ACETYL L-CARNITINE (Potent Anti-Aging Supplement)

Acetylcarnitine (also acetyl-l-carnitine) and carnitine play several important roles in the human body. These nutrients shuttle acetyl groups and fatty acids into mitochondria for energy production. Without carnitine, fatty acids cannot easily enter into mitochondria. The acetyl group of acetylcarnitine is used to form acetyl-CoA, the most important intermediary in the generation of energy from amino acids, fats, and carbohydrates. Therefore, acetylcarnitine serves as an energy reservoir of acetyl groups and both acetylcarnitine and carnitine help improve energy production. The acetyl group of acetylcarnitine is also used to make the important brain chemical acetylcholine. Some studies suggest that perhaps acetylcarnitine can even act as a neurotransmitter itself.

ACTIONS

Supplemental acetyl-L-carnitine may have neuroprotective activity. In addition, it, like L-carnitine, may have cardioprotective activity and may beneficially affect cardiac function. It may enhance sperm motiliy. Acetyl-L-carnitine may also have cytoprotective, antioxidant and anti-apoptotic activity.

MECHANISM OF ACTION

Acetyl-L-carnitine is a delivery form for L-carnitine and acetyl groups. The functions of L-carnitine include transport of long-chain fatty acids across the mitochondrial membranes into the mitochondria (wherein their metabolism produces bioenergy) and transport of small-chain and medium-chain fatty acids out of the mitochondria in order to, among other things, maintain normal coenzyme A levels in these organelles. It may also have antioxidant activity.

The acetyl component of acetyl-L-carnitine provides for the formation of the neurotransmitter acetylcholine. Abnormal acetylcholine metabolism in the brain, leading to acetylcholine deficits in certain brain regions, is thought to be associated with age-related dementias, including Alzheimer’s disease.

Acetyl-L-carnitine has been found to decrease glycation of lens proteins in vitro. It is thought to do so by acetylating certain lens proteins called crystallins. In so doing it protects them from glycation-mediated damage.

Many biochemical changes occur during the aging process. These include decreased cardiolipin synthesis in the heart and impaired mitochondrial function. Cardiolipin is a key phospholipid necessary for mitochondrial transport processes in the heart. Mitochondria are vital for the production of cellular energy. Experiments in aged rats have shown that acetyl-L-carnitine supplementation leads to improved mitochondrial function and increased cardiolipin production.

Acetyl-L-carnitine serves as a readily accessible energy pool for use in both activation of respiration and motility in human spermatozoa.

PHARMACOKINETICS

The pharmacokinetics of acetyl-L-carnitine are similar to L-carnitine (see L-carnitine). There is speculation that it is better absorbed than L-carnitine, but this has not yet been established.

INDICATIONS AND USAGE

Acetyl-L-carnitine has recently demonstrated some efficacy as a possible neuroprotective agent and may be indicated for use in strokes, Alzheimer’s disease, Down’s syndrome and for the management of various neuropathies. It may also have anti-aging properties. Research regarding acetyl-L-carnitine’s possible beneficial effect on sperm motility is early-stage but promising.

RESEARCH SUMMARY

Several studies have now demonstrated some positive effects of acetyl-L-carnitine supplementation in Alzheimer’s patients especially with regard to tasks involving attention and concentration. In a double-blind, parallel design, placebo-controlled pilot study of 30 patients whose mild-to-moderate dementias were believed to be symptoms of Alzheimer’s disease, there were significant, positive results as measured by some of the neuropsychological tests used in the study.

In another early double-blind, placebo-controlled study of 130 patients with clinical diagnoses of Alzheimer’s disease, a slower rate of deterioration was observed in 13 of 14 outcome measures at the end of this one-year study. Some of these measures reached statistical significance, including measures of logical intelligence, long-term verbal memory and selective attention.

More recent studies continue to show beneficial effects in Alzheimer’s disease. Younger patients seem to benefit most.

It has been suggested that cognitive function may be improved in subjects with Alzheimer’s disease by acetyl-L-carnitine’s hypothesized ability to inhibit apoptosis of cerebral nerve cells.

Significant improvement in visual memory and attention in Down’s syndrome subjects treated with acetyl-L-carnitine has also been reported. These researchers hypothesized that acetyl-L-carnitine’s positive actions in both Alzheimer’s disease and Down’s syndrome result from its direct and indirect cholinomimetic effects.

There is also preliminary evidence that acetyl-L-carnitine can slow mental decline in the elderly who are not afflicted with dementias.

