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One of the most researched micronutrients, iron still fosters new
discoveries about its homeostasis and physiological role. Rachel Arthur
explains groups at risk of deficiency and supplementation considerations.
Rachel Arthur, BHSc, ND, is a practising naturopath and lecturer in naturopathic nutrition and a research assistant at NatMED Research in the School of Health and Human Sciences, Southern Cross University The Editor thanks Surinder K Baines, BSc, PhD, GradDipDiet, APD, Lecturer in Nutrition and Dietetics, University of Newcastle, for her kind assistance in the peer review of this article • Although haem iron exhibits superior bioavailability, per capita red-meat consumption in Australia has continued to decline, leaving us heavily reliant on the non-haem form • There are several groups at risk of iron deficiency in Australia, with third-trimester pregnant women and children from some ethnic minorities exhibiting the highest rates of deficiency • Although Australian rates of iron-deficiency anaemia (IDA) remain low in comparison to other countries, a great many more individuals suffer from iron depletion • The human body exhibits sophisticated regulation of iron levels, including an extraordinary capacity for recycling iron that is partly protective in those with borderline iron status but may contribute to unhealthy iron accumulation in others • Hereditary haemochromatosis, estimated to affect 0.33–0.5%8 of Australians, is a genetic iron-metabolism disorder with a low phenotypic penetrance that can result in increased morbidity and mortality due to unregulated uptake of iron from the GI tract • Iron supplementation may be beneficial in some children's behavioural • New research investigating iron supplementation practices, including forms, dose and dosage regimes, have been substantially revised 36 Complementary Medicine May / june 2007

IRON nutrition notes The last few decades have seen iron Dietary sources of iron9
research develop from the singular concern of deficiency (chlorosis or Fe content
anaemia) to an appreciation of its potential toxicity and the body's mechanisms for minimising such risks. Lamb kidneys (130 g) Lamb liver (130 g) Dietary sources and Chicken livers (130 g) Mussels (12=120 g) While iron is widely distributed in food, the average Western diet contains only Oysters (12=120g) about 5–7 mg per 1000 kcal.1 There Soya bean (100 g) are two types of dietary iron: haem iron Lamb sirloin chop (100 g) (hFe) in the form of haemoglobin and Lean beef sirloin, myoglobin, the predominant type found in flesh foods (50–60 per cent), and Dried figs (4=80 g) non-haem iron (n-hFe), which is the Mung beans (100 g) major form in plant and dairy foods.1,2 Dried peach (25 g) Iron fortificants added to some cereal products, yeast extracts and legume- A smal er study made similar findings and based meat substitutes3 are n-hFe and can identified fortified breakfast cereals alone be any number of iron salts (e.g. ferrous as contributing a staggering 15 per cent of fumarate, ferrous lactate, reduced iron) total daily iron in both omnivorous and with elemental amounts restricted to vegetarian women.7 While the fractional <3.5 mg per serve.3 absorption of iron fortificants vary, they are Iron bioavailability is dependent reported to provide ≤0.33 mg per 100 g11 upon the form found in food, with of product consumed. Improved outcomes hFe providing the highest absorbable of iron fortification are hampered by percentage (20–30 per cent4,5). Non-haem the insolubility of metal ic iron and the iron bioavailability varies dramatical y negative interactions between soluble (2–20 per cent), dependent upon a range iron compounds and the food matrix of extrinsic factors6,7 [see ‘Dietary and in terms of palatability, shelf life, etc.4 digestive factors affecting iron absorption' Another consideration is the potential table, p 38]. Consequently, flesh foods interaction between the fortificant and are considered preferable sources of iron, components of the whole meal. With including highly concentrated examples breakfast cereals a key source of dietary such as offal and clams.8,9 The Australian iron7,12, consumption with milk1 may diet, however, typical y has a hFe:n- reduce their absorbable iron content. See hFe of about 1:12.4, and these specific ‘Dietary sources of iron' table, above.
