-IBIS-1.7.0-
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amino acid
Carnitine
Nutrition

definition

Carnitine:

» metabolism:

• Carnitine is an amino acid derivative synthesized from the essential amino acids lysine and methionine. It has similarities to choline and resembles some of the B vitamins because of its amine group and properties. It is made in the liver, kidneys and brain. Iron, vitamin C, steps that are vital for the synthesis of carnitine.

It was originally isolated from meat extracts in 1905 and its structure was determined in 1932. In 1952 it was established as a growth factor of the mealworm, Tenebrio molitor and given the name vitamin BT.

• Certain tissues, including the heart, skeletal muscles, epididymis, liver and kidneys, have specific transport proteins which actively concentrate carnitine into the tissue as high as 10x the rate found in the plasma. In the heart carnitine is particularly concentrated in the sarcoplasma reticulum. In semen carnitine is concentrated 5x higher than in the serum.

• Carnitine synthesis in infants is limited. It has been found that both fetal and umbilical cord blood have higher levels of carnitine than maternal blood. This means that active transport is taking place, offsetting the fetuss inability to adequately synthesize carnitine.

• Because carnitine is synthesized in the body, it is often not considered to be an essential nutrient. However, it is probably essential for preterm infants who can not make enough. It also may be considered conditionally essential in those with heart conditions which might require an additional supply.

» function:

• Carnitine has been determined to be an essential substance in humans for the metabolism of fats. It is involved in the rate limiting step for beta oxidation which allows fats to be transported across mitochrondrial cell membranes. Fatty acids must be transferred from CoA to carnitine. Then the acyl-carnitine molecule can transport the fatty acid into the mitochondria to be oxidized.

• Brown fat (which is metabolically more active than yellow fat) is highly dependent on carnitine to aid in the heat producing beta oxidation reaction.

• Carnitine helps the body oxidize amino acids when necessary as in the case of a fast or low carbohydrate diet. It therefore helps the body metabolize ketones for energy utilization.

• Cardiac L-carnitine content is essential for mitochondrial fatty acid transport and ATP-ADP exchange.

• Carnitine also seems to be involved with prostaglandin production, especially in smooth and skeletal muscles, where it provides these cells with needed energy.

• It is also involved in the conversion of certain amino acids valine, leucine, and isoleucineinto energy products.

• Finally, carnitine appears to decrease ketones in the body. Therefore, it may be useful for diabetics.

» requirements:

• RDA: ? (not considered essential)

• Average intake in the U.S.: 5-100 mg per day

• Lab: A muscle biopsy works best, however RBC will give approximate levels.

» food sources:

• Carnitine is found only in animal products such as human milk, meat, poultry, and dairy products.

Best Sources of Carnitine

Food Amount Mg

Beef, ground 3 oz 640

Beef, steak 3 oz 540

Bacon 3 oz 135

Milk, whole cow's 1 c 45

Fish 3 oz 30

Chicken 3 oz 30

Milk formula based on milk 1 c 25-50

Milk, Human 1 c 25

Infant formula based on beef 1 c up to 150

Wheat whole bread 2 slices 2

Soy based formula 1 c 1 or less

(USDA: Composition of Foods. USDA Handbook #8 Washington DC, ARS, USDA, 1976-1986)

» deficiency:

• Carnitine deficiency can occur in premature infants, people with total parenteral nutrition or on starvation diets, and those with liver damage. Symptoms may include muscle weakness, fatty deposits, impaired ketogenesis with hyperlipidemia, and impaired glucose control. Deficiencies have been found in certain conditions such as Duchenne-type muscular dystrophy, and in people receiving dialysis.

• Children at 2.5 yrs of age synthesize carnitine at about 30% the rate of adults. Full synthesis does not occur until 15 yrs of age. Symptoms in children may resemble Reyes syndrome with acute brain swelling, hypoglycemia, and heart disturbances. Several fatal cases of acute carnitine deficiency have been reported.

» therapeutics:

AIDS: Carnitine may improve symptoms of fatigue and muscle wasting. In addition it may enhance lymphocyte function as involved in immunity. L-carnitine may protect the liver against the deleterious effects of AZT which can damage the mitochondria. (Marz, p. 75, 1997)

Alzheimers disease or related conditions: The L-acetylcarnitine form may significantly improve the symptoms of depression and memory problems. L-acetylcarnitine is a major neurotransmitter in the brain. There have been numerous studies to date which have shown benefits in mental function, particularly in enhancing memory and constructional thinking.

