Iron Deficiency Anemia Due to Malnutrition

Article written and reviewed by Dr Luca Moretti

Iron deficiency anemia due to malnutrition is one of the major forms of iron deficiency anemia and is caused by inadequate nutritional intake of bioavailable iron and/or an unbalanced diet, frequently compounded by adverse socioeconomic conditions, chronic disease or vulnerable stages of life. When reduced intake is the predominant mechanism, the condition may improve with restoration of adequate nutritional status; however, malabsorption and chronic blood loss may coexist and should be investigated when appropriate.

For the general pathophysiology of iron deficiency anemia, see the general detailed page.

Etiology, Pathogenesis and Pathophysiology

Iron deficiency anemia due to malnutrition results from inadequate dietary iron intake sustained over time, causing gradual depletion of iron stores and, without adequate replacement, development of anemia. Etiologically, the condition occurs when dietary iron intake is insufficient for physiologic requirements and represents a relevant cause of iron deficiency; malabsorption or increased losses may nevertheless coexist.

The main causes of reduced intake include:

• Diets low in heme iron, with little red meat, fish or poultry, typical of low income populations, vegetarians or vegans with inadequately planned diets, and restrictive dietary regimens for cultural, religious or medical reasons.
• Monotonous and unbalanced diets in developing countries, where consumption of refined cereals and foods high in phytates or polyphenols, inhibitors of iron absorption, is high and the availability of bioavailable iron is markedly reduced.
• Prolonged fasting, eating disorders such as anorexia nervosa and bulimia, addictions or psychopathologic conditions that reduce overall food intake.
• Clinical conditions that increase requirements, including growth and pregnancy, in association with an inadequate diet.

Dietary iron deficiency causes progressive depletion of iron stores, reflected by ferritin, followed by reduced circulating iron and development of hypochromic, microcytic erythropoiesis. Pathogenesis depends closely on the duration and severity of nutritional deficiency and on any associated micronutrient deficiencies such as zinc, vitamin A and folate, which may act synergistically to worsen erythrocyte synthesis and clinical manifestations.

Pathophysiologically, chronic dietary iron deficiency suppresses hepatic hepcidin production, maximizing the efficiency of residual intestinal absorption and endogenous iron recycling. However, when intake remains persistently inadequate, these compensatory mechanisms become insufficient and typical symptoms of iron deficiency anemia develop. See the general detailed page.

Risk factors and prevention

Specific risk factors for iron deficiency anemia due to malnutrition are conditions that, although not direct causes, substantially increase the probability of developing iron deficiency from inadequate intake:

• Pediatric age: infants fed exclusively with cow’s milk, which is naturally low in iron, rapidly growing children and adolescents with unbalanced diets.
• Older adults: often exposed to reduced food intake because of dental problems, social isolation, chronic disease or depression.
• Pregnancy and postpartum period: iron requirements increase during pregnancy. After delivery, risk may persist because of blood loss and depleted stores, whereas breastfeeding alone does not increase iron requirements.
• Vegetarians and vegans: risk depends on diet quality and planning, iron bioavailability and individual requirements; supplementation should be prescribed when indicated and not automatically.
• Poverty, food insecurity and humanitarian emergency settings.
• Psychiatric eating disorders and substance use disorders.

Prevention is based on educational interventions, early identification of people at risk, fortification of widely consumed foods, targeted supplementation during pregnancy and childhood and in vulnerable groups, and promotion of a balanced diet rich in foods containing highly bioavailable heme iron.

Clinical Manifestations

The clinical picture largely resembles the typical signs and symptoms of iron deficiency anemia, see the general page, but may have some distinctive features:

• Multiple nutritional deficiencies: iron deficiency is frequently associated with deficiencies of other vitamins and trace elements such as zinc, folate, vitamin B12 and protein, producing complex and subtle clinical presentations.
• Growth delay and impaired neuropsychological development in children, with fatigue and apathy in adolescents.
• In older adults, symptoms are often unrecognized or attributed to age, with greater risk of functional decline, worsening frailty and comorbidities.
• In pregnant women, increased obstetric and perinatal risk is already present with mild to moderate anemia.
• With severely unbalanced diets, cutaneous, mucosal and neurologic signs of other micronutrient deficiencies may coexist.

