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Nutmeg

Scientific Name(s): Myristica fragrans Houtt.
Common Name(s): Nutmeg, mace, magic, muscdier, nux moschata, myristica oil, muskatbaum

Clinical Overview

Use

Nutmeg and mace, widely accepted as flavoring agents, have been used in higher doses for their aphrodisiac and psychoactive properties.

Dosing

There are no clinical trials to support therapeutic dosing. Consumption of nutmeg at 1 to 2 mg/kg body weight was reported to induce CNS effects. Toxic overdose occurred at a 5 g dose.

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 doses above those found in foods is unproven; avoid because of possible abortifacient effects.

Interactions

None well documented.

Adverse Reactions

Allergy, contact dermatitis, and asthma have been reported.

Toxicology

CNS excitation with anxiety/fear, cutaneous flushing, decreased salivation, GI symptoms, and tachycardia. Acute psychosis and anticholinergic-like episodes have been documented; death has rarely been reported following the ingestion of large doses of nutmeg.

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. In folk medicine, nutmeg has been used to treat gastric disorders and rheumatism, and also as a hypnotic and an aphrodisiac. During the 6th century AD, nutmeg and mace were imported by Arab traders, and by the 12th century, they 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, 11 Other isolated compounds include the resorcinols malabaricone B and C12 as well as lignans and neolignans.13, 14, 15

Uses and Pharmacology

There are no relevant clinical trials reported in the literature for nutmeg or mace.

Aphrodisiac effects

Animal data

Increased 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.16, 17

Clinical data

Despite anecdotal reports of aphrodisiac effects, clinical studies are lacking.

Cancer

The National Cancer Institute has screened the Myristicaceae plant family for activity against selected leukemia lines. Of the tested extracts, 18.8% exhibited antileukemia activity, and in vitro studies with methanol extract and myristicin have shown increased apoptosis and decreased leukemia and neuroblastoma cell proliferation.18, 19, 20 Several older experiments reveal some action on enzymes involved with activation and detoxification of carcinogens.

Animal data

More recently, experiments have evaluated the radio- and cisplatin-induced hepatoprotective effects in mice.21, 22, 23

Clinical data

Clinical trials are lacking; however, in vitro studies have included isolated human splenocytes and other cell lines.19, 22

CNS effects

Animal data

The effects of nutmeg on the CNS are variable and reflect anticholinergic and CNS excitatory and depressant effects. Dopaminergic and serotonin pathways may be involved.24, 25, 26, 27, 28 Anticonvulsant activity in mice has been demonstrated.29, 30, 31 The chemical constituents responsible for the CNS effects appear to be myristicin, which is a hallucinogenic and weak monoamine oxidase (MAO) inhibitor, elemicin, safrole, and trimyristin (anxiogenic effects), with some components being structurally similar to serotonin agonists.26, 32, 33, 34

Clinical data

Nutmeg has long been known for its psychoactive properties of producing anxiety/fear and hallucinations; however, clinical studies are lacking.24, 35, 36 Long-term nutmeg abuse has been reported.35 Laboratory tests have detected nutmeg metabolites, which are reported to be unlike amphetamine derivatives.37

Diabetes

Nutmeg has shown insulin-like activity in vitro.38 Inhibitory effects on protein tyrosine phosphate 1B, involved in insulin cellular signaling, have been demonstrated.39

Animal data

Serum glucose and lipid profiles improved in mice when mace lignan was administered.40 In rabbits given an ethanolic extract of nutmeg, total and low-density lipoprotein (LDL) cholesterol and triglyceride were reduced; however, high-density lipoprotein levels were not changed.41

Clinical data

Clinical studies are lacking.

Other uses

Antimicrobial effects

The oils of mace and nutmeg and their individual components (trimyristin, myristic acid, myristin, mace lignan) have been assessed for in vitro activity, which has been shown against some oral microorganisms42, 43; however, activity against other human pathogens has been demonstrated in vitro.44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 A modulatory effect on the protein/toxins produced by some bacteria, but not on the microorganisms themselves, has also been described.42, 44, 45, 46 Reports of activity against fungi are conflicting.55, 56, 57 The crude extract of M. fragrans (aril or leaf) was found to have strong inhibitory activity on Helicobacter pylori in vitro with a minimal inhibitory concentration (MIC) of 12.5 mcg/mL; leaf extract had a MIC of 50 mcg/mL. Amoxicillin (MIC range, 0.0039 to 0.25 mcg/mL) and metronidazole (MIC range, 64 to 124 mcg/mL) were used as controls.79

Antioxidant effects

Experiments have evaluated the antioxidant potential of the oils of nutmeg and mace and their chemical components. Eugenol and mace lignans, as well as the phenolic content, have been identified as components of nutmeg with antioxidant activity, and inhibition of nitric oxide production, NO-scavenging, and decreased LDL-oxidation were demonstrated in experiments.6, 10, 15, 58, 59, 60, 61, 62, 63, 64

Other effects

Screening and in vitro experiments in nutmeg components demonstrated ultraviolet-protectant effects and inhibition of melanin biosynthesis.65, 66 Anti-inflammatory and analgesic activities of nutmeg have been recorded in mice, as well as antithrombotic activity.67, 68 Other studies document hepatoprotective properties69 effects on osteoblast differentiation70 and reduced acidity and volume of gastric secretion.71, 72

Dosing

There are no clinical trials to support therapeutic dosing.

Consumption of nutmeg 1 to 2 mg/kg of body weight induced CNS effects. Toxic overdose occurred at 5 g.8, 32, 36

Pregnancy / Lactation

Generally recognized as safe when used in food as a flavoring agent. 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 occurred in rats.30 One death has been associated with concurrent ingestion of large amounts of nutmeg and flunitrazepam.33 Weak MAO inhibitory properties have been noted for the compound myristicin.25

Adverse Reactions

Allergy, contact dermatitis, and asthma have been reported. The chemical constituents limonene and eugenol are contact allergens. Immunoglobulin E reactivity has been demonstrated in nutmeg and mace.73, 74

Toxicology

Acute psychosis and anticholinergic-like episodes caused by nutmeg ingestion have been reported with a wide variety of symptoms. Effects occurred within 0.5 to 8 hours following ingestion and are characterized by cutaneous flushing, tachycardia, decreased salivation, GI symptoms (eg, nausea, vomiting, abdominal pain), fever, and CNS excitation with anxiety/fear; miosis or mydriasis are not considered to be reliable signs, as either may be present. There have been rare reports of shock, coma, and death. Treatment is supportive, with the use of antipsychotic therapy when necessary.24, 25, 32, 35, 36

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.20 Myristic acid found in nutmeg, as in many other plant and animal fats, is a key component of human cellular biochemistry. It is recognized by the US Food and Drug Administration as safe when used as a flavoring agent or food-additive and is of low acute toxicity in rodent studies.75 Safrole, a minor component of the oil, promoted hepatocarcinomas in mice.76, 77, 78

References

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