foods are not commonly consumed.7 In fact, Australian meat consumption has declined significantly since the 1970s, The absorption and bioavailability of iron is coupled with a smal increase in per capita dichotomous as a consequence of its major vegetable consumption.10 dietary presentations as hFe or n-hFe. The major dietary sources of iron Each form undertakes distinct pathways consumed by Australians in 1998 were of digestion and absorption and is subject cereal and cereal products (40 per cent), to contrasting degrees of regulation12 [see fol owed by meat (17–22 per cent) and ‘Regulation of haem and non-haem iron fruits and vegetables (about12 per cent).8 through alterations in uptake' table, p 40]. May / june 2007 Complementary Medicine

nutrition notes IRON Dietary and digestive factors affecting iron absorption Type of Fe affected Mechanism
Acids e.g. ascorbic, n-hFe Act as reducing agents to produce Consumption of 75 mg vitamin C (e.g. ½ glass orange citric, lactic, malic Fe2+ and form a chelate, increasing juice or 1 medium kiwi fruit) maximises bioavailability of and tartaric 2,16,17 solubility in small intestine Fe (e.g. from 2% to 8%)1 Digestion of contractile proteins Consuming 75 g cooked meat with iron-rich vegetables e.g. meat, poultry produces cysteine-containing peptides will maximise absorption of n-hFe in both (from 2% to enhance absorption and fish that form bioavailable chelates and stimulate intestinal secretions that may further ↑ uptake Acidic environment required to Foods and supplements that may help maintain a low pH reduce Fe3+ to more bioavailable in the stomach (e.g. lemon juice, apple cider vinegar) may Fe2+ or to maintain solubility as Fe3+ enhance absorption. Hypo- and achlorhydria have been implicated in Fe deficiency Polyphenols form non-absorbable If tea or coffee are consumed during or within an hour e.g. tea, coffee, complexes with Fe within intestinal of a n-hFe meal/supplement, n-hFe absorption can be ↓ ≥60%.12 This is dose-dependent and may be only of inhibit absorption significance in those already at risk19 Oxalates readily bind n-hFe to form an Despite high iron content, spinach, parsley and other e.g. tea, spinach, insoluble chelate high-oxalate foods do not represent good sources of parsley, rhubarb, chocolatePhytates Phytates bind with n-hFe to form Fermentation of grains or sprouting of legumes will e.g. whole-grains insoluble chelates, increased ingestion increase Fe bioavailability from these foods of Fe will not overcome this effect1,16 Competition for shared transporters, Consuming n-hFe with milk or a Ca supplement (providing inhibition of basolateral transfer12 ≥300 mg elemental Ca) can reduce Fe absorption by or formation of insoluble chelates 70%.1 This partly explains the higher deficiency rates mean that high consumption of these evident in children who consume a high-dairy diet.13–15 One nutrients can ↓ Fe absorption and vice small study did not demonstrate impaired Fe absorption, however, both sample size and amount of Ca were small12 Haem iron is a metal oporphyrin found hydroxide compound. Fe3+ can undergo Distribution, storage, recycling in flesh foods (e.g. haemoglobin and reduction within the intestinal lumen to and ‘excretion' myoglobin). Digestion of this molecule facilitate uptake or bind to solubilising Transferrin carries almost al of the is complete fol owing hydrolysis of the chelators in order to overcome this.1 absorbed and recycled iron around the globin portion, the haem porphyrin ring The overal contribution of Fe3+ to body and is typical y one-third saturated absorbed intact. This means free iron does absorbable iron, while not ful y quantified, with iron.1,16 Due to the bone marrow's not dissociate at any stage within the lumen is speculated to be smal .2 Fe2+, however, high erythropoietic iron demand, and therefore is resistant to unfavourable when favourably chelated, is released and 70–90 per cent is delivered here, facilitated chelation. Although the mechanism is yet readily absorbed across the brush border through transferrin receptors found on the to be completely elucidated, it appears by protein-carrier transporters, including plasma membrane.16 The amount of iron largely impervious to the regulatory the divalent cation or mineral transporter taken up by cel s is influenced by transferrin influences affecting the protein carriers 1 (DMT1). Despite this, fractional saturation, with higher iron content responsible for n-hFe uptake.
absorption of n-hFe remains relatively low promoting increased uptake and the cel s' In contrast to this, n-hFe is released in most instances, principal y the result receptor numbers, which in turn is directly from food producing either ferrous (Fe2+) of interactions between n-hFe, negative proportionate to the cel s' iron demand. or predominantly ferric (Fe3+) ions. As chelating agents and other antagonistic The liver parenchyma is the primary Fe3+, the iron is soluble only in an acidic competitors such as divalent cations1,13–15 iron storage site (about 60 per cent). environment and, upon mixing with co-presenting in the GI tract [see ‘Dietary The remaining 40 per cent occurs in the the alkaline secretions of the pancreas, and digestive factors affecting iron reticuloendothelial cel s (RE) of liver, commonly forms the insoluble ferric absorption' table, above].
