AUTHOR=Lewis Erin D. , Ortega Edwin F. , Dao Maria Carlota , Barger Kathryn , Mason Joel B. , Leong John M. , Osburne Marcia S. , Magoun Loranne , Nepveux V Felix J. , Chishti Athar H. , Schwake Christopher , Quynh Anh , Gilhooly Cheryl H. , Petty Gayle , Guo Weimin , Matuszek Gregory , Pereira Dora , Reddy Manju , Wang Jifan , Wu Dayong , Meydani Simin N. , Combs Gerald F. 

TITLE=Safe and effective delivery of supplemental iron to healthy adults: a two-phase, randomized, double-blind trial – the safe iron study

JOURNAL=Frontiers in Nutrition

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1230061

DOI=10.3389/fnut.2023.1230061

ISSN=2296-861X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>The safety of novel forms of iron in healthy, iron-replete adults as might occur if used in population-based iron supplementation programs was examined. We tested the hypotheses that supplementation with nanoparticulate iron hydroxide adipate tartrate (IHAT), an iron-enriched <italic>Aspergillus oryzae</italic> product (ASP), or ferrous sulphate heptahydrate (FS) are safe as indicated by erythrocyte susceptibility to malarial infection, bacterial proliferation, and gut inflammation. Responses to FS administered daily or weekly, and with or without other micronutrients were compared.</p></sec><sec id="sec2"><title>Methods</title><p>Two phases of randomized, double-blinded trials were conducted in Boston, MA. Phase I randomized 160 volunteers to six treatments: placebo, IHAT, ASP, FS, and FS plus a micronutrient powder (MNP) administrated daily at 60 mg Fe/day; and FS administered as a single weekly dose of 420 mg Fe. Phase II randomized 86 volunteers to IHAT, ASP, or FS administered at 120 mg Fe/day. Completing these phases were 151 and 77 participants, respectively. The study was powered to detect effects on primary endpoints: susceptibility of participant erythrocytes to infection by <italic>Plasmodium falciparum</italic>, the proliferation potential of selected pathogenic bacteria in sera, and markers of gut inflammation. Secondary endpoints for which the study was not powered included indicators of iron status and gastrointestinal symptoms.</p></sec><sec id="sec3"><title>Results</title><p>Supplementation with any form of iron did not affect any primary endpoint. Regarding secondary endpoints, in Phase I participants taking IHAT more frequently reported abdominal pain (27%, <italic>p</italic> = 0.008) than other iron forms; those taking the weekly FS dose more frequently reported nausea (20%, <italic>p</italic> = 0.009) than the other forms and modes of administration. In phase II, no such differences were observed.</p></sec><sec id="sec4"><title>Discussion</title><p>With respect to the primary endpoints, few differences were found when comparing these forms of iron, indicating that 28 days of 60 or 120 mg/day of IHAT, ASP, or FS may be safe for healthy, iron-replete adults. With respect to other endpoints, subjects receiving IHAT more frequently reported abdominal pain and nausea, suggesting the need for further study.</p></sec><sec id="sec60"><title>Clinical Trial Registration</title><p><ext-link xlink:href="https://clinicaltrials.gov/" ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, NCT03212677; registered: 11 July 2017.</p></sec>