PhD defence Nicole Elisabeth Theresia Pinckaers

Keywords: Pre-workout supplements, Cardiovascular system

"Beyond the Boost: Linking Molecular Mechanisms of Phenethylamine and Alkylamine Analogues in Pre-workout Supplements to Cardiovascular Effects"

The aim of this thesis is to improve our understanding of the pharmacological mechanisms and associated cardiovascular effects of phenethylamines (PEAs) and alkylamines (AAs), compounds that are commonly found in pre-workout and weight-loss supplements. The findings demonstrate that PEAs and AAs interact with several key regulators of the sympathetic nervous system involved in cardiovascular control, including adrenergic receptors (ADRs), trace amine-associated receptor 1 (TAAR1), and noradrenaline and dopamine transporters. Several PEAs induced vasoconstriction in isolated rat arteries and were shown to increase blood pressure and heart rate in conscious rats. Modeling of human plasma concentrations following oral intake of PEAs suggests that the reported consumption levels can result in plasma concentrations within the pharmacologically active range. Overall, this research provides both mechanistic and translational evidence that certain PEAs and AAs present in pre-workout and weight-loss supplements possess clinically relevant sympathomimetic activity. These findings indicate a potential risk of adverse cardiovascular effects in consumers and contribute to a more evidence-based safety assessment, while providing a scientific foundation for future human studies and regulatory risk evaluation.

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