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One of the most important functions our body performs is detoxification. This physiological process can be either facilitated or hindered by various influences including our own genetic predispositions. In this blog, I would like to introduce some of the genetic variants to look out for if you’re interested in learning more about the efficiency of your own metabolic detoxification system. Keep reading to learn more. Please note, this information is complex but fascinating!
Metabolic detoxification is the process by which our body excretes toxins which have accumulated from either endogenous or exogenous sources. This activity takes place mainly in the liver where there is a three-phase process. Phase I involves enzymes in the liver which break down xenobiotics, steroid hormones, and pharmaceuticals into water soluble molecules. Interestingly, these molecules temporarily become more toxic as they wait for excretion, and, if not appropriately processed, can further damage the body. This leads us to the important Phase II process, where these highly toxic molecules are conjugated to be easily removed from the body. Phase III is the final phase which eliminates these water-soluble toxins through the output of urine and stool.
By understanding this process, one can further understand the importance of having each of these phases working at optimal levels to avoid a back log at any one point, the consequences of which can range from brain fog, fatigue, and skin issues to more severe conditions such as cancer.
While there are many variables which can contribute to poor detoxification, including nutrient deficiencies, in this post, I want to highlight the genetic variants that are most common, and how to support your system if you have any of them.
Single nucleotide polymorphisms (SNPs), the most common type of genetic variation, are located within the genes of Phase I and II detoxification can affect the function of the detox enzymes that are integral to this important physiological process. Along with age, sex, nutrition, and lifestyle, SNPs play an important role in biotransformation. At this time, only a few genetic variants or SNPs have been validated in clinical trials. These SNPs are CYP and SOD2. There are others, but the research is nascent and not robust enough to give too much importance to at this time.
Cytochrome P450 enzymes are located inside the liver cells and are involved in the process of detoxification of Phase I, the conversion of toxic fat-soluble compounds into even more harmful water-soluble chemicals. If CYP1A variants are present, the liver may have difficulty dealing with the resulting free radicals during this phase of detoxification. Low CYP1A activity may result in the decreased clearance of toxins and a higher risk of certain cancers (Aronica et al., 2022). The consequences of low CYP1A include increased inflammation and lower ability to rid the body of harmful toxins. Alternatively, if there is an increased CYP1A activity in Phase I, but a slow Phase II clearance, this may result in an equally dangerous accumulation of highly toxic intermediates, which can be more dangerous than the original toxins and can cause increased oxidative damage and cancer risk.
Glutathione S- transferases mu 1 (GSTM1) and theta 1 (GSTT1) are two of the three glutathione transferase genes that encode Phase II enzymes. Individuals with two allele copies of these genes may experience a faster excretion of the “good for you” nutrients found in cruciferous vegetables, the Sulphur based nutrients that are vital to this Phase II step. The result of a faster excretion does not allow individuals the time to have the “food as medicine” effect on the body. This means these people may need to consume more broccoli, cauliflower, and kale to benefit from the nutrients.
Individuals with 2 copies of these genes are more likely to remove toxins from the liver and more likely to recover from infections. They are also able to handle higher amounts of alcohol and medications. Those with 1 copy of the allele have an average ability to remove toxins and have normal tolerance to alcohol. Individuals without any copies are at a sub-optimal level and have a harder time recovering from viral infections and have a lower tolerance to alcohol and medications. All this to say, the latter will want to take particular care in eating clean foods and ensuring a toxin-free environment.
Superoxide Dismutase 2 (SOD2) genes control the first part of the SOD pathway and are responsible for the conversion of free radical superoxide into hydrogen peroxide, which is then turned into water and oxygen in Phase II. When functioning well, this enzyme is protective against oxidative stress, inflammation, and radiation induced damage to DNA. Individuals with the desirable allele versions of CT have normal function of these enzymes. Those with a slower conversion, the TT alleles, are stuck with the oxidants remaining in the body for longer causing faster aging. This may look like premature greying hair, rapid aging, or slower recuperation from exercise or injury.
These are just a selection of SNPs related to the efficiency or lack thereof in our body’s detoxification system. Because we are all so unique, the feedback from genetic testing, although still in its infancy, can guide clinicians in helping people looking to optimize health. Should your Phase I detoxification be happening too fast or too slow for, then know there are indeed tips and tricks that you can implement to help you optimize your health.
Check with a trained healthcare practitioner. With this information, we are more likely able to guide you on a bio-individual level to gain optimal health.
Aronica, L., Ordovas, J.M., Volkov, A., Lamb, J.J., Stone, P.M., Minich, D., Leary, M., Class, M., Metti, D., Larson, I.A. and Contractor, N. (2022). Genetic biomarkers of metabolic detoxification for personalized lifestyle medicine. Nutrients, 14(4), 768.
