HSA | FSA CARDS ARE NOW ACCEPTED

How NFE2L2 and NRF2 Affect Phase 2 Detoxification

Phase 2 detoxification is a key part of how your body neutralizes and removes toxins. During this stage partially processed toxins are converted into water soluble forms so they can be eliminated in urine or bile. The NFE2L2 gene makes a protein called NRF2. NRF2 is a master regulator that turns on many antioxidant and detoxification enzymes. These enzymes help protect cells from oxidative stress caused by pollution, alcohol, cigarette smoke, and other environmental toxins.

Common variation at rs2364723 in NFE2L2 can change how well NRF2 works. Depending on your genotype you may have reduced, slightly reduced, or enhanced NRF2 activity, which can affect how efficiently your body completes Phase 2 detoxification and how resilient you are to environmental stressors.

Simple ways to support Phase 2 detoxification

  • Eat a varied, colorful diet high in vegetables and fruits. Cruciferous vegetables such as broccoli, Brussels sprouts, cabbage, and kale are especially supportive.
  • Include foods rich in antioxidants like berries, citrus, leafy greens, and brightly colored vegetables.
  • Prioritize sulfur containing foods that support conjugation reactions such as garlic, onions, eggs, and legumes.
  • Stay hydrated to support kidney and bile flow for elimination.
  • Practice regular physical activity to improve circulation and lymphatic flow.
  • Manage stress and get adequate sleep to reduce oxidative strain on the body.
  • Limit exposure to toxins: avoid cigarette smoke, reduce alcohol intake, choose less processed foods, and minimize unnecessary chemical exposures at home.

Supplements and compounds that may enhance NRF2 activity

  • Curcumin — a bioactive compound from turmeric that can help activate NRF2 pathways. Consider formulations with improved absorption.
  • Sulforaphane — found in cruciferous vegetables and concentrated in broccoli sprout extracts; potently stimulates NRF2.
  • Green tea polyphenols — support antioxidant defenses and may work synergistically with NRF2 pathways.
  • Nutrients that support Phase 2 conjugation — adequate protein for amino acid supply, vitamin C, magnesium, and B vitamins.
  • Consider supplements only after discussing with your healthcare provider, especially if you take medications or have medical conditions.

Genetic interpretations for rs2364723 (NFE2L2)

2 effect alleles (CC)

If you have the CC genotype for rs2364723 you carry two copies of the effect allele. This genotype is associated with reduced NFE2L2 activity and diminished Phase 2 detoxification capacity. The C allele can decrease the expression and activity of NRF2, the master regulator protein that activates your body s antioxidant and detoxification enzymes.

With reduced NRF2 function your body may be less efficient at converting toxins into water soluble forms for elimination and less resilient against oxidative stress from pollution, alcohol byproducts, and environmental toxins. This may increase susceptibility to toxin accumulation and cellular damage.

Recommendations

  • Make cruciferous vegetables a daily habit. Steamed or lightly cooked broccoli, cauliflower, kale, and Brussels sprouts help provide sulforaphane precursors.
  • Add foods high in sulfur such as garlic, onions, eggs, and legumes to support conjugation reactions.
  • Include antioxidant rich foods: berries, citrus, beets, spinach, and brightly colored vegetables.
  • Consider sulforaphane or broccoli sprout supplements and curcumin formulations that enhance NRF2 activity. Talk with your provider before starting.
  • Support methylation and liver pathways with adequate B vitamins, vitamin C, magnesium, and quality protein sources.
  • Reduce toxic exposures: limit alcohol, avoid smoking, use low chemical cleaning and personal care products, and filter drinking water if needed.
  • Prioritize sleep, stress management, and regular exercise to lower overall oxidative load.
  • Monitor organ health with your clinician if you have concerns about toxin exposure or chronic symptoms.
1 effect allele (CG)

If you have the CG genotype for rs2364723 you carry one copy of the effect allele. This genotype is associated with slightly reduced NFE2L2 activity and a mild decrease in detox capacity. The C allele can reduce the expression and activity of NRF2, which activates antioxidant and defense enzymes during Phase 2 detoxification.

With somewhat reduced NRF2 function your body may be moderately less efficient at converting toxins into water soluble forms for elimination through urine or bile. This could increase sensitivity to oxidative stress from environmental pollutants, alcohol byproducts, and other harmful substances.

Recommendations

  • Include cruciferous vegetables several times per week to provide sulforaphane precursors.
  • Eat a wide range of colorful fruits and vegetables to boost antioxidants and support enzyme function.
  • Incorporate sulfur rich foods and ensure sufficient protein intake for conjugation reactions.
  • Consider lifestyle supports that reduce toxic burden: reduce alcohol, avoid smoke exposure, and minimize processed food intake.
  • Sulforaphane or curcumin supplements may be helpful. Discuss options and dosing with your healthcare provider.
  • Maintain regular physical activity, good sleep habits, and stress reduction techniques such as mindfulness or breathing practices.
0 effect alleles (GG)

If you have the GG genotype for rs2364723 you carry two copies of the non effect allele. This genotype is associated with increased NFE2L2 activity and enhanced Phase 2 detoxification capacity compared to carriers of the C allele.

Your GG genotype supports optimal production and function of the NRF2 protein that activates numerous antioxidant and detoxification enzymes. Your cells are better equipped to neutralize and eliminate harmful substances like environmental toxins, alcohol byproducts, and pollutants by efficiently converting them into water soluble compounds for excretion.

Recommendations

  • Maintain a supportive lifestyle to preserve this genetic advantage: a diet rich in vegetables and antioxidants, adequate hydration, regular activity, and sleep.
  • Avoid complacency with toxic exposures. Even with stronger NRF2 activity reducing alcohol intake and avoiding smoke remains important.
  • Consider periodic use of cruciferous vegetables, green tea, and culinary turmeric to sustain NRF2 signaling.
  • Stay proactive with routine health checks and discuss any concerns with your healthcare provider.

Practical next steps

  • Review current diet and identify ways to increase cruciferous vegetables and colorful produce.
  • Reduce sources of avoidable toxins: smoking, excessive alcohol, and heavily processed foods.
  • Talk to your healthcare provider about whether supplements such as curcumin or sulforaphane are appropriate for you.
  • Consider routine labs if you have symptoms or exposures of concern; your clinician can advise on targeted testing.

Important disclaimer

PlexusDx provides educational information about genetic predispositions only. This content does not provide medical advice, diagnose conditions, or recommend specific medical treatments. Always consult with your healthcare provider before making changes to your diet, supplement routine, or lifestyle, especially if you have medical conditions or take medications.