L carnitine: when and how to use this drug

L carnitine - this medication contains substances that trigger the mechanism of burning excess calories. Thanks to its effect, fat molecules accumulated in the subcutaneous tissue enter the blood and then into cellular mitochondria. Here fatty acids are broken down and release energy to the body. The medicine activates metabolism and improves appetite. L-carnitine for weight loss is used in combination with a set of physical exercises. Athletes use it during training to increase endurance and quickly build muscle mass.

general information

Acetyl L-carnitine is a derivative of levocarnitine. In the process of absorption, carnitine undergoes a number of biological processes, one of which is acetylation. For this process to occur successfully, the body must have a sufficient amount of coenzyme Q10, as well as an elevated body temperature. These conditions are usually achieved through cardio exercise or taking thermogenics. Acetylcarnitine is a more bioavailable compound that has already undergone the process of acetylation, and therefore its absorption time is much shorter.

Acetyl-L-carnitine is used to support the functioning of the central nervous system. It takes part in the transport of oxygen to cells, increasing their energy potential. Since it is the brain that consumes the most energy in the human body, taking Alkar is reflected there first. It is used to enhance the production of acetylcholine and neutralize the harmful effects of free radicals. Therefore, this connection is indispensable during periods of increased mental stress.

MRM, Acetyl L-Carnitine, 500 mg, 60 Vegan Capsules

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History of discovery

The compound was first discovered by Russian researcher Gulevich in animal muscle tissue. In 1927, the chemical formula of carnitine was described, but the question of its significance in biochemical reactions remains open. In 1958, the role in stimulating the oxidation of fatty acids in the mitochondria of cellular structures was clarified.

In the 80s of the 20th century, the industrial production of biological additives began to stimulate metabolic processes in the body. The product has become popular both in medicine and in sports nutrition. Modern methods of rejuvenation and increasing endurance to adverse environmental factors offer this amino acid to various groups of the population.

The benefits of alkar for the body

Acetyl L-carnitine has a beneficial effect on the body:

• reduces the volume of fat deposits by breaking down fats into fatty acids and converting them into a source of energy;
• increases physical endurance, making training more effective;
• helps speed up metabolism;
• prevents damage to muscle fibers during intense exercise;
• regulates the activity of the nervous and cardiovascular systems;
• improves psycho-emotional state;
• prevents rapid aging of brain cells;
• helps improve immune status;
• increases performance.

You can take acetyl-L-carnitine supplements regardless of age or exercise. It is prescribed to both young and old people, men and women. It is well suited for people with autoimmune disorders because it is absorbed easier and faster than usual.

Comparison of Alcar and Levocarnitine

Acetyl-L-carnitine differs from regular levocarnitine by the presence of a special acetyl group. During the process of absorption in the human body, this group attaches to the levocarnitine molecule. This process is called acetylation.

In the video, a master of sports in bodybuilding compares two types of carnitine:

Acetyl L - Carnitine or L - Carnitine. What's better? from Papa Smith

General properties

The substances have an identical molecular structure - they are the same amino acid, just in two different isomers. They have a similar effect:

• stimulate fat metabolism, accelerating the breakdown of fats into fatty acids;
• increase the energy potential of the body;
• improve endurance and performance.

Acetyl L-carnitine is a more active version of regular levocarnitine. Therefore, you can take supplements containing acetyl-L-carnitine in smaller dosages.

Difference between substances

The main difference is the presence of an acetyl group. Acetyl L-Carnitine is absorbed and reaches the brain faster than regular L-Carnitine. Therefore, it is widely used in the treatment of central nervous system diseases, cognitive impairment and for the prevention of Alzheimer's disease. This difference leads to different indications for use - L-carnitine is more often used in sports nutrition, and acetyl-L-carnitine is used to improve performance and prevent brain disorders.

Alkar more easily overcomes the blood-brain barrier, which leads to a rapid increase in the concentration of the substance in the nervous tissue. It is excreted faster by the kidneys and retains its concentration in plasma for less time, and therefore is less suitable for sports.

The supplement is easier to digest, and therefore its dosage should be less than that of regular levocarnitine. Acetylcarnitine can be used in lower concentrations; it is less likely to cause side effects and addiction.

Doctor's Best, Acetyl-L-Carnitine, 500 mg, 120 Veggie Caps

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Differences between acetyl-L-carnitine and L-carnitine

Levocarnitine is more common among athletes and bodybuilders due to its ability to burn fat. The active component transports fats from food to mitochondria, which are responsible for the synthesis of ATP, the main source of energy for humans.

Find out more:

“Sports supplement L-carnitine: what it is and how it works.”

Acetyl-L-carnitine (alcar, acetylcarnitine) is most often used as a brain stimulant. The substance improves cognitive abilities: attention, speech, intelligence, perception, memory. Acetylcarnitine is one of the isomers, i.e. derivatives of levocarnitine. An isomer is a substance with the same composition, but a slightly different structure, which determines the differences in properties.

