Thursday, April 9, 2009

L-Carnitine, Acetyl-L-Carnitine and Cognitive Function in Animals

L-Carnitine, Acetyl-L-Carnitine and Cognitive Function in Animals
A 3.5 oz serving of beef steak will give you 95 mg of carnitine. (Photo by

Carnitine is required in the mitochondria for the generation of metabolic energy. It is biosynthesized from lysine and methionine primarily in the liver and kidneys.

Carnitine concentrations in the cells decrease with age, which is why carnitine is also marketed as an anti-aging supplement. Supplementary carnitine is sold as L-carnitine, which is the bioactive form of carnitine, or acetyl-L-carnitine (ALCAR), which is the acetylated form of L-carnitine.

But what is the evidence behind the claimed anti-aging effect? Fortunately, several studies have been done. In this post, we'll look at the currently available animal data on the effects of both forms of carnitine on cognition. I'll save the human studies for next time.

Carnitine and age-related cognitive decline

In one of the earliest studies, Bossoni & Carpi showed that acetyl-L-carnitine supplementation improved the learning ability and memory processes of rats and mice, both with oral treatment and injections. The doses ranged from 0.3 mg/kg to 100 mg/kg body weight. ALCAR also antagonized amnesia, when electroconvulsive shocks were given to the mice during one of the learning tests.

A few years later, Ghirardi et al. reported that 8 months of ALCAR supplementation protected rats from age-related deterioration in spatial learning. Similarly, Valerio et al. showed that aged rats performed better in active and passive avoidance tests when given ALCAR. These tests are used as models of learning and memory capacity. The doses are not mentioned in the abstracts, and the studies are so old that I'm unable to access the full papers.

Recently, Freddi et al. gave 15-month-old male rats 60 mg/kg acetyl-L-carnitine per day orally for six months and tested their spatial memory with a maze-water task. The ALCAR-fed rats found their way through the maze significantly faster than the control rats. The control rats also showed age-related degenerative morphological changes in their basal forebrain regions while the treated rats did not.

Old rats have higher rates of lipid peroxidation than young rats in many brain regions. Lipid peroxidation means the process where free radicals steal electrons from the lipids in cell membranes, which results in cell damage. Rani & Panneerselvam report that when old rats were injected with 300 mg/kg L-carnitine for 21 days, lipid peroxidation decreased in many areas of the brain. Superoxide dismutase activity was restored to youthful levels, which suggests the neuroprotective effect of L-carnitine is in part due to its ability to increase antioxidant levels. L-carnitine had no effect on young rats, however.

Carnitine and stress-related cognitive decline

ALCAR also seems to protect the brain from hypobaric hypoxia, a condition in which the body is deprived of adequate oxygen due to a high altitude. It can cause oxidative stress, neurodegeneration and memory impairment. When Barhwal et al. exposed rats to hypobaric hypoxia for two weeks, their condition improved when they were supplemented with ALCAR. There was a decrease in free radical production, lipid peroxidation and protein oxidation, and a decrease in the levels of glutathione.

The stimulant drug ecstacy (MDMA) is known to increase mitochondrial oxidative stress in the brain. When Alves et al. gave injected rats with acetyl-L-carnitine (100 mg/kg body weight) prior to ecstacy, the oxidative damage from the drug decreased significantly. ALCAR reduced carbonyl formation, decreased mitochondrial DNA deletion, improved the expression of respiratory chain components and prevented the decrease of 5-HT levels in many regions of the brain.

Excessive doses of insulin can also cause mitochondrial swelling and neuronal death in the brain of patients with diabetes mellitus. Hino et al. induced hypoglycemia in rats that were given L-carnitine in their drinking water. Although the mortality rate remained the same as in the control group, the rats that did survive the high insulin dose had improvements in cognitive function. L-carnitine effectively inhibited mitochondrial dysfunction and prevented neuronal injury.

Sezen et al. induced brain damage to rats with radiation and found out that vitamin E (40 mg/kg) and L-carnitine (200 mg/kg) separately reduced the severity of brain damage. Both supplements increased the activity of superoxide dismutase and catalase enzymes, again suggesting that L-carnitine has an antioxidant role. Combining vitamin E and L-carnitine didn't yield additional benefits, however.

Similarly, Túnez et al. compared the effects of vitamin E (20 mg/kg), L-carnitine (100 mg/kg) and melatonin (3 mg/kg) on rat brain and liver damage from a single dose of thioacetamide, which increases lipid peroxidation. All three protected the rats from oxidative stress, with melatonin offering the best protection.


Acetyl-L-carnitine (ALCAR) has been shown to improve learning ability and memory processes in aged rats. L-carnitine was shown to reduce lipid peroxidation and increase superoxide dismutase activity in the brains of old rats but not young rats.

Both ALCAR and L-carnitine also protected rats from artificially induced oxidative stress in the brain. The protective effect was again associated with decreased lipid peroxidation and increased superoxide dismutase activity in the brain.

Taken together, these results suggest that L-carnitine and acetyl-L-carnitine protect the brain from both age-related and stress-related damage in rodents. The protection may be due to carnitine's ability to increase antioxidant levels.

For more information on aging and cognition, see these posts:

Increasing Intelligence by Playing a Memory Game – Experiment Update
Caloric Restriction Improves Memory in the Elderly
Moderate and Severe Caloric Restriction Alter Behavior Differently in Rats
Intermittent Fasting Reduces Mitochondrial Damage and Lymphoma Incidence in Aged Mice

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