What are CYPs?
Cytochrome P450 monooxygenases (CYPs) are enzymes that help with the removal of most of the drugs and toxins from the human body .
They are responsible for the so-called Phase I of the detox process.
For example, CYPs process cancer-causing agents (such as polycyclic aromatic hydrocarbons or PAHs, aromatic amines, heterocyclic amines), pesticides, herbicides, and the vast majority of clinical drugs .
There are 57 human CYP enzymes .
However, these enzymes are not equally involved in the detox process. About 12 liver CYPs are responsible for the removal of the majority of drugs and toxins. These 12 CYP enzymes cover about 93% of the clinical drug metabolism [2, 4].
Why is Balancing CYP Activity Important?
Although many of the CYPs are detox enzymes, their activity can actually convert less toxic molecules into more toxic active products. These then need to be further detoxified by Phase II enzymes. For example, CYP1A1 can activate some cancer-causing agents [5, 6], while CYP2E1 can activate several liver toxins and thereby contribute to alcoholic liver damage .
CYP activity can cause damage to DNA, leading to cancer . That is why elevated Phase I activity is not necessarily a good thing. As Phase I enzymes produce toxic and cancer-causing compounds, you want them to be in balance with Phase II enzymes.
Many health-boosting supplements and herbs actually decrease CYP activity, and thereby reduce the activation of cancer-causing agents .
Tobacco smoke, on the other hand, induces CYPs .
Many foods can both increase or decrease CYP enzyme activity, based on the composition and concentration of active ingredients. Again, other foods increase particular CYP enzymes but decrease others.
- Polycyclic aromatic hydrocarbons (PAHs) activate Ahr, which in turn increases CYP1A and CYP1B enzymes .
- PXR is activated by small molecules such as steroids, rifampicin, and metyrapone, and then it increases CYP3A enzymes .
- CAR binds phenobarbital, orphenadrine and other drugs to activate CYP2B enzymes .
- Clofibrate and similar substances activate PPARα, which in turn activates CYP4A enzymes .
CYP Gene Polymorphism
Thousands of mutations in CYP genes have been described, but certain variants (SNPs) have a larger impact on enzyme activity . Particularly important are the variants in CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP2A6 .
Based on these SNPs, people have distinct drug responses. These drug response types are termed as poor, intermediate, extensive, and ultrarapid .
This means that people can be classified according to the activities of particular CYP enzymes. For example, the most frequent type of CYP2D6 is the normal or so-called extensive-metabolizer, with 78.8% of people. In other words, 78.8% of us are normal metabolizers. This group is followed by intermediate- (12.1%), poor (7.6%) and ultra-rapid metabolizers (1.5%) .
If you are an ultrarapid metabolizer, you can experience a lack of efficacy if the drug itself is responsible for the effect. This happens because the drug gets degraded too quickly to have an effect. On the other hand, you can have a very intense effect if the drug itself is inactive, but the CYP makes it active by processing it .
Again, if you are a poor metabolizer, you may have a stronger effect with the drug, if the drug itself is responsible for the effect. On the other hand, if the drug needs to be processed by the CYP enzyme to be effective, you may experience a weaker effect or a lack of effect.
Other Factors that Influence CYPs
Apart from our genes, our health and the food we eat can also greatly affect CYP enzyme function.
In addition, protein deficiency decreases, while protein-rich diet increases CYP enzyme activity .
On the other hand, a carbohydrate-rich diet was shown to decrease CYP enzymes .
These enzymes are important for the detox of drugs and toxins. Find out more about each of the CYP enzymes by following the links below.
- CYP1A1 – removes toxins, but can also activate some cancer-causing agents. Gene variants increase the risk of certain kinds of cancer.
- CYP1A2 – a key enzyme for clearing caffeine. Gene variants have a big impact on how coffee will affect our bodies.
- CYP1B1 – helps combat oxidative stress. Lower activity of this enzyme may protect against obesity and cancer.
- CYP2A6 – helps process nicotine. There is a link between this enzyme’s activity, smoking, and lung cancer risk.
- CYP2B6 – clears clinical drugs. The gene is highly variable.
- CYP2C8 – helps clear many clinical drugs including NSAIDs (diclofenac, ibuprofen).
- CYP2C9 – clears up to 15 – 20% of all clinical drugs, including warfarin. Gene variants greatly affect the way we react to these drugs.
- CYP2C19 – helps clear about 10% of common clinical drugs, including omeprazole and Plavix. High enzyme activity was linked to depression.
- CYP2D6 – clears 20% of clinical drugs, including codeine. This enzyme also affects dopamine and serotonin levels and affects human personality and behavior traits.
- CYP2E1 – metabolizes alcohol and eliminates Tylenol. It can both clear or activate toxins. It plays a role in alcohol-related disease and cancer.
- CYP3A4 – clears 45 – 60% of currently prescribed drugs. Different foods and supplements can decrease CYP3A4 activity and interfere with drug metabolism.
- CYP3A5 – Do you have this enzyme? Many people don’t. In people who do have it, it helps clear over 50% of clinical drugs.
These enzymes are important because they produce steroid hormones. They affect our estrogen and testosterone levels, our blood pressure and response to stress. You can learn more about each of these CYP enzymes by following the links below.
- CYP11A1 – this enzyme is necessary for the production of all steroid hormones. It acts as an anti-inflammatory agent but can increase susceptibility to allergies.
- CYP11B2 – produces aldosterone, which helps conserve sodium. Some CYP11B2 gene variants increase the risk of having high blood pressure and heart disease.
- CYP17A1 – produces testosterone. Some gene variants increase the risk of high blood pressure, heart disease, Alzheimer’s and cancer.
- CYP19A1 – produces estrogen and affects a variety of processes in the body, including fat production and distribution, bone density, female fertility, and brain function. Gene variants can increase the risk of having migraines, osteoporosis, hardening of the arteries, Alzheimer’s, and estrogen-sensitive cancers.
- CYP21A2 – helps produce cortisol and aldosterone, while it lowers testosterone levels. Variants that decrease enzyme activity are fairly common. They cause more masculine traits in women and lower fertility in both sexes. However, these people also have a lower risk of having mood and stress-related disorders.