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Iron nanoparticles as food additives and food supplements, regulatory and legislative perspectives

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Abstract

Recently, the use of nanotechnology in food has gained great interest. Iron nanoparticles with unique chemical, physical and structural properties allow their potential use mainly as iron fortifiers, colorants and antimicrobial agents. However, in the market we can find only supplements and food colorants based on iron nanoparticles. Their use in food fortification has so far been focused only on in vitro and in vivo experimental studies, since the toxicological evaluation of these studies has so far been the basis for the proposals of laws and regulations, which are still in an early stage of development. Therefore, the aim of this work was to summarize the use of the different forms of iron nanoparticles (oxides, oxyhydroxides, phosphates, pyrophosphates and sulfates) as food additives and supplements and to resume the perspectives of legislation regarding the use of these types of nanoparticles in the food industry.

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References

  • Ajinkya N, Yu X, Kaithal P, Luo H, Somani P, Ramakrishna S. Magnetic iron oxide nanoparticle (IONP) synthesis to applications: present and future. Materials. 13: 4644 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ali A, Zafar H, Zia M, ul Haq I, Phull AR, Ali JS, Hussain A. Synthesis, characterization, applications, and challenges of iron oxide nanoparticles. Nanotechnology, Science and Applications. 9: 49-67 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alves-Peixoto RR, Fernández-Menéndez S, Fernández-Colomer B, Cadore S, Sanz-Medel A, Fernández-Sánchez ML. Quantitative speciation analysis for the in vivo study of iron metabolism and bioavailability from formula milk fortified with stable isotope enriched iron oxo-hydroxide nanoparticles. Journal Analytical Atomic Spectrometry. 34: 774-781 (2019)

    Article  CAS  Google Scholar 

  • Amenta V, Aschberger K, Arena M, Bouwmeester H, Moniz FB, Brandhoff P, Gottardo S, Marvin HJP, Mech A, Pesudo LQ, Rauscher H, Schoonjans R, Vettori MV, Weigel S, Peters RJ. Regulatory aspects of nanotechnology in the agri/feed/food sector in EU and non-EU countries. Regulatory Toxicology and Pharmacology. 73: 463-476 (2015)

    Article  PubMed  Google Scholar 

  • Ansari SAMK, Ficiarà E, Ruffinatti FA, Stura L, Argenziano M, Abollino O, Cavalli R, Guiot C, D’Agata F. Magnetic iron oxide nanoparticles: synthesis, characterization and functionalization for biomedical applications in the central nervous system. Materials. 12: 465 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anselmo AC, Mitragotri S. Nanoparticles in the clinic. Bioengineering & Translational Medicine. 1: 10-29 (2016)

    Article  Google Scholar 

  • Baumgartner J, Winkler HC, Zandberg L, Tuntipopipat S, Mankong P, Bester C, Hilty F, Zeevaart JR, Gowachirapant S, Zimmermann MB. Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women. Scientific Reports. 12: 2792 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonfanti P, Colombo A, Saibene M, Fiandra L, Armenia I, Gamberoni F, Gornati R, Bernardini G, Mantecca P. Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles. Nanotoxicology, 14: 196-213 (2020)

    Article  CAS  PubMed  Google Scholar 

  • Bonyadian M, Moeini E, Ebrahimnejad H, Askari N, Karimi I. The effect of iron sulfate nanoparticles and their fortified bread on Wistar rats and human cell lines. Journal of Trace Elements in Medicine and Biology. 73: 27005 (2022)

    Article  Google Scholar 

  • Bustamante-Torres M, Romero-Fierro D, Estrella-Nuñez J, Arcentales-Vera B, Chichande-Proaño E, Bucio E. Polymeric composite of magnetite iron oxide nanoparticles and their application in biomedicine: a review. Polymers. 14: 752 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Couto C, Almeida A. Metallic nanoparticles in the food sector: a mini-review. Foods. 11: 402 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Francesco T, Borchard G. A robust and easily reproducible protocol for the determination of size and size distribution of iron sucrose using dynamic light scattering. Journal Pharmaceutical and Biomedical Analysis. 152: 89-93 (2018)

