| Summary: | Pre-exercise caffeine ingestion has been shown to increase the workload at ventilatory threshold, suggesting an ergogenic effect of this stimulant on submaximal aerobic exercise. However, the time course of tolerance to the effect of caffeine on ventilatory threshold is unknown. This study aimed to determine the evolution of tolerance to the ergogenic effect of caffeine on the ventilatory threshold. Methods: Eleven participants (age 32.3 ± 4.9 yrs, height 171 ± 8 cm, body mass 66.6 ± 13.6 kg, VO<sub>2max</sub> = 48.0 ± 3.8 mL/kg/min) took part in a longitudinal, double-blind, placebo-controlled, randomized, crossover experimental design. Each participant took part in two identical treatments: in one treatment, participants ingested a capsule containing 3 mg of caffeine per kg of body mass per day (mg/kg/day) for twenty consecutive days; in the other treatment, participants ingested a capsule filled with a placebo for the same duration and frequency. During these treatments, participants performed a maximal ramp test on a cycle ergometer three times per week and the second ventilatory threshold (VT<sub>2</sub>) was assessed by using the ventilatory equivalents for oxygen and carbon dioxide. Results: A two-way ANOVA with repeated measures (substance x time) revealed statistically significant main effects of caffeine (<i>p</i> < 0.01) and time (<i>p</i> = 0.04) on the wattage obtained at VT<sub>2</sub>, although there was no interaction (<i>p</i> = 0.09). In comparison to the placebo, caffeine increased the workload at VT<sub>2</sub> on days 1, 4, 6 and 15 of ingestion (<i>p</i> < 0.05). The size of the ergogenic effect of caffeine over the placebo on the workload at VT<sub>2</sub> was progressively reduced with the duration of the treatment. In addition, there were main effects of caffeine (<i>p</i> = 0.03) and time (<i>p</i> = 0.16) on VO<sub>2</sub> obtained at VT<sub>2</sub>, with no interaction (<i>p</i> = 0.49). Specifically, caffeine increased oxygen uptake at VT<sub>2</sub> on days 1 and 4 (<i>p</i> < 0.05), with no other caffeine–placebo differences afterwards. For heart rate obtained at VT<sub>2</sub>, there was a main effect of substance (<i>p</i> < 0.01), while the overall effect of time (<i>p</i> = 0.13) and the interaction (<i>p</i> = 0.22) did not reach statistical significance. Heart rate at VT<sub>2</sub> was higher with caffeine than with the placebo on days 1 and 4 (<i>p</i> < 0.05). The size of the effect of caffeine on VO<sub>2</sub> and heart at VT<sub>2</sub> tended to decline over time. Conclusion: Pre-exercise intake of 3 mg/kg/day of caffeine for twenty days enhanced the wattage obtained at VT<sub>2</sub> during cycling ramp tests for ~15 days of ingestion, while there was a progressive attenuation of the size of the ergogenic effect of caffeine on this performance variable. Therefore, habituation to caffeine through daily ingestion may reduce the ergogenic effect of this stimulant on aerobic exercise of submaximal intensity.
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