Iron Deficiency

last authored: March 2015, Kelsey Vercammen
last reviewed: April 2015, Terry McCurdy & Kylie Whyte

 

 

Introduction

Iron deficiency, the world’s most prevalent nutritional deficiency and one of the leading causes of anemia worldwide, occurs when there is an inadequate amount of iron in the body. Iron is a trace mineral which is vital for many physiological processes. In particular, iron is a component of hemoglobin and myoglobin, which the body uses in the transport of oxygen and carbon dioxide in the blood. It also helps in energy production, due to its role in the citric acid cycle and the electron transport chain.

 

It is important to understand that iron deficiency and iron deficiency anemia are not interchangeable terms. The term iron deficiency is very broad and refers to the spectrum of stages in which an individual has decreased iron stores (see Table 1). In contrast, iron deficiency anemia is the final and most serious stage of iron deficiency and it affects the functioning of the body’s organ systems.

 

Table 1: Iron depletion progresses in stages (Smolin and Grosvenor, 2010):
STAGE 1	Stored Iron Levels Decrease ● Iron storage levels in the liver, spleen and bone marrow are decreased. ● Levels of serum ferritin, the body’s major iron storage protein, are decreased.
STAGE 2	Transport Iron Levels Decrease ● Transferrin is an iron transport protein responsible for the circulation of iron throughout the body. With inadequate amounts of stored iron (Stage 1), the amount of iron bound to transferrin decreases. ● There is an increase in total iron binding capacity, defined as iron’s ability to bind with transferrin, in order to compensate for the decreased serum iron levels. ● There is a decrease in transferrin saturation, defined as the amount of serum iron able to be bound to the transferrin protein.
STAGE 3	Hemoglobin Levels Decrease = Iron Deficiency Anemia ● Without an adequate amount of iron, hemoglobin cannot be produced. This in turn affects the production of red blood cells. ● Red blood cells produced without adequate hemoglobin are small, pale and incapable of properly delivering oxygen throughout the body.

Within the Canadian context, iron deficiency anemia (IDA) is considered to be a mild public health problem (WHO, 2008), with prevalence rates around 4-5%; however, studies have shown IDA to be of significant concern among the Canadian Aboriginal population with reported prevalence rates as high as 50% (Christofides, 2005).

 

At the global level, it is estimated that 80% of the world’s population may have an iron deficiency, and over 2 billion people in the world suffer from iron deficiency anemia (WHO, 2008). Of all the continents, Africa is most affected by iron deficiency. IDA can have terminal outcomes: in 2004, the WHO estimated that IDA resulted in 273,000 deaths worldwide (Pasricha et al., 2013).

 

 

 

Causes and Risk Factors

 

All ages

Nutritional iron deficiency, the inadequate consumption of iron through dietary sources, is the most obvious cause of iron deficiency.

In addition to inadequate dietary iron intake, various other conditions may cause iron deficiency by damaging the intestines and thus impacting the body’s ability to effectively absorb iron.

• Hookworm infections, caused by a parasitic worm which damages the intestines, decreases the ability of body to absorb iron through intestinal mucosa.
• Individuals with undiagnosed or poorly managed celiac disease often have damaged small intestines due to the inflammatory response of the intestines to gluten exposure, which in turn reduces the body’s ability to absorb iron (Lapid, 2014).
• Unmanaged cow's milk allergy damages the intestine and results in a decreased ability to absorb iron.
• Various malabsorption states, such as cystic fibrosis, cause abnormalities in the way that nutrients, including iron, are absorbed from the intestine into the bloodstream.

 

Infants, Children and Youth

Iron requirements are higher for infants, children and youth because of the rapid growth that occurs during this time. Specifically, there is an increase in muscle mass and blood volume, of which iron is required to facilitate the process. Of particularly high risk include newborns, milk babies, children aged 6-24 months, and youth aged 11-17 year olds.

