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

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European Journal of Nutrition Aims and scope Submit manuscript

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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Magkos F, Kavouras SA (2005) Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Crit Rev Food Sci Nutr 45:535–562. https://doi.org/10.1080/1040-830491379245

    Article  CAS  PubMed  Google Scholar 

  2. Laizure SC, Meibohm B, Nelson K et al (2017) Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects. Br J Clin Pharmacol 83:2687–2694. https://doi.org/10.1111/bcp.13389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Salinero JJ, Lara B, Abian-Vicen J et al (2014) The use of energy drinks in sport: perceived ergogenicity and side effects in male and female athletes. Br J Nutr 112:1494–1502. https://doi.org/10.1017/S0007114514002189

    Article  CAS  PubMed  Google Scholar 

  4. Salinero JJ, Lara B, Del Coso J (2019) Effects of acute ingestion of caffeine on team sports performance: a systematic review and meta-analysis. Res Sport Med 27:238–256. https://doi.org/10.1080/15438627.2018.1552146

    Article  Google Scholar 

  5. Souza DB, Del Coso J, Casonatto J, Polito MD (2017) Acute effects of caffeine-containing energy drinks on physical performance: a systematic review and meta-analysis. Eur J Nutr 56:13–27. https://doi.org/10.1007/s00394-016-1331-9

    Article  CAS  PubMed  Google Scholar 

  6. Grgic J, Grgic I, Pickering C et al (2019) Wake up and smell the coffee: caffeine supplementation and exercise performance—an umbrella review of 21 published meta-analyses. Br J Sports Med. https://doi.org/10.1136/bjsports-2018-100278

    Article  PubMed  Google Scholar 

  7. Cappelletti S, Daria P, Sani G et al (2015) Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol 13:71–88. https://doi.org/10.2174/1570159X13666141210215655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mahoney CR, Giles GE, Marriott BP et al (2019) Intake of caffeine from all sources and reasons for use by college students. Clin Nutr 38:668–675. https://doi.org/10.1016/j.clnu.2018.04.004

    Article  CAS  PubMed  Google Scholar 

  9. Grosso G, Godos J, Galvano F, Giovannucci EL (2017) Coffee, caffeine, and health outcomes: an umbrella review. Annu Rev Nutr 37:131–156. https://doi.org/10.1146/annurev-nutr-071816-064941

    Article  CAS  PubMed  Google Scholar 

  10. Wikoff D, Welsh BT, Henderson R et al (2017) Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chem Toxicol 109:585–648. https://doi.org/10.1016/j.fct.2017.04.002

    Article  CAS  PubMed  Google Scholar 

  11. Guessous I, Eap CB, Bochud M (2014) Blood pressure in relation to coffee and caffeine consumption. Curr Hypertens Rep 16:468. https://doi.org/10.1007/s11906-014-0468-2

    Article  PubMed  Google Scholar 

  12. Zhang Z, Hu G, Caballero B et al (2011) Habitual coffee consumption and risk of hypertension: a systematic review and meta-analysis of prospective observational studies. Am J Clin Nutr 93:1212–1219. https://doi.org/10.3945/ajcn.110.004044

    Article  CAS  PubMed  Google Scholar 

  13. Robertson D, Wade D, Workman R et al (1981) Tolerance to the humoral and hemodynamic effects of caffeine in man. J Clin Investig 67:1111–1117

    Article  CAS  Google Scholar 

  14. Bell DG, McLellan TM (2002) Exercise endurance 1, 3, and 6 h after caffeine ingestion in caffeine users and nonusers. J Appl Physiol 93:1227–1234. https://doi.org/10.1152/japplphysiol.00187.2002

    Article  CAS  PubMed  Google Scholar 

  15. Corti R, Binggeli C, Sudano I et al (2002) Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking. Circulation 106:2935–2940

    Article  Google Scholar 

  16. Vera J, Redondo B, Molina R et al (2019) Effects of caffeine on intraocular pressure are subject to tolerance: a comparative study between low and high caffeine consumers. Psychopharmacology 236:811–819. https://doi.org/10.1007/s00213-018-5114-2

    Article  CAS  PubMed  Google Scholar 

  17. Watson J, Deary I, Kerr D (2002) Central and peripheral effects of sustained caffeine use: tolerance is incomplete. Br J Clin Pharmacol 54:400–406. https://doi.org/10.1046/j.1365-2125.2002.01681.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Childs E, de Wit H (2006) Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users. Psychopharmacology 185:514–523. https://doi.org/10.1007/s00213-006-0341-3

    Article  CAS  PubMed  Google Scholar 

  19. de Gonçalves LS, de Painelli VS, Yamaguchi G et al (2017) Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation. J Appl Physiol 123:213–220. https://doi.org/10.1152/japplphysiol.00260.2017

