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