Thermogenic Activation of Adipose Tissue by Caffeine During Strenuous Exercising and Recovery: A Double-Blind Crossover Study

<b>Background/Objectives:</b> To investigate acute caffeine (CAF: 375 mg, ≈4.8 mg/kg body mass) effects on energy expenditure (EE) and substrate kinetics during high-intensity interval exercise in individuals with high (HBAT) versus low (LBAT) brown adipose tissue activity using time-trend polynomial modeling. <b>Methods</b>: This is a randomized, double-blind crossover study in which 35 highly-trained males [HBAT-CAF, HBAT-PLA (Placebo), LBAT-CAF, LBAT-PLA] performed 30-min treadmill HIIE. Infrared thermography (IRT) assessed BAT activity by measuring supraclavicular skin temperature (SST). Breath-by-breath ergospirometry measured EE (kcal/min) and carbohydrate (CHO), lipid (LIP), and protein (PTN) oxidation. We applied second- and third-order polynomial regression models to depict the temporal trajectories of metabolic responses. <b>Results</b>: HBAT groups showed 25% higher sustained EE versus LBAT (<i>p</i> < 0.001), amplified by CAF. CHO oxidation exhibited biphasic kinetics: HBAT had 40% higher initial rates (0.75 ± 0.05 vs. 0.45 ± 0.04 g/min; <i>p</i> < 0.001) with accelerated decline (k = -0.21 vs. -0.15/min; <i>p</i> = 0.01). LIP oxidation peaked later in LBAT (40 vs. 20 min in HBAT), with CAF increasing oxidation by 18% in LBAT (<i>p</i> = 0.01). HBAT-CAF uniquely showed transient PTN catabolism (peak: 0.045 g/min at 10 min; k = -0.0033/min; <i>p</i> < 0.001). <b>Conclusions</b>: BAT status determines EE magnitude and substrate-specific kinetic patterns, while CAF exerts divergent modulation, potentiating early glycogenolysis in HBAT and lipolysis in LBAT. The HBAT-CAF synergy triggers acute proteolysis, revealing BAT-mediated metabolic switching.