A Review on Chemical Composition, Bioactivity, and Toxicity of Myristica fragrans Houtt. Essential Oil

  • Mega Ferdina Warsito Research Center for Biotechnology, Indonesian Institute of Science, Jl. Raya Bogor Km. 46, Cibinong, Bogor, Indonesia 161911.
Keywords: Nutmeg, volatile oil, chemical composition, bioactivity, toxicity


Myristica fragrans Houtt., commonly known as nutmeg, is an Indonesian indigenous dioecious evergreen tree which contains 5-15% volatile oil. The oil is usually produced from the seed or mace.  Nutmeg oil has been extensively utilized in aromatherapy, natural medicine, and the perfume industry. This article provides an overview of the chemical compounds, biological potency, and toxic effects of nutmeg essential oil compiled from recent literature (2000–2020). Nutmeg oil mainly comprises monoterpenes and phenylpropanoids. Several reports on gas chromatography-mass spectrophotometry analysis of nutmeg oil showed that there were 27–38 chemical constituents detected at various concentrations. Many secondary metabolites of nutmeg oil reported to show biological activities that possibly substantiate its utilization in natural medicine. Numerous studies reported the biological activities of this volatile oil such as antioxidant, analgesic, antiinflammation, anticonvulsant, antibacterial, antiparasitic, insecticidal, and anticancer activity. But large intake of nutmeg oil could cause intoxication which is shown through symptoms in cardiovascular, central nervous system, anticholinergic, and local effects in the stomach. These symptoms are mainly attributed to the effect of myristicin, safrole, and elemicin overdose. This updated review paper intends to attract more attention to nutmeg oil and its potential to be developed into a medicinal product for the prophylaxis and therapy of diseases.


Abourashed EA. and El-Alfy AT., 2016. Chemical diversity and pharmacological significance of the secondary metabolites of nutmeg (Myristica fragrans Houtt.). Phytochem Rev, 15 (6): 1035‑1056, doi: 10.1007/s11101-016-9469-x
Adiani V., Gupta S., Chatterjee S., Variyar PS., and Sharma A., 2015. Activity guided characterization of antioxidant components from essential oil of Nutmeg (Myristica fragrans). Journal of Food Science and Technology, 52 (1): 221‑230, doi: 10.1007/s13197-013-1034-7
Alma MH., Nitz S., Kollmannsberger H., Digrak M., Efe FT., and Yilmaz N., 2004. Chemical Composition and Antimicrobial Activity of the Essential Oils from the Gum of Turkish Pistachio (Pistacia vera L.). J. Agric. Food Chem., 52 (12): 3911‑3914, doi: 10.1021/jf040014e
Al-Rawi SS., Ibrahim AH., Rahman NNNA., Nama MMB., Majid AMSA., and Kadir MOA., 2011. The Effect of Supercritical Fluid Extraction Parameters on the Nutmeg Oil Extraction and Its Cytotoxic and Antiangiogenic Properties. Procedia Food Science, 11946‑1952, doi: 10.1016/j.profoo.2011.09.286
Andrade MA., Cardoso MDG., Gomes M de S., de Azeredo CMO., Batista LR., Soares MJ., Rodrigues LMA., and Figueiredo ACS., 2015. Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis. Brazilian Journal of Microbiology, 46 (1): 189‑194, doi: 10.1590/S1517-838246120130683
Aoshima H., Hossain SJ., Hamamoto K., Yokoyama T., Yamada M., and Shingai R., 2001. Kinetic Analyses of Alcohol-Induced Potentiation of the Response of GABAA Receptors Composed of α1 and β1 Subunits. Journal of Biochemistry, 130 (5): 703‑709, doi: 10.1093/oxfordjournals.jbchem.a003037
Bae GS., Park KC., Choi SB., Jo IJ., Choi MO., Hong SH., Song K., Song HJ., and Park SJ., 2012. Protective effects of alpha-pinene in mice with cerulein-induced acute pancreatitis. Life Sciences, 91 (17‑18): 866‑871, doi: 10.1016/j.lfs.2012.08.035
Bahr TA., Rodriguez D., Beaumont C., and Allred K., 2019. The Effects of Various Essential Oils on Epilepsy and Acute Seizure: A Systematic Review. Evidence-Based Complementary and Alternative Medicine, 20191‑14, doi: 10.1155/2019/6216745
