Author: Radojka Kostić, Master of Pharmacy
Reviewed by: Prim. Dr. Sci. Med. Dragica Vučelić, Transfusion Medicine Specialist
Introduction
Do you feel constantly tired, even after a long sleep? The reason may lie in a deficiency of one of the most important minerals in our body. Iron deficiency is the leading nutritional deficiency worldwide, affecting hundreds of millions of people, and its first symptoms can be quite unexpected—from an unexplained craving for ice to restless legs. Find out how to recognise the hidden signals your body is sending you, who is at greatest risk, and when the right time is to have your blood count checked.
What Is Iron-Deficiency Anaemia and Why Does It Develop?
Iron-deficiency anaemia (also known as sideropenic anaemia) is the most common form of anaemia worldwide. Iron deficiency itself is the leading nutritional deficiency globally, affecting as many as 25% of the world’s population. This condition occurs when the body’s iron stores fall so low that the bone marrow can no longer produce a sufficient number of healthy red blood cells (erythrocytes).
Our body loses iron for various reasons, and the most common causes are:
- Inadequate diet deficient in this mineral.
- Impaired absorption of iron in the digestive tract.
- Chronic blood loss or elimination of iron through the urine.
Any bleeding, regardless of its cause, directly depletes iron. When a sudden, one-time loss of blood occurs, so-called post-haemorrhagic anaemia develops. The body then alerts the bone marrow to rapidly produce hemoglobin in order to compensate for the loss, thereby quickly depleting the remaining iron stores. When the stores are completely exhausted, altered, pale and small red blood cells are produced (microcytic hypochromic erythrocytes).
In everyday clinical practice, the most common culprits behind chronic blood loss and the development of anaemia are:
- Menstruation, pregnancy and childbirth.
- Gastritis, particularly that caused by long-term use of painkillers (NSAIDs—such as ibuprofen, diclofenac and ketoprofen).
- Peptic ulcer and infection with the bacterium Helicobacter pylori.
- Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis).
- Malignant diseases of the gastrointestinal tract and parasitic infections.
How to Recognise the Symptoms: From Fatigue to Changes in the Nails and Tongue
Many forms of anaemia are initially “silent” and show no signs until the iron stores have been completely depleted. Fortunately, once detected, this condition can be treated successfully and easily, with an excellent outcome.
Symptoms in Adults
Many patients first receive their warning through completely unexpected signs. One of the earliest and most interesting signs of hidden iron deficiency is pagophagia—the irresistible and unconscious need to chew ice. Behind this unusual phenomenon lies a clear neurological mechanism. Due to iron deficiency, there is a reduced supply of oxygen to the brain, which causes sluggishness, impaired concentration and chronic sleepiness. Chewing cold ice triggers specific vascular reflexes that immediately accelerate blood flow through the cerebral arteries. In this way, patients unconsciously use ice as a kind of “energy shock” that immediately restores alertness and clarity and alleviates the feeling of brain fog. This specific craving completely disappears within just a few days after the start of iron supplementation.
In addition to pagophagia, early deficiency may also manifest as unpleasant cramps in the legs. However, as iron stores continue to decline, the main symptoms of moderate and severe anaemia come to the forefront: chronic fatigue and muscle weakness, which drastically impair everyday working capacity.
As anaemia progresses, the following symptoms and signs most commonly occur:
- Pallor of the skin and mucous membranes (the inside of the eyelids, gums).
- Dizziness, rapid heartbeat (tachycardia) and frequent headaches.
- Brittle and fragile nails, the appearance of longitudinal ridges or a specific spoon-shaped appearance of the nails (koilonychia).
- Changes in the tongue—inflammation (glossitis), loss of its natural texture (a shiny and smooth tongue), as well as painful cracks at the corners of the lips (angular stomatitis).
- Reduced resistance to infections, intolerance to cold and worsening of existing heart or lung diseases.
Symptoms in Children
In the youngest children, iron deficiency leaves a deeper mark because it directly affects growth and development. More severe anaemia in young children is associated with a lower intelligence quotient (IQ), poorer concentration and suboptimal growth.
Parents and doctors often observe the following manifestations in children:
- Restless Legs Syndrome (RLS) and poor performance at school. This syndrome manifests as an irresistible need to move the legs, accompanied by an unpleasant sensation of tingling, prickling or cramps, which worsens at rest and during the night. In children, this leads to chronic sleep disturbance, distractibility and fatigue.
- Behaviour resembling attention-deficit/hyperactivity disorder—ADHD (Attention Deficit Hyperactivity Disorder). Reduced iron levels directly affect dopamine function in the brain, which in children may cause impulsivity, restlessness and an inability to maintain attention.
- Delayed psychomotor development and an increased risk of associated disorders (anxiety, tics, depressive episodes, autism spectrum disorder).
Who Is at Greatest Risk?
Epidemiological data show that the prevalence of anaemia varies between 1% and 17%, depending on sex and age. The World Health Organization (WHO) estimates that as many as 24.3% of the world’s population suffers from some form of anaemia, with iron deficiency by far the leading cause.
Women of Reproductive Age and Pregnant Women
In developed countries, iron deficiency is most prevalent among women of reproductive age, primarily because of heavy menstrual bleeding. As many as 38% of non-pregnant women have depleted iron stores without developed anaemia, while 13% have clear iron-deficiency anaemia.
Pregnancy carries an even greater risk—a woman loses approximately 500 mg of iron during a single pregnancy, which goes toward the development of the fetus and placenta. As a result, up to 84% of women in the third trimester of pregnancy have iron deficiency.
