Mace

Mace (Myristica fragrans Aril): A Comprehensive Reference

1. Identity and Botanical Description

Botanical and Common Names

Scientific name: Myristica fragrans Houtt. (family Myristicaceae). The part used as mace is the aril — the lacy, reticulated membrane covering the seed of the fruit. Mace is a spice made from the dried aril that covers the seed of the nutmeg fruit. In Indian trade it is called Javitri, in Malay tradition buah pala, and in Thai traditional medicine it is known as Dok-Chan. The genus name Myristica comes from the Greek meaning "myrrh-scented," in reference to the fragrant seeds and arils of the nutmeg plant.

Source Plant and Geography

This aromatic tree is economically significant as the primary source of two distinct spices: nutmeg, derived from its seed, and mace, obtained from the seed's aril. Valued for centuries in global spice trade, M. fragrans is now widely cultivated throughout tropical regions, including parts of Southeast Asia (Indonesia, Malaysia), South Asia (Kerala in India, Sri Lanka), East Asia (Guangdong and Yunnan in China, Taiwan), the Caribbean (notably Grenada), and South America.

Myristica fragrans is an evergreen tree, usually 5–15 m (16–49 ft) tall, but occasionally reaching 20 m (66 ft) or even 30 m (98 ft) on Tidore. Several related species also produce inferior forms of mace with limited use, such as Myristica argentea (Papua mace) and Myristica malabarica (Bombay or wild mace).

Morphology of the Fruit and Mace

The nutmeg fruit, in fact, is a drupe, about the size of an apricot, which when ripe splits up to reveal a single centrally situated oval-shaped hard kernel known as "nutmeg spice." The seed is closely enveloped by crimson-red colored lacy or thread-like arils known as "mace." Both spices have a similar warm, sweet aromatic flavor. The fruit of the nutmeg tree is apricot- or peachlike and bursts open when fully ripe — usually within six to eight months of flowering — exposing the shiny dark seed (nutmeg) enveloped by the crimson-colored aril (mace).

The fruit part of the tree has 78% flesh, 4% mace, 5% shell, and 13% seed. This proportional rarity of mace relative to the whole fruit contributes to its traditionally higher cost per unit weight compared to nutmeg.

Common Forms and Preparations

After harvest, the mace is carefully removed from the nutmeg seed and dried separately. When dry, it turns a warm orange color. The dried mace is sold either as a whole "blade" or as a finely ground powder. Mace is gently peeled off from the kernel surface, flattened into strips, dried, and sold either as whole "mace blades" or finely ground into powder.

Beyond whole and ground forms, mace is also used to produce an essential oil. Mace oil is obtained by the steam distillation of dried aril. The color of mace oil ranges from pale yellow to reddish yellow. A highly aromatic spice, it is sweet, spicy, and has a slightly woody undernote. Additionally, oleoresin preparations are manufactured for food flavoring and pharmaceutical applications.

Mace is flaky, yellow to orange in color, and possesses a delicate aroma. Other East Indian varieties, including Java Estate and Siauw maces, and the West Indian (or Grenada) mace are considered to be inferior in quality to the Banda. Banda mace, originating from the Banda Islands of Indonesia, is regarded as the premium grade.

2. Historical and Traditional Use

Ancient and Indigenous Origins

There is archaeological evidence of nutmeg use by the Indigenous peoples of the Indonesian Banda Islands as early as 1500 BCE. Nutmeg and mace were mentioned in the Indian Vedas (1500 and 1000 BCE), where they were prescribed for digestive and nervous system problems, headaches, and bad breath.

Ayurvedic Tradition

Nutmeg and mace have been used across South and Southeast Asia for medicinal and culinary purposes since ancient times. Traditional Ayurvedic medicine suggests the use of mace as a remedy for stomach ailments. In Ayurveda, mace (Javitri) has been applied in carminative formulations and tonics aimed at digestive health, and nutmeg and mace have a long history in Ayurvedic and traditional Chinese and Persian medicine. They have been used to ease digestion, reduce inflammation, treat acne, promote relaxation, aid erectile dysfunction, and improve mood and sleep.

Traditional Chinese Medicine

Nutmeg is an important ethnomedicinal resource with both dietary and therapeutic significance in traditional Asian medical systems. Its use dates back to its introduction into China around the 3rd–4th centuries CE. Classical medical texts document its core functions of "warming the middle jiao to promote qi flow, and astringing the intestines to relieve diarrhea."