spleen, bone marrow and possibly between 38 Complementary Medicine May / june 2007 IRON nutrition notes May / june 2007 Complementary Medicine

nutrition notes IRON muscle fibres.1 The main storage form the tissues, with amounts sufficient to which then inhibits iron recycling in is ferritin, a dynamic molecule which meet any shortfal in intake. Excluding macrophages. This can cause a substantial is constantly undergoing synthesis and menstruating females, there are no actual (about 30 per cent) drop in serum iron degradation, providing an intracel ular pool excretory pathways for iron22 and losses and, if continued long term, results in of available iron. Ferritin levels correlate in healthy people remain extremely low. the anaemia of chronic disease.16,22 This directly with the amount of iron stored The little iron that is lost occurs primarily is believed to be an important part of the and, consequently, are used as a first-line in the GIT via minute blood loss, bile acute-phase response, limiting the use of indicator of iron status.12,17 Release of products and desquamated mucosal cel s.1 iron by invading pathogens.1,16,22 iron from ferritin requires reduction of Other sources of iron loss include the skin Fe3+ via reducing agents (e.g. vitamin C, (through cel sloughing) and urine. Urine Deficiency prevalence riboflavin, niacin and possibly sulphide).2 concentrations should remain low due Estimates of worldwide prevalence When the iron-binding capacity of ferritin to the large size of most iron-containing of iron deficiency vary, with figures is exceeded, as in iron overload, iron molecules, which prevent glomerular ranging from 700 mil ion to two bil ion, binds to haemosiderin. Healthy iron filtration except in renal pathology.1,2 depending on definitions and cut-off stores for males, which peak in their 30s points used.4,32,33 Australian research to 40s, are 50 mg/kg, while women have Homeostasis/regulation of levels confirms the significance of this issue less due to both smal er body size and Iron absorption, in particular n-hFe, and identifies at-risk groups similar to altered iron status as a result of pregnancy increases with low iron status and most countries. Rates of IDA (overt iron- and menstruation. Women's peak decreases in replete individuals.1,8 The deficiency anaemia) have been reported concentrations occur at the age of 60.2,20,21 GIT is considered to be the primary site to be at most five per cent in children The human body possesses an for overal iron regulation. In spite of this, aged between six months and five years extraordinary recycling capacity for iron, iron deficiency is common, therefore this in Australia and New Zealand34–36, with with about 40–60 per cent of iron salvaged adaptation is not absolute.20 The evidence evidence of increased prevalence in some from the degradation of ferritin and points to three key regulators of Fe ethnic minorities.13,37,38 It is important to haemoglobin being reused for haemoglobin absorption: stores, erythropoietic demand remember, however, that rates of IDA, synthesis within 12 days, and the remainder and dietary intake23 [see ‘Regulation of the end-stage deficiency, present an over- entering storage.2,16 For haemoglobin, this haem and non-haem through alterations simplified view of the problem because occurs in the RE system of phagocytes in uptake' table, below]. they don't take into account individuals of the liver, bone marrow and spleen Another important player in iron exhibiting iron depletion. When these and provides about 20–25 mg iron per metabolism is inflammation. Inflammatory figures are combined, the true magnitude day1, while ferritin breakdown occurs in stimuli rapidly trigger hepcidin release, of the problem becomes apparent. For Regulation of hFe and n-hFe iron through alterations in uptake7,9,13,14,30 Type of Fe
Key regulator secreted by bone marrow and liver, whose release is triggered by hFe and n-hFe. The absorption of high Fe stores and inflammation. In response to elevated hepcidin, enterocytes both hFe and n-hFe are affected stimulate degradation of ferroportin and therefore inhibit Fe efflux into portal by body stores. However, n-hFe blood. Conversely, when hepcidin levels ↓ as a result of anaemia or hypoxemia, shows the greatest adaptive together with low cellular Fe uptake, the same transport proteins can be response (10–15-fold vs. 2–3- upregulated within 24–48 hours. May also ↓ DMIT1 expression Fe-rich meal and ↑ A bolus of Fe enterally administered results in enterocyte resistance to Fe concentration in additional absorption for several days. This trapped Fe is then lost with the rapid turnover of mucosal cells (2–3 days). There is additional evidence of redistribution and ↓ expression of DMIT1 Aconitase hydratase and Detects ↓ cytosolic concentration and binds to Fe-responsive elements (IRE) hFe and n-hFe. n-hFe is affected of ferritin, ferroportin and transferrin genes to increase storage, impair the to a larger extent transfer of iron across the basolateral membrane of the enterocyte and slow the transfer of iron from the GIT and from Fe stores Unknown erythropoietic When the erythropoietic drive is high in relation to Fe supply, Fe absorption ↓. Mediated potentially through increasing transferrin receptors 40 Complementary Medicine May / june 2007

