{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:42:06Z","timestamp":1787730126020,"version":"build-2784847793"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T00:00:00Z","timestamp":1685750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MegaFood"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>(1) Background: Iron deficiency without anemia (IDWA) is a prevalent health concern in premenopausal women. Oral supplementation of iron may be a viable solution to improve blood-iron status in women; however, the effects of a high-dose iron-supplement regimen have been associated with gastrointestinal side effects. Therefore, the purpose of the present study was to evaluate the effectiveness of a low-dose liquid fermented iron-bisglycinate supplement (LIS) on improving blood-iron status in premenopausal women with IDWA without increasing constipation or gastrointestinal distress. (2) Methods: 85 premenopausal women with IDWA (ferritin &lt; 70 ng\/dL and hemoglobin &gt; 11.0 g\/dL) took a LIS (27 mg) or a placebo (PLA) for 8 weeks. Blood draws were taken at Wk0 and Wk8 of the study to measure serum-iron markers. In addition, surveys of gastrointestinal distress were administered at Wk0, Wk4, and Wk8 while the profile of mood states (POMS) was surveyed at Wk0 and Wk8. (3) Results: Compared to the placebo, the LIS was able to increase serum ferritin (p = 0.03), total serum iron (p = 0.03), and mean corpuscular volume (p = 0.02), while exhibiting no significant interaction in subjective gastrointestinal distress (p &gt; 0.05). No significant effects were detected for POMS (p &gt; 0.05). (4) Conclusions: Supplementing with LIS appears to improve blood-iron status without causing significant gastrointestinal distress in premenopausal women with IDWA.<\/jats:p>","DOI":"10.3390\/nu15112620","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T02:18:29Z","timestamp":1685931509000},"page":"2620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Assessment of the Efficacy of a Low-Dose Iron Supplement in Restoring Iron Levels to Normal Range among Healthy Premenopausal Women with Iron Deficiency without Anemia"],"prefix":"10.3390","volume":"15","author":[{"given":"Matthew W.","family":"Stefan","sequence":"first","affiliation":[{"name":"The Applied Science and Performance Institute, Research Division, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Gundermann","sequence":"additional","affiliation":[{"name":"MegaFood, Manchester, NH 03103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2018-9229","authenticated-orcid":false,"given":"Matthew H.","family":"Sharp","sequence":"additional","affiliation":[{"name":"The Applied Science and Performance Institute, Research Division, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke A.","family":"Jennings","sequence":"additional","affiliation":[{"name":"The Applied Science and Performance Institute, Research Division, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raad H.","family":"Gheith","sequence":"additional","affiliation":[{"name":"The Applied Science and Performance Institute, Research Division, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Lowery","sequence":"additional","affiliation":[{"name":"The Applied Science and Performance Institute, Research Division, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tieraona","family":"LowDog","sequence":"additional","affiliation":[{"name":"Medicine Lodge Ranch, Pecos, NM 87552, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somsuvra B.","family":"Ghatak","sequence":"additional","affiliation":[{"name":"MegaFood, Manchester, NH 03103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Barbosa","sequence":"additional","affiliation":[{"name":"MegaFood, Manchester, NH 03103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"The Applied Science and Performance Institute, Research Division, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.18773\/austprescr.2021.052","article-title":"Non-Anaemic Iron Deficiency","volume":"44","author":"Balendran","year":"2021","journal-title":"Aust. Prescr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.7861\/clinmed.2020-0582","article-title":"Iron Deficiency without Anaemia: A Diagnosis That Matters","volume":"21","author":"Sallam","year":"2021","journal-title":"Clin. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/ccr3.1529","article-title":"Iron Deficiency without Anemia\u2014A Clinical Challenge","volume":"6","author":"Soppi","year":"2018","journal-title":"Clin. Case Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/bjh.12311","article-title":"British Committee for Standards in Haematology Guideline for the Laboratory Diagnosis of Functional Iron Deficiency","volume":"161","author":"Thomas","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2165\/00007256-199927040-00003","article-title":"Anaemia and Iron Deficiency in Athletes. Practical Recommendations for Treatment","volume":"27","author":"Chatard","year":"1999","journal-title":"Sports Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1182\/blood.V89.3.1052","article-title":"Serum Transferrin Receptor and Its Ratio to Serum Ferritin in the Diagnosis of Iron Deficiency","volume":"89","author":"Punnonen","year":"1997","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1503\/cmaj.110950","article-title":"Effect of Iron Supplementation on Fatigue in Nonanemic Menstruating Women with Low Ferritin: A Randomized Controlled Trial","volume":"184","author":"Vaucher","year":"2012","journal-title":"CMAJ"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Soppi, E. (2022). Iron Deficiency in the Absence of Anemia\u2014A Common, Complex and Challenging Disease to Treat. Med. Res. Arch., 10.","DOI":"10.18103\/mra.v10i10.3224"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1136\/bmj.326.7399.1124","article-title":"Iron Supplementation for Unexplained Fatigue in Non-Anaemic Women: Double Blind Randomised Placebo Controlled Trial","volume":"326","author":"Verdon","year":"2003","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.18773\/austprescr.2016.069","article-title":"Correcting Iron Deficiency","volume":"39","author":"Bromley","year":"2016","journal-title":"Aust. Prescr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2161-038X.1000187","article-title":"Iron Deficiency Anemia among Women of Reproductive Age, an Important Public Health Problem: Situation Analysis","volume":"5","author":"Mawani","year":"2016","journal-title":"Reprod. Syst. Sex. