Non-invasive assessment of human hepatic mitochondrial function through the C-13-methionine breath test

Background: Mitochondrial metabolism is essential for liver Function, and t he availability of simple and non-invasive tests able to assess hepatic mit ochondrial function could be extremely useful. Since the amino acid methion ine is mostly oxidized by liver mitochondria, we investigated the feasibili ty of a breath test with C-13-methionine in healthy subjects to assess hepa tic mitochondrial function before and after ethanol-induced oxidative stres s. Methods: Twenty healthy male volunteers received 2 mg/kg belly weight [m ethyl-C-13]-methionine. Breath (CO2)-C-13 enrichment was measured at base l ine and every 15 min thereafter for 180 min. Forty-eight hours later the te st was repeated 30 min after the ingestion of ethanol (0.3 g/kg body weight ). Results: After oral administration of methionine, (CO2)-C-13 excretion r eached a peak (4.76% +/- 0.9%) within 30-60 min and then decreased progress ively. The cumulative (CO2)-C-13 excretion within 3 h was 7.81% +/- 0.66%. After ethanol-induced oxidative stress, (CO2)-C-13 excretion increased slow ly, with a delayed and significantly decreased peak 2.13% +/- 0.45%; P < 0. 05). The cumulative (CO2)-C-13 exhalation was significantly decreased alrea dy at 60 min (1.22% +/- 0.29%; P < 0.05. Conclusions: The present results s eem to indicate that the C-13-methionine breath test could act as a marker to estimate the oxidative capacity of liver mitochondria in healthy subject s. Further study. however, is still needed to confirm the validity of the t est, which could yield clinically useful information in various liver patho logic conditions.