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Iron deficiency: the right way to take iron, and the reason it may not be a supplement problem

Absorption is dose-dependent in the wrong direction, so a smaller dose more often beats a bigger one. And the cause matters more than the iron.

remedy

Iron deficiency is the commonest nutritional deficiency worldwide and one of the few where a supplement genuinely treats the disease. Two things matter more than which brand: how it is taken, and why the person is deficient.

The absorption rules, which are the substance of this page.

Vitamin C with the iron raises absorption substantially. This is why iron with a glass of orange juice is the standard advice and why it is real.
Phytate in grains and legumes, polyphenols in tea and coffee, and calcium all inhibit absorption. Tea with an iron tablet is the commonest self-defeating habit.
Fermentation degrades phytate, which is why fermented foods, sourdough and soaked-and-fermented grains increase mineral availability. When the goal is getting iron and zinc out of plants, ferment them.
Take it on an empty stomach if tolerated, but with food if it causes nausea — partial absorption is better than an abandoned course.
Alternate-day dosing is at least as effective as daily dosing in trials, because a dose of iron triggers a rise in hepcidin that blocks absorption of the next dose for about 24 hours. A lower dose more often, or a full dose every other day, is better than a large daily dose. This is counter-intuitive and it is one of the more useful recent findings.
Constipation and black stools are expected. Black stool is the iron, not bleeding. Constipation is the commonest reason people stop.

The cause, which is not optional. In a menstruating person, heavy periods are the usual cause and are worth treating in their own right. In a man, or a postmenopausal woman, iron deficiency requires investigation of the gut — bleeding from a polyp, an ulcer or a cancer is the concern, and it is a diagnosis not to miss. Coeliac disease is another common cause. Pregnancy and breastfeeding raise requirements.

Food-level iron. Heme iron (red meat, liver, shellfish) is better absorbed than non-heme iron (legumes, greens, fortified cereals). Vitamin C alongside, and avoiding tea and coffee with the meal, are the two practical moves.

Iron poisoning. Iron tablets are a leading cause of poisoning death in small children, and the presentation can be delayed. Keep them locked away.

What the studies found

Randomized Controlled Trial2020Nutrients

Oral Supplementation with Sucrosomial Ferric Pyrophosphate Plus L-Ascorbic Acid to Ameliorate the Martial Status: A Randomized Controlled Trial.

Future opportunities may consider to couple ferric pyrophosphate with other nutrients, to pay attention in avoiding absorption disruptors, or to implement interventions to obtain an earlier martial status optimization at the population level.

PubMed 32024027 ↗

Unclassified2020JAMA network open

The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial.

Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption.

PubMed 33136134 ↗

Preparation

Iron supplementation

A common regimen: 65 mg of elemental iron (a ferrous sulfate 325 mg tablet) every other day, or a lower dose daily
Alternate-day dosing is at least as effective as daily because of hepcidin
Take with vitamin C — a glass of orange juice, or 250 mg of ascorbic acid
Take on an empty stomach if tolerated; with food if it causes nausea
Do not take with tea, coffee, milk or a calcium supplement. Separate by 2 hours.
Expect black stools and possible constipation

Managing the constipation

Increase fluid and fibre
A stool softener or a bulk fibre may be needed; separate psyllium from the iron by 2 hours
Some forms (ferrous gluconate, iron bisglycinate) are better tolerated than ferrous sulfate at the cost of elemental iron content

Food-level iron

Heme iron: red meat, liver, shellfish — better absorbed
Non-heme: legumes, dark leafy greens, fortified cereals, tofu
Vitamin C alongside the meal raises non-heme iron absorption
Ferment the grains and legumes — fermentation degrades phytate and measurably raises mineral absorption
Do not drink tea or coffee with an iron-containing meal

If it is not working

Recheck the haemoglobin and ferritin after 4-8 weeks
If oral iron is not working, the question is why: continued bleeding, malabsorption (coeliac disease, H. pylori), or an incorrect diagnosis. This is a clinician's job.
Intravenous iron is used where oral iron fails or is not tolerated

Children — the safety point

Iron tablets are a leading cause of poisoning deaths in small children. Store them locked, out of reach, and never in a pill organiser on a bench.
Never give a child iron without a confirmed deficiency and a prescribed dose.

Cautions and interactions

Do not take iron without a confirmed deficiency unless a clinician has advised it. Iron overload is a real disease.
Iron tablets are a leading cause of childhood poisoning deaths. Lock them away.
Tea, coffee, calcium and antacids block iron absorption. Separate them.
Black stools are expected on iron — but if you are not on iron, black stool means bleeding.
Vitamin C at high doses increases oxalate stone risk in susceptible people.

When this is not a self-care problem — get help

Iron deficiency in a man or a postmenopausal woman — the gut must be investigated for a bleeding source.
Black tarry stool, blood in the stool, or vomiting blood when NOT taking iron — urgent assessment.
Iron overdose in a child (even a few tablets) — emergency care immediately. Symptoms can be delayed by hours and the child may look well first. Take the bottle.
Severe breathlessness, chest pain or fainting with a very low haemoglobin — urgent care; this may need transfusion.

Known interactions

Iron + levothyroxine, tetracyclines, quinolones, bisphosphonates: mutual absorption reduction. Separate by 2-4 hours.
Iron + tea/coffee/calcium: reduced absorption.
Fermentation of grains and legumes: improves absorption.

Sources

Oral Supplementation with Sucrosomial Ferric Pyrophosphate Plus L-Ascorbic Acid to Ameliorate the Martial Status: A Randomized Controlled Trial. Nutrients 2020; doi:10.1038/srep45270 PubMed 32024027
The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial. JAMA network open 2020; doi:10.1136/gut.2010.228874 PubMed 33136134