Exposure Misclassification
Coffee exposure is often assessed using food frequency questionnaires
that collect information regarding the number of cups
of coffee consumed daily or weekly. However, cup size may vary
considerably depending on the population. One study in the US
found that cup sizes used by pregnant women ranged from 2–32
oz, with 7-8-oz cups accounting for only 30% of cup sizes used.28
In epidemiological studies, one cup of coffee is often assumed
to provide 85–100 mg of caffeine. However, the caffeine content
of different coffees can vary considerably (see above), and it is
possible that people who drink many cups of coffee on a daily
basis consume weaker coffee than people who drink only 1–2
cups daily. Until recently, few epidemiological studies collected
information about the brewing process used to prepare coffee.
This information became important when it was discovered that
cholesterol-raising compounds in coffee were largely removed
by paper filters (see above).12 Finally, individual variation in the
metabolism of compounds in coffee may increase or decrease
the exposure of an individual to a bioactive compound in coffee.
For example, NAT2 plays an important role in the metabolism
of caffeine.7 A genetic polymorphism in the NAT2 gene, which
results in “fast acetylators” and “slow acetylators,” is likely to
affect individual exposure to caffeine metabolites (see Considerations
for Future Research below). Additionally, cigarette smoking
increases caffeine clearance by inducing CYP1A2 activity,29
and smokers have been found to have lower plasma levels of
caffeine than nonsmokers at the same level of consumption.30
It is not yet known how genetic and lifestyle factors affect
individual exposure to other bioactive compounds in coffee.
Confounders
A frequent criticism of epidemiological research on coffee
is inadequate adjustment for confounding factors that could in-
fluence the relationship between coffee consumption and health
outcomes. Cigarette smoking is often cited as a potential confounder
because high intakes of coffee are frequently associated
with cigarette smoking.31 Most analyses are adjusted for the
effect of cigarette smoking. However, underreporting of a socially
undesirable behavior, such as smoking, while accurately
reporting a socially neutral behavior, such as coffee consumption,
could lead to inadequate adjustment for the effect of smoking
and overestimation of the effect of coffee consumption on
a health outcome. This concern may be particularly relevant
to studies of pregnant women. Other lifestyle factors may also
confound associations between coffee consumption and health
outcomes. For example, people who drink coffee in Scotland
tend to be younger, have higher incomes, and are generally
healthier than people who drink tea.32 This may not be the case in
other countries. Health outcomes in consumers of regular coffee
are sometimes compared to those in consumers of decaffeinated
coffee in order to determine whether a health effect is related to