Chinese and Southeast Asian Folk Medicine

Chinese healers used them to calm the stomach, and Ayurvedic and Far Eastern Traditional Medicine practitioners continue to do so today. Mace, a common spice which is the aril surrounding the shell enclosing the seed, is used in Indonesian folk medicine as aromatic stomachics, analgesics, and a medicine for rheumatism.

In Thai traditional medicine, the aril (mace) of Myristica fragrans, known as Dok-Chan, is a spice that has long been used for treating stomach discomfort, peptic ulcer, and nausea. It is an ingredient in many remedies in Thai traditional medicine, e.g., Ya-Hom-Thep-Bha-Jit, Ya-Hom-Nao-Wa-Kot, and Ya-That-Bun-Job, which are used to treat dyspepsia and other gastrointestinal tract symptoms.

Islamic and Unani Medicine

Islamic medicine, and its use of herbs and spices such as nutmeg and mace to address bodily imbalances, flourished in the 9th–10th centuries and later influenced European medical practice. In Unani medicine, M. fragrans (nutmeg) has been mentioned to be of value in the management of male sexual disorders.

Classical Mediterranean and European Use

Though its use in ancient Rome is uncertain, a surviving mention of mace in the Roman epicure Apicius cookbook — also in the context of treating stomach troubles — implies Roman familiarity with the spice. Both nutmeg and mace were introduced to medieval Europe by Arab traders and found widespread popularity among noble European gastronomes.

By the 6th century, Byzantine medical texts clearly mentioned the two spices, nutmeg and mace. During the Middle Ages, mace was one of the spices used by physicians and others to help protect against the Black Plague. In the seventeenth century physicians claimed that a nutmeg pomander was a cure for the bloody flux and the sweating sickness, later called the black plague, and nutmeg was also supposed to have aphrodisiac properties.

Mace was a common ingredient in many 17th-century British recipes for the wealthy, appearing more frequently than cinnamon or ginger in The Accomplisht Cook, or the Art & Mystery of Cookery (1660).

Traditional Preparations

Traditional uses have encompassed a wide range of preparation methods: decoctions and infusions of dried mace blades for gastrointestinal complaints; incorporation into complex polyherbal formulations in Ayurveda, Unani, and Chinese medicine; topical application of the essential oil in carrier oils for musculoskeletal pain; and use as a flavoring agent in foods. Mace is used in traditional medicine for fever, digestive issues, asthma, and dental caries. Mace is used in traditional Asian medicine, aromatherapy, and the preparation of soaps and perfumes.

3. Chemical Composition and Key Constituents

Volatile (Essential) Oil

Fixed oils are virtually absent from mace and volatile oil accounts for 4–17% of the composition of mace. The oil yield from mace is 8.1–10.3%.

Gas chromatographic analysis has established that the essential oil of mace consists of a mixture of approximately 87.5% monoterpenes, 5.5% monoterpene alcohols, 6.5% aromatic ethers, together with 0.5% other components. Nine monoterpene hydrocarbons, six monoterpene alcohols, two aromatic hydrocarbons, one sesquiterpene, and six aromatic ethers have been identified.

In one comparative GC-MS study of mace oil, the main components in mace oil were α-pinene (13.975%), sabinene (26.407%), β-myrcene (14.193%), safrole (6.493%), and myristicin (27.279%). The primary chemical constituents of M. fragrans essential oil more broadly include sabinene, eugenol, myristicin, caryophyllene, β‐myrcene, and α‐pinene.

Non-Volatile Phytochemicals

Beyond its volatile fraction, mace contains a rich array of non-volatile secondary metabolites. Numerous studies have indicated that M. fragrans contains diverse phytochemicals such as lignans, neolignans, diphenylalkanes, phenylpropanoids, and terpenoids. Studies have reported that it contains alkaloids, terpenoids, phenols, flavonoids, and glycosides, with myristicin, macelignan, safrole, and sabinene as prime bioactive components.

Phytochemical investigations have identified a total of 328 compounds, with lignans and phenylpropanoids such as macelignan and myristicin recognized as key bioactive substances.

