Several different forms of iron are used in supplements. The actual amount of usable "elemental" iron per milligram of iron compound varies depending on the form. For example, 20% of ferrous sulfate is iron and only 12% of ferrous gluconate is iron. Put another way, to get 50 mg of iron, you could take about 250 mg of ferrous sulfate or about 417 mg of ferrous gluconate. Fortunately, the consumer doesn't need to do the calculations -- the manufacturer does this. The usable amount or iron (elemental iron) is what appears in the Supplement Facts panel on the label.
Generally, the least expensive forms of iron are ferrous sulfate, ferrous fumarate, and ferrous gluconate.
If you have trouble tolerating these forms of iron due to gastrointestinal discomfort, consider ferrous bisglycinate, ferrous glycinate, or iron amino acid chelates. (One study showed ferrous bisglycinate (also known as iron bis-glycinate or Ferrochel) to be absorbed two to four times better than ferrous sulfate when given with food (
Layrisse, J Nutr 2000), although it was not absorbed better than ferrous ascorbate when given only with water (
Olivares, Arch Latinoam Nutr 2001). Timed-release iron supplements may also reduce gastrointestinal discomfort, but there is some concern that they reduce iron absorption.
Some supplements contain
heme-iron polypeptide or HIP, which appears to be better absorbed than iron salts, such as ferrous sulfate. This was shown in a study in which both HIP and ferrous sulfate were taken with breakfast although the food ingested may have interfered with ferrous sulfate absorption. Preliminary evidence suggests that HIP may also be better tolerated than ferrous sulfate (
Seligman, Nutrition Research 2000). A branded version of HIP is Proferrin which is found in
Feosol Bifera in this Review, which also includes another iron ingredient, polysaccharide-iron complex or PIC. The absorption of PIC is about the same as ferrous sulfate, but it is apparently tasteless and odorless and may cause less gastric irritation.
A study in infants and young children with nutritional iron-deficiency anemia comparing equal, low-dose amounts of iron from ferrous sulfate and PIC (as NovaFerrum) found ferrous sulfate to increase hemoglobin levels slightly better PIC and completely resolve anemia in more patients compared to PIC (29% vs 6%). Researchers had expected the opposite. There were also fewer reports of diarrhea in these children with ferrous sulfate than with PIC (35% vs 58%), although somewhat more reports of vomiting with ferrous sulfate (58% vs 45%). The doses were given as liquid drops at bedtime (
Powers, JAMA 2017).
Preliminary research has shown that taking
lactoferrin (a protein in milk) with iron may help prevent sports anemia (a form of iron-deficiency anemia) in athletes better than taking iron-only supplements. One study in Japan among female long-distance runners found that taking tablets providing 1.8 grams of lactoferrin plus 6 mg of iron (as ferric pyrophosphate) daily during 8 weeks of training prevented a significant decline in blood levels of iron compared to baseline, while taking iron-only supplements did not (
Koikawa, Biosci Biotechnol Biochem 2008).
Research has also shown that lactoferrin may help treat iron-deficiency anemia in women and children. A study conducted in Egypt among pregnant women with iron-deficiency anemia found that taking 100-mg lactoferrin oral sachets (
MamyVital, Dulex Lab, Cairo, Egypt) twice daily for 4 weeks increased blood levels of iron by 37% compared to iron supplements alone (
Darwish, J Matern Fetal Neonatal Med 2019). The iron content of this lactoferrin supplement was not described by the researchers, but information on the manufacturer's website suggests that each 200-mg dose of
MamyVital provides about 31 mg of iron. A similar product available in the U.S. is
IronSorb + Lactoferrin by Jarrow Formula, which provides 200 mg of lactoferrin and 18 mg of iron. (Note: This product has not been reviewed by ConsumerLab.com to confirm its ingredients.)
