Acetyl-L-Carnitine Abstracts

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The following is a list of Acetyl-L-Carnitine Abstracts from published scientific research and papers.

Acetyl-L-Carnitine is available in capsule form from www.integratedhealth.com.

(REFERENCE 1 OF 13)

Ido Y McHowat J Chang KC Arrigoni-Martelli E Orfalian Z Kilo C Corr PB Williamson JR

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

In: Diabetes (1994 Dec) 43(12):1469-77

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%), Mg(2+)-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.

(REFERENCE 2 OF 13)

Herrmann WM Stephan K

Efficacy and clinical relevance of cognition enhancers.

In: Alzheimer Dis Assoc Disord (1991) 5 Suppl 1:S7-12

Changes from the end of 4-week placebo (washout) baselines to the end of 3-month therapy with three chemically different cognition enhancers (CEs) [i.e., piracetam, acetyl-L-carnitine, and nimodipine (NIM)], and parallel changes in placebo controls, were compared to determine the influence of the severity of disease at study entry. Four trials published elsewhere, showing significant treatment differences between active drugs and placebo, were selected according to their (a) sharing at least one global measure for treatment outcome and having shown effects on at least one additional scale or test, and (b) presenting an obvious rank order in the severity of disease. Each study was a standard-controlled clinical phase III trial with greater than 100 psychogeriatric in-or outpatients. The patients’ symptoms met the criteria for mild to moderate/severe age-related organic brain syndrome, a core syndrome of senile dementia, either from the primary degenerative, mixed, or multi-infarct type. The extent of changes on placebo was clearly influenced by the mean pretreatment severity of disease. On the whole, the improvements on active drugs reached or exceeded the baseline variability of psychogeriatric scales and tests.

(REFERENCE 3 OF 13)

Carta A Calvani M Bravi D Bhuachalla SN

Acetyl-L-carnitine and Alzheimer’s disease: pharmacological considerations beyond the cholinergic sphere.

In: Ann N Y Acad Sci (1993 Sep 24) 695:324-6

Since ALCAR and L-carnitine are “shuttles” of long chain fatty acids between the cytosol and the mitochondria to undergo beta-oxidation, they play an essential role in energy production and in clearing toxic accumulations of fatty acids in the mitochondria. ALCAR has been considered of potential use in senile dementia of the Alzheimer type (SDAT) because of its ability to serve as a precursor for acetylcholine. However, pharmacological studies with ALCAR in animals have demonstrated its facility to maximize energy production and promote cellular membrane stability, particularly its ability to restore membranal changes that are age-related. Since recent investigations have implicated abnormal energy processing leading to cell death, and severity-dependent membrane disruption in the pathology of Alzheimer’s disease, we speculate that the beneficial effects associated with ALCAR administration in Alzheimer patients are due not only to its cholinergic properties, but also to its ability to support physiological cellular functioning at the mitochondrial level. This hypothetical mechanism of action is discussed with respect to compelling supportive animal studies and recent observations of significant decrease of carnitine acetyltransferase (the catalyst of L-carnitine acylation to acetyl-L-carnitine) in autopsied Alzheimer brains.

(REFERENCE 4 OF 13)

Schoemaker JH

Pharmacological treatment of diabetic peripheral neuropathy:challenges and possibilities.

In: Br J Clin Pract (1994 Mar-Apr) 48(2):91-6

Peripheral neuropathy is a well-recognised late complication in both insulin-dependent and non-insulin-dependent diabetes. However, its exact cause remains unknown. Various pathogenic mechanisms have been proposed as an explanation for the development of nerve fibre damage and associated sensory loss in this disease. As a result, many kinds of drugs are currently under evaluation for the treatment of diabetic peripheral neuropathy. This paper describes the rationale behind the usage of all these drugs and reviews major clinical and preclinical results published so far. Supplementary intake of such natural, non-toxic compounds as vitamin constituents, linoleic acid and flavonoids is encouraged, as well as strict control of hyperglycaemia, until the efficacy of one or another experimental drug is established.

(REFERENCE 5 OF 13)

Bhuiyan AK Jackson S Turnbull DM Aynsley-Green A Leonard JV Bartlett K

The measurement of carnitine and acyl-carnitines: application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.

