Nutmeg

Across European kitchens and folk practice nutmeg is a warming carminative. A pinch of the grated seed is taken for sluggish digestion, nausea and flatulence, and in warm milk as a mild sleep aid.

The dose is always small. Nutmeg was used less as a medicine in its own right than as a corrective added to food.

In Traditional Chinese Medicine the roasted seed is rou dou kou. It is given in small amounts to “astringe the intestines” and check chronic diarrhoea, and to warm the middle burner against cold, deficient digestion ^{4Reference 4Luo et al. · 2026ReviewMyristica fragrans: a comprehensive review of its botanical characterization, traditional uses, phytochemistry and pharmacological propertiesView study →}.

In Ayurvedic and Unani practice the seed is jaiphal, used for weak digestive fire, nausea and insomnia. The Unani tradition in particular regards it as an aphrodisiac.

Both systems use the seed sparingly and treat it as warming and drying.

Large amounts of the ground seed have long been swallowed for their psychoactive effect. Poison centres saw a rise in such cases in 2020 and 2021, when a social-media “nutmeg challenge” circulated ^{46Reference 46Bleisch A et al. · 2026Case reportIntoxication with nutmeg: a case presentation and analysis of Swiss poisons information center (Tox Info Suisse) enquiries 2014-2023 — case report and poison-centre seriesView study →}.

In rats, a nutmeg kernel extract (300 mg/kg orally for seven days) prevented paracetamol-induced liver injury. It lowered transaminases and lipid peroxidation, reduced TNF-α, IL-1β and NF-κB, and induced the Nrf2/HO-1 pathway, with results comparable to silymarin ^{18Reference 18Dkhil et al. · 2019Myristica fragrans kernels prevent paracetamol-induced hepatotoxicity by inducing anti-apoptotic genes and the Nrf2/HO-1 pathwayView study →}.

Mouse work reproduced the pattern against L-asparaginase toxicity ^{19Reference 19Poorbagher et al. · 2022AnimalHepatoprotective effect of nanoniosome-loaded Myristica fragrans phenolic compounds in mice-induced hepatotoxicityView study →}. In a high-fat-diet model of fatty liver disease, a seed extract lowered hepatic IL-6 and TNF-α and improved lipid handling through changes in the gut microbiome ^{20Reference 20Zhao et al. · 2022AnimalMyristica fragrans extract regulates gut microbes and metabolites to attenuate hepatic inflammation and lipid metabolism disorders in NAFLD miceView study →}.

The proposed mechanism is inhibition of the cytochrome P450 step that forms paracetamol’s toxic metabolite, together with stronger antioxidant defences. All of these are chemically induced injuries in rodents, at extract doses far above culinary intake, with no human liver data.

Seed extracts show strong DPPH, ABTS, superoxide and hydroxyl-radical scavenging, with malabaricone C and dehydrodiisoeugenol among the main active molecules ^{12Reference 12Li et al. · 2020Evaluation of antioxidant and anti-α-glucosidase activities of various solvent extracts and major bioactive components from the seeds of Myristica fragransView study →}. Diarylbutane lignans from the seed inhibited LDL oxidation, the most potent with an IC₅₀ of about 2.6 µM ^{13Reference 13Kwon et al. · 2008Low-density lipoprotein (LDL)-antioxidant lignans from Myristica fragrans seedsView study →}.

The essential oil and a lignan from the root add further scavenging data ^{14,15Reference 14Piaru et al. · 2012Antioxidant and antiangiogenic activities of the essential oils of Myristica fragrans and Morinda citrifoliaView study →Reference 15Ginting et al. · 2020Lignan compound isolated from n-hexane extract of Myristica fragrans Houtt. root as antioxidant and antitumorView study →}.

The work is almost entirely in cell-free assays. It shows chemical activity rather than an antioxidant effect in people, and the potent forms are purified lignans rather than the ground spice.

Myristicin suppresses inflammatory signalling in macrophages. In dsRNA-stimulated RAW 264.7 cells it inhibited nitric oxide and a panel of cytokines through a calcium-dependent pathway, at up to 50 µM without cytotoxicity ^{16Reference 16Lee · 2011Anti-inflammatory effect of myristicin on RAW 264.7 macrophages stimulated with polyinosinic-polycytidylic acidView study →}.