    Article  Google Scholar 

  • Ebrahiminezhad A, Zare-Hoseinabadi A, Sarmah AK, Taghizadeh S, Ghasemi Y, Berenjian A. Plant-mediated synthesis and applications of iron nanoparticles. Molecular Biotechnology. 60: 154-168 (2018)

    Article  CAS  PubMed  Google Scholar 

  • EFSA (European Food Safety Authority), Schoonjans R, Tarazona J. Annual report of the EFSA scientific network of risk assessment of nanotechnologies in food and feed for 2020. EFSA Journal. 18: EN-6502 (2021)

    Google Scholar 

  • EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed). Safety and efficacy of iron oxide black, red and yellow for all animal species. EFSA Journal. 14: 4482 (2016)

    Google Scholar 

  • EFSA Panel on Food Additives and Nutrient Sources added to Food. Scientific opinion on the re‐evaluation of iron oxides and hydroxides (E 172) as food additives. EFSA Journal. 13: 4317 (2015)

    Google Scholar 

  • El-Din TAS, Mohamed MB, Kamel HM, Kader MA. (2010). Magnetite nanoparticles as a single dose treatment for iron deficiency anemia. Egypt. Patent WO2010034319A1

  • Elsayed HH, Al-Sherbini ASAM, Abd-Elhady EE, Ahmed KAEA. Treatment of anemia progression via magnetite and folate nanoparticles in vivo. International Scholarly Research Notices. 2014: 287575 (2014)

    Google Scholar 

  • Fernández JG, Sánchez-González C, Bettmer J, Llopis J, Jakubowski N, Panne U, Montes-Bayón M. Quantitative assessment of the metabolic products of iron oxide nanoparticles to be used as iron supplements in cell cultures. Analytica Chimica Acta. 1039: 24-30 (2018)

    Article  PubMed  Google Scholar 

  • Fernández-Menéndez S, Peixoto RRA, Fernández-Colomer B, Romero MC, Sanz-Medel A, Fernández-Sánchez ML. Searching for enhanced iron fortification of formula milk via nanoparticles and Isotope pattern deconvolution. Spectrochimica Acta Part B: Atomic Spectroscopy. 148: 165-171 (2018)

    Article  Google Scholar 

  • Ferreira LP, Reis CP, Robalo TT, Jorge MEM, Ferreira P, Gonçalves J, Hajalilou A, Cruz MM. Assisted synthesis of coated iron oxide nanoparticles for magnetic hyperthermia. Nanomaterials.12: 1870 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fishbane S, Ganz T, Pratt RD. Ferric pyrophosphate citrate for parenteral administration of maintenance iron: structure, mechanism of action, clinical efficacy and safety. Current Medical Research and Opinion. 38: 1417-1429 (2022)

    Article  CAS  PubMed  Google Scholar 

  • Flores-Cano DA, Checca-Huaman NR, Castro-Merino IL, Pinotti CN, Passamani EC, Litterst FJ, Ramos-Guivar JA. Progress toward room-temperature synthesis and functionalization of iron-oxide nanoparticles. International Journal of Molecular Sciences. 23: 8279 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Food and Agriculture Organization of the United Nations (FAO). Food safety and quality-Joint FAO/WHO expert committee on food additives (JECFA). Available at: https://www.fao.org/food-safety/scientific-advice/jecfa/en/#:~:text=JECFA%20is%20an%20international%20scientific,of%20veterinary%20drugs%20in%20food. Accessed June 06, 2023

  • Fütterer S, Andrusenko I, Kolb U, Hofmeister W, Langguth P. Structural characterization of iron oxide/hydroxide nanoparticles in nine different parenteral drugs for the treatment of iron deficiency anaemia by electron diffraction (ED) and X-ray powder diffraction (XRPD). Journal of Pharmaceutical and Biomedical Analysis. 86: 151-160 (2013)

    Article  PubMed  Google Scholar 

  • Garcia-Fernandez J, Turiel D, Bettmer J, Jakubowski N, Panne U, Rivas LG, Llopis J, González CS, Montes-Bayón M. In vitro and in situ experiments to evaluate the biodistribution and cellular toxicity of ultrasmall iron oxide nanoparticles potentially used as oral iron supplements. Nanotoxicology. 14: 388-403 (2020)

