Central and peripheral effects of sustained caffeine use: tolerance is incomplete
Open accessAbstract
Aims It is widely held that tolerance develops to the effects of sustained caffeine consumption. This study was designed to investigate the effects of chronic, staggered caffeine ingestion on the responses of an acute caffeine challenge, during euglycaemia. Methods Twelve healthy volunteers were randomized using a double‐blind, cross‐over design to take either 200 mg caffeine (C‐replete) or placebo (C‐naïve) twice daily for 1 week. Following baseline measurements being made, the responses to 200 mg caffeine (blood‐pressure, middle cerebral artery velocity, mood and cognitive performance) were examined over the subsequent 120 min. Blood glucose was not allowed to fall below 4.0 mmol l−1. Results After the caffeine challenge, middle cerebral artery blood velocity decreased in both conditions but was greater in the C‐naïve condition (−8.0 [‐10.0, −6.1] cm s−1vs−4.9 [‐6.8, −2.9] cm s−1 C‐replete, P < 0.02). Systolic blood pressure rise was not significantly different in C‐naïve, although this rise was more sustained over time (P < 0.04). Mood was adversely affected by regular caffeine consumption with tense aspect of mood significantly higher at baseline in C‐replete 11.6 ± 0.6 C‐naïve vs 16.3 ± 1.6 C‐replete, P < 0.01). Cognitive performance was not affected by previous caffeine exposure. Conclusions Overall these results suggest that tolerance is incomplete with respect to both peripheral or central effects of caffeine.
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Written from the paper’s full text.
TL;DR
In a double-blind crossover study, sustained caffeine use attenuated but did not abolish central and peripheral responses to an acute 200 mg caffeine challenge. The authors conclude that tolerance to caffeine is incomplete for vascular effects, while cognitive performance showed no differential effect.
Key findings
- Middle cerebral artery blood velocity decreased after caffeine challenge in both conditions, but more in C-naïve than C-replete: −8.0 [−10.0, −6.1] cm s⁻¹ vs −4.9 [−6.8, −2.9] cm s⁻¹, P < 0.02.
- Systolic blood pressure rise was not significantly different between conditions (+8.7 [2.1, 13.4] mmHg C-naïve vs +4.5 [0.8, 8.3] mmHg C-replete, P = 0.13), but the AUC for change over time was significantly different (P < 0.04). Initial diastolic rise was greater in C-naïve (+5.5 [3.2, 8.6] vs +1.1 [−0.8, 3.0] mmHg, P < 0.005), with AUC difference P = 0.055.
- Tense mood was higher at baseline in C-replete (16.3 ± 1.6 vs 11.6 ± 0.6 C-naïve, P < 0.01) and decreased more after caffeine in C-replete (−4.7 [−7.5, −1.9] vs −1.1 [−2.6, −0.34], P < 0.02).
- Cognitive performance was not affected by prior caffeine exposure: four-choice reaction time improved by 0.02 ± 0.01 s in both conditions, and VCD/VMD did not improve in either condition.
Methods
- Double-blind, randomized, crossover design: healthy regular caffeine consumers took either 200 mg caffeine (C-replete) or placebo (C-naïve) twice daily for 1 week, then received an acute 200 mg caffeine challenge; the abstract reports 12 healthy volunteers randomized, while the Methods states 14 gave informed consent.
- Measurements included heart rate and blood pressure, middle cerebral artery blood velocity via transcranial Doppler, UWIST mood scores, four-choice reaction time, visual change detection, and visual movement detection; blood glucose was maintained above 4.0 mmol l⁻¹.
- Analysis used summary measures, AUC by trapezoidal method, maximum response, and paired Student’s t-tests, with results as means with 95% CI or mean ± s.e.mean.
Limitations
- The paper does not state a formal limitations section; it notes that identifying population health effects “requires careful, further investigation.”
- Evident from the text: the sample was small (12 randomized per the abstract; 14 consented per Methods), healthy, regular caffeine consumers aged 23–38 years, limiting generalizability.
- Evident from the text: the supplementation period was only 1 week, and the acute challenge was conducted during euglycaemia with glucose maintained above 4.0 mmol l⁻¹, so findings may not extend to other durations or metabolic states.
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Claims the paper makes
0 of 17 cited sources checked · 0 supported · 0 flagged
- Findingown data
Caffeine consumption in the C-replete state was associated with a greater decrease in tense mood (-1.1 vs -4.7, P<0.02).
