Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

Double-blind, randomized, placebo-controlled trial in adults with non-cirrhotic nonalcoholic steatohepatitis at the University of Virginia Hepatology Clinic in Charlottesville, Virginia, enrolled during 2007-2010. Participants received standard counseling on caloric restriction and physical activity and were followed for 1 year; the active and placebo arms each had 17 participants.

Adults randomized to the active arm received 3000 mg/day of n-3 polyunsaturated fatty acids as oral fish oil, given as 3 x 1000 mg capsules daily for 1 year. Each capsule contained triglyceride-form n-3s with 35% EPA, 25% DHA, and 10% other n-3s; the comparator was identical-appearing placebo capsules containing predominantly soybean oil with small amounts of fish and lemon oils.

The n-3 fish oil regimen did not improve the primary histological endpoint in NASH, but it did reduce liver fat content by imaging measures. The primary outcome, NAS reduction of at least 2 points without fibrosis progression, occurred in 4/17 (23.5%) on n-3 versus 3/17 (17.6%) on placebo (p = 0.99). Post-intervention MRI Dixon fat was lower with n-3 than placebo, 8.4 (5.2) versus 12.0 (5.6), with between-group p = 0.015 and within-group p = 0.02 for n-3. Image-assisted morphometry also showed a within-group reduction with n-3, but the between-group difference was not significant (p = 0.13). No consistent independent benefit was seen for ALT, fasting glucose, insulin resistance markers, or hepatocyte injury markers, and no major safety signal was reported; nausea occurred with similar frequency across groups.

Small single-center trial with only 17 participants per arm limits precision and generalizability. The study relied on a 1-year follow-up with standard diet and activity counseling, so concurrent weight change and exercise could influence outcomes and complicate attribution. Histologic benefit on the primary endpoint was not demonstrated, and the positive findings were limited to secondary imaging measures.