Cogent Food & Agriculture

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Nutritional and therapeutic potential of nutmeg

(Myristica fragrans): A concurrent review

Muhammad Tauseef Sultan, Farhan Saeed, Hassan Raza, Aneeqa Ilyas,

Fatima Sadiq, Ali Musarrat, Muhammad Afzaal, Muzzamal Hussain,
Muhammad Ahtisham Raza & Entessar Al JBawi

To cite this article: Muhammad Tauseef Sultan, Farhan Saeed, Hassan Raza, Aneeqa
Ilyas, Fatima Sadiq, Ali Musarrat, Muhammad Afzaal, Muzzamal Hussain, Muhammad
Ahtisham Raza & Entessar Al JBawi (2023) Nutritional and therapeutic potential of nutmeg
(Myristica fragrans): A concurrent review, Cogent Food & Agriculture, 9:2, 2279701, DOI:
10.1080/23311932.2023.2279701

To link to this article: https://doi.org/10.1080/23311932.2023.2279701

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Sultan et al., Cogent Food & Agriculture (2023), 9: 2279701
https://doi.org/10.1080/23311932.2023.2279701

FOOD SCIENCE & TECHNOLOGY | REVIEW ARTICLE

Nutritional and therapeutic potential of nutmeg
(Myristica fragrans): A concurrent review
Muhammad Tauseef Sultan1, Farhan Saeed2*, Hassan Raza1, Aneeqa Ilyas1, Fatima Sadiq1,
Ali Musarrat1, Muhammad Afzaal2, Muzzamal Hussain2, Muhammad Ahtisham Raza2* and
Entessar Al JBawi3*
Received: 06 June 2023
Accepted: 31 October 2023
Abstract: The global health sector is changing with more consensus towards the
*Corresponding author: Entessar Al
Jbawi, Agricultural Extension
consumption of natural products to improve the health of mankind. As a result, the
Directorate, MAAR, Damascus, Syria nutrition market diversified with the inclusion of new herbal products with each
E-mail: dr.entessara@gmail.com
passing day. Myristica fragrans is a traditional spice used to enrich food with
*Farhan Saeed, Department of Food
Science, Government College
a specific aroma in the cuisines of every region. It has two distinctive parts, i.e.
University Faisalabad, Faisalabad nutmeg (seed) & mace (outer covering) that are used for the same purpose but
38000, Pakistan
E-mail: f.saeed@gcuf.edu.pk possess different health benefits. It contains significant amounts of active compo­
nents that are beneficial in reducing oxidative stress, lipid peroxidation, and aller­
*Muhammad Ahtisham Raza,
Department of Food Science, genic responses. In the current review, efforts were made to elucidate the
Government College University
Faisalabad
theoretical background of nutmeg and its health benefits. The antioxidant and
E-mail: maraza.201609935@gcuf. antimicrobial potential of nutmeg has been discussed in length and their commer­
edu.pk
cial applications have been highlighted. The health benefits associated with dia­
Reviewing editor: betes mellitus, cardiovascular diseases, inflammatory disorders, cancer insurgence,
María Luisa Escudero Gilete, Nutrition
and Bromatology, Universidad de neurodegeneration, etc. are in the limelight of the article. The evidence portraying
Sevilla, Spain
the negative aspects of nutmeg consumption and their critical analysis is discussed
Additional information is available at in length. Any plant’s positive and negative aspects depend on its rich phytochem­
the end of the article
istry and pharmaco-kinetics.

Subjects: Agriculture and Food; Food Additives & Ingredients; Food

Keywords: functional foods; medicinal plants; Myristica fragrans; antioxidants; health

benefits

1. Introduction
The dawn of the 21st century has witnessed the peak of research and development that spread to
every nick and corner of life. In the same era, drastic changes in dietary patterns led to the
worsening of health indicators. The changes were coupled with a higher incidence of metabolic
disorders that reverted the focus of the medical experts toward natural products and diet-health
linkages. Accordingly, nutritionists deliberated to get a clear insight into the issues and significance
of innovative and targeted approaches that can cloak the nutritional and medicinal needs of the
people (Wink, 2022). The old proverb “diet be the medicine and medicine be the diet” resurfaced
with more vigor and resultant health experts in collaboration with nutritionists coined terms like
functional and nutraceutical foods. Researchers across the globe conducted targeted research to
elucidate the potential of the inclusion of some traditional remedies. Even, some governments

© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution
License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribu­
tion, and reproduction in any medium, provided the original work is properly cited. The terms on
which this article has been published allow the posting of the Accepted Manuscript in
a repository by the author(s) or with their consent.

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conducted intensive research and declared certain areas of their countries as herbal valleys.
Nowadays, herbal products and their bioactive compounds are an important component of the
global nutrition market resulting in the retrieval of the lost legacy of traditional medicines.
According to WHO, 80% of total world’s population is dependent on herbal plants (Jamshidi-Kia
et al., 2018). Medicines from plants are safe, effective, and have fewer side effects (Yadav &
Agarwala, 2011). Many herbal plants like Ginger (Zingiber officinale), Mulathi (Glycyrrhiza glabra),
Cumin seeds (Nigella sativa), Pepper (Piper nigrum), and Ashwaganda (Withania somnifera) are
used in every corner of the world for treating innumerable health diseases and show highest
efficacy. Myristica fragrans are one of the valuable therapeutic plants for treating health disorders
and offer numerous benefits (Nguyen et al., 2021; Selling, 2021; Singh et al., 2010).

Myristica fragrans is commonly known as “nutmeg” and belongs to the family Myristiceae in the
order Magnoliales which comprises around 150 genera and many species. Myristica species are
natives of Eastern Indonesia, Sri Lanka, and India (Loizzo et al., 2016; Thangaselvabai et al., 2011)
and they are now cultivated in a lot of countries of the world (Pal et al., 2011). It is a common spice
in many food items such as sauces, meats, soups, and confectionery stuff (Gupta et al., 2013;
Leontowicz et al., 2006). M. fragrans is the chief source of three commercial goods such as nutmeg,
mace (fleshy aril), and essential oil, which are broadly used for flavoring purposes in many dishes
and offer valuable health effects (Weerakoon et al., 0000).

In the current review, efforts were made to elucidate the theoretical background of nutmeg and
its health benefits. The valuable effects of nutmeg against different diseases and some risks
associated with its consumption are discussed in separate headings. The nutritional composition,
phytochemistry, and pharmaco-kinetics of nutmeg have been discussed in length. The detailed
discussion has been done under the following headings.

1.1. Methodology for systemic selection of articles

Literature was collected from the databases of Google Scholar, Google search engine, Pubmed,
Science direct, Scoopus, and MDPI. The articles were searched through the keywords of nutmeg,
Myristica fragrans, Nutritional composition, Phytochemistry, Pharmacokinetics, Anti-cancer, Anti-
fungal, antibacterial, Neurological and psychoactive properties, Therapeutic potential, antioxidant,
anti-inflammatory, and cardioprotective effect of nutmeg.