“Caffeine consumption in the C-replete state was associated with a greater decrease in tense mood (-1.1 [-2.6, -0.34] C-naïve vs -4.7 [-7.5, -1.9] C-replete, P < 0.02).”
Quote in the paperSubstantial claim - Findingown data
The decrease in V MCA was sustained for the duration of the study.
“The decrease in V MCA was sustained for the duration of the study (Figure 1).”
Quote in the paperSubstantial claim - Findingown data
Baseline tense mood was significantly higher in C-replete than C-naïve (11.6 vs 16.3, P<0.01).
“Baseline measurements were significantly different (11.6 ± 0.6 C-naïve vs 16.3 ± 1.6 C-replete, P < 0.01).”
Quote in the paperNot a substantial claim - Findingown data
The difference in diastolic blood pressure AUC between C-naïve and C-replete was not statistically sustained for the study duration (P=0.055).
“In contrast the initial rise in diastolic blood pressure was greater in the C-naïve condition ( + 5.5 [3.2, 8.6] mmHg C-naïve vs + 1.1 [-0.8, 3.0] mmHg C-replete, P < 0.005) but this difference was not statistically sustained for the study duration (AUC C-naïve vs C-replete P = 0.055) (Figure 2b).”
Quote in the paperSubstantial claim - Findingown data
In the C-replete state, the caffeine challenge caused a significant rise in systolic blood pressure at 30 min.
“In the C-replete state, the caffeine challenge caused a significant rise in systolic blood pressure at 30 min but this was not significantly different from the rise in Cnaïve study ( + 8.7 [2.1, 13.4] mmHg C-naïve vs + 4.5 [0.8, 8.3] mmHg C-replete, P = 0.13).”
Quote in the paperSubstantial claim
- Findingnone given
Heart rate was unaffected by prevailing caffeine status.
“Heart rate was unaffected by prevailing caffeine status.”
Quote in the paperNot a substantial claim - Findingown data
The rise in systolic blood pressure at 30 min was not significantly different between C-naïve and C-replete conditions (+8.7 vs +4.5 mmHg, P=0.13).
“In the C-replete state, the caffeine challenge caused a significant rise in systolic blood pressure at 30 min but this was not significantly different from the rise in Cnaïve study ( + 8.7 [2.1, 13.4] mmHg C-naïve vs + 4.5 [0.8, 8.3] mmHg C-replete, P = 0.13).”
Quote in the paperSubstantial claim - Findingown data
The AUC for change in systolic blood pressure against time was significantly different between C-naïve and C-replete conditions (P<0.04).
“Although there were no differences in baseline blood pressures (systolic and diastolic) AUCs for change in systolic blood pressure against time were significantly different ( P < 0.04) (Figure 2a).”
Quote in the paperSubstantial claim - Findingown data
The initial rise in diastolic blood pressure was greater in the C-naïve condition (+5.5 vs +1.1 mmHg, P<0.005).
“In contrast the initial rise in diastolic blood pressure was greater in the C-naïve condition ( + 5.5 [3.2, 8.6] mmHg C-naïve vs + 1.1 [-0.8, 3.0] mmHg C-replete, P < 0.005) but this difference was not statistically sustained for the study duration (AUC C-naïve vs C-replete P = 0.055) (Figure 2b).”
Quote in the paperSubstantial claim - Findingown data
Four-choice reaction time improved by 0.02 s following caffeine ingestion in both C-naïve and C-replete conditions.
“Four choice reaction time improved by 0.02 ± 0.01 s, following caffeine ingestion in both the C-naïve and C-replete conditions.”
Quote in the paperSubstantial claim - Findingown data
VCD and VMD did not improve with caffeine consumption in either condition.
“VCD and VMD did not improve with caffeine consumption in either condition (Table 2).”
Quote in the paperSubstantial claim - Findingown data
Caffeine withdrawal questionnaire total scores did not differ after caffeine abstinence or supplementation for 7 days (26.9 vs 27.8, P=0.34).
“Caffeine withdrawal questionnaires showed no difference in total scores after caffeine abstinence or supplementation for 7 days (26.9 ± 2.5 C-naïve vs 27.8 ± 2.3 C-replete, P = 0.34).”
