8.1) Detoxification
Detoxification is the removal of toxic substances from the body. It is what your body does to neutralize, transform or get rid of unwanted materials or toxins. There are two major detoxification pathways inside the liver cells; Phase 1 and Phase 2 detoxification pathways. Phase 1 is primarily responsible for converting toxic substances into less harmful chemicals while Phase 2 works at turning drugs, hormones and various toxins into water soluble substances which can be excreted from the body.
This report contains information about your body’s ability to rid itself of these environmental toxins and free radicals, both of which can be damaging to your tissues. Based on your genetic information, you will know if you have a higher need to support detoxification.
While you cannot completely eliminate harmful substances from entering or being created in your body, you can make choices to decrease your exposure to them:
- Lighten your toxin load.
- Eliminate or decrease your consumption of alcohol, coffee, cigarettes, refined sugars and saturated fats, all of which can act as toxins in the body and are obstacles to your healing process.
- Minimize use of chemical-based household cleaners and personal health care products (cleansers, shampoos, deodorants and toothpastes), and substitute natural alternatives.
- Avoid exposing your body to dangerous chemicals such as herbicides, pesticides, hormones, and unnecessary antibiotics.
- Help your body to clear free radicals using foods with anti-oxidant properties.
8.1.1 Detoxification Phase 1 - Activation
How efficiently your body manages oxidation
Detoxification is the removal of toxic substances and impurities from the body, it is mainly carried out by the liver. In phase 1, toxicants are transformed to more easily eliminated forms through oxidation, reduction, hydrolysis, hydration and dehalogenation reactions.
Toxic substances, either molecules arising from metabolism (diet), or external factors (environmental), are processed by the liver on a continual basis, primarily through the Cytochrome P450 enzymes. CYP450 enzymes initiate the phase 1 biotransformation, oxidizing these compounds into forms which are easily eliminated by the body.
CYP450s are the major oxidative enzymes and the most actively studied in Phase 1. They are responsible for metabolizing the large majority of therapeutic drugs and other foreign compounds. There are numerous CYP450 isozymes that are tested for in this panel. Genetic variants in CYP450 can have a functional impact on the efficiency and side effects of drugs.
Detoxification compounds produced naturally through the body include: cholesterol, fat soluble vitamins, sterols (including bile acids), prostaglandins, thromboxane A2, as well as both products of microbial metabolism and bacterial produced lipopolysaccharides. Chemicals, drugs, naturally occurring toxins or synthetic chemicals in food, food additives, plasticizers, organic solvents, drugs, pesticides, along with industrial waste contaminates are detoxification compounds found in the body from outside sources.
Individuals with variants in genes affecting Phase 1 may be at higher risk for toxic overload as a result of damaging free radicals being produced at high levels. If these reactive molecules are not further metabolized by Phase 2 detoxification, they may cause cell damage.
If you have variations in this panel, you may want to consider the following to improve your health:
- Eat a diet rich in antioxidants.
- Eat non-starchy vegetables, including brassica or crucifer vegetables (broccoli, brussels sprouts, cauliflower, rutabaga, turnips, kohlrabi, cabbage, collard greens, kale and mustard seed) that provide a wide variety of phytochemicals that impact detoxification and biotransformation.
- Include citrus such as tangerines and oranges (but not grapefruit) as well as vitamin C rich foods such as strawberries and bell peppers.
- Include high-quality, absorbable protein in your diet (eggs & whey protein). It is an important source of amino acids for the production of the phase 1 CYP enzymes.
- Consider herbs such as milk thistle, sassafras, caraway and dill.
- Consider a lipotropic to support the liver such as cysteine, methionine, choline and inositol.
- Consider supplementing with vitamin B, C, magnesium and iron.
- Decrease exposure to xenobiotics (drugs, pesticides, or carcinogens) and xenoestrogens (chemical compounds which imitate estrogen).
Some examples of genes that have been associated with detoxification and oxidation are:
CYP1A1: Associated with enzyme activity, suspected production of 2-OH-estrogen metabolites, enzyme inducibility with exposure of toxins and risk of toxic intermediate exposure and reactive oxygen species accumulation. It has an effect on the metabolism of polycyclic aromatic hydrocarbons. Influences the susceptibility of individuals towards toxicity. Polycyclic aromatic hydrocarbons are metabolically activated by phase I enzymes into electrophilic species that have the capacity of interacting with DNA.
CYP1A2: Associated with metabolism of substrates, and risk of potentially toxic intermediate accumulation. Induction of CYP1A2 by cigarette smoking has been reported. Polycyclic aromatic hydrocarbons are believed to be responsible for the induction of CYP1A1 and CYP1A2. Cigarette smoking may increase the risk of cancer by inducing the metabolic activation of carcinogens.
CYP1B1: Associated with enzyme activity towards estrogen and production of 4-OH-estrogen metabolites with risk of tissue damage associated with high 4-OHE levels in the phase 1 metabolic pathway.
