The cardiovascular interaction between caffeine and nicotine in humans

Smits, Paul; Temme, L.; Thien, Theo

doi:10.1038/clpt.1993.131

Cited by 25 publications

(16 citation statements)

References 7 publications

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“…On the contrary, caffeine increased both blood pressure and FBF-effects that can be largely attributed to caffeine-induced release of plasma catecholamines (27). The increase in FBF with caffeine is somewhat unexpected, as earlier studies reported no effects of caffeine on FBF (27,28). Mental stress experienced during the tests might explain this observation because caffeine is known to magnify vasodilator responses induced by mental stress (28,29).…”

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confidence: 38%

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Caffeine Can Decrease Insulin Sensitivity in Humans

Keijzers¹,

Galan²,

Tack³

et al. 2002

Diabetes Care

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303

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OBJECTIVE -Caffeine is a central stimulant that increases the release of catecholamines. As a component of popular beverages, caffeine is widely used around the world. Its pharmacological effects are predominantly due to adenosine receptor antagonism and include release of catecholamines. We hypothesized that caffeine reduces insulin sensitivity, either due to catecholamines and/or as a result of blocking adenosine-mediated stimulation of peripheral glucose uptake.RESEARCH DESIGN AND METHODS -Hyperinsulinemic-euglycemic glucose clamps were used to assess insulin sensitivity. Caffeine or placebo was administered intravenously to 12 healthy volunteers in a randomized, double-blind, crossover design. Measurements included plasma levels of insulin, catecholamines, free fatty acids (FFAs), and hemodynamic parameters. Insulin sensitivity was calculated as whole-body glucose uptake corrected for the insulin concentration. In a second study, the adenosine reuptake inhibitor dipyridamole was tested using an identical protocol in 10 healthy subjects.RESULTS -Caffeine decreased insulin sensitivity by 15% (P Ͻ 0.05 vs. placebo). After caffeine administration, plasma FFAs increased (P Ͻ 0.05) and remained higher than during placebo. Plasma epinephrine increased fivefold (P Ͻ 0.0005), and smaller increases were recorded in plasma norepinephrine (P Ͻ 0.02) and blood pressure (P Ͻ 0.001). Dipyridamole did not alter insulin sensitivity and only increased plasma norepinephrine (P Ͻ 0.01).CONCLUSIONS -Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels. Because dipyridamole did not affect glucose uptake, peripheral adenosine receptor antagonism does not appear to contribute to this effect. Diabetes Care 25:364 -369, 2002C affeine is one of the most widely consumed "drugs" in the world. The average daily intake per capita in the western world is ϳ300 mg (1), and most of it comes from dietary sources such as coffee, tea, cola drinks, and chocolate. Caffeine is a methylxanthine derivative and a potent adenosine receptor antagonist that exerts its effects both centrally and peripherally because it crosses the blood-brain barrier. Systemic effects of caffeine include an increase in blood pressure and stimulation of the release of catecholamines, particularly epinephrine (2). Local effects of caffeine stem from interaction with interstitial adenosine (3).Data from animal studies have indicated that methylxanthines are involved in insulin-mediated glucose handling and insulin responsiveness in adipose and muscular tissue. In obese Zucker rats, the caffeine-related adenosine receptor antagonist 1,3 dipropyl-8-(acrylic) phenylxanthine was found to inhibit glucose uptake in adipose tissue, whereas the reverse was observed in skeletal muscle (4).Both effects were attributed to adenosine receptor antagonism at the tissue site because the compound does not cross the blood-brain barrier. Studies showing that adenosine or adenosine agonists increase insulin sensitivity in adipos...

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contrasting

confidence: 38%

“…The increase in FBF with caffeine is somewhat unexpected, as earlier studies reported no effects of caffeine on FBF (27,28). Mental stress experienced during the tests might explain this observation because caffeine is known to magnify vasodilator responses induced by mental stress (28,29).…”

mentioning

confidence: 45%

Caffeine Can Decrease Insulin Sensitivity in Humans

Keijzers¹,

Galan²,

Tack³

et al. 2002

Diabetes Care

Self Cite

303

205

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“…46,47 This study provided little evidence that the effects of nicotine are influenced by concurrent caffeine (with the exception of working memory accuracy as noted above) and is consistent with other studies examining the combination of these drugs in nonsmoking, moderatecaffeine-consuming individuals. 21,22 This observation may suggest that the coadministration of tobacco and caffeine-containing beverages reflects a behavioral rather than pharmacological mechanism. Sensory characteristics associated with common nicotine and caffeine vehicles (ie, cigarettes, coffee) can influence self-administration.…”

Section: Discussionmentioning

confidence: 93%

“…19,20 Accordingly, there are several reports of the combined effects of nicotine and caffeine in nonnicotine users (N = 10). 21,22 However, these small-sample studies may have been underpowered. Thus, their failure to report an enhanced effect of the nicotine/caffeine combination, relative to either drug alone, may reflect a Type II error.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Caffeine's Influence on Nicotine's Effects in Nonsmokers