In: Clin Chim Acta (1992 May 15) 207(3):185-204

We describe an improved radio-enzymatic method for the measurement of carnitine, short-chain acyl-carnitine and long-chain acyl-carnitine in plasma and tissue. An internal standard, hexadecanoyl-[CH3-3H]-carnitine was synthesised and used to improve the determination of long-chain acyl-carnitine. The between and within batch precisions were 10.4 and 7%, respectively. Control data for neonates, infants, children and adults in the fed and fasted state are documented. In addition we confirm the hypocarnitinaemia associated with pregnancy. Patients with medium-chain acyl-CoA dehydrogenase deficiency were studied during episodes of hypoglycaemia. In both fasted controls and patients there were high concentrations of short-chain acyl-carnitine, however in the latter group there were also low concentrations of free carnitine. We suggest that the monitoring of plasma carnitine and its derivatives is a useful adjunct to the investigation of children suspected to suffer from inherited disorders of mitochondrial beta-oxidation. We also describe a sample preparation procedure suitable for high performance liquid chromatographic analysis of specific acyl-carnitines from urine, plasma and tissue homogenates. The recoveries of acetyl-carnitine, octanoyl-carnitine and hexadecanoyl carnitine from urine were 101.5, 95 and 91% and from plasma 99.5, 91.5 and 85.5%, respectively. Acyl-carnitines (C2-C16) were analysed as their p-bromophenacyl derivatives by reverse-phase high performance liquid chromatography using a ternary gradient of acetonitrile/water/triethylamine phosphate. We report ten patients who excreted octanoyl-carnitine, hexanoyl-carnitine and in some cases a small amount of decanoyl-carnitine. In most of these cases suberylglycine and dicarboxylic acids were also detected by GC/MS. We had access to cultured fibroblasts from five of these patients and were able to demonstrate medium-chain acyl-CoA dehydrogenase deficiency by direct enzyme assay.

(REFERENCE 6 OF 13)

De Falco FA D’Angelo E Grimaldi G Scafuro F Sachez F Caruso G

Effect of the chronic treatment with L-acetylcarnitine in Down’s syndrome

In: Clin Ter (1994 Feb) 144(2):123-7 (Published in Italian)

Neuropsychologic tests were performed in subjects with Down syndrome in order to assess the effect of a 90-day treatment with L-acetyl-carnitine (LAC). Findings were evaluated statistically (Wilcoxon test) and compared to three further groups of subjects: untreated Down syndrome, mental deficiency due to other cases treated and not treated with LAC (Mann-Whitney U-test). Treated Down syndrome patients showed statistically significant improvements of visual memory and attention both in absolute terms and in comparison with the other groups. No improvement was found in mentally deficient non- Down subjects, so that the favourable effect of LAC appears to be specific for Down patients. In view of the analogies of the pathology and neurochemistry between Down syndrome and Alzheimer degenerative deficiency (deficit of cholinergic transmission) it is suggested that the action of LAC in these pathologies is related to its direct and indirect cholinomimetic effect.

(REFERENCE 7 OF 13)

Salvioli G Neri M

L-acetylcarnitine treatment of mental decline in the elderly.

In: Drugs Exp Clin Res (1994) 20(4):169-76

A single-blind clinical trial was carried out on 481 subjects enrolled in 44 geriatric and neurologic units following a strict selection criteria: age, Mini Mental State Examination (MMSE) Global Deterioration Scale and Geriatric Depression Scale (GDS). After the initial screening and enrollment, the trial was run for 150 days in four phases: phase T0 (placebo treatment for 30 days), phases T1 and T2 (L-acetylcarnitine (LAC) 1500 mg/day for 90 days), phase T3 (further 30 days of placebo treatment). Drug efficacy was evaluated according to changes occurring from the beginning to the end of the tests which evaluate either whole and specific cognitive performances, or emotional-affective and relational behaviour. The outcome of phase T3 enabled the authors to estimate the possible favourable effects persisting after termination of L-acetylcarnitine therapy. The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment (p < 0.0001). The Randt Memory Test also revealed that LAC treatment improved the items tested: the total score and the memory index increased significantly and the favourable effect persisted after LAC was discontinued. The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy, and the positive results were confirmed by the Hamilton Rating Scale (p < 0.0001). The behavioural-relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment (p < 0.0004); the same trend was observed in the scores for instability and negative feeling. No significant adverse drug reaction occurred during the trial. In conclusion, the statistical analysis of the data from this single-blind, multicentre trial of mild mental impairment in the elderly showed a significant improvement of several performances during and after LAC treatment. Other reports indicate that this drug may be effective in the treatment of dementia.

(REFERENCE 8 OF 13)

Maccari F Arseni A Chiodi P Ramacci MT Angelucci L

Levels of carnitines in brain and other tissues of rats of different ages: effect of acetyl-L-carnitine administration.

In: Exp Gerontol (1990) 25(2):127-34

Male Sprague-Dawley rats, aged 2, 5, 16, 20 and 30 months and normally fed, were used for determination of carnitines in the brain, serum, heart, tibial muscle, liver and urine. With respect to 5-month-old animals, those aged 30 months exhibited a statistically significant decrement of total carnitine levels in the brain, serum, heart and tibial muscle, accompanied by a dramatic increment in the liver. This suggests impaired net transport of carnitines from the liver to the blood in old age. Urinary excretion was similar in the two age groups. One group received from 5 months on daily 75 mg/kg acetyl-L-carnitine in drinking water. At 20 months, the treated animals showed levels of brain, heart and serum carnitines similar to those of 5-month-old animals. The recovery of brain, heart and serum carnitines in the old animals treated with acetyl-L-carnitine indicates that intestinal absorption and tissue uptake remain sufficiently efficient in the course of aging. The lower level of brain lipofuscins due to acetyl-L-carnitine treatment may be related to the effect of the compound on acetylcholine metabolism.

(REFERENCE 9 OF 13)

Bella R Biondi R Raffaele R Pennisi G

Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders.

