A tolerable dose is not a tolerable exposure: the rate-of-rise hypothesis for caffeine and the cardiovascular safety of energy drinks in children
Year: 2026
Type: preprint
Abstract: This project proposes the rate of rise hypothesis to explain the cardiovascular effects of caffeinated energy drinks in children and adolescents. Rather than the acute pressor response being driven by the total quantity of caffeine administered, we hypothesise that it is governed by the rate of rise in plasma caffeine concentration following ingestion, such that identical doses delivered as a rapid chilled bolus versus a slowly sipped warm beverage produce markedly different cardiovascular stimuli despite equal total exposure. The hypothesis is based on a reanalysis of the published adult and paediatric randomised energy drink literature, including the absence of a dose-response gradient in systolic blood pressure across a nearly sixfold range of delivered caffeine doses, and the close correspondence between paediatric and adult systolic responses at matched weight-adjusted dose despite known developmental differences in caffeine clearance. The project will examine the plausibility of this interpretation using existing arm-level dose, volume, and concentration data from primary trial reports, and define testable predictions, with particular emphasis on the discriminating comparison between concentrated shot formats and standard-format beverages at matched total dose. The hypothesis is explicitly presented as falsifiable and is intended to guide future experimental research, including a proposed crossover trial comparing bolus versus sipped consumption of an identical caffeine dose.
Language: English
Topic: Coffee research and impacts
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204577398