We all know those people who seem to get away with anything — smoking an entire lifetime and not developing a significant illness because of it — and those who may get a headache from walking down the laundry detergent aisle at the grocery store. Some need the high end of medication doses to achieve a benefit, while others require the smallest dose, even at the same body size. What makes the difference?
One significant factor is our genetics, specifically our genetics in detoxification pathways. Certain genetic variants lead to processes that are either more or less active than normal. In the modern age, where we are continually exposed to high levels of environmental toxins, this may cause difficulty in dealing with this toxic load.
Generally, detoxification is considered in three phases:
Phase 1: This phase occurs in the liver, where most environmental toxins and many drugs are transformed into an intermediate. In some cases, the intermediate is more toxic than the original. So, a build-up of these intermediates from a fast Phase 1 and a slow Phase 2 detoxification can cause problems.
Phase 2: During this phase, water-soluble groups are added to the modified chemicals so they can be more readily removed from the body.
Phase 3: The goal of this phase is the final removal from the body, i.e., in feces or urine, also to some degree in the breath, sweat, etc.
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What is The DetoxiGenomic Profile from Genova Diagnostics?
We are now in a time when medicine can be more personalized to the specific genetic makeup of an individual. The DetoxiGenomics Profile by Genova Diagnostics is a genetic test that evaluates over 20 locations of relevant genetic variants (polymorphisms/SNPs) related to phase 1 and phase 2 liver detoxification pathways. Clinically, these are linked with an increased risk of impaired liver detoxification of both environmental toxins and drugs.
While everyone has SNPs, these particular genetic variants predispose one to certain chronic diseases as a result of poor detoxification as well as adverse drug reactions.
Phase 1 Detoxification
Phase 1 detoxification in the liver is evaluated by looking for SNPs in the following Cytochrome p450 pathways:
- CYP1A1 – is important in processing many carcinogens, including combustion byproducts. Also, it's involved in the breakdown of estrogens into forms that increase oxidative stress and cancer formation. This can be linked to increased rates of female cancers.
- CYP2A6 – affects the risk of smoking-related behaviors and cancers. It is able to activate several procarcinogens into carcinogens, including tobacco-related nitrosamines and the aflatoxins produced by certain molds. In this case, the presence of a non-functional polymorphism actually reduces cancer risk even in the presence of smoking or heavy aflatoxin exposure because the procarcinogens are not transformed into carcinogens.
- CYP2C9 – affects the metabolism of about 15-20% of drugs undergoing Phase 1 reactions. It also affects susceptibility to heart disease.
- CYP3A4 – is the most expressed CYP in liver cells. It can be inhibited by eating grapefruit. It is involved in the metabolism of many drugs and can lead to decreased drug effectiveness. Certain polymorphisms may be linked to increased cancer risk, especially prostate cancer in African populations.
- CYP1B1– activates polycystic aromatic hydrocarbons (PAHs) from environmental pollution and tobacco smoke into carcinogenic forms. It processes estrogens. Some polymorphisms are associated with bladder, kidney, endometrial, prostate, and laryngeal cancers, likely due to the increasing carcinogenicity of PAHs. It also metabolizes theophylline from cacao and caffeine. Some polymorphisms are associated with an increased risk of type 2 diabetes.
- CYP2D6 – affects the metabolism of about 20-25% of drugs. It metabolizes neurotransmitters and neurosteroids, such as serotonin. Parkinson's disease risk is related to the speed of function here, with the ultrafast metabolizer having reduced risk and the slow metabolizer having increased risk.
- CYP1C19 – affects the metabolism of many drugs and can dramatically influence the speed of drug clearance. It metabolizes estrogen, progesterone, and testosterone. It is inhibited by CBD.
These enzymes are involved in the first stage of liver detoxification from all environmental toxins (pesticides, solvents, pollutants, medications, etc.) and many of the internally-produced waste products in the body, including steroid hormones.
Phase 2 Detoxification
Phase 2 detoxification and elimination are evaluated with the following SNPs:
- Methylation (COMT) — May predispose individuals to anxiety, ADHD, alcoholism, and rapid cycling bipolar through impaired metabolism of catecholamine neurotransmitters.
- Acetylation (NAT1, NAT2) — Essential for removing many environmental toxins, including tobacco smoke. SNPs may increase the risk of certain cancers.
- Glutathione Conjugation (GSTM1, GSTT1, GSTP1) — Detoxifies many water-soluble toxins, such as solvents, pesticides, and some heavy metals. Certain SNPs can increase the risk of certain cancers and fatigue.
- Oxidative Protection (Superoxide dismutase SOD1, SOD2) — Mutations here may impair the ability to fight free radical damage and lead to a higher risk of developing neurodegenerative disorders.