Among the constituents identified, macelignan (1), meso-dihydroguaiaretic acid (2), myristicin (111), and malabaricone C (Mal C, 104) are the most active compounds. Other compounds uniquely isolated from the aril include neolignans such as fragransol-C, fragransol-D, myristicanol-A, and myristicanol-B, as well as the anti-inflammatory compound malabaricone B and C.

The fixed oil composition of mace differs from nutmeg: the fixed oil content of sound nutmegs varies from 25–40% while that of mace is 20–30%. The principal fixed oil constituent is trimyristin, a triglyceride of myristic acid. The spice contains fixed oil trimyristin and many essential volatile oils which give a sweet aromatic flavor, such as myristicin, elemicin, eugenol, and safrole.

Key Bioactive Compounds: Profiles

Myristicin

Myristicin is methoxysafrole, the principal aromatic constituent of the volatile oil of nutmeg. Myristicin is a colorless and volatile phenyl propane derivative that is insoluble in water. It is mainly used as an insect and pest repellent, exhibiting neurotoxic and anti-cholinergic effects. Medically, it prevents liver damage and tumor formation. Several pharmacological studies of Myristica fragrans show the anti-inflammatory properties of myristicin from mace, and also have antifungal, antibacterial, larvicidal, and antioxidant potential.

Macelignan

Macelignan found in the nutmeg mace of Myristica fragrans obtains increasing attention as a new avenue in treating various diseases. Macelignan has been shown to possess a spectrum of pharmacological activities, including anti-bacterial, anti-inflammatory, anti-cancer, anti-diabetes, and hepatoprotective activities; recently, it has also been shown to have neuroprotective activities.

Elemicin

Twenty-three phytoconstituents were identified in the seed extract with elemicin (24.44%) as the major constituent. Lipid peroxidase, catalase, and DPPH assays were performed using the isolated elemicin, and the results revealed significant antioxidant activity.

Malabaricone C

Malabaricone C showed a strong inhibitory effect on LPS-induced production of NO in RAW264.7 cells and exhibited the LPS-induced COX-2 and iNOS expressions. Other research studies evaluated maceneolignans A, verrucosin, and malabaricone C which were isolated from the methanol extract of mace and inhibited the release of β-hexosaminidase in rat basophilic leukemia cells (RBL-2H3) and also inhibited antigen-stimulated tumor necrosis factor-α production.

Additional Phenylpropanoids and Terpenoids

Other compounds such as dehydrodiisoeugenol, malabaricone B and C, and elemicins have also shown strong antioxidant potential and enzyme inhibitory properties, which enhance insulin sensitivity, inhibit α-glucosidase, reduce oxidative stress, and support neurocognitive function by inhibiting inflammatory cytokines (IL-6, IL-1β, and TNF-α).

Mace contains monoterpene hydrocarbons, oxygenated monoterpenes, and aromatic ethers. It has a higher proportion of essential oil than nutmeg kernel.

4. Established Mechanisms of Action

Anti-Inflammatory Pathways

M. fragrans exhibits antioxidant, anti-inflammatory, antidiabetic, antimicrobial, and anticancer properties by modulating various pathways like PI3K/Akt/mTOR, MAPK, and NF-κB signaling pathways and G0/G1 or G2/M phase arrest. In preclinical animal studies, the methanol extract (1.5 g/kg), ether fraction (0.9 g/kg), n-hexane fraction (0.5 g/kg), Fr-II (0.19 g/kg), and Fr-VI (0.17 g/kg) showed a lasting anti-inflammatory activity, and the potencies of these fractions were approximately the same as that of indomethacin (10 mg/kg). Fr-VI was determined to be myristicin. These results suggest that the anti-inflammatory action of mace is due to the myristicin that it contains.

At the cellular level, protection of skin keratinocytes from UV-B-induced damage has been attained by inhibiting MMP-9 and COX-2 expression by attenuating the activation of MAPKs and PI3K.

Monoamine Oxidase Inhibition

Myristicin acts by moderately inhibiting monoamine oxidase, causing anticholinergic symptoms. It also leads to the formation of the metabolite 3-methoxy-4,5-methylendioxy amphetamine (MMDA), responsible for its psychedelic effects.

