ABSTRACT Phlorotannins have gained significant attention for their potential bioactive and functional properties. However, these compounds are highly sensitive to gastrointestinal digestion, which limits their bioavailability and consequently the in vivo efficacy. To address this limitation, this study explored the use of various concentrations of γ‐ and β‐cyclodextrins in the aqueous microwave‐assisted extraction of phlorotannins from Fucus vesiculosus and submitted the resulting extracts to an in vitro gastrointestinal digestion protocol. While higher cyclodextrin concentrations resulted in an increase in extraction yields (from 47% to approximately 55% for both cyclodextrins), the opposite was observed for the total phlorotannin content. Notably, higher cyclodextrin concentrations markedly improved phlorotannin stability across the different stages of gastrointestinal digestion. Specifically, β‐cyclodextrin exhibited the highest protective effect, preventing phlorotannin degradation almost completely in both oral and gastric phases, and retaining approximately 35% (approximately 1.0 mg/g extract) of the initial content (approximately 3.0 mg/g extract) after the intestinal phase, thereby enhancing the compounds’ resistance and residence time in the intestinal lumen. A comparison between the addition of β‐cyclodextrin during extraction and post‐extraction revealed that, although both approaches reduce the phlorotannin loss throughout the gastrointestinal tract, the β‐cyclodextrin‐assisted extraction showed better efficacy. This indicates that strong guest‐host interactions are formed between phlorotannins and cyclodextrins during the extraction, possibly due to the increased enthalpy generated by microwave heating. Overall, this study highlights β‐cyclodextrin‐microwave‐assisted extraction as a promising approach to enhance the stability of phlorotannins in their transit through the gastrointestinal tract, ensuring their delivery to the intestinal lumen, where they can be released and available for absorption.
Reis et al. (2026) studied this question.