1.1.1. Myristica fragrans: Taxonomical characterization

Nutmeg is a spice herb discovered by the Portuguese and was originated in Indonesia. Dutch
broadcasted the significance of M. fragrans. Nutmeg derives from the Latin word nux muscats
means “musky nut” (Gupta & Rajpurohit, 2011). It is known by many other names in different
countries of the world such as Jaiphal in Hindi, Urdu, and Marathi, Jaepatri in Bengali, Jafal in
Kashmiri, and Pala in Indonesian, while in English, it is named Nutmeg (Ali et al., 2018). Nutmeg
grows well on rich soils and in regions with an annual rainfall of 2000–3000 mm/year (Orwa et al.,
2009). M. fragrans requires a warm climate and survives best at 18–34ºC. Moreover, altitude above
sea level (0–700 m) is optimum for the proper growth of the plant (Saputro et al., 2016). A brief
taxonomy of Myristica fragrans is given in Table 1 (Kumari et al., 2021)

Myristica fragrans is a fragrant evergreen tree that grows to a height of 5–13 m, and occasion­
ally 20 m. Watery red sap or pink sap can be seen in the bark (Sultana et al., 2018). The pointed
alternating dark green leaves (5–15 cm × 2–7 cm) with a shining top surface are placed along the
branches on 1 cm long stems. Flowers are waxy, bell-shaped, pale yellow, and single-sexed. Male
flowers are 5–7 mm in length and are found in groups of 1 to 10 while female flowers are 1 cm
long and exist in a bunch of 1 to 3 flowers per group. Furthermore, nutmeg fruit is ~6–9 cm long
and is smooth, drooping, fleshy, and yellow (Asgarpanah & Kazemivash, 2012). It is interesting to
mention that the nutmeg flowering initiates at the age of 9 years lasts up to 75 years and usually
bears 2–3 crops/year. M. fragrans produces two spices nutmeg and mace, respectively (Kusuma
et al., 2020; Shafiei et al., 2012). Nutmeg is a seed present in the fruit and mace is red covering

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Table 1. Taxonomic description

Taxonomic rank Taxon
Kingdom Plantae
Sub kingdom Viridiplantae
Division Tracheophyta
Class Magnoliopsida
Order Magnoliales
Family Myristicaceae
Genus Myristica
Species Fragrans
Common name Nutmeg
Hindi/Urdu name Jaiphal

(aril) on the seed. M. fragrans seeds are broadly ovoid (about 2–3 cm in length), whitish, and
fleshy, and there are also red-brown veins transversely on their surface. When it is fresh, aril
(mace) is scarlet bright, but when it is dry it becomes brittle and yellowish-brown in color (Kiritikar
& Basu, 1999; Pal et al., 2011). It has a pleasant fragrance and is used as an ingredient to give
a slightly warm taste to the cuisines (Babua et al., 2021). M. fragrans seeds require 3–6 weeks to
dry and then they are all set to use for medicinal purposes (Jaiswal et al., 2009).

1.2. Nutritional composition and characterization

Nutmeg contains appreciable quantities of carbohydrates, dietary fiber, energy, and proteins.
Moreover, it contains fat-soluble vitamins such as A, E and C. It is predominantly rich in copper,
iron, magnesium, phosphorus sodium, potassium, manganese, calcium, and zinc (Agbogidi &
Azagbaekwe, 2013). In this regard, Nkwocha Chinelo et al. (2018) evaluated the African nutmeg
(Monodora myristica) for its proximate composition i.e. carbohydrate (35.92%), crude fiber (19.00 ±
1.00%), moisture (14.50 ± 0.52%), crude protein (12.09 ± 0.52%), crude lipid (16.00 ± 1.00%), and
total ash (2.50 ± 0.50%). Previously, Sharathchandra et al. (2023) reported lower values for fiber
10.91 ± 0.3 mg/g, higher lipids (23.28%), and moisture contents (51.03 ± 0.25 mg/g), and energy
level (1591.8 KJ/100 g). Besides, mineral content (mg/100 g) was also recorded, i.e. Zn (1.52 ± 0.11),
Al (4.98 ± 0.68), Cu (0.19 ± 0.02), Na (17.66 ± 0.32), Fe (21.71 ± 0.52), Mn (1.05 ± 0.35), P (112.03 ±
4.63), K (869.64 ± 4.03), Ca (416.01 ± 1.42), and Mg (86.96 ± 4.01). The biochemistry of the nutmeg
fixed oil is of interest due to the presence of myristic acid, stearic, palmitic, linoleic, and lauric
acids, and these are nutmeg fixed oil’s main components (Duarte et al., 2011). Description of the
phytochemical analysis indicated saponins, carbohydrates, tannins, proteins, amino acids, terpe­
noids, and flavonoids presence.

The phytochemicals present in the nutmeg are mainly centered in its essential oil. The produc­
tion of essential oil of M. fragrans was recently studied for seed, mace, kernel, and leaf at 5.21%,
6.24%, 3.16%, and 8.10%, respectively. Main fractions in the plant were found to be sesquiterpenes
(1.21%–16.76%), phenyl-propenes (1.96%–28.61%), and monoterpenes (53.77%–94.82%), in all
the parts of the plant. Myristicin (2.7%), safrole (1.4%), limonene (3.7–8.32%), terpine-4-ol (5.80–
11.83%), β-pinene (7.30–9.72%), α-pinene (9.40–18.04%), and a large portion of Sabinene (19.07–
41.70%) were notable phytochemicals present in the essential oil of (Ashokkumar et al., 2020;
Hoda et al., 2020; Pal et al., 2011; Zachariah et al., 2008). Monika-Thakur (2014) demonstrated that
M. fragrans active components have antimicrobial, antifungal, antioxidant, and antidepressant
properties. Francis et al. (2014) removed different M. fragrans chemical constituents like sabinene,
myristicin, eugenol, elemicin, and safrole, along with natural repellents and insecticides to control
Lasiodermaserricorne (Du et al., 2014).

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1.3. Phytochemistry
Phytochemicals are bioactive compounds present in plants like fruits, vegetables, leaves, roots,
flowers, and medicinal plants that work with fibers and nutrients to go as a defense system
against infection or more precisely protect against disease (Krishnaiah et al., 2007; Saxena &
Patil, 2012). Joseph and George (2014) examined the M. fragrans phytochemical properties of
phytosterols, saponins, flavonoids, tannins, proteins, and alkaloids as well as antibacterial and
antimicrobial activities (Pal et al., 2011).

Plants are well known to have diverse secondary metabolites and leading phytochemical con­
stituents like glycosides, phenolics, saponins, flavonoids, tannins, steroids, and alkaloids (Saxena &
Patil, 2012). The utilization of phytochemical components with firm antimicrobial characteristics is
of importance in the therapeutic medicine system. Nutmeg is a small bundle with several major
advantages. It is utilized for the healing and prevention of known conditions (Sharathchandra eta
al., 2023). M. fragrans phytochemicals such as machilin A enacted p38 mitogen-initiated protein
kinase by osteoblast separation just as some lignans like licarin B, licarin A, mesodihydroguaiaretic
acid, machilin F, myristargenol, and safrole improve anabolic action in metabolism of bone (Lee
et al., 2009).