Key interactions54 Fe ↓ drug absorption • ACE inhibitors Separate doses by ≥2 hours • Cimetidine• L–dopa and carbidopa• Quinoline antibiotics• Thyroxine Drug ↓ Fe absorption Separate doses by ≥2 hours and monitor Fe levels • Cholestyramine, colestipol• H2-receptor antagonists• Proton pump inhibitors ↓ Fe and ↓ drug absorption • Penicillamine Separate doses by ≥2 hours • Sulfasalazine • Tetracylcines ↓ Fe levels independent of Increased iron intake may be required during long term treatment Additive pharmacological effect • Erythropoietin Beneficial interaction possible example, in one study of six- to 24- the adaptation was not sufficient for those month-old children in New Zealand, 4.3 with low iron stores.39 per cent of the sample were found to be Australian male40 and female7 lacto- anaemic, while an additional 33.5 per cent ovo-vegetarians and vegans demonstrate were diagnosed as either iron deficient or significantly lower ferritin levels and having low iron stores, bringing the real higher rates of iron depletion than their figure to 37.8 per cent.34 omnivorous counterparts, in spite of higher iron intakes. Surprisingly, rates of Vegetarians and vegans anaemia do not differ in women.7 Exclusive consumption of n-hFe results in an overal iron bioavailability of 10 per cent compared to 18 per cent for Iron deficiency is most prevalent an omnivorous diet. This suggests that worldwide in preschool-aged vegetarians would need to consume children.4,11,16,36,41 This apparent 80 per cent more n-hFe, increasing susceptibility is multifactorial, including total daily requirements from 8 mg the rapid growth evident in the first in men and 18 mg in women to 14.4 year, depletion of maternal and infant mg and 32.4 mg respectively.1,16,17 iron stores at six months post-partum28 There is evidence, however, of long- and the low bioavailable iron content of term adaptation to diets with low Fe most complementary foods.23,42,43 The bioavailability and, accordingly, some only national survey investigating rates researchers argue that these figures are of IDA reported an incidence of 2–3.3 probably an overestimation.21 Although per cent among preschoolers36, peaking studies have demonstrated increased among two-year-olds.35 However, n-hFe absorption fol owing long-term the reported percentages affected by (10-week) consumption of a vegetarian suboptimal iron in Australian and New diet by men, later studies in women found Zealand range from 14.4 per cent35 to March / april 2007 Complementary Medicine nutrition notes IRON 40 per cent.34 These figures increase bioavailability.1,14,17 Australian data The demonstrated negative relationship again within several subgroups: indicate that about two per cent of between excess dairy consumption and • low birth-weight and premature children are vegetarians45 poor iron status is controversial but has infants due to inadequate gestational • over-reliance on milk and milk attracted a number of explanations, such as iron accrual33,44 products (≥650 mL/day) in children milk's poor iron content and substitution • prolonged exclusive breastfeeding23,44 >12 months13,14,37,46 for other iron-rich foods, calcium's potential • consumption of meat less than four • Aboriginal children in rural but not to inhibit iron uptake and possible microscopic GIT blood loss.14 • young vegetarian children with • recent maternal immigration47 a reduced stomach capacity, potential y associated with inadequate Adolescent girls48 preventing the 80 per cent increase maternal iron, poverty, reduced food A rapid growth spurt, together with in iron-containing foods necessary diversity and subsequent over-reliance menarche and a trend for declining red- to compensate for reduced iron on cow's milk.13,44 meat consumption in this age group, increase the likelihood of a shortfall Hereditary haemochromatosis – when Fe regulation goes wrong between requirements and intake.49 Hereditary haemochromatosis (HH) is one of a number of genetic iron-metabolism Additional exacerbating factors include disorders that particularly affects individuals with northern European, western and high menstrual losses, strenuous exercise, southern German or Spanish ancestry. Estimations of the percentage of Australians frequent blood donation or other sources with this condition range between about 0.33–0.5%8, increasing to 1.2% of men ≥58 of blood loss (e.g. epistaxis), pregnancy, years of age.26 HH is a human leukocyte antigen (HLA)-linked autosomal recessive low socio-economic status and ethnicity.49 disorder caused by a single nucleotide polymorphism in the HFE gene16, with the While one study estimated that about eight majority of symptomatic individuals being homozygotes (80–100%).27–29 The loss of per cent of Australian teenage girls have low normal HFE protein expression on enterocyte cell membranes results