(Brooks JO 3rd, et al. Int Psychogeriatr 1998 Jun;10(2):193-203; Thal LJ, et al. Neurology 1996 Sep;47(3):705-711; Pettegrew JW, et al. Neurobiol Aging 1995 Jan-Feb;16(1):1-4; Sano M, et al. Arch Neurol 1992 Nov;49(11):1137-1141; Spagnoli A, et al. Neurology 1991 Nov;41(11):1726-1732; Cipolli C, Chiari G. Clin Ter 1990 Mar 31;132(6 Suppl):479-510; Passeri M, et al. Int J Clin Pharmacol Res 1990;10(1-2):75-79; Tempesta E, et al. Int J Clin Pharmacol Res 1990;10(1-2):101-107; Rai G, et al. Curr Med Res Opin 1990;11(10):638-647.)

Angina pectoris: In double blind controlled trials it has been shown that carnitine gives significant benefits to angina patients by improving circulation to peripheral tissues. (Cherchi, A, et al. J Clin Pharm Ther Toxicol 23:569-572, 1985; Orlando, G, Rusconi, C. Clin Trials J 23:338-44, 1986)

Athletic Performance and Peripheral Vascular Circulation: 1-4 g per day, may especially enhance endurance capacity. (Leibovitz, B. New York: Dell Pub Co. Inc, 1984; Anon. Nutrition Reviews 39(11):406-7, 1981)

L-Carnitine also prevents muscle damage after exercise: In one study of six 3 g/day of L-carnitine significantly reduced pain, tenderness and CK release (a measure of muscle breakdown) after exercise as compared to a placebo. Further study concluded that these benefits from L-carnitine were not due to a "training effect" (i.e.. testing L-carnitine after testing placebo).

(Giamberardino MA, et al. Int J Sports Med 1996; 17:320-324.)

COPD and other chronic lung conditions which involve difficulty breathing. Carnitine may improve intercostal muscle strength. (Marz, p. 75, 1997)

Cirrhosis of the liver: Carnitine may prevent or reduce fatty infiltration of the liver. It may also reduce toxicity to various toxic agents.

Depression in elderly: In one double-blind study with twenty-eight patients aged between 70 and 80 years received 500 mg L-acetylcarnitine three times a day was found to be effective in counteracting symptoms of depression in the elderly. (Garzya G, et al. Drugs Exp Clin Res 1990;16(2):101-106.)

Diabetes mellitus: Carnitine can have significant effects on circulation and improve cardiovascular parameters.

Down Syndrome: Down Syndrome shares many of the characteristic brain abnormalities that Alzheimers disease does and its efficacy hs been studied. There have been some favorable studies using L-acetylcarnitine.

(Cipolli, C., and Chiari, G. Clin Ther 132, 479-510, 1990)

Heart diseases including cardiomyopathy, arrhythmias, congestive heart failure, myocardial infarction, mitral valve prolapse: Cardiac L-carnitine content, essential for mitochondrial fatty acid transport and ATP-ADP exchange, decreases during ischemia. 1-4 g per day It has been found that carnitine can increase HDL cholesterol while decreasing LDL and triglycerides. It works by providing energy to the heart muscle. There have been many positive studies concerning L-carnitine. With taurine and Coenzyme Q 10, carnitine may be an effective treatment for acute myocardial infarction and congestive heart failure. (Pola, P, et al. Drugs Exptl Clin Res 9:925-34, 1983; Davini, P, et al. Drugs Exptl Clin Res 18:355-65, 1992; Singh RB, et al. Postgrad Med J 1996 Jan;72(843):45-50; Bartels GL, et al. Cardiovasc Drugs Ther 1995 Dec;9(6):749-753; Iliceto S, et al. J Am Coll Cardiol 1995 Aug;26(2):380-387; Pucciarelli G, et al. Clin Ter 1992 Nov;141(11):379-384; Martina B, et al. Schweiz Med Wochenschr 1992 Sep 12;122(37):1352-1355; Mancini M, et al. Arzneimittelforschung 1992 Sep;42(9):1101-1104.; Lagioia R, et al. Int J Cardiol 1992 Feb;34(2):167-172; Pastoris O, et al. Pharmacol Res 1998 Feb;37(2):115-122.)

Infant formula, especially premature infants or soy milk fed infants or vegetarian babies: Carnitine only occurs in animal foods and strictly fed vegetarian infants may develop a deficiency. It is wise to supplement 250-500 mg per day as a prevention. It may be of value in prevention of Reyes syndrome in children. Preterm infants may require additional carnitine because of a decrease ability to store and synthesize carnitine. It may enhance weight gain and growth.

