Nutmeg
Scientific Name(s): Myristica fragrans Houtt. Family: Myristicaceae
Common Name(s): Nutmeg , mace , magic , muscdier , nux moschata , myristica oil , muskatbaum
Clinical Overview
 |
Uses of Nutmeg
Nutmeg and mace, widely accepted as flavoring agents, are used in higher doses for their aphrodisiac and psychoactive properties.
Nutmeg Dosing
There are no clinical trials to support therapeutic dosing. Consumption of nutmeg 1 to 2 mg/kg body weight was reported to induce CNS effects. Toxic overdose occurred at 5 g.
Contraindications
Contraindications have not been identified. The excessive use of nutmeg or mace is not recommended in people with psychiatric conditions.
Pregnancy/Lactation
Generally recognized as safe when used in food as a flavoring agent. Safety for dosages above those found in foods is unproven and should be avoided (possible abortifacient).
Nutmeg Interactions
None well documented.
Nutmeg Adverse Reactions
CNS excitation with anxiety/fear, cutaneous flushing, decreased salivation, GI symptoms, and tachycardia.
Toxicology
Death has been rarely reported following the ingestion of large doses of nutmeg. Acute psychosis and anticholinergic-like episodes have been noted.
Botany
Mace and nutmeg are 2 slightly different flavored spices, both originating from the fruit of the nutmeg tree, Myristica fragrans . This slow-growing evergreen grows to more than 20 m and is cultivated in India, Ceylon, Malaysia, and Granada. The fruit, which is called a drupe or a nutmeg apple, is similar in appearance to a peach or an apricot. When the mature fruit splits open, the nutmeg (stony endocarp or seed surrounded by a red, slightly fleshy network or aril) is exposed. The dried aril alone is called mace. The nut is removed and dried to produce nutmeg. 1 , 2 , 3
History
Nutmeg is a widely used food spice that has received attention as an alternative hallucinogen. Nutmeg and mace have been used in Indian cooking and folk medicine. The folk uses of nutmeg have included the treatment of gastric disorders and rheumatism, and it has been used as a hypnotic and an aphrodisiac. During the 6th century AD, nutmeg and mace were imported by Arab traders. By the 12th century, these spices were well known in Europe. At the turn of the 19th century, interest developed in the use of nutmeg as an abortifacient and a stimulant for menses. These properties have been largely discounted but remain a persistent cause of nutmeg intoxication in women. 2 , 3 , 4
Chemistry
Nutmeg seeds contain 20% to 40% of a fixed oil, commonly called nutmeg butter. This oil contains myristic acid, trymiristin, and glycerides of lauric, tridecanoic, stearic, and palmitic acids. 5 , 6
Nutmeg also yields 8% to 15% of an essential oil that is believed to be partially responsible for the effects associated with nutmeg intoxication. The essential oil contains myristicin, elemicin, eugenol, and safrole. 5 , 6 , 7 The essential oils of nutmeg and mace are very similar in chemical composition and aroma, with wide color differences (brilliant orange to pale yellow). Mace oil appears to have a higher myristicin content than nutmeg oil. 8
Also present in the oil are sabinene, cymene alpha-thujene, gamma-terpinene, and monoterpene alcohols in smaller amounts. Phenolic compounds found in nutmeg are reported to have antioxidant properties. 6 , 7 , 9 , 10 Other isolated compounds include the resorcinols malabaricone B and malabaricone C, 11 as well as lignans and neolignans. 12 , 13
Nutmeg Uses and Pharmacology
There have been no clinical trials reported in the literature for nutmeg or mace in the past 10 years.
