Iron deficiency anaemia is the most common nutritional deficiency disorder, contributing to 50 percent of all the anaemias in the world. Dietary changes alone are insufficient for the correction and management of iron deficiency anaemia. Hence, iron supplementation is necessary. Conventional oral iron therapy is limited in many patients because of dose dependent side effects, insufficient absorption, lack of compliance and limitation in various inflammatory conditions. Liposomal iron is a technologically designed, innovative form of iron which due to its differential delivery system ensures higher absorption and bioavailability, greater tolerability and least gastro-intestinal side effects unlike conventional oral iron preparations. This review provides a critical discussion and a comprehensive view based on the author’s review of the medical literature concerning the technology of liposomal iron preparation, mechanism of its absorption, its advantage over conventional iron preparations and clinical evidence on its usage in iron deficient states in pregnancy and certain inflammatory conditions.
References
[1]
Abbaspour, N., Hurrell, R. and Kelishadi, R. (2014) Review on Iron and Its Importance for Human Health. Journal of Research in Medical Sciences, 19, 164-174.
[2]
Barragán-Ibaneza, G., Santoyo-Sánchez, A. and Ramos-Penafiel, C.O. (2016) Iron Deficiency Anaemia. Revista Médica del Hospital General de México, 79, 88-97. https://doi.org/10.1016/j.hgmx.2015.06.008
[3]
World Health Organization and United Nations Children’s Fund (2004) Focusing on Anaemia. https://www.who.int/nutrition/publications/micronutrients/WHOandUNICEF_statement_anaemia/en/
[4]
Ministry of Health and Family Welfare (2016) India Fact Sheet. National Family Health Survey 2015-16 (NFHS-4). http://rchiips.org/nfhs/pdf/NFHS4/India.pdf
[5]
Andrews, N.C. (1999) Disorders of Iron Metabolism. The New England Journal of Medicine, 341, 1986-1995. https://doi.org/10.1056/NEJM199912233412607
[6]
Munoz, M., García-Erce, J.A. and Remacha, á.F. (2011) Disorders of Iron Metabolism. Part II: Iron Deficiency and Iron Overload. Journal of Clinical Pathology, 64, 287-296. https://doi.org/10.1136/jcp.2010.086991
[7]
Yeh, K.Y., Yeh, M., Mims, L. and Glass, J. (2009) Iron Feeding Induces Ferroportin 1 and Hephaestin Migration and Interaction in Rat Duodenal Epithelium. The American Journal of Physiology-Gastrointestinal and Liver Physiology, 296, 55-65. https://doi.org/10.1152/ajpgi.90298.2008
[8]
Theil, E.C, Chen, H., Miranda, C., Janser, H., Elsenhans, B., Núnez, M.T., et al. (2012) Absorption of Iron from Ferritin Is Independent of Heme Iron and Ferrous Salts in Women and Rat Intestinal Segments. The Journal of Nutrition, 142, 478-483. https://doi.org/10.3945/jn.111.145854
[9]
Hunt, J.R., Zito, C.A. and Johnson, L.K. (2009) Body Iron Excretion by Healthy Men and Women. American Journal of Clinical Nutrition, 89, 1792-1798. https://doi.org/10.3945/ajcn.2009.27439
[10]
Nicolas, G., Bennoun, M., Devaux, I., Beaumont, C., Grandchamp, B., Kahn, A., et al. (2001) Lack of Hepcidin Gene Expression and Severe Tissue Iron Overload in Upstream Stimulatory Factor 2 (USF2) Knockout Mice. Proceedings of the National Academy of Sciences of the United States of America, 98, 8780-8785. https://doi.org/10.1073/pnas.151179498
[11]
Lin, L., Valore, E.V., Nemeth, E., Goodnough, J.B., Gabayan, V. and Ganz, T. (2007) Iron Transferrin Regulates Hepcidin Synthesis in Primary Hepatocyte Culture through Hemojuvelin and BMP2/4. Blood, 110, 2182-2189. https://doi.org/10.1182/blood-2007-04-087593
[12]
Nicolas, G., Chauvet, C., Viatte, L., Danan, J.L., Bigard, X., Devaux, I., et al. (2002) the Gene Encoding the Iron Regulatory Peptide Hepcidin Is Regulated by Anemia, Hypoxia, and Inflammation. Journal of Clinical Investigation, 110, 1037-1044. https://doi.org/10.1172/JCI0215686
[13]
Vokurka, M., Krijt, J., Sulc, K. and Necas, E. (2006) Hepcidin mRNA Levels in Mouse Liver Respond to Inhibition of Erythropoiesis. Physiological Research, 55, 667-674.
