CYP1A2 is an important enzyme that helps to break down toxins in our bodies. It is also the key enzyme responsible for metabolizing caffeine. Therefore variations in the CYP1A2 gene have a big impact on how coffee will affect our bodies. In addition, CYP1A2 gene variants have also been associated with diabetes, bone density, and cancer. Read on to find out more about this enzyme, and the natural substances that can increase or decrease it.



CYP1A2 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).

Read more about CYPs and CYP metabolizer types here.

CYP1A2 Function

CYP1A2 metabolizes:

This enzyme is activated via the aryl hydrocarbon receptor (Ahr) (R).

CYP1A2 activity shows a remarkable degree of variation (up to 40-fold) between individuals, based on their genes, ancestry, and environmental factors (smoking, coffee consumption, diet) (R, R).

CYP1A2 Location

This enzyme is found mainly in the liver but has also been detected in the pancreas and lungs (R).

It accounts for approximately 13% of total CYPs in the human liver (R).

CYP1A2 The Good

This enzyme is important for removing toxic chemicals from our body and processing hormones and other products of our metabolism.

CYP1A2 The Bad

CYP1A2 activates cancer-causing agents, such as aromatic heterocyclic amines, polycyclic aromatic hydrocarbons (PAHs) and aflatoxin B1 (R).

Both increased and decreased enzyme activity have been linked to increased risk of cancer.

Nonsmokers who are rapid CYP1A2 metabolizers (meaning they have increased CYP1A2 activity) have an increased risk of giving birth to infants with decreased birth size when consuming over 300 mg caffeine/day (R).

CYP1A2 Gene Polymorphism

More than 40 single nucleotide polymorphisms (SNPs) of the CYP1A2 gene have been discovered so far (R).

African and Asian populations seem to have lower enzyme activity (R).

rs762551 A/A is a fast metabolizer, while C/C and AC are slow metabolizers. This means that those having the A/A genotype will process caffeine and other substances metabolized by CYP1A2 much quicker, and these substances will have less effect on the body. On the other hand, C/C and A/C people will process caffeine slower, and it will have more effect on their system.

In line with the above, 31.3% of the C carriers (C/C, A/C) reported increased nervousness after caffeine ingestion, while none of the A/A people had this side effect (pilot study, 21 participants) (R).

Studies have shown that coffee protects C carriers against breast cancer (269 women, 411 women) (R, R).

On the other hand, heavy coffee consumption increases the risk of impaired fasting glucose among C carriers with hypertension (elevated blood pressure) (1,180 subjects)(R) and increases nonfatal heart attack risk also among C carriers (4028 subjects) (R).

Furthermore, rs762551 C/C was associated with tardive dyskinesia (involuntary movements) in patients with schizophrenia receiving antipsychotics for a long time (475 patients) (R).

rs762551 A/A increases carbamazepine clearance (40 patients) (R).

Finally, this SNP increased lung cancer risk, but decreased bladder cancer risk in some populations (meta-analysis, 21 studies, 4,722 cases and 6,555 controls) (R).

rs2470890 C increases the odds of having type 2 diabetes 1.2 times. However, it decreases the odds of caffeine boosting diabetes by 0.77 (7,607 subjects)(R).

T decreased lung cancer risk in Europeans (105 patients, 189 controls) (R).

  • RS2069514

The A was associated with a decreased risk of breast cancer (48 subjects) (R).

  • RS11854147

C/C are rapid metabolizers (more active enzyme), while C/T and T/T are slow metabolizers (less active enzyme).

In elderly people who take a lot of coffee, those with rapid metabolism of caffeine (C/C) had lower bone mineral density (BMD) than slow metabolizers (T/T and C/T genotypes) (717 seniors) (R).

Increasing or Decreasing CYP1A2

These increase CYP1A2 activity:

  • Cigarette smoke – dose dependently (R, R).
  • Coffee consumption (R), 1.45-fold per liter of coffee drunk daily (R).
  • Meat pan-fried at high temperatures – 1.4-fold (R).
  • Chargrilled meat – 1.89-fold (R).
  • Cruciferous vegetables, including broccoli, cabbage, brussel sprouts, and cauliflower (R, R). For example, 500g broccoli daily increases enzyme activity 1.19-fold (R).
  • Diindolylmethane, found in cruciferous vegetables (R).
  • Ginkgo biloba (R).
  • Green and black tea (R).
  • Higher BMI (R).
  • Being female – 0.90-fold (R).
  • Menstrual Cycle – 1.03-fold up to 1.10-fold (R).
  • Insulin (R).
  • Heavy exercise (R).
  • Omeprazole (R).

These decrease CYP1A2 activity:

  • Curcumin (R).
  • Cinnamon’s component o-methoxy cinnamaldehyde (R).
  • Ginseng extract (R).
  • Peppermint, chamomile, and dandelion tea (R).
  • Grapefruit juice and its component naringenin (R).
  • Starfruit juice (R).
  • African lettuce L.  taraxacifolia (R).
  • Propolis (R).
  • Echinacea purpurea (R).
  • Licochalcone A, a major compound in traditional Chinese herbal licorice (R).
  • Caffeic acid (R, R), found at a high level in thyme, sage, spearmint, Ceylon cinnamon and star anise.
  • Quercetin (R).
  • Oleuropein, derived from olive oil (R).
  • Kale ingestion, unlike that of other cruciferous vegetables (R).
  • Apiaceous vegetables (carrots, parsnips, celery, parsley) (R).
  • Raspberry leaf (R).
  • Antibiotic fluoroquinolones (R).
  • Fluvoxamine (R).

These can both increase or decrease CYP1A2:

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