Halal antimicrobials in food: A review on prospects and challenges of antimicrobials from animal sources


  • Muhamad Shirwan Abdullah Sani International islamic University Malaysia (IIUM)
  • Mohammad Aizat Jamaludin International Islamic University Malaysia
  • Nurhidayu Al-Saari International Islamic University Malaysia
  • Azman Azid Universiti Sultan Zainal Abidin (UniSZA)
  • Nur Syatirah Noor Azri International Islamic University Malaysia




Food antimicrobial agents (FAA) provide the first food defence system against pathogens for processed food products. In addition, they function as an antioxidant in preventing colour and taste changes for food safety and quality. Muslim consumers are concerned about the source of FAA which may contain non-permissible ingredients according to Islam including pig and unslaughtered permissible animal sources. They also raise concerns about the increasing risk of toxicity when the FAA is consumed and the possibility of the FAA rendering organoleptic effect on the food. The application of the FAA protects the food from microbial contamination and indirectly combats emerging devastating diseases. Hence, halal FAA (HFAA) can be introduced so that Muslim consumers can accept FAA usage. Generally, HFAA is categorised according to ingredient sources such as animal, plant, bacteria, or synthetic origins. There are doubts on the halal status of animal-origin FAA as the source might be originating from pig, unslaughtered animal, human, or origins which are filthy. The animal-origin FAA shows strong antimicrobial properties against Gram-positive and negative pathogens, as well as toxicity and organoleptic issues. Thus, the FAA should be used within the allowable range. HFAA has become one of the most studied FAAs due to these issues. Many HFAAs are produced from animals without the full verification of halal status. This review presents an overview of the origins and challenges of HFAA production. Furthermore, this study also highlights how FAA could be verified as halal which is the theme of future research in HFAA development.

Author Biographies

Muhamad Shirwan Abdullah Sani, International islamic University Malaysia (IIUM)

International Institute for Halal Research and Training

Mohammad Aizat Jamaludin, International Islamic University Malaysia

International Institute for Halal Research and Training

Nurhidayu Al-Saari, International Islamic University Malaysia

International Institute for Halal Research and Training

Azman Azid, Universiti Sultan Zainal Abidin (UniSZA)

Faculty Bioresources and Food Industry

Nur Syatirah Noor Azri, International Islamic University Malaysia

Department of Biomedical Sciences, Kulliyyah of Allied Health Sciences


Alichanidis, E., Moatsou, G., & Polychroniadou, A. (2016). Composition and properties of non-cow milk and products. Non-Bovine Milk and Milk Products. Elsevier Inc. https://doi.org/10.1016/B978-0-12-803361-6.00005-3

Alqudsi, S. G. (2014). Awareness and Demand for 100% Halal Supply Chain Meat Products. Procedia - Social and Behavioral Sciences, 130, 167–178. https://doi.org/10.1016/j.sbspro.2014.04.021

Aziz, S. A., Musa, R., & Rahman, S. A. (2016). Theorizing Islamic retail experiential value in predicting total Islamic experience quality: A hypothesised model. Procedia Economics and Finance, 37(16), 453–459. https://doi.org/10.1016/S2212-5671(16)30151-4

Barłowska, J., Szwajkowska, M., & Litwi, Z. (2011). Nutritional value and technological suitability of milk from various animal species used for dairy production. Comprehensive Reviews in Food Science and Food Safety, 10, 291–302. https://doi.org/10.1111/j.1541-4337.2011.00163.x

Blanchfield, J. R. (2005). Good manufacturing practice (GMP) in the food industry. In Handbook of Hygiene Control in the Food Industry (pp. 324–347). Woodhead Publishing Limited. https://doi.org/10.1533/9781845690533.3.324

Burling, H. (2018). Process for extracting pure fractions of lactoperoxidase and lactoferrin from milk serum.

Caballero, B., Finglas, P. M., & Toldra, F. (2016). Encyclopedia of food and health.

