L-Carnitine Supplementation in the Diabetic Heart

Carnitine; Energy Metabolism; Polymerase Chain Reaction

Carnitine is a non-essential nutrient, which is derived from amino acids. The main food source of carnitine is red meat, poultry and dairy products. Part of the carnitine can be produced endogenously, from lysine and methionine mainly by the liver and kidneys.¹ It acts primarily as an enzymatic cofactor for the transport of long-chain fatty acids from the cytoplasm into the mitochondria, and subsequent degradation to beta-oxidation, being a very important energy metabolism pathway. Therefore, carnitine is essential as fuel for muscles, and more than 95% of the total body carnitine is found in skeletal muscle.¹ The liver, heart, brain and kidneys have the remainder of the body’s carnitine reserves or are able to synthesize it.¹ This distribution shows the importance of carnitine in these organs. L-carnitine supplementation has been studied in sarcopenia,² in liver diseases,³ in heart failure,⁴ in kidney diseases⁵ and in neurological diseases.⁶ , ⁷

Most studies have shown the benefit of L-carnitine on cardiovascular risk factors. L-carnitine supplementation reduces hypertension, hyperlipidemia, hyperglycemia, insulin-dependent diabetes mellitus, insulin resistance, obesity, inflammation and oxidative stress.⁴ , ⁸ - ¹²

In addition to attenuating risk factors for atherosclerosis, L-carnitine supplementation can improve the energy metabolism of the “diabetic” heart. The improvement can occur by normalizing the manipulation of the acetyl and acyl groups by the mitochondria, as L-carnitine is responsible for their transfer through the mitochondrial membrane.¹³ Another proposed mechanism is that L-carnitine supplementation can improve the inflammatory and oxidative cardiac microenvironment caused by hyperglycemia.¹⁴ Thus, a systematic review article and meta-analysis of randomized clinical trials showed that L-carnitine supplementation was associated with a reduction in the levels of CRP, Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and plasma malondialdehyde, and increased plasma levels of superoxide dismutase.⁹

Regarding obesity, a systematic review showed that L-carnitine supplementation reduced body weight, body mass index (BMI) and fat mass, and the subgroup analysis based on the participants’ basal BMI range showed more reductions in overweight or obese adults than in those within the normal BMI range.¹²

The article published in this issue of the Arquivos Brasileiros de Cardiologia is based on obesity, diabetes and inflammation.¹⁵

The authors presented results of an experimental study, in which obese mice with induced diabetes received L-carnitine. Chemerin protein and Chemokine-like Receptor 1 (CMKLR1) levels in serum, cardiac and adipose tissue, as well as other inflammatory markers were evaluated, in addition to insulin resistance.¹⁵

Chemerin is a new adipokine that participates in the early stages of acute inflammation and participates in the development of hypertension, progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor.¹⁶ The authors were able to demonstrate an association between L-carnitine consumption and a reduction in serum chemerin values and in cardiac and adipose tissue in treated diabetic mice, in addition to a reduction in the levels of other inflammatory markers (IL-1β and TNF-α) after 4 weeks of treatment. They also observed that the group submitted to the intervention had a better insulin resistance profile.¹⁵

The decrease in the levels of chemerin and other inflammatory markers may be showing the importance of the inflammatory process in the diabetic heart. However, it is still too early to recommend L-carnitine supplementation. Some studies have shown that carnitine degradation products by the intestinal microbiota can generate Trimethylamine N-oxide (TMAO).¹⁷ A systematic review showed that TMAO was associated with an increase in cardiovascular events and mortality in a dose-dependent manner.¹⁷ Thus, more studies are necessary to understand the role of L-carnitine supplementation in the adjuvant treatment of the diabetic heart.

