CYP1A1 is an important enzyme involved in the detoxification and metabolism of many substances. However, this enzyme can also activate some toxic compounds into cancer-causing agents. Read on to find out more about CYP1A1, its genetics, and the natural substances that can increase or decrease CYP1A1 activity.
What is CYP1A1?
CYP1A1 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that help eliminate most of the drugs and toxins from the human body [1].
Function in Drug Metabolism
CYP1A1 metabolizes:
- polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene [2]. PAHs are a group of more than 100 different chemicals that are released from burning coal, oil, gasoline, trash, tobacco, wood, or charcoal-broiled meat.
- estrogen [2, 3].
CYP1A1 is increased when environmental pollutants and chemicals bind to AhR [4].
When CYP1A1 processes PAHs, it may “activate” them, converting them into cancer-causing agents [2].
Unlike most other CYP enzymes, this one is mainly found outside of the liver, in tissues such as the lungs [5].
Beneficial Effects of CYP1A1
CYP1A1 is important for the removal of toxic chemicals from our bodies. Mice lacking this enzyme die within 30 days of benzo[a]pyrene treatment, whereas normal mice survive with no signs of toxicity [4].
Although this enzyme can activate cancer-causing substances, it primarily plays an important role in their detoxification [4].
It can also convert natural products found in food into anti-cancer agents [4].
Some anti-tumor drugs, such as phortress and aminoflavone, actually function by increasing CYP1A1 [4].
Negative Effects of CYP1A1
CYP1A1 plays a major role in activating cancer-causing chemicals, such as PAHs [5].
This enzyme is further involved in the activation of aflatoxin B1, a cancer-causing fungal toxin present in foodstuffs [4].
It also activates tobacco-related cancer-causing N-nitrosamines, such as NNK [4].
Elevated CYP1A1 activity is associated with higher lung cancer risk (300 subjects) [5].
Genetics
rs4646903
The C variant (more active than the T variant) is associated with increased susceptibility to DNA damage and cancer risk. In fact, rs4646903 was linked to leukemia, cervical, hepatocellular, lung, prostate, and head and neck cancers (meta-analysis, 268 studies, 55,963 cases, and 76,631 controls) [6, 7, 8].
On the other hand, carriers of the rs4646903 C/C developed rectal cancer at a lower rate than T/T carriers (2769 subjects) [9].
This variant may increase the risk of polycystic ovary syndrome (meta-analysis, 3489 subjects) [10].
rs1048943
The rs1048943 G variant has been associated with lung cancer (561 subjects) [7], leukemia (meta-analysis) [8], and hepatocellular carcinoma (liver cancer) (2016 subjects) [11].
rs2606345
Women with the rs2606345 C/C genotype (two Cs) had higher levels of this enzyme and lower levels of estradiol (1340 subjects) [12].
rs4646421
The rs4646421 A variant has been associated with hepatocellular carcinoma (2021 subjects) [11].
Increasing or Decreasing CYP1A1
Mainly in cell and animal studies, researchers have observed various substances that increase or decrease the activity of CYP1A1. For informative purposes, I have compiled some of these substances below. Talk to your doctor before taking any new supplements.
Natural Substances that Increased CYP1A1 Activity
- Indole-3-carbinol, found in cruciferous vegetables [13].
- Resveratrol and resveratrol-containing foods [3].
- Andrographolide, from the Andrographis paniculata plant [14].
- Astaxanthin, a pigment found in most red-colored aquatic organisms like shrimps and some algae [15].
- Fish oil and garlic oil [16].
- Green and black tea [17].
Natural Substances that Decreased CYP1A1 Activity
- Berries and their component ellagic acid can reduce CYP1A1 overactivity [3].
- Green tea extracts [18].
- Sulforaphane found in broccoli [19].
- St. John’s Wort [20].
- Lycopene, a red pigment found in tomatoes, carrots, and watermelon [21].
- Naringenin and 6′,7′-dihydroxybergamottin (from grapefruit juice) [22].
- Galangin, found in some plants (Alpinia officinarum, Alpinia galanga, and Helichrysum aureonitens) and propolis [23].
- Zyflamend, a widely used herbal 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) [24].
Substances that May Increase or Decrease CYP1A
Many foods appear to act as both inducers and inhibitors of CYP1 enzymes, based on the dose, or the differences in active compounds:
- Curcumin at 0.1% of the diet induces this enzyme, yet a diet of 1% turmeric is inhibitory [3].
- Black tea at 54 mL/d induced CYP1A1, yet 20 mg/kg of theaflavins was inhibitory [3].
- Soybean intake at 100 mg/kg increased enzyme activity, yet at 1 g/kg black soybean extract and 200 mg daidzein twice daily was inhibitory [3].