A 2024 study isolated 33 new neolignan and diarylnonanoid conjugates, several of which inhibited TLR-driven NF-κB/AP1 and IRF signalling ^{17Reference 17Le et al. · 2024Neolignans and diarylnonanoid derivatives with anti-inflammatory activity from Myristica fragrans Houtt. seedsView study →}. Mace extracts inhibited LPS-induced nitric oxide release in the same cell model ^{11Reference 11Suthisamphat et al. · 2020Anti-Helicobacter pylori, anti-inflammatory, cytotoxic and antioxidant activities of mace extracts from Myristica fragransView study →}.

TNF-α, IL-1β and NF-κB also fell in the liver-injury models, so the effect appears in animals as well as in cell culture ^{18,20Reference 18Dkhil et al. · 2019Myristica fragrans kernels prevent paracetamol-induced hepatotoxicity by inducing anti-apoptotic genes and the Nrf2/HO-1 pathwayView study →Reference 20Zhao et al. · 2022AnimalMyristica fragrans extract regulates gut microbes and metabolites to attenuate hepatic inflammation and lipid metabolism disorders in NAFLD miceView study →}.

There is no human anti-inflammatory endpoint. The active molecules are minor components of the whole spice, so the cell-culture doses do not translate directly to dietary use.

Seed constituents (trimyristin, myristic acid, myristicin) gave measurable MICs against Gram-positive and Gram-negative organisms ^{8Reference 8Narasimhan · 2006Antibacterial principles from Myristica fragrans seedsView study →}, and the essential oil inhibited a panel of endodontic pathogens ^{9Reference 9Setty et al. · 2020In vitroIn vitro evaluation of antimicrobial effect of Myristica fragrans on common endodontic pathogensView study →}.

Ester derivatives of α-terpineol and 4-carvomenthenol showed MICs of 40–170 µg/mL, with synergy alongside streptomycin and antibiofilm activity ^{10Reference 10Kaur et al. · 2025Antimicrobial, synergistic and antibiofilm activities of Myristica fragrans Houtt. bioactive compounds and their derivativesView study →}.

An ethanolic mace extract inhibited Helicobacter pylori at 125–250 µg/mL, roughly 250–500-fold weaker than the antibiotic clarithromycin ^{11Reference 11Suthisamphat et al. · 2020Anti-Helicobacter pylori, anti-inflammatory, cytotoxic and antioxidant activities of mace extracts from Myristica fragransView study →}.

These are in-vitro MICs, largely for the essential oil rather than the ingested seed. No animal infection model or human data exists.

Methanolic seed extract inhibited α-glucosidase ^{12Reference 12Li et al. · 2020Evaluation of antioxidant and anti-α-glucosidase activities of various solvent extracts and major bioactive components from the seeds of Myristica fragransView study →}, and an ethanolic extract inhibited pancreatic lipase by about 66% at 100 µg/mL, approaching orlistat ^{21Reference 21VANGOORI et al. · 2019In vitroProminent pancreatic lipase inhibition and free-radical scavenging activity of a Myristica fragrans ethanolic extract in vitroView study →}.

In macrophages, nutmeg promoted cholesterol efflux through ABCA1/LXRα and lowered cytokines ^{22Reference 22Liu et al. · 2021Myristica fragrans promotes ABCA1 expression and cholesterol efflux in THP-1-derived macrophagesView study →}.

In high-fat-diet mice, an alcoholic seed extract reduced body weight, glucose, cholesterol and liver fat without changing food intake, and down-regulated FASN and SREBP-1c ^{23Reference 23Zhao et al. · 2020The protective effect of Myristica fragrans Houtt. extracts against obesity and inflammation by regulating free fatty acid metabolism in NAFLDView study →}.

A benzofuran from mace suppressed fat-cell differentiation in 3T3-L1 cells ^{24Reference 24Shyni et al. · 2021In vitroAn in vitro study reveals the anti-obesity effects of a benzofuran from Myristica fragransView study →}.

This is a mix of in-vitro enzyme assays and rodent diet models, with no glucose or weight endpoint in humans, and the active extracts differ from the whole spice.

An n-hexane seed extract at 5 mg/kg for three days improved learning and memory in young and aged mice, and reversed scopolamine- and diazepam-induced impairment ^{25Reference 25Parle et al. · 2004AnimalImprovement of mouse memory by Myristica fragrans seedsView study →}.