A study in Kenya among 25 infants (average age 4 months), most of whom were iron deficient, found that eating maize porridge fortified with 1.5 mg of iron (as ferrous sulfate) and 1.4 grams of apolactoferrin (a form of lactoferrin with minimal iron) increased iron absorption by 56% compared to eating the iron-fortified meal without lactoferrin. However, eating a meal fortified with lactoferrin as holo-lactoferrin (a form of lactoferrin that is saturated with iron) increased iron levels only as effectively as eating the meal fortified with iron as ferrous sulfate, suggesting no added benefit (Mikulic, J Nutr 2020). Holo-lactoferrin is not the form of lactoferrin included in most lactoferrin supplements available in the U.S. For more information about lactoferrin, particularly its effects on the immune system, see our answer to the question: What is lactoferrin and will it really strengthen my immune system?>
Another form,
carbonyl iron, may present a reduced risk of harm in an accidental overdose. Carbonyl iron, consequently, is the ingredient many children's supplements contain and may be preferred by parents of small children. However, carbonyl iron requires adequate stomach acid for absorption. Therefore, it should be taken with food and not used with medications that reduce stomach acid.
Injectable iron also is available under the supervision of a health professional.
Taking iron supplements with food may also help avoid gastric upset, although it may also decrease iron absorption. Some experts suggest taking iron with a vitamin C-rich food to boost iron absorption and offset this effect. In fact, some iron supplements contain vitamin C as an added ingredient to aid absorption, but some research suggests that it
may not make a difference.
Constipation can be a side-effect of oral iron supplementation, especially when taken in higher doses (
Fei, Clinical Correlations 2015). Ferrous and ferrous salts (ferrous sulfate, ferrous gluconate, ferrous fumarate and ferrous glycinate sulfate) have been found to have similar incidence of constipation when compared in a clinical study (
Hallberg, Acta Med Scand Suppl 1966). However,
heme iron polypeptides, carbonyl iron, iron amino-acid chelates, and PIC may have a lower incidence of gastrointestinal side-effects than ferrous or ferric salts (
NIH Iron Fact Sheet 2016).
Iron protein succinylate has also been found to have a slightly lower incidence of constipation and less gastric irritation. Long term, it may result in somewhat greater improvement in iron measurements in the body than ferrous sulfate (
Liquori, Int J Pharmacol Ther Toxicol 1993). Iron protein succinylate is the form found in
Life Extension Iron Protein Plus in this Review.
Rarely, severe constipation due to iron supplementation may interfere with the intestine's ability to properly contract (to move waste through the body), leading to bowel obstruction, as was reported in a 55-year-old women one week after she began taking iron pills to treat iron deficiency anemia. Increasing dietary fiber intake and/or using stool softeners can help to prevent constipation when taking iron supplements (Parvataneni, Cureus 2020).
What to avoid when taking
Remember that many antacids can decrease iron absorption, and the dose and duration of use of certain antacids may increase the risk of iron deficiency.
For example, taking 20 mg or more daily of a proton pump inhibitor (PPI) drug such as omeprazole (Prilosec), esomeprazole (Nexium) or lansoprazole (Prevacid) for more than one year was associated with 3.6 times the risk of iron deficiency, while "intermittent use" of PPIs during the same time period was associated with a 50% increased risk of deficiency, compared to no use of PPIs, according to an analysis of over 50,000 people in the United Kingdom (
Tran-Duy, J Intern Med 2018). Certain foods and beverages, including soy protein, coffee, eggs, whole-grain cereals and breads, and spinach, can also reduce iron absorption, as can tea (
Gillooly, Br J Nutr 1983;
Hurrell, Am J Clin Nutr 2010). A small study in England showed that consuming about one cup of brewed black tea with an iron containing meal reduced the amount of iron normally absorbed by 37%. However, consuming tea one hour after the meal had no effect on iron absorption (
Fuzi, Am J Clin Nutr 2017).
Iron absorption also can be reduced by high doses of other minerals, such as zinc, manganese, magnesium or copper. When consuming one of these foods or high-dose mineral supplements, wait 2 hours to take your iron supplement. Calcium is particularly prone to inhibiting iron absorption: A study showed that taking a calcium supplement (300 mg or 600 mg of calcium) at the same time as taking an iron supplement reduced iron absorption by as much as 62%. Calcium similarly reduced iron absorption from food (
Cook, Am J Clin Nutr 1991). The problem can be avoided by taking a calcium supplement at least 2 hours apart from taking an iron supplement or consuming an iron-containing meal. This interaction is not likely to be a significant problem with lower doses of calcium (under 200 mg) or for people who are not prone to iron deficiency. Be aware that some
multivitamins for women (who are most at-risk for iron deficiency if they have not yet gone through menopause) contain 500 mg or more of calcium.