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Endogenous and/or exogenous origin of phenolic metabolites in humans (the ENDOPHENOL project): study protocol for a randomized, controlled, crossover trial

Zeraik L, Rosi A, Del Rio D, Crozier A, Bresciani L, Mena P

Trials, 2025

30 participants

Abstract

Background: (Poly)phenols are molecules with various structural complexities that are mostly present in fruits, vegetables, and some cereals, and are widely consumed daily. Following ingestion, the phenolic compounds that are not absorbed in the upper gastrointestinal tract-the majority-are metabolized in the colon to form low-molecular-weight phenolic catabolites (LMWP), which potentially make a substantial contribution to the biological activity of (poly)phenol-containing foods. However, the production of LMWP can also occur through the metabolism of the aromatic amino acids phenylalanine and tyrosine as well as via catecholamine pathways.

Methods: A randomized, controlled, crossover trial in which healthy adults (n = 30) follow a very-low-(poly)phenol diet and restrict physical activity for 5 days is proposed. On the morning of the third day, subjects will consume either coffee (known source of (poly)phenols) or hot water (control).

Discussion: The main objective is the characterization of LMWP in biological samples through metabolomic techniques, attempting to distinguish the possible origin of these metabolites based on the different production of LMWP in the context of a controlled diet with or without a known source of (poly)phenols (primary outcome). Factors leading to interindividual variability and playing a role in phenolic metabolism, such as gut microbiota composition and genetic polymorphisms (secondary outcomes), will also be considered. Emerging evidence…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 30 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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