In: Int J Clin Pharmacol Res (1990) 10(6):355-60

Sixty senile subjects (60-80 years old) with dysthymic disturbances as defined by DSM III (Cat. 390.40) were randomized into two homogeneous groups, one of which was given acetyl-L-carnitine (3 g/day per os) while the other received a placebo. After a washout phase of one week, each patient was evaluated by scoring on the Hamilton Rating Scale for Depression and the Beck Depression Inventory, as well as the Sandoz Clinical Assessment-Geriatric. These tests were administered at the beginning of the trial, prior to drug administration, and repeated during the treatment phase after 30 and 60 days. The results showed that treatment with acetyl-L-carnitine induced a significant reduction, as compared to the placebo (p less than 0.002), in the severity of depressive symptoms and also a significant improvement (p less than 0.0027) in the items measuring the quality of life.

(REFERENCE 10 OF 13)

Herrmann WM Dietrich B Hiersemenzel R

Pharmaco-electroencephalographic and clinical effects of the cholinergic substance–acetyl-L-carnitine–in patients with organic brain syndrome.

In: Int J Clin Pharmacol Res (1990) 10(1-2):81-4

In two double-blind, placebo-controlled clinical studies of the nootropic compound acetyl-L-carnitine on the electroencephalogram (EEG) and impaired brain functions of elderly outpatients with mild to moderate cognitive decline of the organic brain syndrome, statistically significant effects could be detected after eight weeks (on the EEG), and after 12 weeks of treatment (on the physician’s clinical global impression and the patient-rated level of activities of daily living). Side-effects of acetyl-L-carnitine were generally minor and overall rare. Longer treatment periods and further specifications with regard to the aetiopathology and degree of cognitive impairment are recommended for further clinical studies of this promising compound.

(REFERENCE 11 OF 13)

Di Giulio AM Gorio A Bertelli A Mantegazza P Ferraris L Ramacci MT

Acetyl-L-carnitine prevents substance P loss in the sciatic nerve and lumbar spinal cord of diabetic animals.

In: Int J Clin Pharmacol Res (1992) 12(5-6):243-6

Diabetic neuropathy is a disease of peripheral nerves, characterized by axonal atrophy and degeneration that might be preceded by a marked impairment of axonal transport and by a reduced conduction velocity. Sensory nerves are particularly susceptible to diabetes. In the present report it is shown that experimental diabetes in rats causes a significant reduction of the content of the pain-related neuropeptide substance P in sciatic nerve and lumbar spinal cord. Such a loss of substance P is fully prevented by acetyl-L-carnitine treatment. The neuroprotective pharmacological effect is selective and takes place without significant changes of hyperglycaemia and without modifications of the reduced rate of body growth typical of diabetic animals.

(REFERENCE 12 OF 13)

Gorio A Di Giulio AM Tenconi B Donadoni L Germani E Bertelli A Mantegazza P Maccari F Ramacci MT

Peptide alterations in autonomic diabetic neuropathy prevented by acetyl-L-carnitine.

In: Int J Clin Pharmacol Res (1992) 12(5-6):225-30

Autonomic neuropathy and gastrointestinal problems are among the most common complications of diabetes. In this report it is shown that a possible correlation between the two disorders might exist, since diabetes causes a profound alteration of the peptidergic innervation of the gut. It is reported that 14 weeks after diabetes induction with alloxan the levels of substance P and methionine-enkephalin are markedly reduced throughout the intestine, while vasoactive intestinal polypeptide content is dramatically increased. Therefore the enteric innervation of diabetic animals is completely disorganized, with some systems undergoing atrophy and others undergoing hypertrophy. Treatment of diabetic animals with acetyl-L-carnitine prevents the onset of the marked peptide changes described above. The results suggest a potential for acetyl-L-carnitine in the treatment of autonomic neuropathies.

(REFERENCE 13 OF 13)

Corbucci GG Menichetti A Cogliatti A Nicoli P Arduini A Damonti W Marchionni A Calvani M

Metabolic aspects of acute cerebral hypoxia during extracoporeal circulation and their modification induced by acetyl-carnitine treatment.

In: Int J Clin Pharmacol Res (1992) 12(2):89-98

Following their previous research experiences in human tissue hypoxia, in the present study the authors. investigated the metabolic effects of acute brain hypoxia in a group of patients in course of extracorporeal circulation for aorto-pulmonary bypass. One hundred subjects were treated, half with a placebo and half with acetyl-carnitine to evaluate the effects of oxidative stress in some brain plasmatic metabolites and to verify the effect of acetyl-carnitine on the tissue energy capacity. The levels of lactate, pyruvate, succinate and fumarate showed a significant imbalance due to hypoxia, while the acetyl-carnitine treatment confined the metabolic gradients within physiological limits. This means that during the course of extracorporeal circulation brain hypoxia plays a pathological role assuming the typical picture of cellular oxidative damage and the acetyl-carnitine antagonizes these deleterious effects of hypoxia by a protective mechanism on the energy processes and then on the cellular enzymic activities. In this regard, the d-tyrosine levels, considered as a proteolytic index, confirm the action of acetyl-carnitine on the cell morpho-functional integrity.