CYP3A4: Associated with enzyme expression and activity. Abundant in the liver and intestines. The enzyme metabolizes approximately 50% of marketed drugs. The consumption of grapefruit juice with drugs taken orally has been reported to inhibit intestinal CYP3A4 activity, which results in a decrease in the metabolism of many drugs. Patients with deficiency of this enzyme have variability in metabolism efficacy and increased toxicity.
8.1.2 Detoxification Phase 2 - Conjugation
How efficiently your body conjugates drugs, hormones and various toxins into water soluble substances for elimination
Glutathione S-transferases (GSTs) are a multi-gene family of enzymes that are involved in the metabolism of a wide range of compounds and are generally recognized as detoxification enzymes. GSTs detoxify dangerous substances that are foreign to the body as well as those originating from within the body. Glutathione S-transferase P1 (GSTP1) is one such Glutathione S-transferases (GST).
GSTP1 is a multifunctional enzyme involved in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes. Oxidative stress is an imbalance between reactive oxygen species and the antioxidant defense system. It is now known that oxidative stress is involved in many diseases. GSTP1 is important for cancer research because of its role in detoxifying carcinogens, activating antineoplastic prodrugs, metabolizing chemotherapeutic agents, and because of its involvement in cell cycle and cell death regulation.
If you have variation in your GSTP1 gene it may exhibit reduced detoxification ability. Variation in GSTP1 has been implicated in a decreased response to oxidative stress, for example, the response to ozone exposure or smoking. It is also associated with a poorer antioxidant capacity.
Decreased GSTP1 capacity can increase the overall toxic burden, oxidative stress, and risk of various cancers. Variation in the GSTP1 gene, leading to low efficiency, is associated with resistance to certain anticancer drugs and to the risk of developing some types of cancer. GSTP1 has been related to increased risk of bladder cancer in some studies.
If you have a variation in this panel, you may want to consider the following to improve your health:
- Eat a diet rich in colorful vegetables and fruits, cruciferous vegetables (such as cauliflower, cabbage and broccoli), onions, and garlic.
- Supplement your diet with the antioxidant vitamin E, specifically a-tocopherol, a form of vitamin E that is preferentially absorbed and accumulated in humans. If you have lower antioxidant capacity, you will derive a greater advantage from vitamin E supplementation.
- Engage in both cardio and weight training to improve glutathione conjugation.
- If you experience symptoms of liver damage, discuss supplements like acetylcysteine, and silymarin with your health care provider.
An example of a gene that has been associated with detoxification and conjugation is:
GSTP1: Catalyzes conjugation reactions to inactivate reactive metabolites or intermediates, including reactive oxygen species, and facilitates their excretion from the body.
8.1.3 Detoxification Phase 2 - Acetylation
How efficiently your body catalyzes acetylation reactions to detoxify cancer causing carcinogens
Phase 2 detoxification enzymes catalyze conjugation reactions, making dangerous metabolites (toxins) less reactive to your cellular components, more soluble in water, and easier to eliminate in the urine. N-Acetyltransferases (NATs) are phase 2 enzymes found in liver and other tissues. Two closely related NAT genes, NAT1 and NAT2, are present in humans.
NATs are involved in the detoxification and bioactivation of cancer-causing carcinogens via O- and N- acetylation. The process of acetylation is important for several chemical reactions in the body. Variation in the NAT genes modifies both the efficacy and toxicity of numerous arylamine and hydrazine drugs (found in cigarette smoke, car exhaust fumes and in some food by-products) and increases risk towards several arylamine carcinogen-related cancers such as bladder and colon. Certain variations in these genes result in a slow or rapid acetylation phenotype, altering your ability to metabolize cancer causing agents.
For example, NATs are involved in the activation and detoxification of tobacco smoke constituents. A significant interaction was found between the NAT2 slow acetylator genotype rheumatoid arthritis and bladder cancer risk particularly among cigarette smokers. If you are aware that you have variation in your NAT genes you can take preventative measures to increase your quality of life.
If you have variations in this panel, you may want to consider the following to improve your health:
- Avoid environmental toxicants such as heavy metals, persistent organic pollutants, and electromagnetic radiation.
- Optimize your gastrointestinal health, practice excellent nutrition and hydration.
- Mobilize and eliminate toxins via loss of excess fat and use of saunas, chelation therapy, and exercise.
- Monitor your stress levels, get adequate sleep and relaxation.
Some examples of genes that have been associated with detoxification and acetylation are:
NAT1: N-acetyltransferase 1 (NAT1) is expressed in human liver. It encodes a phase 2 detoxification enzyme responsible for the metabolism of arylamine compounds including pharmaceuticals and environmental carcinogens.
