L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes.

BACKGROUND Patients with type 2 diabetes are under high oxidative stress, and levels of hyperglycemia correlate strongly with levels of LDL oxidation. Carnitine favorably modulates oxidative stress. OBJECTIVE This objective of this study was to evaluate the efficacy of L-carnitine on the reduction of oxidized LDL cholesterol in patients with type 2 diabetes. DESIGN Eighty-one patients with diabetes were randomly assigned to 1 of 2 treatment groups for 3 mo. The 2 groups received either 2 g L-carnitine once daily (n = 41) or placebo (n = 40). The following variables were assessed at baseline, after washout, and at 1, 2, and 3 mo of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B-100, oxidized LDL cholesterol, thiobarbituric acid-reactive substances, and conjugated dienes. RESULTS At the end of the study period, the L-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers: oxidized LDL levels decreased by 15.1 compared with 3.0 U/L (P < 0.001); LDL cholesterol decreased by 0.45 compared with 0.16 mmol/L (P < 0.05); triglycerides decreased by 1.02 compared with 0.09 mmol/L (P < 0.001); apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL (P < 0.05); apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL (P < 0.05); thiobarbituric acid-reactive substance concentrations decreased by 1.92 compared with 0.05 (P < 0.001), and conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group (P < 0.001). CONCLUSION Our study indicates that oral administration of L-carnitine reduces oxidized LDL cholesterol levels in patients with type 2 diabetes.

[1]  M. Malaguarnera,et al.  A review on the actual trends of insulin treatment in elderly with diabetes. , 2008, Archives of gerontology and geriatrics.

[2]  M. Malaguarnera,et al.  Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. , 2008, Archives of gerontology and geriatrics.

[3]  M. Malaguarnera,et al.  Insulin-resistance (IR) in older age. , 2008, Archives of gerontology and geriatrics.

[4]  M. Capri,et al.  Diabetes mellitus in the extreme longevity , 2008, Experimental Gerontology.

[5]  B. Morio,et al.  Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. , 2008, The Journal of clinical investigation.

[6]  M. Malaguarnera,et al.  Cardio-cerebrovascular complications in elderly with diabetes. , 2007, Archives of gerontology and geriatrics.

[7]  F. Panza,et al.  Efficacy and tolerability of combined treatment with L-carnitine and simvastatin in lowering lipoprotein(a) serum levels in patients with type 2 diabetes mellitus. , 2006, Atherosclerosis.

[8]  M. Malaguarnera,et al.  L-carnitine reduces severity of physical and mental fatigue and improves daily activities in the elderly. , 2006, Southern medical journal.

[9]  R. Collins,et al.  Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins , 2005, The Lancet.

[10]  F. Aktan,et al.  Effects of L‐carnitine treatment on oxidant/antioxidant state and vascular reactivity of streptozotocin‐diabetic rat aorta , 2003, The Journal of pharmacy and pharmacology.

[11]  R. Fogari,et al.  The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus. , 2003, Clinical therapeutics.

[12]  Z. Binienda Neuroprotective Effects of l‐Carnitine in Induced Mitochondrial Dysfunction , 2003, Annals of the New York Academy of Sciences.

[13]  M. Malaguarnera,et al.  Plasma Lipid Composition and LDL Oxidation , 2003, Clinical chemistry and laboratory medicine.

[14]  Y. Oomura,et al.  Effects of chronic acetyl-L-carnitine treatment on brain lipid hydroperoxide level and passive avoidance learning in senescence-accelerated mice , 2002, Neuroscience Letters.

[15]  L. Pari,et al.  Effect of Cassia auriculata flowers on blood sugar levels, serum and tissue lipids in streptozotocin diabetic rats. , 2002, Singapore medical journal.

[16]  E. Dennis,et al.  Scavenger Receptors, Oxidized LDL, and Atherosclerosis , 2001, Annals of the New York Academy of Sciences.

[17]  Z. Binienda,et al.  Neuroprotective role of L-carnitine in the 3-nitropropionic acid induced neurotoxicity. , 2001, Toxicology letters.

[18]  M. Gad,et al.  L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits. , 2001, Pharmacological research.

[19]  N. N. Available World medical association declaration of Helsinki , 2000, Chinese Journal of Integrative Medicine.

[20]  D. Harrison,et al.  Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. , 2000, Circulation research.

[21]  C. Sirtori,et al.  L-carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a). , 2000, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[22]  G. Brown,et al.  Nitric oxide, cytochrome c and mitochondria. , 1999, Biochemical Society symposium.