    Article  PubMed  Google Scholar 

  • Ghanbariasad A, Taghizadeh SM, Show PL, Nomanbhay S, Berenjian A, Ghasemi Y, Ebrahiminezhad A. Controlled synthesis of iron oxyhydroxide (FeOOH) nanoparticles using secretory compounds from Chlorella vulgaris microalgae. Bioengineered. 10: 390-396 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghibaudo F, Gerbino E, Hugo AA, Dall’Orto VC, Gomez-Zavaglia A. Fortification of water kefir with magnetite nanoparticles. Food Research International. 149: 110650 (2021)

    Article  CAS  PubMed  Google Scholar 

  • Ghosh R, Arcot J. Fortification of foods with nano-iron: its uptake and potential toxicity: current evidence, controversies, and research gaps. Nutrition Reviews. 80: 1974-1984 (2022)

    Article  PubMed  Google Scholar 

  • Góral D, Marczuk A, Góral-Kowalczyk M, Koval I, Andrejko D. Application of iron nanoparticle-based materials in the food industry. Materials. 16: 780 (2023)

    Article  PubMed  PubMed Central  Google Scholar 

  • Grieger KD, Hansen SF, Mortensen NP, Cates S, Kowalcyk B. International implications of labeling foods containing engineered nanomaterials. Journal of Food Protection. 79: 830-842 (2016)

    Article  CAS  PubMed  Google Scholar 

  • Gudkov SV, Burmistrov DE, Serov DA, Rebezov MB, Semenova AA, Lisitsyn AB. Do iron oxide nanoparticles have significant antibacterial properties?. Antibiotics. 10: 884 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen SF, Heggelund LR, Besora, PR, Mackevica A, Boldrin A, Baun A. Nanoproducts–what is actually available to European consumers?. Environmental Science: Nano. 3: 169-180 (2016)

    Google Scholar 

  • He X, Hwang HM. Nanotechnology in food science: functionality, applicability, and safety assessment. Journal of Food and Drug Analysis. 24: 671-681 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang H, Feng W, Chen Y, Shi J. Inorganic nanoparticles in clinical trials and translations. Nano Today. 35: 100972 (2020)

    Article  CAS  Google Scholar 

  • Kim HJ, Bae SH, Kim HJ, Kim KM, Song JH, Go MR, Yu J, Oh JM,Choi SJ. Cytotoxicity, intestinal transport, and bioavailability of dispersible iron and zinc supplements. Frontiers in Microbiology, 8: 749 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim KY, Lee JH, Hosseindoust A, Kim MJ, Mun JY, Moturi J, Tajudeen H, Kim TG, Chae BJ. Enhancement of ferrous sulfate absorption using nano-technology in broiler chickens. Livestock Science. 260: 104869 (2022)

    Article  Google Scholar 

  • Koo JS, Lee SY, Azad MOK, Kim M, Hwang SJ, Nam S, Kim S, Chae BJ, Kang WS, Cho HJ. Development of iron (II) sulfate nanoparticles produced by hot-melt extrusion and their therapeutic potentials for colon cancer. International Journal of Pharmaceutics. 558: 388-395 (2019)

    Article  CAS  PubMed  Google Scholar 

  • Kumar P, Mahajan P, Kaur R, Gautam S. Nanotechnology and its challenges in the food sector: a review. Materials Today Chemistry. 17: 100332 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar SB, Arnipalli SR, Mehta P, Carrau S, Ziouzenkova O. Iron deficiency anemia: efficacy and limitations of nutritional and comprehensive mitigation strategies. Nutrients. 14: 2976 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Macdougall IC, Comin-Colet J, Breymann C, Spahn DR, Koutroubakis IE. Iron sucrose: a wealth of experience in treating iron deficiency. Advances in Therapy. 37: 1960-2002 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahmoud MBM, Helmy SHA. (2014). Novel formula of iron-based nanocomposites for rapid and efficient treatment of iron deficiency anemia. Egypt. Patent WO2014/135170A1

