{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:04:47Z","timestamp":1792105487952,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Black pepper (Piper nigrum L.) has been employed in medicine (epilepsy, headaches, and diabetes), where its effects are mainly attributed to a nitrogen alkaloid called piperidine (1-(1-[1,3-benzodioxol-5-yl]-1-oxo-2,4 pentenyl) piperidine). Piperine co-administered with vitamins and minerals has improved its absorption. Therefore, this study aimed to describe the impact of the joint administration of iron (Fe) plus black pepper in physically active healthy individuals. Fe is a micronutrient that aids athletic performance by influencing the physiological functions involved in endurance sports by improving the transport, storage, and utilization of oxygen. Consequently, athletes have risk factors for Fe depletion, Fe deficiency, and eventually, anemia, mainly from mechanical hemolysis, gastrointestinal disturbances, and loss of Fe through excessive sweating. Declines in Fe stores have been reported to negatively alter physical capacities such as aerobic capacity, strength, and skeletal muscle recovery in elite athletes. Thus, there is a need to maintain Fe storage, even if Fe intake meets the recommended daily allowance (RDA), and Fe supplementation may be justified in physically active individuals, in states of Fe deficiency, with or without anemia. Females, in particular, should monitor their Fe hematological profile. The recommended oral Fe supplements are ferrous or ferric salts, sulfate, fumarate, and gluconate. These preparations constitute the first line of treatment; however, the high doses administered have gastrointestinal side effects that reduce tolerance and adherence to treatment. Thus, a strategy to counteract these adverse effects is to improve the bioavailability of Fe. Therefore, piperine may benefit the absorption of Fe through its bioavailability enhancement properties. Three research studies of Fe associated with black pepper have reported improvements in parameters related to the metabolism of Fe, without adverse effects. Although more research is needed, this could represent an advance in oral Fe supplementation for physically active individuals.<\/jats:p>","DOI":"10.3390\/nu12061886","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T08:54:50Z","timestamp":1592988890000},"page":"1886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Iron and Physical Activity: Bioavailability Enhancers, Properties of Black Pepper (Bioperine\u00ae) and Potential Applications"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6522-8896","authenticated-orcid":false,"given":"Diego","family":"Fern\u00e1ndez-L\u00e1zaro","sequence":"first","affiliation":[{"name":"Department of Cellular Biology, Histology and PHArmacology, Faculty of Health Sciences, University of Valladolid, Campus de Soria, 42003 Soria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6554-4602","authenticated-orcid":false,"given":"Juan","family":"Mielgo-Ayuso","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Physiology, Faculty of Health Sciences, University of Valladolid, Campus de Soria, 42003 Soria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-2817","authenticated-orcid":false,"given":"Alfredo","family":"C\u00f3rdova Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Physiology, Faculty of Health Sciences, University of Valladolid, Campus de Soria, 42003 Soria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-9777","authenticated-orcid":false,"given":"Jes\u00fas","family":"Seco-Calvo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (IBIOMED), Physiotherapy Department, University of Leon, Visiting Researcher of Basque Country University, Campus de Vegazana, 24071 Leon, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gozzelino, R., and Arosio, P. (2016). Iron Homeostasis in Health and Disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17010130"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1515\/hukin-2015-0066","article-title":"Iron Metabolism in Field Hockey Players During an Annual Training Cycle","volume":"47","author":"Konarski","year":"2015","journal-title":"J. Hum. Kinet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1385\/BTER:89:3:205","article-title":"Status and metabolism of iron in elite sportsmen during a period of professional competition","volume":"89","author":"Vicente","year":"2002","journal-title":"Boil. Trace Element Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mielgo-Ayuso, J., Zourdos, M.C., Calleja-Gonz\u00e1lez, J., C\u00f3rdova, A., Fern\u00e1ndez-L\u00e1zaro, D., and Caballero-Garc\u00eda, A. (2018). Eleven Weeks of Iron Supplementation Does Not Maintain Iron Status for an Entire Competitive Season in Elite Female Volleyball Players: A Follow-Up Study. Nutrients, 10.","DOI":"10.3390\/nu10101526"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1753-4887.1970.tb06150.x","article-title":"Anemia during physical training (sports anemia)","volume":"28","author":"Yoshimura","year":"1970","journal-title":"Nutr. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ijcard.2010.10.139","article-title":"Absolute and functional iron deficiency in professional athletes during training and recovery","volume":"156","author":"Reinke","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1249\/MSS.0000000000000593","article-title":"Recent Advances in Iron Metabolism","volume":"47","author":"Buratti","year":"2015","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_8","first-page":"1592","article-title":"Dietary iron intake and deficiency in elite women volleyball players","volume":"27","author":"Urdampilleta","year":"2013","journal-title":"Nutr. Hosp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1139\/apnm-2014-0500","article-title":"Iron supplementation prevents a decline in iron stores and enhances strength performance in elite female volleyball players during the competitive season","volume":"40","author":"Zourdos","year":"2015","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1249\/JSR.0b013e31829a6f6b","article-title":"Iron Supplementation for Female Athletes","volume":"12","author":"Dellavalle","year":"2013","journal-title":"Curr. Sports Med. