Iron Deficiency — Symptoms, Causes & Treatment | MyMedicPlus

Iron deficiency is the most common nutritional deficiency worldwide, affecting approximately 2 billion people globally. Iron is essential for haemoglobin synthesis (oxygen transport in red blood cells), myoglobin function (oxygen storage in muscles), mitochondrial respiratory chain enzymes, and immune function. Iron deficiency exists on a spectrum: early iron depletion (reduced iron stores with normal haemoglobin and function), progressing to iron-deficient erythropoiesis (impaired red blood cell production), and finally iron deficiency anaemia (reduced haemoglobin). All stages can impair function and require treatment. Iron deficiency exists on a spectrum that precedes frank anaemia — understanding this spectrum is essential for early intervention. Iron depletion (Stage 1): serum ferritin below 30 mcg/L with normal haemoglobin and normal red blood cell indices — symptomatic (fatigue, cognitive impairment, hair loss, restless legs) even without anaemia, and frequently missed when clinicians only check haemoglobin. Iron-deficient erythropoiesis (Stage 2): ferritin below 12 mcg/L, falling serum iron, rising TIBC, transferrin saturation below 16% — haemoglobin at low-normal range, MCV beginning to fall; red blood cell production becomes iron-limited. Iron deficiency anaemia (Stage 3): haemoglobin falls below 130 g/L in men (below 120 g/L in women), MCV below 80 fL, hypochromic red blood cells — symptomatic anaemia with impaired oxygen delivery. Iron deficiency is the most common nutritional deficiency globally, affecting over 2 billion people, with the highest burden in sub-Saharan Africa and South Asia. Even iron depletion without anaemia causes measurable impairment of cognitive function, exercise capacity, and immune response.

Inadequate dietary intake: populations dependent on plant-based diets with limited meat (non-haem iron is poorly absorbed); infants relying on cow's milk (low in iron and inhibits absorption); adolescents with poor dietary habits; and elderly with reduced appetite. Increased physiological demand: pregnancy (iron requirements increase from 1 to 7.5 mg/day in the third trimester); infancy and rapid growth phases; intense endurance exercise (sports anaemia from increased red blood cell turnover and GI microbleeding). Blood loss: heavy menstrual bleeding (premenopausal women); GI blood loss (peptic ulcer, colorectal cancer, IBD, hemorrhoids); blood donation. Malabsorption: coeliac disease, gastric bypass surgery, achlorhydria, inflammatory bowel disease.

Early iron deficiency without anaemia can cause significant symptoms: persistent fatigue disproportionate to activity, reduced cognitive performance and concentration, impaired short-term memory, mood changes (irritability, low mood), hair loss (telogen effluvium), brittle or ridged nails, dry skin, reduced physical performance, and restless legs syndrome. As iron deficiency progresses to anaemia, additional symptoms develop: pallor (particularly conjunctival), breathlessness on exertion, palpitations, headache, dizziness, and reduced exercise tolerance. Children with iron deficiency exhibit impaired attention, learning, and behavioral development even before anaemia develops. The symptoms of iron depletion often precede the development of anaemia by weeks to months. Fatigue from iron depletion — even before haemoglobin falls — is mediated by impaired mitochondrial respiratory chain function (iron-containing cytochromes), reduced myoglobin, and impaired dopamine receptor synthesis (iron is required for dopamine production). Hair loss — telogen effluvium — from iron depletion is a common presenting complaint in women; iron deficiency impairs hair follicle cell proliferation (high iron demand) and is the most common reversible cause of telogen effluvium. Restless leg syndrome (RLS) — uncomfortable urge to move the legs at rest, especially at night — responds to iron repletion even when haemoglobin is normal; CSF ferritin below 50 mcg/L is found in RLS patients, and IV iron dramatically relieves symptoms in iron-deficient RLS. Pica — craving for non-food items (most commonly pagophagia: compulsive ice chewing; less commonly chalk, clay, dirt, cornstarch) — is present in 50% of women with IDA and resolves with iron treatment. Reduced immune function: neutrophil bactericidal activity and lymphocyte proliferation are impaired by iron deficiency, increasing susceptibility to infections.

Serum ferritin is the single most sensitive and specific marker of iron stores — ferritin below 30 µg/L confirms iron deficiency in the absence of inflammation. However, ferritin is an acute-phase reactant and is falsely elevated in inflammatory states (infection, elevated CRP, liver disease, renal failure) — functional iron deficiency (ferritin below 100 µg/L with elevated CRP) requires IV iron. Full blood count: normal MCV and Hb in early deficiency; microcytic (low MCV), hypochromic (low MCH) anaemia in established IDA. Serum iron: low; TIBC elevated; transferrin saturation below 20%. In children: finger-prick point-of-care testing allows rapid community screening. Ferritin interpretation in inflammatory conditions is critical. Ferritin is an acute-phase reactant — it doubles or triples with active inflammation, infection, or malignancy, masking true iron depletion. A ferritin level of 80-100 mcg/L with an elevated CRP (above 10 mg/L) may represent iron deficiency in a patient with chronic inflammation (rheumatoid arthritis, IBD, cancer, CKD) — 'functional iron deficiency'. In this scenario, transferrin saturation below 20% combined with elevated CRP confirms functional iron deficiency requiring IV iron (oral iron is ineffective in the presence of elevated hepcidin induced by inflammation). The soluble transferrin receptor (sTfR) assay is not affected by inflammation and rises in iron deficiency — a high sTfR/log ferritin ratio (sTfR-F index above 1.5) identifies true iron deficiency in inflammatory states. Identifying the source of iron loss: in men and postmenopausal women, iron deficiency indicates GI blood loss until proven otherwise — mandatory upper and lower GI endoscopy, coeliac antibodies, and H. pylori testing.