Neuroprotective Mechanisms

Macelignan isolated from the dried seed kernels of M. fragrans could significantly decrease neurodegenerative diseases by slowing down neuroinflammation and oxidative damages at the cellular level. A 2025 preclinical study investigated the mTOR pathway: the study aimed to evaluate the therapeutic effects of mace in preclinical models of vascular dementia (VaD) and to conduct an in-depth investigation into whether it acts by directly modulating the mTOR signaling pathway to restore mitochondrial homeostasis and subsequently inhibit neuronal apoptosis. Through in vivo (BCCAo rat model) and in vitro (CoCl2-induced HT22 cell injury model) experiments, and by integrating transcriptomics, computational biology, and multi-level molecular biology validations, the neuroprotective effects of mace and its core mechanism were comprehensively elucidated.

Using midbrain slice cultures, macelignan treatment protected dopaminergic neurons against the interferon (IFN)-γ and LPS-induced degeneration.

Antidiabetic Mechanisms

Macelignan enhanced insulin sensitivity and improved lipid metabolic disorders by activating peroxisome proliferator receptor (PPAR α/γ) and attenuating endoplasmic reticulum stress, suggesting that it is an antidiabetic agent for the treatment of metabolic disorders. Additionally, mace extracts have demonstrated direct enzyme inhibition: all extracts showed a dose-dependent alpha-amylase inhibitory effect. At concentration 500 µg/ml, all extracts showed more than 60% inhibition of the alpha-amylase enzyme and the highest inhibition (81.3%) at 500 µg/ml was observed in the DCM extract of mace.

Hepatoprotective Mechanisms

The hepatoprotective effect of M. fragrans kernel extract was comparable to that offered by the reference hepatoprotector, silymarin. Results revealed that the extract had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.

Antimicrobial Mechanisms

Macelignan, an active compound from seed of Myristica fragrans, exhibits strong antibacterial activity against Streptococcus mutans with MIC and MBC values of 3.9 µg/mL and 7.8 µg/mL, respectively. Macelignan possessed preferential activity against other oral microorganisms such as Streptococcus sobrinus, Streptococcus salivarius, Streptococcus sanguis, Lactobacillus acidophilus, and Lactobacillus casei in the MIC range of 2–31.3 µg/mL. In particular, the bactericidal test showed that macelignan, at a concentration of 20 µg/mL, completely inactivated S. mutans in 1 minute.

5. Scientific Evidence by Area of Use

5.1 Gastrointestinal Health

Traditional basis: Mace has been employed across Asian medical traditions for stomach discomfort, nausea, diarrhea, and dyspepsia. The aril (mace) of Myristica fragrans is a spice that has long been used for treating stomach discomfort, peptic ulcer, and nausea. It is an ingredient in many remedies in Thai traditional medicine used to treat dyspepsia and other gastrointestinal tract symptoms.

Preclinical (in vitro/in vivo) evidence: A 2020 study published in Evidence-Based Complementary and Alternative Medicine (PMC) tested aqueous and ethanolic mace extracts against Helicobacter pylori and gastric cancer cells. The ethanolic extract of mace exhibited antimicrobial activity against H. pylori ATCC 43504 and six clinical strains with MIC values of 125–250 µg/ml. The aqueous extract MICs against the H. pylori ATCC reference strain and six clinical strains were 500 µg/ml, compared with 0.5 µg/ml for the positive control, clarithromycin. The inhibitory effect of LPS-induced NO release and cytotoxic activity of the ethanolic extract had IC50 values of 82.19 µg/ml and 26.06 µg/ml, respectively, and the EC50 values for the DPPH and ABTS antioxidant assays were 13.41 µg/ml and 12.44 µg/ml, respectively.

A healing activity of malabaricone C against indomethacin-induced gastric ulceration in mice was reported, and it reduced the ulcer indices better than the positive control, omeprazole, with 88.4% and 86.1% reduction, respectively.

Evidence strength: The ethanolic mace extract had anti-H. pylori, anti-inflammatory, antioxidant, and anticancer activities. These data support further preclinical and clinical investigation to see if the mace extract could have a role in treating patients with dyspepsia, peptic ulcers, and possibly gastric cancer. Evidence is currently preclinical; no completed randomized controlled trials in humans on gastrointestinal indications were identified.