Quote in the paperSubstantial claim - Interpretationown data
Tolerance to the vascular effects of caffeine is incomplete both centrally and peripherally.
“In conclusion, whilst the history of exposure to caffeine will influence the effect of a dose, tolerance to this drug's vascular effects is incomplete both centrally and peripherally.”
Quote in the paperSubstantial claim - Premisecitation
Caffeine withdrawal has been shown to decrease performance in humans and animals.
“caffeine withdrawal has been shown to decrease performance in both humans (e.g.finger tapping [9]) and animals [10]).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
Prior caffeine ingestion was not associated with different performance in all the tests compared with C-naïve.
“Here prior caffeine ingestion was not associated with different performance in all the tests, compared with the C-naïve state.”
Quote in the paperSubstantial claim - Premisecitation
Caffeine has been shown to decrease cerebral blood flow.
“Earlier, Mathew et al. demonstrated that cerebral blood flow decreases with caffeine ingestion [13,40].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Earlier studies claiming tolerance to pressor effects of caffeine did not mirror normal staggered caffeine consumption.
“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.”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
The stimulatory visual effects of caffeine are limited to situations with only a few visual inputs.
“it has subsequently been demonstrated that the stimulatory visual effects of caffeine are limited to situations with only a few visual inputs [44].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] source
Not checked in the free run.
- Interpretationown data
Tolerance to caffeine's more arousing effects did not develop.
“This would suggest that tolerance to caffeine's more arousing effects did not develop although this is in contrast to Green & Suls' study [31].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] source
Not checked in the free run.
- Interpretationown data
Tolerance to caffeine's haemodynamic effects is partial.
“This study adds to the body of previous work that tolerance to the haemodynamic effects of caffeine consumption is present but partial.”
Quote in the paperSubstantial claim - Premisecitation
Caffeine consumption is associated with increased awareness of hypoglycaemic events in free-living type 1 diabetic patients.
“caffeine consumption was associated with increased awareness of hypoglycaemic events in free-living type 1 diabetic patients [48].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48] source
Not checked in the free run.
- Interpretationreasoning
The present study suggests that similar parameters continue to be affected despite sustained caffeine use.
“The present study further suggests that similar parameters continue to be affected despite sustained caffeine use.”
Quote in the paperSubstantial claim - Interpretationown data
It was only the tense aspect of mood that was associated with a significantly different response to the caffeine challenge between the two conditions.
“It was only this aspect of mood that was associated with a significantly different response to the caffeine challenge between the two conditions.”
Quote in the paperNot a substantial claim - Interpretationown data
The development of partial tolerance to haemodynamic changes is in contrast to the effect on psychomotor function.
“Development of (partial) tolerance to the haemodynamic changes is in contrast to the effect on psychomotor function.”
Quote in the paperSubstantial claim
- May combine two claims. 12
- Classified as probably not a substantial claim. 7
May combine two claims.
Findingown dataAfter the caffeine challenge, middle cerebral artery blood velocity decreased in both conditions but was greater in the C-naïve condition (-8.0 vs -4.9 cm/s, P<0.02).
“After the caffeine challenge, V MCA decreased significantly in the both conditions, although this was more marked during the C-naïve condition ( -8.0 [ -10.0, -6.1] cm/s C-naïve vs 4.9 [ -6.8, -2.9] cm s -1 C-replete, P < 0.02) (mean difference [95%CI]).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataCaffeine consumption improved energetic mood in both conditions, but this effect was not significantly different between conditions (P=0.24).
“Whilst caffeine consumption improved energetic mood in both conditions this effect was not significantly different between conditions (P = 0.24) (Figure 3).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBaseline V MCA, heart rate and blood pressure were similar in both studies.
“Baseline V MCA , heart rate and blood pressure were similar in both studies.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataHedonic mood increased significantly from baseline during C-naïve only (+2.9, P<0.05), but the increase was not significantly different between conditions (P=0.51).
“Hedonic mood increased significantly from baseline during Cnaïve only (increase in hedonic mood score + 2.9 ± 1.2 above baseline, P < 0.05), although the increase observed was not significantly different between conditions (P = 0.51) (Figure 3).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningThe two study periods were performed at least 2 weeks apart to avoid carry-over effect.
“They were performed at least 2 weeks apart to avoid any carry-over effect.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenThe order of treatments was counter-balanced across participants.
