# Does Genetic Variation in Detoxification Capacity Influence Hepatic Biomarker Responses to a Liver Support Supplementation Regimen?

**Authors:** Markus Schauer, Susanne Mair, Michael Keiner, Christian Werner, Florian Kainz, Mohamad Motevalli

PMC · DOI: 10.3390/ijms262010209 · International Journal of Molecular Sciences · 2025-10-20

## TL;DR

This study explores whether genetic differences in liver detoxification affect how people respond to liver support supplements.

## Contribution

It is the first to investigate the relationship between detoxification genotype and urinary biomarker responses to liver support supplementation.

## Key findings

- Supplementation increased urinary D-glucaric acid and mercapturic acids.
- Weight and BMI decreased modestly after the intervention.
- Genetic differences did not significantly affect biomarker responses.

## Abstract

Genetic polymorphisms contribute to inter-individual variation in liver detoxification, influencing susceptibility to exposures and responses to interventions. While urinary biomarkers reflect Phase II activity, the impact of genotype on supplementation response remains unclear. In a pilot, prospective, open-label cohort study, 30 Austrian adults completed an 8-week multi-ingredient liver support supplementation regimen (e.g., glutathione, N-acetylcysteine, α-lipoic acid). First-morning urine was collected at baseline and follow-up for measurement of D-glucaric acid, mercapturic acids, and creatinine. Dried blood spots were genotyped for polymorphisms in detoxification genes (CYP1A1, GSTM1, GSTP1, GSTT1, and NQO1), and participants were stratified into normal (NDC) or limited (LDC) detoxification capacity groups. Adherence was monitored through logs, mid-study interviews, and product counts. The intervention led to modest reductions in body weight (−0.87 kg, p < 0.05) and BMI (−0.31 kg/m2, p < 0.05), and significant increases in urinary D-glucaric acid (p < 0.05) and mercapturic acids (p < 0.01), with consistent responses across detoxification genotype groups (p > 0.05). The pattern of biomarker responses based on clinically defined categories did not differ significantly between the study groups (adjusted odds ratio = 2.88, p > 0.05). The observed increases in urinary biomarkers and reductions in weight and BMI are consistent with potential modulation of detoxification pathways following liver support supplementation, independent of genetic polymorphisms influencing detoxification capacity.

## Linked entities

- **Genes:** CYP1A1 (cytochrome P450 family 1 subfamily A member 1) [NCBI Gene 1543], GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944], GSTP1 (glutathione S-transferase pi 1) [NCBI Gene 2950], GSTT1 (glutathione S-transferase theta 1) [NCBI Gene 2952], NQO1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 1728]
- **Chemicals:** glutathione (PubChem CID 124886), N-acetylcysteine (PubChem CID 12035), α-lipoic acid (PubChem CID 864), D-glucaric acid (PubChem CID 33037), creatinine (PubChem CID 588)

## Full-text entities

- **Genes:** CYP1A1 (cytochrome P450 family 1 subfamily A member 1) [NCBI Gene 1543] {aka AHH, CP11, CYP1, CYPIA1, P1-450, P450-C}, GSTP1 (glutathione S-transferase pi 1) [NCBI Gene 2950] {aka DFN7, FAEES3, GST3, GSTP, GSTP1-1, HEL-S-22}, NQO1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 1728] {aka DHQU, DIA4, DTD, NMOR1, NMORI, QR1}, GSTT1 (glutathione S-transferase theta 1) [NCBI Gene 2952], GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944] {aka GST1, GSTM1-1, GSTM1a-1a, GSTM1b-1b, GTH4, GTM1}
- **Chemicals:** glutathione (MESH:D005978), alpha-lipoic acid (MESH:D008063), D-glucaric acid (MESH:D005937), N-acetylcysteine (MESH:D000111), creatinine (MESH:D003404)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12564548/full.md

## References

67 references — full list in the complete paper: https://tomesphere.com/paper/PMC12564548/full.md

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Source: https://tomesphere.com/paper/PMC12564548