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Supplement

Iron

Mineral · Iron bisglycinate

Iron is the building block of hemoglobin and therefore a prerequisite for oxygen to be transported at all. When a deficiency has been demonstrated, its effect is as well supported as that of hardly any other nutrient — iron is approved as a medicine for this in Germany. Without a deficiency, the effect has no basis, and the risk remains.

In short

Iron works when there is a deficiency, and then clearly. In pregnancy, daily iron supplementation reduces iron deficiency anemia at term from 18.4 to 5.0 percent — a Cochrane result from 57 studies with 48,971 women. Fatigue also decreases measurably without anemia, but only on questionnaires and not in measured endurance. The catch is the diagnosis: without a deficiency no benefit is seen, and for hereditary hemochromatosis an estimated 0.2 to 0.6 percent of people in Germany are homozygous carriers. With iron, the blood test comes before the capsule.

What it is

Iron is an essential mineral. Most of it is found in hemoglobin, the rest in myoglobin, in enzymes of the respiratory chain and in the storage form ferritin. The body cannot actively excrete excess iron. It therefore regulates at the point of absorption.

Control is exercised by the liver hormone hepcidin. When the stores are full, hepcidin rises, the iron exporter ferroportin in the intestinal wall is degraded, and less iron enters the blood. When the stores are empty, hepcidin falls and absorption increases. This control loop has been measured in humans: in 1,058 pooled isotope measurements in women, upregulation began below a ferritin value of 51.1 micrograms per liter and a hepcidin value of 3.09 nanomoles per liter.

As a supplement, iron usually comes as ferrous sulfate, ferrous fumarate, ferrous gluconate or iron bisglycinate. The proportion of elemental iron varies: around 20 percent for ferrous sulfate, 33 for fumarate, 12 for gluconate.

How it is supposed to work

The chain of action is short. If iron is lacking, hemoglobin production falls, the blood transports less oxygen, and performance drops. That is iron deficiency anemia, and for this iron is an approved medicine.

The stage before that is more interesting. The stores can be empty while hemoglobin is still normal; iron-dependent enzymes in energy metabolism are then already working less well. This is the origin of the expectation that iron also helps against fatigue when only ferritin is low. It is partly confirmed and partly not.

Why the blood test comes before the capsule

Ferritin is the usual marker for the stores. The WHO sets the deficiency threshold in adults at below 15 micrograms per liter. It sees a risk of iron overload above 150 micrograms per liter in women and above 200 in men.

Ferritin, however, is also an acute-phase protein. In infections, inflammation and intensive training it rises independently of iron status and masks empty stores. The WHO therefore raises the deficiency threshold in inflammation from below 15 to below 70 micrograms per liter. An unremarkable ferritin with raised CRP is no all-clear.

What matters when taking it

How much of a dose arrives depends on what it is taken with and when. An isotope study in 34 iron-depleted women followed 204 labeled doses of 100 milligrams each. Ascorbic acid at 80 milligrams increased absorption by 30 percent; 500 milligrams brought no further increase.

In the opposite direction, coffee and meals have a stronger effect than many expect. Coffee reduced absorption by 54 percent, a breakfast including coffee by 66 percent — even though the meal contained around 90 milligrams of ascorbic acid. In the afternoon it was 37 percent lower than in the morning. There are measurements for calcium as well: 500 milligrams of calcium carbonate reduced iron absorption from a meal from 10.2 to 4.8 percent. For the frequently recommended separation from zinc and magnesium, no human data of comparable quality were found.

Iron in endurance sport

Athletes are a group of their own. A meta-analysis of 122 papers with 17,519 college athletes found a ferritin below 50 micrograms per liter in 53.9 percent and below 20 in 23.0 percent. Mechanistically this fits: exercise drives up interleukin-6 and with it hepcidin.

What supplementation achieves is less clear-cut. A meta-analysis of 13 studies with 449 participants found a clear rise in ferritin, but no established effect on maximal oxygen uptake or hemoglobin. The rise occurred mainly at baseline values of no more than 12 micrograms per liter. Iron fills the stores — that this translates into more performance is not established.

