioural disturbances, and impairment of both cognitive function and psychomotor development. (1-4) The World Health Organisation (WHO) has estimated that iron deficiency is one of the most prevalent nutrient deficiencies in the world, affecting an estimated two billion people. (4) This review considers the food sources of iron and the implications for the Australian diet.

FOOD SOURCES OF IRON AND BIOAVAILABILITY 

Dietary iron exists in two forms, haem and non-haem. Haem iron is found in foods that contain haemoglobin or myoglobin, that is, foods from animal sources, especially meat, fish and poultry Non-haem iron is found in plant foods such as vegetables, fruit and nuts, in iron-fortified foods, and in foods of animal origin. (1-3) The bioavailability of iron is dependent on its chemical form and the presence or absence of dietary factors that interact with its absorption. (5)

Haem iron is a digestion product of haemoglobin or myoglobin. This form of iron is soluble in the intestine and is absorbed intact by a specific carrier mechanism known as haem carrier protein 1. (1,2) As the iron is shielded by haem, its absorption is not affected significantly by the composition of the background diet, and its bioavailability is considered relatively high, in the range 15-35%. (5) In contrast to haem iron, the bioavailability of non-haem iron is lower, in the range 2-20%, (5) and is influenced by the presence of promoters or inhibitors. Non-haem iron is absorbed by a divalent metal transporter 1 (DTM 1), which requires iron to be in the ferrous state. (1,2)

The most significant promoters of non-haem iron absorption are vitamin C (ascorbic acid), organic acids and the presence of meat, fish or poultry protein, also known as the 'meat factor'. The specific component of meat, poultry or fish that promotes non-haem iron absorption is not known. (5,6) Vitamin C enhances non-haem iron absorption by acting as a reducing agent, converting iron to its ferrous state, thus enabling it to interact with the transporter, DTM 1. The enhancing effects of meat and vitamin C on the absorption of non-haem iron are dose dependent. (5)

Common inhibitors of non-haem iron absorption are phytate, polyphenols, oxalate and high doses of minerals. (1-5) Phytate from unrefined cereals, and polyphenols from plant sources such as tea or herbs, (7) form insoluble complexes with iron in the intestine and prevent its absorption. High doses of divalent minerals, for example zinc, compete for absorption as they are absorbed also by DTM 1. Diets that are low in total iron, high in inhibitors, with little meat intake, are the most common causes of iron deficiency. (4)

IRON STATUS OF AUSTRALIANS AND NEW ZEALANDERS

Iron deficiency is the result of a gradual reduction in the amount of iron in various body compartments. In the early stages of iron deficiency, low ferritin concentrations reflect depleted tissue iron stores, but there is sufficient iron for the production of red blood cells. If the supply of iron continues to fall, as indicated by low serum iron concentrations and low saturation of transferrin, then the synthesis of red blood cells is compromised (iron-deficiency erythropoiesis). When iron stores become exhausted and the supply of iron to the bone marrow is greatly reduced, the concentration of haemoglobin falls, resulting in smaller (microcytic) and paler (hypochromic) red blood cells (iron-deficiency anaemia). (1-3)

Iron deficiency is a common nutrient deficiency in childhood that arises from an inadequate intake of iron to match the rapid growth rate. (8) The incidence of iron deficiency and iron-deficiency anaemia is reported to be as high as 25% and 14%, respectively, in infants up to the age of 36 months and from varying backgrounds (9-11) (Table 1). All infants, but especially premature and/or low-birthweight infants, are at risk of iron deficiency because of the limited supply of iron in utero and minimal iron stores of the infant. Predictors of iron deficiency include an inadequate intake of iron, the duration of breastfeeding and intake of cow's milk. When the diet of iron-depleted infants was examined, compared with those who were iron replete, the intake of haem iron was found to be significantly lower and there was a tendency for lower intakes of total iron and vitamin C, indicating a diet of low iron bioavailability. (12) Children eating less than 0.7 mg of haem iron (or approximately 50 g of lean beef) were three times more likely to be iron-depleted. This observation is further supported by the positive association between iron status of infants and the consumption of meat, fish and poultry. (11)

Data from the National Survey of Lead in Children showed that the prevalence of low haematocrit (anaemia) in children aged one to four years was 3.3% or 2.0% when the US or WHO criteria are used respectively, with no significant effects of gender, age or Indigenous heritage. Data on other biomarkers of iron status and dietary intake were not collected. (13) A longitudinal study of New Zealand infants showed iron-deficiency erythropoiesis in 19%, 22% and 13% of infants followed up at 9, 12 and 24 months of age. Iron-deficiency anaemia was 7% at 9, 12 and 18 months of age, but absent at 24 months. The decline in iron-deficiency anaemia between 18 and 24 months was explained in part by the increase in the intake of meat, fish and poultry. (14)

