Suchitra Chinthapalli considers the global impact of iron deficiency.

“Let food be thy medicine and medicine be thy food”, was the advice of Hippocrates, the father of modern medicine. This phrase still holds true today in the 21^st century where malnutrition is the cause of more than half of the world’s diseases.(1)  This probably comes as no surprise to most readers, since there is justifiably extensive media coverage about illnesses that ensue from famines in Africa and obesity in the USA. However, these are just two extremes of a spectrum, and a significant proportion of dietary-related diseases are due to deficiencies in micronutrients, such as iron. The WHO recognises that iron deficiency is in fact the commonest nutritional disorder worldwide.(2) An astounding 2000 million people, a third of the world’s population, are anaemic, and at least half due to iron deficiency.(2) The diagnosis, treatment and prevention of iron deficiency are simple, cheap and effective. So then why does this epidemic still exist?

The Body’s Requirement for Iron

Iron is an essential trace element required by our bodies for the vital role of oxygen carriage in haemoglobin and myoglobin. In addition it is also a component of cytochromes, such as P450, which are electron transport carriers involved in oxidative metabolism. When the body’s iron requirements are not met, one of three states of deficiency develop. (Figure 1) The most widely understood; iron deficiency anaemia, is a continuum of iron deficiency. It produces vague symptoms such as fatigue and headaches. It can easily go unrecognised, with only a minority having the hallmark features of koilonychia, and even fewer developing cardiovascular complications like angina and cardiac failure.  For every one person with iron deficiency anaemia, there are another two with iron deficiency alone.(3)

The Personal Impact

The impact of iron deficiency is most common and devastating in those who have the greatest requirements; pregnant women and children.  The impact of this is the focus of a recently published landmark series on Maternal and Child Undernutrition in the Lancet.(4) In developing countries 54% of pregnant women suffer from anaemia, compared to 18% in industrialized countries.(3) Studies also show that there is increased maternal mortality, intrauterine growth retardation and low birth weight with anaemia. Later in life iron deficiency is associated with an increased susceptibility to infection and decreased regulation of body temperature. Also concerning is the permanent cognitive impairment that occurs as well. There is a correlation between anaemia and lower IQ test scores by up to 15 points.(3) Therefore iron deficiency can significantly impair an individual’s physical and intellectual capacity and as a consequence, the national economy.

The Social Impact

Perhaps it is this huge economic burden iron deficiency places on already-fraught governments that has prompted leaders and organisations to take notice. A study by the United States Agency for International Development (USAID) in 1994 revealed that a two-thirds reduction in anaemia in South Asia could improve agricultural production by US$3.2 million  within seven years.(2) The impact on the economy is from sickness and decreased efficiency when at work due to fatigue. This too means higher healthcare costs. A study in 2003 investigating this effect in ten developing countries (Bangladesh, Bolivia, Egypt, Honduras, India, Mali, Nicaragua, Oman, Pakistan, Tanzania) showed a mean decrease in gross domestic product (GDP) of 0.57%, which is equivalent to US$2.32 per capita.(5) The same study also showed that the cost of dietary iron fortification was only US$1.33 per capita.(5)

The Solution

The high prevalence and effects of iron deficiency on the economy in poorer countries has led to the WHO setting up prevention programmes, which aim to markedly reduce anaemia, and other iron deficiency states too.The WHO has approached the challenge with a “three-pronged offensive” of public health policies.(2)

• 1. Increase iron intake
  • a. education
  • b. iron supplements
  • c. fortification of food
• 2. Control infection
  • a. immunisation
  • b. control mechanisms for malaria, schistosomiasis and hookworm 
• 3. Improve nutritional status

  • a. prevent and control other nutritional deficiencies

 Education

Education is undoubtedly the key to success. The importance of recognising the symptoms and seeking treatment for iron deficiency needs to be publicised, along with measures that can be taken to prevent it. This could be in the form of leaflets, poster and television advertisements and the school curriculum.

Individual efforts can be made to improve nutritional intake.  However, often people don’t know how to maximise iron absorption through their diet.There are two types of iron found in food; haem and non-haem. Haem iron absorption in the body is two to three times more efficient and less influenced by dietary factors.(8) Generally haem iron is available from meat, especially offal, whereas non-haem iron is also abundant in green vegetables, cereals and pulses. Even when high iron-containing products are ingested, not all of the iron is absorbed, as bioavailability differs between foods. Also a variety of dietary factors influence absorption (Figure 2). This information needs to be conveyed to the public.