“The order was counter-balanced across participants.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataCaffeine was measured by an enzyme immunoassay with intra- and inter-precision of 4.0% and 3.9% and lower limit of quantification 0.10 mmol l-1.
“The intra-and interprecision of this assay is 4.0% and 3.9%; the lower limit of quantification 0.10 mmol l -1 .”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningSubjects were familiarized with the study protocol to minimize practice effects on cognition tests.
“The first session served to familiarize the subjects with the study protocol, which helped to minimize practise effects on the cognition tests.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S1 (asserted). May combine two claims.
Study design and conductown dataThe study used a double-blind, randomized, crossover design with 200 mg caffeine or placebo twice daily for 1 week.
“Twelve healthy volunteers were randomized using a double-blind, crossover design to take either 200 mg caffeine (C-replete) or placebo (C-naïve) twice daily for 1 week.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningBlood glucose was maintained above 4.0 mmol l-1 to avoid confounding by hypoglycaemia.
“Throughout, blood sugar was maintained above 4.0 mmol l -1 by ingestion 3-6 g of glucose when blood glucose < 3.9 mmol l -1 ; thus avoiding the confounding effect of hypoglycaemia.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataTolerance was not demonstrated in performance (4 CRT) nor improvements in positive aspects of mood.
“In contrast tolerance was not demonstrated in performance (4 CRT) nor improvements in positive aspects of mood.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationOvernight abstinence is enough for sensitivity to be recovered and at best tolerance is partial.
“Given that caffeine consumption is associated with 10-12 h of overnight abstinence with more caffeine consumed in the morning than afternoon hours, it can be demonstrated that overnight abstinence is enough for sensitivity to be recovered and that at best tolerance is partial.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] source
Not checked in the free run.
May combine two claims.
PremisecitationChronic caffeine consumption is associated with increased anxiety, tension, restlessness, nervousness and anger.
“It has been demonstrated with free-living and laboratory studies that chronic caffeine consumption is associated with increased anxiety, tension, restlessness, nervousness and anger [29][30][31].”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCaffeine has been shown to narrow attention and increase selectivity of information processing.
“whilst caffeine has been shown to narrow attention and thus increase selectivity of information processing [42,43]”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Interpretationown dataDaily caffeine consumption was associated with an increase in tense mood, which resolved after further caffeine consumption.
“Interestingly daily caffeine consumption was associated with an increase in tense mood, which resolved after further caffeine consumption.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationCaffeine consumption shows a dose-response relationship with improved cognitive performance with no evidence for tolerance.
“Overall caffeine consumption showed a dose-response relationship with improved cognitive performance with no evidence for the phenomenon of tolerance to caffeine.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] source
Not checked in the free run.
The authors state this as an assumption.
Changes in middle cerebral artery velocity reflect changes in cerebral blood flow because calibre changes in the vessel are small.
“Although measurement of V MCA assumes that calibre changes in the vessel are small, alterations in V MCA reflect changes in cerebral blood flow during euglycaemia and hypoglycaemia [22].”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some studies have shown that habitual consumption results in tolerance to the acute effects of caffeine, while others have found that some individuals continue to experience these acute effects with each drinking episode and that tolerance disappears after 12 hours of abstinence.
“Some studies have shown that habitual consumption results in a tolerance to the acute effects of caffeine, 18,19 while others have found that some individuals continue to experience these acute effects with each drinking episode 20,21 and that the tolerance disappears after 12 hours of abstinence.22”
From Coffee and acute ischemic stroke onset: The Stroke Onset Study (2010) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
C-replete cerebral blood velocity change has conflicting signs
MinorThe Results report a positive 4.9 cm s−1 change for the C-replete condition, while the abstract reports −4.9 cm s−1. The negative confidence interval in the Results also conflicts with its positive point estimate.
“vs 4.9 [ -6.8, -2.9] cm s -1 C-replete”
“vs -4.9 [-6.8, -2.9] cm s -1 C-replete”
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Goldstein, I. B., Shapiro, D., Hui, K. K., & Yu, J. L. (1990) · Psychosomatic Medicine · doi:10.1097/00006842-199005000-00007 · Cited by 25 · see citing works
Cardiovascular responses to occupational stress and caffeine in telemarketing employees.
