Key takeaways:
~ The CYP2C8 gene encodes an enzyme that metabolizes several common medications.
~ Variants in CYP2C8 can impact your risk for GI bleeding from NSAIDs.
~ Understanding your genetic variants can help you understand your reaction to medications.
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CYP2C8: From ibuprofen to arachidonic acid
The CYP (cytochrome) family of genes codes for a number of different enzymes that interact with prescription drugs. This family of enzymes is important in breaking down medications in a process known as phase I detoxification. Genetic variants that alter how these enzymes work can impact your reaction to a medication.
The CYP2C8 gene is essential in the metabolism of several chemotherapy drugs and plays a role in the metabolism of NSAIDs, such as ibuprofen.
Supplements such as quercetin can also inhibit the CYP2C8 enzyme.[ref]
The PharmGKB database is a good source of information on pharmacological and genetic interactions. It has information on the CYP2C8 variants and response to tacrolimus, montelukast, rosiglitazone, and pioglitazone. I’ve put a list of more common medications that utilize CYP2C8 in the Lifehacks section at the end of this article.
Why do we have the CYP2C8 enzyme?
We don’t have the CYP enzymes in the body just to break down new-fangled prescription drugs.
In addition to pharmaceutical drugs, CYP2C8 also metabolizes arachidonic acid in the body, which is important in blood pressure regulation. This may also be important in oxidative stress in the cell. Arachidonic acid is derived from omega-6 PUFAs and can be pro-inflammatory in some situations.[ref]
The metabolism of arachidonic acid by CYP2C8 is also important in eye health in aging.
Hypoxia, or low oxygen, increases CYP2C8, which in turn causes more of the conversion of arachidonic acid into epoxyeicosatrienoic acids (EETs). The increased EETs then promote abnormal vascular development in the retina of the eye.
Additionally, the increased CYP2C8 interacted with omega-3 fatty acids, promoting abnormal vascular development with higher levels of DHA in low oxygen conditions.[ref]
Inhibiting CYP2C8 has been shown in studies to decrease the pathological effects in the eye from increased vascular development. This could be important in age-related macular degeneration and diabetic retinopathy.[ref] Please keep in mind that you don’t want to inhibit CYP2C8 if you are on a prescription medication that relies on the enzyme.
CYP2C8 Genotype Report:
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Lifehacks: What to avoid with CYP2C8
If you have the CYP2C8*3 variant and take a lot of NSAIDs, you should talk with your doctor about the increased risk of gastrointestinal bleeds. Be sure to also check out your CYP2C9 genetic variants. The combination of low function in both CYP2C8 and CYP2C9 increases the risk of problems from NSAIDs such as ibuprofen.[ref]
Eye Health:
Circling back to the information above on how upregulation of CYP2C8 could increase problems with the retina, such as macular degeneration or diabetic retinopathy… Quercetin, an inhibitor of CYP2C8, has been shown to protect the eye from damage from diabetic retinopathy in animal studies.[ref] This may be something to consider if on a diet that is high in the long-chain omega-6 or omega-3 fatty acids (arachidonic acid), especially if AMD (age macular degeneration) or diabetic retinopathy is a concern. Check out your genetic variants for age-related macular degeneration.
Supplements and medications:
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Nrf2 Pathway: Increasing the body’s ability to get rid of toxins
The Nrf2 (Nuclear factor erythroid 2–related factor) signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. This is a fundamental pathway in how well your body functions. Your genetic variants impact how well this pathway functions.