5.2 Anti-Inflammatory and Analgesic Effects

Preclinical evidence: One of the earliest pharmacological studies of mace specifically (Ozaki et al., 1989, published in Japanese Journal of Pharmacology) investigated the anti-inflammatory activity of mace fractions. Mace, which is the aril of the fruit of Myristica fragrans, has been used in Indonesian folk medicine as aromatic stomachics, analgesics, and a medicine for rheumatism. The study was carried out to elucidate the anti-inflammatory effect of methanol extract obtained from mace and its active principles. The anti-inflammatory activity of these fractions was investigated on carrageenin-induced edema in rats and acetic acid-induced vascular permeability in mice. The results demonstrated dose-dependent anti-inflammatory activity attributable principally to myristicin.

The anti-inflammatory effects of macelignan have been extensively studied. Macelignan was reported to prevent the development of allergen-induced asthma in experimental animal models. The protective effect was coupled to a reduction in CD4+ T cells production of interleukin-4 (IL-4), but with no apparent effect on IL-17 or interferon-cells. Animals administered macelignan showed lower expression of the type-2 T helper cell (Th2) transcription factor, GATA3.

Evidence strength: Anti-inflammatory evidence is preclinical (animal and cell-culture models). Human clinical trials are lacking. Some reported pharmacological properties of M. fragrans include anticancer, antidepressant, antidiabetic, anti-obesity, anti-inflammatory, analgesic, antimicrobial, antioxidant, hepatoprotective, and memory-enhancing. However, the clinical efficacy in long-term trials is still to be investigated.

5.3 Antimicrobial and Oral Health

In vitro evidence: The antibacterial properties of mace and its constituents against oral pathogens have been studied in cell-free settings. The specific activity and fast-effectiveness of macelignan against oral bacteria strongly suggest that it could be employed as a natural antibacterial agent in functional foods or oral care products.

One clinical study evaluated M. fragrans preparations as herbal pulpotomy agents in primary teeth. The study evaluated clinical and radiographic success of herbal gels Myristica fragrans (MF)–Nutmeg and Terminalia chebula (TC)–Myrobolan as pulpotomy medicaments in primary teeth. Twenty participants (n = 20), each with at least two primary molars requiring pulpotomy, were selected and divided into two test groups. This represents preliminary human data in a very specific dental context.

Evidence strength: Strong in vitro activity against cariogenic bacteria is documented, but human clinical evidence specific to mace as an oral antimicrobial agent remains limited to small pilot studies.

5.4 Antioxidant Activity

Multiple extraction and assay methods have confirmed the antioxidant capacity of mace. Clinical and experimental investigations have confirmed the antioxidant, antimicrobial, anti-inflammatory, anticancer, antimalarial, anticonvulsant, hepatoprotective, antiparasitic, insecticidal, and nematocidal activities of M. fragrans essential oil. In a study of mace extracts, the DPPH and ABTS assays returned EC50 values of 13.41 µg/mL and 12.44 µg/mL, respectively, for the ethanolic extract. The amount of essential oil extracted by steam distillation ranges between 4% and 16% and comprises 80–90% of monoterpene hydrocarbons.

Evidence strength: Antioxidant activity is well-established in laboratory assays (DPPH, ABTS, FRAP, etc.) using cell-free and cell-based models. Whether these effects translate to meaningful in-vivo antioxidant activity in humans has not been established through controlled trials.

5.5 Neuroprotective and Cognitive Effects

Key components of mace demonstrate multiple pharmacological activities, including neuroprotective, gastrointestinal regulatory, and hypoglycemic effects. M. fragrans has a long history of use in traditional medicine as a nervine tonic for enhancing cognitive function, relieving anxiety, and managing neurological symptoms associated with aging. Given its established ethnopharmacological profile, its principal active lignan, macelignan, could exert potent neuroprotective effects in the context of neurodegenerative diseases like vascular dementia (VaD).

A 2025 preclinical investigation examined macelignan in a rat model of vascular dementia, investigating the neuroprotective properties of macelignan in a preclinical model of vascular dementia (VaD) and elucidating the underlying molecular mechanisms, with a particular focus on its modulation of the mTOR signaling pathway and mitochondrial homeostasis.

Evidence strength: Neuroprotective evidence for mace/macelignan exists in cell-culture models and animal studies; no human clinical trials on cognitive or neuroprotective outcomes attributable specifically to mace have been published.

