Levels of ketone bodies have been reported to be both increased and decreased in individuals with non‐alcoholic fatty liver disease. We investigated whether the metabolism of ketone bodies is different in simple steatosis and in non‐alcoholic steatohepatitis (NASH).

Serum low molecular weight molecules including ketone bodies were measured using high‐throughput proton (1H) nuclear magnetic resonance in 116 (76 categorized unequivocally to those with normal liver, simple steatosis or NASH) morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, body mass index 45.1 ± 6.1 kg/m², 39 men and 77 women] with histological assessment of NASH and analysis of gene expression in the liver. Finally, we correlated β‐hydroxybutyrate (β‐OHB) levels with NASH predicting score in Metabolic Syndrome in Men Study (METSIM) population study (n = 8749 non‐diabetic men).

Levels of ketone bodies were lower in individuals with NASH compared to individuals with simple steatosis (P = 0.004 and P = 0.018 for β‐OHB and acetoacetate respectively). Lower levels of β‐OHB were associated with the NASH predicting score in the METSIM study (P = 0.001). Liver inflammation correlated with mRNA expression of genes regulating ketolysis in the liver (Spearman correlation 0.379–0.388, P < 0.0006 for ACAT1, ACSS2 and BDH1).

Lower levels of ketone bodies in individuals with NASH compared to individuals with simple steatosis suggest a decrease in ketone body metabolism in NASH.