Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial

Abstract

OBJECTIVEWe aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODSEight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTSAfter 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 6 8.05 vs. 6.21 6 8.96, P < 0.008). A significant decrease in HbA 1c was observed in the carnitine-orotate complex group (20.33 6 0.82% [23.6 6 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONSTreatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.Ectopic fat accumulation in a visceral organ is associated with insulin resistance (1). As an example of such ectopic fat accumulation, nonalcoholic fatty liver disease (NAFLD) is now recognized as the hepatic component of metabolic syndrome and is even reportedly associated with insulin resistance independent of obesity and other metabolic components. Therefore, NAFLD can be a major determinant of insulin

Evaluation of L-Carnitine Efficacy in the Treatment of Non- Alcoholic Fatty Liver Disease among Diabetic Patients: A Randomized Double Blind Pilot Study

“…In a Korean study, 12 weeks of treatment with carnitine-orotate complex resulted a significantly higher rate of normalization of serum ALT level (17.9% vs 89.7%, p < 0.001) in comparison with placebo [42] that was also similar to findings of current study and they concluded that carnitine-orotate complex improves serum ALT and may improve hepatic steatosis in patients with diabetes and NAFLD. But they also revealed a significant decrease in HbA1c in the treatment group (-0.33 ± 0.82%, p = 0.007) and this decrease was in contrary to our study (p = 0.299).…”

ESPEN guideline on clinical nutrition in liver disease

“…for 24 weeks) was effective in reducing TNF-a and CRP and in improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH [335]. In diabetic NAFLD patients, oral carnitine-orotate (3 Â 824 mg for twelve weeks) was associated with significant improvement in ALT, hepatic steatosis and HbA1c in a double-blind placebo-controlled trial [336]. These are preliminary results and, therefore L-carnitine cannot be recommended yet.…”

Predicting Hepatic Steatosis in Living Liver Donors via Noninvasive Methods

“…We obtained liver and spleen densities in Hounsfield units (HU) and used the CT liver to spleen (L–S) attenuation difference to assess steatosis. 24 To obtain the indices, hepatic attenuation was measured by averaging the HU of 2 1.5 × 1.5 cm square regions of interest in 8 segments. 25 Median splenic attenuation was also calculated by 3 random attenuation measurements on 3 transverse sections at different splenic levels.…”