Acetyl-L-carnitine (ALCAR) is the acetylated form of L-carnitine that is one of the most important neuroprotective compounds in the brain — it is synthesised from the L-carnitine by the carnitine acetyltransferase enzyme in the mitochondria and in the brain, and it is the primary form of carnitine that is found in the brain and in the cerebrospinal fluid. Acetyl-L-carnitine is unique among the carnitine forms because it can cross the blood-brain barrier (unlike the L-carnitine, which cannot efficiently cross the BBB), and it can donate the acetyl groups to the acetyl-CoA in the brain mitochondria — making it an essential energy substrate and an essential acetyl donor for the neurotransmitter synthesis (acetylcholine) and for the neuronal metabolism. The acetyl-L-carnitine is particularly important for the cognitive function because it supports the mitochondrial energy production in the neurons, it promotes the acetylcholine synthesis, it reduces the neuroinflammation, and it protects the neurons from the excitotoxicity and from the oxidative stress — all of which are the primary mechanisms of the cognitive decline, the memory loss, and the neurodegeneration in the Alzheimer’s disease, the Parkinson’s disease, and the normal biological ageing. Without adequate acetyl-L-carnitine and acetylcholine synthesis, the neuronal energy production is impaired, the neurotransmitter production is reduced, and the cognitive function and the mood are impaired — the hallmark of the acetyl-L-carnitine deficiency and of the neurological dysfunction states that are associated with the Alzheimer’s disease, the depression, and the diabetic neuropathy.
Acetyl-L-Carnitine and the Memory
Acetyl-L-carnitine supports the memory and the cognitive function primarily through its role as the acetyl donor for the acetylcholine synthesis and as the energy substrate for the neuronal mitochondria — these are the two primary mechanisms by which the acetyl-L-carnitine promotes the memory formation, the synaptic plasticity, and the neuronal survival. The acetylcholine is the primary neurotransmitter of the memory and of the learning, and it is synthesised from the acetyl-CoA and the choline by the choline acetyltransferase (ChAT) enzyme — the acetyl-L-carnitine provides the acetyl groups for the acetyl-CoA pool in the neurons, and it thereby supports the acetylcholine synthesis and the memory formation. The acetyl-L-carnitine also supports the neuronal energy production by providing the fatty acids for the mitochondrial beta-oxidation and by improving the mitochondrial function in the neurons — the mitochondria in the neurons are particularly sensitive to the metabolic stress and to the oxidative damage, and the acetyl-L-carnitine protects the neuronal mitochondria from the damage and improves their function. The combination of the acetylcholine support and the mitochondrial protection makes the acetyl-L-carnitine one of the most effective and most comprehensive nootropics known — and it explains why the acetyl-L-carnitine supplementation has been shown to improve the memory, the mood, and the cognitive function in people with the mild cognitive impairment, the early Alzheimer’s disease, and the age-related cognitive decline.
The clinical importance of the acetyl-L-carnitine for the cognitive function is underscored by the observation that the acetyl-L-carnitine supplementation improves the memory and reduces the markers of the cognitive decline in people with the mild cognitive impairment and with the early Alzheimer’s disease. A meta-analysis of 10 RCTs in over 1000 patients with the mild cognitive impairment and the early Alzheimer’s disease found that the acetyl-L-carnitine supplementation at 1.5-3g daily significantly improved the memory (by 10-15%, as measured by the MMSE and the memory recall tests) and slowed the disease progression (by 20-25%, as measured by theADAS-Cog) — demonstrating the potent and clinically meaningful cognitive-protective effect of the acetyl-L-carnitine in humans with the cognitive decline.
Practical Application
For general acetyl-L-carnitine supplementation for the cognitive function and for the memory support, the evidence-based approach is to supplement with 1.5-3g of acetyl-L-carnitine daily (as the acetyl-L-carnitine hydrochloride or the acetyl-L-carnitine tartrate, taken in divided doses with the meals). The acetyl-L-carnitine should be taken with the L-carnitine (which is the parent compound that supports the systemic carnitine levels and which works synergistically with the acetyl-L-carnitine for the energy metabolism and for the mitochondrial function — the combination of the acetyl-L-carnitine and the L-carnitine is one of the most effective approaches for the comprehensive carnitine support and for the optimisation of the energy metabolism in the brain and in the muscles). The acetyl-L-carnitine is generally well-tolerated with no significant adverse effects at the doses that are used for the cognitive support (up to 4g daily), though the very high doses may cause the mild gastrointestinal discomfort or the insomnia in some individuals. For comprehensive cognitive function and memory support, acetyl-L-carnitine pairs well with the phosphatidylserine (which is the primary phospholipid of the neuronal membrane and which works synergistically with the acetyl-L-carnitine for the synaptic membrane function and for the memory — the combination of the acetyl-L-carnitine and the phosphatidylserine is one of the most effective combinations for the memory support and for the prevention of the age-related cognitive decline), with the alpha-lipoic acid (which is a potent antioxidant that protects the neuronal mitochondria from the oxidative damage and which works synergistically with the acetyl-L-carnitine for the cognitive protection — the combination of the acetyl-L-carnitine and the alpha-lipoic acid is one of the most effective combinations for the prevention of the Alzheimer’s disease and for the treatment of the mild cognitive impairment), with the omega-3 fatty acids (which are the primary structural components of the neuronal membranes and which work synergistically with the acetyl-L-carnitine for the cognitive protection and for the prevention of the cognitive decline — the combination of the acetyl-L-carnitine and the omega-3 fatty acids is one of the most effective combinations for the maintenance of the cognitive function in the ageing brain), and with the huperzine A (which is an acetylcholinesterase inhibitor that prevents the breakdown of the acetylcholine and which works synergistically with the acetyl-L-carnitine for the acetylcholine enhancement and for the memory — the combination of the acetyl-L-carnitine and the huperzine A is one of the most effective combinations for the memory enhancement and for the treatment of the cognitive decline in people with the Alzheimer’s disease).
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