To understand the difference between acetyl-L-carnitine and L-carnitine, you need to familiarize yourself with the process of absorption of the latter:

1. During absorption by the body, carnitine must undergo several biological processes. One of them is acetylation (introduction of an acetyl group into a compound).
2. For acetylation, two conditions must be met: a sufficient amount of coenzyme Q10 and elevated temperature. This can usually be achieved by taking thermogenics or cardio exercises.

We recommend:

“Thermogenics and lipotropics - what exactly burns fat.”

Acetylcarnitine has already undergone the acetylation procedure, i.e. it contains an acetyl group. This makes the supplement more bioavailable compared to levocarnitine, which means faster absorption. And this already explains why acetylcarnitine can be taken in smaller doses, because it is a more active version of regular L-carnitine.

Indications for use

Acetyl-L-carnitine is prescribed in the following cases:

• memory impairment;
• anxiety disorders;
• male infertility;
• cataract;
• disorders of the blood supply to the brain;
• smoking or drinking alcohol;
• recovery after ischemic brain damage.

It is recommended to take acetyl-L-carnitine if your immune system is weakened, as it has a positive effect on the bone marrow. The compound has a beneficial effect on the hypothalamus, increasing the secretion of testosterone. This increases the effectiveness of training, and also improves the quality of sperm, increasing the chances of successful conception.

The use of the product increases the energy potential of the body. Reviews indicate that after starting the Alkar course, performance increases, the emotional background improves, and fatigue decreases. The substance can also be used for weight loss, but it must be combined with physical exercise; the usual use of the substance for weight loss will not be enough.

Alzheimer's disease (AD) is recognized by the World Health Organization (WHO) as a priority problem of modern health care due to the steady increase in the number of patients and the particular severity of its medical and social consequences. Biological studies of the pathogenetic mechanisms of AD, which have successfully developed over the last quarter century, as well as the achievements of neuropharmacology, unfortunately, have not led either to the discovery of etiotropic therapy for this destructive neurodegenerative process, or to the introduction into clinical practice of effective methods of its treatment that can stop or significantly slow down the progression dementia. Drugs registered by international regulatory authorities for the treatment of asthma (cholinesterase inhibitors and memantine) can provide only a time-limited, moderate symptomatic effect. Such modest results of psychopharmacotherapy for AD are due not only to difficulties in finding new therapeutic targets and new targeted drugs, but also to the fact that the disease, as a rule, is first diagnosed and, accordingly, treated for the first time only in the stage of dementia syndrome, indicating advanced a neurodegenerative process with irreversible widespread pathological changes in various cortical and subcortical structures of the brain, as well as depletion of compensatory mechanisms aimed at protecting and restoring the brain.

It has now been established [1] that the development of dementia caused by AD is preceded by a long (up to 20 years) period of subclinical course of the disease. According to extensive population studies [2], at least 5% of elderly people (60 years and older) suffer from dementia caused by AD, and another 18% show signs of cognitive impairment that does not reach the level of dementia. According to the results of epidemiological studies [3], the average annual rate of conversion of mild cognitive decline syndrome (MCI) to dementia of the Alzheimer's type is 10-12%, while in the elderly population without cognitive impairment it does not exceed 1-2%.

In this regard, the tasks of paramount importance have become the diagnosis of AD at its earliest (prodromal or pre-dementia) stage and the development of methods of disease-modifying therapy aimed at preventing or slowing down the transition of the disease to the stage clinically determined by the formation of dementia syndrome.

Recent years have been marked by significant progress in the field of early (pre-dementia) diagnosis of AD, which has led to the expansion of its diagnostic boundaries. The research group of the US National Institute of Aging and a group of experts from the Alzheimer's Association developed new criteria (NIA-AA) for the lifetime diagnosis of AD at its subclinical stage, clinically corresponding to the MCI syndrome [4, 5]. MCI syndrome is heterogeneous both in its clinical structure and in its likelihood of progression to dementia. Over 5 years, approximately only ½ of patients with MCI syndrome were diagnosed with dementia due to AD. As a consequence, it was considered necessary, especially for research purposes, to “identify” the criteria for pre-dementia diagnosis of AD from both clinical and biological points of view.

According to the NIA-AA criteria, a diagnosis of AD in the absence of Alzheimer's type dementia in a patient can be made based on the following two symptoms: the presence of amnestic type MCI syndrome (aMCI) and biomarkers reflecting the biological nature of Alzheimer's neurodegeneration. CSF markers (decrease in β-amyloid content and increase in the level of total and phospholated τ-protein) and evidence of amyloid accumulation (according to the RET study with amyloid ligand) in cerebral structures are recognized as diagnostic biomarkers of AD. However, the study of such biomarkers requires either invasive, often traumatic for elderly patients, diagnostic techniques (such as spinal puncture), or the use of high-tech, very expensive diagnostic methods, such as RET with amyloid ligands. Thus, the search for reliable and widely available diagnostic markers remains a task of paramount importance both for researchers and doctors, and for the patients themselves and their families.

