caffeine is a natural trimethylxanthine alkaloid which acts as a pesticide and perhaps herbicide and thus protects the growth of coffee bean plant and similar plants (tea, kola, cacao plants) which produce it.
coffee drinking became popular in Europe in mid-17th century
chocolate was introduced to Europe by the Spaniards and became a popular beverage by 1700.
caffeine was 1st isolated in 1819 and its structure elucidated by the end of the 19th century.
theophylline was first extracted from tea leaves around 1888.
1st Coca-cola recipe invented in 1885 based on coca leaves & the kola nut.
initially Coca Cola also contained ~9mg cocaine per glass but this was removed in 1903 but retained coca flavoring using a cocaine-free coca leaf extract.
Coca-Cola drink created controversy in the U.S. in 1911 over concerns of its caffeine content causing unwanted behaviour, and caffeine was soon added to the U.S. list of “habit-forming” and “deleterious” substances and foods and drinks containing it must label it accordingly.
interacts with mTOR complex (relevant to all facets in learning and memory)
caffeine downregulates a signaling partner of the mTOR complex pathway in a dose-related manner: p70s6k
in 'normal' individuals, excessive levels of caffeine might be pathological in terms of learning and memory function, but these would be at extremely high doses, and in almost a steady-state system due to chronic administration
effects of its 3 main dimethylxanthine metabolites each with methylxanthine effects:
paraxanthine (84%)
theobromine (12%)
theophylline (4%)
pharmacokinetics
almost completely absorbed from GIT within 45min of oral intake.
metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme.
individuals who are homozygous for the CYP1A2*1A allele are “rapid” caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are “slow” caffeine metabolizers.
most adults can safely consume up to 400mg caffeine per day in tea and coffee and many may see beneficial effects at these levels1)
an expresso shot of coffee generally has about 60mg of caffeine, a cup of brewed cup may have twice this amount
energy drinks, bars, gels and caffeine-based supplements often contain other added ingredients that may increase the absorption of caffeine, may accelerate its effects on the body, may raise blood pressure and increase the risk of cardiovascular harm even at these doses - including episodes of AF on young adults
one 250 ml can of Red Bull contains 80 mg of caffeine
excessive amounts well above these levels may also cause:
extreme restlessness
cardiac arrhythmias such as AF, SVT and even potentially lethal ventricular arrhythmias at doses over 10 cups worth (>1000mg doses) 2)
high BP
severe hypokalaemia via high renal losses (along with sodium, calcium and magnesium renal losses)
frequent intake results in pharmacologic tolerance to caffeine:
heavy intakes of 750-1200mg/day may result in complete tolerance
in middle-aged adults who regularly drink coffee, there was little to no association between habitual caffeine intake, sleep quality, and daytime sleepiness3)
lower regular intakes result in incomplete tolerance
caffeine dependency and chronic use effects with regular high intakes