It mainly occurs in the mitochondria, which work to convert food into energy by oxidising fatty acids. Therefore, a disruption in mitochondrial function leads to deficient energy production, an accumulation of fatty acids in the cell, and an increase in reactive oxygen species Virmani and Cirulli, VIRMANI, M.

and CIRULLI, M. The Role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. International Journal of Molecular Sciences, vol. LC is an essential component and plays a role in mitochondrial processes, ATP energy production, and fatty acid metabolism.

It is also involved in controlling gluconeogenesis, ketogenesis, cellular detoxification, and stabilising cell membranes Wang et al. In the mitochondria, the transport of long-chain fatty acids for energy production in peripheral tissues is dependent on LC Center et al.

and ERB, H. Journal of Veterinary Internal Medicine, vol. LC is necessary for the oxidation and transport of fatty acids through the inner mitochondrial membrane Broad et al. and GALLOWAY, S. Effects of exercise intensity and altered substrate availability on cardiovascular and metabolic responses to exercise after oral carnitine supplementation in athletes.

International Journal of Sport Nutrition and Exercise Metabolism, vol. and ANAND, T. Ergogenic effect of dietary L-carnitine and fat supplementation against exercise induced physical fatigue in Wistar rats.

Journal of Physiology and Biochemistry, vol. Carnitine is necessary for the esterification of long fatty acid chains in the mitochondria, which provides energy through beta-oxidation via a series of reactions that convert fatty acids into acetyl-CoA.

In the cytoplasm, fatty acids are converted to acyl-CoA, and LC stimulates the transfer of an acyl group from the cytoplasm to the mitochondria by binding to the carnitine shuttling system on the mitochondrial membrane. L-Carnitine palmitoyltransferase-1 CPT I , which is located on the outer surface of the mitochondria, releases CoA to form an acylcarnitine.

In the mitochondrial matrix, the acyl group of carnitine is dissociated and linked back to coenzyme A by LC palmitoyltransferase-2 CPT II , which is present in the inner mitochondrial membrane, to import long-chain FA into the mitochondria for beta-oxidation, which provides energy for cells Wang et al.

and LI, Q. Carnitine Palmitoyltransferase system: a new target for anti-inflammatory and anticancer therapy? Frontiers in Pharmacology, vol. Carnitine homeostasis is maintained in healthy persons by dietary carnitine absorption, renal carnitine reabsorption, and endogenous LC production.

Cell membrane transporters distribute carnitine between the extracellular compartment and the tissues, maintaining the concentration gradient between them. Humans can obtain carnitine from red meat, chicken, some types of fish, and dairy products; thus, the intake of carnitine for vegetarians is very low because their diets lack foods rich in carnitine sources.

Carnitine from food is absorbed by the epithelial cells lining the small intestine, where it is transported by simple diffusion into the blood circulation. The kidneys reabsorb carnitine through active transport by transporters present in the brush border membranes of the renal tubular cells, and when the dietary intake of carnitine decreases, its reabsorption by the kidneys increases Rebouche, REBOUCHE, C.

and DUNN-LEWIS, C. L-carnitine supplementation: influence upon physiological function. Current Sports Medicine Reports, vol. The amino acids lysine and methionine can be converted to LC in humans via a multi-step process involving numerous cells.

Lysine methyltransferases, which are utilised as methyl donors, are made from the amino acid methionine and methylate protein-bound lysine to generate 6-N-trimethyl lysine, which is essential for carnitine synthesis. The hydroxylation of 6-N-trimethyl lysine yields 3-hydroxyN-trimethyl lysine, which is separated into 4-trimethylaminobutyraldehyde and glycine; subsequently, trimethylaminobutyraldehyde is dehydrogenated to form 4-N-trimethylaminobutyrate γ-butyrobetaine , and this compound produces LC 3-hyroxyN-trimethylaminobutyric acid or β-hydroxy-γ-N-trimethylaminobutyric acid.

Endogenous LC production is mediated by four enzymes, as shown in Figure 3. Except for butyrobetaine hydroxylase, which is not found in the cardiac or skeletal muscle, all four enzymes are widely distributed. However, these enzymes are abundant in the liver, testes, and kidneys in humans Rebouche, REBOUCHE, C.

In: A. CABALLERO, R. COUSINS, K. TUCKER and T. ZIEGLER, eds. Baltimore: Wolters Kluwer Health, pp. L-Carnitine is produced in the liver and transported to the cardiac and skeletal muscle, where it is required for fatty acid oxidation, but it cannot be produced in vegetarians; it was synthesised at a rate of 1.

and FORNASINI, G. Pharmacokinetics of L-carnitine. Clinical Pharmacokinetics, vol. The quantity of methylation on peptide-linked lysine and the average protein rotation controls the pace of LC production. Increased lysine in the diet can boost endogenous LC synthesis; by contrast, LC intake does not affect the rate of endogenous synthesis Rebouche, REBOUCHE, C.