Which Patients is the DetoxiGenomic Profile best used for?
The DetoxiGenomic Profile is most useful for patients with illnesses that may be significantly driven by exposure to toxins or poor processing of toxins. It may be especially useful for patients with a strong family history of such diseases to know vulnerabilities and adopt lifestyle changes that will support optimal prevention. It is also worth considering in cases that appear less responsive than expected to normal treatments.
Some of these conditions include:
- Cancer
- Medication sensitivities or poor response
- Neurodegenerative disorders
- Chemical sensitivities
- Illness after mold or chemical exposure
- High levels of heavy metals on testing
- Hormone-related illnesses
- Mood disorders
- Asthma or other lung problems
- Cardiovascular disease
- Inflammatory conditions
- Fibromyalgia
How to Use the DetoxiGenomic Profile from Genova Diagnostics in Clinic
It is useful to keep in mind that, in most cases, lifestyle factors can still influence health outcomes, especially when guided by the knowledge of one's personal vulnerabilities. Typically, genetics does not equal destiny. This is why this kind of testing and personalized approach can be so helpful.
The sample for the DetoxiGenomic Profile is simple to collect and can be collected at home following some simple guidelines provided with the test kit. Once mailed to the lab, you can expect around a 21-day processing time until results are available.
The results report will show any variants (SNPs) in the tested genetic pathways. It will also suggest actions based on those results.
For individuals with SNPs affecting the Phase 1 enzymes, minimizing toxin exposures and possibly modifying the dosage of certain medications would be helpful.
Individuals with SNPs in Phase 2 enzymes may benefit from focusing on antioxidants in the diet and possibly the addition of broad-spectrum supplementation.
The following nutrients may help to induce internal antioxidant systems by increasing NAD+ levels:
- Niacin (high in many whole animal and plant foods)
- Quercetin (high in shallots, onions, apples, grapefruit, cacao, red wine, and buckwheat, among others)
- Luteolin (high in artichoke, rosemary, oregano, thyme, and extra virgin olive oil, among others)
- Apigenin (high in extra virgin olive oil, beer, sage, oregano, marjoram, rosemary, and pistachio nuts, among others)
- Kuromanin (high in blackberries, elderberries, black currants, black grapes, raspberries, sweet cherries, pomegranate, black olives, and black beans, among others)
And these additional nutrients also have antioxidant effects:
- Omega 3 Fatty acids, such as from fish oil or hemp/flax/chia seeds
- Lycopene
- Curcumin
- Cruciferous vegetables
- Garlic
- Ginger
- Resveratrol
- Coffee
- Isoflavones
Specific SNPs may suggest that a person is at increased risk of certain illnesses. Even if lifestyle interventions are followed, it may make sense to be on the more frequent side of screening for these conditions in those with SNPs that make them more vulnerable.
Labs to Consider for Further Refinement of Treatments
If the presence of SNPs suggests proceeding with the addition of antioxidants, it may be useful to also test for individualized reactions to specific antioxidants, as can be done with the Redox/Antioxidant Protection Assay.
Also, given the essential nature of adequate nutrition for detoxification, certain situations may benefit from also testing micronutrient status.
Labs to Consider Monitoring
When implementing a therapeutic program that can modify genetic expression, there may be some labs that can be particularly helpful in monitoring the success and progress of these treatments: Some examples would include the following:
Oxidative Stress Analysis
Oxidative Stress Analysis – This would give additional insight into the antioxidant status and suggest whether efforts at lifestyle and nutrient interventions to target oxidative stress are adequate or if more intensive measures would be potentially beneficial.
Heavy Metals
Heavy Metals – Levels of heavy metals may be elevated due to poor detoxification capacity. If so, it should be monitored throughout treatment to gauge progress and suggest if alterations to treatment may be helpful.
Urine Mycotoxins
Urine Mycotoxins – This can indicate an increased body accumulation of mold toxins, which may be related to certain detoxification challenges. Monitoring early and later in treatment can be useful information to help direct specific detoxification support strategies.
Summary
The information in the DetoxiGenomics Profile can be very helpful for a person trying to determine what to prioritize regarding a healthy lifestyle and supplementation. In particular, given the ubiquitous exposure to environmental toxins in the present world, optimizing detox pathways with genetic weaknesses can help maximize one's genetic potential for detoxification.
This can be especially clinically useful for people with a strong family or personal history of illnesses that are strongly correlated with toxin exposure. As we learn more, this list grows. Most chronic illnesses at this time do appear to be worsened by chemical exposure. Another finding that may suggest this as a potentially useful route would be high levels of metals, mycotoxins, or other environmental toxins found on testing and correlating to clinical illness.
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