Interestingly, food is not the only source of iron. Beverages account for approximately 0.5mg of the daily iron intake in the UK.(8) Some drinks such as South African home-brewed beers in iron or steel containers have as much as 80mg/l.(8) Cooking utensils made of iron can account for 5-10mg/day. In richer countries utensils are now mainly made of stainless steel or aluminium. A randomised control trial conducted in Ethiopia revealed that children eating food cooked in iron pots had lower rates of anaemia and higher serum ferritin concentrations compared to their counterparts whose food was cooked in aluminium pots.(9)

“Breast is best” is widely publicised to encourage breastfeeding due to its numerous benefits. Simultaneously advice should be given about weaning, as beyond six months a child’s iron requirements cannot be met with breast milk alone.

Supplementation

The mainstay of treatment in the UK is oral therapy with ferrous sulphate complemented with ascorbic acid to improve absorption, both taken twice a day. These preparations are cheap, each costing approximately £0.06 pounds sterling per tablet in the UK, but they come with adverse effects that result in a high rate of non-compliance.(6) These include nausea, epigastric pain, diarrhoea and constipation. Syrups are also available which contain a lower percentage of iron, improving tolerance, and are preferred in children. In addition, numerous studies, including a randomised controlled study in Zanzibar in 2006, showed that iron supplementation in active infections is associated with more adverse events.(7) Possible theories for this include that iron is thought to decrease zinc absorption, which is important for immune function, and also many bacteria and parasites require iron for multiplication.(7)  This is important as those most in need of supplementation are likely to be affected by infections, so joint prophylaxis for endemic illnesses like malaria should be given too.

Dietary Fortification   

Dietary fortification has been routine practice in many developed countries since the 1940s. The main foods that are fortified include infant formulas, weaning foods and wheat flour. Wheat flour is the key ingredient for the production of staple foods such as bread and pasta, and by law must be fortified in the UK. The WHO estimates the process to cost US$1.00 per metric ton of flour, not including initial start-up costs. Therefore it is a sustainable and affordable policy. However, unlike many Western countries, the staple food in much of Asia is rice, which is not flour-based. It also requires co-operation and commitment from governments in developing countries.

Eradicating the Underlying Cause

Depending on the clinical picture more sinister underlying pathology may be present. Figure 3 illustrates some of the commonest causes of iron deficiency in the UK. Infectious diseases play a much greater role in developing countries, and must be concomitantly tackled to help improve iron status.

The Current Situation

The WHO published a guidebook on Nutritional Anaemia last year, in which its eminent authors reminded that in May 2002 the General Assembly of the United Nations pledged to reduce global anaemia by one third by 2010.(10) With 18 months left, that target is not realistically attainable.  The research is there, as are the ideas, but there is no one to translate these aspirations into reality.  In 2000, UNICEF was only able to provide enough iron supplements for 3 % of pregnant women in the developing world.(11) The question of “why”, resonates, but there are no simple answers. For supplementation, fortification and educational programmes to succeed substantial financial aid is needed in combination with political support. Hopefully in the not too distant future iron deficiency anaemia will be eradicated.  

Figure 1: Classification of iron deficiency states. Based on information from: Cook  JD. Diagnosis and Management of Iron Deficiency Anaemia. Best Practice and Research Clinical Haematology. 2005: 18(2); 319-332 and Frewin R et al. ABC of Clinical Haematology: Iron Deficiency Anaemia. BMJ. 1997; 314: 360

Figure 2: Dietary factors affecting non-haem iron absorption

Figure 3: Commonest Causes of Iron Deficiency Anaemia with Prevalence as a Percentage of Total in the UK. Data from: Goddard AF et al. Guidelines for the management of iron deficiency anaemia. British Society of Gastroenterology. May 2005.

References:

• 1. World Food Summit. Food and Agricultural Organisation of the United Nations. June 2002
• 2. Iron Deficiency Anaemia. World Health Organisation. 2007
• 3. Prevention and control of iron deficiency anaemia in women and children. Report of the UNICEF/WHO Regional Consultation. February 1999. 
• 4. Maternal and Child Undernutrition. The Lancet Series. January 2008
• 5. Horton S, Ross J. The economics of iron deficiency. Food Policy 2003; 28: 51-75
• 6. British National Formulary. March 2007; P481, P513
• 7. Sazawal S, Black RE, Ramsan M, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 2006; 367: 133-43.
• 8. Expert group on vitamins and minerals. Diet and Nutrition Surveys Branch. Nutrition Division. Food Standards Agency. March 2002.
• 9. Adish AA et al. Effect of consumption of food cooked in iron pots on iron status and growth of young children: a randomized trial. Lancet. 1999: 353; 712-716
• 10. Nutritional Anaemia. World Health Organization. Sight and life press. 2007.

Suchitra Chinthapalli

5th Year Medical Student

Imperial College, London

suchitra.chinthapalli03@imperial.ac.uk