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The CYP Enzymes: An Introduction

The Cytochromes P450 (CYPs) are a group of enzymes that play an important role in the detoxification process. Detoxification is a process by which toxins and unwanted substances are removed from the body. There are three stages of detoxification, and CYPs help in phase 1 detoxification.

According to the Human Genome Project, 57 different types of CYP enzymes are identified in human beings.

The CYP1 group of enzymes is a major part of the CYP family. The Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) is one of the three CYP1 enzymes that help in detoxification. This enzyme is majorly found in the lungs.

The CYP1A1 gene helps produce the CYP1A1 enzymes. 

What Compounds Does The CYP1A1 Gene Act On?

Xenobiotic Substances

Xenobiotic substances are those that reach the body from external sources. These are not produced or found internally. The CYP1A1 enzymes work on removing Polycyclic Aromatic Hydrocarbons (PAHs) from the body. 

PAHs are groups of chemicals found throughout the environment, in the air, soil, and water. PAHs are produced when fossil fuels like coal, gasoline, and oil are burnt. 

These are also produced when tobacco and wood are burnt. PAHs are common toxins in charred and burnt meat. There are hundreds of PAHs in the atmosphere. Few common ones are:

Endogenous Substances 

Endogenous substances are those that are produced or available in the body. The CYP1A1 enzyme helps in the metabolism of certain endogenous substances.

Polyunsaturated Fatty Acids or PUFAs

The CYP1A1 enzyme converts PUFAs into signaling molecules. These signaling molecules are needed for various bodily functions. 

CYP1B1 enzyme converts arachidonic acid, a type of PUFA, into 19-hydroxyeicosatetraenoic acid (19-HETE). 19-HETE controls high blood pressure and the growth of cancer cells


CYP1A1 enzymes play a role in 17β-estradiol metabolism. 17β-estradiol is an estrogen hormone. This is responsible for regulating the female reproductive system. 

Oxidative Stress

Oxidative stress is a condition where the number of free radicals in the body is higher than the number of antioxidants. This imbalance leads to cell damage and an increased risk of cancer and other diseases. Some studies show that the CYP1A1 enzymes fight against Reactive Oxygen Species (ROS) and prevent oxidative stress

CYP1A1 Gene Changes (Variations) and Detoxification

Multiple changes or variations in the CYP1A1 gene lead to increased or decreased CYP1A1 enzyme activity. These gene variations protect against or increase the risk of conditions like cancer, PolyCystic Ovary Syndrome (PCOS), and diabetes. 

CYP1A1*2CIncreased enzyme activityCYP1A1 enzyme at higher levels can accelerate phase 1 detoxification and result in increased production of free radicals.
CYP1A1*2AIncreased enzyme activityCYP1A1 enzyme at higher levels can accelerate phase 1 detoxification and result in increased production of free radicals.

Recommendations For Maintaining Healthy CYP1A1 Enzyme Levels

Antioxidants Consumption

Overactive CYP1A1 enzymes can result in free radical damage. This can be treated with an antioxidant-rich diet. The following are some great sources of antioxidants:

- Berries

- Fresh fruits and vegetables

- Nuts and seeds

- Chocolates

- Spices and herbs 

Quit Smoking 

The Polycyclic Aromatic Hydrocarbons (PAHs) in tobacco in cigarettes increase CYP1A1 enzyme levels. Overactivity of the enzyme leads to quick phase 1 detoxification and increased free radical damage in the body. Quit smoking to bring down the risk of cancers and other diseases. 

Genetic Testing 

CYP1A1 genetic testing can help you identify changes in your CYP1A1 gene. This can give some insights into your CYP1A1 enzyme levels. If you have increased levels of this enzyme, your doctor may ask you to get screened for different types of cancers frequently. A genetic counselor can also help you interpret the report and understand it better. 


1. The Cytochromes P450 (CYPs) enzymes play a role in phase 1 detoxification. CYP1A1 is one of the important enzymes in this group.

2. The CYP1A1 enzyme helps with the metabolism of toxins like Polycyclic Aromatic Hydrocarbons (PAHs) and certain hormones and fatty acids in the body.

3. Certain changes in the CYP1A1 gene can increase the activity of the CYP1A1 enzyme. As a result, the phase 1 detoxification stage occurs quickly, increasing free radical molecules in the body. 

4. Free radicals can damage DNA and lead to an increased risk of many types of cancer, including breast, biliary, and lung cancer.

5. Including an antioxidant-rich diet plan can help prevent free radical damage. 

6. In people with high CYP1A1 enzyme levels, smoking can increase the risk of free radical damage and can cause cancers in the breast, lungs, liver, and cervix. 

7. Genetic testing can give you insights into your CYP1A1 enzyme levels. For people with errors in the  CYP1A1 gene, regular screening of cancer is recommended. 


CYP1B1 Gene - An Introduction

The CYP1B1 enzyme is a part of the Cytochrome P450 (CYPs) family and was first identified in 1994. The CYP family is a group of enzymes that play a major role in detoxification in the body. 

