Genes Associated with Detoxification
These genes affect how you process toxins, medications, and hormones. Variants don't break detox—they change how it works.
Detox is a three-phase process.
Phase I activates compounds (CYP enzymes). Phase II conjugates them for excretion (GST, NAT, UGT, SULT).Phase III transports them out. The system only works when all phases are balanced. Fast Phase I + slow Phase II = activated toxins with nowhere to go.
The genes.
Organized by phase and function.
Phase I - Activation (CYP450 Enzymes)
Phase I enzymes activate compounds, making them more water-soluble but sometimes more reactive. The CYP family is the star here.
CYP1A2
Caffeine, drugs, toxinsMetabolizes caffeine, some medications, and environmental toxins. Fast metabolizers clear caffeine quickly; slow metabolizers feel it for hours.
CYP2D6
Drug metabolismMetabolizes ~25% of all medications. Ultra-rapid, normal, intermediate, and poor metabolizer phenotypes exist.
CYP2C19
Drug metabolismMetabolizes proton pump inhibitors, antidepressants, and clopidogrel. Variants affect drug efficacy.
CYP1B1
Estrogen & toxin metabolismMetabolizes estrogens and environmental toxins. Some metabolites are more harmful than others.
CYP3A4
Major drug metabolismMetabolizes about 50% of all medications. Affected by grapefruit juice, St. John's Wort, and many drugs.
Phase II - Conjugation
Phase II enzymes attach molecules to toxins, making them water-soluble for excretion. This is often the rate-limiting step.
GSTM1
Glutathione conjugationAttaches glutathione to toxins. About 50% of people have a complete deletion (null genotype).
GSTP1
Glutathione conjugationAnother glutathione transferase. Important for clearing carcinogens and oxidative stress products.
GSTT1
Glutathione conjugationMetabolizes small reactive compounds. Null genotype common in ~20% of Caucasians, ~50% of Asians.
NAT1/NAT2
AcetylationAcetylate aromatic amines and drugs. Slow acetylators clear certain drugs and toxins slowly.
SULT1A1
SulfationAdds sulfate groups to hormones, drugs, and toxins. Important for estrogen and thyroid hormone metabolism.
UGT1A1
GlucuronidationAdds glucuronic acid for excretion. Gilbert's syndrome is a common UGT1A1 variant causing mild jaundice.
Phase III - Transport
Transporters move conjugated toxins out of cells and into bile or urine for elimination.
ABCB1 (MDR1)
Drug effluxPumps drugs and toxins out of cells. Affects drug absorption and brain penetration.
ABCC2 (MRP2)
Bile transportExports conjugated toxins into bile. Variants can affect toxin elimination.
Antioxidant Defense
Detoxification generates oxidative stress. These genes manage the fallout.
SOD2
Mitochondrial antioxidantConverts superoxide to hydrogen peroxide in mitochondria. The Ala16Val variant affects enzyme localization.
CAT
Hydrogen peroxide breakdownConverts hydrogen peroxide to water. Works downstream of SOD.
GPX1
Glutathione peroxidaseUses glutathione to neutralize peroxides. Selenium-dependent enzyme.
NQO1
Quinone detoxificationDetoxifies quinones (from benzene, cigarette smoke). *2 variant has no enzyme activity.
Sulfur Metabolism
Sulfur pathways supply glutathione and sulfate for Phase II reactions.
Converts homocysteine to cysteine (glutathione precursor). The gateway to sulfur metabolism.
SUOX
Sulfite oxidationConverts toxic sulfite to sulfate. Molybdenum is the cofactor. Sulfite sensitivity may indicate issues here.
The GST null problem.
About 50% of people are missing GSTM1 entirely. Here's why that matters—and why it's not the disaster it sounds like.
The concern
GSTM1 null means you have no GSTM1 enzyme. You can't conjugate certain toxins via this pathway. Studies show increased cancer risk with high toxin exposure + null genotype.
The context
- • Other GST enzymes (GSTP1, GSTT1) can partially compensate
- • The null genotype is ancient and common—it's not a new mutation
- • Risk only manifests with significant toxin exposure
- • Reducing exposure matters more than trying to "fix" a missing gene
The strategy
If you have GST nulls: prioritize reducing toxin exposure, support glutathione synthesis, eat cruciferous vegetables (they upregulate other detox pathways), and ensure adequate selenium for GPX function.
What actually matters.
Genes set the baseline. These factors determine actual detox capacity.
Glutathione Status
Phase II conjugation depends on glutathione. If it's depleted, even good genes can't compensate. Support synthesis with NAC, glycine, and glutamine.
Toxin Exposure
The best detox gene variants can be overwhelmed by high exposure. Reduce inputs: clean food, filtered water, low-toxin products.
Nutrient Cofactors
B vitamins, magnesium, zinc, selenium, and molybdenum are required cofactors. Deficiencies impair detox regardless of genetics.
Bile Flow
Phase III requires bile to export toxins. Poor bile flow = toxin recirculation. Support with bitter foods, adequate fat, and liver support.
Gut Health
The gut contains beta-glucuronidase that can reactivate excreted toxins. Dysbiosis impairs elimination.
Phase Balance
Fast Phase I + slow Phase II = trouble. Activated intermediates accumulate. Balance matters more than speed.
"Detox genes don't determine your toxic load. They reveal how carefully you need to manage exposure."← Back to all genes