France, C., & Ditto, B. (1989) · Psychosomatic Medicine · doi:10.1097/00006842-198903000-00004 · Cited by 20 · see citing works
Acute behavioral effects of triazolam and caffeine, alone and in combination, in humans.
Rush, C. R., Higgins, S. T., Hughes, J. R., & Bickel, W. K. (1994) · Experimental and Clinical Psychopharmacology · doi:10.1037/1064-1297.2.3.211 · Cited by 16 · see citing works
Caffeine Consumption in the United Kingdom: A Retrospective Survey
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Flagged first, then by citations
1 of the 50 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
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Cited by
Sorted by citations
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption
Nehlig, A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014407 · Cited by 632 · see citing works
Wikoff, D. S., Welsh, B. T., Henderson, R. G., Brorby, G. P., Britt, J. K., Myers, E. F., Goldberger, J. J., Lieberman, H. R., O’Brien, C. P., Peck, J. D., et al. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.04.002 · Cited by 451 · see citing works
Kallioinen, N., Hill, A., Horswill, M. S., Ward, H. E., & Watson, M. O. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001197 · Cited by 357 · see citing works
Caffeine and cardiovascular health
Turnbull, D., Rodricks, J. V., Mariano, G. F., & Chowdhury, F. (2017) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2017.07.025 · Cited by 216 · see citing works
“…et al., 2014; Umemura et al., 2006; van Dusseldorp et al., 1991; van Dusseldorp et al., 1989; Vlachopoulos et al., 2003b; Waring et al., 2003; Watson et al., 2000, 2002; ZimmermannViehoff et al., 2016; Agudelo-Ochoa et al., 2016; Brothers et al., 2016; Doerner et al., 2015; Domotor et al.,…”
BackgroundChilds, E., & de Wit, H. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0341-3 · Cited by 219 · see citing works
“In some studies, regular caffeine users show complete or partial tolerance to the physiological and subjective effects of the drug (Evans and Griffiths 1992; Watson et al. 2002), whereas other studies find little or no tolerance to the psychomotor effects of caffeine (Jarvis 1993).”
BackgroundLong‐term follow‐up of DYT1 dystonia patients treated by deep brain stimulation: An open‐label study
Cif, L., Vasques, X., González, V., Ravel, P., Biolsi, B., Collod‐Béroud, G., Tuffery‐Giraud, S., Fertit, H. E., Claustres, M., & Coubes, P. A. (2010) · Movement Disorders · doi:10.1002/mds.22802 · Cited by 157 · see citing works
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“It is likely that an overnight abstinence, as used in this study, is partially sufficient to overcome tolerance formation in central nervous system adenosine receptors systems (32,33).”
MethodCaffeine and the Control of Cerebral Hemodynamics
Pelligrino, D. A., Xu, H.-L., & Vetri, F. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-091261 · Cited by 93 · see citing works
“Furthermore, in human subjects, a partial (or incomplete) tolerance to acute caffeine-related CBF reductions was found in association with chronic caffeine intake [66, 67].”
Coffee and acute ischemic stroke onset: The Stroke Onset Study
Mostofsky, E., Schlaug, G., Mukamal, K. J., Rosamond, W. D., & Mittleman, M. A. (2010) · Neurology · doi:10.1212/wnl.0b013e3181fb443d · Cited by 75 · see citing works
Ruiz-Moreno, C., Lara, B., Salinero, J. J., Brito de Souza, D., Ordovás, J. M., & Del Coso, J. (2020) · European Journal of Nutrition · doi:10.1007/s00394-019-02167-2 · Cited by 60 · see citing works
The effects of energy drink in combination with alcohol on performance and subjective awareness
Alford, C., Hamilton-Morris, J., & Verster, J. C. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2677-1 · Cited by 60 · see citing works
“…or withdrawal hypothesis (James 1997; James and Rogers 2005), although improvements in performance are still seen independently of this when additional caffeine is consumed after the usual caffeine intake (Christopher et al. 2005; Smith et al. 2005; Warburton 1995; Watson et al. 2002).”