LC is an essential component of the human body that promotes the proper function of the heart and muscular system. It also aids in the appropriate use of glucose by the cell, improving glucose metabolism in patients with diabetes and reducing problems such as tiredness, sleeplessness, and mental activity Karalis et al.

and KLEISIARI, A. L-carnitine as a diet supplement in patients with type ii diabetes. Cureus, vol. Clinical supplementary LC might help people with poor glucose metabolism improve their glucose tolerance.

LC increases the oxidation of fatty acids, which can contribute to insulin resistance in the skeletal muscle; therefore, it may be advantageous to these patients Ringseis et al. and EDER, K. Mechanisms underlying the anti-wasting effect of L-carnitine supplementation under pathologic conditions: evidence from experimental and clinical studies.

European Journal of Nutrition, vol. Supplemental LC was found to lower insulin resistance compared with placebo in a meta-analysis including patients with weakened fasting glucose, type 2 diabetes T2D , and non-alcoholic steatohepatitis Xu et al.

and CUI, G. L-carnitine treatment of insulin resistance: a systematic review and meta-analysis. Advances in Clinical and Experimental Medicine, vol. A meta-analysis of four randomised, placebo-controlled studies demonstrated a decrease in fasting plasma glucose concentration but no change in glycated haemoglobin concentration in patients with T2D mellitus treated with acetyl-L-carnitine ALCAR Vidal-Casariego et al.

and CUERDA-COMPÉS, C. Metabolic effects of L-carnitine on type 2 diabetes mellitus: systematic review and meta-analysis. Supplementing with acyl -L-carnitine may lower fasting blood glucose and glycated haemoglobin concentrations but not insulin resistance Asadi et al.

and MANSOORI, A. The effect of L-carnitine supplementation on lipid profile and glycaemic control in adults with cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled clinical trials.

Clinical Nutrition, vol. The impact of ALCAR was studied in patients with diabetes, hypertension, and dyslipidaemia in a randomised, controlled experiment. and WARNOCK, D. Blood pressure and metabolic effects of acetyl-l-carnitine in type 2 diabetes: DIABASI randomized controlled trial.

Journal of the Endocrine Society, vol. However, therapy with LC has proven to be beneficial for the control of diabetes, insulin resistance, high blood pressure, and dyslipidaemia in prior investigations Zhang et al. and QIN, L. L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study.

Nutrition Journal, vol. In patients with T2D, LC supplementation resulted in a considerable reduction in lipid profile levels. executive summary of the third report of the National Cholesterol Education Program NCEP expert panel on detection, evaluation, and treatment of high blood cholesterol in adults Adult Treatment Panel III.

Journal of the American Medical Association, vol. About half of people with diabetes mellitus have peripheral nerve dysfunction, and about a third of those with diabetes have persistent neuropathic pain Tesfaye and Selvarajah, TESFAYE, S.

Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. As diabetic peripheral neuropathy progresses, it can cause recurring foot sores and infections, which can require amputation Dy et al. and ROBINSON, K. Preventing complications and treating symptoms of diabetic peripheral neuropathy.

Rockville: Agency for Healthcare Research and Quality. Comparative Effectiveness Reviews, no. Rolim et al. and DIB, S. Acetyl-L-carnitine for the treatment of diabetic peripheral neuropathy.

The Cochrane Library, vol. and Sima et al. and AMATO, A. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials.

Diabetes Care, vol. identified some studies that examined the effects of oral ALCAR supplementation in diabetic patients. ALCAR was shown to decrease the degree of pain and improve clinical symptoms in patients with diabetic peripheral neuropathy, as evaluated by a visual analogue scale, according to low-quality data Li et al.

and TIAN, H. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial. Journal of Diabetes Investigation, vol.

In a range of illnesses, including CVD, diabetes, and dyslipidaemia, high levels of LC have been shown to be beneficial Ferrari et al. and CECONI, C. Therapeutic effects of L-carnitine and propionyl-Lcarnitine on cardiovascular diseases: a review.

Because it is unable to produce carnitine, human skeletal and cardiac muscle absorbs relatively high levels of it from the plasma. The heart obtains most of its energy from this source, so CAC deficiency causes cardiomyopathy, cardiac arrhythmia, cardiac insufficiency, and respiratory distress Palmieri, PALMIERI, F.

Diseases caused by defects of mitochondrial carriers: a review. Bioenergetics, vol. Heart failure has also been linked to a lack of carnitine Cave et al. and MCCLAVE, S. Obesity, inflammation, and the potential application of pharmaconutrition.