in impaired iron stores, with a quarter of these suffering sensing of body iron stores.29 This stimulates increased expression of DMIT1, IDA14, substantial y higher figures have increasing GIT iron absorption. A recent discovery has been the partial hepcidin been reported by other authors (12 per cent deficiency characteristic of HH and considered to be as central to its pathogenesis low ferritin and seven per cent IDA).49 as insulin is to diabetes.22,24,29,30 Ultimately, this annuls the ‘stores regulator', producing ongoing increased absorption (≥ x 2)16 in the face of elevated ferritin. Over time, transferrin and ferritin become saturated22 and excess iron is stored as A number of contributing factors haemosiderin, deposited in the liver, heart and endocrine glands, increasing the merge to place women at an increased risk of malfunction and damage.6,8 The liver is the primary target and 30% of deaths risk of iron deficiency. Most notable is from HH are due to hepatocellular carcinoma.6,29 menstrual blood loss (30 to >80 mL per Individuals can also be heterozygous for HH, with an incidence approximating cycle)1, 50 equivalent to about 13.5–36 10% of Americans.6 Heterozygotes, although potentially displaying abnormal iron mg per month.2 Such direct iron loss status, don't demonstrate the same upregulation of iron absorption28 or develop is exacerbated in IUD users5,50 who organ failure.1 Even HH homozygotes are typically asymptomatic due to the experience 30–50 per cent greater blood low penetrance of the clinical phenotype. Only 60% of homozygotes eventually loss, and is moderated in women on oral develop iron overload27, and results from a large American study suggest that contraception. In addition to this, women <1% develop frank haemochromatosis, although this remains controversial.16 demonstrate a number of dietary patterns Clinical features of HH may take decades to appear, typically presenting midlife, that also compromise intake, consuming and show substantial inter-individual variation. Most notably, the age of onset is less overal iron than men each day (11.1 delayed in females and regular blood donors, and accelerated in patients with mg vs. 15.2 mg)8, as wel as a reduced hFe: existing comorbidities, e.g. viral hepatitis.6,31 n-hFe.8 Restricted calorie consumption While restriction of both dietary Fe and supplemental vitamin C and tea may also play a part.14 The Australian consumption to impair iron uptake is a sensible first step in the management of Longitudinal Study of Women's Health HH, those homozygotes with high ferritin +/- increased transferrin saturation estimates that one in three women have should have regular venesection. If undertaken prior to the development of been diagnosed with iron deficiency by the cirrhosis, this can reduce morbidity and mortality.27,29 age of 45–50.51 Other than vegetarianism, risk factors for women include: 42 Complementary Medicine May / june 2007 IRON nutrition notes • multiparity — risk is increased with
Features of acute and chronic iron deficiency1,4,5,15,16,59 parity, with a threefold greater risk Acute deficiency (early indicators)
Chronic deficiency (late indicators)
for those women with two or three children and almost four times greater • Listlessness, fatigue and lethargy • Microcytic hypochromic anaemia • Pallor of mucous membranes • Pale blue sclera risk for those with four or more50; • Koilonchyia (spoon-shaped nails) • regular strenuous exercise — long-
• Angular stomatitis • Slow tooth growth distance running in particular is • Reversible gastric atrophy • Poor tooth integrity with increased caries associated with increased iron losses • Increased susceptibility to infection • Salivary gland dysfunction through sweat, faeces and intravascular • Increased lead absorption • Irreversible learning impairment in children • Delayed psychomotor development in • Increased maternal morbidity, premature haemolysis (namely footstrike), as well infants and children labour and LBW babies as a dilutional pseudoanaemia.52–54 • Impaired work performance and productivity • Oesophageal webbing (Plummer-Vinson Together, these produce a 20 per cent faster rate of whole-body iron loss in • Pica: geophagia (dirt) and pagophagia (ice) • Exertional dyspnoea female athletes than in non-athletes.15 • Parasthesias in hands and feet • Cold extremities Compounding this is consistent • Impaired thyroid function evidence of energy underconsumption • Diminished menstrual flow by female athletes, which often results • Hyperactivity and possibly ADHD • Night cramps in compromised iron intake52,53; • Cardiac bruits • pregnancy — the total iron cost of
• Cardiomegaly• Cardiac failure pregnancy is reported to be in the vicinity • Spleen enlargement of 700–1400 mg.4,32,55 This is required for the growth and maintenance of both gestation (e.g. low birth weight, fatigue. A diminished oxygen-carrying foetus and mother, with al owances premature labour and increased perinatal capacity can result in the pallor often made for losses at delivery. Increased mortality) remain controversial.