Subjective phytochemical analysis has shown that steroids were distinguished in higher quantity,
terpenoids, and saponin were in moderate amounts, whereas tannin, alkaloid, and phenol were
detected in little quantity. Besides anthroquinone, anthocyanins and glycoside were not identified.
Similarly, the results of the study showed that terpenoid was detected in the quantity of (19.00 ±
3.18%), saponins (12.04 ± 3.33%), and steroid (32.75 ± 5.42%), whereas phenol (0.46 ± 0.10%), an
alkaloid (2.75 ± 0.82%) was detected in low amount (Nkwocha Chinelo et al., 2018). Phytochemical
profiling done by various researchers reported compounds including licarin, neolignan, verrucosin,
nectandrin, elemicin, myristicin, myristicin, isoelemicin, surinamensin, methoxylicarin A, malabar­
icone, myrislignan, dihydro-benzofuran, β-pinene, α-pinene, sabinene, phenylpropanoids, methyl
eugenol, eugenol, elemicin, methyl isoeugenol, triterpenoids, phenolic aldehyde, safrole, virolane,
erythrosurinamensin, and diaryl phenyl propanoid (Chiu et al., 2016; Du et al., 2014; Francis et al.,
2014; Morikawa et al., 2016).

M. fragrans contains calculable bioactive components that are useful in improving allergenic
reactions, repressing lipid peroxidation, and decreasing oxidative stress (Gupta et al., 2013;
Morikawa et al., 2016). Elimicin, safrole, myristicin, myristic acid, and Trimyristin from nutmeg
are accounted for their medicinal properties (Wiart, 2007). Because of nutmeg collection and
widespread along with strongest biological actions, it is now used as herbal medicine and
a kitchen spice in many countries, especially in China and India (Asgarpanah & Kazemivash, 2012).

1.4. Pharmacokinetics of Myristica fragrans

During the recent decade, (ADMET) absorption, distribution, metabolism, excretion, and toxicity
have been brought into early drug development processes rather than sequential development
because pharmacokinetics and ADMET are responsible for clinical trial failure. For absorption and
permeability screening, many in vitro plans have been made, out of which common is the Caco-2
cell monolayer model.

The penetrability and transport in the intestine of 10 neolignans that were isolated from
M. fragrans were contemplated, among 10 neolignans; the type of neolignans 8-O-4′- displayed
elevated permeability, whereas the neolignans of benzofuran-type disclosed poor permeability.
Amongst, almost eight neolignans were transported through passive diffusion. These results
showed that neolignans of 8-O-4′-type are much-assimilated compounds (Yang et al., 2010).
Gao et al. (2017) determined eugenol, iso-psoralen, bakuchiol, and psoralen, centralizations to
explore the M. fragrant pharmacokinetics process. As per the exploratory results, the M. fragrans

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compatibility can remarkably affect the pharmacokinetic cycle of principle components and in vivo
extend their distribution and speed up their metabolism and elimination.

Statistical analyses indicate that Myrislignan (neolignan extracted from M. fragrans) and podo­
phyllotoxin pharmacokinetic activities in rat models have major differences between the two
groups (Zhu et al., 2016). Sohn et al. (2007) stated that Anwuligan, 2, 3 - dibenzylbutane lignan
of M, fragrans has been revealed to hold a wider pharmacological effects range.

Liquid chromatography-mass spectrometry technique was applied to tissue distribution and

pharmacokinetics study of anwuligan after intragastric and intravenous administration. The out­
right bioavailability is about 16.2%, which addresses the current first-pass effect. After the admin­
istration in an intragastric way, enterohepatic dissemination was found. Anwuligan might be
distributed rapidly in numerous tissues as well as kept in high concentration in the liver (Song
et al., 2019).

The blood–brain barrier permeability of 12 lignans and three phenolic malabaricones of nutmeg
were investigated. Malabaricones had poor permeabilities, while Benzonfuran-type, arylnaphtha­
lene-type, and dibenzylbutane-type lignans had low to moderate permeabilities, and heterocyclic
and neolignan had moderate-high permeabilities, among the 15 compounds studied. To nectan­
drin B, verrucosin, acetic acid derivation, and 5-methoxy-dehydrodiisoeugenol an efflux was
counted in and the primary carrier for 9, 8 (P-glycoprotein). Dependency of concentration and
time tests showed the principle transport mechanism for myrislignan 7 and 8 and neolignans
dehydrodiisoeugenol, was passive diffusion (Wu et al., 2016). A technique was created to examine
(+)—licarin A and diastereomers isolicarin A in the blood of rats after administration from the
intravenous route. Lower quantification and detection limits were 0.10 µg/mL and 0.05 for iso­
licarin A and 0.25 and 0.05 Microgram/mL for (+)—licarin A. This analysis method was efficiently
applied to the pharmacokinetics study of (+)—licarin A and diastereomers isolicarin A in rodent
blood.

1.5. Oil chemistry

Oils from the promising medicinal plant Myristica fragrans hold a lot of active components that are
liable for several health benefits (Maya et al., 2004). Adewole et al. (2013) represented the results
of fatty acids such as eicosanoic acid, oleic acid, stearic acid, and palmitic acid; results indicated
that the plants possess fundamental fatty acids that are useful for both infants and adults. The
seed oil of African nutmeg physicochemical properties results in the mean value of these proper­
ties such as acid value (66.50 mg KOH g/1), peroxide value (4.13 ± 0.40), free fatty acids (33.26 mg/
g-1), specific gravity (1.464 g cm/3 refractive index (1.477), iodine value (101.61 mg of Iodine g/1),
saponification value (414.53 mg KOH g/1) and yellow color demonstrated that nutmeg oil (African)
is somehow a kind of dry oil and may not be healthy for cooking purposes (Burubai et al., 2009).

1.6. Pharmacological properties

Myristica fragrans have a wide range of bioactive components that play a central role in the
traditional medicine system and have been recommended for treating numerous chronic diseases,
due to their significant therapeutic effects. Nutmeg’s major constituents as kernel, mace, seed,
and leaf are likewise used in aroma and pharmaceutical industries (Ashokkumar et al., 2020).
Some of the health benefits of nutmeg are listed below.

1.7. Antioxidant properties

Antioxidants play a crucial role in the human body by hindering the oxidation process and thus
contributing to the improvement of health (Shahidi & Zhong, 2015). It was accounted that in
M. fragrans pericarp bioactive compounds limited cyclooxygenase enzymes COX-2 and COX-1
production bioassay method and lipid peroxidation (Zhang et al., 2015). A study reported that
M. fragrans contains cytotoxicity, anti-angiogenic, and antioxidant activities (Piaru et al., 2012).
Cao et al. (2015) announced that M. fragrans hinders the production of nitric oxide. Additionally,

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nutmeg showed strong antioxidant and hepatoprotective properties against isoproterenol-induced

hepatotoxicity and oxidative stress (Kareem et al., 2013).