As evidenced by an analysis of publications over the past two decades, numerous attempts to develop preventive therapy for AD have so far been unsuccessful. Various types of therapeutic interventions have been used as possible preventive therapeutic approaches, including both new generation drugs currently used for the treatment of AD (in particular, donepezil and galantamine) and long-established drugs (ginkgo biloba, non-steroidal anti-inflammatory drugs, statins, tocopherol acetate, ascorbic acid, etc.), however, none of them showed a clinically significant preventive effect.

The search for possible approaches to the development of preventive anti-dementia therapeutic strategies remains, along with the development of new methods of early diagnosis (non-traumatic and inexpensive), one of the main directions of scientific research carried out in the last decade in the Department of Geriatric Psychiatry of the National Center for Healthcare. The subject of special attention has been research aimed at developing preventive neuroprotective and neurotrophic effects, which can be regarded as a kind of barrier to the development of the neurodegenerative process, increasing the survival of neurons in pathological conditions (for example, with abnormal amyloidogenesis, excitoxicity, ischemia, hypoxia, accumulation of free radicals and etc.).

New data have emerged on the role of mitochondrial dysfunction in the development of Alzheimer's-type neurodegeneration. As is known, the normal functioning of the central nervous system depends on the supply of energy substrates and oxygen adequate to cerebral metabolic processes, as well as a number of substances necessary for the occurrence of physiological, anabolic and catabolic processes. The brain has enormous energy needs. In particular, it is known that brain tissue must receive up to 40% of the body’s total oxygen consumption for normal functioning. It is this system that, in the absence of an adequate oxygen supply, turns out to be the most vulnerable of all the vital systems of the body. Moreover, the most sensitive to ischemia are neurons of the hippocampus, pyramidal cells, striatum and Purkinje cells, which are irreversibly damaged under ischemia within 4-6 minutes. Since memory processes and other cognitive functions are provided by the cortical-subcortical-hippocampal structures of the brain, it is cognitive activity that is most severely affected by hypoxia, ischemia and oxidative stress. Recent studies have found that mitochondrial dysfunction plays a trigger role in the destruction of the mechanism that ensures the energy metabolism of neurons and in the triggering of apoptosis, a process of programmed cell death. In this regard, the ability to significantly reduce mitochondrial dysfunction seems to be an urgent task in the development of methods of preventive therapy for AD and other dementias of late age.

L-carnitine (LC) is a natural low-molecular substance that is synthesized in the liver and kidneys of humans and animals. One of the important functions of LA is the transfer of fatty acids from the cytoplasm into the mitochondrial matrix for the formation of energy during the process of β-oxidation, which is necessary for the functioning of all cells of the body [6]. Inside mitochondria, fatty acids, undergoing β-oxidation, form acetyl coenzyme A, which serves as a substrate for the Krebs tricarboxylic acid cycle and subsequent ATP synthesis in the body [7]. LA has a protective effect during apoptosis, which is due to inhibition of ceramide synthesis and caspase activity. The neuroprotective effect of LA, established in a series of experimental studies on animals [8], is presumably associated with the prevention of metabolic processes leading to energy deficiency.

Acetyl-L-carnitine (ALC) is synthesized from LA in brain tissue, liver and kidneys. ALA is a brain-specific derivative of LA; it is an easily accessible substrate for launching energy-dependent metabolic processes in mitochondria, supplying the acetyl group directly to the mitochondrial matrix for the formation of acetyl coenzyme A without consuming ATP and oxygen. The metabolic balance between ALA and LA is the basis of the body's acetyl buffer system. By improving the energy supply of neurons under conditions of reduced oxygen consumption, ALA protects neurons during ischemic hypoxia, the consequences of which are associated with the launch of a cascade of excitotoxic reactions with the accumulation of glutamate in the synaptic cleft, activating NMDA receptors, and causing uncontrolled calcium entry into neurons and their subsequent death [ 9, 10].

A number of experimental studies [11–13] also established the antioxidant effect of ALA. Administration of ALA before acute experimental ischemia reduces the formation of free radicals and promotes ATP conservation. Due to its structural similarity to acetylcholine, ALA has a cholinomimetic effect and also modulates the activity of the dopaminergic and serotonergic systems.

Preparations based on LA and ALA are so-called energy-tropic drugs that can restore impaired cellular energy metabolism. They have found quite wide application in foreign medicine. The ability of carnitine and a number of its derivatives to provide neuronal mitochondria with an energy substrate served as the basis for its administration to patients with acute ischemic stroke, neurodegenerative diseases and a number of somatic diseases [14, 15].

Carnicetine is a domestic drug based on ALA. It demonstrated, under experimental conditions, a pronounced neuroprotective and neurotrophic effect. When administered orally to experimental animals (on a model of AD), its antiamnestic activity and ability to influence learning in the absence of undesirable sedative or muscle relaxant effects were revealed. By improving the energy supply of neurons, ALA protects them during ischemia, the consequence of which is the launch of a cascade of pathological excitotoxic reactions with the release of excitatory amino acids (glutamate and aspartate) into the synthetic gap, activating NMDA receptors and causing uncontrolled entry of calcium-dependent proteases with subsequent death of neurons.

