ACETYL-L-CARNITINE: Benefits, Side Effects, Uses, Dosage, Warnings?
Acetyl L-carnitine promotes oxidation of fatty acids during the recording of acetyl-CoA in the mitochondria, it increases acetylcholine production
acetyl-L-carnitine is usually available in tablet or capsule form. The dosage is usually in the range of 1-3 g per day in several doses. Supplementation with ALC applies in these dose ranges considered safe. Even for long-term (one year), no significant side effects are known. The most common adverse reactions agitation, nausea and vomiting were observed. (2.9)
Source of supply
The functions in the body
Acetyl L-carnitine (ALC) is an ester of three methylated amino acid L-carnitine, and is formed by the enzyme ACL transferase in the brain, liver and kidney of humans. Acetyl L-carnitine promotes oxidation of fatty acids during the recording of acetyl-CoA in the mitochondria, it increases the production of acetylcholine and stimulates the synthesis of proteins and membrane phospholipids. Due to its structural similarities with acetylcholine ALC also acts as a parasympathomimetic. Medical studies demonstrate the successful use of ALC in Alzheimer's disease, senile depression, HIV infection, diabetic neuropathy, cerebral ischemia / reperfusion and in alcohol-induced cognitive impairment. (1-3)
L-carnitine and acetyl L-carnitine can be administered orally or intravenously, and then absorbed by simple diffusion in the jejunum. The transition into the tissue occurs by an active transport mechanism. Studies have shown that under the action of the enzyme carnitine balance the plasma concentrations of ALC and L-carnitine. Both after oral and intravenous administration, can be observed in the CSF, a corresponding increase in ALC concentration. This shows that the substance readily reaches the blood-brain barrier. L-carnitine and its esters are metabolized only to a small extent, and then renally excreted, by way of a tubular reabsorption. The clearance rate increases with the plasma concentrations of these substances. (4-5)
Mechanisms of action
The exact mechanisms of action of acetyl-L-carnitine are so far unknown. Recent research indicates they could be related to the fact that ALC acts as a cholinergic neurotransmitter and is able to stimulate the neuronal metabolism in the mitochondria. Purpura et al. have the cholinergic effects of ALC on the blockade of postsynaptic Inhibitionspotenziale returned, (6) while other authors postulate that they are based on a direct stimulation of the synapses. (7) In connection with the increased cellular energy metabolism in the mitochondria clinical studies have shown that ALC on the regulation of sphingomyelin levels can stabilize the fluidity of the cell membrane and, moreover, is a substrate reservoir for cellular energy production. In this way, it prevents an excessive neuronal cell death. It was also shown that acetyl-L-carnitine enhances the binding of glucocorticoids and nerve growth factor in the hippocampus. (8)
Has been demonstrated in several studies that ALC positively influences cognitive performance in patients with Alzheimer's dementia. The study duration was usually 3 to 6 months. The study medication consisted of oral doses of 1-3 g ALC per day. Although the results were mixed, (recognition of identity) had total observed a significant improvement at the tasks for the assessment of visuo-spatial skills, cognitive performance speed, concentration and discernment, as well as the tests for the assessment of visual memory. (9-11) In a study demonstrated that at a dose of 2 g / ALC deterioration of reaction time decreases and an increase in performance with respect to short-term memory can be achieved. (9) The long-term effect of ALC few studies available, but could Spagnoli et al. prove that the one-year treatment with 1-2 g / ALC resulted in improvement of behavioral disturbances and an increase in long-term memory performance. (2)
In patients with major depression, a change in the circadian rhythm of cortisol secretion in association with an increase in Gesamtkortisolsekretion was detected. (12) The cause of this is probably in an increased activation of the hypothalamic-pituitary-adrenal system (HPA system) lie. Experimental animal studies have shown that the administration of ALC may inhibit HPA activity, reduce cortisol levels accordingly and thus cause an improvement in depressive symptoms. As regards the question whether ALC can cause a modulation of the HPA activity in humans, there are currently no data available. (13) In a two-month study of 24 elderly depressed patients, ALC treatment proved to be highly effective, particularly in the group of patients with particularly severe depression symptoms. (14) In another study of 28 elderly patients Garzya et al reported. after that daily supplementation with 500 mg three times ALC allows an effective treatment of depression symptoms. Participants in both studies were evaluated using the Hamilton Rating Scale for Depression, which is allowed by the decrease of the scores read a clear improvement in depressive symptoms (15).