Intermittent claudication: Just as it can improve problems with angina, carnitine can reduce intermittent claudication by improving oxygenation of the peripheral tissues.

Infertility: It has been found that carnitine is concentrated in semen 5x that of serum.

(Costa, M, et al. Andrologia 26:155-59, 1994; Vitali, G, et al. Drugs Exptl Clin Res 21:157-59, 1995)

Miscellaneous inborn errors in metabolism: Glutaric aciduria, isovaleric acidemia, propionic acidemia and methylmalonic aciduria may all respond to carnitine therapy.

Trauma: Carnitine helps maintain weight when there is a limited intake of nutrients, especially in total parenteral nutrition and during acute trauma.

» dosage: 0.5 - 1.0 g three times daily

» toxicity:

• L-Carnitine is very safe, producing few side effects even at high doses.

• The D,L-carnitine has produced side effects, including muscle pain and decreased exercise tolerance in compromised patients, and can deplete levels of L-carnitine in the heart and skeletal muscles. These effects were reversed when the D,L form was discontinued.

• Some people who are taking carnitine may experience a fishy smell from bacterial amines that are produced. Heartburn can sometimes occur.

• In addition, some people may experience diarrhea if they begin supplementation with a too high dose.

» contraindications:

• Use with caution in patients with kidney problems.

footnotes

Anonymous. Role of carnitine in branched chain ketoacid metabolism. Nutrition Reviews 39(11):406-407, 1981.

Bartels GL, Remme WJ, den Hartog FR, Wielenga RP, Kruijssen DA. Additional antiischemic effects of long-term L-propionylcarnitine in anginal patients treated with conventional antianginal therapy. Cardiovasc Drugs Ther 1995 Dec;9(6):749-753.

Abstract: Cardiac L-carnitine content, essential for mitochondrial fatty acid transport and ATP-ADP exchange, decreases during ischemia. In animal models, administration of the natural derivative, L-propionylcarnitine, may reduce ischemia and improve cardiac function. To evaluate possible antiischemic effects of L-propionylcarnitine was compared with placebo in a randomized, double-blind, parallel design, in addition to preexisting therapy. Patients with > or = 2 anginal attacks per week and objective signs of ischemia with angina during bicycle exercise testing were included. After an initial 2-week, single-blind placebo phase, 37 patients received 500 mg L-propionylcarnitine tid, and 37 patients received placebo for 6 weeks. Both groups were comparable at baseline. Three patients discontinued the study while on placebo (two because of noncompliance, one because of palpitations) and one while on L-propionylcarnitine (noncompliance). Although heart rate, blood pressure at rest, and maximal exercise were not affected, L-propionylcarnitine increased the time to 0.1 mV ST-segment depression [44 +/- 3 vs. 8 +/- 2 seconds (mean +/- SEM) in the placebo group; p = 0.05], and exercise duration improved by 5% compared with placebo. Anginal attacks and the consumption of nitroglycerin were not affected in either group. Thus, following a 6 week treatment period, L-propionylcarnitine induced additional, albeit marginal, antiischemic effects in anginal patients who were still symptomatic despite maximal conventional antianginal therapy. It is questionable whether in these patients this form of metabolic treatment will achieve great benefit, although in some improvement can be expected.

Brooks JO 3rd, Yesavage JA, Carta A, Bravi D. Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. Int Psychogeriatr 1998 Jun;10(2):193-203.

Abstract: OBJECTIVES: To assess the longitudinal effects of acety-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. DESIGN: Longitudinal, double-blind, parallel-group, placebo-controlled. SETTING: Twenty-four outpatient sites across the United States. PARTICIPANTS: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). MEASUREMENTS: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. RESULTS: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC, significant, cutpoint for ALC benefit was 61 years of age. CONCLUSIONS: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

Cherchi, A, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double blind randomized placebo controlled crossover study. J Clin Pharm Ther Toxicol 23:569-572, 1985.

Abstract: 1g twice daily of carnitine or placebo was used to treat 44 males with chronic stable effort induced angina. The trial lasted for 4 weeks and then the patients switched. Carnitine significantly increased the amounts of work required to induce the angina. EKG showed ST segment depression was significantly worse on placebo compared to the carnitine.

