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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 (R).
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 (R).
This enzyme metabolizes:
- Antidepressants: citalopram, escitalopram (R, R), amitriptyline (R), and sertraline (R).
- Proton pump inhibitors: omeprazole (R).
- Anticonvulsants: mephenytoin (R).
- Diazepam (R).
- Methadone (R).
- Antimalarial proguanil (R).
- Anticoagulant warfarin (R).
- Antiplatelet clopidogrel (Plavix) (R).
- Antifungal voriconazole (R).
- MDMA (ecstasy) (R).
This enzyme is found in the liver. However, it is also active in the fetal brain, with a possible role in brain development (R).
CYP2C19 The Good
This enzyme participates in converting arachidonic acid to epoxyeicosatrienoic acids (EETs). EETs have beneficial effects on the heart and blood vessels.
CYP2C19 The Bad
High CYP2C19 activity is associated with depression and smaller hippocampus volume in humans (1418 subjects) (R).
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) (R).
Depressed suicide attempters with high enzyme activity show higher suicidality (209 subjects) (R).
CYP2C19 Gene Polymorphism
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) (R)
On the other hand, ultrarapid metabolizers have an increased risk of being refractory (resistant) to proton pump inhibitor (PPI) therapy (meta-analysis, 19 studies) (R).
rs424485 is also known as CYP2C19*2. This variant (A) reduces enzyme function (R).
Also known as the CYP2C19*3, this variant (A) reduces enzyme function (R).
rs12248560 is also known as the CYP2C19*17 variant. The T in this position increases enzyme function (R).
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) (R).
These decrease CYP2C19:
- Propolis (R)
- Caffeic acid (R)
- Quercetin (R)
- Ginger extract (R)
- Kale (R)
- African lettuce (L. taraxacifolia) (R)
- Licochalcone A, a major compound in traditional Chinese herbal licorice (R)
- Apomorphine, berberine, noscapine, and papaverine (R)
- Bulbocapnine, canadine, and protopine (R)
- Capsaicin (R)
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