 

Newborns may be at increased risk due to the following reasons:

• mother with iron deficiency (thus breastmilk not as rich in iron and probable poor family dietary intake)
• fetal-maternal hemorrhage
• twin-twin transfusion syndrome

Milk babies develop iron deficiency if they primarily drink cow’s milk, with poor intake of iron-fortified formula or iron-rich foods. Milk babies can be deficient due to three main reasons:

• cow’s milk replaces breastmilk which, although low in iron, the iron in breastmilk is very bioavailable
• the iron in cow’s milk is poorly available
• cow milk proteins can be irritating and damaging to the GI tract

Children aged 6-24 months are at the highest risk of iron deficiency, due to the exhaustion of fetal iron reserves. Especially at risk are babies born prematurely, as fetal iron reserves exhaust earlier than 6 months.

 

Youth aged 11-17 years is a time when iron deficiency becomes more common again because of periods of rapid growth, but (particularly in the North American context) also because of poor diet. Females are particularly susceptible, due to the onset of puberty and menstruation. For example, during these years females require 18 mg/day, as compared to the 8 mg/day that males require (Health Canada, 2010).

 

Adults

The main causes of iron deficiency among adults are:

• Menstruation, among premenopausal women
• High fertility rate combined with poor nutrition, among women of childbearing age
• Chronic diseases such as cancer or autoimmune conditions, parasites or other infections
• Occult (hidden) gastrointestinal bleeds, peptic ulcer disease, chronic NSAID use, malignancy, and genitourinary bleeding, among older adults
• Blood loss via multiple blood tests

 

Pregnant Women

During pregnancy, a woman’s iron intake must increase by 50% (Health Canada, 2010). Many pregnant women both in Canada and worldwide are unaware of the huge spike in iron requirements associated with pregnancy and thus fail to adjust their diets accordingly. Pregnant women require additional iron for two main reasons:

• During pregnancy, a woman produces between 1.4-2 kg of additional maternal blood in order to support the growing fetus (Smolin and Grosvenor, 2010). This necessitates the need for additional hemoglobin and myoglobin, of which iron is a major component.
• The fetus and other maternal tissues require high amounts of energy, in the form of ATP, to develop properly. Thus, the amount of iron participating in the citric acid cycle and electron transport chain to produce ATP must also increase.

Low-Income Individuals

It has been shown that food-insecure children are 2.4 times more likely than food secure children to develop IDA (Skalicky et al., 2005). Low-income individuals are at a heightened risk of iron deficiency because:

• Lack of money requires individuals to skip meals or eat insufficient portions.
• Iron rich foods - which include red meats and leafy green vegetables - are often more expensive and less filling than alternatives, so may be omitted by individuals with low incomes.

 

Vegetarians

Iron can be obtained through the diet from animal sources (called “heme”) or plant sources (called “non-heme”). The iron in heme sources is more bioavailable and thus can be absorbed into the body more easily than non-heme sources. As such, vegetarians, who acquire their iron from plant sources exclusively, require more health education and must be more strategic in their diets in order to meet iron requirements.

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Signs and Symptoms

A thorough assessment of the patient is necessary to uncover the cause of iron deficiency and the level of iron depletion so appropriate treatment can be initiated.

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Investigations

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Differential Diagnosis

main article: anemia

The differential diagnosis is extensive and can be seen in the topic above. Other causes of microcytic anemia include:

• Thalassemia
• Anemia of Chronic Disease
• Lead poisoning
• Sideroblastic anemias (including Vitamin B6 deficiency)

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Treatments

This section will focus on the treatment of nutritional iron deficiency, at both the individual and community level. Fortunately, the body can respond quite well to treatment - within three months (the lifecycle of a Red Blood Cell) of treatment iron stores can be replenished.

