Acetyl-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 .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) . ALCAR has also been combined with R-alpha-lipoic acid for a synergistic antioxidant effect .
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 .
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  as well as alzheimers disease , parkinsons  and other neurological conditions .
Studies have shown that acetylcholine is increased in the brain via supplementation of ALCAR. ALCAR does this by crossing the blood-brain-barrier  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 . CoA is derived from vitamin B5  (Pantothentic Acid) which is required to produce acetylcholine. Vitamin B1 (Thiamine) is also required to produce acetylcholine .
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 . One of the users of histone acetylation and deacetylation machinery in the nucleus is CREB .
In my previous writings I talked about how forskolin increases cAMP via adenylyl cyclase , the PDE4 inhibitor luteolin contained in artichoke extract prevents the breakdown of cAMP  and cAMP activated CREB drives the mechanism of Late-LTP  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):
- The Nootropic Why
- Magnesium L-Threonate Can Improve Brain Function and LTP
- CILTEP and Racetams: Evidence for a theory of complementary mechanisms of action
- Some Health Benefits of Resveratrol Could Theoretically Apply to CILTEP
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