Cerven, D., DeGeorge, G., & Bethell, D. (2008). 28-Day repeated dose oral toxicity of recombinant human apo-lactoferrin or recombinant human lysozyme in rats. Regulatory Toxicology and Pharmacology, 51(2), 162–167. https://doi.org/10.1016/j.yrtph.2008.03.007

Claeys, W. L., Verraes, C., Cardoen, S., Block, J. De, Huyghebaert, A., Raes, K., … Herman, L. (2014). Consumption of raw or heated milk from different species: An evaluation of the nutritional and potential health benefits. Food Control, 42, 188–201. https://doi.org/10.1016/j.foodcont.2014.01.045

Corvi, R., Spielmann, H., & Hartung, T. (2019). Alternative approaches for carcinogenicity and reproductive toxicity. The History of Alternative Test Methods in Toxicology (Vol. 4). Elsevier Inc. https://doi.org/10.1016/b978-0-12-813697-3.00024-x

Davidson, P. ., Cekmer, H. B., Monu, E. ., & Techathuvanan, C. (2015). The use of natural antimicrobials in food: an overview. In T. M. Taylor (Ed.), Handbook of Natural Antimicrobials for Food Safety and Quality (1st ed., pp. 49–68). Cambridge: Woodhead Publishing Limited. https://doi.org/10.1016/B978-1-78242-034-7.00003-7

De Sousa Andrade, L. N., De Lima, T. M., Curi, R., & De Lauro Castrucci, A. M. (2005). Toxicity of fatty acids on murine and human melanoma cell lines. Toxicology in Vitro, 19(4), 553–560. https://doi.org/10.1016/j.tiv.2005.02.002

Delves-Broughton, J. (2012). Natural antimicrobials as additives and ingredients for the preservation of foods and beverages. Natural Food Additives, Ingredients and Flavourings. Woodhead Publishing Limited. https://doi.org/10.1016/B978-1-84569-811-9.50006-2

Department of Standards Malaysia. (2009). Malaysian standard MS 1500: 2009 Halal food- Production, preparation, handling and storage - General guidelines (second revision).

Desbois, A. P., & Smith, V. J. (2010). Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Applied Microbiol Biotechnology, 85, 1629–1642. https://doi.org/10.1007/s00253-009-2355-3

Devlieghere, F., Vermeulen, A., & Debevere, J. (2004). Chitosan: Antimicrobial activity, interactions with food components and applicability as a coating on fruit and vegetables. Food Microbiology, 21(6), 703–714. https://doi.org/10.1016/j.fm.2004.02.008

Doe, J., & Botham, P. (2019). Chemicals and pesticides: A long way to go. The History of Alternative Test Methods in Toxicology. Elsevier Inc. https://doi.org/10.1016/b978-0-12-813697-3.00021-4

European Food Safety Authority. (2012). Scientific opinion on bovine lactoferrin. EFSA Journal, 10(5), 1–26. https://doi.org/10.2903/j.efsa.2012.2701.

Feigenbaum, A., & Worth, A. P. (2019). Alternative approaches for the assessment of chemicals in Food. The History of Alternative Test Methods in Toxicology. Elsevier Inc. https://doi.org/10.1016/b978-0-12-813697-3.00022-6

Franco, I., Pérez, M. D., Conesa, C., Calvo, M., & Sánchez, L. (2018). Effect of technological treatments on bovine lactoferrin: An overview. Food Research International, 106(July 2017), 173–182. https://doi.org/10.1016/j.foodres.2017.12.016

German Federal Institute for Risk Assessment (BfR). (2018). Erucic acid: BfR endorses proposed maximum levels, but foods with added fats should be restricted too. https://doi.org/10.17590/20190116-105459-0

Guarda, A., Rubilar, J. F., Miltz, J., & Galotto, M. J. (2011). The antimicrobial activity of microencapsulated thymol and carvacrol. International Journal of Food Microbiology, 146(2), 144–150. https://doi.org/10.1016/j.ijfoodmicro.2011.02.011

Gyawali, R., & Ibrahim, S. A. (2014). Natural products as antimicrobial agents. Food Control, 46, 412–429. https://doi.org/10.1016/j.foodcont.2014.05.047

Harpaz, S., Glatman, L., Drabkin, V., & Gelman, A. (2003). Effects of herbal essential oils used to extend the shelf life of freshwater-reared Asian sea bass fish (Lates calcarifer). Journal of Food Protection, 3, 410–417.

Hashim, H. I. C., & Shariff, S. M. M. (2016). Halal supply chain management training: Issues and challenges. Procedia Economics and Finance, 37(16), 33–38. https://doi.org/10.1016/S2212-5671(16)30089-2

Health, N. I. of, & Services, U. D. of H. and H. (1997). Chitosan 9012-76-4. National Toxicology Program, 21(3), 295–316.

