Condition deep-dive · 6 min read

Iron deficiency anemia — the evidence-based oral repletion strategy

Updated 2026-05-13 · Reviewed by SupplementScore editors · No sponsorships

Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide and a frequent cause of fatigue, dyspnea, palpitations, and exercise intolerance. The 2015 Stoffel/Moretti hepcidin trial (Lancet Haematology, also subsequent 2019 paper) substantially changed best practice: oral iron given on alternate days produces equal or higher cumulative absorption than daily dosing because every dose acutely raises hepcidin and blocks absorption of subsequent doses for ~24 hours. The practical implication: stop dosing daily, start dosing every other day, accept that repletion takes 8–12 weeks for hemoglobin and 3–6 months for ferritin recovery.

Read this first. Iron deficiency requires a cause. Premenopausal women with heavy menstrual bleeding and pregnant women have obvious physiological causes. In men, postmenopausal women, and unexplained cases, IDA warrants evaluation for GI blood loss (occult colon cancer, celiac disease, peptic ulcer, H. pylori, NSAID use). Don't just supplement an unexplained iron deficiency — investigate the cause. Symptoms persisting after repletion, or recurrent deficiency, demand workup.

The repletion strategy that actually works

Tier 1 evidence · Modern evidence-based first line

Ferrous bisglycinate OR ferrous sulfate, alternate-day, single morning dose

60–120 mg elemental iron, taken every other day, morning, with 250 mg vitamin C, on empty stomach if tolerated

The Stoffel/Moretti work demonstrates that alternate-day dosing produces equal or better cumulative absorption than daily dosing because hepcidin doesn't have time to fully reset within 24 h. Bisglycinate has somewhat better GI tolerability and absorption per mg than sulfate at the elemental dose. Either is acceptable. See iron bisglycinate vs sulfate comparison for the deeper dive on form selection.

Tier 1 evidence · Absorption co-factor

Vitamin C (ascorbic acid)

100–250 mg taken with each iron dose

Vitamin C reduces non-heme iron (Fe³⁺ → Fe²⁺) and chelates iron in the duodenum, improving absorption. Even a small dose (100–250 mg) with each iron dose is sufficient. The "iron + orange juice" advice has reasonable physiology behind it.

Avoid in same meal as iron

What blocks iron absorption — separate by 2+ hours

Calcium supplements, dairy, tea (tannins), coffee, soy protein, eggs, antacids/PPIs, levothyroxine

Calcium and dairy reduce iron absorption by ~50%. Tea tannins (and to a lesser extent coffee polyphenols) similarly impair non-heme iron absorption. Antacids and PPIs raise gastric pH and reduce iron absorption. Levothyroxine and iron should be separated by 4 hours. Plan iron dosing accordingly.

When deficiency is dietary

Dietary iron — heme sources outperform non-heme

Red meat, liver, oysters, mussels, sardines for heme iron; lentils, beans, spinach, tofu for non-heme

Heme iron (animal) is absorbed at ~25%; non-heme iron (plant) at 5–15% depending on co-factors. Vegetarians and vegans need higher total intake and benefit from vitamin C pairing and avoiding tea/coffee with meals. See plant-based athletes guide for vegetarian iron strategy.

What to skip

"Gentle iron" without quantified elemental dose — many cheap "gentle" formulations are heme polypeptides at minuscule elemental iron content; not effective for repletion.
Iron infusions without indication — IV iron has real risk (anaphylactoid reactions, infusion-site reactions) and is appropriate when oral fails or is intolerable, not as first-line for uncomplicated IDA.
Iron + calcium combo products — calcium impairs iron absorption; "all-in-one" prenatal/multivitamin products with iron and calcium together deliver less iron than the label suggests.
"Blood-building" herbal formulas without iron — beetroot, chlorophyll, alfalfa do not meaningfully treat iron deficiency.
Iron in users with hemochromatosis or known iron overload — supplementing iron in users with HFE-mutation hemochromatosis worsens overload; screen ferritin and transferrin saturation if family history.
Carbonyl iron at low doses chronically — slow-release; reasonable in some cases but typically takes longer than ferrous salts for repletion.

The clinical framework

Confirm iron deficiency with ferritin first — ferritin <30 ng/mL (or <100 in chronic disease/inflammation) confirms deficiency; CBC may be normal early. Transferrin saturation <20% supports.
Investigate cause — menstrual history, GI bleeding workup (FOBT, endoscopy/colonoscopy in appropriate populations), celiac screening, H. pylori testing as indicated.
Alternate-day oral iron repletion — single morning dose 60–120 mg elemental iron + 250 mg vitamin C, every other day.
Recheck CBC at 8–12 weeks — hemoglobin should rise >1 g/dL; if not, reassess adherence, ongoing blood loss, or absorption issue.
Continue 3–6 months past hemoglobin normalisation — to replete tissue iron stores (ferritin target >100 ng/mL ideally).
IV iron indications — oral intolerance, malabsorption (post-bariatric, celiac, IBD), CKD, ongoing blood loss exceeding oral repletion, pregnancy with low gestational age and severe deficiency, refractory IDA.

Practical quick-start. Get a ferritin, CBC, and transferrin saturation. If iron deficient, start ferrous bisglycinate (or sulfate) 60–120 mg elemental iron every other day, morning, with 250 mg vitamin C, on empty stomach if tolerated. Avoid calcium/dairy/tea/coffee within 2 hours of dose. Recheck CBC at 8–12 weeks. Continue 3–6 months after Hb normalises to rebuild tissue stores. Investigate the underlying cause of deficiency, not just the lab value.

What to track

Ferritin (target >30 minimum, ideally >100 for resolved tissue deficiency). CBC (hemoglobin, MCV, RDW). Transferrin saturation. Symptom resolution — fatigue, dyspnea on exertion, restless legs, hair loss, cold intolerance. Adherence to alternate-day dosing. Ongoing blood loss (menstrual, GI symptoms). If on PPI, reassess whether continued PPI is appropriate. Track resolution over 3–6 months; relapse warrants source investigation.