Detox

What is detox?

Millions of years ago, our ancestors did not know the words "detox" or "toxins", but their bodies encountered plant poisons, campfire smoke, and metabolic waste products daily. To survive, nature developed a powerful detoxification system — a complex biochemical process hidden within our cells. Today, this mechanism works the same way, but the load on it has increased hundreds of times. Industrial pollutants, medications, synthetic additives, heavy metals, plastic, pesticides, herbicides, various household detergents, and many other compounds have been added to natural toxins such as mycotoxins and phytotoxins. Every day our body accepts this invisible challenge, activating defense mechanisms. But how effectively? The answer lies primarily in our genes. Genetic features determine the speed and efficiency of liver enzymes, as well as the kidneys, intestines, skin, and lungs, which are responsible for neutralizing and eliminating harmful substances. They set the rhythm for our detoxification system, influencing resilience to toxic load and overall health.

More about Phase I detoxification

The detoxification process in the body is conventionally divided into three sequential stages, each performing its key function: toxin transformation, modification for safe excretion, and final elimination from the body.

Phase I of metabolic detoxification is the first stage of toxin biotransformation, which helps the body prepare harmful substances for further neutralization and excretion. The main task of this stage is to change the structure of toxic compounds, making them more reactive and water-soluble. This is important because many harmful substances, such as pesticides, drugs, environmental pollutants, steroid hormones, and fat-soluble toxins, are initially insoluble in water and cannot be easily eliminated from the body.

Key reactions of Phase I:

• oxidation (adding oxygen atoms, making the molecule more reactive);
• reduction (changing the compound structure to facilitate further transformations);
• hydrolysis (molecule splitting involving water);
• cyclization (converting linear molecules into cyclic ones, which can affect their biological activity and prepare for Phase II).

The main genes encoding Phase I enzymes belong to the CYP450 family. These genes ensure the synthesis of heme-containing cytochrome P450 enzymes, which are monooxygenases involved in drug metabolism, xenobiotic detoxification, and biosynthesis of various biologically active molecules, including steroids, bile acids, and fatty acids. CYP450 enzymes are located primarily in the endoplasmic reticulum and mitochondria. The CYP450 family includes many subfamilies, such as CYP1, CYP2, CYP3, etc. In addition to them, other enzyme systems participate in Phase I redox reactions: flavin-containing monooxygenases (FMO), monoamine oxidases (MAO), and epoxide hydrolases. Our report provides a detailed description of all participants in the first phase of detoxification (as well as second-phase enzymes) and covers a wide selection of genetic polymorphisms (rs-markers) associated with the activity of detoxification enzyme systems.

Phase II detoxification

The second phase of detoxification is a process in which special conjugase enzymes attach water-soluble groups to toxins, making them ready for excretion from the body. Unlike first-phase enzymes, which break down or alter substances, second-phase enzymes bind them to safe compounds, helping the body get rid of toxins faster.

Key pathways of Phase II are glucuronidation, sulfation, glutathionylation, acetylation, methylation, and conjugation with amino acids (e.g., glycine). These processes convert lipophilic toxins and drugs into more polar forms, facilitating their excretion via bile or urine.

Phase II detoxification enzymes not only neutralize toxins but also interact with each other, creating a flexible body defense system. Different pathways can compensate for each other, and under high load, one mechanism switches to another. However, with a deficiency of cofactors or a combination of unfavorable genetic factors, protection weakens, increasing the risk of toxic effects.

Important! It should be noted that not only a decrease in the activity of Phase I enzymes (specifically cytochrome P450) has negative consequences, but increased activity can also potentially lead to increased toxicity of substances. Intermediate metabolites and free radicals are formed during oxidation, which can damage cells if not neutralized in time. When Phase II (conjugation) does not work effectively enough, the resulting reactive compounds can increase the load on the body, causing oxidative stress. Thus, the balance between Phase I and II of detoxification is critical: Phase I prepares toxins, but their final neutralization occurs only in Phase II. If the first phase works too fast and the second cannot cope with the load, an excess of intermediate toxic compounds may accumulate in the body. Optimal detox depends on the coordinated work of both stages, and genetic features can play a decisive role in the effectiveness of these processes.