Acetylcarnitine

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Acetylcarnitine
Acetylcarnitine.svg
Systematic (IUPAC) name
(R)-3-Acetyloxy-4-trimethylammonio-butanoate
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration
Oral
Legal status
Legal status
  • Over-the-counter
Pharmacokinetic data
Bioavailability >10%
Biological half-life 4.2 hours[1]
Identifiers
CAS Number 3040-38-8 YesY
ATC code N06BX12 (WHO)
PubChem CID 7045767
ChemSpider 5406074 YesY
UNII 6DH1W9VH8Q YesY
ChEBI CHEBI:57589 YesY
ChEMBL CHEMBL1697733 N
Chemical data
Formula C9H17NO4
Molar mass 203.236
 NYesY (what is this?)  (verify)

Acetyl-L-carnitine, ALCAR or ALC, is an acetylated form of L-carnitine. It is naturally produced by the body, although it is often taken as a dietary supplement. Acetylcarnitine is broken down in the blood by plasma esterases to carnitine which is used by the body to transport fatty acids into the mitochondria for breakdown.[2]

Biochemical production and action[edit]

ALCAR is an acetylated derivative of L-carnitine. During strenuous exercise, a large portion of L-carnitine and unused acetyl-CoA are converted to ALCAR and CoA inside mitochondria by carnitine O-acetyltransferase.[2][3] The ALCAR is transported outside the mitochondria where it converts back to the two constituents. The L-carnitine is cycled back into the mitochondria with acyl groups to facilitate fatty acid utilization, but excess acetyl-CoA may block it.[4][5] Excess acetyl-CoA causes more carbohydrates to be used for energy at the expense of fatty acids. This occurs by different mechanisms inside and outside the mitochondria. ALCAR transport decreases acetyl-CoA inside the mitochondria, but increases it outside.[6][7] Glucose metabolism in diabetics improves with administration of either ALCAR[8] or L-carnitine.[9] ALCAR decreases glucose consumption in favor of fat oxidation in non-diabetics.[10] A portion of L-carnitine is converted to ALCAR after ingestion in humans.[11]

Absorption compared to L-carnitine[edit]

It has been claimed ALCAR is superior to L-carnitine in terms of bioavailability.[2][12] Both use the same mechanism for intestinal absorption that improves with sodium.[13] One study shows ALCAR has a lower blood concentration in humans after ingestion[14] possibly because ALCAR is hydrolyzed more in blood.[15]

Health effects[edit]

Early research which seemed to suggest acetylcarnitine had potential as a treatment for dementia were not strongly substantiated by later research, and the substance is not routinely used for this purpose.[16] Combinations with other nutrients, however, have shown better results and are currently under investigation.[17] ALCAR may also have some neuroprotective benefit in the treatment of Parkinson's disease, but further research is required.[18]

It has been suggested that ALCAR may have potential as a drug for treating peripheral neuropathic pain.[19] One way through which ALCAR may accomplish this is by helping regenerate injured or stunted nerves [20] via the release of nerve growth factor.[21]

A single case study published in the March 2015 issue of the Journal of the American Academy of Audiology came to the conclusion that it may be a "valuable pharmacological option in the treatment of tinnitus."[22]

It has been shown that ALCAR interferes with thyroid function by inhibiting triiodothyronine (T3) and thyroxine (T4) from entering the cell nuclei.[23] Therefore, it has some potential in the treatment of hyperthyroidism.[24] Conversely, people with low thyroid function should use it cautiously as large doses could precipitate a drop in thyroid hormones potentially leading to fatigue and mental sluggishness (the opposite of what is usually sought after by starting ALCAR supplementation).

