NASH is a common condition with a rising incidence. There is progression to cirrhosis in some cases and the potential for mortality or requirement of liver transplantation. Currently, there is no approved therapy for NASH. The natural compound YHK has both anti-inflammatory and antifibrotic properties, and can lead to improvement in transaminases in viral hepatitis. Improvement in transaminases may correlate with improved histology in NASH and hence may impact on the natural history. We sought to determine the effects of YHK on NASH. We performed a randomized, double-blind, placebo-controlled pilot study to determine the effects of YHK on transaminases and on quality of life (QoL) in patients with biopsy-confirmed NASH and a persistently abnormal ALT or AST. Eight patients were randomized to YHK or placebo for 8 weeks. The ALT and AST were measured at baseline and weeks 4, 8, and 12. SF-36 surveys were serially completed. All five patients in the YHK group but none in the placebo group had a marked decrease in ALT at both week 4 and week 8 compared to baseline. After discontinuing YHK the ALT returned toward baseline at week 12. The mean decrease in ALT compared to baseline was significantly greater in the YHK group than in the placebo group at both week 4 (-42.8+/-23.2 vs. -6.3+/-6.7 U/L; P=0.036) and week 8 (-45.4+/-23.4 vs. 6.0+/-24.6 U/L; P=0.036). There was also a nonsignificant decrease in AST in the YHK group compared to placebo. QoL was not affected and no severe adverse events were reported. In this controlled pilot study we found the novel nutraceutical agent YHK to be effective at reducing ALT values in patients with NASH. YHK is well tolerated. Further studies are justified to assess the impact of YHK in the natural history of NASH.