Cipolli C, Chiari G. [Effects of L-acetylcarnitine on mental deterioration in the aged: initial results]. Clin Ter 1990 Mar 31;132(6 Suppl):479-510. [Article in Italian]

Abstract: In this paper the preliminary findings of a multicentre study on the effects of Acetyl-L-Carnitine on mildly impaired elderly are reported. Statistical analysis was carried out on 236 out of 469 subjects sampled in 42 different Italian geriatric or hospital units. Each subject was treated over 150 days, and a battery of tests (investigating cognitive functioning, emotional-affective state and relational behavior) was administered at the beginning on the treatment and the conclusion of each of its four phases. In the first and the last phases there was a 30 days placebo treatment (aimed respectively to wash-out the effects of previous drug and to assess the residual effects of the treatment), while in the second and the third ones (both 45 days long) the subjects took 1500 mg/day of Acetyl-L-carnitine. Repeated multivariate analysis of variance and of covariance (taking as independent variables phases of treatment, age, gender, etiology and severity of mental impairment, as dependent variables the scores either of each test administered or of groups of items and as covariants the level of depression and the sensitivity to placebo effect) showed that drug treatment significantly increased the effectiveness of performance on all the measures of cognitive functioning and of emotional-affective state and on some scores of the relational behavior. Age resulted significantly influential on cognitive functioning and relational behavior, but not on emotional-affective state. Severity of mental impairment significantly influenced also several measures of cognitive functioning and relational behavior, while less consistent results were shown for gender and etiology of mental impairment. The placebo effect, although significant for some cognitive processes, was lower than that of treatment. There findings suggest that Acetyl-L-carnitine treatment is effective against the outcomes of mental impairment in the cognitive (in particular, for memory functioning and constructional thinking) and emotional-affective domains, while its effects on relational behaviour are less consistent, probably because they are partly biased in the subjective evaluation of caregivers and relatives by factors such as age and levels of mental impairment and depression.

Costa, M, et al. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Andrologia 26:155-159, 1994.

Abstract: 100 infertile men with poor sperm motility were given L-carnitine 3gms/day for 4 months. There was a significant increase in sperm motility which was especially apparent with the men with the lowest sperm motility.

Davini, P, et al. Controlled study on L-carnitine therapeutic efficacy in most MI patients. Drugs Exptl Clin Res 18:355-365, 1992.

Abstract: 160 patients following MIs were randomly assigned to receive either 4g/day of carnitine in addition to standard treatment or standard treatment alone. During the follow up period the next year, the carnitine group had significant reductions in blood pressure, fewer anginal attacks and a significant reduction in cholesterol levels. The mortality rate in the carnitine group was 1.2% compared to 12.5% in the control group (p=0.005).

Garzya G, Corallo D, Fiore A, Lecciso G, Petrelli G, Zotti C. Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Drugs Exp Clin Res 1990;16(2):101-106.

Abstract: Twenty-eight patients aged between 70 and 80 years affected by depressive disturbance as defined by DSM III R (cat. 300.40) were subdivided at random into two homogeneous groups of 14 each. One group was treated with 500 mg three times a day of L-acetylcarnitine (LAC) in tablet form, while the other received placebo. Each patient was evaluated by the Hamilton Rating Scale for Depression, the Beck Depression Inventory, the Sandoz Clinical Assessment--Geriatric, and by clinical global impression. This investigation establishes that LAC is effective in counteracting symptoms of depression in the elderly. Relief of depressive symptomatology is expressed by decreased scores in the Hamilton Rating Scale for Depression and Beck Depression Inventory and by beneficial effects with regard to behavioural aspects.

Giamberardino MA, Dragani L, Valente R, Di Lisa F, Saggini R, Vecchiet L. Effects of prolonged L-carnitine administration on delayed muscle pain and CK release after eccentric effort. Int J Sports Med 1996 Jul;17(5):320-324.

Abstract: Eccentric muscle effort is known to induce delayed muscle soreness (DOMS) and muscle damage which are not responsive to medical treatment with the most common analgesic agents. The aim of the study was to investigate the effects of oral L-carnitine supplementation on pain (VAS scale), tenderness (pain thresholds) and CK release induced by a 20-min eccentric effort of the quadriceps muscle. A single-blind study was carried out on 6 untrained subjects (mean age: 26 +/- 3.8 yrs; mean height: 173 +/- 4.6 cm; mean body weight, 68.3 +/- 4.5 kg) over 7 weeks during which each subject: a) was given 3 g/day of placebo for 3 weeks and, after a week's interval, 3 g/day of L-carnitine for 3 weeks: b) performed 2 step tests on the first day of the 3rd and 7th week inverting the order of the exercising limb. In a separate set of experiments carried out 8 months later, the possible effects of training on pain parameters and CK levels were also investigated in the same subjects who performed 2 step tests at a 4-weeks' interval, without medication. L-carnitine significantly reduced pain, tenderness and CK release after the effort with respect to placebo. In contrast, no significant difference was found in the parameters measured between the two tests performed without medication. It is concluded that L-carnitine has a protective effect against pain and damage from eccentric effort. This effect is mainly attributed to the vasodilatation property of the compound, which both improves energetic metabolism of the hypoxic/damaged muscle and enhances wash-out of algogenic metabolites.