Iron status of 9-, 12- and 15-year-old children was assessed in a national survey of Australian schools. (15) Iron status, based on plasma ferritin and transferrin saturation, was considered generally satisfactory except in 15-year-old girls, among whom the percentage of iron deficiency was markedly higher (9.2%) compared with younger girls or boys (0-1.6%). There were minimal differences in the quantities of food from the 'meat group' and 'cereals group' between the 10- and 15-year-old girls despite the difference in iron requirement, (15) suggesting that iron requirements have increased greatly among adolescent girls although the diets changed little. In a survey of young Australian women (15-30 years), the prevalence of iron deficiency and iron deficiency anaemia was observed to be similarly high (7.2% and 4.5%, respectively). A large proportion of the study participants classified themselves as vegetarian (13%) or semi-vegetarian (17%), reported high menstrual scores (35%), and consumed minimal amounts of red meat. (16) In a sample of young New Zealand women, mild iron deficiency was observed in 23% of the cohort, with risk factors identified as: a low intake of meat, fish and poultry; high menstrual blood loss; recent blood donation; nose bleeds; and low body mass index. (17) Thus, the combination of increased iron requirement for growth, iron loss through bleeding, and poor food selection, increases the risk of iron deficiency in premenopausal women. (15-17)

Iron status of men has been shown to be lower in those consuming an ovo-lactovegetarian or vegan diet as compared with those eating an omnivorous diet. The reduction in iron status was observed despite a significantly higher intake of iron from the vegetarian diets. (18) In women, vegetarian diets have been shown to contribute similar quantities of total dietary iron; however, iron status is lower in women who consume a vegetarian diet compared with those who consume an omnivorous diet. (19) A low intake of haem iron and presence of factors that inhibit non-haem iron absorption are the most likely contributors to the impairment of iron absorption in those consuming vegetarian diets. (5)

The extent of iron deficiency, especially in young women, can be exacerbated in athletic populations. (20) In a survey undertaken at the Australian Institute of Sport, iron deficiency was reported in 51% of female athletes. (21) Poor diets and a high metabolic turnover rate of body iron are contributing factors.

Iron deficiency in women is associated with decreased general health and increased fatigue. (22) When iron-deficient women were supplemented with iron or advised to consume a diet high in iron, their iron status improved (23,24) along with their mental health and vitality scores, and their levels of fatigue declined. (25) Dietary strategies to improve iron status are shown in Table 2.

IRON AND HAEM IRON INTAKES IN AUSTRALIA: CONTRIBUTION OF RED MEAT

The National Nutrition Survey (27) showed that the mean intake of iron in adult male and female individuals was 16.4 and 11.9 mg/day, respectively Red meat provided 16% and 11% of the total iron in the diet of male and female adults, respectively, and 52% of the haem iron intake. (28)

Based on a recommended dietary intake (RDI) of 7 mg/day, approximately 2% of adult men and 3% of men aged >65 years had iron intake below 70% of the RDI. (28) The recent upward revision of the RDI to 8 mg/day (29) will result in a higher percentage of men at risk of low intakes of iron. A much higher percentage of women (nearly 25%) than men had iron intakes below 70% of the RDI, and approximately one-third of women in the category of 19-54 years had intakes below 70% of the RDI (12-16 mg/day). (28) In the analysis by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), the lower end of the range (12 mg) was used to calculate percentage of women below the RDI. The recently revised RDI, now set at 18 mg to reflect the variation in menstrual blood losses, is likely to increase dramatically the percentage of women who are consuming iron in amounts below recommended levels. In women consuming <70% of the RDI, the intake of iron was inversely correlated with the amount of red meat that was consumed on the day of the survey. (28)

In women aged 19-50 years, the distribution of basal losses of iron is in the range of 0.6-1.42 mg/day (5th-97.5th percentile), a 2.4-fold difference. However, the range of menstrual losses is 0.14-2.32 mg/day a 16.5-fold difference. The estimated average requirement is set at the 50h percentile for basal and menstrual losses (0.89 and 0.51 mg, respectively); however, the RDI, by definition, must include 97-98% of the population. Thus the RDI is based on the upper estimates of basal and menstrual losses, and the figure of 18 mg/day is the amount of dietary iron required to replace iron losses. The average bioavailability of dietary iron is 18% and assumes that iron is derived from a mixed Western diet that includes animal foods. Vegetarians will need intakes that are approximately 80% higher. (29)