This enzyme helps in the metabolism and clearance of the various endogenous (produced internally) and exogenous (produced externally) substances. 

It is especially important for metabolizing cancer-causing agents (procarcinogens) like 17 beta-estradiol (an estrogen hormone) and Polycyclic Aromatic Hydrocarbons (PAHs). This enzyme is also responsible for adding oxygen atoms to other molecules. 

This enzyme is produced in many tissues in the body, including the eyes. The CYP1B1 gene controls the production of the CYP1B1 enzyme. Certain changes (or mutations) in  this gene can lead to overproduction or insufficient production of the enzyme and lead to diseases like primary congenital glaucoma. 

Substances that the CYP1B1 gene act on 

Fatty Acids and Fat-soluble Vitamins

The CYP1B1 enzyme helps in processing polyunsaturated fatty acids and fat-soluble vitamins like vitamins A, D, E, and K.

Steroidal Hormones (like Estrogen)

The CYP1B1 enzyme is the most important enzyme required for 17 beta-estradiol (E2) metabolism. Metabolism is the process by which large and complex food molecules and medicines are broken down into smaller components to produce energy, build or repair body tissues, produce hormones, and do more such activities needed for the body. This hormone is responsible for the female reproductive system management. High levels of E2 in the body can increase the risk for breast, ovarian, and uterine cancer. 


Melatonin is a natural hormone found in the human body. Melatonin is secreted at night by the pineal glands and controls the sleep-wake cycle. Recent studies have identified that melatonin kills certain types of cancer cells in the body - melatonin has anti-cancer properties. The CYP1B1 enzyme helps in the transformation of melatonin into N-acetylserotonin (NAS). NAS helps destroy cancer cells. 

Polycyclic Aromatic Hydrocarbons (PAHs)

PAHs are chemicals commonly found in certain natural sources like fossil fuels and many man-made products like toiletries, tobacco, garbage, and different plastic and rubber products. PAH is also produced when meat and other kinds of food are cooked at high temperatures and charred. PAHs are air-bound and enter the body when people breathe. 

Both the CYP1A1 and the CYP1B1 enzymes help convert PAHs into a more active form in the phase 1 detoxification stage. With more exposure to PAHs, the body produces more CYP1B1 enzymes, and more free radicals are produced. This increases the risk of cancers. 

CYP1B1 Inducers and Inhibitors

Inducers are substances that increase the metabolic activity of the enzyme. Inhibitors are substances that bind to the enzyme to reduce its activity.

Drugs That induce CYP1B1 activity

Drugs That Inhibit CYP1B1 activity

There are many drugs that inhibit CYP1B1 activity. Some of them are:

Variations in the CYP1B1 gene

CYP1B1 enzymes, produced by the CYP1B1 gene, protect the body from oxidative stress. Oxidative stress is caused due to increased free radicals in the body, resulting in cell damage. Changes in the CYP1B1 gene can decrease or increase the levels of the CYP1B1 enzyme produced. 

  1. Changes in this gene are associated with glaucoma - an eye disease that causes nerve damage in the eyes and leads to blindness. 
  2. Increased production of the CYP1B1 enzyme causes obesity, high blood pressure, and glucose intolerance. 
  3. Changes in the CYP1B1 gene also lead to an increased risk of different types of cancers, including breast, ovarian, uterine, renal, and non-small lung cancer. 
CYP1B1*2Increased enzyme activityIncreased risk of oxidative stress and different types of cancer
CYP1B1*3Increased enzyme activityIncreased risk of oxidative stress and different types of cancer
CYP1B1*4Increased enzyme activityIncreased risk of oxidative stress and different types of cancer
CYP1B1*12Decreased enzyme activityLowered risk of oxidative stress and different types of cancer

A haplotype is a group of gene changes that are inherited together. The *2, *3, *4, and *12 are star alleles. Star alleles are used to name different haplotypes.

Recommendations to Boost CYP1B1 Metabolism

Foods that Support CYP1B1 Enzyme Activity

Certain foods can encourage high levels of estrogen production in the body. To process high estrogen levels, the body produces an excess of the CYP1B1 enzyme. 

This can lead to a high risk for different types of cancers, including breast cancer, ovarian cancer, and uterine cancer. 

The foods listed below can naturally bring down estrogen metabolism in the body. 

Quit smoking

Cigarettes contain multiple Polycyclic Aromatic Hydrocarbons (PAHs) and various other chemicals. Smoking encourages PAH-DNA adduct formation in the lungs. PAH-DNA adduct is the accumulation of genetic changes in the DNA cells, leading to the formation of cancerous cells. 

In a 2000 study, the relationship between CYP1B1 enzyme, regular smoking, and PAH-DNA adduct formation was examined. The CYP1B1 enzyme metabolizes PAHs. The study reported that people who smoked had more risk for increased PAH-DNA adduct formation and hence had higher chances of developing lung and other types of cancers.

