Question from a Member:
Which iron supplement (should we recommend)? Also, aren’t some supplements better tolerated from a GI standpoint?
Before discussing how to do iron supplementation most effectively, I want to emphasize that iron deficiency should not be treated without first evaluating what the cause is. Otherwise, some serious medical conditions being missed. The cause of iron deficiency must be treated rather than only giving iron supplementation.
Two things can help us to deal with these side effects: Which supplement to take and How to take it.
The problem of gastrointestinal side effects
Iron supplements frequently cause gastrointestinal side effects (Tolkien et al., 2015). These include (Pereira et al., 2014):
– Nausea, vomiting
– Heartburn, abdominal pain
– Either constipation or diarrhea
– Black or green stools
– Metallic taste
Patients often stop taking iron supplements because of these side effects (Cancelo-Hidalgo et al., 2013). The problem of non-adherence with iron supplements is huge with about half of patients stopping them (Cancelo-Hidalgo et al., 2013).
Which iron supplement?
Many different preparations of iron are available, e.g., ferrous sulfate, ferrous gluconate, ferrous fumarate, etc. and choosing between them can be very confusing.
Here are some principles for choosing an iron supplement:
1. Ferrous salts of iron should be preferred over ferric salts because ferrous salts are better absorbed.
2. Enteric-coated or extended-release preparations may be better tolerated (Cancelo-Hidalgo et al., 2013). But, the concern is that they may not be as well-absorbed.
3. Liquid iron supplements allow slow titration of the dose but can stain the teeth.
While there are many forms of iron supplements for which a claim of better tolerability has been made, we should be skeptical of these claims unless supported by systematic research.
A systematic review on the tolerability of different iron supplements found significant differences in the incidence of overall adverse effects/ gastrointestinal adverse effects:
Ferrous fumarate: 47%/43%
Ferrous gluconate: 31%/30%
Ferrous sulfate without mucoproteose: 33%/30%
Ferrous glycine sulfate: 24%/19%
Iron protein succinylate: 7%/7%
Ferrous sulfate extended-release and with mucoproteose: 4%/ 4%
Ferrous sulfate with mucoproteose was the best tolerated of these but is, unfortunately, not available commercially. And what is mucoproteose you ask? Mucoproteose is a substance that acts as a protectant of the gastrointestinal mucosa (Cancelo-Hidalgo et al., 2013). It is one of the substances in mucin, the substance secreted by the stomach that prevents gastric acid from harming the lining of the stomach.
So, the best choice (out of these ones) is iron protein succinylate. The brand of iron protein succinylate tested and approved by Consumer Lab is the following:
One thing to remember about this product, though, is that each capsule contains only 15 mg of elemental iron. So, if the person is truly iron deficient, we may start with one capsule per day but it would have to be increased to four capsules per day, i.e., 60 mg of elemental iron per day.
How to improve the tolerability of the supplement
With iron supplements, it is not only which iron supplement to take, but also how to take it. Here are some instructions that should be given to patients.
1. If more than a small amount of iron supplement is recommended per day, splitting it into two or three doses over the day is likely to reduce side effects. At any one time, no more than 60 mg of elemental iron should be taken. Note: for each salt of iron, the amount of elemental iron in it varies but will be listed on the packaging.
2. While iron is better absorbed on an empty stomach, for many persons this bothers their stomach. In that case, the supplement should be taken after meals. We will separately discuss what foods/supplements should not be taken along with iron because they are likely to reduce the absorption of iron.
3. The iron supplement should be taken with a full cup of water to make sure it does not get stuck in the esophagus.
4. To reduce the risk of reflux, the person should not lie down for 30 to 60 minutes after taking the iron supplement.
5. To manage constipation, when an iron supplement is prescribed, the person should be told to increase fiber and water intake. But, dietary fiber can decrease the absorption of iron. So, the increased fiber intake should not be taken at the same time as the iron supplement.
6. If one form of iron supplementation is poorly tolerated by the person, another form could be tried.
Cancelo-Hidalgo MJ, Castelo-Branco C, Palacios S, Haya-Palazuelos J, Ciria-Recasens M, Manasanch J, Pérez-Edo L. Tolerability of different oral iron supplements: a systematic review. Curr Med Res Opin. 2013 Apr;29(4):291-303. Review. PubMed PMID: 23252877.
Martínez Francés A, Leal Martínez-Bujanda J. Efficacy and tolerability of oral iron protein succinylate: a systematic review of three decades of research. Curr Med Res Opin. 2020 Apr;36(4):613-623. doi: 10.1080/03007995.2020.1716702. Epub 2020 Jan 24. PMID: 31944128.
Pereira DI, Couto Irving SS, Lomer MC, Powell JJ. A rapid, simple questionnaire to assess gastrointestinal symptoms after oral ferrous sulphate supplementation. BMC Gastroenterol. 2014 Jun 4;14:103. PubMed PMID: 24899360; PubMed Central PMCID: PMC4082414.
Santiago P. Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: a clinical overview. ScientificWorldJournal. 2012;2012:846824. Review. PubMed PMID: 22654638; PubMed Central PMCID: PMC3354642.
Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015 Feb 20;10(2):e0117383. Review. PubMed PMID: 25700159; PubMed Central PMCID: PMC4336293.
Wu TW, Tsai FP. Comparison of the Therapeutic Effects and Side Effects of Oral Iron Supplements in Iron Deficiency Anemia. Drug Res (Stuttg). 2016 May;66(5):257-61. PubMed PMID: 26697889.
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