Nutrition in Clinical Practice, vol. The effects of long-term LC administration on the inflammatory process associated with arterial hypertension were identified in a rat model Miguel-Carrasco et al.

and VAZQUEZ, C. The role of inflammatory markers in the cardioprotective effect of L-carnitine in L-NAME-induced hypertension. American Journal of Hypertension, vol. LC, the physiologically active dietary carnitine 3-hydroxyN-trimethylaminobutyric acid , is a promising alternative medication for secondary heart disease prevention.

OCTN acts as a carnitine transporter in the heart, kidney, liver, pancreas, intestine, brain, placenta, trachea, lung, and thyroid. The carnitine-acylcarnitine carrier CAC is a protein that allows cardiac mitochondria to oxidize fatty acyl, which is the main source of energy for the heart muscle, and deficits in LC or its transporter CAC can cause heart disease Flanagan et al.

and GARRETT, Q. Review role of carnitine in disease. LC supplementation can benefit patients with heart disease because it assists in the return of cardiac energy stores Flanagan et al. LC supplementation for 12 months in patients with chronic heart disease patients was demonstrated to reduce chronic heart diseases and mortality.

As an oral treatment, it was demonstrated to minimise myocardial damage while enhancing glucose metabolism and reducing the toxicity of elevated free fatty acid levels Xue et al.

and REN, H. L-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction.

Cardiovascular Drugs and Therapy, vol. Several studies have found that administering LC right after a heart attack might help to decrease ischemia-induced cardiac muscle damage.

Taking oral LC in addition to normal pharmacological therapy for a year decreased mortality and angina episodes considerably Davini et al. and BOEM, A. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Under Experimental and Clinical Research, vol. Another controlled study including 96 patients found that intravenous LC treatment reduced levels of creatine kinase-MB and troponin-I, two markers of myocardial injury, after myocardial infarction MI Xue et al.

However, not all clinical research has indicated that supplementing with LC after a heart attack is beneficial. In a randomised trial involving 60 people who had an acute MI, no differences in heart function were found between those who received intravenous LC and those who received a placebo Iyer et al.

Does left ventricular function improve with L-carnitine after acute myocardial infarction? Journal of Postgraduate Medicine, vol. Another randomised study found that LC therapy did not affect the incidence of heart failure or death 6 months after MI Tarantini et al.

and ILICETO, S. Metabolic treatment with L-carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology, vol. In individuals who had acute MI, LC treatment reduced the risk of death, ventricular arrhythmias, and angina. The rupture of an atherosclerotic plaque in a coronary artery obstructs the blood flow to the heart muscle, causing injury or damage to the heart muscle and MI DiNicolantonio et al.

L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clinic Proceedings, vol.

Because oral LC supplements are unlikely to be absorbed, procedures that mix intravenous and oral administration are equal to those that employ only oral administration Evans and Fornasini, EVANS, A.

Oral LC supplementation for a long time has been shown to decrease metabolic syndrome and CVD risk factors Wong et al. and RATH, M. Myocardial energetic and the role of micronutrients in heart failure: a critical review. American Journal of Cardiovascular Disease, vol.

According to Wu WU, W. The clinical effects of intravenous L-Carnitine in elderly patients with heart failure of diabetes. Xin Xue Guan Bing Fang Zhi Zhi Shi, vol. When cardiomyocytes experience cardiac failure, they have problems converting substrates into energy; LC levels in the blood are reduced after coronary artery graft surgery, and oxidative stress is increased.

LC supplementation in these individuals has shown benefits in the clinical setting Silva et al. Effect of L-carnitine supplementation on reverse remodeling in patients with ischemic heart disease undergoing coronary artery bypass grafting: a randomized, placebo-controlled trial.

Wang et al. and MAO, C. L-carnitine and heart disease. Life Sciences, vol. mentioned that LC is an endogenous cofactor and may be associated with an increase in mitochondrial oxidation and production of cardiac energy. It increases fatty acid transport across the mitochondrial matrix, lowering oxidative stress, inflammation, and myocyte necrosis while also offering cardioprotective benefits.

LC also adjusts calcium influx, intracellular enzyme release, and membrane phospholipid content, all of which contribute to cellular homeostasis. As a result, dietary and intravenous exogenous carnitine supplementation are efficient strategies for reducing ventricular dysfunction, ischemia-reperfusion damage, cardiac arrhythmia, and toxic myocardial injury are all reduced, all of which are prevalent symptoms of CVD.

Hypertension, hyperlipidemia, diabetic ketoacidosis, hyperglycemia, hyperglycaemia insulin-dependent diabetes mellitus, insulin resistance, obesity, and other variables are all improved by LC.

Individuals with acute and chronic heart failure in various age groups, including infants, juveniles, young adults, adults, and older adults, can benefit from LC. LC boosts fat oxidation and glycogen sparing during exercise, which increases physical performance Johri et al. and SPENCE, J. Carnitine therapy for the treatment of metabolic syndrome and cardiovascular disease: evidence and controversies.