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.freeradbiomed.2016.01.016","article-title":"New strategies in sport nutrition to increase exercise performance","volume":"98","author":"Close","year":"2016","journal-title":"Free. Radic. Boil. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev.nutr.23.011702.073139","article-title":"Physiology and molecular biology of dietary iron absorption","volume":"23","author":"Miret","year":"2003","journal-title":"Annu. Rev. Nutr."},{"key":"ref_13","first-page":"14196","article-title":"Iron deficiency in sports\u2014Definition, influence on performance and therapy","volume":"145","author":"Cordes","year":"2015","journal-title":"Swiss Med. Wkly."},{"key":"ref_14","first-page":"14434","article-title":"The treatment of iron deficiency without anaemia (in otherwise healthy persons)","volume":"147","year":"2017","journal-title":"Swiss Med. Wkly."},{"key":"ref_15","unstructured":"C\u00f3rdova Mart\u00ednez, A. (2015). Clinical Evaluation of the Sportsman in the Laboratory, Synthesis. [1st ed.]."},{"key":"ref_16","first-page":"846824","article-title":"Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: A clinical overview","volume":"1","author":"Palacios","year":"2012","journal-title":"Sci. World J."},{"key":"ref_17","first-page":"338","article-title":"Intravenous iron administration for post-operative anaemia management after colorectal cancer surgery in clinical practice: A single-centre, retrospective study","volume":"16","author":"Vives","year":"2018","journal-title":"High Speed Blood Transfus. Equip."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tolkien, Z., Stecher, L., Mander, A.P., Pereira, D., 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_19","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_20","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s12011-010-8813-z","article-title":"Oral Iron Treatment Has a Positive Effect on Iron Metabolism in Elite Soccer Players","volume":"142","author":"Villanueva","year":"2010","journal-title":"Boil. Trace Elem. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2165\/00007256-199826040-00001","article-title":"Iron Supplementation in Athletes","volume":"26","author":"Nielsen","year":"1998","journal-title":"Sports Med."},{"key":"ref_22","first-page":"w14452","article-title":"Healthy persons at risk for iron substitution","volume":"147","author":"Seiler","year":"2017","journal-title":"Swiss Med. Wkly."},{"key":"ref_23","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":"Can. Med. Assoc. J."},{"key":"ref_24","first-page":"99","article-title":"Supplementing iron bioavailability enhanced mung bean","volume":"17","author":"Purushothaman","year":"2008","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/1550-2783-10-55","article-title":"Changes induced by diet and nutritional intake in the lipid profile of female professional volleyball players after 11 weeks of training","volume":"10","author":"Collado","year":"2013","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12970-015-0099-2","article-title":"Iron and the female athlete: A review of dietary treatment methods for improving iron status and exercise performance","volume":"12","author":"Alaunyte","year":"2015","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_27","first-page":"13","article-title":"Advances in sports nutrigemonics: Impact of supplementation on performance in athletes","volume":"75","year":"2019","journal-title":"Ann. Nutr. Metab."},{"key":"ref_28","first-page":"142","article-title":"Biodisponibilidad de Hierro en Humanos","volume":"33","author":"Olivares","year":"2006","journal-title":"Rev. Chil. Nutr."},{"key":"ref_29","first-page":"332","article-title":"Red blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells","volume":"4","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood-2018-06-856500","article-title":"Anemia of inflammation","volume":"133","author":"Weiss","year":"2019","journal-title":"Blood"},{"key":"ref_31","first-page":"301","article-title":"Homeostasis del hierro. Mecanismos de absorci\u00f3n, captaci\u00f3n celular y regulaci\u00f3n","volume":"39","author":"Vittori","year":"2005","journal-title":"Acta Bioquim Clin. Latinoam."},{"key":"ref_32","first-page":"1","article-title":"Influence of physical training on erythrocyte concentrations of iron, phosphorus and magnesium","volume":"17","author":"Grijota","year":"2020","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"C\u00f3rdova, A., Mielgo-Ayuso, J., Fernandez-Lazaro, C., Caballero-Garc\u00eda, A., Roche, E., and Fern\u00e1ndez-L\u00e1zaro, D. (2019). Effect of Iron Supplementation on the Modulation of Iron Metabolism, Muscle Damage Biomarkers and Cortisol in Professional Cyclists. Nutrients, 11.","DOI":"10.3390\/nu11030500"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1139\/apnm-2014-0147","article-title":"Iron and the endurance athlete","volume":"39","author":"Hinton","year":"2014","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mielgo-Ayuso, J., Calleja-Gonz\u00e1lez, J., Urdampilleta, A., Le\u00f3n-Guere\u00f1o, P., C\u00f3rdova, A., Caballero-Garc\u00eda, A., and Fern\u00e1ndez-L\u00e1zaro, D. (2018). Effects of Vitamin D Supplementation on Haematological Values and Muscle Recovery in Elite Male Traditional Rowers. Nutrients, 10.","DOI":"10.3390\/nu10121968"},{"key":"ref_36","first-page":"174","article-title":"Comparative efficacy of two iron oral supplements on hematological profile and sports performance in professional rowers: Evaluation of a BioPerine\u00ae Bioavailability Enhancer","volume":"23","author":"Alfredo","year":"2019","journal-title":"Rev. Esp. Nutr. Hum. Diet."