Neuroprotective effects of acetyl-L-carnitine have been reported after stroke in both animal models and in humans. Cerebral blood flow reportedly improves in acetyl-L-carnitine treated subjects with cerebrovascular disease.

Peripheral nerve function has been improved with the use of acetyl-L-carnitine in experimental diabetes. There is also early clinical evidence that acetyl-L-carnitine may be helpful in various peripheral neuropathies, and it has been suggested that this supplement might be helpful in alleviating the neurotoxicity associated with the nucleoside analogues used in the treatment of AIDS. This latter hypothesis has yet to be tested.

There is some evidence in animal work that acetyl-L-carnitine might have anti-aging effects. Mitochondrial function and ambulatory activity were assessed in a study of old rats fed acetyl-L-carnitine. Ambulatory activity was significantly increased in the old rats, and an examination of liver cells in the treated animals showed a significant reversal of age-associated decline of mitochondrial membrane potential. Cardiolipin, which declines with age, was significantly restored.

Finally, acetyl-L-carnitine has been reported to increase sperm motility in vitro, and in one human trial, 4 grams daily of this substance given to 20 oligoasthenospermic men, produced increased progressive sperm motility which was associated with a greater number of pregnancies.

Acetylcarnitine Research shows:

In aging rats, chronic administration of acetylcarnitine increases cholinergic synaptic transmission and consequently enhances learning capacity. The memory of aging rats is rejuvenated by giving them a combination of acetylcarnitine and lipoic acid.

Potential Benefits of Acetylcarnitine according to published studies:

Acetylcarnitine may improve mental fatigue in those who suffer from chronic fatigue syndrome.
Patients with multiple sclerosis are helped by acetylcarnitine, which reduces their fatigue.
Acetylcarnitine is a promising treatment for those with diabetic neuropathy.
May reduce alcohol-induced cellular damage to organs.
May be helpful in geriatric patients with mild depression.
Acetylcarnitine improves the function of mitochondria, the organelles within cells that are involved in energy production.
Is more effective than tamoxifen in the therapy of acute and early chronic Peyronie’s disease.
May help individuals with degenerative cerebellar ataxia.
Acetylcarnitine is suitable for clinical use in the prevention of neuronal death after peripheral nerve trauma.
May be helpful in those with Alzheimer’s disease. Acetylcarnitine protects against amyloid-beta neurotoxicity.

ALSO MORE BENEFITS OF ACL (ACETYL L-CARNITINE):