Hakkou F, Jaouen C, Iraki L. A comparative study of cyproheptadine and DL carnitine on psychomotor performance and memory in healthy volunteers. Fundam Clin Pharmacol 1990;4(2):191-200.

Abstract: This study was performed in order to investigate the extent and severity of cyproheptadine effects on psychomotor performance, mood and memory functions and to compare them to the effects of DL carnitine, another appetite stimulant. Twelve healthy volunteers received 2 doses (at 800 am and 1200 am) of 6 mg cyproheptadine, 1600 mg DL carnitine and placebo on separate days at a weekly intervals. The study followed a double-blind, latin-square design. Assessment of dependent variables was performed 1 h after the first and 1 h and 5 h after the second administration of the drug. On each of these occasions, the following measurements were performed: choice reaction time (CRT), critical flicker fusion (CFF), digit symbol substitution test (DSST), short-term memory (paired words association test), long-term memory (picture test) and 100 mm visual analogue scales of subjective ratings (VAS). Cyproheptadine significantly impaired objective measures (CFF) and subjective ratings both at 1 h and 5 h after the second dosage. Compared with cyproheptadine, DL carnitine induced a slight improvement in psychomotor performance as assessed by CRT. None of the drugs had any effect on memory and on appetite at the doses studied. In conclusion, cyproheptadine at usual doses had a sedative effect, the intensity and duration of which implied a certain risk in performing daytime functions eg when driving, or manipulating machines. DL carnitine had no effect on vigilance.

Iliceto S, Scrutinio D, Bruzzi P, D'Ambrosio G, Boni L, Di Biase M, Biasco G, Hugenholtz PG, Rizzon P. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol 1995 Aug;26(2):380-387.

Abstract: OBJECTIVES. This study was performed to evaluate the effects of L-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. BACKGROUND. Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. METHODS. The L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or L-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or L-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. RESULTS. A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with L-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and end-systolic volumes from admission to 3-, 6- and 12-month evaluation was significantly reduced in the L-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the L-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. CONCLUSIONS. L-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event.

Lagioia R, Scrutinio D, Mangini SG, Ricci A, Mastropasqua F, Valentini G, Ramunni G, Totaro Fila G, Rizzon P. Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina. Int J Cardiol 1992 Feb;34(2):167-172.

Abstract: The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.

Leibovitz, B. Carnitine the Vitamin BT Phenomenon. New York: Dell Pub Co. Inc, 1984.

Mancini M, Rengo F, Lingetti M, Sorrentino GP, Nolfe G. Controlled study on the therapeutic efficacy of propionyl-L-carnitine in patients with congestive heart failure. Arzneimittelforschung 1992 Sep;42(9):1101-1104.

Abstract: A double-blind phase II study of propionyl-L-carnitine (CAS 17298-37-2) versus placebo was carried out on a group of 60 patients with mild to moderate (II and III NYHA class) congestive heart failure. The group was made up of men and women aged between 48 and 73 years in chronic treatment with digitalis and diuretics for at least 3 months and who still displayed symptoms. Thirty of these patients were chosen randomly and for 180 days, 500 mg of propionyl-L-carnitine was orally administered, 3 times a day in addition to their usual treatment. At basal conditions and after 30, 90 and 180 days the maximum exercise time was evaluated using an exercise tolerance test performed on an ergometer bicycle and the left ventricular ejection fraction was tested by means of bidimensional echocardiography. After one month of treatment, the patients treated with propionyl-L-carnitine, compared to the control group, showed significant increases in the values of both tests, increases which became even more evident after 90 and 180 days. At the stated times the increases in the maximum exercise time were 16.4%, 22.9%, and 25.9%, respectively. The ventricular ejection fraction increased by 8.4%, 11.6% and 13.6%, respectively. On the basis of these results, having studied the particular mechanism of action of propionyl-L-carnitine the authors conclude that it represents a drug of undoubted therapeutic interest in patients with congestive heart failure, in whom it could be efficaciously administered along with a standard pharmacological therapy.

Orlando, G., Rusconi, C. L-carnitine in the treatment of chronic cardiac ischemia in elderly patients. Clin Trials J 23:338-44, 1986. Abstract: 30 patients experiencing symptoms such as palpitations, asthenia, and precordial pain were treated with 2gms carnitine three times daily for 2 months. Via the NYHA functional class evaluation, 4 of these patients improved significantly. In 30% of the patients EKG and echocardiographic evidence showed improvement. Most of the patients showed significant improvement in their symptoms.