What is well supported

The evidence is strongest where hard endpoints were assessed. The Cochrane review of iron supplementation in pregnancy includes 57 randomized trials with 48,971 women; iron deficiency anemia at term fell from 18.4 to 5.0 percent.

For iron deficiency without anemia, there is a review of 18 randomized trials with 1,170 patients. Self-reported fatigue decreased compared with placebo, with a standardized mean difference of minus 0.38 (minus 0.52 to minus 0.23). A study in 198 women confirms this: the fatigue score fell by 47.7 percent compared with 28.8 percent on placebo.

What the studies show

Cochrane 2024: iron in pregnancy

Meta-analysis of 57 randomized and quasi-randomized trials with 48,971 women that compared daily oral iron with placebo or no iron. Maternal anemia occurred in 4.0 versus 7.4 percent, iron deficiency at term in 44.0 versus 66.0 percent, and iron deficiency anemia at term in 5.0 versus 18.4 percent. All three endpoints were met; the certainty of the evidence is rated low to moderate.

BMJ Open 2018: iron deficiency without anemia

From 11,580 hits, 18 randomized trials with 1,170 adults who were iron-deficient but not anemic were included. The primary endpoint, fatigue, was met: standardized mean difference minus 0.38 from 4 trials with 714 participants. The objective measures were not — maximal oxygen uptake was 0.11 with a confidence interval of minus 0.15 to 0.37 from 9 trials with 235 participants.

EClinicalMedicine 2023: daily or every other day

Double-blind, placebo-controlled trial in 150 women with ferritin of no more than 30 micrograms per liter, 75 per group. One group took 100 milligrams of iron daily for 90 days, the other the same total amount over 180 days alternating with placebo. For the co-primary endpoint, ferritin, there was no difference: 43.8 versus 44.8 micrograms per liter. For the second there was: on intake days, more gastrointestinal complaints occurred with daily dosing, prevalence ratio 1.56.

Where the data stop

The benefit without anemia rests almost entirely on self-report. The same review that finds an effect on fatigue finds none on maximal oxygen uptake. Two studies in similar groups contradict each other: in 198 women with low ferritin, fatigue decreased, while quality of life, depressive symptoms and anxiety remained unchanged. In 154 female blood donors, no clinical effect was found after 4 weeks. A study with 800 milligrams of intravenous iron in 90 non-anemic women missed its primary endpoint; the effect appeared only at a ferritin of no more than 15 nanograms per milliliter.

The statement that iron every other day is better than daily oversimplifies the evidence. It comes from isotope studies in which alternating dosing reached a fractional absorption of 21.8 versus 16.3 percent. The blinded trial with ferritin as the endpoint found no difference at the same total dose. The advantage in side effects is established, not in filling the stores. The question of the form is also open: 18 milligrams of iron bisglycinate did not reach the same ferritin as 60 milligrams of ferrous sulfate, 84 versus 99 micrograms per liter.

Status, approval and legal

Iron leads a double life in Germany. As ferrous sulfate, under ATC code B03AA07, it is a pharmacy-only medicine for iron deficiency, with tablets of 65 or 100 milligrams of elemental iron. At the same time it is freely sold as a food supplement, with no binding EU-wide maximum level. Nationally, the BfR recommends no more than 6 milligrams per daily dose and a warning that men, postmenopausal women and pregnant women should take iron only after consulting a doctor. Regulation (EU) No 432/2012 permits seven health claims, including blood formation, oxygen transport and reduction of tiredness. The reference values of the German Nutrition Society (DGE) are 11 milligrams per day for men aged 19 and over, 16 for premenopausal women, 14 after menopause and 27 in pregnancy. Iron is not on the WADA Prohibited List; however, the intravenous infusion of more than 100 milliliters within 12 hours outside legitimate medical care is prohibited as method M2.

