Bioaccessibility of Cafestol from Coffee Brew: A Metabolic Study Employing an <i>In Vitro</i> Digestion Model and LC-HRMS

Cafestol is an <i>ent</i>-kaurene skeleton diterpene that is present in coffee beans and brews. Although several biological activities have been described in the literature for cafestol, such as hypercholesterolemic, anti-inflammatory, anticerous, and antidiabetic effects, its metabolism within the human body remains poorly understood. Therefore, this study aimed to quantify cafestol in boiled coffee brew, assess its bioaccessibility using a static <i>in vitro</i> digestion model, and investigate the metabolites formed during the digestion process using liquid chromatography coupled to high-resolution mass spectrometry. Cafestol content in the boiled coffee brew ranged from 127.47 to 132.65 mg L^-1. The bioaccessibility of cafestol from boiled coffee brew using the <i>in vitro</i> digestion model was 93.65%; additionally, in the intestinal phase, cafestol was mainly found in its alcohol form. Additionally, a novel carboxylic acid derivative metabolite from cafestol with <i>m</i>/<i>z</i> 331.1909 [M + H]⁺ formed in the oral digestion phase is proposed. This metabolite was also detected in other digestion phases. Thus, this is the first article to investigate the metabolism of cafestol during digestion using an <i>in vitro</i> digestion model. The results indicate that cafestol is bioaccessible, is available to absorption, in its alcohol form, and suffers an oxidation reaction during the oral phase of digestion.