*2.1. Myristicin and Elemicin in Nutmeg and Mace*

The name "myristicin" originally referred to the solids that crystallize from nutmeg oil while in prolonged storage. These, however, are today known to be myristic acid [17]. Elemicin was first identified as a component of the myristicin fraction from nutmeg oil [18].

The nutmeg tree is a tropical tree indigenous to the Maluku Islands of Indonesia (Myristica fragrans Houtt., family Myristicaceae). Its seeds consist of a kernel and a covering aril surrounding the kernel. Whereas mace designates the red lacy aril, the dried kernels of the ripe seeds are named nutmeg. When grounded material or powders are hydrodistilled, about 2.4% crude oil can be obtained [19]. These oils are rich in alkenylbenzenes, such as eugenol (19.9%), methyleugenol (16.7%), methyl iso-eugenol (16.8%), myristicin (2.3%), safrole (1.6%), and elemicin (1.7%). In contrast, a slightly different composition of oils from the dried kernels of Myristica fragrans originating from Sri Lanka was reported, with almost no eugenol (0.2%), or methyleugenol (0.6%), nearly equal amounts of safrole (1.4%) and elemicin (2.1%), but higher levels of myristicin (4.9%) [20]. Numerous reports on the composition of nutmeg oils are published, reporting varying levels of alkenylbenzenes in nutmeg seeds. It is, on the one hand, the storage of ground powders [21], but on the other hand, very much the geographical origin that determines the volatile composition of nutmeg extracts as recognized by Baldry and colleagues [22]. They showed high variabilities in alkenylbenzene contents, with myristicin ranging from 0.5% to 12.4%, safrole from 0.1% to 3.2%, elemicin from 0.3% to 4.6%, methyleugenol from 0.1% to 1.2%, and eugenol from 0.1% to 0.7% in different nutmeg oils from West India and South East Asia. Mace powders and mace oils contain similar constituents as nutmeg powders and nutmeg oils. For example, in 10 powdered genuine Indonesian nutmeg seeds extracted with boiling methanol, myristicin accounted for up to 2.9% and safrole accounted for up to 0.39%. Nutmeg oil from Indonesian nutmegs contained 9.73% myristicin and 2.16% safrole [23].

Nutmeg and mace are used as domestic spices and as flavoring ingredients in many food products, such as in gelatins, puddings, sweet sauces, baked goods, meats, fish, pickles (processed vegetables), candy, ice cream, and non-alcoholic beverages [24,25]. In addition, several globally available PFS contain nutmeg seed powders or nutmeg oils to very varying extents [11].

Further relevant examples for plants and their essential oils containing myristicin and elemicin, as well as other selected alkenylbenzenes, are listed in Table 1.


**Table 1.** Occurrence of safrole, myristicin, methyleugenol, and elemicin found in essential oils (EO) from culinary plants.


**Table 1.** *Cont.*

#### *2.2. Myristicin and Elemicin in Food Flavorings*

Due to the intentional use of essential oils and the dried powder of nutmeg or mace for flavoring reasons, certain types of soft drinks, pastries, and some types of crisps contain high levels of myristicin and elemicin.

Cola-flavored soft drinks may contain nutmeg oil and/or mace oil, which consist of different major compounds, such as sabinenes and myrcene, as well as at least five different alkenylbenzenes. Myristicin, safrole, and elemicin mainly determine the flavor of these oils. Accordingly, myristicin, safrole, elemicin, methyleugenol, and eugenol were detected in cola-flavored soft drinks [57]. In 2013, Raffo et al. published quantitative data on the amounts of safrole and myristicin in the cola-flavored soft drinks of different brands following different processing procedures, including various storage conditions. Levels of safrole and myristicin varied approximately 2–3 orders of magnitude. In flavored soft drinks, average concentrations of safrole and myristicin were 23.0 and 168.3 μg/L, with minimum contents of 0.6 and 0.4 μg/L and maximum levels of 43.9 and 325.6 μg/L, respectively [12]. These variations might be due to variable levels of alkenylbenzenes in the added essential oils. For example, measurements of alkenylbenzene concentrations in different nutmeg oils of specific geographical origins revealed an at least 30-fold variation, e.g., in the levels of safrole (ranging from 0.1 to 3.2%) and myristicin (0.5 to 13.5%), respectively [57]. In the study of Raffo et al., only the levels of myristicin and safrole were measured in cola-flavored soft drinks, but not those of other alkenylbenzenes. Therefore, the total amount of alkenylbenzenes in cola-flavored soft drinks remains unknown so far.

Another important example for processed foods containing alkenylbenzenes is "*Pesto*". This traditional dish from Genova, Italy, mainly consists of olive oil, hard cheese, pine nuts, garlic, salt, and basil leaves. Different alkenylbenzenes were detected at varying levels in basil-containing "*Pesto*", including methyleugenol (22.9–56.4 mg/kg), myristicin (13.2–15.8 mg/kg), estragole (3.2–34.1 mg/kg), and apiol (3.4 mg/kg) [58].

Parsley and dill teas can be purchased without restriction. Recently levels of alkenylbenzenes in such teas were investigated. Myristicin, methyleugenol, apiol, and estragole are detected to varying extents in dry tea samples or in hot water herbal extracts containing parsley, dill leaves, or seeds, or being in a mixture with other herbs. The total amount of alkenylbenzenes in the dry tea samples ranged from 18 to 1269 μg/g dry preparation [59]. In 2017, Alajlouni and colleagues also found relevant levels of the alkenylbenzenes myristicin, apiol, and estragole (17–6487 μg/g) in parsley and dill-based PFS [60].

Beside this, baked goods, meat products, condiments, relishes, soft candy, gelatin, pudding, soups, alcoholic beverages, and gravies may also contain myristicin and elemicin to various and often unknown amounts if refined with oils from parsley, nutmeg or mace [24,61]. This also applies to other alkenylbenzenes [62,63]. Therefore, monitoring of myristicin, elemicin, and other alkenylbenzenes in many food commodities appears justified in order to gain a reliable database for future exposure assessments [25].
