Metabolic detoxification (detox)—or biotransformation—is a physiological function that removes toxic substances of endogenous or exogenous origin from the body. Because the function and regulation of this process varies from person to person, different people can have a different sensitivity to toxic substances and their effects on the development of a variety of diseases such as liver conditions, fertility problems, and cancer. Along with sex, age, and lifestyle, genetics play an important role in this variability.
But do we actually know which genes affect people’s detox function and need? And how may clinicians use this information to personalize lifestyle recommendations to their patients? The answers to these questions are not clear yet. While several genetic variants of detox metabolism have been identified, there is still no clarity on their clinical validity and utility, as most of these variants are based on animal studies or observational studies in humans with very limited proof from clinical studies.1
A recent study supported by Metagenics has provided more clarity on the role of genetic variants in detox metabolism and their utility to develop personalized metabolic detox programs. The researchers reviewed the medical literature to select exclusively those genetic variants shown to affect detox metabolism in the context of clinical trials. These trials assessed the effects of different foods and nutrients on detox function in people of different sex, smoking status, and metabolic health (i.e. body weight, blood sugar and insulin, lipids, etc.). Based on these criteria, only six genetic variants in genes encoding Phase I and Phase II detox enzymes showed evidence of clinical utility: CYP1A2 rs762551; CYP1B1 rs1056836; segmental deletions of GSTT1 and GSTM1; COMT rs4680-A; and insertion variants of UGTA1 (TA/-). To make this information easy to interpret and use for the clinicians, the researcher combined the selected variants into a detox polygenic risk score (PRS), a single number that captures the collective impact of all the selected genetic variants on detox function.
This means that individuals with a high detox PRS may have a higher risk of having a lower detox function and consequently have a higher need for nutritional and lifestyle support. To test this, the researchers analyzed the association between detox PRS and detox function in the participants of the Lifestyle Intervention and Functional Evaluation—Health Outcome Survey (LIFEHOUSE) study. Among the participants, those who had a higher detox PRS had a worse detox function as measured by blood levels of three key detox biomarkers (glutamyltransferase, GGT; homocysteine; and oxidized low-density lipoprotein, oxLDL).
So what lifestyle recommendations should clinicians suggest to patients who have a high detox PRS score? Individuals with a high detox PRS should avoid the consumption of charbroiled food, limit coffee to 1 cup/day and caffeine from other sources to 100 mg/day, and incorporate more cruciferous vegetables, olive oil, fish, and rosemary in their diet. These lifestyle measures have been shown to limit toxic load and enhance detox function in individuals with high detox PRS.
The findings of these studies may therefore facilitate the development of personalized metabolic detox programs that integrate genetic factors with other biological variables and lifestyle factors.
This study was published on 11 February, 2022, in the journal Nutrients.
What are the key takeaways?
- Genetic variants may affect a patient’s detox function and need
- Only a few genetic markers of metabolic detoxification have been validated in clinical trials
- Clinicians may use these genetic variants in conjunction with other biological and lifestyle factors to develop personalized metabolic detox programs
- Hodges RE et al. Modulation of metabolic detoxification pathways using foods and food-derived components: a scientific review with clinical application. J Nutr Metab. 2015;2015:760689.