  • McClements DJ, Xiao H. Is nano safe in foods? Establishing the factors impacting the gastrointestinal fate and toxicity of organic and inorganic food-grade nanoparticles. NPJ Science of Food. 1: 6 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  • Mohammed NI, Wason J, Mendy T, Nass SA, Ofordile O, Camara F, Baldeh B, Sanyang C, Jallow AT, Hossain I, Faria N, Powell JJ, Prentice AM, Pereira DIA. A novel nano-iron supplement versus standard treatment for iron deficiency anaemias in children 6–35 months (IHAT-GUT trial): a double-blind, randomised, placebo-controlled non inferiority phase II trial in the Gambia. EClinicalMedicine. 56: 101853 (2023)

    Article  PubMed  PubMed Central  Google Scholar 

  • Nikravesh N, Borchard G, Hofmann H, Philipp E, Flühmann B, Wick P. Factors influencing safety and efficacy of intravenous iron-carbohydrate nanomedicines: from production to clinical practice. Nanomedicine: Nanotechnology, Biology and Medicine. 26: 102178 (2020)

    Article  CAS  PubMed  Google Scholar 

  • OCU (Organización de Consumidores y Usuarios de España). E172 Óxidos e hidróxidos de hierro. Available at: https://www.ocu.org/alimentacion/seguridad-alimentaria/calculadora/aditivos/172. Accessed May 08, 2023

  • Pai AB. Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation. Annals of the New York Academy of Sciences. 1407: 17-25 (2017)

    Article  CAS  PubMed  Google Scholar 

  • Patil US, Adireddy S, Jaiswal A, Mandava S, Lee BR, Chrisey DB. In vitro/in vivo toxicity evaluation and quantification of iron oxide nanoparticles. International Journal of Molecular Sciences. 16: 24417-24450 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MP, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S, Shin HS. Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology. 16: 71 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  • Pereira DI, Bruggraber SF, Faria N, Poots LK, Tagmount MA, Aslam MF, Frazer DM, Vulpe CD, Anderson GJ, Powell JJ. Nanoparticulate iron (III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans. Nanomedicine: Nanotechnology, Biology and Medicine. 10: 1877-1886 (2014)

    Article  CAS  PubMed  Google Scholar 

  • Perfecto A, Elgy C, Valsami-Jones E, Sharp P, Hilty F, Fairweather-Tait S. Mechanisms of iron uptake from ferric phosphate nanoparticles in human intestinal Caco-2 cells. Nutrients. 9: 359 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  • Rauscher H, Rasmussen K, Sokull‐Klüttgen B. Regulatory aspects of nanomaterials in the EU. Chemie Ingenieur Technik. 89: 224-231 (2017)

    Article  CAS  Google Scholar 

  • Rayamajhi S, Wilson S, Aryal S, DeLong R. Biocompatible FePO4 nanoparticles: drug delivery, RNA stabilization, and functional activity. Nanoscale Research Letters. 16: 169 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Razack SA, Suresh A, Sriram S, Ramakrishnan G, Sadanandham S, Veerasamy M, Nagalamadaka RB, Sahadevan R. Green synthesis of iron oxide nanoparticles using Hibiscus rosa-sinensis for fortifying wheat biscuits. SN Applied Sciences. 2: 898 (2020)

    Article  Google Scholar 

  • Rossi L, Velikov KP, Philipse AP. Colloidal iron (III) pyrophosphate particles. Food Chemistry. 151: 243-247 (2014)

    Article  CAS  PubMed  Google Scholar 

  • Sahoo M, Vishwakarma S, Panigrahi C, Kumar J. Nanotechnology: current applications and future scope in food. Food Frontiers. 2: 3-22 (2021)

    Article  Google Scholar 

  • Saldívar-Tanaka L. Regulando la nanotecnología. Mundo nano revista interdisciplinaria en nanociencias y nanotecnología. 12: 37-57 (2019)

    Google Scholar 

  • Santillán-Urquiza E, Méndez-Rojas MA, Vélez-Ruiz JF. Fortification of yogurt with nano and micro sized calcium, iron and zinc, effect on the physicochemical and rheological properties. LWT-Food Science and Technology. 80: 462-469 (2017)

    Article  Google Scholar 

  • Schaefer B, Meindl E, Wagner S, Tilg H, Zoller H. Intravenous iron supplementation therapy. Molecular Aspects of Medicine. 75: 100862 (2020)