Nutrition, Metabolism, and Cardiovascular Diseases, vol. It has a variety of physiological functions, including antioxidant preservation and increased nitric oxide synthesis Bacurau et al.

and LUÍS, F. Does exercise training interfere with the effects of L-carnitine supplementation? Moreover, LC improves energy generation from fatty acid oxidation Gulcin, GÜLÇIN, I.

Antioxidant and antiradical activities of L-carnitine. and TONKONOGI, M. Turning down lipid oxidation during heavy exercise-what is the mechanism? Journal of Physiology and Pharmacology, vol. LC also regulates the mitochondrial ratio and activates carnitine acyltransferases CAT , which transport fatty acids across the mitochondrial membrane Karlic and Lohninger, KARLIC, H.

and LOHNINGER, A. Supplementation of L-carnitine in athletes: does it make sense? Carnitine may influence triglycerides as well as total cholesterol and its fractions. In obese and insulin-resistant ponies, 14 weeks of carnitine administration reduced blood lipid profile levels Schmengler et al.

and VERVUERT, I. Effects of L-carnitine supplementation on body weight losses and metabolic profile in obese and insulin-resistant ponies during a week body weight reduction programme.

Livestock Science, vol. Furthermore, Coleman and Lee COLEMAN, R. and LEE, D. Enzymes of triacylglycerol synthesis and their regulation. Progress in Lipid Research, vol. suggested that with elevated physiological carnitine levels in the liver, very-low-density lipoprotein LDL , triglyceride, and cholesterol secretion rates were lower.

As a result, reduced LDL production is predicted to raise plasma high-density lipoprotein HDL levels. Athletes have long been interested in using carnitine to improve physical performance by enhancing ATP production, with several types of carnitine being employed.

Previous research suggested that muscle carnitine is reallocated in the muscle after intense physical exercise Muller et al. and RICHTER, T. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults. Metabolism: Clinical and Experimental, vol.

LC is an unbound, water-soluble amine, allowing for an increase in fatty acid metabolism Hoppel, HOPPEL, C. Other studies have found that LC may raise fasting TAG in patients with diabetes Rahbar et al.

and GOLLESTAN, B. Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with type II diabetes mellitus. European Journal of Clinical Nutrition, vol. Therefore, pharmaceutical agents that can correct blood lipid abnormalities, particularly in people with T2D, are critical.

Accordingly, the impact of nutraceuticals on cardiovascular risk factors is a currently a hot research topic Ward et al. and WATTS, G. Recent perspectives on the role of nutraceuticals as cholesterol lowering agents.

Current Opinion in Lipidology, vol. The pharmacological benefits of LC as an additional treatment for dyslipidaemia, notably in individuals with T2D, have been described in several investigations Rahbar et al. LC is a vitamin-like molecule made up of lysine and methionine that is necessary for the fatty acid oxidation in the mitochondria and the protection of cell membranes from free radical damage Peivandi et al.

In patients with chronic renal disease, intake of LC supplements led to a decrease in the level of cholesterol and triglycerides, and an increase in haemoglobin and HDL Naini et al. and NAINI, P. Effects of oral L-carnitine supplementation on lipid profile, anemia, and quality of life in chronic renal disease patients under hemodialysis: A randomized, double-blinded, placebo-controlled trial.

Journal of Nutrition and Metabolism, vol. Effect of L-carnitine supplementation on lipid profiles of patients with liver disease: a systematic review and meta-analysis. Preventive Nutrition and Food Science, vol.

Obesity is a worldwide epidemic that can lead to dyslipidaemia Fried et al. and WIDHALM, K. Interdisciplinary European guidelines on surgery of severe obesity. Obesity Facts, vol. and PASQUALI, R. Pharmacological therapy of obesity.

Giornale Italiano di Cardiologia, vol. Elevated body mass index and fatty liver. Srpski Arhiv za Celokupno Lekarstvo, vol. and VENTURA, H.

The obesity paradox: impact of obesity on the prevalence and prognosis of cardiovascular diseases. Postgraduate Medicine, vol. Individuals often use pharmacotherapy to help them lose weight.

Carnitine is one of the medications that claim to help people with weight loss. Obesity is a severe health issue that has become increasingly linked to elevated rates of mortality and morbidity throughout the world.

Weight reduction is becoming more popular as weight control becomes increasingly challenging in the modern environment. Anti-obesity medicines do not have the same negative side effects as invasive operations, and thus they are more popular than alternative choices, such as physical activity.

Carnitine has been used to treat heart disease Shang et al. and LI, H. Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis.