Reduce Exposure to UV Radiation

According to certain studies, over-exposure to UV-B rays encourages the excess production of the CYP1B1 enzyme. This is one of the top causes of non-melanoma skin cancers. 

Genetic Testing

Genetic testing can tell you if you are at a higher risk for excess production of CYP1B1 enzyme in the body. If so, you may be asked to get yourself screened for different types of cancers. Genetic testing will help diagnose cancers and other health conditions because of CYP1B1 gene mutations early and improve the success rate of treatments. 


  1. The CYP1B1 gene helps produce the CYP1B1 enzyme. This enzyme helps eliminate various toxins, drugs, and chemicals from the body.
  2. The enzyme is regulated by the aryl hydrocarbon receptor (AHR) in the body. 
  3. The CYP1B1 enzyme helps transform fatty acids, fat-soluble vitamins, melatonin, estrogen, and PAHs from the body.
  4. Changes in this gene can cause overactivity of the CYP1B1 enzyme and increase the risk of oxidative stress, glaucoma, and different types of cancers. 
  5. The *2, *3, and *4 alleles of the CYP1B1 gene increase the enzyme activity, while the *12 allele decreases the enzyme activity.
  6. Quitting smoking, consuming antioxidant-rich foods, reducing UV exposure, and preventing estrogen-increasing foods all help normalize CYP1B1 enzyme activity.
  7. Genetic testing can help identify your CYP1B1 enzyme activity. If you happen to have higher levels of the enzyme, regular cancer screening is recommended. 



CYP2C19 Gene - An Introduction 

The CYP2C19 gene is a member of the cytochrome P450 family responsible for the detoxification of drugs and toxins from the body. 

The CYP2C19 gene is primarily found in the liver and provides instructions for the production of the enzyme that participates in the metabolism of at least 10% of commonly prescribed medications. 

An important substrate that the CYP2C19 acts upon is Clopidogrel, an antiplatelet drug. Abnormal changes in the CYP2C19 gene contribute to clopidogrel resistance by affecting enzyme activity. In such individuals, the drug is less effective than in people with the normally functioning enzyme.

CYP2C19 Gene - The Different Metabolizer Types

Considerable differences exist in the efficiency and amount of CYP2C19 enzyme produced across individuals. Depending on this, they are categorized into one of the four metabolizer statuses:

Ultrarapid metabolizers

As the name goes, these individuals have higher than normal levels of the CYP2C19 enzyme. It occurs when a person has one or two copies of a form (variant) of the CYP2C19 gene called CYP2C19*17.

<5% of Asians carry this variant. 

These individuals are resistant to proton pump inhibitors (PPI) therapy. PPIs are used to treat Gastroesophageal Reflux Disease (GERD), gastric or duodenal ulcer, H.Pylori infection, and NSAID damage.

Extensive metabolizers or Normal metabolizers 

Individuals having at least one copy of CYP2C19*1 are considered to be extensive or normal metabolizers. They have normal levels of the CYP2C19 enzyme.

Poor metabolizers

The variants CYP2C19*2 and CYP2C*3 results in loss of function of the gene and cause low enzyme activity. They are called null variants. Individuals having these variants are called poor metabolizers.

Around 10% of people are poor metabolizers, and the antiplatelet drug Clopidogrel has little or no effect on these people. So, alternate antiplatelet drugs are prescribed to them. 

Blood levels of the drug amitriptyline ( a cyclic antidepressant) are found to be high in poor metabolizers. A lower starting dose may benefit these individuals. 

Similarly, the blood levels of voriconazole (an antifungal drug) are found to be high in these individuals, and treatment using this drug usually begins with lower doses.

Compounds That The CYP2C19 Gene Acts On

The CYP2C19 gene acts upon many prescribed drugs and medications. Common substrates of this gene include:

While some substrates induce (or increase) the activity of the gene, some substances reduce it.

Studies have shown a reduced activity of the CYP2C19 gene in women who take oral contraceptives. This is said to occur because the metabolic product of the oral contraceptive reduces the CYP2C19 function.

The CYP2C19 enzyme helps to convert arachidonic acid (a healthy omega-6 fatty acid that is beneficial for health, especially in infants) into Epoxyeicosatrienoic acids (EETs). These EETs have a beneficial and protective effect on the heart and blood vessels. 

A study reported that reduced activity of the CYP2C19 enzyme is associated with heart disease.

Higher activity of the CYP2C19 gene has been associated with depression. Also, low CYP2C19 activity has been associated with a lower prevalence of major depressive disorder and depression symptoms.

CYP2C19 Inducers and Inhibitors

Inducers are substances that increase the activity of an enzyme whereas inhibitors are substances that bind to an enzyme to reduce its activity.

Drugs that Induce CYP2C19 Activity

Drugs that Inhibit CYP2C19 Activity

Variations in the CYP2C19 Gene

There are over 30 known variants (or types) of the CYP2C19 gene. 