Safety

In 2024, EFSA was unable to derive a classic upper limit for iron because the data on liver toxicity come mainly from case reports. Instead, it set a safe level of intake: 40 milligrams per day for adults, 35 milligrams for adolescents aged 15 to 17, 10 milligrams for children aged 1 to 3. The guiding endpoint was black stools. The NIH gives 45 milligrams per day. The most common side effects are nausea, abdominal pain and constipation. Acutely, iron is dangerous: from 20 milligrams per kilogram of body weight, intestinal necrosis is possible, from 60 milligrams multi-organ failure and death. Iron supplements should be kept out of the reach of children. Iron reduces the absorption of levodopa and levothyroxine; a gap of 4 hours is recommended there. Contraindications of the approved products are iron overload, iron utilization disorders and anemias without iron deficiency. In hereditary hemochromatosis, the odds ratio for liver disease in homozygous men in the UK Biobank was 4.30.

BK-Score Well supported, heavily overhyped

Human evidence9
Mechanism9
Safety data9
Hype gap5
Track record of use10

For use in deficiency, the evidence is exceptional: iron is approved in Germany as a medicine for iron deficiency, and the Cochrane review of 57 randomized trials with 48,971 women reduces iron deficiency anemia at term from 18.4 to 5.0 %. For iron deficiency without anemia, the review by Houston et al. (BMJ Open 2018, 18 RCTs, 1,170 patients) shows an effect on self-reported fatigue of SMD −0.38 (95 % CI −0.52 to −0.23), but none on maximal oxygen uptake (SMD 0.11; −0.15 to 0.37). Oxygen transport and the hepcidin control loop have been quantified in humans with isotopes, and safety is known from decades of use as a medicine – including overload in hemochromatosis. The critical point remains diagnostics: taken without a ferritin value, the effect has no basis and the risk remains; in addition, ferritin as an acute-phase protein masks empty stores in inflammation.

The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)

Frequently asked questions about iron

How do I notice that I have too little iron?

Not reliably at all. Fatigue, concentration problems, hair loss and sensitivity to cold fit iron deficiency, but just as well a dozen other causes. That is why the route goes through a blood test and not through how you feel. Useful are ferritin together with an inflammation marker and the blood count.

Is the ferritin value alone enough as a test?

Usually not. Ferritin is an acute-phase protein and rises in infections, inflammation and intensive training independently of iron status. The WHO therefore raises the deficiency threshold in infection or inflammation from below 15 to below 70 micrograms per liter. A ferritin that looks normal with simultaneously raised CRP therefore does not rule out a deficiency.

Should I take iron daily or every other day?

Both have evidence. With alternating dosing, a larger proportion of the dose is absorbed, because hepcidin remains raised for about 24 hours after a dose. In the only blinded trial with ferritin as the main endpoint, however, the result after the same total dose was practically identical, 43.8 versus 44.8 micrograms per liter. It is established that alternating intake causes fewer gastrointestinal complaints.

Is iron bisglycinate better than ferrous sulfate?

In studies it is better tolerated, but not automatically equally effective. In a direct comparison, 18 milligrams of bisglycinate reached a ferritin of 84 micrograms per liter after 12 weeks, whereas 60 milligrams of ferrous sulfate reached 99. Anyone who tolerates ferrous sulfate has no reason to switch. Anyone who does not tolerate it often abandons the therapy otherwise, and then the better-tolerated form is the more effective one.

Can I simply take iron as a precaution?

The authorities advise against this. For iron-containing food supplements, the BfR recommends a warning that men, postmenopausal women and pregnant women should take them only after consulting a doctor. The body cannot actively excrete excess iron, and in undetected hemochromatosis additional iron accelerates the overload. In any case, the studies show a benefit only when a deficiency has been demonstrated.

How long does it take for the ferritin value to rise again?

Considerably longer than the rise in hemoglobin. In the randomized trial in women with a baseline ferritin of no more than 30 micrograms per liter, the value after the same total dose was 43.8 and 44.8 micrograms per liter respectively. The authors of another study recommend a lab check after six weeks to see whether the therapy is working. If the value stays flat, the cause of the loss should be investigated rather than the dose increased.

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Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-09-19.