Men Have a More Stable Balance
Healthy men lose only 1 mg of iron per day (mainly through microscopic bleeding from the intestines of approximately 0.7 mL and the renewal of skin and mucosal cells), which they can easily replace through their usual diet. On the other hand, the needs of women of reproductive age are twice as high. Although menstruation lasts only a few days, individual cycles can result in the loss of between 4 and as much as 100 mg of iron. When these losses are calculated and distributed over the entire month, a woman loses an average of approximately 2 mg of iron per day (1 mg through regular basal processes + 1 mg as the average menstrual loss). Since women, on average, consume less food than men, their bodies must be twice as efficient at absorbing iron from food in order to maintain balance and avoid developing anaemia.
Newborns and Children in Development
A healthy baby is born with a store of approximately 250 mg of iron that it received from the mother during the last trimester. These stores are naturally depleted during the first six months of life because milk is low in iron. In children who start drinking cow’s milk at an early age, the risk is even greater—the high concentration of calcium in cow’s milk directly blocks iron absorption. To keep pace with the rate of growth, developing children must absorb approximately 0.5 mg more iron every day than they lose.
Socioeconomic Factors and Race
Race has no biological influence on the prevalence of anaemia. However, socioeconomic conditions and dietary specifics determine the statistics, so iron deficiency is recorded considerably more often in economically underdeveloped parts of the world. A large meta-analysis from 2022 confirmed that the global prevalence of anaemia among children is 16.42%, with critically high rates in countries in Asia and Africa.
When Is It Time to See a Doctor?
A doctor should be consulted without delay if you notice persistent symptoms such as chronic fatigue, pallor of the skin and mucous membranes, or a racing heart that do not go away after rest and lifestyle changes. Early recognition of the signs is crucial for preventing serious complications involving the heart and nervous system.
Schedule an appointment and have a complete blood count performed if you have been experiencing the following for several weeks:
- Constant fatigue and general weakness that do not disappear even after long periods of sleep.
- Marked pallor of the face, as well as the inside of the eyelids, gums and nail beds.
- Dizziness, frequent headaches or a brief feeling of faintness when standing up suddenly.
- Shortness of breath and rapid fatigue even during light physical exertion.
- Brittle nails, increased hair loss and dry skin.
- Tingling in the hands and feet, poor balance or a smooth and painful tongue.
Risk Groups That Should Have Their Blood Count and Iron Levels Checked Regularly:
- Pregnant and breastfeeding women (because of the increased needs of the fetus and blood loss during childbirth).
- Women with heavy and prolonged menstrual bleeding.
- Vegans and vegetarians (because they consume exclusively non-heme iron from plant sources, which is more difficult to absorb).
- People with chronic stomach and intestinal diseases (where the absorption of nutrients is naturally impaired).
- Active voluntary blood donors who deplete their iron stores more frequently.
Literature
- Vučelić D. Sideropenijska anemija [Iron Deficiency Anaemia]. Gnosis Lux; 2025. 470 p. ISBN: 978-86-82404-08-8.
- Iron Deficiency Anaemia: Overview and Pathophysiology. Medscape Drugs & Diseases. Available from: medscape.com
- Iron Deficiency Anaemia Clinical Presentation: History and Physical Examination. Medscape.
- Hunt MG, Belfer S, Atuahene B. Pagophagia improves neuropsychological processing speed in anaemia patients, but not in healthy controls. Med Hypotheses. 2014;83(4):473-6.
- Camaschella C. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica. 2020;105(2):260-272.
- Georgieff MK. Iron deficiency in pregnancy. Am J Obstet Gynecol. 2020;223(4):516-524.
- Elsayed ME, Sharif MU, Shafi AM, et al. Value of soluble transferrin receptors in the diagnosis of iron deficiency accompanied by acute infection. BMC Hematol. 2021;21(1):45-52.
- Cortese S, Angriman M, Lecendreux M, et al. Iron deficiency and neurological disorders in children: From restless legs syndrome to ADHD. Sleep Med Rev. 2024;68:101-109.
- World Health Organization. Global anaemia estimates: Key findings and trends. Geneva: World Health Organization; 2025. Available from: who.int
- Lalonde R, Strazielle C. Brain effects of iron deficiency-related pagophagia. J Nerv Ment Dis. 2025;213(6):140-4.
- Mayo Clinic. Craving and chewing ice: A sign of anaemia? Rochester: Mayo Foundation for Medical Education and Research; 2023. Available from: mayoclinic.org
- Abbaspour N, Hurrell R, Kelishadi R. Iron, the essential micronutrient: A comprehensive review of iron metabolism. Nutrients. 2026;18(1):109.
- Al-Saadi AM, Al-Asmi A, Al-Mawal AM. Craving for ice and iron-deficiency anaemia: A case series and review of literature. Oman Med J. 2026;41(1):79-85.
- Kawabata H, Germain RS, Ivy DI, Doi T, Said JW, Koeffler HP. Cloning of a novel transferrin receptor, TfR2. J Biol Chem. 1999;274(30):20826-32.
- World Health Organization. Serum transferrin receptor levels for the assessment of iron status and iron deficiency in populations. Geneva: World Health Organization; 2014. Available from: who.int
Disclaimer: The information provided in this article is intended for educational and informational purposes only and is not a substitute for medical examination, diagnosis, or professional medical advice. If you have symptoms of anemia, suspect iron deficiency, or have any other health concerns, please consult your doctor or another qualified healthcare professional.
The visual material accompanying this article was generated using artificial intelligence and serves an illustrative rather than documentary purpose.