CYP2C19*2Inactive (Non functional variant)
CYP2C19*3Inactive (Non functional variant)
CYP2C19*4Inactive (Non functional variant)
CYP2C19*5Inactive (Non functional variant)
CYP2C19*6Inactive (Non functional variant)
CYP2C19*7Inactive (Non functional variant)
CYP2C19*8Decreased enzyme activity
CYP2C19*17Decreased enzyme activity
CYP2C19*27Decreased enzyme activity

A haplotype is a group of gene changes that are inherited together.  The *3, *4, *17, *27, etc., are star alleles. Star alleles are used to name different haplotypes. 

The commonly studied variants are CYP2C19 *2, *3, and *17.


This is the most common type seen in the Caucasian population. This type reduces the activity of the CYP2C19 gene, reduces the metabolism of certain drugs, and increases the risk of cardiovascular diseases.


The presence of this type of gene reduces the metabolism of commonly prescribed drugs in individuals.


Individuals who are carriers of this variant of the CYP2C19 gene show aggravated response to Clopidogrel and have an increased risk of bleeding.

Recommendations For Optimum CYP2C19 Activity

  1. Avoid making significant changes to their lifestyle and diet

Individuals with excessive or reduced activity of the CYP2C19 gene are advised against making significant changes to their diet, lifestyle, or taking supplements with their healthcare provider. 

  1. Genetic Testing

Genetic testing is recommended for individuals who need to be prescribed medications that the CYP2C19 gene acts on to determine the right alternative and the appropriate dosage.

For Poor Metabolizers 

For Ultra Rapid Metabolizers 


  1. CYP2C19 gene is a part of the cytochrome P450 enzymes and participates in the phase I detoxification of drugs (at least 10% of the commonly prescribed drugs).
  2. The gene has been extensively studied in relation to Clopidogrel, an antiplatelet drug.
  3. Some common substrates of the CYP2C19 gene include antidepressants, benzodiazepines, mephenytoin, anticonvulsants, among others.
  4. Some substances increase the activity of the gene (called inducers), and others inhibit (or reduce) its activity.
  5. The commonly studied variants of the CYP2C19 gene include *2, *3, and *17.
  6. Based on the presence of these haplotypes, individuals can be grouped under ultra-rapid metabolizers, extensive metabolizers, and poor metabolizers.
  7. Depending on the type of CYP2C19 gene, dosage changes may be required for drugs like lansoprazole, amitriptyline, and voriconazole can be prescribed.


CYP2E1 Enzyme

The CYP2E1 enzyme is a part of the Cytochrome P450 family and plays a role in drug metabolism

Drug metabolism is the process by which the body breaks down pharmaceutical drugs and other chemicals from the system using enzymatic systems. Drug metabolism can make the drug more active, inactive, or convert it into a more toxic metabolite (intermediary substance).

This enzyme makes up less than 1% of the total CYP450 enzymes and helps in clearing 2% of the total prescription drugs in the market.

CYP2E1 is mostly concentrated in the liver. It is also found in the lungs, brain, and kidney.

There are many variations (changes) in the CYP2E1 gene. These genetic variations create a difference in drug metabolism and increase/decrease the risk of different health conditions like diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), liver inflammation, and cancer.

Substances That The CYP2E1 Gene Act On

The CYP2E1 enzyme can activate small, low molecular weight compounds. Some of them include:


Ethanol is a simple alcohol that is commonly used as a food additive. It is the basic ingredient in most types of alcohol like wine, beer, and brandy. It is also added in food colors to evenly distribute the color. Ethanol is added to varnish and household cleaning products too. 

The CYP2E1 enzyme is responsible for ~20% of ethanol metabolism in the brain. 


Acetone is a flammable colorless liquid that is commonly used as thinners and nail polish removers. Internally, acetone is produced as a result of various metabolic activities in the body. The CYP2E1 enzyme eliminates excess acetone from the body and prevents acetone toxicity.

Fluorinated anesthetics

Inhalational anesthetics are administered using a face mask. Such anesthetics are made stronger and safer by adding fluorine to them. Below are some fluorinated anesthetics.

The CYP2E1 enzyme plays a role in the metabolism of most of these fluorinated anesthetics.  


Benzene is a sweet-smelling chemical that is flammable. Benzene is both man-made and naturally occurring. Naturally, benzene is released during forest fires and volcanic eruptions. Benzene is also a side-product released during the production of pesticides, lubricants, and rubber.

Over-exposure to benzene leads to anemia and certain types of cancers.

The CYP2E1 converts benzene into benzene dioxide and plays a role in clearing the toxin from the body.


N-nitrosodimethylaminen is also called dimethylnitrosamine (DMN), and this is produced as a result of chlorine water treatment. DMN is also found in cured meat and fish. Inhaling tobacco products increases the risk of DMN exposure too.  

CYP2E1 metabolizes DMN in the body. 


