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CYP2C19 Enzyme: Drugs, Gene Variants, & Inhibitors

Written by Biljana Novkovic, PhD | Last updated:

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CYP2C19 is an important detox enzyme responsible for clearing approximately 10% of commonly used clinical drugs, including antidepressants (citalopram), proton pump inhibitors (omeprazole), and antiplatelet drugs (Plavix/clopidogrel). High enzyme activity has been associated with depression. Read on to find out more about CYP2C19 function, gene variants, and supplements that decrease enzyme activity.

What is CYP2C19?

CYP2C19 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body [1].

Read more about CYPs here.

This enzyme is responsible for processing more than 25 clinically important drug groups. It clears about 10% of commonly used clinical drugs that undergo Phase I detoxification [2].


This enzyme metabolizes:

  • Antidepressants: citalopram, escitalopram [3, 4], amitriptyline [5], and sertraline [3].
  • Proton pump inhibitors: omeprazole [6].
  • Anticonvulsants: mephenytoin [6].
  • Diazepam [6].
  • Methadone [2].
  • Antimalarial proguanil [6].
  • Anticoagulant warfarin [6].
  • Antiplatelet clopidogrel (Plavix) [7].
  • Antifungal voriconazole [8].
  • MDMA (ecstasy) [9].


This enzyme is found in the liver. However, it is also active in the fetal brain, with a possible role in brain development [5].

The Good

This enzyme participates in converting arachidonic acid to epoxyeicosatrienoic acids (EETs). EETs have beneficial effects on the heart and blood vessels.

Low enzyme activity increases the risk of heart disease (162 subjects) [10].

The Bad

High CYP2C19 activity is associated with depression and smaller hippocampus volume in humans (1418 subjects) [11].

A study in Sweden shows that people with high enzyme activity (CYP2C191 carriers) are more prone to depression than those with defective enzyme function (CYP2C192 carriers) (1472 subjects) [12].

CYP2C19 deficiency is associated with a lower prevalence of major depressive disorder and lower depression severity in African-Americans (3848 subjects) [11].

Depressed suicide attempters with high enzyme activity show higher suicidality (209 subjects) [11].

Mice with high enzyme activity have impaired serotonin and BDNF production in the hippocampus [11].

Gene Polymorphism


There are more than 30 CYP2C19 variants [6, 3].

Based on the variants they carry, individuals can be categorized as:

  • ultrarapid metabolizers (*1 /*17 or *17 /*17)
  • extensive metabolizers (*1/*1)
  • intermediate metabolizers (*1 /*2, *1 /*3, or *2 /*17)
  • poor metabolizers (*2 /*2 or *2 /*3) [13]

CYP2C19 poor metabolizers (low enzyme activity) have an increased risk of heart disease, correlated with an increase in the circulating levels of CRP in women (162 subjects) [10].

Poor metabolizers have an increased risk of side effects associated with CYP2C19-metabolized drugs like sertraline [3].

On the other hand, ultrarapid metabolizers have an increased risk of being refractory (resistant) to proton pump inhibitor (PPI) therapy (meta-analysis, 19 studies) [14].

  • RS4244285

rs424485 is also known as CYP2C19*2. This variant (A) reduces enzyme function [6].

It is present in 15% of Whites and Africans, and 29-35% of Asians [13]. The highest frequency of 61% is found in Native populations from Oceania [15].

Plavix (clopidogrel) is less effective in people with this variant. Therefore, they are at higher risk of developing heart damage (559 and 523 patients) [7, 16].

  • RS4986893

rs4986893 is also known as CYP2C19*3. This variant (A) reduces enzyme function [6].

This variant is typically only found in Asians (2-9%) [13, 15].

Plavix (clopidogrel) is less effective in people with this variant. They are at higher risk of developing heart damage (559 subjects) [7].

  • RS12248560

rs12248560 is also known as the CYP2C19*17 variant. The T in this position increases enzyme function [6].

The frequency of this variant ranges from 3-21% [13]. It is more frequent in Mediterranean-South Europeans and Middle Easterns [15], and less frequent among Asians [17].

Adults with CYP2C19*17 more often have decreased blood voriconazole levels in therapy (70 patients) [8].

This variant protects against recurrent heart damage. People with this variant have greater therapeutic responsiveness to Plavix (clopidogrel) but they have an increased risk of developing bleeding (meta-analysis, 11 studies) [18].

Decreasing CYP2C19

These decrease CYP2C19:

About the Author

Biljana Novkovic

Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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