The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
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 the citing paper
“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 the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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
Cites
Effects of Caffeine on Plasma Renin Activity, Catecholamines and Blood Pressure
Robertson, D., Frölich, J. C., Carr, R. K., Watson, J. T., Hollifield, J. W., Shand, D. G., & Oates, J. A. (1978) · New England Journal of Medicine · doi:10.1056/nejm197801262980403 · Cited by 757
Self-citationA simplified radiometric assay for plasma norepinephrine and epinephrine
Passon, P. G., & Peuler, J. D. (1973) · Analytical Biochemistry · doi:10.1016/0003-2697(73)90517-4 · Cited by 637
Clutter, W. E., Bier, D. M., Shah, S. D., & Cryer, P. E. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109840 · Cited by 576
Beavo, J. A., ROGERS, N. L., Crofford, O. B., Hardman, J. G., Ew, S., & NEWMAN, E. V. (1970) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)15265-6 · Cited by 471
Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man.
Robertson, D., Johnson, G., Robertson, R. M., Nies, A. S., Shand, D. G., & Oates, J. A. (1979) · Circulation · doi:10.1161/01.cir.59.4.637 · Cited by 467
Self-citationElectromechanical and Pharmacomechanical Coupling in Vascular Smooth Muscle
DROOGMANS, G., & Casteels, R. (1984) · Developments in cardiovascular medicine · doi:10.1007/978-1-4757-1171-4_35 · Cited by 431
Are Methylxanthine Effects Due to Antagonism of Endogenous Adenosine?
Fredholm, B. B. (1979) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(79)90046-4 · Cited by 409
ELECTROMECHANICAL AND PHARMACOMECHANICAL COUPLING IN VASCULAR SMOOTH MUSCLE
Somlyo, A. V., & Somlyo, A. P. (1968) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)27848-x · Cited by 304
Boston Collaborative Drug Surveillance Program
Jick, H. (1978) · BMJ · doi:10.1136/bmj.1.6109.365-a · Cited by 248
Release of norepinephrine in the central nervous system by theophylline and caffeine
Berkowitz, B. A., Tarver, J., & Spector, S. (1970) · European Journal of Pharmacology · doi:10.1016/0014-2999(70)90158-5 · Cited by 212
Cited by
Sorted by citations
Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624
“The tolerance to cardiovascular effects of caffeine is paralleled by a decrease in caffeine-induced increase in plasma adrenaline, noradrenaline, and renin levels (Robertson et al., 1981).”
Nehlig, A., Daval, J., & Debry, G. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90012-b · Cited by 1,463
Caffeinated energy drinks a growing problem
Reissig, C. J., Strain, E. C., & Griffiths, R. R. (2009) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2008.08.001 · Cited by 1,026
A Review of Caffeine’s Effects on Cognitive, Physical and Occupational Performance
McLellan, T. M., Caldwell, J. A., & Lieberman, H. R. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.001 · Cited by 840
Coffee Consumption and Risk of Type 2 Diabetes: A Systematic Review
van Dam, R. M., & Hu, F. B. (2005) · JAMA · doi:10.1001/jama.294.1.97 · Cited by 662
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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