    Article  CAS  PubMed  Google Scholar 

  • Shepherd SJ, Issadore D, Mitchell MJ. Microfluidic formulation of nanoparticles for biomedical applications. Biomaterials. 274: 120826 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shukla A, Dasgupta N, Ranjan S, Singh S, Chidambram R. Nanotechnology towards prevention of anaemia and osteoporosis: from concept to market. Biotechnology & Biotechnological Equipment. 31: 863-879 (2017)

    Article  CAS  Google Scholar 

  • Singh K, Chopra DS, Singh D, Singh N. Nano-formulations in treatment of iron deficiency anaemia: an overview. Clinical Nutrition ESPEN. 52: 12-19 (2022)

    Article  PubMed  Google Scholar 

  • Song Z, Wu H, Niu C, Wei J, Zhang Y, Yue T. Application of iron oxide nanoparticles@ polydopamine-nisin composites to the inactivation of Alicyclobacillus acidoterrestris in apple juice. Food Chemistry. 287: 68-75 (2019)

    Article  CAS  PubMed  Google Scholar 

  • Srinivasu BY, Mitra G, Muralidharan M, Srivastava D, Pinto J, Thankachan P, Suresh S, Shet A, Rao S, Ravikumar G, Thomas TS, Kurpad AV, Mandal AK. Beneficiary effect of nanosizing ferric pyrophosphate as food fortificant in iron deficiency anemia: evaluation of bioavailability, toxicity and plasma biomarker. RSC Advances. 5: 61678-61687 (2015)

    Article  CAS  Google Scholar 

  • Sundararajan S, Rabe H. Prevention of iron deficiency anemia in infants and toddlers. Pediatric Research. 89: 63-73 (2021)

    Article  PubMed  Google Scholar 

  • U.S. Code of Federal Regulations, Title 21, Section 73.1200 Synthetic iron oxide. Available at: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-B/section-73.1200 Accessed May 23, 2023

  • Vargas-Ortiz JR, Gonzalez C, Esquivel K. Magnetic iron nanoparticles: synthesis, surface enhancements, and biological challenges. Processes. 10: 2282 (2022)

    Article  CAS  Google Scholar 

  • Von-Moos LM, Schneider M, Hilty FM, Hilbe M, Arnold M, Ziegler N, Mato DS, Winkler H, Tarik M, Ludwing C, Naegeli H, Langhans W, Zimmermann MB, Sturla SJ, Trantakis IA. Iron phosphate nanoparticles for food fortification: biological effects in rats and human cell lines. Nanotoxicology. 11: 496-506 (2017)

    Article  CAS  PubMed  Google Scholar 

  • Voss L, Hsiao IL, Ebisch M, Vidmar J, Dreiack N, Böhmert L, Stock V, Braeuning A, Loeschner K, Laux P, Thünemann AF, Lampen A, Sieg H. The presence of iron oxide nanoparticles in the food pigment E172. Food Chemistry. 327: 127000 (2020)

    Article  CAS  PubMed  Google Scholar 

  • WHO World Health Organization. (2010). International programme on chemical safety. Human health risk assessment toolkit: chemical hazards. IPCS harmonization project document; no.8. WHO Press, Geneva, pp 14-30

  • Yang F, Zhang H, Shao Y, Song H, Liao S, Ren J. Formic acid as additive for the preparation of high-performance FePO4 materials by spray drying method. Ceramics International. 43: 16652-16658 (2017)

    Article  CAS  Google Scholar 

  • Zhang X, Zhang L, Liu H, Cao B, Liu L, Gong W. Structure, morphology, size and application of iron phosphate. Reviews on Advanced Materials Science. 59: 538-552 (2020)

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the Consejo Nacional de Humanidades, Ciencia y Tecnología (CONAHCYT/grant no. 797746) for the grant awarded for this research.

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Chavarría-Fernández, S.M., Jiménez-Alvarado, R., Santos-López, E.M. et al. Iron nanoparticles as food additives and food supplements, regulatory and legislative perspectives. Food Sci Biotechnol 33, 1295–1305 (2024). https://doi.org/10.1007/s10068-024-01518-y

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