According to T.A. Voronina and R.U. Ostrovskaya [16], carnitine is comparable in effectiveness and safety to foreign drugs based on ALA. Compared to carnitine, ALA exhibits pronounced neuroprotective and neurotrophic activity, promoting restoration processes in the cell structure, which has been proven in various experimental models. In particular, the modeling effect of carnitine and the ability to maintain the normal functioning of the glial system were established [17]. ALA stimulates the synthesis of acetylcholine from choline, acting as a supplier of activated acetyl groups. With long-term use, ALA increases the density of NMDA receptors in the hippocampus, cortex and striatum and prevents an age-dependent decrease in their density [18]. In a series of experimental studies [19], it was found that the administration of ALA can slow down pathological processes caused by oxidative destruction of mitochondria in old rats. Using a model of experimental ischemia, it was shown [20] that subsequent administration of ALA protects the structures of the frontal cortex from free radical oxidation and thereby reduces the severity of brain damage.

Of particular importance from the point of view of the development of pathogenetic therapy for asthma are the data of R. Epis et al. [19], concerning the effect of ALA on β-amyloid metabolism, which was established in models of neuroblastoma cells and in hippocampal neurons of experimental animals. The results obtained by the authors gave reason to assume that the antiamnestic activity of ALA, confirmed in both clinical and experimental studies, may be due not only to an increase in the production of acetylcholine, but also to its specific metabolic effect on the abnormal metabolism of β-amyloid, which is considered as a primary link in cascade of pathogenetic events during the development of Alzheimer's neurodegeneration. ALA enhances physiological α-secretase activity and thereby reduces the likelihood of conversion (by β- and γ-secretases) of amyloid precursor protein into an amyloidogenic metabolite with neurotoxic properties.

There is increasing evidence of the positive effect of ALA on the processes of neurogenesis and stem cell differentiation in the hippocampus [21, 22], which opens up new opportunities for the use of ALA in neurodegenerative diseases as a means of preventive therapy.

A series of clinical studies [23–26] of ALC were performed in patients with dementia, including AD, and in age-dependent (non-dementia) cognitive disorders. Controlled clinical trials conducted in Japan, the USA and several European countries in patients with AD or other dementia have proven the ability of ALA-based drugs to improve memory and other cognitive functions in both non-demented elderly people and in patients with dementia due to AD or cerebral -vascular pathology. The results of foreign clinical studies of the effectiveness of ALA drugs in asthma were not entirely comparable (due to methodological heterogeneity), however, most researchers noted the positive effect of ALA on cognitive functions, comparable to the effect of anticholinergic drugs. One study examined the therapeutic efficacy of combination therapy with an acetylcholinesterase inhibitor (donepezil or rivastigmine) in combination with ALA in those patients with asthma who were resistant to treatment with these drugs. The addition of ALA to donepezil or rivastigmine therapy increased the effectiveness of therapy from 38 to 50%.

The results of a meta-analysis [26] of data from 21 randomized controlled clinical trials in patients with MCI syndrome and early stage AD dementia showed significant benefits of ALC compared to placebo. The meta-analysis included data from 1204 patients (mean age 71.9±0.5 years), of which 591 patients received ALC, 631 received placebo. The daily dose of ALA varied from 1.5 to 3.0 g per day. The duration of treatment also differed: from 3 to 12 months. Because the set of cognitive scales varied across studies, a special coefficient was used for the analysis that took into account change in all scales, and the coefficient reflecting performance on the Clinical Global Impression (CGI) scale or the CIBIC scale was also separately assessed. The results of the analysis showed a significantly higher effectiveness of ALC compared to placebo, both according to psychometric assessment using cognitive scales and overall clinical assessment. At the same time, a high degree of correlation between these parameters was established. Significant changes on the CGI scale in most studies were observed by the end of 3 months of therapy, and the total indicator of therapeutic effectiveness on psychometric scales reached a maximum after 6 months of treatment with ALC. All studies showed that ALC was well tolerated; the number of adverse effects during ALC therapy was comparable to the placebo group.

Also, over the past 6 years, a series of clinical studies have been conducted in the Department of Geriatric Psychiatry of the NCPH on the use of carnicetine in patients with the initial stage of dementia caused by AD or vascular dementia, in patients with aMCI, as well as in elderly depressed patients with concomitant mild organic cerebral disorders of various origins.