M. fragrans extracts of acetone and ethanol have antioxidant activities with the method of
(FRAP) and (DPPH) assay due to myristicin, sabinene, and eugenol presence (Assa et al., 2014;
Gupta et al., 2013). In another research, mace extracts of nutmeg obtained EC50 values of 13.41 g/
ml and 12.44 g/ml, respectively, for DPPH and ABTS antioxidant tests, exhibiting radical antioxidant
and scavenging properties (Suthisamphat et al., 2020). Vangoori Yakaiah and Kavimani (2019)
clearly showed 88% inhibition of DPPH free radicals at the standard dose of 5 mg/mL. The standard
ascorbic acids also showed a similar inhibition (~90%) that depicts the significance of the MF
extract as a potential antioxidant.

The current era of nutrition usually revolves around determining the molecular targets of
bioactive compounds. In a study, Zhao et al. (2020) examine the nutmeg alcohol extract effects
on lipid synthesis and inflammation inhibition. They reported that nutmeg alcohol extract treat­
ment downregulated the sterol-regulating element-connecting protein 1c and gene expression of
fatty acid synthase thus decreasing the accumulation of lipids in cells. It was found that nutmeg
alcohol extract remarkably decreased liver function indexes, blood glucose, lipid accumulation,
cholesterol levels, and inflammation levels in mice. The root of nutmeg has a strong potential as
an antioxidant agent as compared to other plant parts of nutmeg. Strong antioxidant activity was
confirmed by DPPH activity with a 12.67 ppm IC50 value (Ginting et al., 2020).

1.8. Anti-cancer properties

Anticancer action is due to the effect of some biological or chemical substances to inhibit or
reverse carcinogenic advancement. Many plants have been reported in recent years that showed
anticancer activity; results support their use as chemotherapeutic agents and Myristica fragrans is
one of the most used anti-cancer agents with beneficial satisfying effects (Ginting et al., 2021;
Saydam & Nalkiran, 2021).

M. fragrans is quite effective for various cancer types of treatment such as colon cancer breast
cancer and skin papilloma (Piras et al., 2012). Gupta et al. (2013) demonstrated that nutmeg holds
antitumor and anticancer activities against different types of cancers. M. fragrans anti-
inflammatory properties were determined in the fibroblast cell culture which was then treated
with viral dsRNR mimetic.

Thuong et al. (2014) indicated that lignans like nectandrin B, fragransin A2, meso-
dihydroguaiaretic acid, and mace lignan, showcased their antitumor activity and cytotoxic against
the cancer cell lines. The root of nutmeg has solid potential as the anticancer agent in the nutmeg
plant parts as a dependent MFHR, MIT assay which showed moderate activity of anticancer against
MCF-7 cell lines (Ginting et al., 2020).

Phytochemicals, for example, quercetin, and myristicin, found in the ethanolic extract of nutmeg
hinder cytokines production and nitric oxide just as they contain inflammatory properties (Dewi
et al., 2015; Lee & Park, 2011). LPS-induced nitric oxide suppression in RAW264.7 cells and its
toxicity were found to be protective against stomach cancer when M. fragrans mace extract was
used (Suthisamphat et al., 2020).

1.9. Antifungal and antibacterial properties

At present, infectious diseases are the leading cause of death around the world. Almost half of the
deaths reported in temperate countries are due to bacterial contamination. But now, antibiotics
and many drugs are helpful in the treatment of several infectious diseases (Ayoola et al., 2008).

Myristica fragrans have anti-secretory and anti-diarrheal properties against various microbes and
pathogens (Grover et al., 2002). Two antimicrobial resorcinol malabaricone C and malabaricone

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B were separated from the mace, which is the outer covering of the seed of M. fragrans. Orabi et al.
(1991) showed that mace and nutmeg disclosed strong antifungal and antibacterial properties. It
is valuable to show the inhibitory activity against the bacterial strain of Streptococcus mutants and
to treat period ontic (Jangid et al., 2014). Shafiei et al. (2012) researched the M. fragrans anti­
bacterial capacity against various bacterial strains just as it is extremely effective against different
microorganisms. Furthermore, Dorman and Deans (2000) also examined the M. fragrans extracts
to establish that it has antifungal and antibacterial properties. It repressed the bacterial spores’
development and was utilized as an antiseptic, disinfectant, and food preservative. Akinboro et al.
(2012) studied M. fragrans anti-mutagenic and mutagenic effects on Mus musculus and Salmonella
typhimurium. Likewise, Radwan et al. (2014) demonstrated that it is effective as an antifungal
agent against plant microorganisms like Phomopsis viticola and Phomopsis obscurans. Nutmeg
alkaloids have been shown to have antibacterial activity against Gram-positive and Gram-negative
bacteria (Azeez et al., 2019).

Myristica fragrans leaf extracts a good source of tannin are associated with in vitro inhibition of
Ceratobasidium ramicola (a phytopathogenic fungus) growth. The 1% concentration of Tannin
extract of M. fragrans produced radial inhibition by 27.0% at 24 h of incubation (Firmansyah
et al., 2019). In a recent study, the essential oil of nutmeg showed antimalarial properties against
Plasmodium falciparum D6 (Ibrahim et al., 2020). Conversely, in situ, the efficacy of nano encap­
sulated and un-encapsulated (essential oil of Myristica fragrans) showed compelling protection
against contamination of aflatoxin B1 and fungal pervasion. Un-encapsulated MFEO displayed
fungitoxicity against food-borne molds and restrained aflatoxin B1 discharge by Aspergillus flavus
however nano-embodied MFEO indicated better inhibitory impact and fungitoxicity on the aflatoxin
biosynthesis (Das et al., 2020).

Furthermore, M. fragrans extract was found to have an antibacterial effect against Klebsiella
pneumoniae, Proteus vulgaris, and Staphylococcus aureus, when used regularly. Salmonella typhi­
murium, Bacillus subtilis and Pseudomonas aeruginosa were all resistant to M. fragrans extract
(Ibrahim & Oyinloye, 2011). Myristica fragrans (nutmeg) seeds extract and (AgNPs) silver nanopar­
ticles are accounted for to be viable against (MDR) multidrug-resistant Salmonella enterica in the
antibiofilm activity. In one study, nutmeg aqueous seed concentrate displayed 87% antibiofilm
activity, on the other hand, the biosynthesized silver nanoparticles showed antibiofilm activity of
99.1% (Balakrishnan et al., 2020). In the comparative study, Cherian et al. (2019) featured that
nutmeg leaf ester (MFLE) zinc oxide nanoparticles (MFLE-ZnONPs) are utilized as environmentally
friendly and cost-effective antibiotic agents against the MDR clinical isolates. Antibacterial effec­
tiveness was assessed by checking the development of 15 bacterial strains which were treated by
various dilution ranges of hydrolats and essential. Excipient essential oil inhibited P. multocida,
S. mutants, and E. faecalis growth, though the oil was effective against the strain (Matulyte et al.,
2020). Adewole et al. (2013) conducted a study to notice the antibacterial activity of nutmeg
against the standard of streptomycin. The antimicrobial screening result indicated the oil was
extremely sensitive against tried isolates. Following the incubation duration of 24 hours, the
inhibition zone against Staphylococcus aureus (11 mm), Bacillus subtilis (8 mm), and Escherichia
coli (11 mm). The outcome compares well with the standard of streptomycin; the inhibition zone
result against E. coli of the sample (11 mm) was higher than that recorded for the standard of
streptomycin (7 mm) (Adewole et al., 2013). Nurjanah et al. (2017) studied nutmeg oil’s antibac­
terial impact against pathogenic microbes (gram-positive bacteria: Staphylococcus epidermis,
Staphylococcus aureus, and gram-negative bacteria: Salmonella Typhi, Shigella Dysenteriae) (Setty
et al., 2020). Resistance design was researched by the method of in vitro disc diffusion utilizing the
essential oil concentration of 100%, 80%, 60%, 40%, and 20%. The result suggested that two
essential oils of nutmeg countered all bacterial species. The highest zone of inhibition for nutmeg
oil was achieved on 60% convergence (12.96 mm for S. aureus, 16.79 mm for S. epidermis, 13.46
mm for S. Dysenteriae and 16.50 mm for S. Typhi), while on the Sulawesi nutmeg oil the result on
concentration of 100% (18.84 mm for S. aureus, 16.54 mm for S. epidermis, 17.84 mm for
S. Dysenteriae, and 12.54 mm for S. typhi. Similarly, Sipahelut et al. (2019) determined the