Acrylamide is a chemical released when food is roasted, baked, or fried at very high temperatures. The chemical is found more in starchy foods like potatoes. This chemical is highly toxic and can increase the risk of developing cancer.  

 CYP2E1 metabolizes acrylamide in the body and prevents its build-up in the body.


4-nitrophenol is a chemical used in the manufacturing of pesticides, fungicides, dyes, and leather. People who work in these manufacturing units are at high risk for 4-nitrophenol exposure. Exposure to this chemical can lead to nausea, drowsiness, and headaches. The long-term effects of exposure to this chemical are still being researched. The CYP2E1 enzyme metabolizes this chemical in the body.  


Acetaminophen is a pain-reliever. It is also commonly called paracetamol. This drug is used in treating fever and mild body aches. The CYP2E1 enzyme metabolizes acetaminophen and converts it into a more toxic form called N-acetyl-p-benzoquinone imine (NAPQI).  

Acetaminophen Hepatotoxicity

Hepatotoxicity is also called toxic hepatitis and causes serious liver damage. CYP2E1 encourages acetaminophen hepatotoxicity. NAPQI, in large amounts in the body, can lead to cellular damage. NAPQI needs to be quickly removed from the body with the help of glutathione or converted back to acetaminophen. 

CYP2E1 Inducers and Inhibitors

Inducers are substances that increase the metabolic activity of the enzyme. Inhibitors are substances that bind to the enzyme to reduce its activity.

Drugs that Induce CYP2E1 Activity

Drugs that Inhibit CYP2E1 Activity

Variations In The CYP2E1 Gene

There are multiple variations in the CYP2E1 gene that influence the activity of the CYP2E1 enzyme. 

CYP2E1*2Decreased enzyme activity
CYP2E1*6/CYP2E1_marker9Increased enzyme activity
CYP2E1*7BIncreased enzyme activity
CYP2E1 *5BIncreased enzyme activity

A haplotype is a group of gene changes that are inherited together.  The *2, *6, *5B, and *7B are all star alleles. Star alleles are used to name different haplotypes. 

Recommendations To Boost CYP2E1 Metabolism

Foods that Induce CYP2E1 Enzyme Activity

Foods rich in omega-3 fatty acids induce CYP2E1 levels in the body. 

Some food sources of omega-3 fatty acids are:

Foods that Inhibit CYP2E1 Enzyme Activity

Here is a list of foods that inhibit CYP2E1 activity.

Vitamins and Minerals That Support CYP2E1 Enzyme Activity

Both Vitamin C and vitamin E prevent oxidative stress and lipid peroxidation (free radicals damage the lipids in cell membranes, leading to cell damage) in the body. These vitamins also prevent a decrease in the CYP2E1 enzyme activity in the liver and improve CYP2E1 drug metabolism.

Genetic Testing 

Genetic testing can help identify the metabolizer status of an individual for a gene (or group of genes) or a drug (or group of drugs). Depending on the genetic results, doctors can then plan drug dosages and opt for safer medications. 


  1. The CYP2E1 gene helps produce the CYP2E1 enzyme. This enzyme is responsible for clearing 2% of all the prescription drugs sold in the market. 
  2. The CYP2E1 enzyme is an important enzyme involved in the metabolism of ethanol.
  3. Certain drugs like isoniazid, ethanol, and pyrazole can induce CYP2E1 activity in the body. Drugs like Chlorzoxazone, Disulfiram, Indazole, and Fomepizole inhibit the CYP2E1 activity.
  4. The *2, *6, *5B, and *7B haplotypes of the CYP2E1 gene decrease or increase the enzyme activity. This can lead to drug overexposure or increased levels of toxic intermediates.
  5. Genetic testing can be used to learn more about your enzyme levels.  


CYP2D6 Gene - An Introduction 

The CYP2D6 gene or the cytochrome P450 2D6 contains instructions for the production of the CYP2D6 enzyme. The enzyme production predominantly occurs in the liver. CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs. 

Drug metabolism is the process by which the body breaks down pharmaceutical drugs and other chemicals from the system using enzymatic systems. Drug metabolism can make the drug more active, inactive, or convert it into a more toxic metabolite (intermediary substance).

CYP2D6 belongs to the group of enzymes that are responsible for activating and metabolizing certain drugs. In some cases, the enzyme converts the inactive drug (called the prodrug) into its active form. Most ACE inhibitor drugs used to treat hypertension are prodrugs. 

Amitriptyline, an antidepressant drug, on the other hand, is broken down and inactivated by the CYP2D6 in the liver

CYP2D6 - The Different Metabolizer Types

Considerable differences exist in the efficiency and amount of CYP2D6 enzyme produced across individuals. Depending on this, they are categorized into one of the four metabolizer statuses:

Poor metabolizers (PM) - These are people who produce no or very little of the CYP2D6 enzyme. These individuals cannot process certain medicines well, and in some cases, drugs remain in the body for a longer time without getting cleared out. This increases the toxicity of the drug.  