CNS effectsNutmeg has long been known for its psychoactive properties (producing anxiety/fear, hallucinations), from as early as 16th century writings to current Internet-based sites. 14 , 15 , 16 Doses of 5 to 15 g (1 to 3 whole nuts) are required for effect, but toxic overdose occurred at 5 g. 8 , 16 , 17 Chronic nutmeg abuse has been reported. 14
The effects of nutmeg intoxication are variable and reflect anticholinergic and CNS excitatory effects. 15 , 18 The chemical constituents responsible for the CNS effects appear to be myristicin, which is a hallucinogenic and weak monoamine oxidase (MAO) inhibitor, 18 elemicin, safrole, 18 , 19 and trimyristin (anxiogenic effects), 17 , 20 with some components being structurally similar to serotonin agonists. 18
Experiments conducted in mice found anticonvulsant activity and other behavioral effects. 21 , 22
Antimicrobial effectsThe oils of mace and nutmeg and their individual components have been assessed for their activity in vitro. A modulatory effect on the protein/toxins produced by some bacteria ( Listeria , Staphylococcus aureus , Streptococcus mutans ) but not on the microorganisms, has been reported. 23 , 24 , 25 , 26
Activity has been shown against some oral microorganisms, including S. mutans , Porphyromonas gingivalis , and others. 23 Activity against other bacteria includes some strains of Escherichia coli , 26 , 27 , 28 , 29 human rotavirus, 30 some strains of Salmonella typhi , 31 Bacillus subtilis , 26 S. aureus , 25 , 26 and Listeria . 24
Reports of activity against fungi is conflicting, with no activity against Aspergillus and other plant fungi, 32 , 33 but activity against some dermatophytes has been found. 34
Antioxidant effectsExperiments have been conducted to evaluate the antioxidant potential of the oils of nutmeg and mace and their chemical components, with some estimations considered to be weak. 6 , 35 , 36 Eugenol has been identified as one component of nutmeg with antioxidant activity, 37 and inhibition of nitric oxide production and NO-scavenging has been shown in experiments using the methanol extract of nutmeg. 38
AphrodisiacIncreased sexual activity (libido and potency) has been demonstrated in male rats with ethanolic extracts of nutmeg, providing some support for the use of nutmeg as an aphrodisiac. Eugenol may be responsible for some of the aphrodisiac effect because of its vasodilatory and smooth muscle relaxant properties. 39 , 40
CancerThe National Cancer Institute has screened the Myristicaceae plant family for activity against selected leukemia lines. Of the tested extracts, 18.8% exhibited antileukemia activity. 41
Mace is capable of modulating the activity of enzymes involved with activation and detoxication of carcinogens. 42 , 43 , 44 , 45 , 46 , 47 , 48 This property may be passed to lactating mice progeny. 42
The cytotoxic and apoptotic effects of myristicin have been studied. Cell viability was reduced by exposure to myristicin in a dose- and time-dependent manner. 49
Safrole, a minor component of the oil, promoted hepatocarcinomas in mice. 50
OtherExtracts of nutmeg were bacteriostatic against H. pylori in vitro. 51 , 52 Reduced gastric acidity and volume of gastric secretion have been demonstrated in rabbits given nutmeg extracts. 53 , 54
In rabbits given an ethanolic extract of nutmeg, total and low-density lipoprotein cholesterol and triglyceride were reduced while high-density lipoprotein levels were not changed. 31 In another screening study, nutmeg demonstrated hepatoprotective properties. 55
Anti-inflammatory and analgesic activities of nutmeg have been reported in mice. Antithrombotic activity also was reported. 56 Nutmeg has shown insulin-like activity in vitro. 57
Dosage
There are no clinical trials to support therapeutic dosing.
Consumption of nutmeg 1 to 2 mg/kg body weight was reported to induce CNS effects. Toxic overdose occurred at 5 g. 8 , 16 , 17
Pregnancy/Lactation
Nutmeg traditionally has been used as an abortifacient. Although this use has been largely discounted, it remains a persistent cause of nutmeg intoxication in women. 2 , 3 , 4
Interactions
Because of anxiogenic properties, a theoretical interaction may occur with nutmeg/mace and anxiolytics. 2 , 4 Interactions with nutmeg and diazepam, ondansetron, or buspirone have been reported in rats. 22 One death has been associated with concurrent ingestion of large amounts of nutmeg and flunitrazepam. 19 Weak MAO-inhibitory properties have been noted for the compound myristicin. 18
Adverse Reactions
Allergy, contact dermatitis, and asthma have been reported. The chemical constituents limonene and eugenol are reported contact allergens, and IgE reactivity has been demonstrated in nutmeg and mace. 58 , 59
Toxicology
Acute psychosis and anticholinergic-like episodes have been reported 14 , 15 , 16 , 17 , 18 with a wide variety of symptoms. Effects occured within 0.5 to 8 hours following ingestion.
