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Tolerance to the humoral and hemodynamic effects of caffeine in man.
Open accessAbstract
Acute caffeine in subjects who do not normally ingest methylxanthines leads to increases in blood pressure, heart rate, plasma epinephrine, plasma norepinephrine, plasma renin activity, and urinary catecholamines. Using a double-blind design, the effects of chronic caffeine administration on these same variables were assessed. Near complete tolerance, in terms of both humoral and hemodynamic variables, developed over the first 1-4 d of caffeine. No long-term effects of caffeine on blood pressure, heart rate, plasma renin activity, plasma catecholamines, or urinary catecholamines could be demonstrated. Discontinuation of caffeine ingestion after 7 d of administration did not result in a detectable withdrawal phenomenon relating to any of the variables assessed.
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“These opinions and advisories are based upon a relatively small collection of caffeine studies that have been publicised in both scientific and lay literature and in the media over the past few decades [10], [17], [25].”
From No Evidence of Dehydration with Moderate Daily Coffee Intake: A Counterbalanced Cross-Over Study in a Free-Living Population (2014) · cites this paper as [25]
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“In short-term studies, it has been shown to increase blood pressure and peripheral vascular resistance, but tolerance rapidly develops. 4”
From Acute Effect of Caffeine on Arterial Stiffness and Aortic Pressure Waveform (2001) · cites this paper as [4]
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“In short-term studies, it has been shown to increase blood pressure and peripheral vascular resistance, but tolerance rapidly develops. 4”
From Acute Effect of Caffeine on Arterial Stiffness and Aortic Pressure Waveform (2001) · cites this paper as [4]
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“In short-term studies, it has been shown to increase blood pressure and peripheral vascular resistance, but tolerance rapidly develops. 4”
From Acute Effect of Caffeine on Arterial Stiffness and Aortic Pressure Waveform (2001) · cites this paper as [4]
In the citing paper
“Earlier studies which claimed to show tolerance to the pressor effects of caffeine [11,[16][17][18] have not mirrored 'normal' staggered caffeine consumption but are characterized by a prior period of prolonged abstinence followed by a high dose of caffeine administered once or twice daily.”
From Central and peripheral effects of sustained caffeine use: tolerance is incomplete (2002) · cites this paper as [11]
In the citing paper
“the effects of CAF on epinephrine are blunted within 1-4 d (36) of ingestion”
From The Glucose Intolerance Induced by Caffeinated Coffee Ingestion Is Less Pronounced than That Due to Alkaloid Caffeine in Men (2006) · cites this paper as [36]
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Citations
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“However, subsequent studies demonstrated that tolerance to these humoral and haemodynamic effects rapidly develops [13], so that in habitual coffee drinkers caffeine has no effect on PRA [ 14].”
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“European Journal of Clinical Nutrition (2007) 61, 796–802 & 2007 Nature Publishing Group All rights reserved 0954-3007/07 $30.00 www.nature.com/ejcn (Robertson et al., 1981; Lovallo et al., 2004), there are data that coffee consumption is associated with chronic increases in blood pressure (Jee et…”
BackgroundInfluentialRegular or decaffeinated coffee and subsequent human aggressive behavior
Cherek, D. R., Steinberg, J. L., & Brauchi, J. T. (1984) · Psychiatry Research · doi:10.1016/0165-1781(84)90073-8 · Cited by 27
Svenningsson, P., Johansson, B. A., & Fredholm, B. B. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(95)00202-4 · Cited by 27
Grosso, G., Stepaniak, U., Micek, A., Stefler, D., Bobák, M., & Pająk, A. (2016) · Public Health Nutrition · doi:10.1017/s1368980016001749 · Cited by 26
Roondhe, B., Dabhi, S. D., & Jha, P. K. (2018) · Applied Surface Science · doi:10.1016/j.apsusc.2018.01.249 · Cited by 26
Caffeine withdrawal symptoms and rate of metabolism
LADER, M. H., Cardwell, C., Shine, P. J., & Scott, N. (1996) · Journal of Psychopharmacology · doi:10.1177/026988119601000205 · Cited by 26
“has focused on tolerance to caffeine’s effects: for example, the diuretic effect of caffeine wanes on repeated dosing (Myers, 1924; Eddy and Downs, 1928), as do the stimulation of salivation (Winsor and Strongin, 1933) and the cardiovascular effects (Robertson et al., 1981).”