Identify and treat the underlying cause concurrently with iron replacement. Oral iron is first-line: ferrous sulfate 200 mg (65 mg elemental iron), ferrous fumarate 200 mg, or ferrous gluconate 300 mg (35 mg elemental iron). Take on an empty stomach with a glass of orange juice (vitamin C enhances absorption) — 30 minutes before meals if tolerated. Alternate-day dosing reduces GI side effects with similar efficacy. Continue for 3 months after ferritin normalization (typically above 50 µg/L). IV iron (ferric carboxymaltose, low molecular weight iron dextran) is used when oral iron causes intolerable side effects, is ineffective due to malabsorption, or when rapid repletion is required (pre-surgery, third trimester pregnancy, CKD on ESA therapy). The relationship between oral iron dose and absorption is non-linear — beyond 25 mg elemental iron per dose, additional iron does not proportionally increase absorption due to hepcidin upregulation. This explains why some RCTs show equivalent haemoglobin response with 40 mg/day versus 200 mg/day elemental iron, with significantly fewer side effects. Ferrous bisglycinate (iron glycine chelate) is better tolerated and absorbed than ferrous sulfate — a useful alternative for patients who cannot tolerate standard preparations. Lactoferrin-bound iron preparations are emerging as well-tolerated alternatives with comparable efficacy. Concurrent Helicobacter pylori eradication in H. pylori-positive IDA patients (triple therapy: PPI + clarithromycin + amoxicillin or metronidazole for 7-14 days) significantly improves iron repletion — H. pylori consumes iron and impairs gastric acid production required for iron absorption. Monitoring treatment: recheck FBC and ferritin at 4-6 weeks to confirm haemoglobin is rising by at least 10-20 g/L (if not, investigate non-adherence, ongoing blood loss, or malabsorption); continue supplementation for 3 months after haemoglobin normalises to replenish stores (target ferritin above 50 mcg/L).

Untreated iron deficiency progresses to iron deficiency anaemia with cardiovascular strain from reduced oxygen-carrying capacity. In children, iron deficiency causes irreversible impairments in neurodevelopment, cognitive function, and school achievement — particularly if severe in the first 2 years of life (critical brain development period). In pregnancy, severe iron deficiency anaemia increases preterm birth risk, low birth weight, maternal postpartum hemorrhage risk, and poor neonatal outcomes. In competitive athletes, iron deficiency without anaemia measurably impairs endurance performance. Pica — craving for non-food substances (ice, dirt, chalk) — is associated with iron deficiency and resolves with iron treatment.

Dietary strategies: increase haem iron intake (red meat, poultry, fish absorb at 15–35% efficiency) and non-haem iron (legumes, tofu, fortified cereals, pumpkin seeds) — consume with vitamin C to enhance non-haem absorption 3-fold. Avoid iron absorption inhibitors at meal time: tea, coffee, calcium supplements, and high-phytate foods. Universal supplementation in high-risk groups: iron and folic acid in pregnancy; vitamin drops or fortified formula for exclusively breastfed infants from age 4–6 months; iron supplementation for premature infants from 2–4 weeks of age. Food fortification programs (iron-fortified flour, rice, salt) in high-prevalence regions are the most cost-effective public health intervention.

See a GP for: persistent fatigue, hair loss, poor concentration, or restless legs that may be related to iron deficiency — a serum ferritin and FBC will confirm the diagnosis within days. Iron deficiency in men of any age or postmenopausal women requires urgent investigation for the source of iron loss — particularly gastrointestinal bleeding. Do not assume diet is the cause without ruling out an underlying pathology. Seek urgent assessment for: iron deficiency with gastrointestinal symptoms (rectal bleeding, dark tarry stools, unexplained weight loss, change in bowel habit) — these require urgent endoscopy to exclude colorectal cancer; iron deficiency anaemia with haemoglobin below 8 g/dL or with cardiovascular symptoms (chest pain, severe breathlessness); and iron deficiency in pregnancy with haemoglobin below 10.5 g/dL (requires IV iron to achieve adequate stores before delivery). Children with pale skin, poor growth, excessive cow's milk intake, or developmental concerns should be assessed for iron deficiency promptly.