Referências

• ¹
  Dahash BA, Sankararaman S. Carnitine deficiency. Treasure Island: StatPearls Publishing LLC; 2021.
• ²
  Ebadi M, Bhanji RA, Mazurak VC, Montano-Loza AJ. Sarcopenia in Cirrhosis: From Pathogenesis to Interventions. J Gastroenterol. 2019;54(10):845-59. doi: 10.1007/s00535-019-01605-6.
• ³
  Ishikawa H, Takaki A, Tsuzaki R, Yasunaka T, Koike K, Shimomura Y, et al. L-carnitine Prevents Progression of Non-Alcoholic Steatohepatitis in a Mouse Model with Upregulation of Mitochondrial Pathway. PLoS One. 2014;9(7):e100627. doi: 10.1371/journal.pone.0100627.
• ⁴
  Wang ZY, Liu YY, Liu GH, Lu HB, Mao CY. l-Carnitine and Heart Disease. Life Sci. 2018;194:88-97. doi: 10.1016/j.lfs.2017.12.015.
• ⁵
  Morgans HA, Chadha V, Warady BA. The Role of Carnitine in Maintenance Dialysis Therapy. Pediatr Nephrol. 2021;36(8):2545-51. doi: 10.1007/s00467-021-05101-z.
• ⁶
  Kpka A, Ochociska A, Chojnowska S, Borzym-Kluczyk M, Skorupa E, Kna M, et al. Potential Role of L-Carnitine in Autism Spectrum Disorder. J Clin Med. 2021;10(6):1202. doi: 10.3390/jcm10061202.
• ⁷
  Kepka A, Ochocinska A, Borzym-Kluczyk M, Skorupa E, Stasiewicz-Jarocka B, Chojnowska S, et al. Preventive Role of L-Carnitine and Balanced Diet in Alzheimer’s Disease. Nutrients. 2020;12(7):1987. doi: 10.3390/nu12071987.
• ⁸
  Abbasnezhad A, Hasanavand A, Falahi E, Kashkooli S, Asbaghi O, Choghakhori R. Effect of L-Carnitine Supplementation on Lipid Profiles of Patients with Liver Disease: A Systematic Review and Meta-Analysis. Prev Nutr Food Sci. 2020;25(2):124-32. doi: 10.3746/pnf.2020.25.2.124.
• ⁹
  Fathizadeh H, Milajerdi A, Reiner Ž, Amirani E, Asemi Z, Mansournia MA, et al. The Effects of L-Carnitine Supplementation on Indicators of Inflammation and Oxidative Stress: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Diabetes Metab Disord. 2020;19(2):1879-94. doi: 10.1007/s40200-020-00627-9.
• ¹⁰
  Alanazi WA, Al-Harbi NO, Imam F, Ansari MA, Alhoshani A, Alasmari AF, et al. Role of Carnitine in Regulation of Blood Pressure (MAP/SBP) and Gene Expression of Cardiac Hypertrophy Markers (/-MHC) During Insulin-Induced Hypoglycaemia: Role of Oxidative Stress. Clin Exp Pharmacol Physiol. 2021;48(4):478-89. doi: 10.1111/1440-1681.13455.
• ¹¹
  Serban MC, Sahebkar A, Mikhailidis DP, Toth PP, Jones SR, Muntner P, et al. Impact of L-Carnitine on Plasma Lipoprotein(a) Concentrations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sci Rep. 2016;6:19188. doi: 10.1038/srep19188.
• ¹²
  Talenezhad N, Mohammadi M, Ramezani-Jolfaie N, Mozaffari-Khosravi H, Salehi-Abargouei A. Effects of L-Carnitine Supplementation on Weight Loss and Body Composition: A Systematic Review and Meta-Analysis of 37 Randomized Controlled Clinical Trials with Dose-Response Analysis. Clin Nutr ESPEN. 2020;37:9-23. doi: 10.1016/j.clnesp.2020.03.008.
• ¹³
  Savic D, Ball V, Curtis MK, Fialho MDLS, Timm KN, Hauton D, et al. L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI. Metabolites. 2021;11(3):191. doi: 10.3390/metabo11030191.
• ¹⁴
  Vacante F, Senesi P, Montesano A, Frigerio A, Luzi L, Terruzzi I. L-Carnitine: An Antioxidant Remedy for the Survival of Cardiomyocytes under Hyperglycemic Condition. J Diabetes Res. 2018;2018:4028297. doi: 10.1155/2018/4028297.
• ¹⁵
  Amiri R, Tabandeh MR, Hosseini SA. Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues. Arq Bras Cardiol. 2021; 117(4):715-725.
• ¹⁶
  Kostopoulos CG, Spiroglou SG, Varakis JN, Apostolakis E, Papadaki HH. Chemerin and CMKLR1 Expression in Human Arteries and Periadventitial Fat: A Possible Role for Local Chemerin in Atherosclerosis? BMC Cardiovasc Disord. 2014;14:56. doi: 10.1186/1471-2261-14-56.
• ¹⁷
  Schiattarella GG, Sannino A, Toscano E, Giugliano G, Gargiulo G, Franzone A, et al. Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide as Cardiovascular Risk Biomarker: A Systematic Review and Dose-Response Meta-Analysis. Eur Heart J. 2017 Oct 14;38(39):2948-2956. doi: 10.1093/eurheartj/ehx342.

• Short Editorial related to the article: Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues

Publication Dates

• Publication in this collection
  25 Oct 2021
• Date of issue
  Oct 2021