Chapter
6
Caffeine
N N O
N
N
Caffeine
Café-au-lait
46 MOLECULES THAT AMAZE US
Is Caffeine a Drug?
It is the most widely ingested psychoactive drug in the world,
but it’s legal. And it is safe, at least to drink coffee or tea, within
reason.
Why the Qualification?
Health Canada says that
the recommended
daily limit for a healthy
adult is around 400 mg
a day, while the UK
Food Standards Agency
recommends a limit of
half that for a pregnant
woman. Caffeine
can readily cross the
If this giant can on the back of a mini was
really full of Red Bull it would contain ~270 g placental barrier so
of caffeine (Courtesy of © Red Bull Media it is sensible for a
House. With permission) pregnant woman to
restrict caffeine intake
to about two cups a day (or less). An 8-oz cup of ‘instant’ coffee
contains around 90 mg of caffeine, but if you drink a ‘Grande’
cup from Starbucks, with over 300 mg, this is coming close to the
recommended daily amount. 8-oz cans of drinks like Red Bull and
Monster Energy contain about the same amount of caffeine as a cup
of ‘instant’ coffee, so all of these are safe – it just depends on how
much you are drinking.
There have been cases where consuming a lot has been linked with
health problems, like the 28-year-old Australian motor-cross rider
CAFFEINE 47
who drank seven to eight cans of an energy drink over a seven-hour
period, and whose heart stopped (happily, he recovered). Part of
the problem is that the safe amount can vary a lot from person to
person depending upon how quickly they metabolize it, and also
upon factors like gender (on average, men metabolize it faster
than women) and whether you are a smoker or not, together with
genetic factors.
But the Lethal Dose?
Again this would vary from person to person, but it would normally
be in the range of 5–10 g.
That Means a Lot of Cups of Coffee!
Agreed, you would have to
drink well over 50 cups of
coffee in rapid succession
to get near that, but the
real problems seem to
be linked with caffeine
‘energy tablets’, which
are sold under a number
of trade names such as
Caffeine pills are very popular with
Proplus, Vivarin, No-Doz students staying up all night to cram for
and Stay Awake. exams
Why Is That?
They represent a very concentrated form of caffeine, and
while there is a physical limit to how much tea or coffee can
be drunk, it is possible to consume a lethal dose of caffeine
48 MOLECULES THAT AMAZE US
by eating these tablets. A coroner reporting on the death of a
23-year-old man in England in 2010 said that the man’s blood
caffeine level of 251 mg per liter was 70 times more than that
usually obtained from a high-energy caffeine drink. Apparently
the man had consumed two spoonfuls of caffeine dissolved in
an energy drink!
How Does Caffeine Work on the Body?
NH2 Caffeine acts as a stimulant because
it is an antagonist of adenosine,
N
N an inhibitor of the central nervous
HO
system. Structurally, caffeine
N N
O resembles adenosine, and therefore
binds to the adenosine receptor,
blocking its action. With nothing
OH OH to slow them down, there’s greater
dopamine and glutamate activity
Adenosine
leading to increased neuron activity
in the brain and more adrenaline
production. Caffeine is slightly addictive because it is a cardiac
stimulant.
And Then?
Caffeine (a ‘trimethylxanthine’) is metabolized in the human liver
by cytochrome P450 oxidase enzymes, which rip methyl groups off
the caffeine molecule, producing three ‘dimethylxanthines’ called
paraxanthine (84%), theobromine (12%) and theophylline (4%) –
followed by further demethylation and oxidation, leading to urates
and uracil derivatives.
CAFFEINE 49
N N O
N
N
H
N N O
N N O N O
N
N
N N N
N N H H
O
O O
Paraxanthine Theobromine Theophylline
What Do They Do?
There is particular interest in paraxanthine, the main metabolite.
Studies on rats – which metabolize caffeine much faster than we
do – show that paraxanthine has a greater stimulating effect on
motion than caffeine itself or the other two metabolites. Scientists
have evidence that paraxanthine in particular may have a protective
role against Parkinson’s disease, though, on the downside, extremely
high serum paraxanthine concentrations can be associated
with spontaneous abortion in pregnant women. Interestingly,
theobromine is one of the main active ingredients in chocolate,
which may be why coffee and chocolate go so well together.
Theobromine is also toxic to dogs, which is why you should never
feed chocolate to your dog.
Does Caffeine Just Come from Coffee?
No, in addition to coffee plants (Coffea arabica or Coffea canephora),
the tea bush (Camellia sinensis) is another major source. There are
50 MOLECULES THAT AMAZE US
others, like the kola nut (Cola acuminata and Cola nitida), while
there are small amounts in cocoa beans.
Red Catucaí coffee, a variety of Roasted coffee beans
Coffea arabica, showing the beans in
different stages of maturity
Why Do Plants Make Caffeine?
Plants make caffeine to protect themselves against insects because
methylxanthines inhibit insect feeding. They are also pesticides,
owing to their ability to inhibit the activity of some insect
enzymes.
How Do These Plants Make It?
The biosynthesis of caffeine begins with xanthosine, which
is converted into 7-methylxanthosine, 7-methylxanthine,
theobromine and caffeine, in that order. The genes encoding
three distinct N-methyltransferase enzymes used to make caffeine
from xanthosine have been isolated and then expressed in tobacco
plants. The resulting caffeine-containing tobacco plants are
unpalatable to tobacco cutworms (Spodoptera litura).
CAFFEINE 51
So You Can Get Decaf-Coffee Plants?
Cameroon produces a caffeine-free Coffea species, Coffea
charrieriana, but in the West solvents such as dichloromethane,
ethyl acetate or even supercritical CO2 are used to dissolve the
caffeine from the coffee beans to make decaffeinated coffee.
Scientists can now engineer low-caffeine coffee plants, too.
Is Coffee Good for You?
Coffee and tea contain polyphenolic antioxidants believed to be
beneficial to health. The smell of your tea and coffee has nothing
to do with the caffeine, which is quite an involatile substance.
The Smell?
More than 1000 volatile organic compounds are found in roasted
coffee, but only around 50 of them are important contributors
to the overall aroma. When coffee beans are roasted, complex
reactions occur, including the Maillard reaction, which uses sugars,
O N N
N N
2-Isobutyl-3-methoxpyrazine 2-Ethyl-3,5-dimethylpyrazine
N
HS
N O
2,3-Diethyl-5-methylpyrazine Furfuryl mercaptan
52 MOLECULES THAT AMAZE US
amino acids and peptides to form a wide range of volatile and
smelly molecules that cause the fragrance of the beans. Important
odorants in coffee include substituted pyrazines, such as 3-isobutyl- 2-
methoxypyrazine, 2-ethyl-3,5-dimethylpyrazine and 2,3-diethyl-5-
methylpyrazine, as well as furfuryl mercaptan, which contribute the
‘burnt, roasted’ note.
Is It Just Humans Who Get a Buzz from Caffeine?
Caffeine can be toxic to other animals, including birds and dogs,
probably because they have less ability to metabolize it. Famously,
NASA scientists tested a variety of drugs on ordinary house spiders,
including LSD, mescaline, amphetamine and marijuana, as well as
caffeine. Strikingly, caffeine was the drug with most effect on the
spiders’ ability to spin webs, the results having no patterns and just
consisting of a few random threads.
Enjoy your coffee.