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DuraBlast was designed to biochemically manipulate the natural production of energy via the body’s own Kreb’s Cycle, reduce lactic acid (the burn felt during intense training) and maximize antioxidant protection for fast recovery. Clinically, supplementation of the oxaloacetate precursors aspartate and asparagine as well as carnitine indicated an increase in the capacity of the muscles to utilize fatty acids as energy and spare glycogen with respect to muscle metabolism and exercise endurance. It was also documented that these vital nutrients support oxidative metabolic energy as well as delay fatigue during intense exercise. Am J Clin Nutr. 2004 Jan;79(1):40-6. Related Articles, Links Metabolic effects of caffeine in humans: lipid oxidation or futile cycling? Acheson KJ, Gremaud G, Meirim I, Montigon F, Krebs Y, Fay LB, Gay LJ, Schneiter P, Schindler C, Tappy L. Nestle Research Center, Lausanne, Switzerland. [email protected] Caffeine BACKGROUND: ingestion stimulates both lipolysis and energy expenditure. OBJECTIVES: Our objectives were to determine whether the lipolytic effect of caffeine is associated with increased lipid oxidation or futile cycling between triacylglycerol and free fatty acids (FFAs) and whether the effects of caffeine are mediated via the sympathetic nervous system. DESIGN: Respiratory exchange and [1-(13)C]palmitate were used to trace lipid oxidation and FFA turnover in 8 healthy, young men for 90 min before and 240 min after ingestion of placebo, caffeine (10 mg/kg), or caffeine during beta-adrenoceptor blockade. RESULTS: During fasting conditions, there were few differences in measured variables between the 3 tests. During steady state conditions (last hour of the test) after ingestion of caffeine, lipid turnover increased 2-fold (P < 0.005), and the mean (+/-SEM) thermic effect was 13.3 +/- 2.2% (P < 0.001), both of which were greater than after ingestion of placebo or caffeine during betaadrenoceptor blockade. After ingestion of caffeine, oxidative FFA disposal increased 44% (236 +/- 21 to 340 +/- 16 micro mol/min), whereas nonoxidative FFA disposal increased 2.3-fold (455 +/- 66 to 1054 +/- 242 micro mol/min; P < 0.01). In postabsorptive conditions, 34% of lipids were oxidized and 66% were recycled. Caffeine ingestion increased energy expenditure 13% and doubled the turnover of lipids, of which 24% were oxidized and 76% were recycled. betaAdrenoceptor blockade decreased, but did not inhibit, these variables. CONCLUSIONS: Many, but not all, of the effects of caffeine are mediated via the sympathetic nervous system. The effect of caffeine on lipid mobilization in resting conditions can be interpreted in 2 ways: lipid mobilization alone is insufficient to drive lipid oxidation, or large increments in lipid turnover result in small increments in lipid oxidation. J Nutr Sci Vitaminol (Tokyo). 2001 Apr;47(2):139-46. Related Articles, Links Caffeine as a lipolytic food component increases endurance performance in rats and athletes. Ryu S, Choi SK, Joung SS, Suh H, Cha YS, Lee S, Lim K. Institute of Elderly Health, Seoul, Korea. Caffeine is one of the famous ergogenic aids in the athletic field. Caffeine has been known to stimulate lipolysis that spares stored glycogen utilization during moderate intensity exercise. Therefore, we investigated the effects of caffeine ingestion on exercise performance in rats and athletes. Rats were administered the caffeine (6 mg/kg) 1 h prior to the exercise then were run on a treadmill at a speed of 20 m/min. They were decapitated at 0 min, 30 min, 60 min of exercise, and exhausted time point. Human subjects ingested the caffeine (5 mg/kg) 1 h prior to the exercise. They exercised on a cycle ergometer at 60% of their VO2max for 45 min, and then the exercise intensity was increased to 80% of their VO2max until exhaustion. Blood and breathing gas samples were collected and calculated every 10 min during exercise. Respiratory exchange ratio of the caffeine trial was significantly lower than that of the placebo trial in the athletes' study (p<0.05). Blood free fatty acid (FFA) levels in studies of both rats and athletes were increased by caffeine ingestion during exercise (p<0.05). Blood lactate levels were also increased during exercise