The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 103 of 207
Tryptophan
significantly higher, than intake from cigarettes. Since tryptophan is an endogenous
compound, it is not expected that the inhaled amount will significantly affect the
tryptophan plasma level.
Tryptophan is an essential constituent of the diet. It plays an important role in protein
synthesis and is also precursor of a variety of biologically active compounds
including serotonin, melatonin, tryptamine, quinolinic acid and kynurenic acid. In
addition, tryptophan is precursor to the coenzymes NAD and NADP and can replace
niacin as an essential nutrient. Large tryptophan doses are needed to observe any
effects on the cardiovascular, the renal system and the CNS. Tryptophan deficiency
affects also the CNS. No data were available on the effect of tryptophan on the
pulmonary system.
Tryptophan is well absorbed from the mammalian small intestine and to some extent
from the stomach. The bioavailability is between 85 % and 100 % for most of
tryptophan products. Tryptophan is extensively bound to plasma albumin.
Quantitatively, the most important pathway for tryptophan metabolism, after protein
synthesis, is the kynurenine pathway, which is responsible for over 90% of
tryptophan catabolism. About one percent of ingested tryptophan is metabolised in
the brain to serotonin, which is a neurotransmitter of a large family of receptors.
After two hours of ingestion a plasma peak for tryptophan is observed.
Pharmacokinetic data from respiratory studies were not available.
Tryptophan alone seems to produce no more side effects than placebo when given at
a moderate dose (3 g per day). The LD50 of rat (1.6 g/kg body weight) would result in
a LD50 of 100 g in human. Nausea, headache, light-headedness and drowsiness have
been reported as side effects of tryptophan. Animal studies have indicated that
tryptophan may act as a co-carcinogen or tumor promoter. Tryptophan is probably
involved in glucose intolerance and into cataract formation. No toxicological data
were available from tryptophan inhalation studies. During heating several pyrolysis
products are formed which are mutagens, carcinogens and comutagens..
During smoking tryptophan reacts with other reactive compounds in cigarettes,
generating complex and potentially hazardous compounds. Several compounds
interact with the metabolisation of tryptophan in the body and bind competitively to
the binding site of tryptophan with plasma albumin or with the binding site of the
transport system from blood to brain, thereby affecting the free plasma/brain
tryptophan level.
Large tryptophan doses are used in diets or as medicine.
The tryptophan level in the body affects the serotonin level in the brain. By increasing
the tryptophan availability to the brain through carbohydrate diets or tryptophan
intake, the brain serotonin level can be increased. A decreased serotonin level is
related with substance abuse. Therefore tryptophan intake seems to reduce the
negative withdrawal effect of cigarette smoking. However the tryptophan level in
cigarette is likely insufficient to affect the brain serotonin level and subsequently will
not play any role in smoking cessation.