ALCAR is also known to increase sperm motility.[25]

A note ought to be made about ALCAR's purported relationship to seizures. People with epileptic disorders/vulnerability are advised, on product monographs and pharmacy databases, to avoid carnitine and its derivatives as it is claimed to promote epileptic discharges. It now appears that this advice has been misguided. According to a systematic review of epileptics treated with valproic acid, these claims are unsubstantiated both in the scientific literature and in clinical practice and may have done more harm than good.[26] This is unfortunate as many epileptics actually have decreased levels of carnitine (especially those under valproate treatment) and might need to supplement with this substance in order to avoid troubling side effects (e.g., hepatotoxicity, hyperammonemic encephalopathy). The exact reason for these cautionary notes against carnitine is not known. One possibility is that a well-intended, but ultimately false, disclaimer has propagated uncontrollably throughout pharmacy texts and electronic databases worldwide. Another possibility is that some of the side effects of ALCAR (e.g., overstimulation, dizziness, headache, nausea) may mimic, and thus be mistaken for, a mild epileptic fit.

Ethanol neurotoxicity[edit]

Acetylcarnitine has been shown to reduce ethanol-induced neurotoxicity in mice.[27]

References[edit]

  1. ^ "Acetyl-L-carnitine. Monograph." (PDF). Alternative Medicine Review 15 (1): 76–83. April 2010. PMID 20359271. 
  2. ^ a b c Activation and transportation of fatty acids to the mitochondria via the carnitine shuttle.
  3. ^ Zeyner A, Harmeyer J (1999). "Metabolic functions of L-carnitine and its effects as feed additive in horses. A review". Archiv für Tierernährung 52 (2): 115–38. doi:10.1080/17450399909386157. PMID 10548966. 
  4. ^ Longnus SL, Wambolt RB, Barr RL, Lopaschuk GD, Allard MF (October 2001). "Regulation of myocardial fatty acid oxidation by substrate supply". American Journal of Physiology. Heart and Circulatory Physiology 281 (4): H1561–7. PMID 11557544. 
  5. ^ Lysiak W, Lilly K, DiLisa F, Toth PP, Bieber LL (January 1988). "Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-CoA and CoASH in rat heart and liver mitochondria". The Journal of Biological Chemistry 263 (3): 1151–6. PMID 3335535. 
  6. ^ Kiens B (January 2006). "Skeletal muscle lipid metabolism in exercise and insulin resistance". Physiological Reviews 86 (1): 205–43. doi:10.1152/physrev.00023.2004. PMID 16371598. 
  7. ^ Lopaschuk GD, Gamble J (October 1994). "The 1993 Merck Frosst Award. Acetyl-CoA carboxylase: an important regulator of fatty acid oxidation in the heart". Canadian Journal of Physiology and Pharmacology 72 (10): 1101–9. doi:10.1139/y94-156. PMID 7882173. 
  8. ^ Giancaterini A, De Gaetano A, Mingrone G, et al. (June 2000). "Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients". Metabolism: Clinical and Experimental 49 (6): 704–8. doi:10.1053/meta.2000.6250. PMID 10877193. 
  9. ^ Mingrone G, Greco AV, Capristo E, et al. (February 1999). "L-carnitine improves glucose disposal in type 2 diabetic patients". Journal of the American College of Nutrition 18 (1): 77–82. doi:10.1080/07315724.1999.10718830. PMID 10067662. 
  10. ^ Stephens FB, Constantin-Teodosiu D, Greenhaff PL (June 2007). "New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle". The Journal of Physiology 581 (Pt 2): 431–44. doi:10.1113/jphysiol.2006.125799. PMC 2075186. PMID 17331998. 