Intermediate metabolizers (IM) - These people can produce and process moderate amounts of the CYP2D6 enzyme. About 3 in 10 people are intermediate metabolizers. 

Normal/extensive metabolizers (EM) - About 6 in 10 people are normal metabolizers. Their bodies produce normal levels of the CYP2D6 enzyme and activate and clear drugs at a normal rate.

Ultra-rapid metabolizers (UM) - These people have excess CYP2D6 enzyme activity. Drugs are metabolized very quickly and cleared from the body rapidly. This reduces the effectiveness of the drugs.

Drugs That The CYP2D6 Gene Act On

Codeine - Codeine is an opioid pain reliever commonly prescribed to treat chronic cough, pain, and diarrhea. It needs to be activated to morphine by the CYP2D6 enzyme for it to function efficiently. 

PM have low CYP2D6 enzyme levels and may not convert codeine to morphine effectively. As a result, they may not experience the pain-relieving effect of morphine at normal codeine doses. 

Tramadol - Tramadol is also an opioid pain reliever used to treat moderate to moderately severe pain. It is converted into O-desmethyltramadol (M1) in the liver, which produces the opioid pain-relieving effect. This conversion is facilitated by the CYP2D6 enzyme.

Amitriptyline - Amitriptyline helps treat anxiety and depression by preventing serotonin reuptake and thereby boosting serotonin levels in the body. CYP2D6 is involved in the metabolism of amitriptyline. 

The FDA-approved drug label for amitriptyline states that CYP2D6 PM have higher than expected plasma concentrations of tricyclic antidepressants when given usual doses. In such cases, a lower starting dose or an alternative drug is recommended. 

Metoprolol and propranolol - Both metoprolol and propranolol are beta-blockers. These are used in the treatment of heart diseases and hypertension. 

They are primarily metabolized by CYP2D6. PM who lack CYP2D6 activity tend to have almost 5-fold higher levels of metoprolol and may be at an increased risk of side effects if administered the normal start dose. 

Fluoxetine, Paroxetine  - Both Fluoxetine and Paroxetine are Selective Serotonin Reuptake Inhibitors (SSRI) and are popular antidepressants. 

The CYP2D6 enzyme helps convert the drugs into their active forms.

In PM, the drugs remain in the system for a longer time, risking overexposure. A lower starting dosage is recommended for such individuals.

Natural hormones and lipid - The CYP2D6 enzyme also metabolizes few naturally occurring substances in the body, including:

CYP2D6 Inducers and Inhibitors

Inducers are substances that increase the metabolic activity of the enzyme. Inhibitors are substances that bind to the enzyme to reduce its activity.

Drugs that Induce CYP2D6 Activity

Inducers speed up the metabolism of the drugs, resulting in lower concentrations for drugs that are metabolized to an inactive form. In the case of antibiotics, inducers make the enzymes quickly convert them into their inactive forms, not giving the drugs enough time to fight the bacterial infections.

Drugs that Inhibit CYP2D6 Activity

Many drugs inhibit the activity of the CYP2D6 enzyme. Some of them include:

Estimates suggest that up to nearly a third of patients on tamoxifen are also taking antidepressants. Tamoxifen is a drug used to prevent breast cancer in women and treat breast cancer in women and men. Antidepressants like Fluoxetine (Prozac) and Paroxetine (Paxil) can substantially inhibit CYP2D6 and may reduce tamoxifen efficacy. 

Variations in the CYP2D6 gene

The  CYP2D6 gene has a lot of variations (changes) that affect the efficiency of the CYP2D6 enzyme. 

CYP2D6*3Inactive enzyme
CYP2D6*4Inactive enzyme
CYP2D6*6Inactive enzyme
CYP2D6*7Inactive enzyme
CYP2D6*8Inactive enzyme
CYP2D6*9Decreased enzyme activity
CYP2D6*11Inactive enzyme
CYP2D6*12Inactive enzyme
CYP2D6*14Inactive enzyme
CYP2D6*41Decreased enzyme activity

A haplotype is a group of gene changes that are inherited together.  The *3, *4, *14, *41, etc., are star alleles. Star alleles are used to name different haplotypes. 

The *4 allele is one of the most common mutations in Caucasians, resulting in a decrease in or complete lack of CYP2D6 enzyme activity. This allele accounts for 70% of all inactivating alleles that Caucasians are born with. 

Recommendations To Boost CYP2D6 Metabolism

Foods that Induce CYP Enzyme Activity

Vitamins and Minerals That Support CYP Enzyme Activity

Genetic Testing

Genetic testing will help identify the metabolizer status of an individual for a gene (or group of genes) or a drug (or group of drugs). Depending on the genetic results, doctors can then plan drug dosages and opt for safer medications. 

CYP2D6 Inhibitors

Even if you are not a poor metabolizer genetically, the use of  CYP2D6 inhibitors will bring down the enzyme activity. This can cause over-exposure to drugs that the CYP2D6 enzyme acts on.

