The Iron Paradox: Discrepancies in Iron Chemical Forms Found in Prenatal Supplements and Tested in Clinical Trials
Authors: Saldanha Leila , Dwyer Johanna , Brown LaVerne , Andrews Karen , Gusev Pavel , Pehrsson Pamela 
Published: November 2023

The risk of anemia among pregnant women in the US remains high and dietary intake of iron from food is low. An estimated 17% of pregnant women according to the WHO are anemic and 96% of pregnant women according to the 2015–20 Dietary Guidelines Advisory Committee have iron intakes from food and beverages below 22 mg/d, which is the EAR for iron. Iron‐containing prenatal supplements are routinely recommended and an estimated 70% of women use supplements during pregnancy. Although it is known that the absorption and tissue uptake of iron varies depending on the iron dose and compounds used, little is known about the characteristics of prenatal supplements in these regards. Our objective was to identify and compare the chemical formula of compounds and amount of iron used in prenatal supplements, with those reported in clinical trials. We extracted label information from the 82 prescription (P) and 132 nonprescription (NP) prenatal supplements available in the Dietary Supplement Label Database (DSLD) and DailyMed and compared it with 70 NP products purchased in 2009–10 and 31 P products purchased in 2016 for our Dietary Supplement Ingredient Database (DSID) studies. We identified the chemical form and amount used in the 61 clinical trials reported in the 2015 Cochrane Database of Systematic Review of daily oral iron supplementation during pregnancy. Most (94%) of the prenatal supplements contained iron. The mean and most frequently labeled amount of iron in the P and NP prenatal supplements was approximately 27 mg, with a labeled dose ranging from 9 to 90 mg/d. In contrast, the amount of iron reported in clinical trials ranged between 9 – 900 mg/d. Of the 295 iron‐containing P and NP prenatal supplements in the DSLD, DailyMed, and DSID, only one P purchased in 2016 contained ferrous sulfate; 48% contained ferrous fumarate (60% of the P and 44% of the NP in DSLD and DailyMed, and 52% of the P and 39 % of the NP in the DSID studies). In contrast, 10% and 59% of the Cochrane clinical trials review reported ferrous fumarate and ferrous sulfate as the source of iron. The paradox is while ferrous sulfate was the most commonly used form of iron reported in clinical trials in the US and globally, prenatal supplements sold in the US rarely contain it. A 1980 Select Committee on GRAS Substances report (SCOGS‐35) stated that ferrous fumarate in food was absorbed as well as ferrous sulfate and had side effects similar to ferrous sulfate in normal human subjects. However, ferrous fumarate had less acute toxicity (in animals) and its effects in dietary supplements may be different from foods. Other forms of iron found in prenatal supplements (amino acid iron chelates) were not evaluated in the SCOGS report. Further research is needed to determine the bioavailability of these compounds in supplements to help explain another iron paradox, whether the high incidence of anemia, despite the high supplement usage during pregnancy, is due to iron deficiency.Support or Funding InformationOffice of Dietary Supplements, NIH