Phase 2 Detoxification: An Introduction
The phase 1 detoxification process transforms toxins, drugs, and other harmful substances in the body into active forms. The active forms are more toxic and have to be quickly removed to avoid damage to the body.
This is done by phase 2 detoxification. This phase is called the conjugation phase. Conjugation is the process of joining two things together. In phase 2 detoxification, the active compounds from phase 1 are modified to lower the toxicity and make them water-soluble for easy elimination from the body.
The phase 2 detoxification stage is very important in protecting the cells from cancer-causing chemicals (carcinogens).
Phase 2 Detoxification Pathway
There are six different pathways in phase 2 detoxification that are aided by different enzymes. All these pathways need to work harmoniously for efficient detoxification. The conjugated products are sent to phase 3 detoxification and are finally eliminated.
Glutathione Conjugation
Glutathione conjugation is a pathway that uses glutathione to neutralize toxins. Glutathione is a type of antioxidant that helps prevent cell damage and oxidative stress. The Glutathione S-transferases (GSTs) are a group of enzymes that help combine glutathione with active toxin elements.Â
The conjugation makes the toxins water-soluble and makes it easy to remove them from the body.
GSTs helps detoxify the following:
- Different types of drugs
- Polycyclic Aromatic Hydrocarbons (PAH) (found in smoked, curated foods, burnt meat, barbecues, and shellfish)
- Synthetics found in food and cookware/tableware
- Heavy metals like mercury
- α,β-unsaturated carbonylsÂ
GSTs are distributed throughout the body in the liver, kidneys, brain, spleen, intestines, lungs, and skeletal muscles.
The Right Nutrition To Support Glutathione Conjugation
Proteins: Amino acids are the bases of glutathiones. Lowered levels of protein intake may alter amino acid levels in the body and lead to reduced ability to produce glutathione.
Omega-3 fatty acids: Inflammation in the body reduces glutathione supply. Omega-3 fatty acids can help reduce chronic inflammation. Include omega-3 rich foods like fatty fish, nuts and seeds, avocados, and fish oil in your food. Â
Vitamins: Vitamins B, C, and E are all important to produce and maintain glutathione activity in the body.
Amino Acid Conjugation
Amino acids are building blocks of proteins. Some of the amino acids can attach themselves to toxins and make them water-soluble and easy for excretion.
Two enzymes help with amino acid conjugation – Acyl-CoA synthetases and Acyl-CoA amino acid N-acyltransferases.
A common amino acid – glycine, helps in removing toxic benzoate from the body. Benzoate is a very common preservative used in foods.
The Right Nutrition To Support Amino Acid Conjugation
Protein: Food sources like meat, seafood, poultry, eggs, and dairy products are rich sources of proteins. They help improve amino acid levels in the body.Â
Amino acid supplements: Amino acid supplements are a mix of essential amino acids in the right quantities and help improve amino acid levels in the body.
Methylation
Methylation is the process of substituting one atom in a substance by a methyl group. In this pathway, a methyl group is added to toxins to make them biologically less active to help transport them out. This pathway uses the Methyltransferases (MT) enzyme group for conjugation.
There are many MT enzymes, but the most important ones are the Thiopurine S-methyltransferase (TPMT) and the Catechol-O-methyltransferase (COMT).
TPMT helps in the methylation of heterocyclic sulfhydryl compounds like thiopurines (immunosuppressive drugs).
COMT helps in the methylation of neurotransmitters like dopamine, epinephrine, and norepinephrine. There are two forms of COMT. The membrane-bound catechol-O-methyltransferase (MB-COMT) is produced by the brain’s nerve cells. The shorter version called the soluble catechol-O-methyltransferase (S-COMT) helps send out excess hormones in the body.Â
Also Read: COMT Gene Influences Worrier And Warrior Personality
The Right Nutrition To Support Methylation
Folate: Folate is a methyl donor and helps make methyltransferases (MT). Foods like legumes, dark leafy greens, beetroots, and cruciferous vegetables are rich in folate.Â
Choline: Choline is an essential nutrient that acts as a methyl donor and helps in the methylation process. Foods like red meat, eggs, seafood, whole grains, legumes, and dairy products are choline-rich.Â
Vitamins B2, B6, and B12: – These three vitamins play a role in methyl metabolism and help act as methyl donors. Foods like dairy, liver and kidney, shellfish, dark green vegetables, and red meat are rich sources of B vitamins.Â
Sulfonation
Sulfonation is the process of attaching sulfates to toxins to neutralize them. In sulfonation, sulfotransferase enzymes (SULTs) transform various steroids, peptides, vitamin D, serotonin, and catecholamines (neurotransmitters) in the body. SULTs also help remove the following toxins from the body.