A methanolic extract protected rat cortex against scopolamine-induced oxidative damage and apoptosis through HO-1 induction ^{26Reference 26Al-Quraishy et al. · 2020AnimalMyristica fragrans seed extract reverses scopolamine-induced cortical injury via stimulation of HO-1 expression in male ratsView study →}. The seed lignan macelignan preserved mitochondrial function and prevented cognitive decline in a rat model of vascular dementia ^{27Reference 27Qi et al. · 2026Macelignan, a lignan from Myristica fragrans Houtt., rescues mitochondrial homeostasis and prevents cognitive decline in vascular dementiaView study →}.

A 2023 systematic review of plant-derived nootropics in humans did not list nutmeg among the agents with human cognitive evidence ^{28Reference 28Lorca et al. · 2023Systematic reviewPlant-derived nootropics and human cognition: a systematic reviewView study →}.

Gap: all positive data are rodent, and a human nootropic review found no clinical evidence for nutmeg.

In a rodent study, both a crude suspension and a petroleum-ether fraction (but not the aqueous extract) reduced loose stools or delayed their onset. The petroleum-ether fraction inhibited intestinal contractions evoked by acetylcholine, histamine and prostaglandin, an antispasmodic mechanism ^{29Reference 29Grover et al. · 2002Pharmacological studies on Myristica fragrans — antidiarrhoeal, hypnotic, analgesic and haemodynamic parametersView study →}.

Chinese and Ayurvedic texts describe the seed as “astringing the intestines to relieve diarrhea” ^{4Reference 4Luo et al. · 2026ReviewMyristica fragrans: a comprehensive review of its botanical characterization, traditional uses, phytochemistry and pharmacological propertiesView study →}.

The controlled evidence is one animal study, and no human antidiarrhoeal trial exists.

Cytotoxic and pro-apoptotic activity has been reported across several cell lines, mainly for myristicin. It induced mitochondrial apoptosis in K562 leukaemia cells ^{32Reference 32Martins et al. · 2014Myristicin from nutmeg induces apoptosis via the mitochondrial pathway in human leukaemia K562 cellsView study →}, suppressed gastric cancer in vitro and in a xenograft through EGFR/ERK (7.8–31 µM) ^{30Reference 30Li et al. · 2023Myristicin suppresses gastric cancer growth via targeting the EGFR/ERK signalling pathwayView study →}, induced apoptosis in MCF-7 breast cancer cells ^{31Reference 31Sufina Nazar · 2024Mechanistic evaluation of myristicin on apoptosis and cell-cycle regulation in breast cancer cellsView study →}, and inhibited liver-cancer cell growth through PI3K/AKT/mTOR at millimolar concentrations ^{33Reference 33Bao · 2021Anticancer effect of myristicin on hepatic carcinoma and related molecular mechanismView study →}.

The mace neolignan licarin A reduced NF-κB p65 activation in prostate cancer cells, with low toxicity in zebrafish ^{34Reference 34Blanco Carcache et al. · 2024Molecular networking, docking and biological evaluation of licarin A from Myristica fragrans as a potential cancer chemopreventive agentView study →}.

Gap: almost entirely cell-line work, several studies at millimolar concentrations unreachable by dietary or medicinal use. The single in-vivo result is a gastric xenograft, and myristicin’s own toxicity limits any therapeutic use.

A 50% ethanolic seed extract at 500 mg/kg for seven days increased mounting and intromission frequency and shortened mounting latency in male rats, compared against sildenafil ^{35Reference 35Tajuddin et al. · 2005An experimental study of the sexual-function-improving effect of Myristica fragrans Houtt. (nutmeg)View study →}.

A study in male mice found the same 50% ethanolic extract (500 mg/kg) stimulated mounting and mating performance without obvious short-term toxicity ^{36Reference 36Tajuddin et al. · 2003AnimalAphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt. (nutmeg) and Syzygium aromaticum (clove) in male miceView study →}.

Both come from the same research group at a fixed high dose. There is no human sexual-function data, and the mechanism is uncharacterised.

An alkaloid fraction reduced acetic-acid writhing in mice at 1 g/kg, but only in females, and 0.5 g/kg had no effect. The fraction was classed as slightly toxic (LD₅₀ 5.1 g/kg) ^{37Reference 37Hayfaa et al. · 2013AnimalEvaluation of analgesic activity and toxicity of alkaloids in Myristica fragrans seeds in miceView study →}.

An earlier study found only a weak effect for the crude suspension ^{29Reference 29Grover et al. · 2002Pharmacological studies on Myristica fragrans — antidiarrhoeal, hypnotic, analgesic and haemodynamic parametersView study →}.

