Detoxification rate: what it depends on and whether it can be sped up

The body’s ability to metabolize a given compound is not determined by a single characteristic: it is the sum of processes occurring at different stages of biotransformation (the chemical conversion of compounds in the body). For one substance, the critical step may be oxidation by a specific enzyme; for another, subsequent conjugation (the attachment of another molecule that makes excretion easier), transport, or excretion of the metabolite. 

Genetic variants can change the activity or expression of enzymes and transporters, but their function depends on the substrate, the tissue, and the regulatory environment. These same processes are also influenced by diet, medications, age, hormonal status, and physiological state (Zanger & Schwab, Pharmacology & Therapeutics, 2013). Consequently, the same genetic feature can have different significance depending on the metabolic context.

So the question of an individual detoxification rate needs clarification: which compound the body is metabolizing, which pathway it engages, and which step of that pathway determines the final result.

What detoxification means in biology

Foreign compounds — medications, food additives (preservatives, dyes, and other components of processed foods), household chemicals, air pollutants — are eliminated from the body in a modified form after being transformed by enzymes. 

Such foreign compounds are called xenobiotics. Most of them are fat-soluble. The kidneys mainly excrete water-soluble compounds, so fat-soluble molecules without chemical modification would simply return to the bloodstream. Metabolic transformations make xenobiotics polar and therefore suitable for elimination by the liver, kidneys, or intestine (Almazroo et al., Clinics in Liver Disease, 2017).

The body can transform and eliminate xenobiotics thanks to enzymes that also take part in the metabolism of its own compounds — steroid hormones, bile acids, and products of fat metabolism. These enzymes can act on a variety of molecules, so they also help process substances that enter from outside (Hossam Abdelmonem et al., Biomedicines, 2024).

Phases of xenobiotic transformation

Xenobiotic transformation involves three phases, which do not always occur sequentially: functionalization, conjugation, and transport.

Phase I: functionalization (oxidation, reduction, and hydrolysis)

The task of this phase is to introduce or expose a chemical group to which a conjugating molecule will then attach. The main enzymes here are the cytochromes P450. In the human genome they are encoded by 57 functional genes in 18 families (Hossam Abdelmonem et al., Biomedicines, 2024), but about a dozen enzymes from the CYP1, CYP2, and CYP3 families are responsible for the biotransformation of most xenobiotics (Zanger & Schwab, Pharmacology & Therapeutics, 2013).

Phase II: conjugation

Phase II enzymes attach various groups to the molecule, including glucuronic acid, sulfate, glutathione, and acetyl or methyl groups, which makes the molecule more polar, that is, more soluble in water (Almazroo et al., Clinics in Liver Disease, 2017).

Phase III: transport

Transport proteins move the conjugate out of the cell into bile, urine, or feces (Almazroo et al., Clinics in Liver Disease, 2017).

Advertising for detox products describes liver detoxification as two phases: in the first, the toxin is transformed; in the second, it is neutralized. The third phase — transport, without which the conjugate will not leave the cell — is not mentioned by marketing. In addition, this scheme fails to account for two more things: 

1. Some compounds go straight to conjugation, bypassing phase I

2. Oxidation does not always make a molecule safer: some intermediate products of phase I are more reactive than the original substance and can bind to proteins and DNA if conjugation does not manage to intercept them (Almazroo et al., Clinics in Liver Disease, 2017).

Hence the misconception that phase I can be sped up for more effective body cleansing. But an accelerated phase I without matching phase II capacity raises the risk to the body rather than protecting it.

Genetic variants of biotransformation enzymes

For some cytochromes P450, the difference in activity between people is so pronounced that it has its own classification: phenotypes ranging from poor to ultrarapid metabolism. It is described in greatest detail for the CYP2D6 gene (cytochrome P450 family 2 subfamily D member 6) (Zanger & Schwab, Pharmacology & Therapeutics, 2013). The fastest of these phenotypes, ultrarapid metabolism, usually arises not from a change in the enzyme itself but from gene duplication — a person has several functional copies instead of one, and the enzyme is produced in excess (Zanger & Schwab, Pharmacology & Therapeutics, 2013).

Single nucleotide polymorphism (SNP) rs1800566 in the NQO1 gene (NAD(P)H quinone dehydrogenase 1) reduces the activity of the corresponding enzyme. 