Pastoris O, Dossena M, Foppa P, Catapano M, Arbustini E, Bellini O, Dal Bello B, Minzioni G, Ceriana P, Barzaghi N. Effect of L-carnitine on myocardial metabolism: results of a balanced, placebo-controlled, double-blind study in patients undergoing open heart surgery. Pharmacol Res 1998 Feb;37(2):115-122.

Abstract: The effects of L-carnitine on cardiac performance after open heart surgery were evaluated in a balanced, placebo-controlled, double-blind study in 38 patients. Preoperative haemodynamic status was good in all of them. Seventeen subjects underwent mitral valve replacement and 19 patients coronary artery bypass grafting. Five grams L-carnitine were given intravenously over 2 h, twice daily for 5 consecutive days; moreover, 10 g L-carnitine in 1500 ml cardioplegia were administered through the aortic root after aortic cross-clamping. Surgery was always planned on treatment day 3. The post-ischaemic functional recovery of the heart was assessed by clinical parameters, as well as by biochemical and ultrastructure evaluations on biopsy specimens. No differences were found between the control and the treatment group with respect to all clinical parameters of cardiac performance after cardiopulmonary bypass. At anaesthesia induction, serum carnitine was significantly increased in treated patients, but carnitine concentrations in the right atrial biopsy obtained just before aortic declamping were similar in the two groups. In patients with mitral valve replacement, L-carnitine therapy was associated with significantly higher concentrations of pyruvate, ATP and creatine phosphate in papillary muscle. Glycogen levels were also higher in the treated group, but the difference was not statistically significant. Myocardial ultrastructure on septal biopsies, obtained within 5 min from weaning from extracorporeal circulation, showed better preservation scores for all considered parameters (nucleus, sarcoplasmic reticulum, mitochondria and cellular oedema) in the treated subjects, although the difference reached statistical significance only for nuclei. When biochemical and ultrastructural data are considered, these findings suggest that L-carnitine improves myocardial metabolism. However, it cannot be concluded that L-carnitine provides an advantageous support therapy for well-compensated patients requiring cardiac surgery. In contrast, the positive effects of L-carnitine on cardiac recovery after bypass might become clinically relevant in the surgical setting for haemodynamically compromised patients, in which further investigations are required.

Pola, P., et al. Statistical evaluation of long term L-carnitine therapy in hyperlipoproteinemias. Drugs Exptl Clin Res 9:925-934, 1983.

Abstract: 39 patients aged 50-60yrs of age with Fredricksons type II, IV, or V hyperlipoproteinemia were studied. 1/3 of these patients were unresponsive to previous therapy with cholesterol lowering drugs. Patients were treated with 1gm per day and after 4 months serum cholesterol fell from 295 to 234 and HDL increased by 15%. TGs fell from 345 to 208 (40% reduction). In type IV patients and from 170 to 124 in type II patients. In 3 type V patients TG levels of 950 avg. fell rapidly to below 400. The L-carnitine eventually brought cholesterol levels down below 240 in 90% of the patients, and 66% of them occurred in 4 months.

Martina B, Zuber M, Weiss P, Burkart F, Ritz R. [Anti-arrhythmia treatment using L-carnitine in acute myocardial infarct]. Schweiz Med Wochenschr 1992 Sep 12;122(37):1352-1355. [Article in German]

Abstract: Carnitine, a quaternary amine (3-hydroxy-4-N-trimethylaminobutyric acid), plays an important physiologic role in fatty acid transport and metabolism as well as in energy production of the myocardial cell. L-carnitine in high doses has been postulated to have an antiarrhythmic effect and this has also been clinically proven. We studied 20 patients with acute myocardial infarction (AMI), 4-12 hours after onset of pain. The patients were randomized and treated double-blind with 5 g L-carnitine (n = 12) or placebo (n = 8) at hours 0, 12, 24, 36, and with 2 x 3 g on days 3 to 7 by intravenous infusion over 2 hours. The two groups were similar for age, sex, infarct site, maximum CPK and conventional antiarrhythmic therapy. 24-hour Holter-ECG was performed on days 1, 2 and 7 and showed no significant difference between the two groups with respect to incidence of ventricular premature beats (VPB) per hour. On the second day following AMI, however, only 4 of 12 carnitine-treated patients showed high-grade VPB (Lown IVa and IVb), in comparison with 7 of 8 patients in the placebo group. The difference is significant: p = 0.028 (Fisher's Exact Test). Carnitine was well tolerated and the efficacy demonstrated on the second day following AMI must be interpreted with caution.

