Iron-Deficiency Anemia: The Evidence-Based Supplement Protocol

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Iron-deficiency anemia is the most common nutritional deficiency globally. Conventional daily-dose iron supplementation is poorly tolerated and inefficient — the Stoffel trials in Lancet Haematology (2017–2020) rewrote the protocol. Modern hematology now recommends alternate-day dosing for outpatient repletion.

Alternate-Day Ferrous Bisglycinate, 60–100 mg Elemental

The Stoffel et al. 2017 trial showed splitting iron doses across the day reduces fractional absorption due to hepcidin elevation. Alternate-day single morning dosing produced higher cumulative absorption. Take 60–100 mg elemental iron as ferrous bisglycinate every other day, fasted, with vitamin C. Re-check ferritin and TSAT at 8–12 weeks. See our iron dosing piece.

Vitamin C, 200 mg With Each Iron Dose

Ascorbic acid converts ferric iron to ferrous and forms a soluble chelate. Stable-isotope studies show 100–200 mg vitamin C with non-heme iron can double or triple fractional absorption. See vitamin C dossier.

Lactoferrin, 100–200 mg Daily — Tolerability Alternative

Lactoferrin produces hemoglobin and ferritin gains comparable to ferrous sulfate with substantially fewer GI side effects. The most useful option when oral iron is poorly tolerated and IV iron is not yet indicated. See our lactoferrin piece.

Vitamin B12 — Test and Replete if Co-Deficient

Iron deficiency and B12 deficiency frequently co-exist (vegetarians, post-bariatric, elderly with atrophic gastritis). Test serum B12 + MMA. Replete with oral high-dose cyanocobalamin or methylcobalamin. See B12 form piece.

IV Iron — When to Escalate

IV iron (ferric carboxymaltose, iron isomaltoside) is indicated when oral iron fails after 3 months, is not tolerated, or the patient has active GI bleeding, IBD, or hemodialysis. Restores ferritin much faster than oral.

What NOT to Take

Avoid iron with calcium, tea, coffee, or phytate-rich foods at the same dose — significant absorption reduction. Skip "blood-building" herbal blends (yellow dock, nettle, chlorophyll) — no evidence for treating IDA. Don't supplement iron without confirmed deficiency on labs — overload risk in adults with hereditary hemochromatosis or chronic transfusion. See our iron overload piece.

How to Run the Protocol

Confirm IDA with ferritin <30 ng/mL (with CRP for inflammation context), TSAT <20%, CBC. Identify etiology — menstrual loss, GI loss workup (FOBT, age-appropriate colonoscopy), malabsorption (celiac antibodies, B12). Start alternate-day ferrous bisglycinate 60–100 mg + vitamin C 200 mg morning. Re-test at 8–12 weeks. Restoring ferritin from 10 → 50 ng/mL typically takes 12–24 weeks. Switch to lactoferrin if intolerant; escalate to IV iron if oral fails. See the broader iron recovery stack.