- – Benzyl alcohol
- – Hydroxylamines
- – Aromatic amines
- – NaphtholsÂ
The Right Nutrition To Support Sulfonation
Retinoic acid (Vitamin A): Vitamin A can induce (promote the production of) SULT enzyme in the body. Food sources like liver, fish, eggs, dairy products, fruits, and vegetables like apples, asparagus, and carrots are rich in vitamin A.Â
Caffeine: Certain studies show that caffeine sources like coffee, tea, green tea, and cocoa can increase SULT activity.Â
Acetylation
In acetylation, the N-terminal acetyltransferases (NATs) enzymes make use of acetyl CoA to attach themselves to the toxins. NATs are responsible for removing different types of carcinogens (cancer-causing agents) present in food and the environment. These also are responsible for removing excess folate from the body.
There are two NAT enzymes – NAT1 and NAT2 that are important parts of acetylation.
The Right Nutrition To Support Acetylation
Quercetin: Quercetin is a natural flavonoid found in various fruits and vegetables like cherry tomatoes, broccoli, blueberries, kale, and apples. A small study found that consuming 500 mg of quercetin a day helps improve NAT enzyme levels.Â
Glucuronidation
The glucuronidation pathway is the most important one of phase 2 detoxification. This pathway uses the help of the UDP-glucuronosyltransferases (UGTs) enzymes.
UGT enzymes metabolize up to 70% of all drugs in the body.
UGTs help in the elimination of the following toxins and hormones.
- – Aromatic hydrocarbons like benzopyrene (found in smoked food, burnt food, cigarettes)
- – Heterocyclic amines (HCAs) found in overcooked and charred meat like fish, poultry, beef
- – Aromatic amines, common in industries that manufacture tobacco, hair dyes, and other chemicals. Cooked meat like chicken, mutton, beef, and pork also have traces of aromatic amines. Â
- – Bisphenol-A (BPA) – a common chemical added in the production of plastic containers, canned foods, household electronics, and toiletries
- – Medically prescribed opioids (drugs prescribed for pain management)
- – Estrogens T3 and T4 that are produced in the body
- – Bilirubin, a yellow liquid necessary for removing waste products from the body (excess bilirubin levels lead to various health problems)
The Right Nutrition To Support Glucuronidation
– Cruciferous vegetables: Cruciferous vegetables like cabbage, cauliflower, Brussel sprouts, and broccoli help increase UGT enzymes
– Lycopene: Lycopene is a type of carotenoid that has antioxidant properties. It helps increase UGT enzymes. Some sources of lycopene include pink and red-colored fruits and vegetables like watermelons, pink grapefruits, and tomatoes.
– Ellagic acid: Ellagic acid is a type of natural antioxidant that increases UGT enzymes. Foods like pomegranate, berries, blackcurrants, and walnuts are rich sources of ellagic acid.
– Ferulic acid: Ferulic acid is another antioxidant that increases UGT enzymes. Foods like broccoli, carrots, parsnip, olives, berries, and roasted coffee are rich in ferulic acid.
Summary
1. The phase 2 detoxification stage is called the conjugation phase. The toxins transformed in phase 1 are made “less dangerous” to the body in phase 2.
2.There are six pathways in this phase 2 detoxification. – Glutathione Conjugation, Amino Acid Conjugation, Methylation, Sulfonation, Acetylation, and Glucuronidation.
3. The glutathione conjugation pathway makes use of Glutathione S-transferase (GSTs) enzymes to make toxins water-soluble and less active.
4. The amino acid conjugation pathway makes use of amino acids to combine with toxins and makes them easier to send out of the body.
5. The Methylation pathway adds a methyl group to the toxins and makes them biologically less active.
6. The Sulfonation pathway attaches sulfates to toxins to neutralize them.
7. In the Acetylation pathway, the N-terminal acetyltransferases (NATs) enzymes are used to remove different carcinogens that enter the body through food.
8. The glucuronidation pathway is one of the most important phase 2 detoxification pathways. This uses UDP-glucuronosyltransferases (UGTs) enzymes to remove a wide range of toxins from the body.
