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How CTH Variants Affect Your Transsulfuration Pathway, Glutathione, and Detoxification

The CTH gene encodes the enzyme cystathionine gamma-lyase, a key player in the transsulfuration pathway. This enzyme converts cystathionine into cysteine using vitamin B6 as a cofactor. Cysteine is a building block for glutathione, the body’s primary antioxidant that supports cellular protection, redox balance, and detoxification. Genetic changes that reduce CTH activity can lower cysteine and glutathione levels, which may increase oxidative stress, elevate homocysteine, and reduce detox capacity. Below is an explanation of how different genotypes at rs1021737 can influence this process and practical steps you can take to support these pathways.

What this means for health and wellness

  • Lower CTH activity can reduce cysteine production and limit glutathione synthesis, which may increase susceptibility to oxidative stress.
  • Reduced transsulfuration can contribute to elevated homocysteine, which places additional demand on methylation pathways.
  • Supporting nutrient intake and lifestyle choices can help maintain healthy glutathione levels and detoxification even with reduced CTH function.
  • Regular monitoring of key lab markers can guide targeted interventions and help you and your provider make informed decisions.

Practical diet, supplement, and lifestyle recommendations

Use these strategies to support transsulfuration, glutathione production, methylation, and detoxification. Always review any new supplements or major diet changes with your healthcare provider.

Diet

  • Eat sulfur-rich foods: include garlic, onions, leeks, cruciferous vegetables like broccoli, cauliflower, Brussels sprouts, kale, and cabbage, plus eggs and animal proteins if appropriate for your diet.
  • Increase cysteine and glycine precursors: bone broth, collagen, gelatin, and high quality protein sources support substrate availability for glutathione synthesis.
  • Boost antioxidant intake: colorful fruits, berries, leafy greens, and foods high in vitamin C and E help reduce oxidative stress.
  • Support methylation: include folate-rich foods such as leafy greens, legumes, and foods containing B12 where diet allows.
  • Limit processed foods and excess alcohol: these increase oxidative stress and detox load.

Supplements

  • Vitamin B6: an essential cofactor for CTH. Consider pyridoxal 5 phosphate forms if recommended by your provider.
  • N-acetylcysteine (NAC) or other cysteine donors: these can help raise cysteine availability and support glutathione synthesis in people with reduced endogenous production.
  • Glycine: supports glutathione formation and can be taken as a standalone supplement or via collagen peptides.
  • Liposomal or reduced glutathione: direct glutathione supplements may provide short term support, particularly when synthesis is limited.
  • Standard B-complex: a balanced B-complex helps support methylation and transsulfuration pathways together.
  • Antioxidants: vitamin C, vitamin E, and plant polyphenols can reduce oxidative burden while pathways are being supported.

Lifestyle

  • Prioritize sleep and stress management: chronic stress and poor sleep increase oxidative stress and impair detox processes.
  • Regular moderate exercise: supports cellular redox balance and circulation of detoxification systems. Avoid excessive high intensity training while correcting nutritional imbalances.
  • Avoid smoking and reduce environmental exposures: minimize exposure to toxins, pesticides, and unnecessary chemical additives where possible.
  • Hydration: adequate water intake supports renal elimination of metabolites and overall detox.

Blood tests and monitoring

  • Plasma homocysteine: elevated levels may indicate stress on methylation and transsulfuration pathways.
  • Glutathione status: where available, reduced and oxidized glutathione measurements help assess antioxidant capacity.
  • B vitamins: check levels of B6, folate, and B12 to ensure cofactors are adequate.
  • Liver function and standard metabolic panels: evaluate organ function and detox capacity as part of a comprehensive assessment.
2 effect alleles (TT at rs1021737)

Carrying two copies of the effect allele is associated with reduced CTH enzyme activity. This may impair the conversion of cystathionine to cysteine and limit glutathione production. Potential consequences include higher oxidative stress, weaker detoxification, and elevated homocysteine that burdens methylation pathways. Consider the following targeted actions in discussion with your healthcare provider.

  • Increase intake of sulfur containing foods such as garlic, onions, cruciferous vegetables, and high quality protein sources.
  • Discuss vitamin B6 supplementation, preferably in the active form pyridoxal 5 phosphate, to support residual CTH activity and other B6 dependent processes.
  • Consider cysteine donors such as N-acetylcysteine or glycine and collagen peptides to support glutathione synthesis.
  • Short term use of glutathione formulations may be helpful while building endogenous capacity.
  • Monitor plasma homocysteine, B6, and glutathione status periodically to guide dosing and effectiveness.
  • Adopt antioxidant rich diet and reduce exposures that increase oxidative load.
1 effect allele (GT at rs1021737)

Having one effect allele may lead to moderately reduced CTH activity. Many people with this genotype maintain adequate glutathione, but some may experience mild inefficiency in cysteine production, raising vulnerability to oxidative stress under high demand. Consider these supportive measures.

  • Eat a diet rich in sulfur foods and adequate protein to provide substrates for cysteine and glutathione synthesis.
  • Ensure adequate vitamin B6 intake from food or supplements if levels are low. Discuss the best form and dose with your provider.
  • Use glycine or collagen supplements to help maintain glutathione precursors during times of increased oxidative stress or detox demand.
  • Monitor homocysteine and B vitamin status if you have symptoms or additional risk factors for impaired methylation.
  • Maintain healthy lifestyle habits that reduce oxidative stress, including good sleep, stress management, and moderate exercise.
0 effect alleles (GG at rs1021737)

Carrying two copies of the non-effect allele is associated with normal CTH function. This supports efficient conversion of cystathionine to cysteine and robust glutathione production. General guidance to maintain health and protect these pathways is below.

  • Follow a balanced, nutrient-dense diet with adequate B6 and sulfur containing foods to maintain efficient transsulfuration and antioxidant capacity.
  • Include regular antioxidant rich fruits and vegetables and avoid excess alcohol and environmental toxins.
  • Periodic monitoring of B vitamin status and homocysteine can help ensure continued metabolic health, especially with aging or increased environmental exposures.
  • Supportive lifestyle habits such as sufficient sleep, regular exercise, and stress reduction help preserve glutathione and detox function over time.

Important disclaimer

PlexusDx provides educational information about genetic predispositions and related lifestyle and nutritional strategies. This content is not medical advice. Always consult your healthcare provider before making changes to medications, supplements, or treatment plans, and before starting new testing or therapies. Your healthcare provider can interpret these results in the context of your personal medical history, symptoms, and other laboratory findings.