Marz, Russell. Medical Nutrition From Marz. Second Edition. Portland, OR. 1997.

Passeri M, Cucinotta D, Bonati PA, Iannuccelli M, Parnetti L, Senin U. Acetyl-L-carnitine in the treatment of mildly demented elderly patients. Int J Clin Pharmacol Res 1990;10(1-2):75-79.

Abstract: It has been hypothesized that acetyl-L-carnitine has a cholinomimetic action. It is for this reason that it has been used in the therapy of Alzheimer's type senile dementia impairment. In the present controlled double-blind study the authors followed two randomized homogeneous groups of both sexes of 30 patients each, aged over 65 years and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results was carried-out using non-parametric methods (Friedman-Nemenyi two-way ANOVA). It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales, in the memory tests, in the attention barrage test and in the Verbal Fluency test. These satisfactory results confirm the therapeutic importance of acetyl-L-carnitine in the treatment of elderly patients with mental impairment, which could be related principally to acetylcholine defects.

Pettegrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging 1995 Jan-Feb;16(1):1-4.

Abstract: 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.

Pucciarelli G, Mastursi M, Latte S, Sacra C, Setaro A, Lizzadro A, Nolfe G. [The clinical and hemodynamic effects of propionyl-L-carnitine in the treatment of congestive heart failure]. Clin Ter 1992 Nov;141(11):379-384. [Article in Italian]

Abstract: In order to evaluate the clinical and hemodynamic effects of propionyl-L-carnitine (PLC) a randomized, double-blind study versus placebo was performed in 50 patients of both sexes, between 48 and 69 years of age, affected by mild-moderate congestive heart failure. All patients participating in said study were on digitalis and diuretic treatment. 25 of these belonged to the control group, while the other 25 were treated with an oral dose of 1 g twice daily of propionyl-L-carnitine. At the end of six months of treatment maximum exercise time on the treadmill increased 11.1% after 90 days and 16.4% after 180 in the group treated with PLC. From a hemodynamic standpoint, after 30, 90 and 180 days the ejection fraction increased by 7.3%, 10.7% and 12.1%. At the same time, moreover, the systemic vascular resistances were reduced by 14.9%, 20% and 20.6%. In the patients treated with placebo, however, the above-mentioned parameters showed no significant variation. Finally, no unexpected events or toxic effects were observed in any of the patients in either group. As a consequence of these results it is possible to affirm that propionyl-L-carnitine, due to its clinical and hemodynamic effects, represents a drug of notable therapeutic interest in patients with congestive heart failure, in whom it may be usefully combined with the usual pharmacological therapy.

Rai G, Wright G, Scott L, Beston B, Rest J, Exton-Smith AN. Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia. Curr Med Res Opin 1990;11(10):638-647.

Abstract: A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the acetyl-l-carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.

Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux R. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol 1992 Nov;49(11):1137-1141.

Abstract: Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer's disease. In a double-blind, parallel design, placebo-controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer's disease, tests of memory, attention, language, visuospatial, and constructional abilities were administered, and the level of acetyl levocarnitine was measured in the cerebrospinal fluid. Patients were then randomly assigned to receive acetyl levocarnitine hydrochloride (2.5 g/d for 3 months followed by 3 g/d for 3 months) or placebo. After 6 months, the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span (forward) and a trend toward less deterioration in a timed verbal fluency task. No differences were found in any other neuropsychological test results. A subgroup with the lowest baseline scores, receiving acetyl levocarnitine, had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo. These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug.

Singh RB, Niaz MA, Agarwal P, Beegum R, Rastogi SS, Sachan DS. A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected acute myocardial infarction. Postgrad Med J 1996 Jan;72(843):45-50.

Abstract: In a randomised, double-blind placebo-controlled trial, the effects of the administration of oral L-carnitine (2 g/day) for 28 days were compared in the management of 51 (carnitine group) and 50 (placebo group) patients with suspected acute myocardial infarction. At study entry, the extent of cardiac disease, cardiac enzymes and lipid peroxides were comparable between the groups, although both groups showed an increase in cardiac enzymes and lipid peroxides. At the end of the 28-day treatment period, the mean infarct size assessed by cardiac enzymes showed a significant reduction in the carnitine group compared to placebo. Electrocardiographic assessment of infarct size revealed that the QRS-score was significantly less in the carnitine group compared to placebo (7.4 +/- 1.2 vs 10.7 +/- 2.0), while serum aspartate transaminase and lipid peroxides showed significant reduction in the carnitine group. Lactate dehydrogenase measured on the sixth or seventh day following infarction showed a smaller rise in the carnitine group compared to placebo. Angina pectoris (17.6 vs 36.0%), New York Heart Association class III and IV heart failure plus left ventricular enlargement (23.4 vs 36.0%) and total arrhythmias (13.7 vs 28.0%) were significantly less in the carnitine group compared to placebo. Total cardiac events including cardiac deaths and nonfatal infarction were 15.6% in the carnitine group vs 26.0% in the placebo group. It is possible that L-carnitine supplementation in patients with suspected acute myocardial infarction may be protective against cardiac necrosis and complications during the first 28 days.