    Article  CAS  Google Scholar 

  20. Kennedy DO, Haskell CF (2011) Cerebral blood flow and behavioural effects of caffeine in habitual and non-habitual consumers of caffeine: a near infrared spectroscopy study. Biol Psychol 86:298–306. https://doi.org/10.1016/j.biopsycho.2010.12.010

    Article  PubMed  Google Scholar 

  21. Fredholm BB, Yang J, Wang Y (2017) Low, but not high, dose caffeine is a readily available probe for adenosine actions. Mol Aspects Med 55:20–25. https://doi.org/10.1016/j.mam.2016.11.011

    Article  CAS  PubMed  Google Scholar 

  22. Fredholm BB, Bättig K, Holmén J et al (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133

    CAS  PubMed  Google Scholar 

  23. Shi D, Nikodijević O, Jacobson KA, Daly JW (1993) Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain. Cell Mol Neurobiol 13:247–261. https://doi.org/10.1007/BF00733753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bühler E, Lachenmeier DW, Schlegel K, Winkler G (2014) Development of a tool to assess the caffeine intake among teenagers and young adults. Ernährungs Umschau 61:58–63

    Google Scholar 

  25. Beevers G, Lip GY, O’Brien E (2001) ABC of hypertension: blood pressure measurement. BMJ 322:981–985. https://doi.org/10.1136/bmj.322.7292.981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lara B, Ruiz-Moreno C, Salinero JJ, Del Coso J (2019) Time course of tolerance to the performance benefits of caffeine. PLoS ONE One 14:e0210275. https://doi.org/10.1371/journal.pone.0210275

    Article  CAS  Google Scholar 

  27. Hopkins WG, Marshall SW, Batterham AM, Hanin J (2009) Progressive statistics for studies in sports medicine and exercise science. Med Sci Sports Exerc 41:3–13

    Article  Google Scholar 

  28. Mozaffarian D, Benjamin EJ, Go AS et al (2016) Heart disease and stroke statistics—2016 update. Circulation. https://doi.org/10.1161/CIR.0000000000000350

    Article  PubMed  PubMed Central  Google Scholar 

  29. Echeverri D, Montes FR, Cabrera M et al (2010) Caffeine’s vascular mechanisms of action. Int J Vasc Med 2010:834060. https://doi.org/10.1155/2010/834060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nehlig A, Daval JL, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Rev 17:139–170

    Article  CAS  Google Scholar 

  31. Davis JM, Zhao Z, Stock HS et al (2003) Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Integr Comp Physiol 284:R399–R404. https://doi.org/10.1152/ajpregu.00386.2002

    Article  CAS  Google Scholar 

  32. Elmenhorst D, Meyer PT, Matusch A et al (2012) Caffeine occupancy of human cerebral A1 adenosine receptors: in vivo quantification with 18F-CPFPX and PET. J Nucl Med 53:1723–1729. https://doi.org/10.2967/jnumed.112.105114

    Article  CAS  PubMed  Google Scholar 

  33. European Food Safety Authority (2015) Why did EFSA carry out its risk assessment? www.efsa.europa.eu. Accessed 3 Dec 2019

  34. Anker D, Santos-Eggimann B, Santschi V et al (2018) Screening and treatment of hypertension in older adults: less is more? Public Health Rev 39:26

    Article  Google Scholar 

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Acknowledgements

The authors wish to thank the subjects for their invaluable contribution to the study.

Funding

This investigation did not receive any funding.

Author information

Authors and Affiliations

  1. Exercise Physiology Laboratory, Camilo José Cela University, Madrid, Spain

    Carlos Ruiz-Moreno, Beatriz Lara, Juan José Salinero & Diego Brito de Souza

  2. USDA ARS, Human Nutrition Research Center On Aging At Tufts University, Boston, MA, 02111, USA

    José M. Ordovás

  3. IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain

    José M. Ordovás

  4. Centre for Sport Studies, Rey Juan Carlos University, C/Camino del Molino, s/n, 28943, Fuenlabrada, Spain

    Juan Del Coso

Authors
  1. Carlos Ruiz-Moreno
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  2. Beatriz Lara
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  3. Juan José Salinero
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  4. Diego Brito de Souza
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  5. José M. Ordovás
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  6. Juan Del Coso
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Contributions

CRM, BL, JJS, JMO, JC: formulated the research question. CRM, BL, JJS, JC: designed the study. CRM, BL, JJS, JC : carried it out. CRM, DBS, BL, JJS, JC: analysed the data. DBS, JMO, JC: wrote the article. CRM, DBS, BL, JJS, JMO: revised the article.

Corresponding author

Correspondence to Juan Del Coso.

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Conflict of interest

All authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work.

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Ruiz-Moreno, C., Lara, B., Salinero, J.J. et al. Time course of tolerance to adverse effects associated with the ingestion of a moderate dose of caffeine. Eur J Nutr 59, 3293–3302 (2020). https://doi.org/10.1007/s00394-019-02167-2

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  • DOI: https://doi.org/10.1007/s00394-019-02167-2

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