BMC Cardiovascular Disorders, vol. and CHEN, X. L-carnitine supplementation for adults with end-stage kidney disease requiring maintenance hemodialysis: a systematic review and meta-analysis. The American Journal of Clinical Nutrition, vol.

and BRUNELLI, S. Effects of L-carnitine on dialysis-related hypotension and muscle cramps: a meta-analysis. and HÄRTER, M. Efficacy and acceptability of acute treatments for persistent depressive disorder: a network meta-analysis.

Depression and Anxiety, vol. Only seven participants had suitable data for quantitative examination. This study had good methodological quality, demonstrated that LC had a positive influence on weight and BMI, and showed that LC could help people with chronic illnesses, including diabetes and obesity, lose weight Pooyandjoo et al.

The effect of L- carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. Obesity Reviews, vol. LC, which is important for lipid catabolism and energy generation, is also important for muscle fuel metabolism during exercise and regulating muscle fuel metabolism Kim et al.

and KIM, Y. L-carnitine enhances exercise endurance capacity by promoting muscle oxidative metabolism in mice. Biochemical and Biophysical Research Communications, vol. With its two impacts on glucose and lipid metabolism, LC may aid metabolic illnesses such as T2D and hypertriglyceridemia. LC is a well-known weight-loss and fat-burning substance, and according to a meta-analysis, supplementing with LC lowered body weight, BMI, and fat mass Pooyandjoo et al.

and 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. Clinical Nutrition ESPEN, vol.

Supplementing with LC lowers blood pressure by minimising interactions with the nitric oxide system and insulin resistance Rajasekar et al. and ANURADHA, C. Increase in nitric oxide and reductions in blood pressure, protein kinase C beta II and oxidative stress by L-carnitine: A study in the fructose-fed hypertensive rat.

Clinical and Experimental Hypertension, vol. According to Askarpour et al. and GHAEDI, E. Effects of L-carnitine supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials. Journal of Human Hypertension, vol. LC plays a key role in fatty acid beta-oxidation and lowers the availability of free fatty acids for triglyceride production.

In a study conducted by Malaguarnera et al. and MOTTA, M. L-carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. The intake of LC in patients who are obese and overweight leads to a decrease in body weight and BMI, suggesting that it has an anti-obesity effect Askarpour et al.

Beneficial effects of L-carnitine supplementation for weight management in overweight and obese adults: an updated systematic review and dose-response meta-analysis of randomized controlled trials. Pharmacological Research, vol. The most prevalent dose-limiting adverse effects of cisplatin-induced chemotherapy are hepatic and renal damage Neamatallah et al.

and EID, B. Using LC to reduce the possible negative effects of cisplatin is beneficial during chemotherapy. Elevated liver enzyme activity is recognised as an indication of cellular infiltration and loss of function of hepatocytes because these enzymes are discharged into the blood when the hepatocyte plasma membrane is disrupted Jia et al.

and XU, L. International Immunopharmacology, vol. and ABDELHIEE, E. Anti-inflammatory, anti-oxidant and hepatoprotective effects of lactoferrin in rats.

Drug and Chemical Toxicology, vol. and ABDO, W. Trial for reduction of Ochratoxin A residues in fish feed by using nanoparticles of hydrated sodium aluminum silicates NPsHSCAS and copper oxide.

Toxicon, vol. It was shown that cisplatin-induced hepatotoxicity was accompanied by a considerable change in blood liver enzymes. Cisplatin is absorbed by and deposited in the liver cells, producing damage and an elevation in liver enzyme activity Mohamed and Badawy, MOHAMED, H.

and BADAWY, M. Modulatory effect of zingerone against cisplatin or g-irradiation induced hepatotoxicity by molecular targeting regulation. Applied Radiation and Isotopes, vol.

Furthermore, cisplatin raises creatinine and urea levels Sadeghi et al. Antioxidant and protective effect of Stachys pilifera Benth against nephrotoxicity induced by cisplatin in rats.

Journal of Food Biochemistry, vol. and indicates cisplatin-induced nephrotoxicity. By contrast, Cayir et al. and KELES, M. Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats. Central European Journal of Medicine, vol.

ascribed cisplatin hepatotoxicity and nephrotoxicity to free radical formation in kidney and liver cellular, which causes cellular damage. Furthermore, LC is a naturally occurring substance that is required to generate ATP Tunez et al. and MONTILLA, P.

Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide. Cell Biochemistry and Function, vol. As a result, it contains antioxidant qualities and protects numerous tissues from oxidative stress Cayir et al.

In a rat model, LC lowered liver enzyme activity, oxidative stress, and thioacetamide and tilmicosin-induced damage Aboubakr et al. L-carnitine and vitamin E ameliorate cardiotoxicity induced by tilmicosin in rats.

Environmental Science and Pollution Research International, vol. In rats with acute renal failure, LC increased the antioxidant enzyme activity in kidney tissues Aydogdu et al. and KAYMAK, K. Protective effects of L-carnitine on myoglobinuric acute renal failure in rats. L-carnitine in the lipid and protein protection against ethanol-induced oxidative stress.

