{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T14:16:44Z","timestamp":1762957004777,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Flavors &amp; Fragrances Inc. (IFF)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral supplementation with AB-Fortis\u00ae, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg\/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints\/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.<\/jats:p>","DOI":"10.3390\/ijms232012282","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T02:29:46Z","timestamp":1665973786000},"page":"12282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tolerability of Oral Supplementation with Microencapsulated Ferric Saccharate Compared to Ferrous Sulphate in Healthy Premenopausal Woman: A Crossover, Randomized, Double-Blind Clinical Trial"],"prefix":"10.3390","volume":"23","author":[{"given":"Marina","family":"Friling","sequence":"first","affiliation":[{"name":"IFF Health, Migdal Haemeq 23106, Israel"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1021-5385","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"Garc\u00eda-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Health Science Department, Campus de los Jer\u00f3nimos, Universidad Cat\u00f3lica San Antonio de Murcia UCAM, 30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-7225","authenticated-orcid":false,"given":"Tania","family":"Perrinjaquet-Moccetti","sequence":"additional","affiliation":[{"name":"IFF Health, 8820 W\u00e4denswil, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-9477","authenticated-orcid":false,"given":"Desir\u00e9e","family":"Victoria-Montesinos","sequence":"additional","affiliation":[{"name":"Health Science Department, Campus de los Jer\u00f3nimos, Universidad Cat\u00f3lica San Antonio de Murcia UCAM, 30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-9075","authenticated-orcid":false,"given":"Silvia","family":"P\u00e9rez-Pi\u00f1ero","sequence":"additional","affiliation":[{"name":"Health Science Department, Campus de los Jer\u00f3nimos, Universidad Cat\u00f3lica San Antonio de Murcia UCAM, 30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2952-4783","authenticated-orcid":false,"given":"Mar\u00eda Salud","family":"Abell\u00e1n-Ruiz","sequence":"additional","affiliation":[{"name":"Health Science Department, Campus de los Jer\u00f3nimos, Universidad Cat\u00f3lica San Antonio de Murcia UCAM, 30107 Murcia, Spain"}]},{"given":"Antonio J.","family":"Luque-Rubia","sequence":"additional","affiliation":[{"name":"Health Science Department, Campus de los Jer\u00f3nimos, Universidad Cat\u00f3lica San Antonio de Murcia UCAM, 30107 Murcia, Spain"}]},{"given":"Ana Isabel","family":"Garc\u00eda-Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Health Science Department, Campus de los Jer\u00f3nimos, Universidad Cat\u00f3lica San Antonio de Murcia UCAM, 30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-1927","authenticated-orcid":false,"given":"Fernando","family":"C\u00e1novas","sequence":"additional","affiliation":[{"name":"Health Science Department, Campus de los Jer\u00f3nimos, Universidad Cat\u00f3lica San Antonio de Murcia UCAM, 30107 Murcia, Spain"}]},{"given":"Eran","family":"Ivanir","sequence":"additional","affiliation":[{"name":"IFF Health, Migdal Haemeq 23106, Israel"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/ajh.1114","article-title":"Iron Absorption: Relative Importance of Iron Transport Pathways","volume":"67","author":"Conrad","year":"2001","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"118535","DOI":"10.1016\/j.bbamcr.2019.118535","article-title":"Iron Homeostasis and Oxidative Stress: An Intimate Relationship","volume":"1866","author":"Galaris","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_3","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. Off. J. Isfahan Univ. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood-2018-05-815944","article-title":"Iron Deficiency","volume":"133","author":"Camaschella","year":"2019","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1079\/BJN20051493","article-title":"Impact of Menstrual Blood Loss and Diet on Iron Deficiency among Women in the UK","volume":"94","author":"Harvey","year":"2005","journal-title":"Br. J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7631306","DOI":"10.1155\/2019\/7631306","article-title":"Dietary Iron Intake in Women of Reproductive Age in Europe: A Review of 49 Studies from 29 Countries in the Period 1993\u20132015","volume":"2019","author":"Milman","year":"2019","journal-title":"J. Nutr. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"de Lourdes Samaniego-Vaesken, M., Partearroyo, T., Olza, J., Aranceta-Bartrina, J., Gil, \u00c1., Gonz\u00e1lez-Gross, M., Ortega, R.M., Serra-Majem, L., and Varela-Moreiras, G. (2017). Iron Intake and Dietary Sources in the Spanish Population: Findings from the ANIBES Study. Nutrients, 9.","DOI":"10.3390\/nu9030203"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3945\/cdn.116.000042","article-title":"The Impact of Tannin Consumption on Iron Bioavailability and Status: A Narrative Review","volume":"1","author":"Delimont","year":"2017","journal-title":"Curr. Dev. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1461S","DOI":"10.3945\/ajcn.2010.28674F","article-title":"Iron Bioavailability and Dietary Reference Values","volume":"91","author":"Hurrell","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_10","unstructured":"World Health Organization (2022, August 02). Anaemia. Available online: https:\/\/www.who.int\/health-topics\/anaemia#tab=tab_1."