Factors That Affect Caffeine Sensitivity

Caffeine sensitivity refers to how much effect caffeine has on our bodies. People who have unusual caffeine sensitivity may experience significant symptoms — such as anxiety, tremors, headache, palpitations, and insomnia — after ingesting even small amounts of caffeine-containing foods. People with caffeine sensitivity should generally try to avoid caffeine altogether.

In women, caffeine sensitivity is also strongly modulated by the use of contraceptives , and by pregnancy.

Caffeine is rapidly absorbed from the intestines into the bloodstream, and it readily crosses the blood-brain barrier into the brain. It also freely crosses the placenta in pregnant women.

In the brain, caffeine binds to the adenosine receptors, thus preventing adenosine from attaching to them. Because adenosine sends the brain a message that it is time to sleep, blocking the adenosine receptors has the effect of producing wakefulness.

Caffeine is metabolized in the liver by an enzyme called CYP1A2 to theophylline, paraxanthine, and theobromine, and is then excreted by the kidneys into the urine. The half-life of caffeine is typically 4 - 6 hours, which is typically how long caffeine affects us.

Sensitivity to caffeine is largely determined by the activity of the CYP1A2 enzyme in the liver. The more active the CYP1A2, the less sensitive we are to caffeine. Several factors affect CYP1A2 activity:

• Age: CYP1A2 activity tends to decrease with age, so older people tend to be more sensitive to caffeine
• Sex: Women tend to have lower CYP1A2 activity than men.
• Oral Contraceptive Use and Pregnancy: Estrogens inhibit CYP1A2 activity and caffeine sensitivity increases
• Genetic Makeup: Several gene variants have now been identified that affect CYP1A2 activity.

Genetic testing has revealed three general categories of caffeine sensitivity related to our genetic makeup:

• Hypersensitive to Caffeine: These individuals have very low CYP1A2 activity. They will have a strong response to even small amounts of caffeine, and will commonly experience jitters and insomnia.
• Normal Sensitivity to Caffeine: This is the vast majority of individuals. They can consume up to 400 mg of caffeine per day without adverse side effects.
• Low Sensitivity to Caffeine: These people have very high CYP1A2 activity, and often experience no effect at all from consuming caffeine. Smokers often have increased CYP1A2 activity.

While genetic testing can categorize your level of caffeine sensitivity, having formal testing is generally not necessary for you to know — at least generally speaking — whether or not you are very sensitive to caffeine. And if you are, it is likely that nobody needs to tell you to cut back.​

Pregnancy reliably increases sensitivity to caffeine. The half-life of caffeine in pregnant women is often four times longer than it is for non-pregnant women — often up to 16 hours. Furthermore, caffeine readily enters the bloodstream of the fetus — and the fetus has very very little CYP1A2 activity.

While serious adverse effects on the fetus caused by the mother’s caffeine intake have not been documented, this issue has not been studied extensively. In general, pregnant women should try to limit or avoid caffeine.