ALC facilitates both the release and synthesis of Acetylcholine.
ALC’s ability to increase the synthesis of Acetylcholine occurs as a result of it donating its Acetyl group towards the production of Acetylcholine.
ALC increases the Brain’s levels of Choline Acetylase (which in turn facilities the production of Acetylcholine).
ALC enhances the release of Dopamine from Dopaminergic Neurons and improves the binding of Dopamine to Dopamine Receptors.
ALC improves the reaction times of persons afflicted with Cerebral Insufficiency.
ALC (2-4 grams per day) improves walking distance without Pain in persons afflicted with Intermittent Claudication.
ALC prevents the age-related impairment of Eyesight (by protecting the Neurons of the Optic Nerve and the Occipital Cortex of the Brain.
ALC enhances the ability of Macrophages to function as Phagocytes.
ALC given prior to exercise increased the maximum running speed of animals.
ALC enhances the function of Cytochrome Oxidase (an essential enzyme of the Electron Transport System (ETS).
ALC improves the Energy metabolism of Neurons (by enhancing the transport of Medium-Chain Saturated Fatty Acids and Short-Chain Saturated Fatty Acids across the Cell Membranes of Neurons into the Mitochondria).
ALC inhibits the damage caused by Hypoxia.
ALC transports Lipids into the Mitochondria of Cells.
ALC improves Memory in persons afflicted with Age Associated Memory Impairment.
ALC improves Mental Function where Alcohol induced cognitive Impairment exists.
Acetyl-L-Carnitine inhibits the deterioration in Mental Function associated with Alzheimer’s Disease and slows the progression of Alzheimer’s Disease [persons afflicted with Alzheimer’s Disease exhibited significantly less deterioration in Mental Function following the administration of supplemental ALC for 12 months. This finding was verified by using nuclear magnetic resonance on the subjects].
ALC increases Alertness in persons afflicted with Alzheimer’s Disease – 2,500-3,000 mg per day for 3 months].
ALC inhibits the toxicity of Amyloid-Beta Protein (ABP) to Neurons.
ALC improves Attention Span in persons afflicted with Alzheimer’s Disease.
ALC improves Short Term Memory in persons afflicted with Alzheimer’s Disease.
High concentrations of ALC are naturally present in various regions of the Brain.
ALC reverses the age-related decline that occurs in Cholinergic Receptors (i.e. the Receptors that receive Acetylcholine).
ALC improves (eye to hand) Coordination [supplemental ALC @ 1.5 grams per day for 30 days improved eye to hand coordination in healthy, sedentary subjects by a factor of 300-400%].
ALC improves the Interhemispheric Flow of Information across the Corpus Callosum of the Brain.
ALC retards the decline in the number of Dopamine Receptors that occurs in tandem with the Aging Process and (more rapidly) with the onset of Parkinson’s Disease.
ALC enhances the release of Dopamine from Dopaminergic Neurons and improves the binding of Dopamine to Dopamine Receptors.
ALC can prevent the destruction of Dopamine Receptors by MPTP (a neurotoxin capable of causing Parkinson’s Disease via Dopaminergic Receptor death.
ALC improves Attention Span and Memory in persons afflicted with Down’s Syndrome.
ALC retards the inevitable decline in the number of Glucocorticoid Receptors that occurs in tandem with the Aging Process.
ALC enhances the recovery of persons afflicted with Hemiplegia (Paralysis of one side of the body) and improves their Mood and Attention Span.
ALC retards the age-related deterioration of the Hippocampus [research – rats].
Acetyl-L-Carnitine (ALC) improves Learning ability [women aged 22 – 27 were supplemented with ALC for 30 days. Complex video game tests before and after supplementation concluded that supplemental ALC caused large increases in speed of Learning, speed of reaction and reduction in errors].
ALC improves both Short-Term Memory and Long-Term Memory.
ALC improves Mood [ALC improves Mood in 53% of healthy subjects].
ALC inhibits (and possibly reverses) the degeneration of Myelin Sheaths that occurs in tandem with the progression of the Aging Process [scientific research – hyperglycemic mice treated with ALC for 16 weeks exhibited improved nerve conduction velocity and exhibited thicker Myelin Sheaths and larger myelinated Nerve Fibers].
ALC retards the inevitable decline in the number of Nerve Growth Factor (NGF) Receptors that occurs in tandem with the Aging Process.
ALC stimulates and maintains the growth of new Neurons within the Brain (both independently of Nerve Growth Factor (NGF) and as a result of preserving NGF) and helps to prevent the death of existing Neurons [ALC inhibits Neuron death in the Striatal Cortex, Prefrontal Cortex and the Occipital Cortex of the Brain].
ALC inhibits the degeneration of Neurons that is implicit in Neuropathy.
ALC rejuvenates and increases the number of N-Methyl-D-Aspartate Receptors (NMDA Receptors) in the Brain [even a single dose of ALC increases the number of functional NMDA Receptors]:
ALC protects the NMDA Receptors in the Brain from the natural decline that occurs in tandem with the Aging Process [research – animals].
ALC is presently being researched as a treatment for Parkinson’s Disease.
ALC inhibits the loss of Vision, degeneration of Neurons and damage to the Retina associated with Retinopathy (including Diabetic Retinopathy).
ALC improves the quality of Sleep and reduces the quantity of Sleep required.
ALC improves the function of (reduces the over-excitability of) Motor Nerves in persons afflicted with Spasticity.
ALC improves Spatial Memory (an aspect of Short Term Memory that involves remembering one’s position in space).
ALC inhibits the excessive release of Cortisol in response to Stress and inhibits the depletion of Luteinising Hormone Releasing Hormone (LHRH) and Testosterone that occurs as a result of excessive Stress.
ALC improves Verbal Fluency.
ALC enhances the function of Cytochrome Oxidase (also called Complex IV) – an essential enzyme of the Electron Transport System.
ALC normalizes Beta-Endorphin levels.
ALC reduces Stress-induced Cortisol release [research – animals].
ALC prevents the depletion of Luteinising Hormone Releasing Hormone (LHRH) caused by exposure to excessive Stress.
ALC retards the decline in the production of Nerve Growth Factor (NGF) that occurs in tandem with the Aging Process.
ALC increases plasma Testosterone levels (via its influence on Acetylcholine neurotransmission in the Striatal Cortex of the Brain) and prevents the depletion of Testosterone caused by exposure to excessive Stress [research – rats].