BackgroundCaffeine, Glucose Metabolism, and Type 2 Diabetes
Lane, J. D. (2011) · Journal of Caffeine Research · doi:10.1089/jcr.2010.0007 · Cited by 27
“40 Perhaps the strongest doubt arises from the common belief that habitual consumption of coffee or other caffeinated beverages leads to the development of tolerance to caffeine 41,42 and the disappearance of acute effects after daily use.”
Methodological and metabolic considerations in the study of caffeine-containing energy drinks
Shearer, J. (2014) · Nutrition Reviews · doi:10.1111/nure.12131 · Cited by 26
ALGUNAS VERDADES SOBRE EL CAFÉ
Gotteland, M., & de Pablo, S., V (2007) · Revista chilena de nutrición · doi:10.4067/s0717-75182007000200002 · Cited by 25
“Dicha actividad antioxidante podria ser de importancia en el caso de la diabetes, patologia que se caracteriza por un mayor estres oxidativo (25, 50, 51 ).”
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Caffeine: Clinical and experimental effects in humans
Bruce, M. S., & LADER, M. H. (1986) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.470010203 · Cited by 25
Caffeine Timing Improves Lower-Body Muscular Performance: A Randomized Trial
Harty, P. S., Zabriskie, H. A., Stecker, R. A., Currier, B. S., Tinsley, G. M., Surowiec, K., Jagim, A. R., Richmond, S. R., & Kerksick, C. M. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.585900 · Cited by 31
“Though peak plasma caffeine concentration (Cmax) is typically reached within 30–60min of oral ingestion of aqueous caffeine, Cmax values have been observed 15–150min post-consumption in subjects who consumed identical caffeine solutions (32, 33, 35).”
BackgroundConsumption of Green Tea Extract Results in Osteopenia in Growing Male Mice , ,
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Diabetic autonomic neuropathy—Part II
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Nicotine and caffeine effects on the task-elicited blood pressure response
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A pharmacodynamic interaction between caffeine and phenylpropanolamine
Brown, N. J., Ryder, D., & Branch, R. A. (1991) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1991.152 · Cited by 24
Coffee consumption and total mortality in a Mediterranean prospective cohort
Navarro, A., Martínez‐González, M. Á., Gea, A., Grosso, G., Martin-Moreno, J. M., López‐García, E., Martín‐Calvo, N., & Toledo, E. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy198 · Cited by 23
Diabetic autonomic neuropathy—part I
Schumer, M., Burton, G. V., Burton, C., Crum, D., & Pfeifer, M. A. (1988) · The American Journal of Medicine · doi:10.1016/0002-9343(88)90406-8 · Cited by 23
Drug Treatment of Orthostatic Hypotension and Vasovagal Syncope
Frishman, W. H., Azer, V., & Sica, D. A. (2003) · Heart Disease · doi:10.1097/01.hdx.0000050416.53995.43 · Cited by 23
Selected health and behavioral effects related to the use of caffeine
Lamarine, R. J. (1994) · Journal of Community Health · doi:10.1007/bf02260326 · Cited by 23
van Dam, R. M. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2008.111542 · Cited by 22
Caterina, R. D., & El‐Sohemy, A. (2016) · Lifestyle Genomics · doi:10.1159/000446801 · Cited by 22
Metadata
- Authors
- Robertson, D., Wade, D., Workman, R., Woosley, R. L., & Oates, J. A.
- Affiliations
- Vanderbilt University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1981-04-01
- Volume
- 67
- Issue
- 4
- Pages
- 1111-1117
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC370671
- OpenAlex
- W1970693682
- Cited by
- 501
- References
- 35
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 10 · 2019: 9 · 2018: 15 · 2017: 9 · 2016: 13 · 2015: 5 · 2014: 16 · 2013: 16 · 2012: 9
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- caffeine, tolerance (pharmacology and immunology), blood pressure, heart rate, plasma epinephrine, plasma norepinephrine, plasma renin activity, urinary catecholamines, methylxanthines, caffeine withdrawal, hemodynamic effects
- MeSH terms
- Adult, Blood Pressure, Caffeine, Catecholamines, Double-Blind Method, Drug Tolerance, Female, Hemodynamics, Humans, Male, Middle Aged, Renin
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