The Contribution of cocoa additive to cigarette smoking addiction

Page 38 of 207 RIVM report 650270002
Caffeine
smoking; smoking blocked the subjective stimulant effects of caffeine. The only
cardiovascular effect noted was an increase in heart rate after smoking. Caffeine did
not influence puffing behaviour; however, the increase in end-expired CO
concentration after smoking was greater in the caffeine condition, suggesting subjects
inhaled more smoke after caffeinated than decaffeinated coffee (48).
In a placebo-controlled, double blind randomized design, the cardiovascular
interaction between caffeine (250 mg intravenously) and nicotine (4 mg chewing
gum) in 10 healthy volunteers was investigated, both under baseline conditions and
during physical and mental stress (standing up and mental arithmetic). It was
concluded that the combined administration of caffeine and nicotine showed additive
effects on cardiovascular parameters during baseline conditions but less than additive
effects during sympathoadrenal stimulation (49).
The effects of caffeine (1.0-30.0 mg/kg) and nicotine (0.1-3.0 mg/kg) administered
alone and in combination on ventilation in unanesthetized rhesus monkeys was
investigated. Caffeine produced marked, dose-dependent increases in ventilation. In
contrast, acute administration of nicotine had less pronounced respiratory-stimulant
effects. The joint effects of caffeine and nicotine on ventilation generally did not
differ from those obtained with caffeine alone. Chronic administration of nicotine
(1.0 mg/kg/day) for 4 consecutive weeks via osmotic pumps significantly decreased
the half-life of caffeine but had little effect on ventilation or on sensitivity to the
respiratory-stimulant effects of caffeine. Two primary metabolites of caffeine,
theophylline and paraxanthine, were active as respiratory stimulants and were
equipotent to caffeine, and the joint effects of caffeine and its metabolites were
additive. The results indicate that caffeine and nicotine stimulate respiration through
different pharmacological mechanisms, in contrast to caffeine and its metabolites,
which exhibit a similar pharmacological profile. Moreover, significant
pharmacokinetic interactions may be obtained when caffeine and nicotine are
coadministered (50).
Critical assessment
Chemical
By heating/combustion nitrous gases are formed. Caffeine is able to react with strong
oxidants, resulting in radicals. It also forms complexes with compounds.
In vivo
Caffeine shows interaction effects with agonists/antagonists of the adenosine
receptors, the liver enzyme system and phosphodiesterase. It has also mutagenic
interaction effects.
Conclusion
Chemical
Caffeine is able to form complexes with several chemicals; it forms also reactive
radicals after oxidation.
In vivo
Caffeine has several systemic interaction effects in the body. Based on the low
caffeine dose in cigarettes, it is unlikely whether these interactions play a role in the
health effects of smoking. Of importance is the potential mutagenic effect of caffeine;
the question is whether the low caffeine dose is able to display local mutagenic
effects in the pulmonary system.