BackgroundAlcohol and Acute Ischemic Stroke Onset
Mostofsky, E., Burger, M. R., Schlaug, G., Mukamal, K. J., Rosamond, W. D., & Mittleman, M. A. (2010) · Stroke · doi:10.1161/strokeaha.110.580092 · Cited by 58 · see citing works
Effect of chronic caffeine intake on choice reaction time, mood, and visual vigilance
Judelson, D. A., Armstrong, L. E., Sökmen, B., Roti, M. W., Casa, D. J., & Kellogg, M. D. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.06.011 · Cited by 55 · see citing works
“Interestingly, other aspects of mood (Tense, as measured with the UWIST Mood Adjective Checklist [44]) have also resisted tolerance to chronic caffeine use [17], suggesting that tolerance to caffeine’s effects on mood may develop slower, to a lesser degree, or not at all.”
BackgroundAcute effects of caffeine on arterial stiffness, wave reflections, and central aortic pressures
PAPAIOANNOU, T., Karatzi, K., Karatzis, E. N., Papamichael, C. M., & Lekakis, J. P. (2005) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2004.08.017 · Cited by 50 · see citing works
Accuracy of home blood pressure readings: monitors and operators
Stryker, T., Wilson, M. P., & Wilson, T. (2004) · Blood Pressure Monitoring · doi:10.1097/01.mbp.0000130224.18777.ce · Cited by 48 · see citing works
International society of sports nutrition position stand: coffee and sports performance
Lowery, L. M., Anderson, D. E., Scanlon, K. F., Stack, A., Escalante, G., Campbell, S. C., Kerksick, C. M., Nelson, M. T., Ziegenfuss, T. N., VanDusseldorp, T. A., et al. (2023) · Journal of the International Society of Sports Nutrition · doi:10.1080/15502783.2023.2237952 · Cited by 50 · see citing works
“(2002) [130] provided non-exercising caffeine-habituated and caffeine-naïve healthy volunteers a 200 mg caffeine challenge and concluded that the central and peripheral effects of tolerance are incomplete.”
BackgroundVera, J., Redondo, B., Molina, R., Bermúdez, J., & Jiménez, R. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5114-2 · Cited by 42 · see citing works
Kerr, D., Barua, S., GLANTZ, N. M., et al. (2020) · BMJ Nutrition Prevention & Health · doi:10.1136/bmjnph-2020-000133 · Cited by 36 · see citing works
Self-citationCaffeine-dependent changes of sleep-wake regulation: Evidence for adaptation after repeated intake
Weibel, J., Lin, Y.-S., Landolt, H., Garbazza, C., Kolodyazhniy, V., Kistler, J., Rehm, S., Rentsch, K., Borgwardt, S., Cajochen, C., et al. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109851 · Cited by 35 · see citing works
Dekker, M. J., Gusba, J. E., Robinson, L. E., & Graham, T. E. (2007) · British Journal Of Nutrition · doi:10.1017/s0007114507730738 · Cited by 31 · see citing works
Caffeine Tolerance is Incomplete: Persistent Blood Pressure Responses in the Ambulatory Setting
FARAG, N., VINCENT, A., SUNG, B., WHITSETT, T., WILSON, M., & LOVALLO, W. (2005) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2005.03.738 · Cited by 29 · see citing works
Caffeine attenuates practice effects in word stem completion as measured by fMRI BOLD signal
Bendlin, B. B., Trouard, T. P., & Ryan, L. (2006) · Human Brain Mapping · doi:10.1002/hbm.20295 · Cited by 30 · see citing works
Methylxanthines and Drug Dependence: A Focus on Interactions with Substances of Abuse
Morelli, M., & Simola, N. (2010) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-13443-2_20 · Cited by 26 · see citing works
“In humans, tolerance to the behavioral effects of caffeine is of low magnitude and incomplete (Fredholm et al. 1999; Watson et al. 2002).”
BackgroundThe effects of caffeine administration on the early stage of bone healing and bone density
Duarte, P. M., Marques, M. R., Bezerra, J. P., et al. (2009) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2009.05.001 · Cited by 26 · see citing works
Time to Recover From Daily Caffeine Intake
Lin, Y.-S., Weibel, J., Landolt, H., Santini, F., Garbazza, C., Kistler, J., Rehm, S., Rentsch, K., Borgwardt, S., Cajochen, C., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.787225 · Cited by 24 · see citing works
“In the current analyses, we corroborated the withdrawal-induced vasodilation by the elevated cerebral blood flow in the withdrawal condition (37-42).”