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antifungal and antibacterial action of flesh oil of nutmeg fruit inhibiting the action growth of food-
destroying fungi, food-destroying bacteria, and pathogenic bacteria. The tested bacteria incorpo­
rate Escherichia coli and Staphylococcus aureus, while the tested fungi are Fusarium moniliforme
and Aspergillus flavus. The outcomes indicated that the nutmeg fruit flesh oil might suppress the
isolates’ growth at entire concentration. A higher concentration of the oil of nutmeg fruit flesh
increases the inhibition zone of bacterial growth. Flesh-derived oil utilization showed compact
antibacterial action against every tested bacterium. In any case, it showed feeble antifungal
activity against every tested fungus (Sipahelut et al., 2019). But the malabaricones C and B and
resorcinols, separated from the mace of nutmeg by exhibiting strong antifungal and antibacterial
activities (Khare, 2008). Potential antifungal properties were studied by Hoda et al. (2020) against
Aspergillus fumigatus demonstrated that the M. fragrans extract of hexane inhibited the produc­
tion of melanin by 76.09%, decreased the ergosterol content by 83.63% and A. fumigatus cell
hydrophobicity by 72.2% at MEC of about 0.078 mg/mL. It was tracked that the mace ethanolic
concentrate displayed antimicrobial action against six strains with MIC upsides of 125–250 μg/ml
and H. pylori (Suthisamphat et al., 2020). Another study was conducted by Firempong et al. (2016)
to decide Calabash nutmeg seeds, bark, root, and leaves extract against antifungal activity
(Monodora myristica). The M. myristica ethanolic extracts contained a compound mixture of
triterpenoids, flavonoids, saponins, alkaloids, general glycosides, steroids, and tannins. Roots and
seeds of nutmeg were best in repressing the C. albicans growth. Most plant extracts antifungal
activities were also the same as to Clotrimazole drug (standard).

Wang et al. (2019) contemplated a Myristica fragrans essential oil (MFEO), contrasting the β-CD
/MFEO antimicrobial activity and essential oil against Bacillus subtilis, the yeast Saccharomyces
cerevisiae, Klebsiella pneumoniae, Escherichia coli, Staphylococcus epidermidis, and Staphylococcus
aureus. Results indicated that the antimicrobial impact was improved after the inclusion of com­
plex formation. Ansory et al. (2020) reported nutmeg major antimicrobial compounds 1–4-terpi­
neol, safrole, 2-β-pinene, α-pinene, sabinene, and myristicin. Results indicated that MBC and MIC
on the Shigella sp. essential oil of nutmeg showed 12.11 mm inhibitory impacts at 1.25%, division 4
has 9.67 mm at 1.25%, and portion 2 at 2.5% displayed 5.88 mm inhibitory impacts. Escherichia
coli MBC and MIC nutmeg oils exhibit inhibitory impacts (10.89 mm) at 2.5%; part one showed
10.22 mm at 10%, and part 4 at 2.5% has 10.11 mm inhibitory impacts.

1.10. Neurological properties

The neurological disorder is mainly characterized by loss of memory, behavioral disorder, loss of
interest in daily activities, and cognitive disability. This disorder is increasing daily in developed
countries and is most common in older people (Orhan et al., 2004).

Myristica fragrans neuropharmacological activities in (CNS) are actually because of their bioac­
tive components (Sultana et al., 2018). Methanolic extract of M. fragrans seed on neuroprotective
effect on the scopolamine-prompted impacts have been reported. Methanolic extract treatment
shielded the subject cortex scopolamine effects by turning around the poisonousness markers
effects. Surprisingly, the Methanolic extract neuroprotective impact was practically identical to
that applied by antioxidant NAC reference (Al-Quraishy et al., 2020). The anxiogenic property of
Hexane and Trimyristin extract of nutmeg was evaluated in the rat models through the whole
board paradigm and elevated plus maze. The seeds concentrated by hexane additionally exhibited
stimulant action in rats by swim and tail tests by suspension (Asgarpanah & Kazemivash, 2012).
The ethyl acetic acid fraction indicated high metal chelating and neuroprotectivity ability. Results
affirmed the 5, 7-diacetyl chrysin, and trimyristin in the comparing fraction (Omidpanah et al.,
2022). Dhingra and Sharma (2006) showed that n-hexane extracts of Myristica fragrans seeds
exhibited a significant anti-depressant effect by using tail suspension test (TST) and forced swim
test (FST) in rat models. Nutmeg extract administration displayed a significant decline in the
immobility of mice. Furthermore, a 10 mg/kg dose of nutmeg showed similar effects to standard
drugs.

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The Myristica fragrans Houtt seed’s activity anti-cholinesterase was assessed. Compounds, for
example, (hydroxy-3’− methoxyphenyl hydroxypropyl benzene) indicated the effective action with
an IC50 estimation of 35.1 microM, trailed by [11 (malabaricone C), methylenedioxyphenyl—
dimethyl (dihydroxyphenyl)- butane] with IC50 estimations of 44.0 pM and 42.1, respectively.
This is the primary report on M. fragrans seeds anticholinesterase properties. M. fragrans may be
effective in the treatment of Alzheimer’s disease, according to the findings (Cuong et al., 2014).
Extract of Myristica fragrans has shown anxiogenic and antidepressant effects. Myristicin in the
nutmeg is termed a standard aromatic constituent of essential oil. In this specific context, McCall
(2011) revealed myristicin anxiolytic properties and its possible interactivity with the GABAA
receptor site. Afterward, Sonavane et al. (2002) reported that myristicin plays a role at the
GABAA receptor site apart from the benzodiazepine site. Phytochemical compounds of
M. fragrans, elemicin, and myristicin, offer pain-relieving effects, a mild narcotic, and antianxiety
by actuation of neurotransmitters dopamine and serotonin (Dhingra & Sharma, 2006; Leiter et al.,
2011; Romana et al., 2020).