Beyer J., Ehlers D., and Maurer HH., 2006. Abuse of Nutmeg (Myristica fragrans Houtt.): Studies on the Metabolism and the Toxicologic Detection of its Ingredients Elemicin, Myristicin, and Safrole in Rat and Human Urine Using Gas Chromatography/Mass Spectrometry: Therapeutic Drug Monitoring, 28 (4): 568‑575, doi: 10.1097/00007691-200608000-00013
Calcabrini A., Stringaro A., Toccacieli L., Meschini S., Marra M., Colone M., Arancia G., Molinari A., Salvatore G., and Mondello F., 2004. Terpinen-4-ol, The Main Component of Melaleuca Alternifolia (Tea Tree) Oil Inhibits the In Vitro Growth of Human Melanoma Cells. Journal of Investigative Dermatology, 122 (2): 349‑360, doi: 10.1046/j.0022-202X.2004.22236.x
De Brito Passos FF., Lopes EM., De Araújo JM., De Sousa DP., Veras LMC., Leite JRSA., and De Castro Almeida FR., 2015. Involvement of Cholinergic and Opioid System in γ-Terpinene-Mediated Antinociception. Evidence-based Complementary and Alternative Medicine, 2015, doi: 10.1155/2015/829414
de Cássia da Silveira e Sá R., Andrade L., dos Reis Barreto de Oliveira R., and de Sousa D., 2014. A Review on Anti-Inflammatory Activity of Phenylpropanoids Found in Essential Oils. Molecules, 19 (2): 1459‑1480, doi: 10.3390/molecules19021459
de Sousa DP., Nóbrega FFF., Santos CCMP., and de Almeida RN., 2010. Anticonvulsant Activity of the Linalool Enantiomers and Racemate: Investigation of Chiral Influence. Natural Product Communications, 5 (12): 1934578X1000501, doi: 10.1177/1934578X1000501201
Dorman HJD. and Deans SG., 2004. Chemical Composition, Antimicrobial and In Vitro Antioxidant Properties of Monarda citriodora var. citriodora, Myristica fragrans, Origanum vulgare ssp. hirtum, Pelargonium sp. and Thymus zygis Oils. Journal of Essential Oil Research, 16 (2): 145‑150, doi: 10.1080/10412905.2004.9698679
Dragland S., Senoo H., Wake K., Holte K., and Blomhoff R., 2003. Several Culinary and Medicinal Herbs Are Important Sources of Dietary Antioxidants. The Journal of Nutrition, 133 (5): 1286‑1290, doi: 10.1093/jn/133.5.1286
Du SS., Yang K., Wang CF., You CX., Geng ZF., Guo SS., Deng ZW., and Liu ZL., 2014. Chemical Constituents and Activities of the Essential Oil from Myristica fragrans against Cigarette Beetle Lasioderma serricorne. Chemistry and Biodiversity, 11 (9): 1449‑1456, doi: 10.1002/cbdv.201400137
Ehrenpreis JE., DesLauriers C., Lank P., Armstrong PK., and Leikin JB., 2014. Nutmeg Poisonings: A Retrospective Review of 10 Years’ Experience from the Illinois Poison Center, 2001–2011. J. Med. Toxicol., 10 (2): 148‑151, doi: 10.1007/s13181-013-0379-7
Felipe CFB., Albuquerque AMS., de Pontes JLX., de Melo JÍV., Rodrigues TCML., de Sousa AMP., Monteiro ÁB., Ribeiro AE da S., Lopes JP., de Menezes IRA., and de Almeida RN., 2019. Comparative study of alpha- and beta-pinene effect on PTZ-induced convulsions in mice. Fundam Clin Pharmacol, 33 (2): 181‑190, doi: 10.1111/fcp.12416
Ferrero-Miliani L., Nielsen OH., Andersen PS., and Girardin SE., 2006. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1β generation. Clin Exp Immunol, 147 (2): 227-235, doi: 10.1111/j.1365-2249.2006.03261.x
Gnankiné O. and Bassolé ILHN., 2017. Essential oils as an alternative to pyrethroids’ resistance against Anopheles species complex giles (Diptera: Culicidae). Molecules, 22 (10): 1-23, doi: 10.3390/molecules22101321
Grant MJ. and Booth A., 2009. A typology of reviews: an analysis of 14 review types and associated methodologies. Health Information and Libraries Journal, 26: 91‑108, doi: 10.1111/j.1471-1842.2009.00848.x
Gupta AD. and Rajpurohit D., 2011. Chapter 98. Antioxidant and Antimicrobial Activity of Nutmeg (Myristica fragrans), in: Nuts and Seeds in Health and Disease Prevention (1st ed.), edited by Preedy VR., Watson RR., and Patel VB, Academic Press, London, UK. pp 831‑839.
