ALCAR (Acetyl L Carnitine)

Acetyl L-Carnitine (ALCAR)

Key Studies on Acetyl L Carnitine (ALCAR)

  • Carnitines play an important role as carriers of activated fatty acids across the inner mitochondrial membrane and are essential for energy production through fatty acid metabolism.
  • Carnitine in humans is derived from diet and de novo biosynthesis using lysine and methionine.
  •  After synthesis, carnitine is transported through the circulation and is then taken up by other tissues through active transport systems.
  • It enhances acetylcholine production, and stimulates protein and membrane phospholipids synthesis, provides a substrate reservoir for cellular energy production, thereby preventing excessive neuronal cell death. (R1)
  • Carinitine helps with the removal of accumulated toxic fatty acyl-CoA metabolites, and help in buffering the balance between free and acyl-CoA.

How ALCAR aids Mitochondrial Dysfunction?

  • Mitochondrial function is maintained by the Acyltransferase pathway, where fatty acids are transported into the mitochondria via Carnitine for subsequent oxidation to generate ATP. Carnitines also remove the Acyl groups from the mitochondria. However an increase in fatty acid levels can cause mitochondrial dysfunction resulting in cell death and reactive oxygen species. (R2) However these effects have been seen to be attenuated by Carnitine, which works by decreasing the free fatty acid levels in serum and tissues. (R3) 
  • Other studies have also shown that Carnitine even enhances fatty acid metabolism and helps to revive the myocardium. (R4)  
  •  Acetyl-L-carnitine administration has shown the recovery of neuropsychological activities related to attention/concentration, physical fatigue (R5), mental flexibility, language short-term memory, attention, depression and computing ability. (R6) In fact, Acetyl-L-carnitine induces ureagenesis leading to decreased blood and brain ammonia levels. (R7)
  • In rodents, L-Carnitine supplementation appeared to prevent ammonia toxicity on three levels: Activation of cycle enzymes (R8), Interaction with glutamate receptors (R9) ; Reduction of free radicals. (R10)

References

  • R1. Di Cesare Mannelli, L.; Ghelardini, C.; Toscano, A.; Pacini, A.; Bartolini, A., The neuropathy-protective agent acetyl-L-carnitine activates protein kinase C-gamma and MAPKs in a rat model of neuropathic pain. Neuroscience 2010, 165 (4), 1345-52.
  • R2. Sharma, S.; Black, S. M., Carnitine Homeostasis, Mitochondrial Function, and Cardiovascular Disease. Drug discovery today. Disease mechanisms 2009, 6 (1-4), e31-e39.
  • R3. (a) Kuwajima, M.; Horiuchi, M.; Harashima, H.; Lu, K.; Hayashi, M.; Sei, M.; Ozaki, K.; Kudo, T.; Kamido, H.; Ono, A.; Saheki, T.; Shima, K., Cardiomegaly in the juvenile visceral steatosis (JVS) mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-carnitine injection. Febs Lett 1999, 443 (3), 261-6; (b) Chang, B.; Nishikawa, M.; Nishiguchi, S.; Inoue, M., L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria. Int J Cancer 2005, 113 (5), 719-29.
  • R4. Bayeva, M.; Gheorghiade, M.; Ardehali, H., Mitochondria as a therapeutic target in heart failure. J Am Coll Cardiol 2013, 61 (6), 599-610.
  • R5. Malaguarnera, M.; Vacante, M.; Giordano, M.; Pennisi, G.; Bella, R.; Rampello, L.; Malaguarnera, M.; Li Volti, G.; Galvano, F., Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. The American journal of clinical nutrition 2011, 93 (4), 799-808.
  • R6. Malaguarnera, M.; Bella, R.; Vacante, M.; Giordano, M.; Malaguarnera, G.; Gargante, M. P.; Motta, M.; Mistretta, A.; Rampello, L.; Pennisi, G., Acetyl-L-carnitine reduces depression and improves quality of life in patients with minimal hepatic encephalopathy. Scandinavian journal of gastroenterology 2011, 46 (6), 750-9.
  • R7. Malaguarnera, M.; Gargante, M. P.; Cristaldi, E.; Vacante, M.; Risino, C.; Cammalleri, L.; Pennisi, G.; Rampello, L., Acetyl-L-carnitine treatment in minimal hepatic encephalopathy. Digestive diseases and sciences 2008, 53 (11), 3018-25.
  • R8. Ratnakumari, L.; Qureshi, I. A.; Butterworth, R. F., Effect of L-carnitine on cerebral and hepatic energy metabolites in congenitally hyperammonemic sparse-fur mice and its role during benzoate therapy. Metabolism: clinical and experimental 1993, 42 (8), 1039-46.
  • R9. Rodrigo, R.; Cauli, O.; Boix, J.; ElMlili, N.; Agusti, A.; Felipo, V., Role of NMDA receptors in acute liver failure and ammonia toxicity: therapeutical implications. Neurochem Int 2009, 55 (1-3), 113-8.
  • R10. Rose, C.; Felipo, V., Limited capacity for ammonia removal by brain in chronic liver failure: potential role of nitric oxide. Metabolic brain disease 2005, 20 (4), 275-83.

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