 

Diet

The introduction of a healthy diet, which includes adequate amounts of iron, is the first step to treating an individual in iron deficiency. The Recommended Dietary Allowance for iron intake varies depending on age, gender and if an individual is pregnant/lactating. American and Canadian Nutrition Guidelines recommend the following amounts for individuals (Health Canada, 2010):

• 11 mg/day for infants aged 7-12 months
• 7-10 mg/day for children aged 1-13 years old
• 8-11 mg/day for males 14 years and older
• 15-18 mg/day for females 14 to 50 years
• 8 mg/day for females 50 years and older
• 27 mg/day for pregnant females

 

An individual’s overall diet will greatly affect the amount of iron absorption that occurs with each meal, for example:

• Certain acids, such as Vitamin C, improve the absorption of non-heme iron.
• Meat protein also improves the absorption of non-heme iron, thus eating red meat with plant-soured iron is beneficial, this is called the “meat protein factor”
• Foods which contain large amounts of minerals of the same charge as non-heme iron (such as calcium or magnesium) will inhibit its absorption, thus dairy products affect the bioavailability of iron.
• Products with caffeine in them (such as tea and coffee) can inhibit the absorption of iron if consumed at the same meal.

Table 2: Sources of Iron in Diet
Heme (animal) Sources		Non-Heme (plant) Sources
Duck (75g)	1.8-7.4 mg	Spinach (½ cup cooked)	2.0-3.4 mg
Chicken (75g)	0.4-2.0 mg	Asparagus (6 spears)	2.1 mg
Beef (75g)	1.4-3.3 mg	Beets (½ cup)	1.6 mg
Pork liver (75g)	13.4 mg	Soybeans (½ cup, cooked)	1.9-2.4 mg
		Millet (½ cup)	3 mg
		Corn (½ cup)	2.3 mg
		White Rice (½ cup, cooked)	0.9 mg

 

Supplements

Generally individuals who are iron deficient will need to take supplements to build up their iron stores. Often, oral iron pills are prescribed for three months and then a CBC is conducted again.

 

Supplements are available in either ferrous (2+ charge) or ferric (3+ charge) forms. Because of its high solubility, ferrous iron is absorbed more easily and is thus considered to be more bioavailable than ferric iron (National Institute of Health, 2015). Within the ferrous iron supplements, there is variability in the amount of elemental iron present (see Table 3).

Table 3: Oral Ferrous (2+) Supplements
Oral ferrous gluconate:	contains 11.6% elemental iron	Most expensive
Oral ferrous sulfate	contains 20% elemental iron	Least expensive
Oral ferrous fumarate	contains 33% elemental iron	Moderately expensive

Individuals taking iron supplements need to be aware of possible gastrointestinal side effects including constipation and nausea. Additionally, individuals taking calcium supplements should be aware that calcium interferes with the absorption of iron so should not be taken at the same time as iron supplements.

 

Supplements as Preventative Measure for Infants

When infants are born, they have stored iron which the body can use for the first 4-6 months of life. However, after this time, infants require external sources of iron additional to breast milk (Ziegler, 2009). As such, it is recommended that infants are introduced to iron rich foods (such as meat & alternatives, and iron-fortified cereals) as their first solid food around 6 months (Johnson, 2010). Preterm or low birth weight infants, who may have decreased iron stores to begin with, may need to take oral iron supplements if recommended by their primary care provider. Despite these recommendations, there is a risk for iron overload in infants who are receiving supplements (see Iron Overload section below).

 

Iron Overload

While treating individuals for iron deficiency, it is important to be conscientious of iron toxicity, which can occur when the body has an overload of iron, generally from supplement intake. The American/Canadian current tolerable upper intake level is set at 40 mg/day for those aged 0-14 years, and 45 mg/day for those aged 14 years and older (Health Canada, 2010). Iron overload can occur as an accumulation over time, or due to a single, large dose of iron. Too much iron in the body builds up in tissues and organs, can cause abnormalities in pH, and often leads to liver failure.

 

 

 

Community Level/Public Health Initiatives

Because there are known populations at risk for iron deficiency, public health measures are taken to prevent and/or treat low dietary iron intake amongst appropriate groups. This section will discuss two distinct initiatives.