CURRENT DIETARY RECOMMENDATIONS

The Dietary Guidelines for Australian Adults (30) and for Children and Adolescents (31) encourage individuals to 'include lean meat, fish, poultry and/or alternatives'. The Guidelines state that red meats (defined as muscle meat from cattle, sheep, goat and kangaroo) are the best sources of bioavailable iron in the Australian diet. (28,30) The Australian Guide to Healthy Eating (32) identifies red meats as particularly good sources of iron that is more easily absorbed by the body than the iron in vegetable foods, and recommends that red meat should be eaten three to four times a week or high-iron replacement foods will be required. This is especially true for girls, women, vegetarians and athletes. (32)

The RDI for iron is 8 mg/day for men, 18 mg/day for women 19-50 years, and 8 mg/day for women aged >51 years, with an additional 27 mg for pregnancy and 9-10 mg per day for lactation. (29) The current RDI is higher than the previous Australian RDI for all genders and age groups. The upper limit of intake is 45 mg/day.

CONCLUSIONS

Iron is required for the transport of oxygen and numerous metabolic functions, including the production of energy Haem iron from animal foods is absorbed with much greater efficiency than non-haem iron, which is found mainly in plant foods. Absorption of non-haem iron is enhanced by vitamin C and the presence of meat, poultry or fish; and inhibited by phytate and polyphenols. The combination of increased iron requirement for growth, iron loss through bleeding, and poor food selection, increases the risk of iron deficiency especially in young women and children. Diets that are low in iron, high in inhibitors, with little haem iron intake, are the most common causes of iron deficiency. The Australian Guide to Healthy Eating and the Dietary Guidelines for Australian Adults, Children and Adolescents identify red meat as the best source of bioavailable iron in the Australian diet.

REFERENCES

1 MacPhail P. Iron. In: Mann JI, Truswell AS, eds. Essentials of Human Nutrition, 3rd edn. Oxford: Oxford University Press, 2007; 125-37.

2 Wood RJ, Ronnenberg AG. Iron. In: Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease, 10th edn. Philadelphia, PA: Lippincott, Williams & Wilkins, 2006; 248-70.

3 Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism, 4th edn. Belmont, CA: Thomson Wadsworth, 2005.

4 World Health Organisation. The World Health Report 2002: Reducing Risks, Promoting Healthy Lifestyles. Geneva: WHO, 2002.

5 Monson ER. Iron nutrition and absorption: dietary factors which impact iron bioavailability. J Am Diet Assoc 1988; 88: 786-90.

6 Hurrell RF, Reddy MB, Juillerat M, Cook JD. Meat protein fractions enhance nonheme iron absorption in humans. J Nutr 2006; 136: 2808-12.

7 Samman S, Sandstrom B, Toft MB et al. Green tea or rosemary extract added to foods reduces nonheme-iron absorption. Am J Clin Nutr 2001; 73: 607-12.

8 Allen JR, Baur LA. Iron deficiency in infants and young children. Med Today 2000; 1: 2-7.

9 Oti-Boateng P, Seshadri R, Petrick S, Gibson RA, Simmer K. Iron status and dietary iron intake of 6-24-month-old children in Adelaide. J Paediatr Child Health 1998; 34: 250-53.

10 Karr MA, Mira M, Alperstein G et al. Iron deficiency in Australian-born children of Arabic background in central Sydney. Med J Aust 2001; 174: 165-8.

11 Nguyen ND, Allen JR, Peat JK, Beal P, Webster BH, Gaskin KJ. Iron status of young Vietnamese children in Australia. J Paediatr Child Health 2004; 40: 424-9.

12 Mira M, Alperstein G, Karr M et al. Haem iron intake in 12-36 month old children depleted in iron: case-control study. Br Med J 1996; 312: 881-3.

13 Mackerras DE, Hutton SI, Anderson PR. Haematocrit levels and anaemia in Australian children aged 1-4 years. Asia Pac J Clin Nutr 2004; 13: 330-35.

14 Heath AL, Tuttle CR, Simons MS, Cleghorn CL, Parnell WR. Longitudinal study of diet and iron deficiency anaemia in infants during the first two years of life. Asia Pac J Cin Nutr 2002; 11: 251-7.

15 English RM, Bennett SA. Iron status of Australian children. Med J Aust 1990; 152: 582-6.

16 Rangan AM, Aitken I, Bligh GD, Binns CW. Factors affecting iron status in 15-30 year old female students. Asia Pac J Clin Nutr 1997; 6: 291-5.

17 Heath AL, Skeaff CM, Williams S, Gibson RS. The role of blood loss and diet in the aetiology of mild iron deficiency in premenopausal adult New Zealand women. Public Health Nutr 2001; 4: 197-206.