The episodes are characterized by cutaneous flushing, tachycardia, decreased salivation, GI symptoms (nausea, vomiting, abdominal pain), fever, and CNS excitation with anxiety/fear. 17 , 18 Miosis or mydriasis are not considered to be reliable signs, as either may be present. 17 , 18 Shock, coma, and death have been reported. Treatment is supportive, with the use of antipsychotic therapy when necessary. 15 , 18
The cytotoxic and apoptotic effects of myristicin have been explored. Cell viability was reduced by exposure to myristicin in a dose- and time-dependent manner. 49 Safrole, a minor component of the oil, has been shown to promote hepatocarcinomas in mice. 50
Bibliography
1. PLANTS Database . United States Department of Agriculture. Natural Resources Conservation Services. Myristica fragrans Houtt. nutmeg. Available at: http://plants.usda.gov/java/profile?symbol=MYFR3 . Accessed: August 7, 2006.2. De Milto L, Frey RJ. Nutmeg. In: Longe JL, project editor. Gale Encyclopedia of Alternative Medicine . Vol 3. 2nd ed. Detroit, MI: Thomson Gale;2005:1461-1463.
3. Van Gils C, Cox PA. Ethnobotany of nutmeg in the Spice Islands. J Ethnopharmacol . 1994;42:117-124.
4. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;19:227-235.
5. Spricigo CB, Pinto LT, Bolzan A, Novais AF. Extraction of essential oil and lipids from nutmeg by liquid carbon dioxide. J Supercritical Fluids . 1999;15:253-259.
6. Dorman HJ, Figueiredo AC, Barroso JG, Deans SG. In vitro evaluation of antioxidant activity of essential oils and their components. Flavour Fragr J. 2000;15:12-16.
7. Shan B, Cai YZ, Sun M, Corke H. Antioxidant capacity of 26 spice extracts and characterization of their phenolic constituents. J Agric Food Chem . 2005;53:7749-7759.
8. Hallstrom H, Thuvander A. Toxicological evaluation of myristicin. Nat Toxins . 1997;5:186-192.
9. Su L, Yin JJ, Charles D, Zhou K, Moore J, Yu L. Total phenolic contents, chelating capacities, and radical-scavenging properties of black peppercorn, nutmeg, rosehip, cinnamon and oregano leaf. Food Chem . 2005.
10. Valderrama JC. Distribution of flavonoids in the Myristicaceae . Phytochemistry . 2000;55:505-511.
11. Orabi KY, Mossa JS, el-Feraly FS. Isolation and characterization of two antimicrobial agents from mace ( Myristica fragrans ). J Nat Prod . 1991;54:856-859.
12. Zacchino SA, Badano H. Enantioselective synthesis and absolute configuration assignment of erythro-(3,4,5 trimethoxy-7hydroxy-1'allyl-2',6'-dimethoxy)-8.0.4'-neolignan from mace ( Myristica fragrans ). J Nat Prod . 1988;51:1261.
13. Kasahara H, Miyazawa M, Kameoka H. Absolute configuration of 8-o-4'-neolignans from Myristica fragrans . Phytochemistry . 1995;40:515-517.
14. Kelly BD, Gavin BE, Clarke M, Lane A, Larkin C. Nutmeg and psychosis. Schizophr Res . 2003;60:95-96.
15. Forrester MB. Nutmeg intoxication in Texas, 1998-2004. Hum Exp Toxicol . 2005;24:563-566.
16. Brenner N, Frank OS, Knight E. Chronic nutmeg psychosis. 1993;86:179-180.
17. Demetriades AK, Wallman PD, McGuiness A, Gavalas MC. Low cost, high risk: accidental nutmeg intoxication. Emerg Med J . 2005;22:223-225.
18. Sangalli BC, Chiang W. Toxicology of nutmeg abuse. J Toxicol Clin Toxicol . 2000;38:671-678.
19. Stein U, Greyer H, Hentschel H. Nutmeg ( myristicin ) poisoning — report on a fatal case and a series of cases recorded by a poison information centre. Forensic Sci Int . 2001;118:87-90.
