Optimal Performance

Acetyl-L-Carnitine : Exploring Its Cognitive and LTP Related Effects

acetylcarnitine-alcarAcetyl-L-Carnitine (ALCAR) is an amino acid that is naturally produced by the body during normal metabolic processes. It is widely available as a dietary supplement. It is also an ingredient of the Natural Stacks CILTEP formulation.

It has many functions in the body including providing components for the production of acetylcholine, maintaining the body’s antioxidant defenses and providing co-factors for DNA transcription and, as I will explain, perhaps sustaining LTP.

A benefit of acetyl-l-carnitine is that it acts as an antioxidant and thus prevents damage caused by free radicals. The free-radical theory of aging says that damage caused by free radicals, primarily to cell membranes, mitochondria and DNA is one of the primary cause of aging. These free radicals are generated in a small percentage of energy producing reactions in the mitochondria during normal biological processes [1].The anti-oxidant trend in supplementation has been aimed at mitigating some of this free-radical damage with the aim of reducing the effects of aging. ALCAR has been shown in studies to reduce free radical damage due to oxidative stress induced by conditions of low oxygen (hypoxia) [2]. ALCAR has also been combined with R-alpha-lipoic acid for a synergistic antioxidant effect [3].

One of the body’s natural antioxidant enzymes is superoxide dimutase (SOD). SOD catalyzes superoxide free radicals into oxygen and hydrogen peroxide, preventing them from doing oxidative damage to other parts of the cell. Its levels are stabilized by ALCAR in the brain, especially under higher than normal oxidative conditions such as alcohol exposure [4].

Studies have also indicated that ALCAR may be beneficial in a wide variety of diseases. Several studies have been performed showing positive effects from ALCAR supplementation in counteracting animal models of age related cognitive decline [5] as well as alzheimers disease [6], parkinsons [7] and other neurological conditions [8].

Studies have shown that acetylcholine is increased in the brain via supplementation of ALCAR. ALCAR does this by crossing the blood-brain-barrier [9] and providing the acetyl group to Coenzyme A (CoA) to make acetyl-CoA which in turn donates the acetyl group to choline to produce acetylcholine. This process is increased based on the availability of ALCAR [10]. CoA is derived from vitamin B5 [11] (Pantothentic Acid) which is required to produce acetylcholine. Vitamin B1 (Thiamine) is also required to produce acetylcholine [12].

The LTP connection arises in that ALCAR is also important in supplying the nucleus with a supply of acetyl-COA that is used to regulate the access of the nucleus’ transcriptional machinery to the DNA through histone acetylation and deacetylation [13]. One of the users of histone acetylation and deacetylation machinery in the nucleus is CREB [14].

In my previous writings I talked about how forskolin increases cAMP via adenylyl cyclase [15], the PDE4 inhibitor luteolin contained in artichoke extract prevents the breakdown of cAMP [16] and cAMP activated CREB drives the mechanism of Late-LTP [17][18] which is essential to long-term memory. It would be plausible to me that this mechanism of late LTP needs a steady supply of acetyl-CoA to sustain CREB’s transcription activities in the nucleus and mitochondria.

The previously referenced study suggested the acetyl-CoA needed for transcription is provided by acetyl-l-carnitine. Thus, I propose that this could be the reason why acetyl-l-carnitine subjectively improves the effects of CILTeP in that it provides a steady supply of acetyl-COA to the transcription machinery in the nucleus and mitochondria to support Late-LTP.

Additional posts by Abelard Lindsay (@ciltep):

[expand title=”References:”]

  1. Judge S, Jang YM, Smith A, Hagen T, Leeuwenburgh C. Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB J. 2005;19(3):419-21. PMID 15642720
  2. Barhwal K, Hota SK, Jain V, Prasad D, Singh SB, Ilavazhagan G. Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation. Neuroscience. 2009;161(2):501-14. PMID 19318118
  3. Zhang H, Jia H, Liu J, et al. Combined R-alpha-lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease. J Cell Mol Med. 2010;14(1-2):215-25. PMID 20414966
  4. Haorah J, Floreani NA, Knipe B, Persidsky Y. Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: novel protective approach. Free Radic Biol Med. 2011;51(8):1601-9. PMID 21782933
  5. Ando S, Tadenuma T, Tanaka Y, et al. Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res. 2001;66(2):266-71. PMID 11592123
  6. Gavrilova SI, Kalyn IaB, Kolykhalov IV, Roshchina IF, Selezneva ND. [Acetyl-L-carnitine (carnicetine) in the treatment of early stages of Alzheimer’s disease and vascular dementia]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(9):16-22. PMID 22027664
  7. Beal MF. Bioenergetic approaches for neuroprotection in Parkinson’s disease. Ann Neurol. 2003;53 Suppl 3:S39-47. PMID 12666097
  8. Malaguarnera M. Carnitine derivatives: clinical usefulness. Curr Opin Gastroenterol. 2012;28(2):166-76. PMID 22333562
  9. Inano A, Sai Y, Nikaido H, et al. Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2. Biopharm Drug Dispos. 2003;24(8):357-65. PMID 14595704
  10. White HL, Scates PW. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem Res. 1990;15(6):597-601. PMID 2215852
  11. Daugherty M, Polanuyer B, Farrell M, et al. Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. J Biol Chem. 2002;277(24):21431-9. PMID 11923312
  12. Jankowska-kulawy A, Bielarczyk H, Pawełczyk T, Wróblewska M, Szutowicz A. Acetyl-CoA and acetylcholine metabolism in nerve terminal compartment of thiamine deficient rat brain. J Neurochem. 2010;115(2):333-42. PMID 20649840
  13. Madiraju P, Pande SV, Prentki M, Madiraju SR. Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation. Epigenetics. 2009;4(6):399-403. PMID 19755853
  14. Zhang Q, Vo N, Goodman RH. Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB. Mol Cell Biol. 2000;20(14):4970-8. PMID 10866654
  15. Seamon KB, Daly JW. Forskolin: a unique diterpene activator of cyclic AMP-generating systems. J Cyclic Nucleotide Res. 1981;7(4):201-24. PMID 6278005
  16. Ko WC, Shih CM, Lai YH, Chen JH, Huang HL. Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships. Biochem Pharmacol. 2004;68(10):2087-94. PMID 15476679
  17. Lee J, Kim CH, Simon DK, et al. Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J Biol Chem. 2005;280(49):40398-401. PMID 16207717
  18. Deisseroth K, Bito H, Tsien RW. Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity. Neuron. 1996;16(1):89-101. PMID 8562094 [/expand]

Abelard Lindsay

I am the creator of the CILTEP stack. View the thread on Longecity | @ciltep

3 comments

  • Abelard, I currently am taking aniracetam twice a day at 750mg. So I am not on CILTEP because of the warnings you’ve had about the two together. But I do take ALCAR. I am dosing 500mg twice a day. Is that a good dose?

    • What were the warnings about aniracetam and alcar together? I take Aniracetam and ALCAR together every day as part of my Aniracetam-Noopept-ALCAR-Choline Bitartrate stack and the stack seems pretty effective.

      • Abelard does not recommend taking aniracetam and CILTEP together. ALCAR and Ani are perfectly fine. How much ALCAR a day do you take?

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