Blank¹,

Kleykamp²,

Jennings³

et al. 2007

am j health behav

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Objective-To determine if nicotine's effects are influenced by caffeine in nonsmoking, moderate-caffeine consuming individuals (N=20).Methods-The first 3 sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75, or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in ascending order. The fourth session (single blind) repeated the 0 mg caffeine condition.Results-Nicotine increased heart rate and subjective ratings indicative of aversive effects, and decreased reaction times. These effects were independent of caffeine dose and reliable across sessions. Conclusions-In nonsmokers, nicotine effects are not influenced by moderate caffeine doses.Keywords nicotine; caffeine; interaction; subjective effect; cognition Nicotine and caffeine are mild psychomotor stimulants and the most widely used drugs in the United States. 1,2 Interestingly, 80-97% of nicotine users also use caffeine: 3 smokers drink more coffee than nonsmokers and self-administer more nicotine when using caffeine. 4,5 This frequent co-administration may reflect the influence of pharmacokinetics 6,7 and/or environment. 8 Also, the effects of the nicotine-caffeine combination may differ from those of either drug alone. 1,9 Individually, nicotine and caffeine increase heart rate, 10 produce stimulation and arousal, 11,12 and improve attention. 13,14 Some of these effects may be enhanced when the drugs are combined. For example, oral caffeine, but not placebo, increased the subjective and reinforcing effects of intravenous (IV) nicotine (eg, higher ratings of "stimulated" and monetary crossover point, or amount of money willing to be paid to receive drug; [N = 9] 9 ; see also [N = 12] 1 ). Also, 2 mg nicotine gum increased accuracy on a digit-recall task when administered with active, but not placebo, caffeine [N = 6]. 15 Importantly, results from these studies may be influenced by the fact that all participants were regular nicotine users. When regular nicotine users are included in studies examining nicotine effects, results can be influenced by tolerance and dependence. For instance, recent NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript nicotine exposure may result in a marked reduction of drug effect (ie, tolerance), 16 whereas dependence can produce withdrawal signs and symptoms after a period of drug abstinence. 17 Drug-induced suppression of these signs and symptoms 18 can be mistaken for a direct effect of the drug. One way to understand the direct effects of drugs is to include individuals who are not tolerant to or dependent on them. 19,20 Accordingly, there are several reports of the combined effects of nicotine and caffeine in nonnicotine users (N = 10). 21,22 However, these small-sample studies may have been underpowered. Thus, their failure to report an enhanced effect of the nicotine/caffeine combination, relative to either drug alone, may reflect a Type II error. Although including individuals with no history of caffeine use would also be valuable, this goal is vi...

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“…Specifically, in empirical studies, nicotine administration decreased body weight in humans and rats (Grunberg, 1982;Winders & Grunberg, 1989), decreased aggression in humans (Cherek, 1981;Cherek et aI., 1991) and in rats (Silvennan, 1971;ScheufeJe, 1997), and altered biochemical and behavioral responses to stress in rats (Benwell & Balfour, 1982;Cam & Bassett, 1983;1984;Sharp, Beyer, Levine, Morley, & McAllen. 1987;Peck, Dilsaver, & McGee, 1991;Acri, 1992Acri, , 1994Takada, Thara, Vrano, & Takada, 1995) and in humans (MacDougall, Musante, Castillo, & Acevedo, 1988;Gilbert, Robinson, Chamberlin, & Spielberger, 1989;Pomerleau & Pomerleau, 1990;Levin, Rose, Behm, & Caskey, 1991;Smits, Temme, & Thien, 1993).…”

Section: ) Effects Of Nicotinementioning

confidence: 99%

Effects of Nicotine Administration and Stress on Sensory-Gating Depend on Rat Strain and Sex

Faraday¹

1998

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The present experiments investigated effects of nicotine administration, nicotine cessation, and stress (environmental and physical) on the acoustic startle reflex (ASR) and pre-pulse inhibition (ppn of the ASR (measures of sensory-gating) in males and females of two rat strains. Experiment 1 examined effects of nicotine on 192 Long-Evans rats (a non-albino strain) in individual or crowded housing. For males, nicotine increased startle and PPI in the crowded condition but decreased these responses in the individually-housed condition. For females, nicotine reduced ASR and PPI regardless of housing condition. Experiment 2 examined effects of nicotine (0, 6, or 12 mg/kglday) and immobilization (llv1) stress on ASR and PPI of male and female Long-Evans and

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The cardiovascular interaction between caffeine and nicotine in humans

Cited by 25 publications

References 7 publications

Caffeine Can Decrease Insulin Sensitivity in Humans

Caffeine Can Decrease Insulin Sensitivity in Humans

Caffeine's Influence on Nicotine's Effects in Nonsmokers

Effects of Nicotine Administration and Stress on Sensory-Gating Depend on Rat Strain and Sex

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