title: Effect of carnitine-orotate complex on glucose metabolism and fatty liver: a double-blind, placebo-controlled study.
abstract: OBJECTIVE
  Effective medicines have not been introduced for insulin resistance-related fatty liver. The efficacy and safety of treatment between a combination of metformin and carnitine-orotate complex and metformin alone in a 12-week, double-blind, randomized, placebo-controlled study on drug-naïve patients with impaired glucose metabolism and fatty liver were compared.
  
  
  METHODS
  Fifty-two patients with fasting glucose 100-240 mg/dL or glycosylated hemoglobin (HbA1c) ≥ 6.0% and alanine aminotransferase (ALT) 40-250 IU/L were randomized to receive metformin (250 mg t.i.d.), or metformin (250 mg t.i.d.) and carnitine-orotate complex (300 mg t.i.d.) for 12 weeks (n = 26 per group). The primary end-point was a change from baseline ALT level. Secondary end-points were changes in fasting glucose, HbA1c, aspartate aminotransferase levels, mitochondrial DNA (mtDNA) copy number in the peripheral blood, and urinary output of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress.
  
  
  RESULTS
  The combined treatment reduced ALT level significantly more than metformin alone (-51.5 ± 33.2 IU/L vs -16.7 ± 31.3 IU/L, P = 0.001). The HbA1c levels also decreased significantly in both groups but there was no significant difference between them (-0.9% ± 1.0% vs -0.7% ± 0.9%). Treatment with the complex decreased the urinary 8-hydroxy-2'-deoxyguanosine level and increased mtDNA copy number significantly compared with metformin alone (both P < 0.05). No severe adverse events were observed.
  
  
  CONCLUSIONS
  A 12-week treatment with metformin and carnitine-orotate complex significantly improved liver function enzyme levels. This was associated with changes in oxidative stress and mtDNA copy number compared with metformin alone in patients with impaired glucose metabolism and fatty liver (clinical trial number: KCT0000193).
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Eun Shil
authors.initials: ES
authors.lastname: Hong
authors.forename: Eun Ky
authors.initials: EK
authors.lastname: Kim
authors.forename: Seon Mee
authors.initials: SM
authors.lastname: Kang
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Khang
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
authors.forename: Soo
authors.initials: S
authors.lastname: Lim
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002331:Carnitine / Q000008:administration & dosage*; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics; D004311:Double-Blind Method; D004338:Drug Combinations; D023381:Endpoint Determination; D005215:Fasting / Q000097:blood; D005234:Fatty Liver / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D044882:Glucose Metabolism Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D009963:Orotic Acid / Q000008:administration & dosage*; D018384:Oxidative Stress; D015990:Placebo Effect
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D015415:Biomarkers; D001786:Blood Glucose; D002331:Carnitine; D004272:DNA, Mitochondrial; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D008687:Metformin; D009963:Orotic Acid; C517652:hemoglobin A1c protein, human
keywords: carnitine-orotate; fatty liver; insulin resistance; metformin; oxidative stress