A detailed nutritional history, together with assessment of body weight and general condition, is essential for guiding clinical suspicion.

Investigations and Diagnosis

Diagnosis of iron deficiency anemia due to malnutrition is based on integration of clinical, historical and laboratory data, with particular attention to the differential diagnosis from other deficiency and microcytic anemias.
Key points include:

• Dietary history: careful assessment of consumption of iron rich foods, dietary restrictions, cultural habits and possible signs of eating disorders.
• Physical examination: assessment of nutritional status, signs of multiple deficiencies, findings suggestive of iron deficiency anemia such as fatigue, pallor, glossitis and brittle nails, and neurologic and cutaneous signs.
• Laboratory tests: the typical pattern is microcytic hypochromic anemia, reduced ferritin, low serum iron, reduced transferrin saturation and increased transferrin. In multiple deficiencies, normocytic or macrocytic anemia due to folate or vitamin B12 deficiency may coexist.
• Exclusion of other causes: active investigation of malabsorption, gastrointestinal, gynecologic or urinary blood loss and inflammatory conditions using tests appropriate to the context. Absence of symptoms does not exclude occult bleeding or malabsorption.

In the presence of risk factors, improvement in hematologic findings after restoration of an adequate diet and iron supplementation confirms that iron deficiency responds to treatment, but does not by itself prove a nutritional origin.

Treatment and Prognosis

Treatment of iron deficiency anemia due to malnutrition is based on three pillars:

• Dietary correction: introduction of foods rich in heme iron, such as red meat, fish and poultry, increased dietary iron bioavailability through concomitant vitamin C intake, and reduced intake with meals of inhibitors such as tea, coffee and phytates.
• Iron therapy: oral iron administration, with dose and duration adapted to the severity of deficiency and the pace of clinical and hematologic recovery. In most cases oral treatment is sufficient; intravenous iron is indicated when oral therapy is not tolerated, does not adequately restore iron stores or when effective intestinal absorption is unlikely.
• Treatment of associated deficiencies: supplementation with folic acid, vitamin B12, zinc or other micronutrients as needed under medical supervision.

Nutrition education and follow up in groups at risk, including children, pregnant women and older adults, are essential to prevent recurrence. Prognosis is generally favorable when diagnosis is early and dietary correction effective; chronic or recurrent forms may permanently affect neuropsychophysical development and quality of life.

Complications

Complications of iron deficiency anemia due to malnutrition overlap with those of iron deficiency from other causes, see general complications, but coexistence of multiple micronutrient deficiencies may worsen the clinical picture and slow recovery. In children and adolescents, the main sequelae include:

• Neurocognitive and growth impairment, which is often not completely reversible if correction is delayed.
• General impairment in severe malnutrition with multiple deficiencies, with possible delayed wound healing.
• Increased risk of obstetric complications and neonatal complications in pregnant women.

Early identification and multidisciplinary management drastically reduce the risk of permanent harm.

Bibliography
1. Kassebaum NJ et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123(5):615-624.
2. World Health Organization. Guideline: Daily iron supplementation in adult women and adolescent girls. Geneva: WHO. 2016.
3. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832-1843.
4. Lopez A et al. Iron deficiency anaemia. Lancet. 2016;387(10021):907-916.
5. Bhutta ZA et al. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet. 2013;382(9890):452-477.
6. Allen L, de Benoist B, Dary O, Hurrell R, eds. Guidelines on food fortification with micronutrients. Geneva: WHO/FAO. 2006.
7. Petry N et al. Review: The potential of the common bean (Phaseolus vulgaris) as a vehicle for iron biofortification. Nutrients. 2015;7(2):1144-1173.
8. Pasricha SR, Drakesmith H, Black J, Hipgrave D, Biggs BA. Control of iron deficiency anemia in low- and middle-income countries. Blood. 2013;121(14):2607-2617.
9. Stevens GA et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011. Lancet Glob Health. 2013;1(1):e16-e25.
10. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93(4):1721-1741.