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/jhn.12213","article-title":"Gender Differences in Dietary Intakes: What Is the Contribution of Motivational Variables?","volume":"28","author":"Leblanc","year":"2015","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3324\/haematol.2019.220830","article-title":"Iron Absorption from Supplements Is Greater with Alternate Day than with Consecutive Day Dosing in Iron-Deficient Anemic Women","volume":"105","author":"Stoffel","year":"2020","journal-title":"Haematologica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100865","DOI":"10.1016\/j.mam.2020.100865","article-title":"Oral Iron Supplementation in Iron-Deficient Women: How Much and How Often?","volume":"75","author":"Stoffel","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tolkien, Z., Stecher, L., Mander, A.P., Pereira, D.I.A., and Powell, J.J. (2015). Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117383"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1475-2891-13-71","article-title":"Effect of Supplementation with Ferrous Sulfate or Iron Bis-Glycinate Chelate on Ferritin Concentration in Mexican Schoolchildren: A Randomized Controlled Trial","volume":"13","author":"Duque","year":"2014","journal-title":"Nutr. J."},{"key":"ref_17","first-page":"42","article-title":"Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women","volume":"51","author":"Fujimori","year":"2001","journal-title":"Arch. Latinoam. De. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00394-014-0815-8","article-title":"Iron Bioavailability from Commercially Available Iron Supplements","volume":"54","author":"Christides","year":"2015","journal-title":"Eur. J. Nutr."},{"key":"ref_19","unstructured":"Institute of Medicine Panel on Micronutrients (2001). Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc, National Academies Press."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"768","DOI":"10.3945\/ajcn.112.040626","article-title":"Effect of Iron Intake on Iron Status: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"96","author":"Casgrain","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1477-7525-6-12","article-title":"Reliability and Validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) Questionnaire in Dyspepsia: A Six-Country Study","volume":"6","author":"Kulich","year":"2008","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/apt.14349","article-title":"The PAC-SYM Questionnaire for Chronic Constipation: Defining the Minimal Important Difference","volume":"46","author":"Yiannakou","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_23","first-page":"93","article-title":"Preliminary Evidence for the Reliability and Validity of an Abbreviated Profile of Mood States","volume":"23","author":"Grove","year":"1992","journal-title":"Int. J. Sport Psychol."},{"key":"ref_24","unstructured":"Cumming, G. (2022, December 28). Understanding The New Statistics | Effect Sizes, Confidence Intervals. Available online: https:\/\/www.taylorfrancis.com\/books\/mono\/10.4324\/9780203807002\/understanding-new-statistics-geoff-cumming."},{"key":"ref_25","first-page":"164","article-title":"Review on Iron and Its Importance for Human Health","volume":"19","author":"Abbaspour","year":"2014","journal-title":"J. Res. Med. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"846824","DOI":"10.1100\/2012\/846824","article-title":"Ferrous versus Ferric Oral Iron Formulations for the Treatment of Iron Deficiency: A Clinical Overview","volume":"2012","author":"Santiago","year":"2012","journal-title":"Sci. World J."},{"key":"ref_27","unstructured":"Maner, B.S., and Moosavi, L. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kuragano, T., Joki, N., Hase, H., Kitamura, K., Murata, T., Fujimoto, S., Fukatsu, A., Inoue, T., Itakura, Y., and Nakanishi, T. (2020). Low Transferrin Saturation (TSAT) and High Ferritin Levels Are Significant Predictors for Cerebrovascular and Cardiovascular Disease and Death in Maintenance Hemodialysis Patients. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0236277"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.amjmed.2005.01.065","article-title":"Are We Giving Too Much Iron? Low-Dose Iron Therapy Is Effective in Octogenarians","volume":"118","author":"Rimon","year":"2005","journal-title":"Am. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1136\/gutjnl-2017-314418","article-title":"Prebiotic Galacto-Oligosaccharides Mitigate the Adverse Effects of Iron Fortification on the Gut Microbiome: A Randomised Controlled Study in Kenyan Infants","volume":"66","author":"Paganini","year":"2017","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1136\/gutjnl-2014-307720","article-title":"Iron Fortification Adversely Affects the Gut Microbiome, Increases Pathogen Abundance and Induces Intestinal Inflammation in Kenyan Infants","volume":"64","author":"Jaeggi","year":"2015","journal-title":"Gut"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1093\/ajcn\/69.2.250","article-title":"Oral Ferrous Sulfate Supplements Increase the Free Radical-Generating Capacity of Feces from Healthy Volunteers","volume":"69","author":"Lund","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1093\/jn\/131.11.2928","article-title":"Chronic Exposure to High Levels of Dietary Iron Fortification Increases Lipid Peroxidation in the Mucosa of the Rat Large Intestine","volume":"131","author":"Lund","year":"2001","journal-title":"J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1177\/15648265030244S106","article-title":"Iron Deficiency: Global Prevalence and Consequences","volume":"24","author":"Stoltzfus","year":"2003","journal-title":"Food Nutr. Bull."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/11\/2620\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:48:25Z","timestamp":1760125705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/11\/2620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,3]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["nu15112620"],"URL":"https:\/\/doi.org\/10.3390\/nu15112620","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,3]]}}}