CYP1B1 is an important detox enzyme that metabolizes many compounds and is important for the development of the eye. If activity is too high or too low, CYP1B1 can be at the root of a variety of problems. Read on to learn more.
What is CYP1B1?
The enzyme CYP1B1 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body [1].
CYP1B1 Function
This enzyme metabolizes:
- steroid hormones [2], including estrogens [3, 4]. CYP1B1 is also responsible for the final steps in the production of cortisol and aldosterone [5].
- fatty acids and fat-soluble vitamins [2, 6].
- melatonin [2].
- retinol and dietary plant flavonoids [7].
- polycyclic aromatic hydrocarbons (PAHs), biphenyls, N-heterocyclic amines, arylamines, amino-azo dyes, and other cancer-causing and toxic environmental chemicals [8, 2].
- CYP1B1 metabolizes few, if any, clinical drugs [8].
CYP1B1 Location
This enzyme is found in the liver, but also in various other tissues including fat, skin, breast gland, prostate, heart, blood vessels, kidney, thymus/marrow and immune cells, breast, uterus, brain, and eyes [6, 2, 7, 8, 9].
Beneficial Functions
An important role of CYP1B1 is that it helps reduce oxidative stress [6, 10]. CYP1B1 deficiency results in increased oxidative stress in mice [11].
Also, this enzyme is important for eye development [9, 12]. Many mutations in CYP1B1 cause primary congenital glaucoma [12, 13].
This enzyme can protect from cancer. CYP1B1 deficient mice have more lung tumors [14].
Potentially Detrimental Functions
This enzyme is produced by fat tissue, and it helps increase fat uptake [6].
In mice, CYP1B1 deficiency increases AMPK, reduces obesity, reduces blood pressure, and improves glucose tolerance [6, 15].
Furthermore, this enzyme is capable of activating a wide range of cancer-causing compounds. Increased CYP1B1 activity has been associated with a range of cancers [16, 10].
CYP1B1 activity was shown to promote the growth and metastasis of non-small lung cancer cells [17] and may promote the growth of renal cell carcinoma (kidney cancer) cells [18].
CYP1B1 Gene Polymorphisms
More than 150 SNPs have been reported for this gene [13, 11].
Many mutations of this gene are linked to primary congenital glaucoma [12, 6].
rs10012
rs10012 alters androgen (testosterone) concentrations (1499 cases and 1373 controls) [19], with the C variant being more active [20].
This may explain the association of the C variant with increased disease aggressiveness in prostate cancer (1387 subjects) [21].
The C variant was also associated with an increased risk of endometrial cancer (200 subjects) [22].
On the other hand, the G variant was associated with urinary bladder cancer (492 subjects) [23].
rs1056827
This variant is also known as Ala119Ser.
At rs1056827, the A allele is the more active variant of the enzyme [20].
This variant (A) correlates with urinary bladder cancer (492 subjects) [23], higher risk of prostate cancer (meta-analysis, 34 studies, 17,796 cases, and 19,891 controls) [24] and breast cancer (same meta-analysis, 17,796 cases, and 19,891 controls) [24].
rs1056836
rs1056836 is also known as Leu432Val.
People with the G variant at rs1056836 tend to have higher enzyme activity (about 3 fold) [25, 26].
G is associated with increased susceptibility to hepatocellular carcinoma (983 subjects) [27], multiple myeloma (1061 subjects) [28], lung cancer (meta-analysis, 22 studies, 2881 cases, and 3653 controls) [29], and endometrial cancer, but decreased susceptibility to ovarian cancer (meta-analysis of 115 studies: 54,124 cases and 62,932 controls) [24] and prostate cancer (1387 subjects) [21].
The CC genotype (two C alleles) is associated with bloating, facial hair, palpitations, and involuntary urination in premenopausal women. CC is also linked to nausea, bloated stomach, facial hair, and vaginal dryness in peri- and postmenopausal women. Carriers of CC or CG were approximately five times more likely to suffer from vaginal dryness than women with the GG genotype (299 women) [30].
G was associated with shorter average telomere length in postmenopausal women taking hormonal therapy (259 subjects) [26]. Short telomere length is associated with premature aging and age-related disease.
rs1800440
Rs1800440 is also known as Asn453Ser. At this SNP, the C allele was associated with a decreased risk of endometrial cancer (meta-analysis, 48 studies, 30,532 cases, and 39,193 controls) [24].
rs150799650
The T allele at rs150799650 was associated with bladder cancer (in 492 subjects) [23].
Factors Affecting CYP1B1 Activity
Researchers have observed many factors that increased or decreased CYP1B1 activity in cells or animals; however, it is unclear how relevant these studies may be to CYP1B1 activity in the human body.
Because of the degree of uncertainty and lack of clinical studies, we strongly recommend talking to your doctor before making any significant changes to your diet, lifestyle, or supplement regimen.
Factors that Increase CYP1B1:
- Diesel exhaust particles (DEP) [31]
- Tetrahydrocannabinol (THC), found in cannabis [31]
- UV exposure [32]
- Biotin supplementation [33]
Factors that Decrease CYP1B1:
- St. John’s wort [34]
- Apigenin [34]
- Ginseng [35]
- Lycopene, a red pigment found in tomatoes, carrots, and watermelon [36]
- Chrysoeriol, present in rooibos tea and celery [37]
- Naringenin, found in grapefruit juice [38]
- Zyflamend, a polyherbal formulation produced from the extracts of ten common herbs (rosemary, turmeric, ginger, holy basil, green tea, hu zhang, Chinese goldthread, barberry, oregano, and Baikal skullcap) [39]
- Quercetin [40]