The effect is weak and sex-specific, and appears only at doses close to the toxic range.

A petroleum-ether fraction lengthened barbiturate-induced sleeping time in rodents ^{29Reference 29Grover et al. · 2002Pharmacological studies on Myristica fragrans — antidiarrhoeal, hypnotic, analgesic and haemodynamic parametersView study →}.

⚠ A controlled rat study found that myristicin did not reduce anxiety, showed no GABA-A modulation, tended to increase anxiety, and blunted the effect of midazolam ^{38Reference 38Leiter E et al. · 2011AnimalEvaluation of the anxiolytic properties of myristicin, a component of nutmeg, in the male Sprague-Dawley rat. https://pubmed.ncbi.nlm.nih.gov/21560973/View study →}.

Gap: only a sleep-lengthening signal is supported, in one rodent study. The anxiolytic claim failed its direct test.

Intoxication. Features include euphoria, hallucinations, agitation, delirium, drowsiness, a racing heart, headache, nausea and vomiting, and changes in pupil size ^{46Reference 46Bleisch A et al. · 2026Case reportIntoxication with nutmeg: a case presentation and analysis of Swiss poisons information center (Tox Info Suisse) enquiries 2014-2023 — case report and poison-centre seriesView study →}. Most cases are mild. In a Swiss poison-centre series of 236 patients over ten years, there were no severe or fatal cases, and people with mild symptoms had taken a median of about 18 g ^{46Reference 46Bleisch A et al. · 2026Case reportIntoxication with nutmeg: a case presentation and analysis of Swiss poisons information center (Tox Info Suisse) enquiries 2014-2023 — case report and poison-centre seriesView study →}.

Timing. Symptoms begin one to six hours after ingestion and usually settle within 24 hours, with a maximum of about 72 hours. Myristicin, safrole and elemicin have half-lives of 8.5–19 hours, which is why symptoms persist ^{46Reference 46Bleisch A et al. · 2026Case reportIntoxication with nutmeg: a case presentation and analysis of Swiss poisons information center (Tox Info Suisse) enquiries 2014-2023 — case report and poison-centre seriesView study →}.

Myristicin. The compound behind much of nutmeg’s reported pharmacology is metabolically activated to reactive species ^{40Reference 40Zhu et al. · 2019Metabolic activation of myristicin and its role in cellular toxicityView study →} and is directly toxic to human neuroblastoma cells ^{41Reference 41Lee et al. · 2005Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cellsView study →}. It has been reviewed as a toxicological principle ^{5,39Reference 5Seneme et al. · 2021ReviewPharmacological and therapeutic potential of myristicin: a literature reviewView study →Reference 39Hallström H · 1997ReviewToxicological evaluation of myristicin — reviewView study →}. The classic pharmacology paper is Truitt’s 1967 work ^{43Reference 43Truitt et al. · 1967The pharmacology of myristicin and nutmeg. https://pubmed.ncbi.nlm.nih.gov/5615547/View study →}.

Other drugs. In an Illinois poison-centre series, people who took nutmeg together with psychoactive medicines had more serious toxicity. An additive serotonergic effect with SSRIs is plausible, though a Swiss case on fluoxetine ran a mild course ^{46Reference 46Bleisch A et al. · 2026Case reportIntoxication with nutmeg: a case presentation and analysis of Swiss poisons information center (Tox Info Suisse) enquiries 2014-2023 — case report and poison-centre seriesView study →}.

Drug metabolism. In laboratory tests, myristicin, the main active compound of nutmeg oil, irreversibly inhibited the drug-metabolising enzyme CYP1A2 ^{47Reference 47Yang et al. · 2015Identification and characterization of reactive metabolites in myristicin-mediated mechanism-based inhibition of CYP1A2View study →}. Myristicin is itself broken down by CYP3A4 and CYP1A2 ^{48Reference 48Yun et al. · 2003Roles of human liver cytochrome P450 3A4 and 1A2 enzymes in the oxidation of myristicinView study →}. None of this has been tested in people.

Anxiety. Myristicin did not reduce anxiety in rats and blunted the effect of midazolam ^{38Reference 38Leiter E et al. · 2011AnimalEvaluation of the anxiolytic properties of myristicin, a component of nutmeg, in the male Sprague-Dawley rat. https://pubmed.ncbi.nlm.nih.gov/21560973/View study →}.