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Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids

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Abstract

Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on metabolic and nutritional aspects. Effects of 3 g/day paracetamol for 14 days on fasting blood glutathione, plasma amino acids and sulfate, urinary paracetamol metabolites, and urinary metabolomic were studied in independently living older persons (five women, five men, mean (±SEM) age 74 ± 1 years). Dietary intakes were recorded before and at the end of the treatment and ingested sulfur amino acids were evaluated. Fasting blood glutathione, plasma amino acids, and sulfate were unchanged. Urinary nitrogen excretion supported a preservation of whole body proteins, but large-scale urinary metabolomic analysis revealed an oxidation of some sulfur-containing compounds. Dietary protein intake was 13% higher at the end than before paracetamol treatment. Final sulfur amino acid intake reached 37 mg/kg/day. The increase in sulfur amino acid intake corresponded to half of the sulfur excreted in urinary paracetamol conjugates. In conclusion, older persons accommodated to long-term paracetamol treatment by increasing dietary protein intake without any mobilization of body proteins, but with decreased anti-oxidative defenses. The extra demand in sulfur amino acids led to a consumption far above the corresponding population-safe recommendation.

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Acknowledgments

We thank all persons who collaborated in the study, especially Bertille Lamandé for clinical study setting-up, Nordine Hafnaoui for amino acid analysis, Jean-François Martin for statistical analysis of metabolomic raw data, Charlotte Joly for large-scale metabolomic analysis, Hélène Lafarge for literature acquisition and the volunteers who participated in the study. The research was supported by the Institut National de la Recherche Agronomique (INRA), France.

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Authors and Affiliations

  1. Plateforme d’Exploration du Métabolisme, INRA, Centre Clermont-Ferrand—Theix, UMR 1019 Nutrition Humaine, Saint-Genès-Champanelle, 63122, France

    Estelle Pujos-Guillot & Bernard Lyan

  2. Centre de Pharmacologie Clinique, Inserm CIC 501, INSERM U766, Faculté de Médecine, Clermont-Ferrand, 63003, France

    Gisèle Pickering, Gilles Ducheix & Claude Dubray

  3. CRNH Auvergne, Unité d’Exploration en Nutrition, Clermont-Ferrand, 63003, France

    Marion Brandolini-Bunlon

  4. INRA, Centre Clermont-Ferrand—Theix, UMR 1019 Unité de Nutrition Humaine, 63122, Saint-Genès-Champanelle, France

    Françoise Glomot, Dominique Dardevet & Isabelle Papet

  5. Univ Clermont 1, UFR Médecine, UMR 1019, Unité Nutrition Humaine, 63001, Clermont-Ferrand, France

    Françoise Glomot, Dominique Dardevet & Isabelle Papet

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  1. Estelle Pujos-Guillot
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  2. Gisèle Pickering
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  3. Bernard Lyan
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  4. Gilles Ducheix
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  5. Marion Brandolini-Bunlon
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  6. Françoise Glomot
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  7. Dominique Dardevet
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  8. Claude Dubray
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  9. Isabelle Papet
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Corresponding author

Correspondence to Isabelle Papet.

Additional information

This paper is dedicated to Christiane Obled (retired), who had the idea of the study.

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Pujos-Guillot, E., Pickering, G., Lyan, B. et al. Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids. AGE 34, 181–193 (2012). https://doi.org/10.1007/s11357-011-9218-4

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  • DOI: https://doi.org/10.1007/s11357-011-9218-4

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