5.6 Antidiabetic and Metabolic Effects

Preclinical/in vitro evidence: Multiple in vitro studies have examined the capacity of mace extracts to inhibit carbohydrate-digesting enzymes. One study evaluated the anti-diabetic effect of sequentially extracted (hexane, dichloromethane, ethyl acetate, and ethanol) Myristica fragrans (mace) extracts. The in vitro anti-diabetic effect was evaluated for alpha-amylase inhibitory activity. All extracts showed a dose-dependent alpha-amylase inhibitory effect. At concentration 500 µg/ml, all extracts showed more than 60% inhibition of the alpha-amylase enzyme and the highest inhibition (81.30%) at 500 µg/ml was observed in the DCM extract of mace.

The lignan macelignan has shown PPAR-mediated mechanisms relevant to insulin sensitivity. A total extract of Myristica fragrans (nutmeg) activated the AMPK enzyme in differentiated C2C12 cells. As major constituents of nutmeg, seven lignans including macelignan, meso-dihydroguaiaretic acid, (+/−)-trans-dehydrodiisoeugenol, nectandrin B, licarin A, otobaphenol, and myristicin were isolated from this extract.

Evidence strength: All available evidence for antidiabetic activity is from in vitro enzyme assays and animal studies. No human clinical trials have been conducted.

5.7 Hepatoprotective Effects

In a rodent model study, liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). Rats were pre-treated with either oral administration of M. fragrans kernel extract (MFKE) at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin.

Evidence strength: Hepatoprotective effects have been demonstrated in animal models and are mechanistically plausible via Nrf2/ARE pathway activation. Human data are absent.

5.8 Anticancer Activity

Macelignan has been shown to possess a spectrum of pharmacological activities, including anti-cancer activities. This research has emphasized the importance of understanding and treating complex diseases such as cancer and Alzheimer's disease. Multiple in vitro cell-line studies have demonstrated cytotoxicity against various cancer cell lines, including gastric cancer (Kato III cells, as noted above). Evidence strength: Entirely preclinical (in vitro cell lines and animal models). No human clinical evidence exists.

6. Body Systems and Health Areas Associated with Mace

• Gastrointestinal system: Carminative, antidiarrheal, antiulcer, stomachic, anti-H. pylori, antinausea (traditional and preclinical support).
• Central nervous system: Traditional nervine tonic; preclinical neuroprotection via macelignan; monoamine oxidase inhibition by myristicin at higher doses.
• Metabolic/endocrine system: Alpha-amylase and alpha-glucosidase inhibition, PPAR activation, AMPK activation (all preclinical).
• Hepatic system: Nrf2/ARE pathway-mediated hepatoprotection (preclinical).
• Immune/inflammatory system: NF-κB and COX-2 inhibition, cytokine (TNF-α, IL-6, IL-1β) modulation (preclinical).
• Oral health: Bactericidal against cariogenic oral pathogens; explored as a pulpotomy agent in preliminary clinical work.
• Musculoskeletal system: Traditional topical use for rheumatic pain; anti-inflammatory mechanisms in animal models.
• Respiratory system: Macelignan shown to suppress Th2-mediated allergen-induced asthma in animal models; traditional use for asthma mentioned in Ayurveda.

7. Dosage Forms and Reported Dosages

The principal constituents of the spices nutmeg and mace are steam volatile oil (essential oil), fixed (fatty) oil, proteins, cellulose, pentosans, starch, resin, and mineral elements. Percentages of constituents differ between the spices and this is a consequence of geographical origin, quality, and duration of storage and even growing locations.

The following dosages are those stated in or implied by the cited sources:

• Anti-inflammatory preclinical model (Ozaki et al., 1989): The methanol extract (1.5 g/kg), ether fraction (0.9 g/kg), n-hexane fraction (0.5 g/kg), Fr-II (0.19 g/kg), and Fr-VI (0.17 g/kg) showed lasting anti-inflammatory activity — potencies approximately the same as indomethacin (10 mg/kg). These are rodent oral gavage doses and cannot be directly extrapolated to humans.
• Hepatoprotective preclinical model: M. fragrans kernel extract (MFKE) at 300 mg/kg daily for seven days was pre-administered orally in rats.
• In vitro antidiabetic testing: At a concentration of 500 µg/ml, all extracts showed more than 60% inhibition of alpha-amylase enzyme.
• Culinary/spice use: Mace is generally recognized as safe when used in food as a flavoring agent. No standardized therapeutic dosage for human supplemental use has been established.
• Essential oil (aromatic/topical): No clinical dose-ranging studies for mace essential oil applied aromatically or topically were identified in authoritative sources.

