Alkenylbenzenes in Foods: Aspects Impeding the Evaluation of Adverse Health Effects

Abstract

Alkenylbenzenes are naturally occurring secondary plant metabolites, primarily present in different herbs and spices, such as basil or fennel seeds. Thus, alkenylbenzenes, such as safrole, methyleugenol, and estragole, can be found in different foods, whenever these herbs and spices (or extracts thereof) are used for food production. In particular, essential oils or other food products derived from the aforementioned herbs and spices, such as basil-containing pesto or plant food supplements, are often characterized by a high content of alkenylbenzenes. While safrole or methyleugenol are known to be genotoxic and carcinogenic, the toxicological relevance of other alkenylbenzenes (e.g., apiol) regarding human health remains widely unclear. In this review, we will briefly summarize and discuss the current knowledge and the uncertainties impeding a conclusive evaluation of adverse effects to human health possibly resulting from consumption of foods containing alkenylbenzenes, especially focusing on the genotoxic compounds, safrole, methyleugenol, and estragole.

Myristicin and Elemicin: Potentially Toxic Alkenylbenzenes in Food

“…The occurrence of the alkenylbenzenes safrole and methyleugenol in plants used as foods was described in detail elsewhere [5]. Beside this, aromatic plants, as well as powders, extracts, or essential oils made thereof can also serve as sources for myristicin and elemicin, which are described here.…”

“…The other metabolic routes observed were allylic hydroxylation and the epoxide-diol pathway [70,79]. Oxidations of the allylic side chain of safrole may proceed (i) via an epoxide resulting in side chain propane diols during different stages of the metabolic steps [72], or (ii) via 1 -hydroxylation followed by sulfonation that might lead to a reactive carbocation intermediate [5]. Other possible steps of metabolic ways of safrole are (iii) the subsequent oxidation of the 1 -hydroxysafrole to the 1 -oxo-safrole [81], (iv) oxidation at the 3 -position to yield 3 -hydroxy-isosafrole, and (v) the demethylenation of safrole to 4-allylcatechol that may isomerize to its quinone-methide [82][83][84].…”

“…It is assumed that the toxicity of safrole and methyleugenol is mainly caused by metabolic activation at the allylic side chain, namely 1 -hydroxylation and subsequent sulfonation to the resulting allylic sulfate esters. These intermediates are instable and may subsequently react with cellular nucleophiles including DNA and proteins [5]. The relevance of further metabolites, e.g., quinone methides or other so far unknown reactive intermediates possibly involved in hepatotoxic effects are far less clear.…”

“…Nevertheless, for all the four compounds, the toxic principle that is assumed to lead to toxification is the 1 -hydroxylation and subsequent sulfonation to the resulting allylic sulfate esters [5].…”

“…Intake of myristicin, elemicin, safrole, and methyleugenol is presumed to occur mainly from the consumption of spices and essential oils made thereof [9,10]. High levels may also be present in plant-based food supplements (PFS) as well as in various processed flavored foods such as sauces, baked goods, and beverages, such as cola-flavored softdrinks [5,[10][11][12][13].…”