Iron deficiency should be treated with supplementation because diet alone is insufficient for replenishing iron stores. Iron replacement can be oral or IV. Oral replacement is effective, safe, inexpensive, easy to obtain, and easy to administer.27 Oral replacement is recommended for adults whose anemia is not severe or who do not have a comorbid condition such as pregnancy, inflammatory bowel conditions, gastric surgery, or chronic kidney disease. When anemia is severe or a patient has one of these comorbid conditions, IV is the preferred method of replacement.27 In these cases, defer treatment to the patient’s primary care physician or specialist.
There are no clear recommendations on the amount of iron per dose to prescribe.27 The maximum amount of oral iron that can be absorbed is approximately 25 mg/d of elemental iron. A 325 mg ferrous sulfate tablet contains 65 mg of elemental iron, of which approximately 25 mg is absorbed and utilized.27
Emerging evidence suggests that excessive iron dosing may reduce iron absorption and increase adverse effects. In a study of 54 nonanemic young women with iron deficiency who were given iron supplementation, Moretti et al28 found that a large oral dose of iron taken in the morning increased hepcidin, which decreased the absorption of iron taken later for up to 48 hours. They found that 40 to 80 mg of elemental iron given on alternate days may maximize the fractional iron absorbed, increase dosage efficacy, reduce GI exposure to unabsorbed iron, and improve patients’ ability to tolerate iron supplementation.28
Adverse effects from iron supplements occur in up to 70% of patients.27 These can include metallic taste, nausea, vomiting, flatulence, diarrhea, epigastric pain, constipation, and dark stools.27 Using a liquid form may help reduce adverse effects because it can be more easily titrated.27 Tell patients to avoid enteric-coated or sustained-release iron capsules because these are poorly absorbed. Be cautious when prescribing iron supplementation to older adults because these patients tend to have more adverse effects, especially constipation, as well as reduced absorption, and may ultimately need IV treatment. Iron should not be taken with food, calcium supplements, antacids, coffee, tea, or milk.27
The amount of iron present, cost, and adverse effects vary by supplement. The Table27,29-33 provides more information on available forms of iron. Many forms of iron supplementation are available over-the-counter, and most are equally effective.27 Advise patients to use iron products that have been tested by an independent company, such as ConsumerLab.com. Such companies evaluate products to see if they contain the amount of iron listed on the product’s label; for contamination with lead, cadmium, or arsenic; and for the product’s ability to break apart for absorption.34
Six to 8 weeks of treatment with oral iron supplementation may be necessary before anemia is fully resolved, and it may take up to 6 months for iron stores to be repleted.27 If a patient cannot tolerate an iron supplement, reducing the dose or taking it with meals may help prevent adverse effects, but also will reduce absorption. Auerbach27 recommends assessing tolerability and rechecking the patient’s CBC 2 weeks after starting oral iron replacement, while also checking hemoglobin and the reticulocyte count to see if the patient is responding to treatment. An analysis of 5 studies found that a hemoglobin measurement on Day 14 that shows an increase ≥1.0 g/dL from baseline predicts longer-term and sustained treatment response to continued oral therapy.35 There is no clear consensus for target ferritin levels, but we suggest aiming for a ferritin level >100 ug/L based on recommendations for the treatment of restless legs syndrome.36 We recommend ongoing monitoring every 4 to 6 weeks.
Bottom Line
Iron deficiency is common and can cause or contribute to psychiatric symptoms and disorders. Consider screening patients for iron deficiency and treating it with oral supplementation in individuals without any comorbidities, or referring them to their primary care physician or specialist.
Related Resources
- Berthou C, Iliou JP, Barba D. Iron, neuro-bioavailability and depression. EJHaem. 2021;3(1):263-275.