Avenanthramides as digestion-stage modulators: Mechanistic links across the gastrointestinal continuum

Oat avenanthramides (AVNs) are phenolic alkaloids unique to oats and are widely recognised for their antioxidant and anti-inflammatory properties. However, human studies consistently report very low oral bioavailability (<2%), highlighting a disconnect between dietary intake and systemic exposure. This review presents a digestion-stage-resolved conceptual framework integrating current evidence on AVN fate during gastrointestinal digestion, including matrix entrapment, digestive release, limited absorption, microbial biotransformation, and interindividual metabotype variability. AVN bioaccessibility is influenced by food matrix composition, processing conditions, and enzymatic activity. Evidence indicates that AVNs may modulate starch hydrolysis, glucose transport, and resistant starch formation while undergoing chemical and Phase I transformations. In the colon, microbial metabolism produces dihydroavenanthramides (DH-AVNs), which may contribute to biological activity in a metabotype-dependent manner. Overall, AVNs appear to exert physiological effects primarily through local gastrointestinal mechanisms, although proposed pathways require confirmation in well-designed human intervention studies.