Acetylcarnitine Short term effects

The mind boosting effect of acetylcarnitine is often noticed within a few hours, or even within an hour. Most people report feeling mentally sharper, having more focus and being more alert. Some find a mild mood enhancement. Acetylcarnitine may be used as an overall mind booster. The typical dosage is 250 to 500 mg once a day, preferably in the early part of the day. Side effects of overstimulation may occur at dosages greater than 500 mg.

AcetylCarnitine Research Update

Combined treatment with L-carnitine, a popular dietary supplement, and acetylcarnitine, a related chemical, appears to improve sperm motility in men with fertility problems, according to a new study. In the study, 60 infertile men between the ages of 20 and 40 years were randomly selected to take a combination of L-carnitine and L-acetyl-carnitine or an inactive “placebo” for 6 months. In the medical journal Fertility and Sterility, researchers at the University of Rome led by Dr. Andrea Lenzi report that 2 months after the completion of therapy, men who took L-carnitine and L-acetyl-carnitine had increases in sperm concentration, forward movement, and total movement. The most significant improvements in sperm motility, both forward and total, were observed in men who had the lowest levels of moving sperm when the study began. The researchers note that four

Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides

Bruno G; Scaccianoce S; Bonamini M; Patacchioli FR; Cesarino F; Grassini P; Sorrentino E; Angelucci L; Lenzi GL
Dipartimento di Scienze Neurologiche, Universita di Roma La Sapienza, Italy
Alzheimer Dis Assoc Disord (U.S.) Fall 1995, 9 (3) p128-31,

Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer disease (AD) therapy. ALCAR seems to exert a number of central nervous system (CNS)-related effects, even though a clear pharmacological action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal fluid (CSF) and plasma biological correlates of ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly higher than the ones at baseline, reflecting a good penetration through the blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and their metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic hormone remained unchanged, beta-endorphins significantly decreased after treatment; plasma cortisol levels matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity. At present, no clear explanation can be proposed for the specific mechanism of this action.

Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease

Pettegrew JW; Klunk WE; Panchalingam K; Kanfer JN; McClure RJ
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, School of Medicine, PA 15213, USA.
Neurobiol Aging (UNITED STATES) Jan-Feb 1995, 16 (1) p1-4,

In a double-blind, placebo study, acetyl-L-carnitine was administered to 7 probable Alzheimer’s disease patients who were then compared by clinical and 31P magnetic resonance spectroscopic measures to 5 placebo-treated probable AD patients and 21 age-matched healthy controls over the course of 1 year. Compared to AD patients on placebo, acetyl-L-carnitine-treated patients showed significantly less deterioration in their Mini-Mental Status and Alzheimer’s Disease Assessment Scale test scores. Furthermore, the decrease in phosphomonoester levels observed in both the acetyl-L-carnitine and placebo AD groups at entry was normalized in the acetyl-L-carnitine-treated but not in the placebo-treated patients. Similar normalization of high-energy phosphate levels was observed in the acetyl-L-carnitine-treated but not in the placebo-treated patients. This is the first direct in vivo demonstration of a beneficial effect of a drug on both clinical and CNS neurochemical parameters in AD.

Clinical pharmacodynamics of acetyl-L-carnitine in patients with Parkinson’s disease.

Int J Clin Pharmacol Res. 1990. 10(1-2). P 139-43

Two groups of 10 patients with Parkinson’s disease received doses of either 1g acetyl-L-carnitine (ALC) per day for seven days or 2g. The effects of this drug on intermittent luminous stimulation and on nocturnal sleep patterns were studied. In both cases with either dose of ALC the effect was an improvement of the H response, sleep stages and spindling activity. However a further study of the complexity of action of acetyl-L-carnitine is necessary.

The effects of acetyl-L-carnitine and sorbinil on peripheral nerve structure, chemistry, and function in experimental diabetes.

Metabolism: Clinical and Experimental (USA), 1996, 45/7 (902-907)

Nerve conduction velocity (NCV) increased with age in nondiabetic male Wistar rats for the first 26 weeks of life. The NCV of animals made hyperglycemic at age 6 weeks by administration of streptozotocin (STZ) also increases, but at a slower rate. Animals with 4 weeks of hyperglycemia and reduced NCV treated with an aldose reductase inhibitor (sorbinil) or a short- chain acyl-carnitine (acetyl-L-carnitine (ALC)) daily for 16 weeks showed an improvement in NCV. Morphometric studies of tibial nerves collected from animals after 20 weeks of hyperglycemia (age 26 weeks) showed a consistent reduction in the width of the myelin sheath and little change in axon area. The number of large myelinated fibers (>6.5 microm) found in nerves collected from hyperglycemic animals was less than the number found in nondiabetic animals. Treatment of hyperglycemic rats with either sorbinil or ALC was associated with increased NCV, myelin width, and large myelinated fibers. The apparent metabolic effect of these agents was similar for fatty acid metabolism, but different for polyol pathway activity. We conclude that in animals hyperglycemic long enough to slow NCV, sorbinil and/or ALC treatment reduces the functional, structural, and biochemical changes associated with hyperglycemia that occur in the myelin sheath.

