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

Abstract

Background Nonalcoholic steatohepatitis (NASH) is common and severe in patients with diabetes mellitus. Although, there are no effective treatments for NASH in diabetic patients, preliminary reports suggest that polyunsaturated fatty acids (PUFA) may be beneficial in these patients. Aim A prospective, randomized, double blind placebo controlled study (NCT 00323414) was performed in NASH patients with diabetes. Methods 37 patients (50.6±9.8y) with well controlled diabetes (HbA1C<8.5%) were randomized to receive either PUFA containing eicosapentaenoic acid 2160 mg and docosahexaenoic acid 1440 mg daily or an isocaloric, identical placebo containing corn oil for 48 weeks under CONSORT guidelines. Clinical, demographics, biochemical laboratory tests, body composition using DEXA® and liver biopsy were done at randomization and at the end of treatment. Liver biopsy was scored by the NASH CRN criteria. An intention to treat analysis was performed. Results At inclusion, gender, age, body weight, biochemical tests, glucose control and liver histology were similar in the 2 treatment groups. There was no change in liver enzymes, body weight or body composition during the study in either group. At the end of treatment, hepatic steatosis and the activity score improved (p<0.05) and lobular inflammation worsened (p<0.001) with placebo but was unchanged with PUFA. At the end of treatment, insulin resistance (serum glucose and HOMA) worsened with PUFA but not placebo. Conclusions PUFA provided no benefit over placebo in NASH patients with diabetes. The effects of PUFA on histology and insulin resistance were inferior to placebo. These data provide no support for PUFA supplements in NASH.

The Role of Nuclear Receptors in the Pathophysiology, Natural Course, and Drug Treatment of NAFLD in Humans

“…Paradoxically, a recent study suggested that PUFA treatment may even worsen IR and liver histology in diabetic patients with NASH [197]. Accordingly, despite improving dyslipidemia [198,199] [211], and, on the other hand, treatment extension over time has not been associated with additional improvement of NASH histological features [206].…”

El efecto de omega 3 en la salud humana y consideraciones en la ingesta

“…Es importante mencionar que los estudios en pacientes con diabetes mellitus, síndrome metabólico y obesidad suplementados con omega 3 muestran variabilidad en sus efectos en parámetros metabólicos como la glucosa y en lípidos sanguíneos como el colesterol y el LDL (22,23). Sin embargo, se han encontrado similitudes entre humanos y ratones en cuanto a algunos mecanismos.…”

Pharmacologic Management of Non-Alcoholic Fatty Liver Disease

“…A meta-analysis of 9 trials and 355 patients found that there were beneficial changes in hepatic steatosis but less convincing evidence of improvement in aminotransaminases with PUFA therapy [55]. Two recent randomised controlled trials which provided histological outcome measures did not demonstrate improved liver histology, but in fact suggested worsening of insulin resistance with PUFA therapy in one trial [56,57]. More studies are required before PUFA can be recommended as a treatment option in NAFLD.…”