Trigonelline and Cardiovascular Health: A Narrative Review of Mechanisms, Preclinical Evidence, and Translational Considerations

Trigonelline is a pyridine alkaloid abundant in fenugreek and coffee that has attracted growing interest for its potential cardiometabolic relevance. This narrative review summarizes mechanistic pathways and available evidence linking trigonelline to vascular and cardiac outcomes and highlights key translational gaps. A literature search was conducted in PubMed, Scopus, and Web of Science using combinations of the terms “trigonelline,” “cardiovascular disease,” and “natural alkaloid,” prioritizing English-language in vitro, animal, and human studies focused on vascular function, cardiometabolic risk, and atherosclerotic mechanisms. Preclinical evidence suggests that trigonelline may improve endothelial function, including nitric oxide-related signaling, attenuate oxidative stress and inflammatory pathways, modulate glucose and lipid metabolism, and reduce gut microbiota-linked Trimethylamine N-Oxide (TMAO) generation, mechanisms plausibly relevant to atherosclerosis and hypertension. In contrast, human evidence remains limited and heterogeneous, with few controlled trials and unclear dose-response relationships. Safety data are more robust for trigonelline exposure through dietary sources such as coffee than for long-term isolated supplementation. Overall, trigonelline represents a promising bioactive compound, but clinical translation will require well-designed randomized trials, standardized dosing strategies, detailed pharmacokinetic characterization, and rigorous long-term safety evaluation.