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

Background: Mitochondrial metabolism is essential for liver Function, and the availability of simple and non-invasive tests able to assess hepatic mitochondrial function could be extremely useful. Since the amino acid methionine is mostly oxidized by liver mitochondria, we investigated the feasibility of a breath test with C-13-methionine in healthy subjects to assess hepatic mitochondrial function before and after ethanol-induced oxidative stress. Methods: Twenty healthy male volunteers received 2 mg/kg belly weight [methyl-C-13]-methionine. Breath (CO2)-C-13 enrichment was measured at base line and every 15 min thereafter for 180 min. Forty-eight hours later the test 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 reached a peak (4.76% +/- 0.9%) within 30-60 min and then decreased progressively. The cumulative (CO2)-C-13 excretion within 3 h was 7.81% +/- 0.66%. After ethanol-induced oxidative stress, (CO2)-C-13 excretion increased slowly, with a delayed and significantly decreased peak 2.13% +/- 0.45%; P < 0.05). The cumulative (CO2)-C-13 exhalation was significantly decreased already at 60 min (1.22% +/- 0.29%; P < 0.05. Conclusions: The present results seem to indicate that the C-13-methionine breath test could act as a marker to estimate the oxidative capacity of liver mitochondria in healthy subjects. Further study. however, is still needed to confirm the validity of the test, which could yield clinically useful information in various liver pathologic conditions.