The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 41 of 207
Caffeine
A source of caffeine in tobacco is cocoa powder, which is used as a flavouring agent.
Little is known about the profile of the pyrolysis/combustion products of caffeine.
The daily intake via cigarettes smoke (estimated to be 0.5 mg/day) is low compared
to the oral intake via coffee, tea, chocolate and cocoa drinks (estimated 12 – 405
mg/day).
Caffeine affects the adenosine receptor sites (A1 and A2) and antagonize the effect of
adenosine. Caffeine has various effects in the body. It has a relaxation effect on the
smooth muscles, notably on the bronchial muscle, stimulates the CNS, stimulates the
cardiac muscle and increases the diuresis. Caffeine has contradicting effect on the
vascular system, which is explained by the central action of caffeine. Relatively large
oral doses are needed (> 200 mg) to exert effects on the respiration system. There are
no data on pharmacology in animals and humans from respiratory studies of caffeine.
Based on the respiratory effects of the caffeine derivative theophylline it is concluded
that the pharmacological effects of caffeine doses occurring in cigarettes should have
negligible effects on the respiratory system. As other methylxanthines (theobromine)
also occur in cigarettes, the combined effects with these methylxanthines on the
pulmonary system is not known.
The oral data indicate a high bioavailabilty (99 %) and extensive distribution (crosses
the blood brain-barrier, the placenta and is present in milk) and metabolism (mediated
by microsomal CYP450 reductase system) of caffeine. The average half-life of
caffeine range from 4 – 6 hours, which is shorter in smokers. There are no data on
pharmacokinetics in animals and humans from respiratory studies.
Acute toxicity of caffeine is very uncommon; adverse effects that are observed are
gastric symptoms, insomnia and diuresis, tremor, tinnitus and headache. The lowest
human toxic dose was 2 – 3 g. Animal lethal dose (LD50) (I.V.) range from 105
mg/kg body weight for rats to 175 mg/kg body weight for dogs. Semichronic (100
days) administration of caffeine (110 mg/kg body weight) daily to rats evoked several
clinical manifestation. Chronic consumption of coffee in moderate amounts does not
seem to cause persistent increase in blood pressure in normotensive human subjects.
There is inadequate evidence for the carcinogenicity of caffeine in humans and
animals. Caffeine may have mutagenic properties. No data on the toxicological
effects of caffeine exposure through inhalation are available.
Caffeine is able to react with strong oxidants, resulting in radicals. It also forms
complexes with compounds. Caffeine shows interaction effects with
agonists/antagonists of the adenosine receptors, the liver enzyme system and
phosphodiesterase. It has also mutagenic interaction effects. Based on the low
caffeine dose in cigarettes, it is unlikely whether these interactions play a role in the
health effects of smoking.
Caffeine has some addictive properties and some causal relationship exists between
caffeine intake from coffee and smoking. However, the low doses in the cigarettes is
marginal compared with the high intake from other caffeine sources, such as coffee.
At the other hand, caffeine could increase the nicotine availability through
bronchodilatation, which subsequently might increase the addictive property of
tobacco. As the bronchodilatation effects of caffeine are expected to be negligible at
the caffeine dose present in tobacco, it seems unlikely that caffeine plays a role in
tobacco addiction through the bronchodilatory effect.