A double-blind, placebo-controlled study of carnicetine in elderly people with mild dementia due to AD or cerebrovascular pathology involved 60 patients who met the inclusion and exclusion criteria, from which 2 groups of comparable size were composed [27]. All patients received coded drugs: in the 1st group - carnicetine at a dosage of 2250 to 3000 mg/day, in the 2nd group - placebo. The demographic and syndrome-diagnostic distribution of patients in both groups did not have significant differences. The study lasted 4 months, of which 1 month was spent on screening, 3 months on course treatment. The effectiveness of therapy was assessed using clinical and psychometric scales: MMSE, CGI, subtests “initiation”, “conceptualization” and “memory” of the Mattis Dementia Scale, and the Clock Drawing Test. In addition, activities of daily living (IADL scale) were assessed. The assessment was carried out before the start and after the end of treatment.

The results of the study showed a significantly higher frequency of positive effects (on the CGI scale) in patients taking carnitine compared to the placebo group. The therapeutic effect of carnicetine was confirmed by a significant improvement in the cognitive functions of patients when assessed on a number of scales: MMSE, clock drawing test, one of the tests of the Mattis Dementia Scale, as well as the Assessment of Daily Functioning Scale (IADL). Moreover, the therapeutic effect in terms of overall clinical improvement (CGI scale) was significantly higher in patients with AD than in patients with vascular dementia. Differences in the therapeutic effect of carnitine in patients with AD and vascular dementia did not depend on the initial severity of cognitive deficit.

Taking into account the spectrum of pharmacological activity of carnitine (the ability to neutralize the negative effects of pathogenetic factors involved in the development of neurodegeneration, and strengthen the components of the internal system of protection and restoration of the brain due to its inherent neurotrophic, neuroprotective and anti-apoptotic effects), as well as due to the proven safety of its long-term use It seemed very promising to try to develop a strategy and tactics for using the drug as part of preventive anti-dementia therapy, especially for elderly people at risk of AD or other neurodegenerative dementia.

To find an approach to solving this problem, an open comparative study of the dose-dependent effects of carnitine in the treatment of patients from groups at risk of AD, i.e. the elderly, whose state of cognitive functions corresponded to the aMCI syndrome, was undertaken. A 3-month study compared two daily doses of carnicetine: 1770 mg/day (i.e., 2 capsules 3 times a day) and 2360 mg/day (2 capsules 4 times a day). There were no significant differences in baseline and cognitive characteristics between the groups of patients receiving different doses of the drug. Inclusion criteria were: age from 50 to 90 years, meeting the diagnostic criteria for aMSI syndrome, a Khachinsky scale score of less than 4 points and a Hamilton scale score of less than 18 points.

To assess the effectiveness of treatment, the following scales and tests were used: MMSE, frontal dysfunction battery, clock drawing test, Boston Naming Test, 10-word memory test, sound and categorical associations of the Mattis Dementia Scale. The CGI scale was used to assess the overall clinical effect. The safety of therapy was determined by vital signs and by recording adverse events [28].

By the middle of the treatment course, a significant improvement in cognitive functions was noted in most of the tests used in both groups of patients. By the end of therapy, in the group receiving carnitine at a dose of 1770 mg/day, a significant improvement was found in all assessment tests and scales, except for the frontal dysfunction battery. At the same time, patients who used a higher dosage of the drug (2360 mg/day) showed significant improvement in only 3 of 7 scales. However, the therapeutic effect indicator, determined by the difference between the final and initial assessments, did not have significant differences between groups.

According to the general clinical impression, the therapeutic effect was assessed as a marked improvement in most cases, regardless of the doses of the drug used. Patients' subjective assessment of the treatment effect was reduced to improvement in concentration, memory, intelligence and mood. During the treatment period, adverse events were observed in 2 patients - the appearance of heartburn. One patient took the drug before meals, the other after preliminary dissolution in water. In both patients, heartburn and discomfort disappeared after changing the medication regimen.

The study showed the effectiveness and safety of carnicetine and the feasibility of using a dose of 1770 mg/day (6 capsules in 3 doses) for the treatment of cognitive disorders in elderly people at risk for AD (patients with aMCI syndrome).

The results obtained from this pilot study suggest the feasibility of conducting a larger, dedicated, prospective, placebo-controlled clinical trial of carnicetine 1770 mg/day (orally administered) in biannually repeated 3-month courses. The basis for this conclusion are both the pharmacological characteristics of the drug and the presence of multimodal neurotropic properties, as well as its proven clinical effectiveness in the treatment of the initial stages of AD, vascular dementia and pre-dementia cognitive impairment, as well as the convenience of the oral route of administration and the safety of the drug.

Of particular practical interest were reports on the antidepressant effects of ALA, in particular data on the results of its use in so-called “senile depression” [17]. As previously proven, depression is accompanied by neurodegenerative changes in the dentate gyrus of the hippocampus, the severity of which correlates with the duration of depression. The most important component of the action of modern antidepressants is their effect on neuroplasticity by stimulating the release of neurotrophins. The established neurotrophic effects of ALA and its thymoleptic effect observed in individual clinical studies became the basis for conducting a double-blind randomized trial [29] of the use of ALA in comparison with fluoxetine in the elderly. ALA was prescribed at a dose of 1.5 to 3.0 g/day, fluoxetine - 40 mg/day. The results of a clinical study showed that ALA has an antidepressant effect comparable to that of fluoxetine. Moreover, in the ALC group it was detected already after a week of administration, significantly ahead of the corresponding effect of fluoxetine. The advantage of ALC was also a significant improvement in cognitive activity at the end of therapy, which was absent in the fluoxetine group. Based on this study's evidence of the effectiveness of ALA in elderly patients with depression and possible cognitive dysfunction, it was suggested that carnitine may potentiate the therapeutic effect of antidepressants, at least in elderly patients.