Hawiger J. and Zienkiewicz J., 2019. Decoding inflammation, its causes, genomic responses, and emerging countermeasures. Scand J Immunol, 90 (6): 1-32, doi: 10.1111/sji.12812
Hossain SJ., Hamamoto K., Aoshima H., and Hara Y., 2002. Effects of Tea Components on the Response of GABAA Receptors Expressed in Xenopus Oocytes. J. Agric. Food Chem., 50 (14): 3954‑3960, doi: 10.1021/jf011607h
Huang CW., Chow JC., Tsai JJ., and Wu SN., 2012. Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability. Psychopharmacology, 221 (4): 575‑587, doi: 10.1007/s00213-011-2603-y
Huang D., Ou B., and Prior RL., 2005. The Chemistry behind Antioxidant Capacity Assays. J. Agric. Food Chem., 53 (6): 1841‑1856, doi: 10.1021/jf030723c
Ibrahim MA., Cantrell CL., Jeliazkova EA., Astatkie T., and Zheljazkov VD., 2020. Utilization of Nutmeg (Myristica fragrans Houtt.) Seed Hydrodistillation Time to Produce Essential Oil Fractions with Varied Compositions and Pharmacological Effects. Molecules, 25 (565): 1-10, doi: 10.3390/molecules25030565
Jaganathan SK. and Supriyanto E., 2012. Antiproliferative and Molecular Mechanism of Eugenol-Induced Apoptosis in Cancer Cells. Molecules, 17 (6): 6290‑6304, doi: 10.3390/molecules17066290
Asgarpanah J. and Kazemivash N., 2012. Phytochemistry and pharmacologic properties of Myristica fragrans Hoyutt.: A review. Afr. J. Biotechnol., 11 (65): 12787-12793, doi: 10.5897/AJB12.1043
Kapoor IPS., Singh B., Singh G., De Heluani CS., De Lampasona MP., and Catalan CAN., 2013. Chemical Composition and Antioxidant Activity of Essential Oil and Oleoresins of Nutmeg (Myristica fragrans Houtt.) Fruits. International Journal of Food Properties, 16 (5): 1059‑1070, doi: 10.1080/10942912.2011.576357
Khalilzadeh E., Saiah GV., Hasannejad H., Ghaderi A., Ghaderi S., Hamidian G., Mahmoudi R., Eshgi D., and Zangisheh M., 2015. Antinociceptive effects, acute toxicity, and chemical composition of Vitex agnus-castus essential oil. Avicenna Journal of Phytomedicine, 5 (3): 218‑30, doi: 10.22038/ajp.2015.4048
Kovač J., Šimunović K., Wu Z., Klančnik A., Bucar F., Zhang Q., and Možina SS., 2015. Antibiotic Resistance Modulation and Modes of Action of (-)-α-Pinene in Campylobacter jejuni. PLoS ONE, 10 (4): e0122871, doi: 10.1371/journal.pone.0122871
Kuete V., 2017. Chapter 23. Myristica fragrans: A Review, in: Medicinal Spices and Vegetables from Africa, edited by Kuete V, Academic Press, London, UK. pp 497‑512
Lee BK., Kim JH., Jung JW., Choi JW., Han ES., Lee SH., Ko KH., and Ryu JH., 2005. Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells. Toxicology Letters, 157 (1): 49‑56, doi: 10.1016/j.toxlet.2005.01.012
Lee JY. and Park W., 2011. Anti-Inflammatory Effect of Myristicin on RAW 264.7 Macrophages Stimulated with Polyinosinic-Polycytidylic Acid. Molecules, 16 (8): 7132‑7142, doi: 10.3390/molecules16087132
Liguori I., Russo G., Curcio F., Bulli G., Aran L., Della-Morte D., Gargiulo G., Testa G., Cacciatore F., Bonaduce D., and Abete P., 2018. Oxidative stress, aging, and diseases. CIA, Volume 13757‑772, doi: 10.2147/CIA.S158513
Medzhitov R., 2008. Origin and physiological roles of inflammation. Nature, 454 (7203): 428‑435, doi: 10.1038/nature07201
Monzote L., Herrera I., Satyal P., and Setzer W., 2019. In-Vitro Evaluation of 52 Commercially Available Essential Oils Against Leishmania amazonensis. Molecules, 24 (1248): 1-11, doi: 10.3390/molecules24071248
