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Supplement

Iron

An essential mineral for blood and energy; deficiency (with or without anemia) causes tiredness. Do not supplement without confirming it is needed.
Category
Scientific evidence
Low-moderate
Number of findings
2
Sources
Our own summaries · Cited studies
Recommended dose and how to use
Only if deficiency is confirmed. Taken on alternate days and with vitamin C, it is absorbed better and is better tolerated.

How to take it

Only if deficiency is confirmed. Taken on alternate days and with vitamin C, it is absorbed better and is better tolerated.

Safety

Excess is toxic and damages the liver; do not take iron without a blood test. Keep it out of the reach of children.

Interactions

Reduces the absorption of levothyroxine, bisphosphonates, and some antibiotics: take them apart. Vitamin C increases it.

Effect by goal · level of evidence

Energy and fatigue

improves Low-moderate meta-analysis (AAA)

Reduces fatigue, especially if there is iron deficiency/low ferritin

View the study (meta-analysis) →

Iron bioavailability depending on diet

association Low study (A)

Review: heme iron (from meat) is absorbed better than non-heme (plant) iron, and non-heme absorption varies widely depending on other foods that enhance it (e.g., vitamin C) or inhibit it. The body does not eliminate excess iron: it regulates how much enters.

View the study (study) →

In depth

⏱ 3 min read

Iron is one of the most essential minerals in the body: it is part of hemoglobin (which carries oxygen from the lungs to every cell in the body), of myoglobin (which stores it in muscle), and of countless enzymes involved in energy metabolism, neurotransmitter synthesis, and immunity; its deficiency is the most prevalent nutritional deficiency in the world, especially affecting women of childbearing age, young children, strict vegetarians, endurance athletes, and people with chronic blood loss.

Unlike most minerals and vitamins, iron requires more careful handling because the body has no efficient mechanism for eliminating the excess, which means that supplementation without a documented deficiency can accumulate and cause long-term oxidative tissue damage; the basic rules of clinical iron use are: measure before supplementing, dose only what is needed, and monitor the response.

Diagnosis: ferritin as the key marker

The most important biomarker for assessing the body's iron status is serum ferritin: it reflects total iron stores and is the most sensitive indicator of deficiency (it falls before hemoglobin, which drops only once stores are already depleted); values below 30 ng/mL in healthy adults indicate functional deficiency and below 15 ng/mL indicate frank deficiency, although some clinical contexts (female athletes, cognitive decline, unexplained fatigue) suggest higher targets (50-100 ng/mL).

Hemoglobin, the classic marker of anemia, is less sensitive: many people have functional iron deficiency with symptomatic consequences (fatigue, reduced mental performance, hair loss) before hemoglobin falls below the normal range; measuring only hemoglobin and not ferritin is one of the most frequent diagnostic errors in primary care regarding iron management.

Iron-deficiency anemia and functional deficiency

In documented iron-deficiency anemia (low hemoglobin + low ferritin), supplementation with 30-100 mg of elemental iron daily (typically ferrous sulfate, ferrous gluconate, or ferrous bisglycinate) for 3-6 months normalizes hemoglobin and, most importantly, replenishes ferritin stores; treatment should continue for several months after hemoglobin normalizes to ensure stable stores and prevent relapse.

In functional deficiency without anemia (low ferritin with normal hemoglobin), lower doses (20-50 mg/day) for 8-12 weeks usually resolve the associated symptoms (fatigue, exercise intolerance, mental sluggishness); in female athletes and in women of childbearing age with heavy periods, maintenance supplementation may be reasonable to avoid cyclical fluctuations in stores.

Chemical forms: which is absorbed best

The classic ferrous salts (sulfate, fumarate, gluconate) are the most studied and the cheapest, but also the ones that cause the most gastrointestinal discomfort (constipation, nausea, epigastric pain, darkening of stools); ferrous bisglycinate and heme iron (from meat) are better tolerated and have better bioavailability in terms of percentage absorbed, which justifies their preferred use in people who do not tolerate the classic salts.

Newer intermittent iron regimens (one dose every 2-3 days instead of daily) have shown in recent studies that total absorption can be similar or even higher with fewer adverse effects, because continuous daily dosing raises hepcidin (a hormone that blocks intestinal absorption) and paradoxically reduces efficiency with each successive dose.

Critical precautions: the other side of iron

Iron accumulated in excess is toxic: it causes oxidative stress and liver, heart, and joint damage, and it is associated with a higher risk of several cancers in long epidemiological studies; people with hereditary hemochromatosis (frequency of 1 in 200 in Europeans), those who have received repeated transfusions, and adult men without chronic blood loss should not supplement iron without a documented deficiency.

How to take it correctly

Therapeutic doses are ideally taken on an empty stomach with vitamin C (which improves absorption) and separated by at least 2 hours from coffee, tea, dairy, calcium, and antacids (which inhibit it); if gastrointestinal discomfort is intolerable, taking iron with a light meal improves tolerance although it somewhat reduces absorption; in female athletes with heavy periods, a dose after each monthly period for 2-4 weeks may be more efficient than small continuous doses.

References

  1. Camaschella, C. (2015). Iron-deficiency anemia. N Engl J Med 372, 19. doi:10.1056/NEJMra1401038
  2. Stoffel, N.U. et al. (2017). Iron absorption from oral iron supplements given on consecutive versus alternate days. Lancet Haematol 4, 11. doi:10.1016/S2352-3026(17)30182-5
  3. Pasricha, S.R. et al. (2021). Iron deficiency. Lancet 397, 10270. doi:10.1016/S0140-6736(20)32594-0
  4. Mei, Z. et al. (2017). Adjusting total body iron for inflammation: biomarkers of inflammation have similar effects on total body iron. Am J Clin Nutr 106, Suppl 1. doi:10.3945/ajcn.116.142307
  5. Krayenbuehl, P.A. et al. (2011). Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin. Blood 118, 12. doi:10.1182/blood-2011-04-346304

Information, not medical advice. Scientific evidence reflects the quality of the studies.

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