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Understanding GSTP1 and Phase 2 Detoxification

Phase 2 detoxification is a crucial part of how your body neutralizes and removes potentially harmful compounds. During this phase, enzymes like glutathione S-transferases attach water-soluble groups such as glutathione to toxic molecules, making them easier to excrete. The GSTP1 gene encodes one of these enzymes, glutathione S-transferase P1, which is especially active in the liver and lungs. Variations in GSTP1 can change how well this enzyme works and influence individual sensitivity to environmental toxins.

What the rs1695 (Ile105Val) Variant Means

The rs1695 variant, also known as Ile105Val, changes the GSTP1 enzyme structure and can affect how effectively it binds toxins to glutathione. The G allele (Val) is associated with reduced enzyme activity compared with the A allele (Ile). Depending on whether you carry 0, 1, or 2 copies of the effect allele, your Phase 2 detox capacity may be higher or lower. Below are practical explanations of each genotype and evidence-based steps you can take to support detoxification pathways.

Practical Diet, Supplement, Lifestyle and Testing Recommendations

Regardless of genotype, supporting your body's detox systems is beneficial. The suggestions below are educational and intended to help you discuss appropriate steps with your healthcare provider.

Dietary Recommendations

  • Eat a variety of colorful fruits and vegetables daily to provide antioxidants that reduce oxidative stress and support detox enzymes.
  • Prioritize cruciferous vegetables (broccoli, Brussels sprouts, kale, cauliflower) to boost Phase 2 enzyme activity and support glutathione-related pathways.
  • Include allium vegetables (garlic, onions, leeks) which contain sulfur compounds that aid glutathione production.
  • Consume adequate high-quality protein (fish, poultry, legumes) to supply amino acids cysteine, glycine and glutamate for glutathione synthesis.
  • Include healthy fats (olive oil, avocados, nuts, fatty fish) to support cell membranes and reduce inflammation.
  • Limit processed foods, excessive fried or charred foods, and reduce processed sugars which can increase oxidative stress.

Supplements to Consider

Discuss these options with your healthcare provider. Supplements may help when diet alone is insufficient.

  • L-Glutathione or N-acetylcysteine (NAC) to support glutathione levels and Phase 2 conjugation.
  • Alpha-lipoic acid for antioxidant support and regeneration of glutathione.
  • Vitamin C and vitamin E as complementary antioxidants.
  • Sulfur-containing supplements such as milk thistle or SAMe may support liver detox pathways.
  • Multivitamin with adequate B vitamins, particularly B6, B12 and folate, which support methylation and detox cofactor needs.

Lifestyle Recommendations

  • Minimize exposure to toxins: avoid smoking and secondhand smoke, limit consumption of high-mercury fish, reduce use of plastic food containers and canned foods that may leach BPA, and choose lower-pesticide produce when possible.
  • Improve indoor air: use ventilation, HEPA filtration, and avoid idling vehicles or heavy chemical use near living spaces.
  • Maintain regular physical activity to support circulation, lymphatic flow and sweat-mediated elimination of some toxins.
  • Stay well hydrated to promote renal clearance of water-soluble conjugates.
  • Practice safe food preparation: avoid charring meats and reduce consumption of heavily grilled or smoked foods.
  • Manage stress and get sufficient sleep, as recovery supports efficient detox and cellular repair.

Blood Tests and Monitoring

  • Basic metabolic panel and liver function tests (ALT, AST, GGT) to screen organ systems involved in detox.
  • Urinary or blood heavy metal testing if exposure is suspected.
  • Nutrient panels to check levels of vitamins, selenium, and markers related to oxidative stress and glutathione status if clinically indicated.
  • Discuss targeted testing with your healthcare provider based on exposure history and symptoms.

Genetic Interpretation: GSTP1 rs1695

Two effect alleles (GG) — Reduced GSTP1 activity

Individuals with the GG genotype have two copies of the G (Val) allele for rs1695. This genotype is associated with reduced GSTP1 enzyme activity. As a result, Phase 2 conjugation with glutathione may be less efficient, which can lead to decreased capacity to neutralize and eliminate common environmental toxins. Substances that may be more challenging to process include:

  • Polycyclic aromatic hydrocarbons from air pollution and charred foods
  • Organophosphate pesticide residues
  • Mercury from certain fish and dental amalgams
  • Benzene from vehicle exhaust and industrial sources
  • BPA and other plastic-derived chemicals
  • Heavy metals such as cadmium and arsenic

Actionable steps:

  • Emphasize cruciferous and allium vegetables, adequate protein, and sulfur-rich foods to support glutathione production.
  • Consider discussing supplements such as NAC, glutathione, and alpha-lipoic acid with your provider.
  • Reduce known exposures at home and work, improve indoor air quality, and choose lower-toxin personal care and household products.
  • Monitor liver function and heavy metals if exposure risk is present.
One effect allele (AG) — Moderately reduced GSTP1 activity

With the AG genotype, you carry one copy of the G (Val) allele and one copy of the A (Ile) allele. This tends to result in a modest reduction of GSTP1 activity compared with the AA genotype but generally better activity than GG. You may have slightly lower efficiency in conjugating glutathione to toxins, which could translate to increased sensitivity to environmental pollutants including cigarette smoke, pesticides, mercury, and BPA.

Actionable steps:

  • Follow a detox-supportive diet rich in cruciferous and allium vegetables and ensure adequate high-quality protein intake.
  • Hydrate well and maintain regular exercise and sleep habits.
  • Consider antioxidant support and discuss targeted supplements with your healthcare provider if needed.
  • Minimize exposures by choosing safer household products and reducing consumption of high-mercury fish and heavily processed foods.
Zero effect alleles (AA) — Typical or enhanced GSTP1 activity

The AA genotype indicates two copies of the A (Ile) allele and is associated with favorable GSTP1 enzyme function. This genotype generally supports effective Phase 2 conjugation with glutathione, enabling more efficient neutralization and elimination of many environmental toxins. While this is a protective factor, maintaining healthy lifestyle and exposure-reduction practices remains important.

Actionable steps:

  • Continue a balanced diet rich in antioxidants, cruciferous and allium vegetables, and adequate protein to preserve optimal detox capacity.
  • Maintain healthy lifestyle habits—exercise, hydration, sleep, and stress management—to support ongoing detoxification.
  • Practice exposure minimization strategies even when genetic capacity is favorable.

Important Disclaimer

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice and should not replace consultation with a qualified healthcare professional. Discuss genetic results, testing, or any changes to diet, supplements, or medications with your healthcare provider to determine what is safe and appropriate for your individual health circumstances.