CYP2D6 Poor Metabolizers

For CYP2D6 poor metabolizers, CPIC recommends using an alternative hormonal therapy instead of tamoxifen for postmenopausal women.


  1. The CYP2D6 gene helps produce the CYP2D6 enzyme. This enzyme is responsible for clearing 25% of all clinically used drugs from the body. 
  2. People can be grouped into 4 categories, depending on the CYP2D6 enzyme activity – Poor metabolizers, Intermediate metabolizers, Normal/extensive metabolizers, Ultra-rapid metabolizers. 
  3. In poor metabolizers, the drug is cleared very slowly from the system, and the person is exposed to the drug for a longer time. 
  4. Ultra-rapid metabolizers metabolize drugs very fast, and the drugs don’t have the time to work. 
  5. The CYP2D6*4 haplotype and the CYP2D6*7 haplotype both lead to reduced enzyme activity and, as a result, increase the risk for drug overexposure.
  6. Genetic testing will tell what kind of a metabolizer a person is. This will be useful to plan optimal drug doses.



How Do Pesticides Enter The Body?

Pesticides are routinely used in agrochemical industries to prevent, repel, mitigate or kill pests that can damage the produce. It is a broad term and usually includes fungicides, herbicides, acaricides, bactericides, nematicides, rodenticides, etc. 

Based on their chemical structure, pesticides can be of the following types – Organochlorine, Organophosphorus, Carbamates, and Pyrethroids. Unfortunately, while consuming fruits, vegetables, and other products, we inadvertently consume some pesticides. 

Pesticides are called xenobiotics, i.e., foreign compounds that are not produced by the body but found in it. The organochlorine group of pesticides are the most widely used and are predominant pesticides in the environment. They also have the potential to accumulate in the body’s adipose (or fat) tissues. These pesticides alter enzyme activities and cause harmful effects on the nervous system.

Since pesticides have a long half-life (they take a long time to reduce to half of their concentration in the body), the body has to eliminate them regularly. 

Pesticides In Food

The metabolism of pesticides occurs in two phases – Phase I and Phase II reactions. Metabolism is the process by which chemicals like pesticides that enter our body are broken down into smaller components, made less toxic, and more water soluble to enable their easy elimination from the body.

In some cases, detoxification can result in the formation of a toxic product. This is called the bioactivation of a pesticide.

Pesticides are lipophilic (or fat-soluble) substances. This nature helps them to enter the cell membrane and bind to various lipoproteins in the blood. Since they are fat-soluble, they are insoluble in water and are not easily eliminated from the body. To remove them, they are converted into polar compounds that are easily eliminated from the body.

Phase I: In the first phase, these fat-soluble pesticide molecules are converted into polar compounds by adding a polar group. This process occurs either by oxidation, reduction, or hydrolysis reaction. The end product of the phase I reaction now serves as a substrate (or starting compound) for phase II reaction.

Phase II: In Phase II of pesticide metabolism, the polar compound gets attached to substances in the body such as sugars, amino acids, glutathione, phosphates, and sulfates. This conversion to a polar compound makes pesticides less toxic and easy to eliminate.

Where Does Pesticide Metabolism Take Place?

Metabolism of xenobiotics like pesticides occurs in all tissues and organs as it is a defense mechanism to eliminate toxic products and reduce any harmful effects on the organism. Though all organs and tissues show some amount of pesticide metabolism, detoxification occurs more actively in organs like the kidney, liver, and intestine. 

Enzyme groups like the Cytochrome P450 (or the CYP enzymes), NADPH Cytochrome C Reductase, and Flavin-Containing Monooxygenase (FMO) play an important role in the metabolism of pesticides in the body. Other enzymes that play a role in pesticide detoxification include dehydrogenases, reductases, and Glutathione S Transferase.

 What is Pesticide Toxicity?

Failure to eliminate pesticides from the body can lead to their accumulation and subsequent toxicity. The toxicity of pesticides is expressed in terms of LD50. It is defined as the single exposure dose of a substance per unit bodyweight of the organism and is the abbreviation for Lethal Dose 50%.

Based on this LD50 value, pesticides can be of the following types, based on their toxicity scale:

Extremely Toxic1 mg/kg(ppm) or lessParathion, aldicarb
Highly Toxic1-50 mg/kg(ppm)Endrin
Moderately Toxic50-500 mg/kg(ppm)DDT, Carbofuran
Slightly Toxic500-1000 mg/kg(ppm)Malathion
Non-Toxic 1-5 gm/kg

Organophosphorus pesticides hinder the activity of an enzyme (acetylcholinesterase enzymes) important for the proper functioning of the nervous system. The toxicity effects of organophosphorus compounds are rapid, and symptoms appear immediately after exposure. Exposure to these pesticides can be hazardous for people with reduced lung function and a history of convulsive disorders.

