CYP3A4 is an important CYP enzyme, responsible for clearing approximately 45 – 60% of currently prescribed drugs. Different supplements, food additives, and other substances can decrease CYP3A4 activity and, as a result, interfere with drug metabolism. Find out more about CYP3A4 function, gene variants, and supplements that can increase or decrease CYP3A4 activity.
What is CYP3A4?
- Opioids: sufentanil (R) and methadone (R)
- Immune suppressants: cyclosporine (R), tacrolimus (R), and sirolimus (R)
- Antihypertensive drugs: felodipine (R) and nifedipine (R)
- Anticancer drugs: endoxifen (R), tamoxifen (R), and sunitinib (R)
- Sedatives: midazolam (R)
- Cholesterol-lowering drugs (statins): simvastatin (R), atorvastatin, and lovastatin (R)
- Antibiotics: erythromycin (R)
- Corticosteroids: fluticasone propionate (R)
- Metabolizes many internal compounds such as cholesterol, fatty acids, prostaglandins, leukotrienes, retinoids and biogenic amines (R).
- Detoxifies bile acids and decreases their toxicity (R).
- Deactivates testosterone to biologically less active metabolites (R).
- Partly degrades vitamin D (R).
The activity of this enzyme varies up to 40-fold and is affected by health, environment (smoking, diet, and co-medication), hormones, and genetics (R).
CYP3A4 is the most active CYP enzyme in the gut (R). Therefore it is not surprising that what we eat and drink has a great effect on the activity of this enzyme.
Components in foods, drinks, food additives, and other drugs usually decrease CYP3A4 activity producing one of the following effects:
- Decreasing the inactivation or degradation of the drug, thus, increasing the actual dose of the active form in the blood, which often causes unfavorable and long-lasting effects (R).
- Decreasing the activation of some those medications that are administered as a pro-drug, thus, decreasing the actual dose of the active form of the drug that reaches the blood, which decreases the biological efficacy of the drug (R).
Increasing or Decreasing CYP3A4
These increase CYP3A4:
- St. John’s wort (R, R, R)
- Capsaicin (R, R)
- Common valerian (R)
- Echinacea purpurea (R)
- Vitamin D and UV exposure (R)
- Being female (R)
- Diabetes (R)
- Fatty acids (R)
- Polycyclic aromatic hydrocarbons (PAH) found in cigarettes (R)
- Aflatoxin B1 (R)
- Some drugs such as carbamazepine (R) and dexamethasone (R)
These decrease CYP3A4:
- Grapefruit juice (and its compounds bergamottin, naringenin, and paradicin-A) (R, R, R)
- Starfruit juice (R)
- Aloe vera juice (R)
- Mixed vegetable juices (R)
- Kale (R)
- Garden cress (R, R)
- Goldenseal (R)
- Fennel (R)
- Raspberry leaf (R)
- Quercetin (R, R, R)
- Kaempferol (R)
- Berberine (R, R)
- Piperine, a constituent of black pepper (R, R)
- Licochalcone A, a compound in traditional Chinese herbal licorice (R)
- Oleuropein, derived from olive oil (R)
- Sesamin found in sesame seeds (Sesamum indicum) (R)
- Resveratrol (R, R, R)
- Sulforaphane (R)
- Apigenin (R)
- Coumestrol (R)
- Caffeic acid (R, R)
- Tannic acid (R)
- Gallic acid (R, R)
- Allyl isothiocyanate (R)
- Ginsenoside Rd (R), derived from Ginseng
- Milk thistle (compounds silybin and isosilybin) (R)
- Gomisin C and gomisin G found in the traditional Chinese medicine Schisandra Chinensis (R)
- Green tea flavonols epigallocatechin gallate and epicatechin gallate (R, R)
- Crohn’s disease (R)
- Drugs ritonavir, itraconazole (R), miconazole, ketoconazole (R), verapamil (R), sertraline (R), metformin (R), nefazodone (R), and clarithromycin (R)
CYP3A4 Genetic Variants
Unlike variable enzymes such as CYP2D6, CYP2C9 or CYP2C19, the CYP3A4 enzyme has fewer gene variants, and only a few of them are known to influence enzyme function (R).
Most of the SNPs (around 20) found in this enzyme have no functional significance (R).
Also known as CYP3A4*22 (T), rs35599367 is associated with decreased enzyme activity (R).
T/T people have around 2 times lower enzyme activity (R).
G variant increases prostate cancer susceptibility (meta-analysis, 39 studies, 14,334 cases, and 18,183 controls)(R).
This SNP is commonly found in Asians (R).