},{"key":"ref_37","first-page":"106","article-title":"Iron bioavailability in food","volume":"49","author":"Ros","year":"1999","journal-title":"Arch. Latinoam. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev.nutr.24.012003.132306","article-title":"New Insights into Erythropoiesis: The Roles of Folate, Vitamin B12, and Iron","volume":"24","author":"Koury","year":"2004","journal-title":"Annu. Rev. Nutr."},{"key":"ref_39","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":"2014","journal-title":"Eur. J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/17425255.2018.1418854","article-title":"Piperine-mediated drug interactions and formulation strategy for piperine: Recent advances and future perspectives","volume":"14","author":"Lee","year":"2017","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_41","first-page":"16","article-title":"Role of piperine as a bioavailability enhancer","volume":"4","author":"Patil","year":"2011","journal-title":"Int. J. Recent Adv. Pharm. Res."},{"key":"ref_42","first-page":"8114","article-title":"Bioperine\u00ae Nature\u2019s own thermonutrient\u00ae and natural bioavailability enhancer","volume":"1","author":"Majeed","year":"1999","journal-title":"Nutr. Publ. Inc."},{"key":"ref_43","unstructured":"Majeed, M., and Prakash, L. (2007). Targeting Optimal Nutrient Absorption with Phytonutrients, Sabinsa Corporation."},{"key":"ref_44","first-page":"18","article-title":"A clinical study on iron deficiency anemia whit bioiron","volume":"4","author":"Majeed","year":"2016","journal-title":"Int. J. Ayurveda PHArma Res."},{"key":"ref_45","first-page":"72","article-title":"An evaluation of bioavailability enhancement of organic elemental iron with BioPerine\u00ae in rabbits","volume":"5","author":"Majeed","year":"2016","journal-title":"Int. J. Pharm. Pharm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1517\/17425255.2011.570332","article-title":"The effects of black pepper on the intestinal absorption and hepatic metabolism of drugs","volume":"7","author":"Han","year":"2011","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0955-2863(99)00074-1","article-title":"Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation","volume":"11","author":"Badmaev","year":"2000","journal-title":"J. Nutr. Biochem."},{"key":"ref_48","first-page":"871","article-title":"Effect of black pepper (Piper nigrum Linn.) and piperine on growth, blood constituents and organ weights in rats","volume":"23","author":"Srinivasan","year":"1981","journal-title":"Nutr. Rep. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0300-483X(86)90048-X","article-title":"Studies on the metabolism of piperine: Absorption, tissue distribution and excretion of urinary conjugates in rats","volume":"40","author":"Bhat","year":"1986","journal-title":"Toxicology"},{"key":"ref_50","first-page":"972","article-title":"Assessment of genotoxic effect of piperine using Salmonella typhimurium and somatic and somatic and germ cells of Swiss albino mice","volume":"46","author":"Karekar","year":"1996","journal-title":"Arzneimittelforschung"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.tox.2003.10.006","article-title":"Immunotoxicological effects of piperine in mice","volume":"196","author":"Dogra","year":"2004","journal-title":"Toxicology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1080\/10408390601062054","article-title":"Black Pepper and its Pungent Principle-Piperine: A Review of Diverse Physiological Effects","volume":"47","author":"Srinivasan","year":"2007","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-L\u00e1zaro, D., Mielgo-Ayuso, J., Seco-Calvo, J., Mart\u00ednez, A.C., Garc\u00eda, A.C., and Fernandez-Lazaro, C. (2020). Modulation of Exercise-Induced Muscle Damage, Inflammation, and Oxidative Markers by Curcumin Supplementation in a Physically Active Population: A Systematic Review. Nutrients, 12.","DOI":"10.3390\/nu12020501"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s11357-019-00077-z","article-title":"Lipotoxicity, aging, and muscle contractility: Does fiber type matter?","volume":"41","author":"Carter","year":"2019","journal-title":"GeroScience"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s11357-019-00109-8","article-title":"Age-dependent effects of caloric restriction on mTOR and ubiquitin-proteasome pathways in skeletal muscles","volume":"41","author":"Chen","year":"2019","journal-title":"GeroScience"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s11357-019-00147-2","article-title":"Magnetic resonance elastography (MRE) shows significant reduction of thigh muscle stiffness in healthy older adults","volume":"42","author":"Kennedy","year":"2019","journal-title":"GeroScience"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/6\/1886\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:42:15Z","timestamp":1760175735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/6\/1886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,24]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["nu12061886"],"URL":"https:\/\/doi.org\/10.3390\/nu12061886","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,24]]}}}