Moreira MR., Cruz GMP., Lopes MS., Albuquerque AAC., and Leal-Cardoso JH., 2001. Effects of terpineol on the compound action potential of the rat sciatic nerve. Braz J Med Biol Res, 34 (10): 1337‑1340, doi: 10.1590/S0100-879X2001001000015
Muchtaridi, Subarnas A., Apriyantono A., and Mustarichie R., 2010. Identification of Compounds in the Essential Oil of Nutmeg Seeds (Myristica fragrans Houtt.) That Inhibit Locomotor Activity in Mice. IJMS, 11 (11): 4771‑4781, doi: 10.3390/ijms11114771
Narasimhan B. and Dhake AS., 2006. Antibacterial Principles from Myristica fragrans Seeds. Journal of Medicinal Food, 9 (3): 395‑399, doi: 10.1089/jmf.2006.9.395
Norris EJ., Gross AD., Dunphy BM., Bessette S., Bartholomay L., and Coats JR., 2015. Comparison of the Insecticidal Characteristics of Commercially Available Plant Essential Oils Against Aedes aegypti and Anopheles gambiae (Diptera: Culicidae). J Med Entomol, 52 (5): 993‑1002, doi: 10.1093/jme/tjv090
Nurjanah S., Putri IL., and Sugiarti DP., 2017. Antibacterial Activity of Nutmeg Oil. KLS, 2 (6): 563, doi: 10.18502/kls.v2i6.1076
Oke F., Aslim B., Ozturk S., and Altundag S., 2009. Essential oil composition, antimicrobial and antioxidant activities of Satureja cuneifolia Ten. Food Chemistry, 112 (4): 874‑879, doi: 10.1016/j.foodchem.2008.06.061
Parija T. and Das BR., 2003. Involvement of YY1 and its correlation with c-myc in NDEA induced hepatocarcinogenesis, its prevention by d-limonene. Molecular Biology Reports, 30 (1): 41‑46, doi: 10.1023/A:1022207630482
Parise-Filho R., Pastrello M., Camerlingo CEP., Silva GJ., Agostinho LA., de Souza T., Magri FMM., Ribeiro RR., Brandt CA., and Polli MC., 2011. The anti-inflammatory activity of dillapiole and some semisynthetic analogues. Pharmaceutical Biology, 49 (11): 1173‑1179, doi: 10.3109/13880209.2011.575793
Periasamy G., Karim A., Gibrelibanos M., Gebremedhin G., and Gilani AH., 2016. Chapter 69. Nutmeg (Myristica fragrans Houtt.) Oils, in: Essential Oils in Food Preservation, Flavor and Safety, edited by Preedy VR., Academic Press, London, UK. pp 607‑616
Piaru SP., Mahmud R., Majid AMSA., and Nassar ZDM., 2012. Antioxidant and antiangiogenic activities of the essential oils of Myristica fragrans and Morinda citrifolia. Asian Pacific Journal of Tropical Medicine, 5 (4): 294‑298, doi: 10.1016/S1995-7645(12)60042-X
Pillai S., Mahmud R., Lee WC., and Perumal S., 2012. Anti-Parasitic Activity of Myristica Fragrans Houtt. Essential Oil Against Toxoplasma Gondii Parasite. APCBEE Procedia, 292‑96, doi: 10.1016/j.apcbee.2012.06.017
Piras A., Rosa A., Marongiu B., Atzeri A., Dessì MA., Falconieri D., and Porcedda S., 2012. Extraction and Separation of Volatile and Fixed Oils from Seeds of Myristica fragrans by Supercritical CO2: Chemical Composition and Cytotoxic Activity on Caco-2 Cancer Cells. Journal of Food Science, 77 (4): C448‑C453, doi: 10.1111/j.1750-3841.2012.02618.x
Prabuseenivasan S., Jayakumar M., and Ignacimuthu S., 2006. In vitro antibacterial activity of some plant essential oils. BMC Complement Altern Med, 6 (1): 39, doi: 10.1186/1472-6882-6-39
Rahardiyan D., Poluakan M., and Moko EM., 2020. Physico-chemical Properties of Nutmeg (Myristica fragrans Houtt) of North Sulawesi Nutmeg. Fullerene, 5 (1): 23-31.