Holowachuk, S. A., Bal’a, M. F., & Buddington, R. K. (2003). A kinetic microplate method for quantifying the antibacterial properties of biological fluids. Journal of Microbiological Methods, 55(2), 441–446. https://doi.org/10.1016/S0167-7012(03)00190-8

Introduction, I. (2003). Milk and dairy products. In Microorganisms in Foods 6 (pp. 1–73).

Jabatan Kemajuan Islam Malaysia. (2014). Manual procedure for Malaysia halal certification. https://doi.org/10.1017/CBO9781107415324.004

Juneja, V. K., Dwivedi, H. P., & Yan, X. (2012). Novel natural food antimicrobials. Annual Review of Food Science and Technology, 3, 381–403. https://doi.org/10.1146/annurev-food-022811-101241

Keefe, D. M. (2011). Agency response letter GRAS notice no. GRN 000397 (chitosan from Aspergillus niger). Retrieved from https://wayback.archive-it.org/7993/20171031010838/https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm287638.htm

Kelly, P., Woonton, B. W., & Smithers, G. W. (2009). Improving the sensory quality, shelf-life and functionality of milk. Functional and Speciality Beverage Technology. Woodhead Publishing Limited. https://doi.org/10.1533/9781845695569.2.170

Kenna, J. G., & Ram, R. (2017). Safety assessment of pharmaceuticals. In The History of Alternative Test Methods in Toxicology (Vol. 9–15, pp. 14–23). Elsevier Inc. https://doi.org/10.1016/B978-0-12-801238-3.01942-5

Khare, A. K., Biswas, A. K., & Sahoo, J. (2014). Comparison study of chitosan, EDTA, eugenol and peppermint oil for antioxidant and antimicrobial potentials in chicken noodles and their effect on colour and oxidative stability at ambient temperature storage. LWT - Food Science and Technology, 55(1), 286–293. https://doi.org/10.1016/j.lwt.2013.08.024

Knutsen, H. K., Alexander, J., Barregård, L., Bignami, M., Brüschweiler, B., Ceccatelli, S., … Vleminckx, C. (2016). Erucic acid in feed and food. EFSA Journal, 14(11), 1–173. https://doi.org/10.2903/j.efsa.2016.4593

Limited, W. P. (2012). Emerging food pacaking technologies: Principles and practice. (K. L. Yam & D. S. Lee, Eds.), Semiconductor Nanowires. Cambridge, UK: Woodhead Publishing Limited. https://doi.org/10.1016/B978-1-78242-253-2.09001-0

Lucera, A., Costa, C., Conte, A., & Del Nobile, M. a. (2012). Food applications of natural antimicrobial compounds. Frontiers in Microbiology, 3(August), 1–13. https://doi.org/10.3389/fmicb.2012.00287

Ma, Z., Garrido-Maestu, A., Lee, C., Chon, J., Jeong, D., Yue, Y., … Jeong, K. C. (2018). Comprehensive in vitro and in vivo risk assessments of chitosan microparticles using human epithelial cells and Caenorhabditis elegans. Journal of Hazardous Materials, 341, 248–256. https://doi.org/10.1016/j.jhazmat.2017.07.071

Malaysia, D. of S. (2013). Malaysian standard MS 2393: 2013 Islamic and halal principles - Definitions and interpretations on terminology.

Martini, M., Altomonte, I., & Salari, F. (2014). Amiata donkeys: Fat globule characteristics, milk gross composition and fatty acids. Italian Journal of Animal Science, 13(3118), 123–126. https://doi.org/10.4081/ijas.2014.3118

Mattia, A. (2013). Agency response letter GRAS notice no. GRN 000443 (shrimp-derived chitosan). Retrieved from https://wayback.archive-it.org/7993/20171031005742/https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm347791.htm

Ministry of Health Malaysia. P.U.(A) 437/85 Food Regulations 1985 (2017). Retrieved from http://www.albayan.ae

Morash, M. G., Douglas, S. E., Robotham, A., Ridley, C. M., Gallant, J. W., & Soanes, K. H. (2011). The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents. Disease Models & Mechanisms, 4(5), 622–633. https://doi.org/10.1242/dmm.007310

National Institutes of Health, & US Department of Health and Human Services. (2017). NTP technical report on the toxicity study of chitosan administered in feed to Sprague Dawley rats. National Toxicology Program, 93(93), 1–93. Retrieved from https://ntp.niehs.nih.gov/ntp/htdocs/st_rpts/tox093_508.pdf