The most serious immunological changes in HIV-infected patients consists in a decrease in CD4 cells as a result of lymphocyte apoptosis. In a smaller study of eleven asymptomatic HIV-infected patients examined Di Marzio et al. the effect of ALC on CD4 and CD8 counts to apoptosis and eventually the concentration of the insulin-like growth factor 1 (IGF-1). Over a period of five months, the subjects received ALC at a dosage of 3 g / day. The results showed that the ALC substitution led to a significant decrease in the lymphocyte apoptosis. Possible cause for this is a decreased ceramide and / or an increase in IGF-1 serum levels. IGF-1 is critical for the inhibition of apoptosis. (16) In HIV-infected patients treated with nucleoside analogues, occurs as a side effect of medication frequently a peripheral neuropathy. In patients receiving stavudine, zalcitabine or didanosine discontinuation of treatment is for this reason sometimes necessary. Recent studies suggest that acetyl-L-Carnitine can be just as recombinant human nerve growth factor in the situation of use. (17)
Diabetic neuropathy / cataract:
Approximately one third of all diabetics suffer from peripheral neuropathy. (18) In animal studies, a link between an imbalance in carnitine metabolism and several metabolic and functional disturbances in diabetic polyneuropathy has been demonstrated. (19) At present, no clinical studies on the efficacy of oral ALC-substitution in diabetic neuropathy before. In the clinical studies carried out to date, the supplementation was carried out with an injectable formulation. In these studies, it was with the injection of ALC in the relief of neuropathic pain and an improvement in nerve function can be achieved. (20-21) The formation of advanced glycation end products (AGE) occurs frequently in diabetic patients and to the development of cataracts. Studies in rats with experimentally induced diabetes mellitus a dramatic depletion of L-carnitine and acetyl L-carnitine in the lens memory was detected. In another study, lens tissue was incubated calves over a period of 15 days with L-carnitine and ALC. It was found that acetyl-L-carnitine in vitro reduced the glycation of lens crystallins by 42 percent, while L-carnitine had no effect on this process (22).
Cerebral ischemia and reperfusion:
Animal models of cerebral post-ischemic damage the neuro regenerative effect of ALC has been studied extensively. Documenting these studies that ALC the degree of neurological impairment is reduced, (23) prevents the mediated free radical protein oxidation, the concentration of metabolites in the cerebral energy metabolism normalized (24) and lowers the lactic acid content in the early post-ischemic reperfusion. (25) Although the number of animal studies clearly predominates, are also results of clinical trials. So examined Rosadini et al. of ten male patients with cerebral ischemia, the effects of ALC on the regional blood flow in the brain. The authors observed one hour after intravenous administration of 1500 mg of ALC in eight of ten patients positive changes. (26)
Acetyl-L-carnitine stimulates as well as L-carnitine required for the production of ATP transport of fatty acids into the mitochondria of skeletal muscles and the heart muscle and protects against damage by free radicals. (27) Animal studies also demonstrate dassw the gift of ALC makes the age-related decline in myocardial mitochondria of Cardiolipingehalts reversed. (28)
In various animal models was investigated how the administration of carnitine and ALC affects alcohol metabolism in the liver. Cha and Sachan made the observation that delayed ALC carnitine and alcohol oxidation, but that the carnitine concentration must be a hundred times higher than the acetyl L-carnitine concentration to achieve the same maximum inhibition. The authors arrived at the conclusion that acetyl-L-carnitine acts as a mediator in the carnitine-induced inhibition of ethanol oxidation and the inhibition competitively + takes place in competition with NAD. (29-30) In a 90-day study in 55 chronic alcoholics improved ALC the cognitive performance of patients. This speaks of cognitive disorders in alcoholic patients for potential benefit of acetyl-L-carnitine in the treatment. (31)