title: Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients.
abstract: OBJECTIVE
  Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue.
  
  
  METHODS
  Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured.
  
  
  RESULTS
  Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043).
  
  
  CONCLUSIONS
  This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.
authors: *Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; †Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan; ‡Division of Nephrology, Wada Cardiovascular Clinic, Tosu, Japan; §Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan; and ¶Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan.
authors: Kei
authors: K
authors: Fukami
authors: Sho-ichi
authors: S
authors: Yamagishi
authors: Kazuko
authors: K
authors: Sakai
authors: Yusuke
authors: Y
authors: Kaida
authors: Miyuki
authors: M
authors: Yokoro
authors: Seiji
authors: S
authors: Ueda
authors: Yoshifumi
authors: Y
authors: Wada
authors: Masayoshi
authors: M
authors: Takeuchi
authors: Makiko
authors: M
authors: Shimizu
authors: Hiroshi
authors: H
authors: Yamazaki
authors: Seiya
authors: S
authors: Okuda
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000172:deficiency*; D016022:Case-Control Studies; D003677:Deficiency Diseases / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007564:Japan; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D006435:Renal Dialysis / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D057772:Vascular System Injuries / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; C573420:ICAM1 protein, human; D008744:Methylamines; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; C005855:trimethyloxamine; D002331:Carnitine