Rother E., 2007. Editorial: Systematic Review X Narrative Review. Acta Paulista de Enfermagem, 20 (2): 7‑8, doi: 10.1590/S0103-21002007000200001
Serhan CN., Chiang N., and Van Dyke TE., 2008. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol, 8 (5): 349‑361, doi: 10.1038/nri2294
Sipahelut SG., Kastanja AY., and Patty Z., 2020. Antioxidant activity of nutmeg fruit flesh-derived essential oil obtained through multiple drying methods. EurAsian Journal of BioSciences 14: 21-26.
Soni R., Sharma G., and Jasuja ND., 2016. Essential Oil Yield Pattern and Antibacterial and Insecticidal Activities of Trachyspermum ammi and Myristica fragrans. Scientifica, 2016: 1‑7, doi: 10.1155/2016/1428194
Srivastava S., Gupta MM., Prajapati V., Tripathi AK., and Kumar S., 2001. Insecticidal activity of myristicin from Piper mullesua. Pharmaceutical Biology, 39 (3): 226‑229, doi: 10.1076/phbi.
Stein U., Greyer H., and Hentschel H., 2001. Nutmeg (myristicin) poisoning - report on a fatal case and a series of cases recorded by a poison information centre. Forensic Science International 118: 87-90.
Vatanparast J., Khalili S., and Naseh M., 2017. Dual effects of eugenol on the neuronal excitability: An in vitro study. NeuroToxicology, 58: 84‑91, doi: 10.1016/j.neuro.2016.11.011
Wahab A., Haq RU., Ahmed A., Khan RA., and Raza M., 2009. Anticonvulsant activities of nutmeg oil of Myristica fragrans. Phytotherapy Research, 23 (2): 153‑158, doi: 10.1002/ptr.2548
Yashin A., Yashin Y., Xia X., and Nemzer B., 2017. Antioxidant Activity of Spices and Their Impact on Human Health: A Review. Antioxidants, 6 (3): 70, doi: 10.3390/antiox6030070
Zamyad M., Abbasnejad M., Esmaeili-Mahani S., Mostafavi A., and Sheibani V., 2019. The anticonvulsant effects of Ducrosia anethifolia (Boiss) essential oil are produced by its main component alpha-pinene in rats. Arq. Neuro-Psiquiatr., 77 (2): 106‑114, doi: 10.1590/0004-282x20180147
Zhang WK., Tao SS., Li TT., Li YS., Li XJ., Tang HB., Cong RH., Ma FL., and Wan CJ., 2016. Nutmeg oil alleviates chronic inflammatory pain through inhibition of COX-2 expression and substance P release in vivo. Food and Nutrition Research, 60: 30849, doi: 10.3402/fnr.v60.30849
Zhao L., Tian S., Wen E., and Upur H., 2017. An ethnopharmacological study of aromatic Uyghur medicinal plants in Xinjiang, China. Pharmaceutical Biology, 55 (1): 1114‑1130, doi: 10.1080/13880209.2016.1270971
Zheljazkov VD., Gawde A., Cantrell C.L., Astatkie T., and Schlegel V., 2015. Distillation Time as Tool for Improved Antimalarial Activity and Differential Oil Composition of Cumin Seed Oil. PLoS ONE, 10 (12): e0144120, doi: 10.1371/journal.pone.0144120
How to Cite
Warsito, M. F. (2021). A Review on Chemical Composition, Bioactivity, and Toxicity of Myristica fragrans Houtt. Essential Oil. Indonesian Journal of Pharmacy, 32(3), 304-313. https://doi.org/10.22146/ijp.1271
Review Article