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 longterm 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. AGE (2012) 34:181-193 DOI 10.1007 This paper is dedicated to Christiane Obled (retired), who had the idea of the study. Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids

Paracetamol in Older People: Towards Evidence-Based Dosing?

“…Twenty studies on paracetamol pharmacokinetics were included [ 24 – 43 ]. Eighteen reported on pharmacokinetics parameters, the other two focused mainly on the amount of paracetamol metabolites in older people during prolonged administration [ 34 , 35 ]. Table 2 provides the characteristics of the included pharmacokinetics studies.…”

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“…However, contrary to this opinion, we believe that in the specific case of COVID-19 it is of paramount importance taking due account of the fact that PAC and its metabolites decrease GSH levels, also when given at relatively low doses in healthy volunteers ( Burgunder et al., 1989 ; Nuttall et al., 2003 ; Pujos-Guillot et al., 2012 ; Stahl et al., 2015 ).…”

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