Nagaraju et al. (2013) contemplated M. fragransin anxiolytic impact open field model utilizing
various parameters. They discovered that high dose has more anxiolytic action than little dosages.
Three compounds, malabaricone C, 5’- methoxylicarin A, and licarin A, were discovered to be
generally dynamic in the inhibition of FAAH in the rodent anxiety model. These compounds have
high potency and FAAH selectivity just as anxiolytic activity (El-Alfy et al., 2019). Patricia et al.
(2019) suggested that the DCM (as the nutmeg powder was fractionated using Dichloromethane
(DCM)) has high memory-improving activity, which might be because of the enhancement of
cholinergic transmission and antioxidant activity. The lessening of ketamine impact by DCM may
potentially result from oxidative stress attenuation and NMDA receptor interceded neurotransmis­
sion (Patricia et al., 2019).

Ghorbanian et al. (2019) evaluated the composition of nutmeg using GC-MS and they claimed
that there are three main components, i.e. myristicin (11.17%), myristic acid (39.93%), and
elemicin (22.16%). They further suggested that nutmeg extract pre-treatment successfully
decreased cell death, diminished seizure behavior, and enhanced glial initiation that is trailed by
the administration of PTZ. Taking everything into account, nutmeg extract may be viewed as
a helpful supplementary agent in the treatment of epilepsy through its neural loss attenuation
and glial activation

1.11. Antidiabetic properties

Diabetes mellitus is an enduring metabolic condition characterized by elevated glucose levels and
the insufficient secretion or action of insulin. Generally, many drugs are available in the market for
the management of diabetes and its complications (Abebe et al., 2014). Apart from their valuable
therapeutic effects, these drugs have surplus adverse effects such as hypoglycemia, secondary
failure, and cell death (Suji & Sivakami, 2003). In a study, Tahrani et al. (2010) demonstrated that
special consideration has been paid to alternative remedies for the treatment of diabetes using
herbal plants and their phytochemical components.

Nguyen et al. (2010) inspected M. fragrans; they found lignans of (THF) tetrahydrofuran which
are successful in diminishing levels of LDL, adipose tissue mass, and body weight. It has properties
of anti-obese nature because of the essence of adenosine monophosphate (AMP) initiated protein
kinase enactment system.

Vangoori Yakaiah and Kavimani (2019) evaluated the effects of anti-obesity MF extracts in
cafeteria diet-induced obese rats. The 10 weeks of the feeding of MF extract MFE 200 mg/kg and
400 mg/kg reduced the weight of the rats by 9.29% and 12.87%, respectively. The higher doses
were more effective and can be comparable to the standard drug or list at 50 mg. The results

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might be due to the inhibition of some digestive enzymes especially pancreatic lipase thus
resulting in reduced absorption of lipids ultimately reducing the energy intake.

M. fragrans seed extract showed strong antidiabetic properties by controlling hyperglycemia in

artificially induced diabetic rats (Somani & Singhai, 2008). Likewise, Lestari et al. (2012) indicated
that the anti-diabetic effect agonist PPAR γ/α present in the nutmeg extract. Arulmozhi et al.
(2007) demonstrated that the hydroalcoholic extract of nutmeg has been reported to be effective
against chlorpromazine-induced increased glucose levels and triglyceride advancements in animal
models. Oral administration of extracts reduced metabolic abnormalities as well as glucose levels.
Similarly, Myristica fragrans extract significantly reduced the raised cholesterol and triglyceride
levels of rats. So, it was confirmed that nutmeg extract improved the hyperglycemic condition and
irregular fatty acid metabolism in rat models.

The nutmeg extract administration to the diabetic rats caused a significant drop in the low-
density lipoprotein, malondialdehyde levels, and total cholesterol and triglycerides levels. Whereas
a remarkable elevation was noticed in the HDL serum levels and antioxidant capacity (Pashapoor
et al., 2020).

Myristica fragrans seed extract’s hypoglycemic potential in the in vivo study was determined
with glimepiride. This combination of therapy with glimepiride remarkably reduced the level of
glucose as compared to the standard (glimepiride). Dynamic simulation on a molecular basis
revealed that complexes of macelignan γ and α were more stable than those complexes of
pioglitazone (Nasreen et al., 2020).

The antidiabetic effect of nutmeg was investigated by Lestari et al. (2019), which indicated that
the level of blood glucose levels decreased by 20% after two days of therapy, 30% after four days
of therapy, and 40% after six days of treatment with nutmeg extracts. Luciferase assay indicated
that without safrole, as per dose-dependent action, nutmeg improved the PPAR α and γ activities,
which denoted the expected mechanism in bringing down the glucose levels. M. fragrans extracts
of petroleum ether diminished blood glucose levels in a normal diet, glucose diet, and alloxan-
prompted diabetic rodents (Sultana et al., 2018). The hypo-glycemic impact might be because of
the insulin release potentiation from beta-cells. Orally administered extract additionally smoth­
ered the glucose level expansion by the loading of glucose. This impact may be because of
diminishing intestinal glucose assimilation rate pancreatic discharge potentiation or glucose take-
up increase. The concentrate expanded the body weight in diabetic rodents, which may be because
of better glycemic control and increased levels of insulin secretion (Somani & Singhai, 2008).

The Myristica fragrans and its products can be used in conjunction with potential antidiabetic
drugs, e.g. glimepiride. In this context, Nasreen et al. (2020) reported the effect of combined
therapy including nutmeg extract and glimepiride that drastically decreased blood glucose levels.
Figure 1 presents a thematic diagram illustrating the anti-diabetic properties of nutmeg.

1.12. Anti-inflammatory activity

Inflammation is the body’s natural, defensive response to damaged tissue resulting from toxic
chemicals, physical trauma, or microbes. Acute and chronic inflammations are the two most
common types of inflammation. For millennia, medicinal plants have been a source of a wide
range of active substances, which have been widely employed as crude material to treat a variety
of inflammatory disorders (Kumar et al., 2013).

Many researchers reported the anti-inflammatory action of nutmeg as well as its extracted oil.
A study described that nutmeg reduced the cytokines such as tumor necrosis factor and inter­
leukin. The extract also reduced the cyclooxygenase-2 pathway and contributed to the significant
reduction of inflammatory markers (Mueller et al., 2010).

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Figure 1. Thematic diagram

showing the antidiabetic
potential of nutmeg.

The anti-inflammatory activity of flavonoid-rich fractions from M. fragrans’s ethanolic extract

was confirmed, demonstrating the plant’s importance as an anti-inflammatory medicine
(Akinwunmi & Oyedapo, 2014). Myrislignan, a phytochemical component of M. fragrans inhibited
the protein expressions and mRNA expression of cyclooxygenase-2 and inducible iNOS in LPS-
stimulated macrophage cells. The results disclosed that myrislignan exerts strong anti-
inflammatory properties in LPS-stimulated macrophage cells by impeding the NF-kB signaling
pathway activation (Jin et al., 2012). Figure 2 presents a thematic diagram illustrating the anti-
inflammatory properties of nutmeg.