CYP2D6 and NQO1 act in different enzyme systems: the former mainly in phase I oxidative metabolism, the latter in quinone reduction. The activity of one is unrelated to the activity of the other. Each enzyme system processes its own range of molecules, and a genetic variant shifts precisely that narrower processing — not metabolism as a whole.

What is actually known about speeding up detoxification

Enzyme systems can indeed be influenced from outside. But an effect on a specific enzyme is not the same as a proven benefit of a cleanse for the body. The two claims are often confused.

In a 12-week randomized study among residents of a region with high air pollution, a broccoli sprout beverage containing glucoraphanin and sulforaphane increased the excretion of glutathione conjugates of benzene by 61% and of acrolein by 23% (Egner et al., Cancer Prevention Research, 2014). 

The data from existing studies do not confirm a benefit of detox diets either for eliminating toxins or for weight control (Klein & Kiat, Journal of Human Nutrition and Dietetics, 2015).

For more on why the same diet works differently for different people, see the article Why the same diet gives different results in different people.

Genetic context for specific substances

Genetic variants of enzymes matter primarily where a specific substance and the specific enzyme that processes it are known.

The broccoli sprout beverage study found an effect of the GSTT1 genotype (glutathione S-transferase theta 1) on the excretion of benzene — an air pollutant that participants inhaled regardless of whether they took part in the study (Egner et al., Cancer Prevention Research, 2014). In carriers of the functional allele, benzene mercapturate was excreted more actively than in people with the null genotype, and this effect persisted regardless of whether they received the broccoli sprout beverage or placebo.

The effect of a genotype is limited to the substrates the specific enzyme works with. For other substances, the same variant will have no predictive value. In addition, a genetic variant shows an innate property of the enzyme system, not the current state of the body: it does not replace laboratory markers of liver or kidney function.

A broader view of the relationship between metabolism, digestion, and genetics can be found in the article Metabolism, digestion, and genetics: what shapes the response to food.

The Apixmed Prism genetic test analyzes genetic variants associated with biotransformation enzyme systems — another layer of personalized context alongside laboratory tests and lifestyle. Laboratory tests show the body’s current functional state for specific markers. Genetic data show which innate enzyme differences a person lives with all the time.

Explore your genetic profile with Apixmed Prism — see your health through the lens of DNA → Genetic test “Liver, Gallbladder and Pancreas”

Knowing your own genetic variability in these systems is not a way to speed up something abstract. It is a way to understand what features of detoxification your body has and how it processes the specific substances you encounter every day.

The results of a genetic test are not a diagnosis and not a substitute for a consultation with a doctor. The Apixmed Prism report provides genetic context that complements examination results and helps you make decisions together with your doctor.

Sources

1. Almazroo O.A., Miah M.K., Venkataramanan R. (2017). Drug metabolism in the liver. Clinics in Liver Disease, 21(1), 1–20. https://doi.org/10.1016/j.cld.2016.08.001 

2. Hossam Abdelmonem B., Abdelaal N.M., Anwer E.K.E., Rashwan A.A., Hussein M.A., Ahmed Y.F., Khashana R., Hanna M.M., Abdelnaser A. (2024). Decoding the role of CYP450 enzymes in metabolism and disease: a comprehensive review. Biomedicines, 12(7), 1467. https://doi.org/10.3390/biomedicines12071467 

3. Zanger U.M., Schwab M. (2013). Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics, 138(1), 103–141. https://doi.org/10.1016/j.pharmthera.2012.12.007 

4. Zhou H., Wan H., Zhu L., Mi Y. (2022). Research on the effects of rs1800566 C/T polymorphism of NAD(P)H quinone oxidoreductase 1 gene on cancer risk involves analysis of 43,736 cancer cases and 56,173 controls. Frontiers in Oncology, 12, 980897. https://doi.org/10.3389/fonc.2022.980897 

5. Egner P.A., Chen J.-G., Zarth A.T., Ng D.K., Wang J.-B., Kensler K.H., Jacobson L.P., Muñoz A., Johnson J.L., Groopman J.D., Fahey J.W., Talalay P., Zhu J., Chen T.-Y., Qian G.-S., Carmella S.G., Hecht S.S., Kensler T.W. (2014). Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. Cancer Prevention Research, 7(8), 813–823. https://doi.org/10.1158/1940-6207.CAPR-14-0103 

6. Klein A.V., Kiat H. (2015). Detox diets for toxin elimination and weight management: a critical review of the evidence. Journal of Human Nutrition and Dietetics, 28(6), 675–686. https://doi.org/10.1111/jhn.12286