20. Sonavane GS, Sarveiya VP, Kasture VS, Kasture SB. Anxiogenic activity of Myristica fragrans seeds. Pharmacol Biochem Behav . 2002;71:247-252.
21. Sonavane GS, Palekar RC, Kasture VS, Kasture SB. Anticonvulsant and behavioural actions of Myristica fragrans seeds. Indian J Pharm Sci . 2002;34:332-338.
22. Sonavane GS, Sarveiya V, Kasture V, Kasture SB. Behavioural actions of Myristica fragrans seeds. Indian J Pharm Sci . 2001;33:417-424.
23. Shinohara C, Mori S, Ando T, Tsuji T. Arg-gingipain inhibition and anti-bacterial activity selective for Porphyromonas gingivalis by malabaricone C . Biosci Biotechnol Biochem . 1999;63:1475-1477.
24. Smith-Palmer A, Stewart J, Fyfe L. Influence of subinhibitory concentrations of plant essential oils on the production of enterotoxins A and B and alpha-toxin by Staphylococcus aureus . J Med Microbiol . 2004;53(pt 10):1023-1027.
25. Smith-Palmer A, Stewart J, Fyfe L. Inhibition of listeriolysin O and phosphatidylcholine-specific production in Listeria monocytogenes by subinhibitory concentrations of plant essential oils. J Med Microbiol . 2002;51:567-574.
26. Singh G, Marimuthu P, DeHeluani CS, Catalan C. Antimicrobial and antioxidant potentials of essential oil and acetone extract of Myristica fragrans Houtt. (aril part). J Food Sci . 2005;70:141-148.
27. Chung JY, Choo JH, Lee MH, Hwang JK. Anticariogenic activity of macelignan isolated from Myristica fragrans (nutmeg) against Streptococcus mutans . Phytomedicine . 2006;13:261-266.
28. Takikawa A, Abe K, Yamamoto M, et al. Antimicrobial activity of nutmeg against Escherichia coli O157. J Biosci Bioeng . 2002;94:315-320.
29. De M, Krishna De A, Banerjee AB. Antimicrobial screening of some Indian spices. Phytother Res . 1999;13:616-618.
30. Goncalves JL, Lopes RC, Oliveira DB, et al. In vitro anti-rotavirus activity of some medicinal plants used in Brazil against diarrhea. J Ethnopharmacol . 2005;99:403-407.
31. Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for their anti-enteric potential against multi-drug resistant Salmonella typhi . Phytother Res . 2004;18:670-673.
32. Sridhar SR, Rajagopal RV, Rajavel R, Masilamani S, Narasimhan S. Antifungal activity of some essential oils. J Agric Food Chem . 2003;51:7596-7599.
33. Zacchino SA, Lopez SN, Pezzenati GD, et al. In vitro evaluation of antifungal properties of phenylpropanoids and related compounds acting against dermatophytes. J Nat Prod . 1999;62:1353-1357.
34. Zacchino SA, Rodriguez G, Pezzenati G, Orellana G. In vitro evaluation of antifungal properties of 8.O.4′-neolignans. J Nat Prod . 1997;60:659-662.
35. Dew TP, Day AJ, Morgan MR. Xanthine oxidase activity in vitro: effects of food extracts and components. J Agric Food Chem . 2005;53:6510-6515.
36. Tomaino A, Cimino F, Zimbalatti V, et al. Influence of heating on antioxidant activity and the chemical composition of some spice essential oils. Food Chem . 2005;89:549-554.
37. Kumaravelu P, Subramaniyam S, Dakshinamoorthy DP, Devaraj NS. The antioxidant effect of eugenol on Ccl,-induced erythrocyte damage in rats. J Nutr Biochem . 1996;7:23-28.
38. Tezuka Y, Irikawa S, Kaneko T, et al. Screening of Chinese herbal drug extracts for inhibitory activity on nitric oxide production and identification of an active compound of Zanthoxylum bungeanum . J Ethnopharmacol . 2001;77:209-217.