[23]  I. Singh,et al.  Studies on hepatic injury and antioxidant enzyme activities in rat subcellular organelles following in vivo ischemia and reperfusion , 1997, Molecular and Cellular Biochemistry.

[24]  Daniel Steinberg,et al.  Low Density Lipoprotein Oxidation and Its Pathobiological Significance* , 1997, The Journal of Biological Chemistry.

[25]  M. Boemi,et al.  Diabetes mellitus and chronic heart failure. , 1996, Archives of gerontology and geriatrics.

[26]  E. van der Velde,et al.  Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atheroscerosis. , 1995, Clinica chimica acta; international journal of clinical chemistry.

[27]  T. O. Abney,et al.  Biosynthesis and Metabolism of Carnitine , 1995, Journal of child neurology.

[28]  A. To,et al.  Biosynthesis and metabolism of carnitine. , 1995 .

[29]  S. Grundy Atherogenic dyslipidemia: lipoprotein abnormalities and implications for therapy. , 1995, The American journal of cardiology.

[30]  U. Garbin,et al.  Determination of lipid hydroperoxides in native low-density lipoprotein by a chemiluminescent flow-injection assay. , 1993, Biochimica et biophysica acta.

[31]  A. Hamsten,et al.  Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man , 1992, The Lancet.

[32]  J. Baynes Role of Oxidative Stress in Development of Complications in Diabetes , 1991, Diabetes.

[33]  J L Witztum,et al.  Low density lipoprotein undergoes oxidative modification in vivo. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[34]  V. Menon,et al.  Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol. , 1989, Indian journal of experimental biology.

[35]  M. Haberland,et al.  Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits. , 1988, Science.

[36]  Leighton R. James,et al.  L-carnitine treatment in the hyperlipidemic rabbit. , 1987, Metabolism: clinical and experimental.

[37]  N. Siliprandi,et al.  Favorable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: decisive role of low levels of high-density lipoprotein-cholesterol. , 1983, The American journal of clinical nutrition.

[38]  D. Penn,et al.  Carnitine and carnitine esters in plasma and adipose tissue of chronic uremic patients undergoing hemodialysis. , 1983, Metabolism: clinical and experimental.

[39]  K. Yagi,et al.  Lipid peroxide levels of serum lipoprotein fractions of diabetic patients. , 1981, Biochemical medicine.

[40]  C. Casciani,et al.  EFFECT OF L-CARNITINE ON LIPID PATTERN IN HAEMODIALYSIS , 1980, The Lancet.

[41]  N. Unwin,et al.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National , 2009 .

[42]  W. Howard Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins , 2007 .

[43]  M. Malaguarnera,et al.  Diabetes mellitus in the elderly: diagnostic features. , 2006, Archives of gerontology and geriatrics.

[44]  A. Mitwalli,et al.  L-carnitine supplementation in hemodialysis patients. , 2005, Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia.

[45]  M. Malaguarnera,et al.  Levocarnitine Administration in Elderly Subjects with Rapid Muscle Fatigue , 2003, Drugs & aging.

[46]  C. Panneerselvam,et al.  Effects of Levocarnitine on Mitochondrial Antioxidant Systems and Oxidative Stress in Aged Rats , 2003, Drugs in R&D.

[47]  N. Hongu,et al.  Carnitine and choline supplementation with exercise alter carnitine profiles, biochemical markers of fat metabolism and serum leptin concentration in healthy women. , 2003, The Journal of nutrition.

[48]  N. Hongu,et al.  Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise. , 2000, The Journal of nutrition.

[49]  R. Ramsay,et al.  Selective modulation of carnitine long-chain acyltransferase activities. Kinetics, inhibitors, and active sites of COT and CPT-II. , 1999, Advances in experimental medicine and biology.

[50]  P. Holvoet Oxidative modification of low-density lipoproteins in atherothrombosis. , 1998, Acta cardiologica.

[51]  Farris K. Timimi,et al.  Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. , 1996, The Journal of clinical investigation.

[52]  I. Singh,et al.  Nitric Oxide Regulates Peroxisomal Enzyme Activities , 1995, European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies.

[53]  Recommendations guiding physicians in biomedical research involving human subjects. World Medical Association Declaration of Helsinki. , 1994, Le Journal medical libanais. The Lebanese medical journal.

[54]  S. Rankin,et al.  Role of oxidized low density lipoprotein in atherogenesis. , 1992, Progress in lipid research.

[55]  M. Crabbe Diabetic complications : scientific and clinical aspects , 1987 .

[56]  F. Donzelli,et al.  Effect of carnitine on lipid metabolism in the newborn. I. Carnitine supplementation during total parenteral nutrition in the first 48 hours of life. , 1983, Biology of the neonate.