NAT2: The N-acetyltransferase 2 (NAT2) gene encodes phase 2 detoxification enzymes that play a central role in the metabolism of aromatic, heterocyclic amines and hydra-zines via N-acetylation and O-acetylation. Variations in NAT2, result in rapid or slow acetylation. Slow acetylation decreases enzymatic activity leading to decreased detoxification efficiency.
8.1.4 Detoxification Phase 2 - Methylation
How efficiently your body metabolizes dopamine, epinephrine (adrenalin), norepinephrine (noradrenaline), and estrogen
Catecholamine methyl-transferase (COMT) is a phase II enzyme that catalyzes the detoxification of reactive oxygen species by O-methylation. It detoxifies polycyclic aromatic hydrocarbons, which are environmental carcinogens, as well as catechol estrogens (active natural estrogen metabolites). Estrogens are often thought of as a female hormone. However, they are also present in both sexes, but in larger amounts for women. Estrogens produced by your body can become carcinogenic via formation of catechol estrogen quinones if you have decreased COMT mediated detoxification.
The COMT enzyme modulates adrenergic, noradrenergic and dopaminergic signaling. Through these neurotransmitters the COMT gene plays a role in many neurological disorders. Variation is a possible risk factor for anxiety, depression, schizophrenia, eating disorders, attention deficit hyperactivity disorder, insomnia, bipolar disorder, panic disorder, and obsessive-compulsive disorder.
Variation in the COMT gene reduces enzyme activity. If you have a variation in the COMT gene, you may wish to talk with your healthcare provider about maximizing your health.
If you have a variation in this panel, you may want to consider the following to improve your health:
- Eat foods high in antioxidants.
- Have adequate supplementation with trimethylglycine, vitamins B12, vitamin B6, and folate.
- Include GABA-promoting botanicals which can provide relief. Examples are theanine, inositol, magnesium, noni fruit, and chamomile.
- Consider nighttime magnesium glycinate and a morning vitamin B complex containing methylcobalamin, L-5MTHF, and pyridoxine-5-phosphate which may also be helpful.
- Avoid elevated homocysteine (amino acids found in your blood mostly from eating meat), amphetamines (used to treat ADHD), catechol drugs, and equine estrogens.
- Reduce risk and improve quality of life through detoxification strategies of sweating, fasting, infrared sauna, and botanical liver support such as milk thistle.
- Modulate estrogen to reduce or eliminate premenstrual syndrome by supplementing with Indole-3-carbinol, a compound found in cruciferous vegetables which has the ability to shift the ratio of estrogen metabolites. Black cohosh contains triterpene glycosides that also have estrogen modulating impacts on metabolism.
An example of a gene that has been associated with detoxification and methylation is:
COMT: Catecholamine-O-methyl transferase (COMT) degrades catecholamines such as dopamine, epinephrine, and norepinephrine.
8.1.5 Detoxification Phase 2 - Oxidative Protection
How efficiently your antioxidant enzymes can protect you against reactive oxygen species
When your oxidant defense system is healthy, it can protect you against the toxicity of reactive oxygen species. Reactive oxygen species are reactive chemical species containing oxygen, that are formed as a natural by-product of the metabolism of oxygen and have important roles in cell signaling and homeostasis. During times of environmental stress, reactive oxygen species levels can increase dramatically. This may result in significant damage to cell structures.
SOD2 is one of the major antioxidant enzymes and constitutes the first-line of defense against reactive oxygen species. The SOD2 gene maintains normal levels of reactive oxygen species in your body. Genetic variations in SOD2 can lead to an imbalance in oxidative stress. Variations may change the enzyme antioxidant capacity and subsequently lead to synergic effects induced by oxidative stress.
Cell damage induced by reactive oxygen species is involved in several pathological processes. Defects in antioxidant pathways are connected to diseases including diabetes, age-related disease, chronic obstructive pulmonary disease, and cancer.
If you have a variation in this panel, you may want to consider the following to improve your health:
- Support SOD2 and protect against oxidative stress by consuming foods rich in antioxidants such as colorful vegetables and fruits. Foods including broccoli, spinach, artichokes, berries, pecans, and turmeric are high in antioxidants.
- Include dietary sources of manganese, a cofactor for SOD2, found in chickpea, spinach, sweat potato and brown rice.
- Consider supplementation such as coenzyme Q10, alpha-lipoic acid, n-acetyl cysteine, zeaxanthin, lutein and glutathione, selenium and zinc to support antioxidant function.
- Reduced exposure to carcinogenic toxins and environmental pollutants, including alcohol, tobacco smoke, cured meats and self-care products with phthalates.
An example of a gene that has been associated with detoxification and antioxidation is:
SOD2: As a member of the iron/manganese superoxide dismutase family, this protein transforms toxic superoxide into hydrogen peroxide and diatomic oxygen. This function allows SOD2 to clear mitochondrial reactive oxygen species and confer protection against cell death. This protein plays an antiapoptotic role against oxidative stress, ionizing radiation and inflammatory cytokines.