[14]
Maliken, B.D., Nelson, J.E. and Kowdley, K.V. (2011) The Hepcidin Circuits Act: Balancing Iron and Inflammation. Hepatology, 53, 1764-1766. https://doi.org/10.1002/hep.24267
[15]
De Domenico, I., Ward, D.M. and Kaplan, J. (2007) Hepcidin Regulation: Ironing Out the Detail. Journal of Clinical Investigation, 117, 1755-1758. https://doi.org/10.1172/JCI32701
[16]
National Institute of Nutrition (2010) Nutrient Requirements and Recommended Dietary Allowances for Indians. A Report of the Expert Group of the Indian Council of Medical Research. Indian Council of Medical Research. National Institute of Nutrition, Hyderabad.
[17]
Camaschella, C. (2015) Iron-Deficiency Anemia. The New England Journal of Medicine, 372, 1832-1843. https://doi.org/10.1056/NEJMra1401038
[18]
Danielson, J. (2004) Structure, Chemistry, and Pharmacokinetics of Intravenous Iron Agents. American Society of Nephrology, 15, S93-S98.
[19]
Evans, R.W., Rafique, R., Zarea, A., Rapisarda, C., Cammack, R., Evans, P.J., et al. (2008) Nature of Non-Transferrin-Bound Iron: Studies on Iron Citrate Complexes and the Thalassemic Sera. Journal of Biological Inorganic Chemistry, 13, 57-74. https://doi.org/10.1007/s00775-007-0297-8
[20]
Bhandare, B., Satyanarayana, V. and Kauser, S. (2014) Prescribing Pattern of Iron Preparations in Antenatal Women in a Tertiary Care Hospital. Journal of International Medicine and Dentistry, 1, 23-27
[21]
Stanley, L.S. and Michael, A. (2019) Treatment of Iron Deficiency Anemia in Adults. https://www.uptodate.com/contents/treatment-of-iron-deficiency-anemia-in-adults
[22]
Tolkien, Z., Stecher, L., Mander, A.P., Pereira, D.I. and Powell, J.J. (2015) Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis. PLoS ONE, 10, e0117383. https://doi.org/10.1371/journal.pone.0117383
[23]
Singhal, S.R., Kadian, V., Singh, S. and Ghalaut, V.S. (2015) Comparison of Various Oral Iron Salts in the Treatment of Iron Deficiency Anemia in Pregnancy. Indian Journal of Obstetrics and Gynaecology Research, 2, 155-158. https://doi.org/10.5958/2394-2754.2015.00005.3
[24]
Bregman, D.B., Morris, D., Koch, T.A., He, A. and Goodnough, L.T. (2013) Hepcidin Levels Predict Nonresponsiveness to Oral Iron Therapy in Patients with Iron Deficiency Anemia. American Journal of Hematology, 88, 97-101. https://doi.org/10.1002/ajh.23354
[25]
Moretti, D., Goede, J.S., Zeder, C., Jiskra, M., Chatzinakou, V., Tjalsma, H., et al. (2015) Oral Iron Supplements Increase Hepcidin and Decrease Iron Absorption from Daily or Twice-Daily Doses in Iron-Depleted Young Women. Blood, 126, 1981-1989. https://doi.org/10.1182/blood-2015-05-642223
[26]
Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hani-Fehpour, Y., et al. (2013) Liposome: Classification, Preparation, and Applications. Nanoscale Research Letters, 8, Article No. 102. https://doi.org/10.1186/1556-276X-8-102
[27]
Radhika, M.S., Nair, K.M., Kumar, R.H., Rao, M.V., Ravinder, P., Reddy, C.G., et al. (2011) Micronized Ferric Pyrophosphate Supplied through Extruded Rice Kernels Improves Body Iron Stores in Children: A Double-Blind, Randomized, Placebo-Controlled Midday Meal Feeding Trial in Indian School Children. The American Journal of Clinical Nutrition, 94, 1202-1210. https://doi.org/10.3945/ajcn.110.007179