 

Government Food Fortification

Governments may choose to fortify commonly consumed foods in order to increase the likelihood of a population meeting the daily nutrient requirements . These types of programs have generally been met with high levels of success in the countries in which they are implemented. Two examples include:

• In Canada refined wheat (which will eventually be made into cereals, pastas, flour, etc.) is enriched with iron during processing (Health Canada, 2013).
• In South America milk products are fortified with iron (WHO, 2008).

 

Cookware Initiatives

The preparation of food in iron pots can actually decrease the prevalence of iron deficiency as iron from the pot is absorbed into the food (Geerligs, 2003). As a result, many governments and NGOs are promoting the use of iron cookware among populations at risk for iron deficiency. A particularly successful example is the “Lucky Iron Fish” initiative in Cambodia. This simple and affordable solution encourages families to place a reusable iron fish in a pot while cooking meals. Studies have shown that after only 9 months of using the lucky iron fish, there was a 50% decrease in the incidence of IDA (Lucky Iron Fish, 2015).

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Resources and References

Center for Disease Control and Prevention

National Institutes of Health: Iron Fact Sheet

WHO: Worldwide Prevalence of Anaemia

American Family Physician - IDA

Dietitians of Canada: Food Sources of Iron

 

Christofides, A., Schauer, C., & Zlotkin, S. (2005). Iron Deficiency and Anemia Prevalence and Associated Etiologic Risk Factors in First Nations and Inuit Communities in Northern Ontario and Nunavut. Revue Canadienne De Sante Publique, 96(4).

 

Cooper, M. (2012). Iron sufficiency of Canadians. Statistics Canada.

 

Dietitians of Canada,. (2014). Food Sources of Iron.

 

Geerligs, P. (2003). Food prepared in iron cooking pots as an intervention for reducing iron deficiency anaemia in developing countries: a systematic review. - PubMed - NCBI . PubMed.

 

Health Canada,. (2009). Prenatal Nutrition Guidelines for Health Professionals: Iron Contributes to a Healthy Pregnancy [Health Canada, 2009].

 

Health Canada,. (2010). Dietary Reference Intakes Tables.

 

Health Canada,. (2013). Whole Grains - Get the Facts.

 

Iron Disorders Institute,. (2009). Anemia of Chronic Disease.

 

Johnson, D. (2015). First AAP recommendations on iron supplementation include directive on universal screening. AAP News, E101005-1.

 

Lucky Iron Fish (2015). The Lucky Iron Fish Project.

 

National Institutes of Health,. (2015). Iron: Dietary Supplement Fact Sheet. National institutes of Health.

 

National Institute of Diabetes and Digestive and Kidney Diseases,. (2013). Testing for Celiac Disease.

 

Lapid, N. (2014). Is There a Relationship Between Anemia and Celiac Disease?. About Health.

 

Pasricha, S., Drakesmith, H., Black, J., Hipgrave, D., & Biggs, B. (2013). Control of iron deficiency anemia in low- and middle-income countries. Blood, 121(14), 2607-2617. doi:10.1182/blood-2012-09-453522

 

Skalicky, A., Meyers, A., Adams, W., Yang, Z., Cook, J., & Frank, D. (2005). Child Food Insecurity and Iron Deficiency Anemia in Low-Income Infants and Toddlers in the United States. Matern Child Health J, 10(2), 177-185. doi:10.1007/s10995-005-0036-0

 

Smolin, L., & Grosvenor, M. (2003). Nutrition. Hoboken, NJ: John Wiley.

 

World Health Organization,. (2008). Worldwide prevalence of anaemia 1993 to 2005. Geneva, Switzerland: World Health Organization. Retrieved from

 

World Health Organization,. (2015). Micronutrient deficiencies: Iron Deficiency Anemia.

 

Ziegler, E., Nelson, S., & Jeter, J. (2009). Iron supplementation of breastfed infants from an early age. American Journal Of Clinical Nutrition , 89(2), 525-532. doi:10.3945/ajcn.2008.26591

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