There are no clinical trials to support therapeutic dosing of mace as a dietary supplement in humans. Safety for doses above those found in foods is unproven; such doses should be avoided because of possible abortifacient effects.

8. Safety Considerations and Interactions

Myristicin Toxicity — the Principal Safety Concern

The chief safety concern associated with mace and nutmeg at supradietary doses is myristicin toxicity. Toxic outcomes related to myristicin in humans are largely associated with acute overdoses of nutmeg, the symptoms of which are generally attributed to myristicin.

Ingestion of excessive amounts of nutmeg (as little as one and a half seeds and up to 19 seeds) can result in a delirious stupor, with a combination of stimulation and drowsiness or weakness similar to opium and other narcotics. Patients with nutmeg overdose present with facial flushing, tachycardia, hypertension, blurred vision, dry mouth, psychoactive hallucinations, and feelings of euphoria, anxiety, and fear; symptoms typically subside after 24 to 36 hours.

Mechanism of Psychoactive/Toxic Effects

Myristicin acts by moderately inhibiting monoamine oxidase, causing anticholinergic symptoms. It also leads to the formation of the metabolite 3-methoxy-4,5-methylendioxy amphetamine (MMDA), responsible for its psychedelic effects. Myristicin is metabolized to 3-methoxy-4,5-methylenedioxyamphetamine, also known as MMDA. MMDA is a sympathomimetic with hallucinogenic properties and is believed to be the compound associated with nutmeg's hallucinogenic effects. Myristicin is also implicated in monoamine oxidase inhibition.

Documented Toxic Dose

The minimum dosage of nutmeg that can cause psychogenic effect is 5 g (ground nutmeg) with 1 to 2 mg myristicin content, and this dosage is considered the "toxic dose." Those symptoms usually occur 3 to 6 hours after ingestion of myristicin or foodstuffs containing it, and effects may persist up to 72 hours.

Mace-Specific Poisoning Reports

A published case report documented acute mace poisoning in a child. A six-year-old child presented with serotonergic and anticholinergic symptoms, with an altered level of consciousness and respiratory acidosis after unintentionally ingesting six pieces of mace. She recovered with supportive care alone and was discharged 36 hours post-ingestion. Symptoms can affect the gastrointestinal system, causing nausea, vomiting, abdominal pain, or constipation. Cardiovascular effects are usually the result of a weak monoamine oxidase inhibitor effect causing tachycardia, hypertension, or hypotension. CNS toxicity commonly results in anticholinergic effects and psychotropic effects causing anxiety, confusion, hallucinations, psychosis, and seizures with altered levels of consciousness ranging from delirium to coma.

Fatalities

Nutmeg poisoning alone is not commonly known to be fatal, with only two reported fatal cases: one more than a century ago and another a few decades ago. The most recent case of fatality from nutmeg overdose involved the simultaneous abuse of a fatal dose of flunitrazepam.

Psychiatric Conditions

The excessive use of nutmeg or mace is not recommended in people with psychiatric conditions.

Pregnancy

Safety for doses above those found in foods is unproven; such doses should be avoided because of possible abortifacient effects.

Drug Interactions

Myristicin is also implicated in monoamine oxidase inhibition. Given myristicin's MAO inhibitory activity, theoretically significant interactions may occur with serotonergic drugs, sympathomimetics, and other CNS-active medications at supratherapeutic mace doses. Nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. CYP450 inhibition could affect the metabolism of drugs that are CYP substrates, though the clinical relevance at culinary doses is uncertain. No drug interactions are well documented at dietary intake levels.

Allergic Reactions

Allergy, contact dermatitis, and asthma have been reported with mace/nutmeg exposure.

General Safety Status

Mace is generally recognized as safe when used in food as a flavoring agent. Attention is required for its toxic constituent myristicin and the detoxification mechanisms involved in processing. It has been well known that myristicin is a principal aromatic constituent of M. fragrans, and its overdose intake in humans causes severe psychopharmacological effects.

References

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• Myristica Fragrans — ScienceDirect Topics Overview
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