described as the key clinical feature requirements begin in the second of iron deficiency. However, this can trimester and have increased eightfold by often be hard to detect in patients of the third.4 Accordingly, rates of anaemia Comorbidities associated with increased varying skin tones and is best observed fol ow similar step-wise increases, from blood loss place other individuals at risk in the mucous membranes57, e.g. inside about 6.7 per cent in the first trimester to of a secondary iron deficiency, including lower eyelid or mouth. Other features 45.6 per cent in the third, indicative of any form of haemorrhage, renal disease, are listed in the ‘Features of acute and the widening gap between demand and steatorrhoea, some GIT parasite chronic iron deficiency' table, above.
consumption.50 A comparison between infestations1, coeliac and IBD and the current RDI (27 mg/day) and the menorrhagia.50 In addition to this, factors indications for iron average dietary intake of iron by Australian associated with compromised absorption Prevention and treatment of IDA pregnant women (12 mg/d) makes plain of iron may also precipitate a secondary Studies in anaemic children have the principle cause.56 Some authors state deficiency, such as protein calorie demonstrated that ferrous sulphate 300 mg that unless preconception iron stores are malnutrition, hypo- or achlorhydria [see weekly dosing was successful in increasing ≥500 mg, the high iron requirements of JCM 2007;6(1):55–7], Helicobacter pylori both haemoglobin and IQ.54 Prophylactic pregnancy necessitate supplementation.4 infections or infestations of certain iron supplementation (40 mg/d) from 18 This position is supported by a study of parasites, e.g. hookworm.1 weeks' gestation prevented iron deficiency over 2000 unsupplemented pregnant in 90 per cent of women and anaemia women, whose haemoglobin levels signs of deficiency in 95 per cent, and these benefits carried remained low throughout gestation and at Early indicators of iron depletion are through into the post-partum period.59 An one year postpartum.4 This suggests that generalised, due partly to the rapid Australian study found comparable results iron depletion in pregnancy can have long- compromise of the Kreb's cycle Fe with 20 mg/d from 20 weeks' gestation.56 lasting ef ects for the mother.
metalloenzymes and ETC cytochromes, which are essential to the production of Fatigue without anaemia The suggested consequences of cellular energy. Consequently, patients Braun and Cohen54 report that iron inadequate maternal iron during classically present with listlessness and supplementation (80 mg/d) is useful for May / june 2007 Complementary Medicine nutrition notes IRON some fatigued women in the absence patients with confirmed suboptimal An increasing number of studies show of abnormal iron studies, reducing status49, others argue that although more improved success with low-dose (≤20 fatigue by 29 per cent over four weeks. slow to correct ferritin levels (at least nine mg) long-term supplementation (at least However, this was only true for those months), dietary treatment of mild iron six months) in many patients including with baseline ferritin <50 mcg/L.
deficiency is preferable.51 This argument is children and pregnant women.33,56,67 convincing because dietary modification Certain clinical situations necessitate may also prevent subsequent IDA through parenteral administration, including:4 Iron has attracted attention as a potential addressing dietary causes. Additional y, • impaired iron absorption contributor in ADHD due to the more sustained improvements have • poor tolerance or non-compliance similarities between some of the disease been demonstrated with dietary of oral iron supplements features and the deficiency presentation. treatment in comparison to short-term • inflammatory bowel conditions Development of this theory includes supplementation. However, in severe iron • chronic GIT blood loss non-responsive the recent finding that IDA potential y depletion IDA or patient non-compliance, to oral treatment alters blood–brain barrier permeability, supplementation is vital.
• haemodialysis patients who cannot al owing a range of substances normal y Al oral iron supplements (e.g. ferrous achieve a positive iron balance with blocked to pass through, such as [beta] sulphate, lactate and fumarate) are n-hFe oral treatment alone.