To test this hypothesis, an open comparative study of antidepressant monotherapy using one of the modern antidepressants (venflaxin, agomelatine or fluvoxamine) and combination therapy with the same drugs in combination with carnicetine was undertaken in the Department of Geriatric Psychiatry of the National Center for Clinical Prevention [30]. The study involved 40 patients aged 60 to 79 years with mild or moderate depression (according to ICD-10), distributed into two groups of equal size, demographic and clinical characteristics. Patients in both groups received antidepressant therapy. In the combination therapy group, carnicetine was taken at a dose of 1000 mg/day. The duration of treatment was 8 weeks in both groups. The effectiveness of therapy was assessed using the Hamilton Depression Scale (HAM-D-17) and the Hamilton Anxiety Scale (HAM-A). The level of cognitive activity was assessed using the MMSE scale. The examination was carried out 4 times during the therapeutic course (before the start of treatment, on the 14th, 28th, 56th day of treatment). Tolerability and safety of therapy were assessed based on the Adverse Effects Registration Scale (SARS).

The results of the study showed that the inclusion of carnicetine in a daily dose of 1000 mg in antidepressant therapy allows one to achieve a faster and more complete therapeutic response: after 4 weeks of treatment, complete remission was achieved in the combination therapy group in 30% of cases, while in the monotherapy group - only in 15.8%. The effect achieved by the end of the 8-week treatment was more pronounced in the combination therapy group: complete remission was achieved in the majority (73.6%) of patients who took additional carnitine, and only in 26.3% of patients treated only with antidepressants. The advantage of combination therapy (carnicetine + antidepressant) is also confirmed by the dynamics of test scores on the Hamilton Depression and Anxiety Scales, as well as on the Clinical General Impression scale.

The dynamics of cognitive indicators turned out to be positive in both groups, however, in the combination therapy group (with the inclusion of carnicetine), a significant procognitive effect was achieved already by the 28th day of treatment, whereas in the monotherapy group - only at the end of the course of therapy. Tolerability of the therapy used was also better in the combination therapy group. Undesirable effects of mild or moderate severity were observed more often (not significantly) in the monotherapy group. However, no serious adverse effects were observed in any of the groups.

Thus, the study made it possible to come to the conclusion about the accelerating effect of carnicetine (in a daily dose of 1000 mg) on ​​the development of an antidepressant therapeutic response and to recommend combination therapy with carnitine to optimize antidepressant therapy in elderly and senile patients.

Some authors [31] associate the antidepressant effect of ALA with its ability to participate in the regulation of metabotropic glutamate receptors in the hippocampus and prefrontal cortex. However, according to the authors, the mechanisms of the antidepressant action of drugs based on ALA, including carnitine, require further study.

Not long ago, Italian authors published 2 meta-analytic studies on the antidepressant effects of acetyl-L-carnitine. N. Veronese et al. [32] conducted an analysis of literature sources using all available databases. All published results of randomized clinical trials on the use of acetyl-L-carnitine or combination studies involving this drug in the treatment of depression were considered. The control group consisted of patients with depression who received a placebo or were left without treatment. The data analyzed were from 9 randomized trials, including 231 patients treated with acetyl-L-carnitine and 216 patients treated with placebo or no treatment. The overall conclusion was that the use of acetyl-L-carnitine significantly reduced symptoms of depression compared to placebo (or no treatment). In 3 studies comparing the effects of acetyl-L-carnitine and known antidepressants (162 patients in each group), it was shown that the drug in question exhibits a therapeutic effect similar to the effects of registered antidepressants. At the same time, the number of undesirable effects during treatment with acetyl-L-carnitine turned out to be significantly lower in comparison with antidepressants. The greatest effectiveness of acetyl-L-carnitine in the treatment of elderly people with depression is also indicated.

A recent review published in 2021 [33] analyzes the effects of acetyl-L-carnitine. In addition to the drug’s role in improving energy metabolism, the authors focused on modern research that established its antioxidant, neuromodulatory and neuroprotective therapeutic properties. Their results became the basis for studying the therapeutic potential of the drug in a number of neurological disorders, as well as in the treatment of depressive conditions (see table).

Acetyl-L-carnitine in clinical studies

Today acetyl-L-carnitine is registered as a drug for the treatment of neuropathic pain. Recent preclinical and clinical studies that have proven its new molecular, cellular and energetic mechanisms of action, combined with the results of clinical studies, have given the authors of the review grounds to consider acetyl-L-carnitine as a drug of a new generation of antidepressants, comparable in effectiveness to a number of other drugs of the same group , but with a higher safety profile.