No, H. K., Meyers, S. P., Prinyawiwatkul, W., & Xu, Z. (2007). Applications of chitosan for improvement of quality and shelf life of foods: A review. Journal of Food Science, 72(5). https://doi.org/10.1111/j.1750-3841.2007.00383.x

Novoselova, M. V., & Prosekov, A. Y. (2016). Technological options for the production of lactoferrin. Foods and Raw Materials, 4(1), 90–101. https://doi.org/10.21179/2308-4057-2016-1-90-101

Nuijens, H. J. H., & Veen, B. H. H. Van. (1999). Isolation of lactoferrin from milk. https://doi.org/10.1016/j.(73)

Ouattara, B., Sabato, S. F., & Lacroix, M. (2001). Combined effect of antimicrobial coating and gamma irradiation on shelf life extension of pre-cooked shrimp (Penaeus spp.). International Journal of Food Microbiology, 68(1–2), 1–9. https://doi.org/10.1016/S0168-1605(01)00436-6

Oussalah, M., Caillet, S., Saucier, L., & Lacroix, M. (2007). Inhibitory effects of selected plant essential oils on the growth of four pathogenic bacteria: E. coli O157:H7, Salmonella Typhimurium, Staphylococcus aureus and Listeria monocytogenes. Food Control, 18(5), 414–420. https://doi.org/10.1016/j.foodcont.2005.11.009

Padmaja, R., Arun, P. C., Prashanth, D., Deepak, M., Amit, a, & Anjana, M. (2002). Brine shrimp lethality bioassay of selected Indian medicinal plants. Fitoterapia, 73(6), 508–510. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12385875

Parfene, G., Horincar, V., Tyagi, A. K., Malik, A., & Bahrim, G. (2013). Production of medium chain saturated fatty acids with enhanced antimicrobial activity from crude coconut fat by solid state cultivation of Yarrowia lipolytica. Food Chemistry, 136(3–4), 1345–1349. https://doi.org/10.1016/j.foodchem.2012.09.057

Parra, A. L., Yhebra, R. S., Sardiñas, I. G., & Buela, L. I. (2001). Comparative study of the assay of Artemia salina L . and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts. Phytomedicine, 8(5), 395–400.

Pisoschi, A. M., Pop, A., Georgescu, C., Turcuş, V., Olah, N. K., & Mathe, E. (2018). An overview of natural antimicrobials role in food. European Journal of Medicinal Chemistry, 143, 922–935. https://doi.org/10.1016/j.ejmech.2017.11.095

Rahman, F. A., Jaafar, H. S., Idha, S., & Muhammad, A. (2014). Ethics of Food Handlers Throughout the Supply Chain in the Halal Food Industry: Halal Perspective. Contemporary Issues and Development in the Global Halal Industry. https://doi.org/10.1007/978-981-10-1452-9

Rodriguez-Moya, M., & Gonzalez, R. (2015). Proteomic analysis of the response of Escherichia coli to short-chain fatty acids. Journal of Proteomics, 122, 86–99. https://doi.org/10.1016/j.jprot.2015.03.033

Roller, S., & Seedhar, P. (2002). Carvacrol and cinnamic acid inhibit microbial growth in fresh-cut melon and kiwifruit at 4° and 8°C. Letters in Applied Microbiology, 35(5), 390–394. https://doi.org/10.1046/j.1472-765X.2002.01209.x

Saarela, M. (2012). Functional foods: Concept to product. (M. Saarela, Ed.) (Second). Cambridge, UK: Woodhead Publishing Limited. https://doi.org/10.1533/9780857097415.frontmatter

Sahgal, G., Ramanathan, S., Sasidharan, S., Mordi, M. N., & Ismail, S. (2010). Brine shrimp lethality and acute oral toxicity studies on Swietenia mahagoni ( Linn .) Jacq . seed methanolic extract. Pharmacognosy Research, 2(4), 215–220. https://doi.org/10.4103/0974-8490.69107

Shahidi, F., Arachchi, J. K. V., & Jeon, Y. J. (1999). Food applications of chitin and chitosans. Trends in Food Science and Technology, 10(2), 37–51. https://doi.org/10.1016/S0924-2244(99)00017-5

Sharma, S. G. P. P., Jerzy Sobczyk, Stanislaw Garwacki Wieslaw Barej, & Bjorn Westrom. (1993). Comparative study of antibacterial activity of pancreatic juice in six mammalian species. Pancreas, 8(5), 546–550.