endorphin, which is associated with poor and, as such, their bioavailability can be Administered intravenously, iron learning and memory.60 Links have also significantly improved with the inclusion polymaltose (Ferrum H Injection) been made with the delayed maturation of 75 mg of vitamin C in each tablet.1 has been associated with anaphylactic of the frontal cortex and low thyroid levels Ferrous sulphate is the least expensive and reactions in susceptible patients. However, also evident in IDA. Building on this most frequently prescribed form, providing for many it remains the method of choice, hypothesis, one study demonstrated that between 80 mg (FGF) and 105 mg (Ferro- as intramuscular injection produces a staggering 84 per cent of children with Gradumet) elemental iron per tablet.66 increased discomfort and al ergic reactions ADHD were iron depleted (ferritin <30 One of the major complaints about this in a larger patient population.66 Ferric ng/mL) compared to only 18 per cent of preparation is GIT side-effects, including sodium gluconate and iron sucrose controls. Ferritin levels correlated with abdominal cramps and constipation. were recently approved in the US and the severity of the cognitive impairment.61 However, researchers argue that al iron reportedly have improved safety profiles.4 Other studies have produced similar salts when given at an equivalent dose A response to iron therapy is evidenced results.62 Unfortunately, the only clinical have comparable adverse events.4 This is by a clinical benefit and characterised trial to date was a smal open-label study not surprising given that these amounts by a haemoglobin rise of about 1 g/dL of iron-replete boys supplemented with far exceed the established tolerable upper per week. Patients with IDA require iron. Although there was some cognitive levels of intake16 and, as such, have supplemental iron for a minimum of and behavioural improvement, trials in ID received much criticism for being routinely six months4 to one year1 to replenish or IDA ADHD sufferers are warranted.63 recommended by some in pregnancy.4,56,67 stores. Other areas under investigation Suboptimal iron has also been linked to As with most minerals, to optimise concerning supplementation include juvenile delinquency and aggression and uptake, iron should be taken on an empty improved athletic performance15, 53, conduct disorders in children.64 stomach. However, this exaggerates cognition and haemodialysis.54 side-effects and can create additional GIT discomfort in the form of reflux Contraindications, toxicity Some studies suggest an association and nausea. It is therefore recommended and adverse reactions between iron deficiency and breath- that patients start on a lower dose Accidental excess consumption of iron holding spells, with supplementation ( 30 mg ferrous sulphate), increasing supplements is the most common cause of significantly reducing the frequency gradual y over time, and consume their poisoning in infants, producing vomiting, of episodes.65 However, potential supplements with foods, excluding those upper abdominal pain, pal or, cyanosis, mechanisms have not been explained.65 that negatively affect iron absorption i.e. diarrhoea, drowsiness, shock and death.2,57 tea, to maximise compliance.4 Although The human body goes to Choosing a supplement daily dosing is frequently recommended, enormous lengths to avoid excess iron While some researchers suggest that a number of studies have revealed weekly accumulation. Consequently, iron supplements are required for those dosing to have comparable effects.54,68 supplementation should always be 44 Complementary Medicine May / june 2007 IRON nutrition notes May / june 2007 Complementary Medicine nutrition notes IRON conservative and restricted to cases of deficiency and overload in our patients. 23 Domel of M, et al. AJCN 2002;76:198–204.
demonstrable deficiency. Supplemental As such, we need to be as competent in 24 Nemeth E, et al. Annu Rev Nutr iron is contraindicated in any form recognising and managing iron excess as 25 Wessling-Resnick M. AJP Gastrointest Liver of haemochromatosis or iron-loading we have become in our daily encounters anaemias (thalassemia, sideroblastic with its deficiency. Future developments 26 El iot R, et al. Aust NZ J Med 1986;16(4):491–5.
anaemia). Iron increases, either elevated in understanding iron dyshomeostasis will 27 Gertig D, et al. MJA 2003;179(10):517–8.
ferritin and/or unbound iron, may 28 Roe M, et al. AJCN 2005;81;814–21.
advance our knowledge further regarding 29 Limdi J, et al. QJM 2004;97:315–24.
increase the risk of: the metabolism of this extraordinary 30 Pietrangelo A. Annu Rev Nutr 2006;26:251–70.
• oxidative stress via the generation of mineral, and potential y offer new 31 Robertson I, et al. Asia Pacific J Clin Nutr the hydroxyl radical exacerbated in treatments for a range of chronic conditions those individuals with low baseline 32 O'Brien K, et al. AJCN 2003;77:924–20.
associated with iron accumulation. ◗ 33 Iannotti L, et al. AJCN 2006;84(6):1261–6.
34 Soh P, et al. Eur J Clin Nutr 2004;58(1):71–9.
• oxidative stress in pregnancy implicated in references 35 Karr M, et al. Aust NZ J Public Health pre-eclampsia and gestational diabetes69 1 Gropper S, et al. Advanced Nutrition and Hu- • abnormal offspring behaviour of man Metabolism, 4th edn. California: Thomson 36 Mackerras D, et al. Asia Pacific J Clin Nutr Wadsworth, 2005.
mothers routinely supplemented 2 Kohlmeier M. Nutrient Metabolism. London: 37 Nguyen N, et al. J Paediat Child Health during pregnancy67 Academic Press, 2003.
• infection and morbidity from 3 Australia New Zealand Food Standards Code. 38 Heath A, et al. Asia Pacific J Clin Nutr infectious diseases in children in Barton: FSANZ, 2006. Report No. 90.
4 Chitambar C, et al. Nutritional Aspects of 39 Hunt J. AJCN 2003;78:1168–77.
Hematologic Diseases. In: Shils M, et al. Modern 40 Wilson A, et al. Eur J Clin Nutr 1999;53:189–94.
