CYP1A2 and Caffeine: Are You a Fast or Slow Metabolizer?

CYP1A2 is the primary enzyme responsible for metabolizing caffeine in your liver. The speed at which you process caffeine is largely determined by a single SNP: rs762551 in the CYP1A2 gene.

AA genotype (Fast metabolizer): ~50% of people. Caffeine is cleared quickly from your system. You can drink coffee in the evening and still sleep fine. Multiple cups per day have minimal cardiovascular impact — and some studies show coffee is actually cardioprotective for fast metabolizers.

AC genotype (Intermediate): ~40% of people. Moderate caffeine metabolism. Standard advice about limiting afternoon coffee applies.

CC genotype (Slow metabolizer): ~10% of people. Caffeine lingers in your system much longer. One cup can affect sleep even 8+ hours later. More importantly, slow metabolizers who drink 2+ cups per day have increased risk of heart attack and hypertension.

A landmark 2006 study by Cornelis et al. in JAMA found that among CYP1A2 slow metabolizers (AC/CC), drinking 2–3 cups of coffee per day increased heart attack risk by 36%, and 4+ cups increased risk by 64%. But among fast metabolizers (AA), coffee was actually protective — reducing heart attack risk by up to 22%.

This is one of the clearest examples of gene-environment interaction in nutrition. The same food (coffee) can be protective or harmful depending on your genotype.

CYP1A2 doesn't just metabolize caffeine. It also processes:

• Theophylline (asthma medication) — slow metabolizers may need dose adjustment • Melatonin — slow metabolizers may be more sensitive to melatonin supplements • Some antipsychotics (clozapine, olanzapine) — affected by CYP1A2 status • Cruciferous vegetables (broccoli, cauliflower) — these actually *induce* CYP1A2, making you metabolize caffeine faster • Smoking — cigarette smoke strongly induces CYP1A2, which is why smokers often drink more coffee (they metabolize it faster)

Interestingly, if you're a slow metabolizer who eats a lot of cruciferous vegetables and exercises regularly, your functional CYP1A2 activity may be closer to normal.

Fast metabolizers (AA): ☕ Feel free to enjoy 3-4 cups of coffee daily ☕ Evening coffee is fine if it doesn't bother you personally ☕ Coffee may actually protect your heart health ☕ Pre-workout coffee is especially effective for you

Intermediate metabolizers (AC): ☕ 2-3 cups daily is reasonable ☕ Avoid caffeine after 2 PM for better sleep ☕ Monitor blood pressure if consuming regularly

Slow metabolizers (CC): ☕ Limit to 1-2 cups daily, before noon ☕ Consider switching to green tea (lower caffeine, same antioxidants) ☕ Avoid energy drinks and pre-workouts with high caffeine ☕ Be especially careful if you have hypertension or heart disease risk ☕ Eating cruciferous vegetables may help compensate