  11. ^ Cao Y, Wang YX, Liu CJ, Wang LX, Han ZW, Wang CB (2009). "Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers". Clinical and Investigative Medicine 32 (1): E13–9. PMID 19178874. 
  12. ^ Jane Higdon (October 2002). "L-Carnitine". Linus Pauling Institute at Oregon State University. 
  13. ^ Hamilton JW, Li BU, Shug AL, Olsen WA (July 1986). "Carnitine transport in human intestinal biopsy specimens. Demonstration of an active transport system". Gastroenterology 91 (1): 10–6. PMID 3710058. 
  14. ^ Eder K, Felgner J, Becker K, Kluge H (January 2005). "Free and total carnitine concentrations in pig plasma after oral ingestion of various L-carnitine compounds". International Journal for Vitamin and Nutrition Research 75 (1): 3–9. doi:10.1024/0300-9831.75.1.3. PMID 15830915. 
  15. ^ Rebouche CJ (November 2004). "Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism". Annals of the New York Academy of Sciences 1033: 30–41. doi:10.1196/annals.1320.003. PMID 15591001. 
  16. ^ Hudson S, Tabet N (2003). "Acetyl-L-carnitine for dementia". Cochrane Database Syst Rev (Systematic review) (2): CD003158. doi:10.1002/14651858.CD003158. PMID 12804452. 
  17. ^ Remington R, Bechtel C, Larsen D, Samar A, Doshanjh L, Fishman P, Luo Y, Smyers K, Page R, Morrell C, Shea TB (2015). "A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer's Disease". J Alzheimers Dis 45 (2): 395–405. doi:10.3233/JAD-142499. PMID 25589719. 
  18. ^ Beal MF (2003). "Bioenergetic approaches for neuroprotection in Parkinson's disease". Annals of Neurology 53 (Suppl 3): S39–47; discussion S47–8. doi:10.1002/ana.10479. PMID 12666097. 
  19. ^ Chiechio S, Copani A, Gereau RW, Nicoletti F (2007). "Acetyl-L-carnitine in neuropathic pain: experimental data". CNS Drugs. 21 Suppl 1: 31–8; discussion 45–6. doi:10.2165/00023210-200721001-00005. PMID 17696591. 
  20. ^ Farahpour MR, Ghayour SJ (2014). "Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat". Int J Surg 12 (12): 1409–1415. PMID 25448663. 
  21. ^ Taglialatela G, Angelucci L, Ramacci MT, Werrbach-Perez K, Jackson GR, Perez-Polo JR (1992). "Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine". Biochem Pharmacol 44 (3): 577–585. PMID 1324679. 
  22. ^ Gopal KV, Thomas BP, Mao D, Lu H (2015). "Efficacy of carnitine in treatment of tinnitus: evidence from audiological and MRI measures-a case study". Journal of the American Academy of Audiology 26 (3): 311–24. doi:10.3766/jaaa.26.3.10. PMID 25751698. 
  23. ^ Benvenga S, Amato A, Calvani M, Trimarchi F (2004). "Effects of carnitine on thyroid hormone action". Ann. N.Y. Acad. Sci 1033: 158–167. PMID 15591013. 
  24. ^ Chee R, Agah R, Vita R, Benvenga S (2014). "L-carnitine treatment in a seriously ill cancer patient with severe hyperthyroidism". Hormones (Athens) 13 (3): 407–412. doi:10.14310/horm.2002.1494. PMID 25079466. 
  25. ^ [unreliable medical source?]Hathcock JN, Shao A (October 2006). "Risk assessment for carnitine". Regulatory Toxicology and Pharmacology 46 (1): 23–8. doi:10.1016/j.yrtph.2006.06.007. PMID 16901595. 
  26. ^ Zeiler FA, Sader N, Gillman LM, West M (2016). "Levocarnitine induced seizures in patients on valproic acid: A negative systematic review". Seizure 36: 36–39. doi:10.1016/j.seizure.2016.01.020. PMID 26889779. 
  27. ^ Rump TJ, Abdul Muneer PM, Szlachetka AM, Lamb A, Haorei C, Alikunju S, Xiong H, Keblesh J, Liu J, Zimmerman MC, Jones J, Donohue TM, Persidsky Y, Haorah J (2010). "Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain". Free Radical Biology & Medicine 49 (10): 1494–504. doi:10.1016/j.freeradbiomed.2010.08.011. PMC 3022478. PMID 20708681. 

Further reading[edit]

Other reviews[edit]