[28]
Moretti, D., Zimmermann, M.B., Wegmuller, R., Walczyk, T., Zeder, C. and Hurrel, R.F. (2006) Iron Status and Food Matrix Strongly Affect the Relative Bioavailability of Ferric Pyrophosphate in Humans. The American Journal of Clinical Nutrition, 83, 632-638. https://doi.org/10.1093/ajcn.83.3.632
[29]
Kozubek, A., Gubernator, J., Przeworska, E. and Stasiuk, M. (2000) Liposomal Drug Delivery, a Novel Approach: Plarosomes. Acta Biochimica Polonica, 47, 639-649. https://doi.org/10.18388/abp.2000_3985
[30]
Xu, Z., Liu, S.Y., Wang, H.J., Gao, G.F., Yu, P. and Chang, Y.Z. (2014) Encapsulation of Iron in Liposomes Significantly Improved the Efficiency of Iron Supplementation in Strenuously Exercised Rats. Biological Trace Element Research, 162, 181-188. https://doi.org/10.1007/s12011-014-0143-0
[31]
Dra. Francesca Reig Isart (1999) Iron Absorption after Oral Administration of Different Dosage Forms. https://www.kingnature.ch/content/uploads/Estudio-CSIC-Lipofer-1999.pdf
[32]
Plesea-Condratovici, A., Plesea-Condratovici, C., Rosoga, N. and Nedelcu, N. (2015) Efficacy and Tolerability of a Novel Food Supplement (Turbofer®) Containing Microencapsulated Iron in Liposomal Form, in Female Iron Deficiency Anaemia. Progress in Nutrition, 17, 214-219.
[33]
Ding, B.M., Yi, X.Z., Li, L. and Yang, H.L. (2017) Evaluation of Iron Transport from Ferrous Glycinate Liposomes Using Caco-2 Cell Model. African Health Sciences, 17, 933-941. https://doi.org/10.4314/ahs.v17i3.37
[34]
Parisi, F., Fusè, F., Brunetti, M., Mazzocco, M., Berti, C. and Cetin, I. (2017) Effects of Different Regimens of Iron Supplementation on Iron Status and Pregnancy Out-Comes in a Cohort of Healthy Pregnant Women: A Randomized Control Trial. The Journal of Maternal-Fetal & Neonatal Medicine, 30, 1787-1792. https://doi.org/10.1080/14767058.2016.1224841
[35]
Blanco-Rojo, R., Pérez-Granados, A.M., Toxqui, L., González-Vizcayno, C., Delgado, M.A. and Vaquero, M.P. (2011) Efficacy of a Microencapsulated Iron Pyrophosphate-Fortified Fruit Juice: A Randomised, Double-Blind, Placebo-Controlled Study in Spanish Iron-Deficient Women. British Journal of Nutrition, 105, 1652-1659. https://doi.org/10.1017/S0007114510005490
[36]
Pisani, A., Riccio, E., Sabbatini, M., Andreucci, M., Del Rio, A. and Visciano, B. (2015) Effect of Oral Liposomal Iron versus Intravenous Iron for Treatment of Iron Deficiency Anaemia in CKD Patients: A Randomized Trial. Nephrology Dialysis Transplantation, 30, 645-652. https://doi.org/10.1093/ndt/gfu357
[37]
Giordano, G., Mondello, P., Tambaro, R., De Maria, M., D’Amico, F., Sticca, G., et al. (2011) Intravenous Iron Support vs Oral Liposomal Iron Support in Patients with Refractory Anemia Treated with Epo Alpha. Monocentric Prospective Study. Leukemia Research, 35, S137. https://doi.org/10.1016/S0145-2126(11)70343-5
[38]
Giordano, G., Vittorio, S., D’Amico, F., Antonietta, D., De Maria, M., Nicola, P., et al. (2013) Liposomial Iron Has an Anti-Inflammatory Effect and Is Better Than Iron Sulfate in Correction of Anemia of Chronic Inflammatory Disease of Young Women. https://www.artoi.it/wp-content/uploads/2013/11/Abstract_Giordano_Giulio2.pdf