18 Wilson AK, Ball MJ. Nutrient intake and iron status of Australian male vegetarians. Eur J Clin Nutr 1999; 53: 189-94.

19 Ball MJ, Bartlett MA. Dietary intake and iron status of Australian vegetarian women. Am J Clin Nutr 1999; 70: 353-8.

20 Beard J, Tobin B. Iron status and exercise. Am J Clin Nutr 2000; 72 (Suppl. 2): 594S-7S.

21 Fallon KE. Utility of hematological and iron-related screening in elite athletes. Clin J Sport Med 2004; 14: 145-52.

22 Patterson AJ, Brown WJ, Powers JR, Roberts DCK. Iron deficiency, general health and fatigue: results from the Australian Longitudinal Study on Women's Health. Qual Life Res 2000; 9: 491-7.

23 Heath AL, Skeaff CM, O'Brien SM, Williams SM, Gibson RS. Can dietary treatment of non-anemic iron deficiency improve iron status? J Am Coll Nutr 2001; 20: 477-84.

24 Patterson AJ, Brown WJ, Roberts DCK, Seldon MR. Dietary treatment of iron deficiency in women of childbearing age. Am J Clin Nutr 2001; 74: 650-56.

25 Patterson AJ, Brown WJ, Roberts DCK. Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age. J Am Coll Nutr 2001; 20: 337-42.

26 Gibson RS, Heath AL, Ferguson EL. Risk of suboptimal iron and zinc nutriture among adolescent girls in Australia and New Zealand: causes, consequences, and solutions. Asia Pac J Clin Nutr 2002; 11 (Suppl. 3): S543-52.

27 Australian Bureau of Statistics. National Nutrition Survey. Selected Highlights Australia 1995. Canberra: Commonwealth of Australia, 1998.

28 Baghurst K, Record S, Leppards P. Red meat consumption in Australia: intakes, nutrient composition and changes over time. Aust J Nutr Diet 2000; 57: S3-36.

29 Department of Health and Ageing. Nutrient Reference Values for Australia and New Zealand. Executive Summary. Canberra: Commonwealth of Australia, 2006.

30 Commonwealth Department of Health and Ageing. Dietary Guidelines for Australian Adults. A Guide to Healthy Eating Canberra: Commonwealth of Australia, 2003.

31 Commonwealth Department of Health and Ageing. Dietary Guidelines for Children and Adolescents in Australia. A Guide to Healthy Eating. Canberra: Commonwealth of Australia, 2003.

32 Commonwealth Department of Health and Family Services. The Australian Guide to Healthy Eating. Canberra: Commonwealth of Australia, 1998.

Samir SAMMAN

Human Nutrition Unit, University of Sydney, Sydney, New South Wales, Australia

Table 1 Iron status of infants

Age (months); ethnicity  Iron status                          Reference

6-24; Caucasian          25% iron deficient; (a)               9
                           6% anaemic. (a,b)
                         Prolonged breastfeeding associated
                           with deficiency.
6-24; Asian              14% iron deficient, (a)               9
                           14% anaemic. (a,b)
12-36; Arabic            23% iron deplete, (c)                10
                           9% iron deficient, (c,d)
                           6% anaemic. (b-d)
                         Intake of cow's milk >600 mL/day is
                           negatively correlated with iron
                           status.
0-18; Vietnamese         19% iron deplete, (c)                11
                           3% iron deficient, (c,e)
                           4% anaemic. (b,c,e)
                         Meat, fish and poultry intake
                           positively associated with iron
                           status.

(a) Haemoglobin >110 g/L and serum ferritin <15 [micro]g/L and/or
transferrin >3.0 g/L, transferrin saturation >12%, and serum iron
<8.0 [micro]mol/L.
(b) Haemoglobin <110 g/L.
(c) Plasma ferritin <10 [micro]g/L.
(d) Mean corpuscular volume (MCV) <70 fL (age 12-23 months) or <73 fL
(age 24-38 months), mean corpuscular haemoglobin <22 pg.
(e) MCV <70 fL.

Table 2 Dietary strategies that enhance iron status in women (23,26)

Dietary strategy                       Recommendation

Increase intake of iron-containing     Consume one serving of foods rich
  foods                                  in haem iron (e.g. red meat,
                                         liver) and one serving of
                                         medium iron food (e.g. chicken,
                                         legumes).
Increase intake of enhancers of iron   Consume foods or beverages
  absorption                             containing at least 50 mg of
                                         vitamin C in each meal. With
                                         meals, replace tea, coffee and
                                         wine with beverages rich in
                                         vitamin C.
Decrease intake of inhibitors of iron  Decrease consumption of foods
  absorption                             high in phytate (wheat bran,
                                         nuts) and polyphenols (e.g.
                                         spinach). Choose beans other
                                         than soybeans.