Acetyl-L-carnitine corrects the altered peripheral nerve function of experimental diabetes.

Metabolism: Clinical and Experimental (USA), 1995, 44/5 (677-680)

Acetyl-L-carnitine (ALC) has been shown to facilitate the repair of transacted sciatic nerves. The effect of ALC (50 mg/kg/d) on the diminished nerve conduction velocity (NCV) of rats with streptozotocin (STZ)-induced hyperglycemia of 3 weeks’ duration was evaluated. The aldose reductase inhibitor, sorbinil, which is reported to normalize the impaired NCV associated with experimental diabetes, was used as a positive control. Aldose reductase inhibitors are thought to have an effect by decreasing peripheral nerve sorbitol content and increasing nerve myo-inositol. Treatment of STZ- diabetic rats with either ALC or sorbinil resulted in normal NCV. Sorbinil treatment was associated with normalized sciatic nerve sorbitol and myo- inositol; ALC treatment did not reduce the elevated sorbitol levels, but sciatic nerve myo-inositol content was no different from nondiabetic levels. Both ALC and sorbinil treatment of STZ-diabetic rats were associated with a reduction in the elevated malondialdehyde (MDA) content of diabetic sciatic news, indicating reduced lipid peroxidation. The beneficial effects of sorbinil and ALC on the altered peripheral nerve function associated with diabetes were similar, but their effects on the polyol pathway (frequently implicated in the pathogenesis of peripheral neuropathy) were different.

Diabetic neuropathy in the rat: 1. Alcar augments the reduced levels and axoplasmic transport of substance P.

RES. (USA), 1995, 40/3

This study examined the sciatic nerve axonal transport of substance P-like immunoreactivity (SPLI) and its basal content in stomach, sciatic nerve and lumbar spinal cord of 8- and 12-week alloxan-diabetic rats, respectively. One group of diabetic rats received acetyl-l-carnitine (ALCAR) throughout the experimental period. Alloxan treatment caused hyperglycemia and reduced body growth. Axonal transport of SPLI was studied by measurement of 24-hour accumulation at a ligature on the sciatic nerve. There was a marked reduction (from 50% to 100% according to the nerve segment examined) of anterograde and retrograde accumulation of SPLI in the constricted nerve of 8-week diabetic rats. In the sciatic nerve of ALCAR-treated diabetic rats, the accumulation of SPLI was comparable to control values. In the sciatic nerve, lumbar spinal cord and stomach of 12-week diabetic rats, there is a significant reduction of SPLI content. ALCAR treatment prevented SPLI loss in these tissues. Sciatic nerves showed the typical sorbitol increase and myo-inositol loss that were significantly counteracted by ALCAR. This study suggests that ALCAR treatment prevents diabetes-induced sensory neuropathy by improving altered metabolic pathways such as polyol activity and myo-inositol synthesis, and by preventing the reduction of synthesis and axonal transport of substance P.

Neural dysfunction and metabolic imbalances in diabetic rats: Prevention by acetyl-L-carnitine.

DIABETES (USA), 1994, 43/12 (1469-1477)

The rationale for these experiments is that administration of L-carnitine and/or short-chain acylcarnitines attenuates myocardial dysfunction 1) in hearts from diabetic animals (in which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabetic animals; and 3) in nondiabetic humans with ischemic heart disease. The objective of these studies was to investigate whether imbalances in carnitine metabolism play a role in the pathogenesis of diabetic peripheral neuropathy. The major findings in rats with streptozotocin-induced diabetes of 4-6 weeks duration were that 24-h urinary carnitine excretion was increased approximately twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). These changes in carnitine levels/excretion were associated with decreased caudal nerve conduction velocity (10-15%) and sciatic nerve changes in Na+-K+-ATPase activity (decreased 50%), Mg2+- ATPase (decreased 65%), 1,2-diacyl-sn-glycerol (DAG) (decreased 40%), vascular albumin permeation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L- carnitine levels and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in DAG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and several metabolic and functional abnormalities associated with diabetic polyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of diabetes is associated with decreased DAG.