Alcohol, vol. LC protects against mitochondrial toxic chemicals and oxidative stress Barhwal et al. Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats.

European Journal of Pharmacology, vol. It also enables beta-oxidation, which reduces the detrimental effects of free fatty acids Furuno et al. and UTSUMI, K. Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition.

Biochemical Pharmacology, vol. People with acute or chronic liver illness can exhibit hepatic encephalopathy, which refers to a variety of neuropsychiatric signs and symptoms. There may be no indications of subclinical hepatic encephalopathy other than aberrant conduct on psychometric tests or vague symptoms.

Disorientation, evident personality changes, inappropriate conduct, somnolence, stupor, confusion, and coma are among the symptoms of overt hepatic encephalopathy.

Hepatic encephalopathy. The New England Journal of Medicine, vol. Although excess valproic acid does not cause toxidrome, it can deplete hepatic LC reserves, making mitochondrial transport via the carnitine shuttle more difficult.

Despite a lack of evidence, LC has been recommended as a feasible treatment for restoring mitochondrial function, minimising toxic metabolite formation, and counteracting or reversing the toxic effects of valproic acid.

A comprehensive analysis identified only eight occurrences of acute valproic acid exposure in adults and children, as well as one study that published safety data from people. Because LC has low oral bioavailability, intravenous therapy was recommended; in addition, most overdose patients were given activated charcoal, rendering oral LC ineffective.

Despite the dearth of data and the likelihood of publication bias, the authors concluded that LC treatment was appropriate for individuals with acute overdose and low levels of consciousness Perrott et al.

and ZED, P. L-carnitine for acute valporic acid overdose: a systematic review of published cases. The Annals of Pharmacotherapy, vol. In addition, a case report described the use of LC to treat PEG-asparaginase-induced hepatotoxicity in a patient with acute lymphoblastic leukaemia Alshiekh-Nasany and Douer, ALSHIEKH-NASANY, R.

and DOUER, D. L-carnitine for treatment of pegasparaginase -induced hepatotoxicity. Acta Haematologica, vol. Yang et al. and SUN, L. Effect of L-carnitine therapy on patients in maintenance hemodialysis: a systematic review and meta-analysis.

Journal of Nephrology, vol. conducted a systematic review and meta-analysis to assess prior findings showing that LC had favourable effects on haemoglobin and erythropoietin dosage in patients undergoing maintenance haemodialysis.

Although LC supplementation reduced LDL cholesterol and C-reactive protein CRP , it had no effect on other lipid markers, haemoglobin, haematocrit, albumin, or the erythropoietin dosage required. The drop in LDL cholesterol was assumed to be insignificant in clinical terms.

There were no known negative consequences Chen et al. Because of a lack of evidence, the Renal Illness Improving Global Outcomes KDIGO clinical practice guidelines for anaemia in chronic renal disease do not advocate LC as an adjuvant treatment KDIGO, KIDNEY DISEASE: IMPROVING GLOBAL OUTCOMES — KDIGO, KDIGO clinical practice guideline for anemia in chronic kidney disease.

Kidney International. Supplement, vol. According to several small studies, it can help with energy generation, cardio-respiratory fitness, and endurance capacity during physical activity Fielding et al.

and BELLAMINE, A. L-carnitine supplementation in recovery after exercise. Nutrients, vol. Because of its function in converting fat into energy, LC is a popular substance among athletes as a potential ergogenic aid Kim et al.

and BLOOMER, R. Effect of glycine propionyl-L-carnitine on aerobic and anaerobic exercise performance. However, the carnitine levels in skeletal muscle phosphocreatine, ATP, glycogen, and lactate were equal in vegetarians and omnivores, as were the measures of physical performance after exercise.

Although LC treatment raised plasma carnitine levels in vegetarians above the levels reported in omnivores, no differences in energy metabolism or physical performance were observed between the two groups Novakova et al.

and KRÄHENBÜHL, S. Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians. and GREENHAFF, P. New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle.

The Journal of Physiology, vol. Frailty is a serious age-related health problem marked by a considerable decrease in physiological reserves and a greater sensitivity to shock. Its phenotype from pre-frailty to frailty is a major predictor of severe unfavourable health problems, such as cardiovascular illnesses Veronese et al.

and CORRELL, C. Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: results from a meta-analysis and exploratory meta-regression analysis.

Ageing Research Reviews, vol. and NG, T. Frailty predicts new and persistent depressive symptoms among community-dwelling older adults: findings from Singapore longitudinal aging study.

