Acetyl-L-carnitine (ALCAR, also called acetyl-carnitine) is the acetylated form of the L-carnitine that is the preferred fuel for the brain — it is synthesised in the mitochondria from the L-carnitine and the acetyl-CoA, and it is transported to the brain and to the peripheral nervous system where it plays a critical role in the neuronal energy metabolism, the acetylcholine synthesis, and the mitochondrial function. The ALCAR is unique among the carnitine forms because it crosses the blood-brain barrier (unlike the L-carnitine, which does not efficiently cross the BBB) and because it is directly used by the neurons for the energy production and for the acetylcholine synthesis — making it one of the most effective nootropics and neuroprotective compounds available. The ALCAR is particularly important for the cognitive function because it provides the acetyl groups for the acetylcholine synthesis (thereby supporting the memory and the learning), it transports the fatty acids into the neuronal mitochondria for the beta-oxidation (thereby providing the energy for the neuronal function), and it protects the neurons from the oxidative damage and from the excitotoxicity (thereby preventing the neurodegeneration). Without adequate ALCAR and neuronal energy metabolism, the cognitive function declines, the peripheral nerves become dysfunctional, and the neurodegeneration accelerates — the hallmark of the ALCAR deficiency and of the age-related cognitive decline. The typical supplement dose is 1-3g of ALCAR daily — making it one of the most evidence-based and most widely used nootropics for the cognitive support and for the neuroprotection.
ALCAR and the Cognitive Function
ALCAR supports the cognitive function primarily through three mechanisms — it provides the energy for the neuronal function (by transporting the fatty acids into the neuronal mitochondria for the beta-oxidation), it provides the acetyl groups for the acetylcholine synthesis (thereby supporting the memory and the learning), and it protects the neurons from the oxidative damage and from the mitochondrial dysfunction (which are the primary drivers of the age-related cognitive decline and of the neurodegenerative diseases). The brain is one of the most energy-demanding organs in the body — it consumes approximately 20% of the resting metabolic rate (approximately 3.5mL of oxygen per 100g of brain tissue per minute, or approximately 6kcal per hour for the whole brain), and this high energy demand is met almost exclusively by the glucose oxidation (through the glycolysis and the oxidative phosphorylation in the neuronal mitochondria). The ALCAR supports this high energy demand by providing the fatty acids for the mitochondrial oxidation — and during the fasting or the carbohydrate restriction (when the glucose availability is limited), the ALCAR becomes an increasingly important energy substrate for the brain. The ALCAR also provides the acetyl groups for the acetylcholine synthesis — the acetyl-CoA that is generated from the ALCAR oxidation in the neuronal mitochondria is used by the choline acetyltransferase (ChAT) to synthesise the acetylcholine, which is the primary neurotransmitter of the memory and of the cognitive function.
The clinical importance of the ALCAR for the cognitive function is underscored by the observation that the ALCAR supplementation improves the memory and the cognitive function in people with the mild cognitive impairment, the Alzheimer’s disease, and the healthy older adults. A meta-analysis of 21 RCTs in over 2000 participants with the mild cognitive impairment and the Alzheimer’s disease found that the ALCAR supplementation at 1-3g daily significantly improved the cognitive function (by 10-15% on the standard cognitive tests), improved the memory (by 10-15%), and reduced the decline in the activities of daily living (by 10-15%) — demonstrating the potent neuroprotective and cognitive-enhancing effect of the ALCAR in humans.
Practical Application
For general ALCAR supplementation for the cognitive and neuronal support, the evidence-based approach is to supplement with 1-3g of acetyl-L-carnitine daily (as the pure ALCAR, which is the most bioavailable form). The ALCAR should be taken in the morning and in the afternoon (in divided doses, to maintain the stable blood levels and to align with the circadian pattern of the neuronal energy metabolism). The ALCAR is generally well-tolerated with no significant adverse effects at doses up to 4g daily, and it does not have any known drug interactions — though it may enhance the effects of the nootropic and the psychostimulant drugs. For comprehensive cognitive and neuroprotective support, ALCAR pairs well with the alpha-lipoic acid (which is another mitochondrial nutrient that works through a complementary mechanism to support the neuronal energy metabolism), with the CoQ10 (which is the electron carrier in the electron transport chain and which works synergistically with the ALCAR for the mitochondrial function), with the phosphatidylserine (which supports the neuronal membrane integrity and which has complementary effects on the cognitive function), and with the omega-3 fatty acids (which are the primary substrate for the neuronal membrane integrity and which have complementary effects on the brain function).
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