Route Of Exposure

The Nutmeg tree is a large evergreen native to the Spice Islands but now also cultivated in the Caribbean and Mauritius. The tree produces 2 spices, Mace and Nutmeg. Nutmeg is the oval, 25 mm brown seed kernel inside the fruit pit, and Mace is the bright red or purple lacy covering on the pit. Nutmeg is dried and sold whole or ground, and Mace is dried and powdered. Both Mace and Nutmeg spice are strongly aromatic, Mace somewhat more so. Its higher price is principally due to the yield of Mace being much smaller. It is not certain whether Nutmeg and Mace became known in Europe only in the 11th century AD or were known to the Romans.

In the cuisines of Asia, Nutmeg and Mace are traditional ingredients of a variety of dishes, such as curries. In Western cuisine, Nutmeg and Mace are used in cakes, crackers and stewed fruits. Nutmeg is used to flavour drinks such as eggnog, and in fondue and béchamel (white sauce). Nutmeg oil is, moreover, an additive in a wide range of commercial foods and medicines, especially colas. The more aromatic Mace is a frequent ingredient of sausages and other prepared meats. Both Nutmeg and Mace are used to relieve digestive ailments.

Nutmeg contains up to 10% essential oil, which can be toxic. The component myristicin (methoxy-safrole) is responsible for the hallucinogenic effect of Nutmeg. (See under Other Reactions). Oil of Mace (up to 12% in the spice) contains the same aroma components in slightly different amounts. Apparently only excessive ingestion of either spice, however, can produce hallucinogenic or toxic effects.

Nutmeg on expression yields about 24 to 30 percent fixed oil called Nutmeg butter or oil of Mace, the principal component of which is trimyristin. The oils are used as condiments and flatulence treatments and to scent soaps and perfumes. An ointment of Nutmeg butter is used as a treatment for topical irritations and rheumatism.

The content of eugenol is only slightly changed before and after processing of various processed forms of Nutmeg, but methyleugenol and methylisoeugenol increase.

Clinical Relevance

Allergen description

No allergens from this plant have yet been fully characterised.

Potential Cross Reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected, and particularly between Mace and Nutmeg.

Clinical Experience

IgE-mediated reactions

As Nutmeg and Mace are integrally related, this article should be read in conjunction with Mace Rf266. Nutmeg may uncommonly induce symptoms of food allergy or contact dermatitis in sensitised individuals. Few studies, however, have investigated or reported adverse reactions to spices, including Nutmeg. The composition of Nutmeg may depend upon its country of origin and also on the quality of the Nutmeg harvest. Therefore, the occurrence of antigens and the incidence of Nutmeg allergy may vary among different Nutmeg preparations, which may influence the prevalence and severity of allergic reactions.

In a French study, skin-specific IgE tests to spices were carried out in a pool of 589 patients with food allergy and suspected allergies to spices. Frequent sensitisation to members of the Apiaceae was observed: Coriander, Caraway, Fennel, or Celery in 32% of children and 23% of adults. Sensitisation to members of the Liliaceae family (Garlic, Onion, or chive) was observed in 4.6% of children and 7.7% of adults. No tests were positive to Nutmeg.

In skin-specific IgE tests with powdered commercial spices performed in 70 patients with positive tests to Birch and/or Mugwort pollens and Celery, 24 patients were reported to be positive to tests for food belonging to the Apiaceae family, which includes Celery. Spices from unrelated families (Red Pepper, White Pepper, Ginger, Nutmeg, Cinnamon) elicited positive immediate skin test reactions in only 3 of 11 patients.

It should be kept in mind, however, that the methodology of specific IgE determination varies between studies and may result in discordant results. It may well be that Nutmeg’s predominant pathogenesis involves delayed-hypersensitivity reactions, as illustrated by the following studies.