in both rats and athletes (p<0.05). Increased FFA and glycerol concentrations reduced glycogen utilization during exercise compared with placebo group in rats. In addition, endurance time to exhaustion was significantly increased by the caffeine ingestion in both rats and athletes (p<0.05). These results suggest that the caffeine ingestion enhanced endurance performance resulting from spare stored glycogen with increasing lipolysis from adipose tissues and fat oxidation during exercise both in rats and in athletes. Am J Vet Res. 2003 Oct;64(10):1265-77. Related Articles, Links Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation in the liver of cats during weight gain and weight loss. Ibrahim WH, Bailey N, Sunvold GD, Bruckner GG. Department of Clinical Sciences/Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA. OBJECTIVE: To determine the effects of carnitine (Ca) or taurine (Ta) supplementation on prevention of lipid accumulation in the liver of cats. ANIMALS: 24 adult cats. PROCEDURE: Cats were fed a weight-gaining diet sufficient in n-6 polyunsaturated fatty acids (PUFAs), low in long-chain n-3 PUFAs (n-3 LPUFA), and containing corn gluten for 20 weeks. Cats gained at least 30% in body weight and were assigned to 4 weight-reduction diets (6 cats/diet) for 7 to 10 weeks (control diet, control plus Ca, control plus Ta, and control plus Ca and Ta). RESULTS: Hepatic lipids accumulated significantly during weight gain and weight loss but were not altered by Ca orTa after weight loss. Carnitine significantly increased n-3 and n-6 LPUFAs in hepatic triglycerides, decreased incorporation of 13C palmitate into very-low-density lipoprotein and hepatic triglycerides, and increased plasma ketone bodies. Carnitine also significantly increased weight loss but without altering the fat to lean body mass ratio. Taurine did not significantly affect any variables. Diets low in n-3 LPUFAs predisposed cats to hepatic lipidosis during weight gain, which was further exacerbated during weight loss. Mitochondrial numbers decreased during weight gain and weight loss but were not affected by treatment. Carnitine improved fatty acid oxidation and glucose utilization during weight loss without correcting hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: The primary mechanism leading to hepatic lipidosis in cats appears to be decreased fatty acid oxidation. Carnitine may improve fatty acid oxidation but will not ameliorate hepatic lipidosis in cats fed a diet low in n-3 fatty acids. Clin Pharmacokinet. 2003;42(11):941-67. Related Articles, Links Pharmacokinetics of L-carnitine. Evans AM, Fornasini G. Centre for Pharmaceutical Research, School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, Adelaide, South Australia, Australia. [email protected] L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. Exogenous L-carnitine is used clinically for the treatment of carnitine deficiency disorders and a range of other conditions.In humans, the endogenous carnitine pool, which comprises free Lcarnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. In addition, carrier- mediated transport ensures high tissue-to-plasma concentration ratios in tissues that depend critically on fatty acid oxidation. The absorption of L-carnitine after oral administration occurs partly via carrier-mediated transport and partly by passive diffusion. After oral doses of 1-6g, the absolute bioavailability is 5-18%. In contrast, the bioavailability of dietary L-carnitine may be as high as 75%. Therefore, pharmacological or supplemental doses of L-carnitine are absorbed less efficiently than the relatively smaller amounts present within a normal diet.LCarnitine and its short-chain esters do not bind to plasma proteins and, although blood cells contain L-carnitine, the rate of distribution between erythrocytes and plasma is extremely slow in whole blood. After intravenous administration, the initial distribution volume of L-carnitine is typically about 0.2-0.3 L/kg, which corresponds to extracellular fluid volume. There are at least three distinct pharmacokinetic compartments for L-carnitine, with the slowest equilibrating pool comprising skeletal and cardiac muscle.L-Carnitine is eliminated from the body mainly via urinary excretion. Under baseline conditions, the renal