Time course of tolerance to adverse effects associated with the ingestion of a moderate dose of caffeine

Authors: RUIZ-MORENO, CARLOS - University Camilo José Cela; LARA, BEATRIZ - University Camilo José Cela; SALINERO, JUAN - University Camilo José Cela; BRITO DE SOUXA, DIEGO - University Camilo José Cela; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DEL COSO, JUAN - Universidad Rey Juan Carlos

Submitted to: European Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/17/2019
Publication Date: 1/3/2020
Citation: Ruiz-Moreno, C., Lara, B., Salinero, J.J., Brito De Souxa, D., Ordovas, J.M., Del Coso, J. 2020. Time course of tolerance to adverse effects associated with the ingestion of a moderate dose of caffeine. European Journal of Nutrition. https://doi.org/10.1007/s00394-019-02167-2.
DOI: https://doi.org/10.1007/s00394-019-02167-2

Interpretive Summary: The current knowledge about consumption of coffee and/or caffeine supports a protective effect against age-related diseases. However, caffeine is not without side effects. A better understanding of the presence and permanence over time of these effects will help to better understand who is affected and what will be the optimal intakes for disease prevention. Therefore, this study aimed to identify and describe the time course of tolerance to the most common caffeine-induced side effects. For this purpose, we carried out a crossover, double-blind placebo-controlled intervention trial. In one phase, participants ingested 3 mg/kg/day of caffeine for 20 days, while in another phase, they ingested a placebo. Resting heart rate and blood pressure were measured three times per week during each 20-day phase and a quantitative survey was used to categorize the magnitude of side effects. Our results show that in comparison with the placebo, the ingestion of caffeine increased systolic and diastolic blood pressure for the first 8 days of ingestion, but then these effects became attenuated for both outcomes and disappeared by day 20. The ingestion of caffeine did not affect heart rate at any time point. However, caffeine increased the feelings of nervousness and vigor and the rating of gastrointestinal complaints, insomnia and diuresis at several time points in the treatment and they did not disappear after 20 days of ingestion. In conclusion the daily intake of 3 mg/kg of caffeine, the equivalent to large cup of drip coffee, induced elevation in arterial blood pressure that disappeared after 8 days. However, other caffeine-induced effects such as increased nervousness and vigor, irritability, insomnia and diuresis remained after 20 days of consecutive caffeine ingestion. Although there was clear tolerance to the effect of caffeine on blood pressure, the persistence of other side effects suggests the inconvenience of maintaining a chronic caffeine intake, especially in susceptible individuals.

Technical Abstract: Purpose: This study aimed to identify and describe the time course of tolerance to the most common caffeine-induced side effects. Methods: Eleven participants took part in a crossover, double-blind placebo-controlled experimental design. In one phase, participants ingested 3 mg/kg/day of caffeine for 20 days, while in another phase, they ingested a placebo. Resting heart rate and blood pressure were measured three times per week during each 20-day phase and a quantitative survey was used to categorise the magnitude of side effects. Results: In the pairwise comparison with the placebo, the ingestion of caffeine increased systolic (+ 7.8 +/- 10.1%, P < 0.05)and diastolic blood pressure (+ 6.4 +/- 12.9% P < 0.05) for the first 8 days of ingestion, but then this effect became attenuated for both outcomes (on day 20, - 1.1 +/- 4.3% and + 0.9 +/- 9.6%, respectively). The ingestion of caffeine did not affect heart rate at any time point. Caffeine increased the feelings of nervousness and vigour and the rating of gastrointestinal complaints, insomnia and diuresis at several time points in the treatment (P < 0.05) and they did not disappear after 20 days of ingestion. Conclusions: The daily intake of 3 mg/kg of caffeine induced a meaningful elevation in arterial blood pressure that disappeared after 8 days. However, other caffeine-induced effects such as increased nervousness and vigour, irritability, insomnia and diuresis remained after 20 days of consecutive caffeine ingestion. Although there was clear tolerance to the effect of caffeine on blood pressure, the persistence of other side effects suggests the inconvenience of maintaining a chronic caffeine intake, at least at the dose of 3 mg/kg/day.