This is one of the most common things I get asked, often apologetically. In most cases the tablets are being taken correctly. Your body has no regulated way of excreting iron, so absorption is tightly controlled at the gut wall.
Time on tablets before retesting
Australian prescribing guidance is to repeat iron studies after 60 to 90 days of oral iron supplements, and to investigate further only if the deficiency has not corrected by then.
That is longer than most people wait before deciding the tablets are useless. If you were rechecked at six weeks and told nothing had changed, you were rechecked early.
Ferritin is a storage measure, and it fills last. How you feel can improve before the number does, and the number can improve before you feel different.
Hepcidin and iron
Hepcidin is a small hormone made by the liver, and it is the master switch on iron absorption. When hepcidin is high, the gut absorbs less iron. When it is low, the gut absorbs more.
A dose of iron raises hepcidin, and the rise lasts long enough to interfere with the next dose.
In a study of 54 non-anaemic young women with plasma ferritin at or below 20 micrograms per litre, doses of 60 mg or more raised serum hepcidin and cut fractional iron absorption by 35 to 45 per cent when the next dose came 24 hours later.
So a tablet every morning works against itself: each dose puts up a barrier that the following dose has to climb.
Dose size and absorption
Taking more is the intuitive response to a flat ferritin, and it is the wrong lever.
In the same study, increasing the dose sixfold, from 40 mg to 240 mg of iron, produced only about a threefold increase in the iron absorbed, from 6.7 mg to 18.1 mg.
| What you change | What actually happens |
|---|---|
| Dose goes up 6x, 40 mg to 240 mg | Iron absorbed goes up about 3x, 6.7 mg to 18.1 mg |
| Same tablet taken twice a day instead of once | Hepcidin rises, and total absorption does not improve |
| Same tablet taken every second day | A higher fraction of each dose is absorbed |
Unabsorbed iron stays in the gut, and that is where the nausea, the constipation and the metallic taste come from. A bigger dose buys you a modest amount of extra iron and a substantial amount of extra misery, which is a large part of why people stop taking it.
Split doses
Older advice was to divide the daily dose to improve tolerance. When this was tested directly, twice-daily dosing produced a higher hepcidin concentration than the same total taken once in the morning, and no improvement in how much iron was absorbed.
Take one dose in the morning, on an empty stomach if you can tolerate it.
Alternate-day dosing
The trials on alternate-day dosing point in different directions.
In a randomised trial in iron-depleted women, giving 60 mg on alternate days rather than consecutive days raised cumulative fractional absorption from 16.3 per cent to 21.8 per cent, and cumulative total iron absorbed from 131 mg to 175 mg.
A larger randomised, double-blind, placebo-controlled trial in 150 women then compared the two schedules at equal total iron doses over six months. Median serum ferritin came out essentially identical: 43.8 micrograms per litre on consecutive days against 44.8 on alternate days.
Two things in that same trial did favour alternate days. Gastrointestinal side effects were substantially more common on the days iron was taken in the consecutive-day group. And after six months, 11.4 per cent of the consecutive-day group were still iron deficient against 3.0 per cent of the alternate-day group.
Alternate-day dosing gets a higher fraction of each dose across the gut wall and is easier to tolerate, and in the one trial that followed women for six months it left fewer of them still deficient. It has not been shown to push ferritin higher at equal total doses. Anyone telling you it definitively beats daily dosing is ahead of the evidence, and so is anyone telling you it does not matter.
A flat ferritin despite correct dosing
If you have given it two to three months, you are taking one dose in the morning, and your ferritin is still flat, the schedule is probably not the problem. Three broad explanations remain, and each needs a doctor to investigate.
1. Ongoing iron loss
Absorption is slow and losses can be fast. Heavy menstrual bleeding is the most common reason a woman of reproductive age cannot get ahead of her own iron balance, and it is routinely under-asked about. Gastrointestinal bleeding has to be excluded.
If iron is leaving at a similar rate to the few milligrams a day you are absorbing, the tablets are holding the line against that loss.
2. Poor absorption
Coeliac disease is the classic one, because it can present as iron deficiency with no bowel symptoms at all. Reduced stomach acid, including from long-term acid-suppressing medication, and Helicobacter pylori are others worth raising. Ask about them by name if you are two or three months in and nothing has shifted.
3. Inflammation
Hepcidin also rises with inflammation, a sensible defence, since bacteria need iron too. With ongoing inflammation, oral iron works poorly however well you time it.
Ferritin itself also rises with inflammation, because it is an acute phase protein as well as an iron store. So a person can have depleted iron and a ferritin reading that looks acceptable, purely because something inflammatory is running in the background. That is why a ferritin result is best read alongside transferrin saturation and a marker such as C-reactive protein (CRP).
Questions for your general practitioner (GP)
If you are going back to your general practitioner (GP) after a few months of tablets that have not worked, ask these.
- How long have I been on this, and when is the right time to recheck? If it is under 60 days, you may simply need to keep going.
- Can we look at transferrin saturation and C-reactive protein (CRP) as well as ferritin? One number in isolation is the weakest version of this test.
- Is my dosing schedule worth changing? One morning dose, and whether alternate days is worth trying in your case.
- Have we established the cause? Guidance is explicit that the cause of iron deficiency should be identified and managed.
- Have we ruled out coeliac disease? Particularly if there are no obvious bleeding losses.
- At what point would intravenous iron be reasonable? Guidance recognises that some people who do not respond to oral supplements benefit from it.
Summary
A ferritin that will not rise is most often one of four things: not enough time yet, a dosing schedule that fights its own biology, an uncorrected cause draining iron out, or inflammation holding the gate shut and inflating the very number being used to check.
If you have been told your levels are fine and you do not feel fine, that gap is worth investigating.
Related articles
Sources
The four papers behind the figures in this article.
- Moretti D, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood 2015;126(17):1981-9. doi:10.1182/blood-2015-05-642223
- Stoffel NU, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women. The Lancet Haematology 2017;4(11):e524-e533. doi:10.1016/S2352-3026(17)30182-5
- von Siebenthal HK, et al. Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study. EClinicalMedicine 2023;65:102286. doi:10.1016/j.eclinm.2023.102286
- Balendran S, Forsyth C. Non-anaemic iron deficiency. Australian Prescriber 2021;44(6):193-196. doi:10.18773/austprescr.2021.052
This article is educational and not medical advice. Always discuss significant changes to supplementation or testing with a qualified clinician who knows your full history.