Iron Supplementation: When You Need It, and When You Do Not

Why Iron Is Different

Most nutrients that are surplus to requirement are excreted or stored harmlessly. Iron is neither. Absorption is regulated at the intestine by the hormone hepcidin, which reduces uptake when stores are adequate, and there is no physiological mechanism for excreting excess iron other than blood loss and cell shedding.

That asymmetry means iron status is a balance between intake, absorption and loss, and that anyone taking supplemental iron without a demonstrated need is loading a system with no exit. Free iron catalyses the Fenton reaction, generating hydroxyl radicals, which is why iron overload damages liver, heart, pancreas and joints over time.

It also explains a piece of aging biology that is under-discussed: tissue iron tends to accumulate with age, and higher ferritin within the normal range is associated with less favourable metabolic and inflammatory profiles in population data.

Recognising Genuinely Low Iron

Low iron status progresses through stages, and only the last is anaemia.

Depleted stores. Ferritin falls while haemoglobin remains normal. Fatigue, reduced exercise capacity, cold intolerance, hair shedding and restless legs can appear here, before any anaemia exists. This is the stage most often missed because a full blood count looks normal.

Iron-restricted erythropoiesis. Transferrin saturation falls, soluble transferrin receptor rises, red cell size begins to fall.

Anaemia from depleted iron. Haemoglobin falls with small, pale red cells.

Groups where low status is common: menstruating women, particularly with heavy periods; pregnant women, where requirements rise substantially; endurance athletes, through foot-strike haemolysis, sweat losses, gastrointestinal losses and hepcidin elevation after hard sessions; vegetarians and vegans, since non-haem iron is absorbed less efficiently; people with coeliac disease, inflammatory bowel conditions or after bariatric surgery; frequent blood donors; and anyone with gastrointestinal blood loss, which is why unexplained low iron in men and postmenopausal women requires investigation rather than supplementation.

That last point deserves emphasis. In a man or a postmenopausal woman, low iron is a finding to be explained, not a gap to be filled. Supplementing it without investigation can delay an explanation that matters.

Testing Properly

• Ferritin. The best single measure of iron stores, and an acute phase reactant that rises with inflammation, infection, liver involvement and heavy alcohol use. A normal ferritin alongside elevated C-reactive protein does not rule out low stores.
• Transferrin saturation. Serum iron divided by total iron binding capacity. Useful for both ends: low saturation supports inadequacy, high saturation is the screening signal for overload.
• Full blood count. Haemoglobin, mean cell volume and red cell distribution width give the downstream picture.
• Soluble transferrin receptor. Rises with iron-restricted erythropoiesis and is not an acute phase reactant, which makes it useful when inflammation confounds ferritin.
• C-reactive protein alongside. Not optional if ferritin is being interpreted.

Interpretation shorthand: ferritin below roughly 30 nanograms per millilitre indicates depleted stores in most laboratories, and thresholds up to 50 or higher are used in specific contexts such as restless legs and athletic populations. Optimisation practice often targets the middle of the range rather than the bottom, and high-normal ferritin with normal inflammatory markers is not a target to aim for.

Supplementing Well

Iron supplementation is frequently done badly, and getting it right shortens the process considerably.

Dose and frequency. A key finding from controlled work: a single dose raises hepcidin for roughly twenty-four hours, which blocks absorption of subsequent doses. Alternate-day dosing therefore absorbs a greater fraction than daily dosing, and split daily dosing is the least efficient arrangement. Doses of 60 to 120 mg elemental iron on alternate days achieve better absorption with fewer gastrointestinal effects than the traditional three-times-daily approach.

Form. Ferrous sulfate is the standard and the cheapest. Ferrous bisglycinate is better tolerated at equivalent absorbed iron and costs more. Iron polysaccharide complexes are gentler and absorbed less. Heme iron polypeptide is well absorbed and expensive.

Timing. Absorption is best on an empty stomach with vitamin C, and worst with calcium, tea, coffee, and phytate-rich foods. Take it away from those, and away from thyroid medication and certain antibiotics by at least four hours.

Duration. Replenishing stores takes months, not weeks. Haemoglobin responds within weeks; ferritin lags well behind, and stopping when haemoglobin normalises leaves stores empty and the problem recurring.

Recheck. Ferritin and a full blood count after three months of consistent supplementation, then decide.

Overload and Why It Is Not Rare

Hereditary haemochromatosis, most commonly from HFE gene variants, is among the most common inherited conditions in people of Northern European ancestry, with carrier frequencies high enough that many people are unaware. It causes progressive iron accumulation with consequences for liver, heart, pancreas, joints and endocrine function.

Screening is simple: transferrin saturation and ferritin. A persistently elevated transferrin saturation is the signal that warrants further investigation, and the management, regular phlebotomy, is straightforward when identified early and less so when the damage is established.

The relevance to supplementation is direct: anyone with unrecognised haemochromatosis taking a multivitamin containing iron is accelerating a problem. This is a strong argument for iron-free multivitamins as the default for adult men and postmenopausal women, which is exactly how many are formulated.

The Rule

Iron is the supplement where the general rule of this Journal, measure before intervening, is not a preference but a requirement.

Test first: ferritin, transferrin saturation, a full blood count and C-reactive protein. Supplement only against a demonstrated need, using alternate-day dosing with vitamin C away from calcium and tea. Investigate rather than supplement when low iron appears in a man or a postmenopausal woman. And avoid iron-containing multivitamins by default unless there is a reason to include it.

The review point is three months, with the same tests, and the endpoint is restored stores rather than a normal haemoglobin.