By means of patch tests to determine delayed-type hypersensitivity to spices, a group of 103 patients with suspected contact allergy to spices was tested with the European standard series. Among the spices, the highest numbers of reactions were found to Nutmeg (28%), Paprika (19%) and Cloves (12%). Fragrance mix turned out to be a particularly important allergen, especially for Paprika, Nutmeg and Cloves. The authors pointed out that difficulties in distinguishing between irritant and allergic reactions may arise, resulting in a high number of dubious irritant or allergic (±) responses, in particular to Nutmeg. The authors postulated that the high incidence of Nutmeg allergy in this study may reflect the increasing use of Nutmeg (and other spices) in cosmetics in Western society. In the study, a patient with contact allergy to Nutmeg complained of discomfort in the mouth after eating Nutmeg. Two other patients, both with contact allergy to Celery and Nutmeg, experienced generalised itching after eating Celery or spicy Pork. The authors suggested that when patients suffer from suspected contact eczema, allergic stomatitis or similar problems, it is worthwhile testing for contact allergy to spices.

Similarly, in a series of 55 patients with suspected contact dermatitis tested for sensitivity to a group of spices, positive patch test were most common with Ginger, Nutmeg, and Oregano. The authors pointed out the difficulty in interpreting responses at various concentration levels of the test material. There may be a threshold for detecting true allergy or, as an alternative, a marginal irritant reaction. Those responding to only 10% concentrations generally did so weakly. Three patients were deemed to have relevant patch test responses to spices.

Other authors have advised maintaining a high level of awareness of contact and systemic contact-type dermatitis reactions resulting from spices such as Nutmeg, Mace, Cardamom, Curry, Cinnamon, and laurel. Reactions may be rare but may well be overlooked. Patch testing with these spices "as is" was reported to be very useful; if there is a positive reaction, testing with dilutions is helpful

Other reactions

Nutmeg is a common household spice sometimes abused for its hallucinogenic properties. This abuse is well reported in the medical literature over the last century. Ingestion of less than 1 tablespoon of Nutmeg can produce symptoms similar to those of an anticholinergic toxic episode.

Common presenting complaints are hallucinations, palpitations, and feelings of impending doom. A study reports on a case of intentional Nutmeg intoxication in a 23-year-old college student.

Other reports are similar. Several intoxications were reported after ingestion of approximately 5 g of Nutmeg, corresponding to 1 - 2 mg myristicin/kg body weight. The authors suggested that although the symptoms may be ascribed to the actions of myristicin, it is likely that other components of Nutmeg are also involved. Other authors have stated that 6 - 7 mg/kg b.w. may be enough to cause psychopharmacological effects in man. Intake estimations indicate that nonalcoholic drinks may be the most important single source of myristicin intake. Based on available data, it seems unlikely that the intake of myristicin from essential oils and spices in food, estimated at a few mg per person and day in this report, would cause adverse effects in humans.

Side-effects associated with the abuse of Nutmeg occasionally generate emergency department referrals and may be frightening. A 13-year-old female who ingested 15-24 g of Nutmeg over a 3-hour period, and smoked and shared 2 joints of marijuana, developed bizarre behaviour and visual, auditory, and tactile hallucinations. She also experienced nausea, gagging, hot/cold sensations, and blurred vision followed by numbness, double, and "triple" vision, headache, and drowsiness. Nystagmus, muscle weakness, and ataxia were present.

A fatal case of poisoning has also been reported. In a 55-year-old woman who died from Nutmeg poisoning, the post-mortem serum level of myristicin was documented to be 4 microg/ml. From 1996 to 1998, in a series of cases, 7 poisonings with Nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed. In 1 of these cases, a myristicin blood level of 2 microg/ml was measured 8 hours after ingestion of 2 to 3 tablespoonsful of Nutmeg powder (approx. 14-21 g, or 280-420 mg/kg).

Adverse reactions may extend beyond central nervous system effects. Acute Nutmeg poisoning occurred in a 16-year-old youth who had ingested the substance for recreational purposes. He developed a number of neurological symptoms and signs along with non-specific electrocardiographic changes and anti-cholinergic-type symptoms.

Occasionally, pest-infested Nutmeg is ground and sold illegally. Its molds may produce aflatoxins