• gallstone disease in men (increased hFe Nutrition in Health and Disease. Baltimore: Lip- 41 Walker S, et al. Lancet 2007;369(9556):145–57.
pincott Wil ians & Wilkins, 2006:1436–61.
42 Krebs N, et al. AJCN 2007;85(2):639S–45S.
• colorectal cancer with long-term high 5 Hal berg L, et al. AJCN 1991;54:1047–58.
43 Szymlek-Gay E, et al. Asia Pacific J Clin Nutr 6 Whitlock E, et al, Annals Int Med consumption of hFe from red and 44 Couper R, et al. MJA 2001;174:162–5.
processed meats72–74 7 Bal M, et al. Am J Clin Nutr 1999;70(3):353–8.
45 Cashel K. MJA 2000;173(suppl 7):S4–5.
• type 2 diabetes on both healthy and 8 Jones G. Minerals. In: Wahlqvist M (ed). Food 46 Oti-Boateng P, et al. J Paediatr Child Health HH populations (increased hFe & Nutrition. 2nd edn. Sydney: Al en & Unwin, consumption from red meat and 47 Tiong A, et al. MJA 2006;185(11/12):602–6.
9 US Department of Agriculture ARS. USDA 48 English R, et al. MJA 1990;152(11):582–6.
National Nutrient Database for Standard 49 Gibson R, et al. Asia Pacific J Clin Nutr • results from studies investigating links Release, Release 18.
between hFe consumption and iron 10 Australian Bureau of Statistics. 4306.0 Apparent 50 Schol T. AJCN 2005;81(suppl):1218S–22.
consumption of foodstuffs Australia 1997–98 and stores and cardiovascular risks have 51 Patterson A, et al. AJCN 2001;74:650–6.
1998–99. Canberra: ABS, 25/10/2000.
52 Akabas S, et al. AJCN 2005;81(15):1246S–51S.
been equivocal78–80 11 Uauy R, et al. Food-Based Dietary Guidelines for 53 Read R, et al. Nutrition for activity, sport and • possible links with neurodegenerative Healthier Populations: International Considera- survival. In: Wahlqvist M, ed. Op cit.
conditions such as Friedrich's tions. In: Shils M, et al (eds), op cit.
54 Braun L, Cohen M. Herbs & Natural Sup- 12 Roughead Z, et al. AJCN 2002;76:419–25.
ataxia, Huntington's, Alzheimer's plements: an evidence based guide. 2nd edn. 13 Karr M, et al. MJA 2001;174:165–74.
and Parkinson's disease, as well as Sydney: Elsevier, 2007.
14 Rutishauser I. Childhood and Adolescence. In: 55 Turner R. Nutrition During Pregnancy. In: Shils amyotrophic lateral sclerosis and Wahlqvist M (ed), op cit.
M, et al (eds). Op cit.
atypical parkinsonian syndromes.2,82,83 15 Beard J, et al. AJCN 2000;72(suppl.):594S–7.
56 Makrides M, et al. AJCN 2003;78:145–53.
16 Wood R, et al. Iron. In: Shils M, et al. Op cit.
It remains possible, however, that this 57 Heimburger D, et al. Clinical manifesta- 17 NHMRC. Nutrient Reference Values for Australia is due to a genetic iron dyshomeostasis tions of nutrient deficiencies and toxicities: a And New Zealand Including Recommended resume. In: Shils M, et al (eds). Op cit.
rather than an overt excess.84,85 Dietary Intakes. Australian Government Depart- 58 DePaola D, et al. Nutrition and Dental Medicine. ment of Health and Ageing National Health and In: Shils M, et al (eds). Op cit.
Medical Research Council, 2006.
59 Mil man N, et al. Acta Obstet Gynecol Scand 18 Morck T, et al. AJCN 1983;37:416–20.
The balance between adequacy and excess 19 Mennen L, et al. Eur J Clin Nutr 2007, Epub 60 Yehuda S, et al. J Paediar Gastro Nutr in the case of iron is subtle and individual ahead of print.
but must be paramount in the practitioner's 20 Hal berg L, et al. AJCN 1997;66:347–56.
61 Konofal E, et al. Arch Pediatr Adolesc Med mind. In contrast to most other 21 Hunt J, et al. AJCN 2000;71:94–102.
22 Ganz T, et al. AJP Gastrointest Liver Physiol micronutrients, we are likely to see both Iron continued on page 66>>
46 Complementary Medicine May / june 2007

Source: http://rachelarthur.com.au/downloads/JCM_Winter07.pdf