title: Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids.
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.
authors.affiliation: Plateforme d'Exploration du Métabolisme, INRA, Centre Clermont-Ferrand-Theix, UMR 1019 Nutrition Humaine, Saint-Genès-Champanelle, 63122, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Pujos-Guillot
authors.forename: Gisèle
authors.initials: G
authors.lastname: Pickering
authors.forename: Bernard
authors.initials: B
authors.lastname: Lyan
authors.forename: Gilles
authors.initials: G
authors.lastname: Ducheix
authors.forename: Marion
authors.initials: M
authors.lastname: Brandolini-Bunlon
authors.forename: Françoise
authors.initials: F
authors.lastname: Glomot
authors.forename: Dominique
authors.initials: D
authors.lastname: Dardevet
authors.forename: Claude
authors.initials: C
authors.lastname: Dubray
authors.forename: Isabelle
authors.initials: I
authors.lastname: Papet
mesh_terms: D000082:Acetaminophen / Q000097:blood* / Q000627:therapeutic use / Q000652:urine*; D000368:Aged; D000375:Aging; D000465:Algorithms; D000603:Amino Acids, Sulfur / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D018712:Analgesics, Non-Narcotic / Q000097:blood* / Q000627:therapeutic use / Q000652:urine*; D001168:Arthritis / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004044:Dietary Proteins / Q000008:administration & dosage; D005260:Female; D019803:Glutathione Disulfide / Q000097:blood / Q000652:urine; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013431:Sulfates / Q000097:blood / Q000652:urine
chemical_list: D000603:Amino Acids, Sulfur; D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D004044:Dietary Proteins; D013431:Sulfates; D000082:Acetaminophen; D019803:Glutathione Disulfide