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a011866","DOI":"10.1101\/cshperspect.a011866","article-title":"Iron Deficiency Anemia: A Common and Curable Disease","volume":"3","author":"Miller","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Skolmowska, D., and G\u0142\u0105bska, D. (2019). Analysis of Heme and Non-Heme Iron Intake and Iron Dietary Sources in Adolescent Menstruating Females in a National Polish Sample. Nutrients, 11.","DOI":"10.3390\/nu11051049"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3945\/ajcn.111.031500","article-title":"Effect of Iron-Fortified Foods on Hematologic and Biological Outcomes: Systematic Review of Randomized Controlled Trials","volume":"96","author":"Gera","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1080\/10408398.2021.1876623","article-title":"Iron Supplementation and Iron-Fortified Foods: A Review","volume":"62","author":"Man","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_16","unstructured":"World Health Organization (2022, August 02). Guideline: Iron Supplementation in Postpartum Women. Available online: http:\/\/apps.who.int\/iris\/handle\/10665\/249242."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1185\/03007995.2012.761599","article-title":"Tolerability of Different Oral Iron Supplements: A Systematic Review","volume":"29","author":"Palacios","year":"2013","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-0500-4-444","article-title":"Daily versus Intermittent Iron Supplementation in Pregnant Women","volume":"4","author":"Bouzari","year":"2011","journal-title":"BMC Res. Notes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1447-0756.2004.00223.x","article-title":"Daily versus Intermittent Iron Supplementation in Pregnant Women: Hematological and Pregnancy Outcome","volume":"30","author":"Mukhopadhyay","year":"2004","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_21","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. Aspects Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1590\/S0102-311X2009000600005","article-title":"Adherence and Side Effects of Three Ferrous Sulfate Treatment Regimens on Anemic Pregnant Women in Clinical Trials","volume":"25","author":"Filho","year":"2009","journal-title":"Cad. de Saude Publica"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3390\/microbiolres12020033","article-title":"Oral Iron Supplementation\u2014Gastrointestinal Side Effects and the Impact on the Gut Microbiota","volume":"12","author":"Bloor","year":"2021","journal-title":"Microbiol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1111\/j.1365-2621.2011.02703.x","article-title":"Efficiency of Novel Iron Microencapsulation Techniques: Fortification of Milk","volume":"46","author":"Abbasi","year":"2011","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bryszewska, M.A. (2019). Comparison Study of Iron Bioaccessibility from Dietary Supplements and Microencapsulated Preparations. Nutrients, 11.","DOI":"10.3390\/nu11020273"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"806S","DOI":"10.1093\/jn\/132.4.806S","article-title":"Fortification: Overcoming Technical and Practical Barriers","volume":"132","author":"Hurrell","year":"2002","journal-title":"J. Nutr."},{"key":"ref_27","unstructured":"World Health Organization (2022, August 02). Guidelines on Food Fortification with Micronutrients. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/43412."},{"key":"ref_28","unstructured":"Nguyen, M., and Tadi, P. (2022). Iron Supplementation, StatPearls."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.3945\/ajcn.114.103366","article-title":"Guidelines on the Diagnosis and Treatment of Iron Deficiency across Indications: A Systematic Review","volume":"102","author":"Williet","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0140-6736(07)61235-5","article-title":"Nutritional Iron Deficiency","volume":"370","author":"Zimmermann","year":"2007","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/10245330500093419","article-title":"Divalent Metal Transporter 1","volume":"10","author":"Mims","year":"2005","journal-title":"Hematology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.freeradbiomed.2018.07.020","article-title":"DMT1 and Iron Transport","volume":"133","author":"Yanatori","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1080\/10408398.2019.1630599","article-title":"Mechanism and Intervention Measures of Iron Side Effects on the Intestine","volume":"60","author":"Qi","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1007\/s13197-017-2729-y","article-title":"Recovery from Dietary Iron Deficiency Anaemia in Rats by the Intake of Microencapsulated Ferric Saccharate","volume":"54","author":"Santas","year":"2017","journal-title":"J. Food Sci. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00394-013-0565-z","article-title":"Comparative Study of the Oral Absorption of Microencapsulated Ferric Saccharate and Ferrous Sulfate in Humans","volume":"53","author":"Contreras","year":"2014","journal-title":"Eur. J. Nutr."},{"key":"ref_36","unstructured":"World Health Organization (2022, August 02). Guideline: Daily Iron Supplementation in Adult Women and Adolescent Girls. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/204761."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pereira, D.I.A., Couto Irving, S.S., Lomer, M.C.E., and Powell, J.J. (2014). A Rapid, Simple Questionnaire to Assess Gastrointestinal Symptoms after Oral Ferrous Sulphate Supplementation. BMC Gastroenterol., 14.","DOI":"10.1186\/1471-230X-14-103"},{"key":"ref_38","unstructured":"Guideline ICH Harmonised (2015). Integrated Addendum to ICH E6 (R1): Guideline for Good Clinical Practice E6 (R2). Curr. Step, 2, 1\u201360."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects","volume":"310","author":"Association","year":"2013","journal-title":"JAMA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"920","DOI":"10.3109\/00365529709011203","article-title":"Stool Form Scale as a Useful Guide to Intestinal Transit Time","volume":"32","author":"Lewis","year":"1997","journal-title":"Scand. J. Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12282\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:54:01Z","timestamp":1760144041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":40,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms232012282"],"URL":"https:\/\/doi.org\/10.3390\/ijms232012282","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,10,14]]}}}