A wide range of possible mechanisms of action have been proposed to explain the drug's multiple effects. The most significant of the newly established mechanisms of pharmacological action include its neurotrophic property, realized through an increase in the activity of nerve growth factor (NGF) and an increase in the expression of NGF in the receptors of the striatum and hippocampus. This mechanism of action has been proven in a number of experimental studies on old rats [50-52]. The results of experiments conducted by the authors of this review [53, 54] show that acetyl-L-carnitine regulates the activity of the NF-kB signaling pathway, thereby increasing the transcriptional activity of the protein. This effect correlates with the drug's ability to induce the expression of glutamate receptor type 2 (mGlu2), which can be considered as a potential mechanism underlying its wide range of pharmacological activities from analgesic to proneurogenic and antidepressant components of action.

Currently, the antidepressant effect of acetyl-L-carnitine is not yet entirely clear. Obviously, the drug has a different mechanism of action than classical antidepressants. According to the authors [54], the mechanism of the antidepressant effect of acetyl-L-carnitine can be explained by its high potential neurogenetic activity, accompanied by an effect on the neuronal differentiation of progenitor neurons in the hippocampus. In this regard, the drug shows similarities with classical antidepressants, which also increase neurogenesis in experimental animals when administered chronically [55]. However, the neurogenic effect caused by acetyl-L-carnitine turned out to be longer lasting than that of classical antidepressants, and lasted more than 2 weeks after stopping the drug, whereas after the end of the administration of the tricyclic antidepressant it disappeared immediately.

Another explanation for the antidepressant effect of acetyl-L-carnitine was proposed by T. Lau et al. [56], who suggested that the drug may act as an antidepressant through increasing levels of the glial neurotrophic factor artemin.

In addition, acetyl-L-carnitine has been shown [57] to increase the levels of norepinephrine and serotonin in the hippocampus, which are positive modulators of neurogenesis in adult animals.

Finally, the authors of [56] admit the possibility that the antidepressant effect of acetyl-L-carnitine is realized through an increase in the energetic synaptic mechanism. Experimental studies have revealed that not only the hippocampus, but also the prefrontal cortex and amygdala neurons are the structures in which the drug improves structural plasticity.

Thus, acetyl-L-carnitine, which is a drug with a broad spectrum of action, appears to be superior to classical monoaminergic antidepressants, which is reflected in the rapid onset of the therapeutic effect with better tolerability. The established multimodal mechanisms of action of acetyl-L-carnitine open up new possibilities for its use not only in the treatment of cognitive disorders in neurodegenerative diseases, but also in the treatment of chronic pain in myalgic syndromes (including those widespread in elderly patients with fibromyalgia), as well as depressive disorders . It must be emphasized that this drug can be widely used in geriatrics as an effective and safe treatment for widespread cognitive, depressive and pain syndromes in the elderly population, which in a significant proportion of cases occur within the same clinical condition, regardless of its etiology.

The author declares no conflict of interest.

e-mail; https://orcid.org/0000-0001-6683-0240

Contraindications for use

Acetyl-L-carnitine is not used in the following cases:

• individual sensitivity to the active component;
• cirrhosis of the liver;
• hepatitis;
• diabetes;
• hypothyroidism;
• epilepsy;
• renal failure.

The compound reduces blood clotting, so it is not recommended for use before surgery. For the same reason, it is prescribed with caution for hemophilia.

The instructions for use of acetyl-L-carnitine indicate that use during pregnancy and lactation is possible only after consultation with a doctor. It is not advisable to take the compound on your own, since clinical trials have not been conducted on its effect on a growing organism.

Side effects and contraindications

Sometimes it is possible to increase the level of activation (mild euphoria) 1-2 hours after administration. Very rarely, when taking large doses, a feeling of mild nausea may occur - in these cases, reduce the dose.

Contraindications: Individual intolerance to the components, pregnant and lactating women. It is recommended to consult a doctor before use.

Storage conditions . Store at a temperature not exceeding 25 °C, in a dry place out of reach of children.

Release forms

Acetyl-L-carnitine is available in several variations:

1. Capsules. The best option for use in the presence of gastrointestinal pathologies. Does not irritate the stomach walls. The capsule shell begins to dissolve only in the intestines, which is why the capsule product begins to act later than ever.
2. Pills. The most popular release variation. One tablet contains the required daily dose (500 or 1000 mg). The advantage of this form is ease of use.
3. Solution. Acetyl-L-carnitine in this form begins to be absorbed most quickly. Within 20-30 minutes it begins to be absorbed into the blood from the gastrointestinal tract. But such solutions are not suitable for people with stomach pathologies, since additional components can have an irritating effect on the gastric wall.
4. Powder. The product in powder form is very economical. According to the instructions, one scoop per application is enough. As a disadvantage, it is worth noting that the powder must be diluted in 500 ml of water, which must be drunk at a time. Also, you cannot prepare the solution for future use; you need to re-dilute the powder each time.