Shin, S. Y., Bajpai, V. K., Kim, H. R., & Kang, S. C. (2007). Antibacterial activity of bioconverted eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) against foodborne pathogenic bacteria. International Journal of Food Microbiology, 113(2), 233–236. https://doi.org/10.1016/j.ijfoodmicro.2006.05.020

Simopoulos, A. P. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine and Pharmacotherapy, 56, 365–379. https://doi.org/10.1016/S0753-3322(02)00253-6

Skarp, C. P. A., Hänninen, M. L., & Rautelin, H. I. K. (2016). Campylobacteriosis: The role of poultry meat. Clinical Microbiology and Infection, 22(2), 103–109. https://doi.org/10.1016/j.cmi.2015.11.019

Souza, J. L. S., Da Silva, A. F., Carvalho, P. H. A., Pacheco, B. S., Pereira, C. M. P., & Lund, R. G. (2014). Aliphatic fatty acids and esters: Inhibition of growth and exoenzyme production of Candida, and their cytotoxicity in vitro: Anti-Candida effect and cytotoxicity of fatty acids and esters. Archives of Oral Biology, 59(9), 880–886. https://doi.org/10.1016/j.archoralbio.2014.05.017

Sun, E., Belanger, C. R., Haney, E. F., & Hancock, R. E. W. (2017). Host defense (antimicrobial) peptides. Peptide Applications in Biomedicine, Biotechnology and Bioengineering. Elsevier Ltd. https://doi.org/10.1016/B978-0-08-100736-5.00010-7

Tao, R., Tong, Z., Lin, Y., Xue, Y., Wang, W., Kuang, R., … Ni, L. (2011). Antimicrobial and antibiofilm activity of pleurocidin against cariogenic microorganisms. Peptides, 32(8), 1748–1754. https://doi.org/10.1016/j.peptides.2011.06.008

Tiwari, B. K., Valdramidis, V. P., O’Donnell, C. P., Muthukumarappan, K., Bourke, P., & Cullen, P. J. (2009). Application of natural antimicrobials for food preservation. Journal of Agricultural and Food Chemistry, 57(14), 5987–6000. https://doi.org/10.1021/jf900668n

Tsigarida, E., Skandamis, P., & Nychas, G. J. E. (2000). Behaviour of Listeria monocytogenes and autochthonous flora on meat stored under aerobic, vacuum and modified atmosphere packaging conditions with or without the presence of oregano essential oil at 5??c. Journal of Applied Microbiology, 89(6), 901–909. https://doi.org/10.1046/j.1365-2672.2000.01170.x

U.S. Food and Drug Administration. (1999). Guidance for industry: Antimicrobial food additives. Retrieved February 3, 2019, from http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm077256.htm

U.S. Food and Drug Administration. (2018). Final determination regarding partially hydrogenated oils.

VanGarde, S. J., & Woodburn, M. (1994). Food preservation and safety: Principles and practice. Food Microbiology and Food Safety Research and Development Microbial Control and Food Preservation Theory and Practice. https://doi.org/https://doi.org/10.1007/978-1-4939-7556-3

Wood, J. D., Enser, M., Fisher, A. V., Nute, G. R., Sheard, P. R., Richardson, R. I., … Whittington, F. M. (2008). Fat deposition, fatty acid composition and meat quality: A review. Meat Science, 78(4), 343–358. https://doi.org/10.1016/j.meatsci.2007.07.019

Yamauchi, K., Toida, T., Nishimura, S., Nagano, E., Kusuoka, O., Teraguchi, S., … Tomita, M. (2000). 13-week oral repeated administration toxicity study of bovine lactoferrin in rats. Food and Chemical Toxicology, 38(6), 503–512. https://doi.org/10.1016/S0278-6915(00)00036-3

Yunos, R. M., Mahmood, C. F. C., & Mansor, N. H. A. (2014). Understanding mechanisms to promote halal industry-The stakeholders’ views. Procedia - Social and Behavioral Sciences, 130, 160–166. https://doi.org/10.1016/j.sbspro.2014.04.020

Zivanovic, S., Davis, R. H., & Golden, D. A. (2014). Chitosan as an antimicrobial in food products. Handbook of Natural Antimicrobials for Food Safety and Quality. https://doi.org/10.1016/B978-1-78242-034-7.00008-6