Journal of the American Medical Directors Association, vol. and JANSEN, B. Frailty and the prediction of negative health outcomes: A meta-analysis. Frailty is more frequent in older adults because of the steady decline in their functional ability and the increase in functional dependency that occurs as people age Siriwardhana et al.

and WALTERS, K. Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: A systematic review and meta-analysis. BMJ Open, vol. Furthermore, being female, single marital status, a lack of social support, a greater prevalence of comorbidities, disability, and functional restriction have all been identified as important risk factors for the emergence of frailty Manfredi et al.

and COSTA, E. Prevalence of frailty status among the European elderly population: Findings from the Survey of Health, Aging and Retirement in Europe.

Frailty is a condition that affects older populations and is marked by a deterioration in function and a loss of independence in performing everyday tasks.

Unintentional weight loss, fatigue, weakness, sluggishness, and physical inactivity are indications of frailty Fried et al. and ANDERSON, G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. Early stages of frailty are thought to be responsive to therapies that might prevent negative outcomes, such as increased hospitalisation and premature mortality Vermeiren et al.

One study investigated the theory that carnitine deficit leads to frailty by causing mitochondrial malfunction Crentsil, CRENTSIL, V.

Mechanistic contribution of carnitine deficiency to geriatric frailty. The results of study on 50 older adult showed that participants who received LC supplementation exhibited a lower frailty index score and improved strength in a hand grip test, whereas those given a placebo did not Badrasawi et al.

and SINGH, D. Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial.

Clinical Interventions in Aging, vol. Skeletal and muscle mass loss is linked to a loss of muscular strength and occurs as people age Dhillon and Hasni, DHILLON, R. and HASNI, S. Pathogenesis and management of sarcopenia.

Clinics in Geriatric Medicine, vol. as well as in a variety of clinical diseases Ebadi and Montano-Loza, EBADI, M. and MONTANO-LOZA, A. Clinical relevance of skeletal muscle abnormalities in patients with cirrhosis. Digestive and Liver Disease, vol. A low proportion of protein synthesis and degradation leads to skeletal muscle atrophy; according to a preclinical study, LC supplementation may help increase this proportion Ringseis et al.

In a randomised controlled experiment including 28 older women, LC supplementation had no impact on serum pro-inflammatory cytokine concentrations, body mass and composition, or measures of skeletal muscle strength Sawicka et al.

and OLEK, R. L-carnitine supplementation in older women. A pilot study on aging skeletal muscle mass and function. The presence of a defect in liver function in patients with cirrhosis led to weakness and loss of skeletal muscle mass; this study was the first to show the protective effect of LC supplementation on the muscles.

In a retrospective analysis of patients with cirrhosis, those who received LC had lower rates of skeletal muscle loss for at least 6 months compared with those who did not Ohara et al.

and SAKAMOTO, N. L-carnitine suppresses loss of skeletal muscle mass in patients with liver cirrhosis. Hepatology Communications, vol. Muscle cramps are painful involuntary skeletal muscle contractions. LC supplementation at levels of 0. and IZUMI, N. L-carnitine reduces muscle cramps in patients with cirrhosis.

Clinical Gastroenterology and Hepatology, vol. and MICHITAKA, K. Can L-carnitine supplementation and exercise improve muscle complications in patients with liver cirrhosis who receive branched-chain amino acid supplementation?

However, supplemental LC has not yet been proven to be effective in reducing muscular cramps in cirrhotic individuals. A study of 69 patients with diabetes revealed that those who took LC once per day for four months had lower blood sugar levels, fewer muscle cramps, and a higher quality of life than those who took a placebo Imbe et al.

and HANAFUSA, T. Effects of L-carnitine supplementation on the quality of life in diabetic patients with muscle cramps. Endocrine Journal, vol. By contrast, there is currently no evidence that supplementary LC can prevent muscular cramps in individuals receiving haemodialysis Lynch et al.

To determine whether LC can assist with cramping, researchers will need to conduct well-designed experiments. Patients with ongoing symptoms of painful, involuntary contractions of skeletal muscles at rest or waking them up at least three times in the previous month were included in a prospective uncontrolled, nonrandomised study evaluating the effects of LC on reducing muscle cramps in patients with cirrhosis.

Participants were given LC for 8 weeks and reported decreased cramping, and no negative consequences were observed Nakanishi et al. The regulation of cell proliferation and differentiation is dependent on cellular metabolic activity, particularly mitochondrial metabolism.

When applying engineering methods to drive tissue formation and repair, metabolism may be a significant component to consider. Carnitine and its derivative, acetylcarnitine, are tiny metabolites that influence the activity of multiple mitochondrial metabolic pathways.

Adult stem cells were employed as a platform in both monolayer and 3D hydrogel culture systems to investigate the impact of these two small compounds on mesenchymal tissue engineering. The authors examined the effects of these two small compounds on adult stem cell differentiation, as well as gene expression, cell proliferation, and extracellular matrix deposition.