Genetics Of Pesticide Detoxification/Metabolism

Two primary groups of genes are involved in the metabolism of pesticides, particularly organophosphates. These include the CYP genes and PON gene family.

Variations in the CYP Genes

CYP Genes

The CYP genes and enzymes perform a vital role in the metabolism of pesticides. Some genes that play a role include CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6. In addition, CYP2B6 and CYP2C19 play an essential role in phase I detoxification of pesticide metabolism.

The CYP2B6 Gene

The CYP2B6 gene and its variants (different forms) are studied in relation to chlorpyrifos (CPS), a broad-spectrum organophosphate insecticide. This substance is said to be neurotoxic to humans, which means it affects the nervous system. 

Chlorpyrifos oxon (CPO) is a toxic by-product of CPS metabolism and is produced by the CYP2B6. Two forms, CYP2B6 *5 and *8, convert chlorpyrifos to chlorpyrifos oxon.

CYP2B6*6 is another form of interest in the metabolism of chlorpyrifos. Studies suggest that CYP2B6*6 has increased activity but a reduced potential to activate chlorpyrifos in the human liver cells compared to other variants. Due to this, people with the *6 form of the CYP2B6 gene are less susceptible to chlorpyrifos toxicity.

The CYP2C19 Gene

The CYP2C19 gene has many forms, with CYP2C19*2 being the most common one. CYP2C19 acts as a catalyst in the metabolism of methoxychlor, a pesticide. However, in people having the non-functional form of the gene (also called poor metabolizers), the role of the CYP2C19 gene is performed by the CYP1A2 gene.

Variations in the PON1 Gene

The PON1 Gene

The PON gene family comprises three genes– PON1, PON2, and PON3. PON1 or Paraoxonase 1 is a calcium-dependent enzyme and is located on chromosome 7. This means that the activity of this enzyme depends upon the availability of calcium. There is increasing evidence from studies that variations in the PON1 gene increase an individual’s susceptibility to organophosphate toxicity (

Organophosphates induce low-grade inflammation in humans, and PON1 gene variations have shown to cause intoxication in Cameroonian and Pakistani pollution ( Two variations or SNPs of this PON1 gene are essential in the metabolism of pesticides. These include rs662 and rs7493.

Individuals having the T allele are said to be at a higher risk of developing organophosphate toxicity than those having the C allele.

Studies show that children with the C allele exposed to pesticides before their birth tend to have a greater abdominal circumference, more body fat content, high blood pressure, and BMI than those who have not been exposed. However, these features were not observed in children having TT genotype.

Recommendations To Boost Pesticide Detoxification

Prevent Inadvertent Exposure to Pesticides

Exposure to Pests

Avoiding exposure to pests by preventing their entry into your home, garden, and lawn is an excellent way to stay clear of any pesticides they have.

Non-Chemical Pest Control Methods

Since pesticides can cause toxicity, it is a good idea to use non-chemical pest control methods. Some of these options include natural pesticides, mechanical traps, sticky traps for more minor pests, and vacuuming during a flea infestation.

Follow Label Instructions While Using Pesticides

If you have to use pesticides, always read label instructions before you purchase the product. Then, follow the instructions on the label to use the pesticide. Always wear protective gear to avoid direct contact with the chemical, and make sure you prepare and use the pesticide away from food or other consumables.

Safe Storage and Disposal of Pesticides

The risk of exposure to pesticides is high even when you store them in your home. Ensure safe storage of pesticides in your house by keeping them under tightly closed containers. Keep them out of reach of children and yours. If your skin gets exposed to a pesticide, wash your hands properly. Always change your clothes or have a bath after working with pesticides to avoid any form of accidental inhalation of particles or their consumption.

How Genetic Testing Help In Removing Pesticides From Your System

If you are exposed to pesticides regularly due to your job or profession; it may be a good idea to get genetic testing done as individuals having the T allele in SNP rs662 are said to be at a higher risk of developing organophosphate toxicity as compared to those having the C allele. 


  1. Pesticides are chemicals used in the agrochemical industry and at homes to kill, repel or mitigate pests.
  2. Pesticides are of different types, based on their source.
  3. Organochlorine and organophosphorus are commonly used pesticides.
  4. Pesticides are harmful to the body as they alter enzyme activity and cause harmful effects to the nervous system. 
  5. In addition, some pesticides have an affinity to get stored in the body’s fatty tissue. For this reason, they are regularly eliminated from the body.
  6. Metabolism of pesticides in the body occurs in two phases – Phase I and Phase II.
  7. The CYP and PON gene families are associated with the metabolism of pesticides.
  8. Among the CYP family of genes, CYP2B6 and CYP2C19 play pivotal roles.
  9. The PON1 gene and its variations are also said to affect the metabolism of organophosphate pesticides.
  10. Avoiding pest exposure and storing and preparing pesticides safely can help limit pesticide exposure.
  11. Individuals who work with pesticides regularly can get a genetic test to identify any high-risk genes associated with pesticide metabolism.


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