The human body has a natural detoxification system that helps to remove toxins from the body. The liver, kidneys, digestive tract, lymphatic system, respiratory system, and skin all play a role in this process. By following healthy lifestyle habits, such as eating a healthy diet, drinking plenty of water, and getting regular exercise, you can support your body’s natural detoxification system and help to keep your body healthy.
How the Detoxification System Works
Toxins present in our bodies come from various sources. Some enter from the external environment, while others are produced as a result of normal metabolic processes within the body. The primary exogenous sources include the air we breathe, the food and water we consume, and pharmaceutical drugs. Statistically, over 75,000 synthetic chemicals, including medications, carcinogenic substances, pesticides, herbicides, exhaust gases, and more, impact the human body in the modern world. All of these substances pass through the body’s detoxification system.
Products formed as a result of digestion, energy metabolism, tissue regeneration, and hormone transformations, as well as by-products of microbial activity, constitute the endogenous pool of toxins. Up to 90% of the substances produced within the body require detoxification. These include neurotransmitters and hormones, eicosanoids, fatty acids, and retinoids.
Throughout the course of phylogenesis, a system has evolved that is responsible for the transformation and elimination of potentially harmful products, thereby ensuring the chemical resistance and stability of the body’s internal environment.
The detoxification system is a coordinated effort of several systems working together:
- The immune system of the blood: proteins and formed elements;
- The cleansing system of the liver;
- The excretory organ system: gastrointestinal tract, kidneys, lungs, and skin. During this process, toxic substances of exogenous and endogenous origins (xenobiotics) are neutralized. The transformation or biotransformation process of substances is influenced not only by the type of toxicants but also by individual human characteristics. These include age, gender, the presence of concomitant diseases and deficiency states, genetic predisposition, dietary preferences, environmental factors (home environment and professional factors), and medications taken.
Enzymes involved in biotransformation reactions are found in many body tissues but are primarily concentrated in the liver, which serves as the main detoxifying organ. Other tissues include the kidneys, lungs, intestines, and skin.
Neutralization and removal of xenobiotics in the body occur in several stages:
Stage 1 – Neutralization of the Xenobiotic
In this stage, the liver converts xenobiotics into water-soluble compounds with lower molecular weights. These substances are easier to excrete from the body by the excretory organs compared to the original substances.
Liver metabolism occurs in two phases involving enzymes:
Phase I – Hydroxylation Phase
Phase I enzymes neutralize chemical substances, transforming them into intermediate compounds, which are then processed by Phase II enzymes.
The enzyme system of Phase I primarily consists of the supergene family of cytochrome P450 (CYP or CYP450). “P” stands for pigment and “450” represents the wavelength of light absorption. Phase I is characterized by a group of enzymes comprising 50–100 cytochrome enzymes. Such a large variety arises because the body encounters a vast number of toxins. In addition to detoxification, cytochromes play a role in the synthesis processes of steroids, cholesterol, and vitamin D.
Phase I introduces or reveals a reactive group of the toxin, making it more polar but not entirely water-soluble. The emerging intermediate toxins can be chemically active (reactive intermediate metabolites and/or active forms of oxygen) and, hence, more toxic. Phase I reactions consist of oxidation, reduction, dehalogenation, and hydrolysis. All these reactions involve oxygen.
The activity of cytochrome enzymes may vary due to genetic polymorphisms. From a clinical perspective, these differences can have serious implications when prescribing pharmaceutical drugs, biological and dietary supplements.
Most toxins need to undergo the second phase for their structure to be made available for excretion through urine or bile.
Phase II – Conjugation and Synthesis Reaction
Detoxification Phase II includes six types of reactions:
- Glutathione conjugation;
- Amino acid conjugation;
- Glucuronidation. All these reactions require ATP energy and cofactors for proper functioning
Stage 2 – Excretion of Toxins from the Body
Toxins are excreted from the body through the kidneys, liver, stomach, intestines, lungs, sweat glands, and salivary glands.
Regulation of Detoxification
The activity of enzymes involved in detoxification is influenced by a range of factors, including genetics, diet, environmental toxins, medications, and nutritional status.
Some substances can upregulate Phase I enzymes without a corresponding increase in the activation of Phase II enzymes. When Phase I enzymes are activated or induced without an increase in Phase II activity, oxidative stress can increase because the intermediate metabolites may be more toxic than the original compound that activated Phase I enzymes. An example of this is the polycyclic hydrocarbons from cigarette smoke, which induce CYP1A2. Another example is the drug phenobarbital, which induces CYP2B6.
Substances that induce Phase I include:
- Medications: phenobarbital, steroids, sulfonamides; nicotine, alcohol;
- Foods: broccoli, high-protein diet;
- Environmental toxins: exhaust fumes, paint vapors, dioxins, pesticides; meat cooked over coals;
- Nutrients: see list below.
- Glutathione Conjugation: glutathione, vitamin B6, acetylcysteine. Family of inducers: brassica, dill, cumin;
- Amino Acid Conjugation: glycine. Inducers: glycine;
- Methylation: S-adenosylmethionine. Inducers: lipotropic nutrients – choline, methionine, betaine, folic acid, vitamin B12;
- Sulfation: cysteine, methionine, molybdenum. Inducers: cysteine, methionine, taurine;
- Acetylation: acetyl-CoA, vitamin B5;
- Glucuronidation: glucuronic acid. Inducers: fish oil.
The Brassica family (broccoli, common and Brussels sprouts) stimulates Phase I and Phase II simultaneously.
Enzyme systems of Phase I and Phase II can be inhibited by several mechanisms, including medications, food, nutrient deficiencies, and herbal preparations. For example, grapefruit inhibits CYP3A4, suppressing detoxification.
- Medications: benzodiazepines, chloramphenicol, teturam, silymarin, antihistamines, gastric acid secretion blockers;
- Foods: grapefruit (naringenin), curcumin (also stimulates Phase II);
- Gut dysbiosis.
Substances that inhibit Phase II include:
- Glutathione Conjugation: Inhibitors — deficiency of selenium, vitamin B12, zinc, and glutathione;
- Amino Acid Conjugation: Inhibitors — low-protein diet;
- Methylation: S-adenosylmethionine. Inhibitors — deficiency of vitamin B12 or folic acid;
- Sulfation: Inhibitors — NSAIDs, molybdenum deficiency, tartrazine (a yellow food dye);
- Acetylation: Inhibitors — deficiency of vitamins B2, B5, or C;
- Glucuronidation: Inhibitors — probenecid, aspirin.
The detoxification process is extremely complex. The interaction between Phase I and Phase II, as well as the biochemical uniqueness of an individual, are the most significant factors when assessing detoxification ability. Optimal health requires a balance between all phases of the process, as well as the proper functioning of the gastrointestinal tract.