In both culture systems, the compounds inhibited adipogenesis while stimulating osteogenesis and chondrogenesis. According to the findings of our previous study, carnitine and acetylcarnitine may impact the differentiation rate of adult stem cells by influencing mitochondrial metabolism.

The action of these two compounds suggests that such metabolites may be used in tissue-engineering systems to improve cell differentiation and tissue formation Lu et al. and ELISSEEFF, J. Carnitine and acetylcarnitine modulate mesenchymal differentiation of adult stem cells.

Journal of Tissue Engineering and Regenerative Medicine, vol. and KURTOĞLU, F. The effects of L-carnitine on blood and tissue parameters of male rats fed with different levels of fish oil.

Eurasian Journal of Veterinary Sciences, vol. LC plays an important role in intracellular energy metabolism in two ways. First, it participates in beta-oxidation by transporting long-chain fatty acids 12 to 20 carbon atoms to mitochondria, providing an energy source in the form of acylcarnitine.

Second, it reduces the toxicity of free CoA, which is produced when short-chain carbon atoms and medium-chain carbon atoms fatty acids are digested in the mitochondria Calabrese et al.

LC is a naturally occurring molecule that aids long-chain fatty acid entrance into cellular mitochondria, providing a substrate for oxidation and subsequent energy generation. The structure of LC improves and preserves cognitive performance and contributes to improved cognitive ageing over time, and multiple controlled human clinical trials using LC have provided evidence that this substance can improve cognitive function.

Furthermore, because LC is a key cofactor in mammalian mitochondrial energy metabolism, it was hypothesised that acute LC treatment of human tissue cultures would result in observable improvements in mitochondrial function. LC hydrochloride was given to cultures of SH-SY-5Y human neuroblastoma and N1 human astrocytoma cells cultured in well cell culture plates.

and GEIER, M. L-carnitine exposure and mitochondrial function in human neuronal cells. Neurochemical Research, vol. Oxidation is a process that occurs in the cells of the body. This process results in reactive oxygen species ROS and antioxidants; the body is normally able to maintain a balance between ROS and antioxidants, but an imbalance leads to oxidative stress.

When ROS production is increased, it oxidises biomolecules or modifies proteins and activates transcription factors and pro-inflammatory genes, causing inflammation. Oxidative stress, inflammation, and disease. In: T. DZIUBLA and D. Oxidative stress and biomaterials. Amsterdam: Elsevier, pp.

LC plays an active role in the work of the immune system by increasing antioxidant activity and reducing oxidative stress and inflammation Bellamine et al. and COHEN, E. L-carnitine tartrate downregulates the ACE2 receptor and limits SARS-CoV-2 infection.

Effects of L-carnitine on oxidative stress responses in patients with renal disease. Medicine and Science in Sports and Exercise, vol. Administration of LC reduced oxidative damage by increasing glutathione GSH levels and decreasing malondialdehyde MDA , a marker for oxidative stress; an increase in GSH protects cells from free radicals Fathizadeh 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. Journal of Diabetes and Metabolic Disorders, vol. A dose of mg per day of this supplement in patients with sepsis contributed to a reduction in oxidative stress and inflammation Keshani et al.

The effects of L-carnitine supplementation on inflammatory factors, oxidative stress, and clinical outcomes in patients with sepsis admitted to the intensive care unit ICU : study protocol for a double blind, randomized, placebo-controlled clinical trial. Trials, vol. and HARIRI, M. The effect of L-carnitine on inflammatory mediators: a systematic review and meta-analysis of randomized clinical trials.

European Journal of Clinical Pharmacology, vol. A meta-analysis showed that LC reduces inflammatory cytokines in the blood, such as interleukin 6 IL-6 , CRP, MDA, and tumour necrosis factor-α TNF-α , and promotes superoxide dismutase SOD levels in healthy patients.

SOD works to reduce the damage of radicals inside the cells Fathizadeh et al. Lebda et al. and EDRES, H. L-carnitine mitigates bisphenol A-induced hepatic toxicity via activation of Nrf2 and inhibition of pro inflammatory cytokine gene expression in rats.

Veterinarski Arhiv, vol. showed that carnitine protects against bisphenol A-induced hepatic toxicity, as it acts as an antioxidant and increases endogenous antioxidative defences. Carnitine contributes to the protection of mitochondria from oxidative stress, which causes mitochondrial damage and programmed cell death in various cells.

LC contributes to the protection of mitochondria from oxidative stress, which causes mitochondrial damage and programmed cell death in various cells Elkomy et al. and ABOUBAKR, M. Clin Chim Acta. Kumaran S, Panneerselvam KS, Shila S, Sivarajan K, Panneerselvam C. Age-associated deficit of mitochondrial oxidative phosphorylation in skeletal muscle: role of carnitine and lipoic acid.

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