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The CYP1A2 gene produces an enzyme that belongs to the cytochrome P450 superfamily.

These cytochrome P450 proteins are monooxygenases, responsible for facilitating various reactions linked to the metabolism of drugs and the synthesis of steroids and cholesterol.

The protein originating from this gene is located in the endoplasmic reticulum and can be activated by certain polycyclic aromatic hydrocarbons (PAHs), some of which are present in cigarette smoke.

While the enzyme’s natural substrate remains unidentified, it can transform certain PAHs into cancer-causing intermediates. Additionally, this enzyme can metabolize various foreign substances, including caffeine, aflatoxin B1, and acetaminophen. Although CYPA12 is best known for its role in caffeine metabolism, it plays a much larger role in the body.

Interestingly, the gene’s transcript contains four Alu sequences surrounded by direct repeats in its 3′ untranslated region.

A large meta analysis in BMC Cancer found an increased cancer risk for C/C genotypes.

P450 1A2

Science Grade
rsID Number Major Allele Minor Allele
rs762551 a c

Risk Description

rs762551(A) encodes the “high inducibility” variant of the enzyme, which is characterized by increased enzyme activity when exposed to an inducer like smoking or heavy coffee consumption. 1

A/A genotypes are categorized as fast caffeine metabolizers, which means the half life of caffeine is less in an A/A genotype than for a C/C or CYP1A2 A/C genotype.

In individuals who do not smoke, there was no notable disparity in CYP1A2 activity based on their genotypes. However, in smokers, those with the A/A genotype exhibited enzyme activity that was 1.6 times higher than individuals with A/C and C/C genotypes. 2

Likewise, among non-smokers, only those who consumed heavy amounts of coffee (more than 3 cups daily) and possessed the A/A genotype displayed approximately 1.4 times greater CYP1A2 activity. 3

Thus, in a “fast metabolizer,” consuming more caffeine increases CYP1A2 activity. 

Nutritional Contraindications:*

Ingredient Active Ingredient Effect
Caffeine 1,3,7-trimethylxanthine

A/C and C/C genotypes may want to avoid caffeine, especially in large doses as their body’s will metabolize the caffeine more slowly than A/A genotypes.

While not all studies are in agreement, there is some evidence in the literature that slow metabolizers increase their heart attack risk when they consume large amounts of caffeine, and this is true even for younger individuals.

Discuss this information with your doctor before taking any course of action.


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