Dosage form

L carnitine is produced in the form of syrup, tablets and capsules. The liquid form is sold in dark glass bottles. The syrup is packaged in 100 ml containers, which contain 10 g of the main active ingredient – ​​levocarnitine.

Elcarnitine tablets can have different dosages - 100 mg and 500 mg. They are packaged in blisters of 10 pieces, the package can contain from 3-5 to 8 blisters. An additional ingredient here is ascorbic acid.

The medicine is also sold in capsules of 250 and 500 mg, packaged in bottles made of polymer material. There are 60, 150 pieces in one jar.

Daily dosages

Acetyl-L-carnitine can be used in different dosages, depending on the purpose of its use:

• increased mental stress, stress, prevention of cognitive impairment - from 1500 to 4000 mg per day;
• as part of complex therapy for diseases of the nervous system - from 1500 to 3000 mg per day;
• for weight loss during drying and for weight loss - up to 2000 mg per day;
• to increase testosterone levels and treat male infertility - from 3000 to 4000 mg per day.

The daily dosage is divided into 2-3 applications. The latter should not be later than 15:00, so as not to cause problems with night sleep. The exact dose of acetyl L-carnitine is calculated individually, based on the patient’s health status, age, weight and purpose of use.

Special instructions for use

Acetyl L-carnitine should be consumed in the first half of the day, as it has a pronounced stimulating effect on the nervous system. The duration of the course is up to 30 days. The product can be drunk half an hour before training if the goal of taking it is to lose weight. To improve the functioning of the nervous system, you can take the supplement with or after food. People with gastrointestinal pathologies are not recommended to use alkar before meals.

Directions for use and dosage

The tablets are taken orally; if necessary, you can take the medicine with water. The dosage and duration of treatment are determined by the attending physician after examining the patient. The average dose for an adult is 250 or 500 mg 2-3 times a day. People involved in sports take L-carnitine once before physical activity in the amount of 500-1500 mg.

Capsules with levocarnitine are swallowed without chewing and washed down with the required volume of liquid. Dosage for adults – 250 or 500 mg 2-3 times a day, for athletes from 500 to 1500 mg per day before training.

Sweet syrup with L kartinin is consumed orally, regardless of food intake. The dose and course of therapy are prescribed by the doctor. Adults take 5 ml of liquid product three times a day. Athletes use the medicine immediately before physical activity, 15 ml 1 time.

For children, the medication is prescribed according to the following scheme:

• from 0-1 year, 8-20 drops;
• from 1-6 years, 20-28 drops;
• from 6-12 years, 2.5 ml.

You need to take Elkartinin 2 or 3 times a day for 30 days. After some time, the use of the product can be repeated. It is better to use the drug in courses and only as prescribed by a doctor.

Side effects

Acetyl L carnitine can cause the following side effects:

• migraine;
• sleep disorders;
• increased blood pressure;
• nausea, vomiting;
• increased excitability.

Diabetics may experience a sharp drop in glucose levels.

Allergic reactions

An allergy to acetyl-L-carnitine is accompanied by the following symptoms:

• feeling of heat throughout the body;
• dizziness;
• nausea;
• vomit;
• stool disorders;
• skin rash.

If the above reactions occur, it is recommended to stop using the supplement.

Explanation of the principle of table formation

The high bioavailability of acetyl-L-carnitine allows it to be taken in small quantities, daily intake is 500-1000 mg. If signs of nervous system diseases appear, the dosage can be increased several times by the attending physician.

Today, many manufacturers offer various dosage options and the number of capsules per package.

After analyzing the proposals, we came to the conclusion that the most economical is to take Acetyl-L-carnitine from the company. The package contains 60 capsules, and the total amount of active substance is 30,000 mg. The cost of the entire jar will be 450 rubles; purchasing a dietary supplement from this company is the most profitable. The ratio of total milligrams to price is 66.7.

Next in terms of economic feasibility are the following manufacturers:

• with a mg/ruble ratio of 64.3;
• (61,2);
• (60,0).

The most expensive for the buyer is acetyl-L carnitine from the manufacturers Solgar (ratio 12.9), Life Extension (13.3), Natures Bounty (13.3).

Signs of overdose

An overdose of acetyl L-carnitine is extremely rare, since the compound is water-soluble and is quickly eliminated by the kidneys without accumulating in the body. When consuming large doses, increased excitability and sleep problems may occur.

First aid if recommended dosages are exceeded is gastric lavage. Then you need to take enterosorbent and drink more clean water. In this case, the use of the additive should be stopped.

Compound

Weight of 1 capsule is 0.6 g. Ingredients: acetyl-L-carnitine, microcrystalline cellulose (carrier), potato starch, anti-caking agents: talc, calcium stearate, silicon dioxide.
Taking 1 capsule (recommended daily dose - RDP) will provide:

* does not exceed the upper permissible level.