How to Take Iron Supplements Correctly

Iron deficiency is, of course, one of the most common deficiency states.

“IDA, when diagnosed in time, with the cause identified and with proper treatment, is curable in 100% of cases. So-called ‘relapses’ of IDA most often indicate that the cause of the disease has not been identified or eliminated, or that diagnosis and treatment were incorrect.”

Clinical guidelines.

However, iron supplements need to be taken correctly in order to achieve the best effect.

How should iron supplements be taken?

1. Ideally, in the morning on an empty stomach, 30 minutes before meals.
   This is related to the low concentration of the protein that binds iron: hepcidin. However, side effects may be stronger in this case. If side effects occur, discuss the timing of intake with your doctor.
2. Iron should be taken 1.5–2 hours before or after certain foods.
   This applies to dairy products and other foods high in calcium, foods containing phenols, such as coffee, tea and cocoa, as well as foods containing phytates, such as grains, nuts and seeds.
   These foods reduce iron absorption.
3. Antibiotics, antacids and L-thyroxine reduce iron absorption.
   Taking iron supplements together with these medications is not recommended. If there are indications for taking iron supplements along with these medications, discuss the dosing schedule with your doctor.
4. Iron intake to replenish iron stores should be long-term.
   Depending on the severity of anemia, treatment may last up to 6 months. On average, treatment lasts about 3 months.
5. Alternate-day iron intake is recommended, meaning every other day and once daily.
   This recommendation is related to the same protein, hepcidin: once you take iron, the concentration of this protein increases and remains elevated for 24–48 hours.
   Therefore, if the daily dose is divided into several doses throughout the day, all subsequent doses will be ineffective. Daily intake may also be less effective.
   This regimen significantly reduces the frequency of side effects from iron intake, such as nausea, abdominal pain, constipation and others.

What the guidelines say

This recommendation is included both in our clinical guidelines and in international ones:

“Prescribe oral iron no more than once a day. Iron dosing over several days may be better tolerated for some patients, with the same or an equal rate of iron absorption as daily dosing.”

“Evidence has now been obtained that the use of low-dose iron supplements in short courses, 2 weeks per month, or in alternating regimens, every other day for one month, has sufficient effectiveness and a lower frequency of side effects than previously used high-dose iron supplements, including repeated intake 2–3 times per day.”

Key points from studies

“Evidence is currently accumulating that the use of low-dose iron supplements in short courses, 2 weeks per month, or in alternating regimens, every other day for one month, has higher effectiveness and a lower frequency of adverse events than previously used high-dose iron supplements, including repeated intake 2–3 times per day.
Recent studies of iron absorption and the factors affecting it in iron deficiency may provide grounds for revising traditional iron supplementation regimens. As is known, iron absorption is regulated by hepcidin, a protein produced in the liver. In the study by Moretti D. et al. (2015), absorption of iron labeled with a radioactive isotope was assessed in women with iron deficiency, ferritin below 20 ng/ml, without anemia, while taking oral iron supplements in different doses, from 40 to 80 mg of elemental Fe.
It was shown that higher doses and more frequent intake of iron supplements increase hepcidin levels, which leads to reduced iron absorption. Elevated hepcidin levels remain for about 48 hours after a single dose of iron. Because of this, absorption of iron after the next dose, taken one day later, decreases under the influence of the still elevated hepcidin level.
However, these findings require confirmation and clarification, since the study was conducted in women with iron deficiency without anemia, who may respond to iron supplementation differently from patients with overt IDA. Nevertheless, these results appear fundamentally important, as they may change the dosing paradigm for iron supplements, including daily dose and frequency of intake, in patients with IDA.
It is possible that the effect can be achieved by prescribing iron supplements with a lower content of elemental iron and with a longer interval between doses, every other day, which provides optimal bioavailability and a lower risk of side effects.
Subsequent randomized studies of women with iron deficiency, with or without anemia, also documented improved iron absorption with every-other-day dosing compared with daily intake.
For example, in a 2017 study, 40 women were randomly assigned to take oral iron, 60 mg FeSO4, once daily for 14 days or once every other day for 28 days, with the same cumulative dose. The second regimen resulted in greater total iron absorption, 175 mg versus 131 mg.
In the every-other-day group, there was a tendency toward less nausea, although the incidence of constipation was not assessed in this study.
A sixfold increase in iron dose, from 40 to 240 mg, led to only a threefold increase in absorbed iron, from 6.7 to 18.1 mg. In study 3, the total amount of iron absorbed from 3 doses, 2 in the morning and 1 in the afternoon, was not significantly greater than from 2 morning doses.
Providing lower doses, 40–80 mg Fe, and avoiding twice-daily dosing maximizes fractional absorption. The duration of the hepcidin response supports every-other-day supplementation, but the long-term effects of these schedules require further study.”

Source:

https://pubmed.ncbi.nlm.nih.gov/26289639/

Why the second dose of iron may be absorbed worse

“They found that hepcidin reached its peak concentration after six to eight hours, but even 24 hours after the first iron dose, it was still present in large enough amounts to noticeably reduce absorption of the second dose. The body was only partially able to absorb this second dose of iron, which was given either on the same day or 24 hours after the first dose.”

Source:

https://www.sciencedaily.com/releases/2015/11/151106062318.htm

Why it is better not to split the dose into two intakes

“Divided doses twice daily resulted in a higher serum hepcidin concentration than once-daily dosing.
In iron-depleted women, daily iron supplementation in divided doses increases serum hepcidin and reduces iron absorption. Providing iron supplements every other day and in single doses optimizes iron absorption and may be a preferable dosing regimen.”

Source:

https://pubmed.ncbi.nlm.nih.gov/29032957/

A little physiology

The release of iron from enterocytes and macrophages is carried out by the protein ferroportin. In plasma, the main iron-transport protein is transferrin, while iron is stored and kept in the form of ferritin.

Ferroportin is located on the membrane of macrophages, which recycle Fe, as well as on enterocytes of the duodenum and hepatocytes. By binding to ferroportin, hepcidin causes ubiquitination, endocytosis and degradation of ferroportin. This blocks the release of Fe from enterocytes and leads to the accumulation of Fe in macrophages. As a result, intracellular Fe concentration increases, while serum Fe decreases.

Source:

https://neonatology-nmo.ru/ru/jarticles_neonat/649.html?SSr=510134b36b12ffffffff27c__07e70a130c332a-536&ysclid=mmre8mpghk156726261