BATM (2016) detected that ethanolic extract from wood, nutmeg, and mace showed an anti-
inflammatory effect, but the extract from wood revealed more powerful anti-inflammatory action
than others. Lee and Park (2011) evaluated that myristicin holds the strong anti-inflammatory
property.

According to the researchers, Myristicin suppressed the production of NO, monocyte chemotactic
protein (MCP)-1, MCP-3, interferon-inducible protein-10, IL-6, IL-10, calcium, macrophage inflam­
matory protein, granulocyte-macrophage colony-stimulating factor, and leukemia inhibitory fac­
tor. Results disclosed that myristicin has powerful anti-inflammatory effects by reducing the
chemokines, growth factors, and cytokines.

1.13. Miscellaneous health benefits

For quite a while, utilization of M. fragrans in conventional medicines as an abortifacient, emme­
nagogue, narcotic, stimulant, and carminative. Nutmeg is additionally endorsed for various ail­
ments treatment, like diarrhea, decreased appetite, muscle spasms, and rheumatism (Khare,
2008). Therapeutically, nutmeg contains strong antimicrobial properties. It is viable in killing off
various cavity-causing microorganisms in the mouth. Nutmeg such as cloves contains
a compound, eugenol that benefits the heart. Myristicin present in the nutmeg has appeared to
repress an enzyme in the cerebrum that adds to Alzheimer’s illness and is utilized to improve

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Figure 2. Thematic diagram

showing anti-inflammatory
potential of nutmeg.

memory. It is utilized in small doses to lessen flatulence (intestinal gas or excessive stomach), help
assimilation, and improve craving (Jaiswal et al., 2009). Nutmeg can assist with combatting
asthma. It is additionally used to loosen up muscles. Nutmeg oil drops can likewise be blended
in with nectar to treat indigestion, chronic diarrhea, gastroenteritis, and nausea. In homeopathy,
the use of nutmeg to treat depression and anxiety is evident. Essential oils of nutmeg are excellent
antimicrobial sources. The restorative usage of essential oils is turning out to be popular in light of
their fewer side effects and low obstruction towards microorganisms (Saxena & Patil, 2012;
Suthisamphat et al., 2020).

M. fragrans’s anti-oxidant and anti-inflammatory capabilities have been shown to boost learning
and memory in mice (Parle et al., 2004). Hayfaa et al. (2013) stated that the alkaloid concentrate
of the seed kernel of ground nutmeg significantly declined the writhing reactions in rat models.

A previous study reported the hepatocurative effect of water extract of nutmeg. Hepatotoxicity
was induced by isoproterenol and the nutmeg extract improved the liver enzymes together with
hepatocurative effects (Kareem et al., 2013). Similar results have been reported by Zhao et al.
(2020) that nutmeg’s alcohol extract upgraded nonalcoholic fatty liver disease (NAFLD). An in vivo
study by the author showed that nutmeg extract considerably reduced inflammation, body weight,
cholesterol levels, blood glucose, and mainly lipid accumulation resulting in an effective hepato­
curative agent. Investigations reported that nutmeg can fight against hepatotoxicity because of

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a particular phytochemical compound identified as myrislignan, which protects against liver

damage condition. Chloroform, methanol, petroleum ether, and n-hexane fractions of Myristica
fragrans (200 and 400 mg/kg body weight) reported anti-inflammatory and analgesic properties.
Results showed that all extracts inhibited the carrageenan-induced inflammation but the metha­
nol extract displayed significant results (90.9%). The petroleum ether showed good analgesic
action (60.7%) among other extracts but was not as effective as diclofenac sodium (Standard)
(76.3%). So, it was concluded that several nutmeg extracts hold anti-inflammatory and analgesic
potential (Bhuiyan et al., 2018). Kelble (2005) exposed the nutmeg anti-aggregatory and hypolipi­
demic effects in an animal model. They discovered that it lessens the LDL and VLDL levels and
diminishes the levels of cholesterol in the liver and heart. Likewise, Sharma et al. (1995) prompted
M. fragrans extract in hypercholesterolemic animals to contemplate the hypolipidemic impact
which likewise inhibits cholesterol accumulation, fats in the heart and liver, etc.

The administration of M. fragrans extract for constant 21 days reduced the arthritic indices
induced by complete fruend’s adjuvant (CFA). While 300 mg/kg extract significantly reduced the
TNF-α levels. Extract administration reduced cartilage destruction and showed powerful anti-
arthritic action (Najafzadeh et al., 2014). Chung et al. (2012) reported that after the extraction of
some bioactive components such as safrole and myristicin from the ethanolic extract of Myristica
fragrans, it is considered to be a strong nutraceutical candidate for the treatment of skin diseases
such as atopic dermatitis.

An antiulcer property of Myristica fragrans seed extract was reported by Sattar et al. (2019) in rat
models. Administration of extract for a constant 15 days reduced the gastrointestinal lesions by
41.68%. The pH of gastrointestinal contents of extract-treated rats was increased (4.25 ± 0.25) when
compared to the control group (2.25 ± 0.25). Moreover, the extract also upgraded the Ulcer index
(41.74%) and the acidity of the extract-treated group was diminished. Results suggested that
Myristica fragrans exhibited noteworthy gastroprotective action against ethanol-induced ulcers.

Hydroalcoholic extract of M. fragrans reduced the lipoprotein levels in artificially induced trigly­
ceride and glucose elevations in rat models. Doses of 450 mg/kg for 7 days improved the metabolic
abnormalities as well as extract reduced the triglyceride level by 47%, and cholesterol by 66.7%.
According to the findings, nutmeg extract improved impaired lipid metabolism in mouse models
(Arulmozhi et al., 2007). Mary et al. (2012) reported the cytotoxic property of the essential oil
Myristica fragrans against epidermal skin cancer cells and breast cancer cells. According to Morita
et al. (2003), myristicin is amongst the most active phytochemical components reported to have
a strong hepato-curative effect. Figure 3 presents a thematic diagram illustrating the miscella­
neous health benefits of nutmeg.

1.14. Psychoactive potential

Nutmeg is a common spice used in the kitchen and for many other medicinal purposes, it also acts
as an analgesic, antioxidant, antimicrobial, and aphrodisiac agent yet little is thought about the
harmful impacts of nutmeg (Beckerman & Persaud, 2019). Phytochemical screening aftereffects
uncovered phytates, oxalates, steroids, tannins, saponins, flavonoids, glycosides, and cyanogenic
glycosides, presence, and the antinutrient components which included cyanogenic glycosides
(0.32 ± 0.08), saponins (1.58 ± 0.60), phytates (4.08 ± 0.10), tannins (0.64 ± 0.08), oxalates (1.05 ±
0.02) propose that Nutmeg (African) is usually considered to be safe to use.