39. Tajuddin S, Ahmad S, Latif A, Qasmi IA. Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a comparative study. BMC Complement Altern Med . 2003;3:6.
40. Tajuddin S, Ahmad S, Latif A, Qasmi IA, Amin KM. An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg). BMC Complement Altern Med . 2005;5:16.
41. Cragg GM, Newman DJ, Yang SS. Natural product extracts of plant and marine origin having antileukemia potential. The NCI experience. J Nat Prod . 2006;69:488-498.
42. Chhabra SK, Rao AR. Transmammary modulation of xenobiotic metabolizing enzymes in liver of mouse pups by mace ( Myristica fragrans Houtt.). J Ethnopharmacol . 1994;42:169-177.
43. Banerjee S, Sharma R, Kale RK, Rao AR. Influence of certain essential oils on carcinogen-metabolizing enzymes and acid-soluble sulfhydryls mouse liver. Nutr Cancer . 1994;21:263-269.
44. Hashim S, Aboobaker VS, Madhubala R, Bhattacharya RK, Rao AR. Modulatory effects of essential oils from spices on the formation of DNA adduct by aflatoxin B1 in vitro. Nutr Cancer . 1994;21:169-175.
45. Singh A, Rao AR. Modulatory effect of Areca nut on the action of mace ( Myristica fragrans , Houtt) on the hepatic detoxification system in mice. Food Chem Toxicol . 1993;31:517-521.
46. Jannu LN, Hussain SP, Rao AR. Chemopreventive action of mace ( Myristica fragrans , Houtt) on DMBA-induced papillomagenesis in the skin of mice. Cancer Lett . 1991;56:59-63.
47. Hussain SP, Rao AR. Chemopreventive action of mace ( Myristica fragrans , Houtt) on methylcholanthrene-induced carcinogenesis in the uterine cervix in mice. Cancer Lett . 1991;56:231-234.
48. Park S, Lee DK, Yang CH. Inhibition of fos-jun-DNA complex formation by dihydroguaiaretic acid and in vitro cytotoxic effects on cancer cells. Cancer Lett . 1998;127:23-28.
49. Lee BK, Kim JH, Jung JW, et al. Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells. Toxicol Lett . 2005;157:49-56.
50. Miller EC, Swanson AB, Phillips DH, Fletcher TL, Liem A, Miller JA. Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole. Cancer Res . 1983;43:1124-1134.
51. O'Mahony R, Al-Khtheeri H, Weerasekera D, et al. Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori . World J Gastroenterol . 2005;11:7499-7507.
52. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Helicobacter pylori to botanical extracts used traditionally for the treatment of gastrointestinal disorders. Phytother Res . 2005;19:988-991.
53. Jan M, Faqir F, Hamida, Mughal MA. Comparison of effects of extract of Myristica fragrans and verapamil on the volume and acidity of carbachol induced gastric secretion in fasting rabbits. J Ayub Med Coll Abbottabad . 2005;17:69-71.
54. Jan M, Faqir F, Qureshi H, Malik SA, Mughal MA. Evaluation of effects of extract from seeds of Myristica fragrans on volume and acidity of stimulated gastric secretion, liver and kidney function. J Postgrad Med Inst . 2004;18:644-650.
55. Morita T, Jinno K, Kawagishi H, et al. Hepatoprotective effect of myristicin from nutmeg ( Myristica fragrans ) on lipopolysaccharide/d-galactosamine-induced liver injury. J Agric Food Chem . 2003;51:1560-1565.
56. Olajide OA, Ajayi FF, Ekhelar AI, Awe SO, Makinde JM, Alada AR. Biological effects of Myristica fragrans (nutmeg) extract. Phytother Res . 1999;13:344-345.
57. Broadhurst CL, Polansky MM, Anderson RA. Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro. J Agric Food Chem . 2000;48:849-852.
58. Brancaccio RR, Alvarez MS. Contact allergy to food. Dermatol Ther . 2004;17:302-313.
59. Scholl I, Jensen-Jarolim E. Allergenic potency of spices: hot, medium hot, or very hot. Int Arch Allergy Immunol . 2004;135:247-261.
 |
Link to Page |  |
Print Page |  |
Email Page |  | Add to List |
