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Acetyl-L-Carnitine: Benefits and Side Effects

B12, B6, B9

Acetyl-L-Carnitine (ALCAR) is the acetylated form of the amino acid L-carnitine (LC), which means ALCAR is L-carnitine tagged with an acetyl molecule.

Whilst both forms can be used as a supplement, ALCAR is often preferred due to its ability to cross the blood-brain barrier allowing it to interact with nerves in the brain, and also donate its acetyl molecule, a key step in neurotransmitter formation, required for healthy brain activity.

ALCAR and LC are naturally produced in the body and occur naturally in the diet, usually when we eat animal protein. However, ALCAR is commonly taken as a nutritional supplement due to numerous potential health benefits.

A major function of ALCAR is to transport fatty acids across the membrane of the mitochondria (the powerhouse of the cell) in order to generate ATP (the energy currency of the body).

During this process it is converted into LC as it donates its acetyl group.

Where Acetyl-L-Carnitine comes from

ALCAR can be produced or sourced in several ways. A major source are the liver and kidneys which produce ALCAR from the amino acids lysine and methionine, although the majority of LC is actually stored in skeletal muscle tissue.

In the body, ALCAR is converted into L-carnitine once it has donated its acetyl group to help with fatty acid transport into the mitochondria. However, it is possible to revert this reaction and convert L-carnitine back into ALCAR, and this frequently occurs in the cell as part of normal metabolism. The final natural source of ALCAR is the diet, with red meats, especially leaner muscle rich cuts being, a particularly high source. Other foods such as white meats, cheeses and some fruits and vegetables like avocados and asparagus also contain L-carnitine, although to a much lesser degree.

Supplementation with Acetyl-L-Carnitine

Whilst ALCAR deficiency is very rare, ALCAR supplementation is very common and popular due to numerous potential health benefits. ALCAR is preferred to LC as a supplement due to its increased bio-availability,1 meaning it is more readily absorbed from the gut, and its ability to cross the blood-brain barrier allowing it to modulate numerous functions in the brain.2

Benefits and of Acetyl-L-Carnitine

Numerous health benefits have been described for ALCAR and LC, below we cover the potential major benefits and inform you of the latest research.

Enhanced cognition and neuroprotection

A major function of ALCAR and LC in the brain is in the formation of neurotransmitters, required for proper function of the brain. Several promising studies in animal models demonstrated a marked improvement in cognition.3 A similar improvement was seen in elderly populations4 and those suffering from Alzheimer’s Disease.5 Of particular interest was the ability of ALCAR to slow the progression of Alzheimer’s Disease in early onset patients.

Together these findings suggest that ALCAR is a potent neuroprotectant, facilitated by its ability to cross the blood brain barrier. It is not yet clear how ALCAR exerts its protective effect in the brain, but potential hypotheses include improved neurotransmitter synthesis, or improved energy generation in neurons preventing their damage.

What is also unknown is the effect on cognition, and any neuroprotective benefit, in younger or healthy individuals remains unknown, some positive results have been reported,6 however a large scale confirmatory study is still required.7

Mood Boosting

Due to its important role in the brain as a supplement for neurotransmitter formation another logical investigation was the role of ALCAR and LC on mood.

In both animal8 and human studies9 a significant improvement in mood was observed following ALCAR supplementation.

A review of numerous studies recommended that a large scale clinical trial be performed to identify exactly who may be of benefit. However, they suggest that ALCAR may be an important antidepressant therapy, either alone or in conjunction with other mood enhancers, especially in those with other medical conditions who may not tolerate high dose antidepressants.10

Improved sleep quality

Rather than a general improvement of sleep quality, ALCAR has been shown to have several highly specific benefits. In those suffering from narcolepsy, a rare disorder where the brain cannot regulate the normal sleep cycle, LC treatment promoted daytime wakefulness.11 A beneficial effect in those who suffer from sleep apnea was also observed.1213 Again, its benefit in healthy individuals remain unknown.

Fat busting and muscle promotion

Due to its role in energy generation, specifically involving fat metabolism, and its abundance in muscle tissue there was much excitement about using ALCAR as a fat buster or muscle builder. However, several studies in both animal models14 and humans,15 have shown no benefit on either activity, or even on muscle LC content in normal individuals. Some studies have reported a benefit in elite endurance athletes with a high energy intake and expenditure. In these athletes, LC is thought to promote the usage of fat in energy generation, preserving some of the muscles natural energy source, therefore delaying the point when they “hit the wall.”1617

Interestingly in a rat model, ALCAR and alpha-lipoic acid co-supplementation was able to improve metabolic function, burning energy more efficiently, whilst also reducing oxidative stress.18 No similar improvement was observed in a human trial looking at depression.19 Again their role in healthy individuals remains un-investigated.

Genes and SNPs

At the genetic level ALCAR has been shown to be of significant direct benefit to those carrying the risk ‘C’ allele of rs5770917, located between the CPT1B and CHKB genes, which is associated with narcolepsy.2021 In these individuals a daily dose of 510 mg ALCAR was effective at reducing daytime sleepiness.

Due to ALCAR’s important role in energy generation it may be of interest to those who carry risk SNPs in the IL-4, IL-6, IL-1β, IL-10, TNFα, TRPM3 and TRPA1 genes, although to date no studies have been performed to investigate this effect.222324

Our mitochondria within our cells contain their own DNA, and this DNA DNA is also subject to variation in the form of SNPs like our main genome. Two SNPs within the mitochondrial genome have been identified which associate with fatigue, but again no studies investigating ALCAR as a potential therapeutic have been performed.25

Dosing ALCAR

ALCAR is approved by the FDA for the treatment of certain LC deficiency syndromes. It is also available as an over the counter nutritional supplement. No official dosing advice has been provided however doses of 500 – 2000 mg per day are typically used.26

Any described side effects?

At doses of approximately 3,000 mg per day, carnitine supplements can cause nausea, vomiting, abdominal cramps, diarrhea, and a “fishy” body odor. Rarer side effects include muscle weakness in uremic patients and seizures in those with seizure disorders.27

Furthermore, some research indicates that intestinal bacteria can break down carnitine to form a substance called TMAO that might increase the risk of cardiovascular disease, particularly in those who eat a meat rich diet.28 Interestingly a study published by the Mayo Clinic29 reported seemingly opposite findings, showing a protective cardiac effect.

Carnitine and TMAO

Whilst these may seem counterintuitive the negative reference refers to the formation of TMAO from intestinal bacteria rather than from cells within the body. It is possible therefore that a poor gut biome, or indeed even the source of ALCAR/LC may be important in describing outcomes. A diet rich in red meat has been shown to disrupt the gut biome and so other ALCAR/LC sources may be preferred.3031

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.

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