Volatile oils present in nutmeg contain a derivative of alkyl benzene named myristicin. The
myristicin acid is that it goes about as a weak inhibitor of monoamine oxidase and some segments
of myristicin have serotonin agonist-like structures. Myristicin might be processed to show com­
pounds like amphetamine with psychedelic impacts comparable to tolysergic acid (Forrester,
2005). As Myristicin is considered a hallucinogenic agent, it very well may be utilized as
a modest psychedelic intoxicant, while successive utilization can prompt lethal occurrences that
result in organ failure and affect cardiovascular muscles. M. fragrans essential oil is portrayed by

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Figure 3. Thematic diagram

showing miscellaneous health
benefits of nutmeg.

phenylpropanoids, terpenoids, and terpenes presence, for example, safrole and methyl eugenol
which are viewed as carcinogenic and genotoxic (Lanari et al., 2018).

The nutmeg effect on the central nervous system may be excitatory or depressant. Pathways of
serotonin and dopaminergic may assume a part. Elemicin and myristicin have been considered to
be nutmeg chemical compounds liable for their CNS impacts (Beckerman & Persaud, 2019). During
rodent trials, Myristicin was found to produce focal inhibition of monoamine oxidase (Hategan &
Bourgeois, 2013). These fixings have both psychotropic and anticholinergic. Common effects of CNS
incorporate stupor, seizures, incoherent speech, hallucinations (visual, tactile, and auditory), hyper­
activity, headache, giddiness, euphoria, drowsiness, dizziness, confusion, and anxiety (Pytte &
Rygnestad, 1998).

Research led by Demetriades et al. (2005) indicates the poisoning of nutmeg to be rare yet most
likely underreported and ought to cause strong psychotic side effects such as CNS neuromodula­
tory signs that may emulate to some degree anticholinergic hyperstimulation. One substance that
nutmeg possesses is safrole. Past studies indicate that safrole is present in nutmeg, which has
negative effects on human wellbeing. Safrole has been accounted to be a potential hepatocarci­
nogen (Yang et al., 2018). A study reported that 4 g/kg of nutmeg causes abnormal behavior signs,
which include dizziness, hyperactivity, and unstable gait in animal models. Moreover, alkaloid
administration improved the strange behavior (Hayfaa et al., 2013).

1.15. Safety and toxicity

There are not many cases of nutmeg overdose and abuse. Nutmeg effects can be observed after
the ingestion around the time of 0.5 to 8 h and go away in about 1–2 days (Akinboro et al., 2011).
Nutmeg in low doses shows no noticeable response of a neurological or physiological nature, but

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nutmeg (both freshly ground and raw) in large doses, as well oil of Nutmeg oil, impart some
Psychoactive effects, which derive from mechanisms of Anticholinergic- attributes to Elemicin and
Myristicin (Ehrenpreis et al., 2014; McKenna et al., 2004). The nutmeg toxic dose is about 2–3
teaspoons, while less than one spoon consumption can initiate similar effects to the toxic episode
of anticholinergic. Likewise, larger consumption, a minimum of 2 tablespoons, results in psychotic
effects which include delusions and hallucinations. To define this 1 teaspoon is equivalent to 5 g
and 1 tablespoon is equal to 15 g. Persistent use of nutmeg causes severe mental illness which is
identified by distorted thinking and emotions (Hategan & Bourgeois, 2013). Myristicin
a psychoactive substance and monoamine oxidase inhibitor can initiate generalized body pain,
eventual Dehydration, Nausea, Palpitations, and Convulsions when it is ingested in large quantities.
Poisonings of nutmeg happen due to unintentional ingestion and also its recreational use inten­
tionally (Ehrenpreis et al., 2014).

Nutmeg substance intoxication varies individually and occurs with different side effects, such as
amnesia, eye irritation, dry mouth, dizziness, nausea, headaches, confusion, anxiety, or excited
delirium (Ehrenpreis et al., 2014). It takes several hours for intoxication before the experience of
maximum effect is attained. The toxic effects of nutmeg can be sustained for many days
(Demetriades et al., 2005; Ehrenpreis et al., 2014)

It is rarely reported that nutmeg overdose can be a cause of death, especially when it is
combined with different drugs. Fatal poisoning incidents individually from myristicin or nutmeg
are uncommon (Ehrenpreis et al., 2014). As per Stein et al. (2001), the first nutmeg poisoning case
was perceived in 1576 when an English pregnant lady reported prompt inebriety by 10–12 nutmeg
ingestion (about 70–84 g) (Rahman et al., 2015).

2. Conclusion
The extract from different fractions of Myristica fragrans is used for several pharmaceutical proper­
ties. The majority of studies are focused on the phytochemical constituents of nutmeg responsible
for a range of therapeutic impacts such as antibacterial, anticancer, antioxidant, antifungal,
antidiabetic, antidepressant activity, hepatoprotective, anti-obesity, anti-inflammatory, cardiopro­
tective, and many other therapeutic effects. According to the literature, myristicin is one of the
most active compounds accountable for many health benefits. More struggles are required to
revise the customary uses of nutmeg, its remedial activity as well and the mechanism of action.
Much experimental work on this plant has been done in rodent models but very limited clinical
data are available, so more investigations are needed to evaluate its efficacy on the human body.
However, nutmeg is a storehouse of therapeutically active constituents that are accountable for
many positive effects. Therefore, this plant stimulates researchers to search more about its unique
pharmaceutical properties. This study highlights the potential of M. fragrans for usage in thera­
peutic medications and provides a theoretical foundation for future research on nutmeg and its
pharmacological features.

Author details E-mail: dr.entessara@gmail.com

Muhammad Tauseef Sultan1 ORCID ID: http://orcid.org/0000-0002-1804-1770
1
Farhan Saeed2 Institute of Food Science and Nutrition, Bahauddin
E-mail: f.saeed@gcuf.edu.pk Zakariya University, Multan, Pakistan.
2
ORCID ID: http://orcid.org/0000-0001-5340-4015 Department of Food Sciences, Government College
Hassan Raza1 University Faisalabad, Faisalabad, Pakistan.
3
Aneeqa Ilyas1 Agricultural Extension Directorate, MAAR, Damascus,
Fatima Sadiq1 Syria.
Ali Musarrat1
Muhammad Afzaal2 Disclosure statement
ORCID ID: http://orcid.org/0000-0001-9047-9075 No potential conflict of interest was reported by the
Muzzamal Hussain2 author(s).
ORCID ID: http://orcid.org/0000-0001-6508-1962
Muhammad Ahtisham Raza2 Citation information
E-mail: maraza.201609935@gcuf.edu.pk Cite this article as: Nutritional and therapeutic potential of
ORCID ID: http://orcid.org/0000-0002-5648-2825 nutmeg (Myristica fragrans): A concurrent review,
Entessar Al JBawi3 Muhammad Tauseef Sultan, Farhan Saeed, Hassan Raza,

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https://doi.org/10.1080/23311932.2023.2279701
Aneeqa Ilyas, Fatima Sadiq, Ali Musarrat, Muhammad
Afzaal, Muzzamal Hussain, Muhammad Ahtisham Raza &
Entessar Al JBawi, Cogent Food & Agriculture (2023), 9:
2279701.
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