Screening for drugs to reduce zebrafish aggression identifies caffeine and sildenafil
Gutiérrez, H. C., Vacca, I., Schoenmacker, G., Cleal, M., Tochwin, A., O’Connor, B., Young, A. M. J., Vásquez, A. A., Winter, M. J., Parker, M. O., et al. (2019) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2019.10.005 · Cited by 24 · see citing works
Olateju, T. O., Begley, J., Green, D. J., & Kerr, D. E. (2014) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2014.07.220 · Cited by 22 · see citing works
“The rise in systolic blood pressure seen here was similar to that seen in previous studies of caffeine-containing drinks, with similar achieved plasma caffeine levels, although tolerance does appear to develop with sustained caffeine use (8).”
BackgroundResultSelf-citationCognition-Enhancing Drugs and Their Appropriateness for Aviation and Ground Troops: A Meta-Analysis
Kelley, A. M., Webb, C., Athy, J. R., Ley, S. L., & Gaydos, S. (2010) · doi:10.21236/ada533727 · Cited by 17 · see citing works
Cheng, Y., Roach, G. D., & Petrilli, R. M. (2014) · Emergency Medicine Australasia · doi:10.1111/1742-6723.12319 · Cited by 16 · see citing works
“Humans develop partial tolerance to caffeine albeit short lived; overnight abstinence is sufficient for return of sensitivity.(56,57) Caffeine affects recovery sleep if consumed within 5 h of starting post-shift recovery sleep.”
BackgroundNutritional Concerns in Recreation, Exercise, and Sport
Driskell, J. A., & Wolinsky, I. (2009) · CRC Press eBooks · doi:10.1201/9781420068160 · Cited by 10 · see citing works
Influences of caffeine, acetazolamide and cognitive stimulation on cerebral blood flow velocities
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Carbone, M. G., Pagni, G., Tagliarini, C., Maremmani, I., & Maremmani, A. G. I. (2025) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph22081171 · Cited by 9 · see citing works
Coffee, diabetes and insulin sensitivity
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Self-citationDependence upon Coffee and Caffeine: An Update
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Zebrafish gender-specific anxiety-like behavioral and physiological reactions elicited by caffeine
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Dependence upon Coffee and Caffeine
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Daily Caffeine Intake and the Effect of Caffeine on Pilots’ Performance After Extended Wakefulness
Wingelaar-Jagt, Y. Q., Wingelaar, T. T., de Vrijer, L., Riedel, W. J., & Ramaekers, J. G. (2023) · Aerospace Medicine and Human Performance · doi:10.3357/amhp.6253.2023 · Cited by 6 · see citing works
Effects of Caffeine on Salivation
Barasch, A., & Gordon, S. C. (2016) · Oral Health Case Reports · doi:10.4172/2471-8726.1000107 · Cited by 3 · see citing works
“Among documented clinical effects of caffeine are increased heart rate, systolic blood pressure and left ventricular output [7,8,11] stimulation of autonomic responses [12,13] decreased tone of the gastrointestinal smooth muscles increased ocular pressure in glaucoma patients [14] central nervous system excitation and…”
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Lin, Y.-S., Weibel, J., Landolt, H., Santini, F., Slawik, H. C., Borgwardt, S., Cajochen, C., & Reichert, C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.19.440520 · Cited by 2 · see citing works
How to Induce Arrhythmias with Caffeine?
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Time to recover from daily caffeine intakePreprint
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BackgroundMedicinal fatigue management in military aviation
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- Authors
- Watson, J., Deary, I., & Kerr, D.
- Affiliations
- Royal Bournemouth Hospital (GB)
- University of Edinburgh (GB)
- Corresponding author
- Kerr, David
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2002-10
- Volume
- 54
- Issue
- 4
- Pages
- 400-406
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC1874449
- OpenAlex
- W1496048461
- Semantic Scholar
- 8fa67e6bee46387cd33f211b0d8694ccc34cfdac
- Cited by
- 47
- References
- 50
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2014: 2 · 2012: 2
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- caffeine, caffeine tolerance, middle cerebral artery blood flow velocity, cerebral blood flow, systolic blood pressure, mood, cognitive performance, normoglycemia
- MeSH terms
- Adult, Affect, Central Nervous System Stimulants, Blood Flow Velocity, Blood Pressure, Caffeine, Cognition, Double-Blind Method, Humans, Psychometrics, Cross-Over Studies, Middle Cerebral Artery
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