Spagnoli A, Lucca U, Menasce G, Bandera L, Cizza G, Forloni G, Tettamanti M, Frattura L, Tiraboschi P, Comelli M, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology 1991 Nov;41(11):1726-1732. Abstract: In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.

Tempesta E, Troncon R, Janiri L, Colusso L, Riscica P, Saraceni G, Gesmundo E, Calvani M, Benedetti N, Pola P. Role of acetyl-L-carnitine in the treatment of cognitive deficit in chronic alcoholism. Int J Clin Pharmacol Res 1990;10(1-2):101-107.

Abstract: Preliminary data are reported from a multicentred double-blind placebo-controlled study concerned with the effects of acetyl-L-carnitine (LAC) on some cognitive deficits of at least one month-abstinent alcoholics. Fifty-five patients, showing impaired performance in at least two out of six mnemonic, praxic and verbal tasks, were randomly assigned to either LAC 2 g/day or a placebo group. They were tested by means of a neuropsychological battery exploring the areas of memory, constructional praxia, deductive-logical functions and language. Testing time was on baseline (T0), after 45 (T45) and 90 (T90) days. On the Rey's 15 word memory test (long-term), the Wechsler memory scale (logical memory), and the Similarities WAIS subtest, the T90 difference between LAC and the placebo was significant in favour of the former treatment. On the copying drawing test (simple copy), the placebo group did not show any T0-T90 variation, while significant improvement in the LAC group was greater than in the placebo group. As LAC has proved to ameliorate the performance or to accelerate the recovery on tests representative of all cognitive areas explored, it is conceivable that the drug acts diffusely, either at the cholinergic transmission or at the neuronal metabolism level. It is concluded that acetyl-L-carnitine can be a useful and safe therapeutic agent in the subtle cognitive disturbances of chronic alcoholics.

Thal LJ, Carta A, Clarke WR, Ferris SH, Friedland RP, Petersen RC, Pettegrew JW, Pfeiffer E, Raskind MA, Sano M, Tuszynski MH, Woolson RF. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology 1996 Sep;47(3):705-711.

Abstract: A 1-year, double-blind, placebo-controlled, randomized, parallel-group study compared the efficacy and safety of acetyl-L-carnitine hydrochloride (ALCAR) with placebo in patients with probable Alzheimer's disease (AD). Subjects with mild to moderate probable AD, aged 50 or older, were treated with 3 g/day of ALCAR or placebo (1 g tid) for 12 months. Four hundred thirty-one patients entered the study, and 83% completed 1 year of treatment. The Alzheimer's Disease Assessment Scale cognitive component and the Clinical Dementia Rating Scale were the primary outcome measures. Overall, both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial. In a subanalysis by age that compared early-onset patients (aged 65 years or younger at study entry) with late-onset patients (older than 66 at study entry), we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints. In addition, early-onset patients tended to decline more rapidly than older patients in the placebo groups. Conversely, late-onset AD patients on ALCAR tended to progress more rapidly than similarly treated early-onset patients. The drug was very well tolerated during the trial. The study suggests that a subgroup of AD patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly. However, these preliminary findings are based on past hoc analyses. A prospective trial of ALCAR in younger patients is underway to test the hypothesis that young, rapidly progressing subjects will benefit from ALCAR treatment.

USDA: Composition of Foods. USDA Handbook #8. Washington DC, ARS, USDA, 1976-1986.

Vitali, G., et al. L-carnitine supplementation in human idiopathic asthenospermia: clinical results. Drugs Exptl Clin Res 21:157-159, 1995.

Abstract: 47 infertile males of at least 2 years duration who had failed to respond to previous therapy and who had at least 10 million sperm per ml were given 1 g three times daily L-carnitine for 3 months. 79% of the patients responded. Of those who responded, the mean sperm count increased from 88 million to 159 million per ml and the mean number of motile sperms increased from 27 to 54 million per ml.