Double-blind Randomized Placebo-controlled Clinical Trial of Omega 3 Fatty Acids for the Treatment of Diabetic Patients With Nonalcoholic Steatohepatitis

Double-blind, randomized, placebo-controlled trial in adults with type 2 diabetes and biopsy-confirmed nonalcoholic steatohepatitis. Participants had well-controlled diabetes and metabolic syndrome and were recruited from Cleveland Clinic and MetroHealth Medical Center in Cleveland, Ohio.

Oral omega-3 fatty acid capsules containing 2160 mg EPA plus 1440 mg DHA per day, given in 2 divided doses for 48 weeks. The active supplement was a marine fish concentrate (Opti-EPA); the comparator was isocaloric corn oil placebo capsules taken in the same manner.

Omega-3 PUFA did not improve NASH histology or insulin resistance versus placebo, and the overall conclusion was that PUFA supplementation was not beneficial in diabetic patients with NASH. In the PUFA arm, NAFLD activity score changed from 6.12 ± 0.99 to 5.41 ± 1.20, but histologic components did not show significant favorable change. Fasting glucose increased from 129.9 ± 36.5 to 150.4 ± 43.7 and HOMA-IR from 12.0 ± 6.8 to 16.1 ± 10.3, while AST fell from 47.7 ± 22.8 to 41.7 ± 17.4 and ALT from 60.1 ± 27.6 to 56.9 ± 30.9 without a meaningful clinical benefit. The intervention was well tolerated, but the data do not support PUFA supplements for NASH in this population.

The active intervention group was small, and the trial lasted only 48 weeks. The population was limited to adults with well-controlled type 2 diabetes and biopsy-confirmed NASH from two medical centers, which may limit generalizability. Benefits were not demonstrated on the key histologic outcome, and the report provides limited support for clinically meaningful metabolic improvement.