clearance of L-carnitine (1-3 mL/min) is substantially less than glomerular filtration rate (GFR), indicating extensive (98-99%) tubular reabsorption. The threshold concentration for tubular reabsorption (above which the fractional reabsorption begins to decline) is about 40-60 micromol/L, which is similar to the endogenous plasma L-carnitine level. Therefore, the renal clearance of L-carnitine increases after exogenous administration, approaching GFR after high intravenous doses.Patients with primary carnitine deficiency display alterations in the renal handling of L-carnitine and/or the transport of the compound into muscle tissue. Similarly, many forms of secondary carnitine deficiency, including some druginduced disorders, arise from impaired renal tubular reabsorption. Patients with end-stage renal disease undergoing dialysis can develop a secondary carnitine deficiency due to the unrestricted loss of L-carnitine through the dialyser, and Lcarnitine has been used for treatment of some patients during long-term haemodialysis. Recent studies have started to shed light on the pharmacokinetics of L-carnitine when used in haemodialysis patients. http://www.smart-drugs.net/Smart/info-ALC.htm Clin Immunol. 1999 Jul;92(1):103-10. Related Articles, Links Acetyl-L-carnitine administration increases insulin-like growth factor 1 levels in asymptomatic HIV-1-infected subjects: correlation with its suppressive effect on lymphocyte apoptosis and ceramide generation. Di Marzio L, Moretti S, D'Alo S, Zazzeroni F, Marcellini S, Smacchia C, Alesse E, Cifone MG, De Simone C. Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy. The aim of this study was to investigate the impact of long-term acetyl-Lcarnitine administration on CD4 and CD8 absolute counts, apoptosis, and insulinlike growth factor-1 (IGF-1) serum levels in HIV-1-infected subjects. The generation of cell-associated ceramide and HIV-1 viremia were also investigated. Eleven asymptomatic, HIV-1-infected subjects were treated daily with acetyl-Lcarnitine (3 g) for 5 months. Immunologic and virologic measures and safety were monitored at the start of the treatment and then on days 90 and 150. Altogether our findings suggest that acetyl-L-carnitine administration has a substantial impact on the main immunologic abnormality associated with HIV infection, the loss of CD4 cells, by reducing the rate of apoptotic lymphocyte death. The reduction of ceramide generation and the increase of the serum levels of IGF1, a major survival factor able to protect cells from apoptosis by different stimuli and conditions, could represent two important mechanisms underlying the observed anti-apoptotic effects of acetyl-L-carnitine. Copyright 1999 Academic Press. J Ren Nutr. 2003 Jan;13(1):2-14. Related Articles, Links History of L-carnitine: implications for renal disease. Matera M, Bellinghieri G, Costantino G, Santoro D, Calvani M, Savica V. Department of Pharmacology 2, Medical Faculty, University of Catania, Italy. L-carnitine (LC) plays an essential metabolic role that consists in transferring the long chain fatty acids (LCFAs) through the mitochondrial barrier, thus allowing their energy-yielding oxidation. Other functions of LC are protection of membrane structures, stabilizing a physiologic coenzyme-A (CoA)-sulfate hydrate/acetyl-CoA ratio, and reduction of lactate production. On the other hand, numerous observations have stressed the carnitine ability of influencing, in several ways, the control mechanisms of the vital cell cycle. Much evidence suggests that apoptosis activated by palmitate or stearate addition to cultured cells is correlated with de novo ceramide synthesis. Investigations in vitro strongly support that LC is able to inhibit the death planned, most likely by preventing sphingomyelin breakdown and consequent ceramide synthesis; this effect seems to be specific for acidic sphingomyelinase. The reduction of ceramide generation and the increase in the serum levels of insulin-like growth factor (IGF)-1, could represent 2 important mechanisms underlying the observed antiapoptotic effects of acetyl-LC. Primary carnitine deficiency is an uncommon inherited disorder, related to functional anomalies in a specific organic cation/carnitine transporter (hOCTN2). These conditions have been classified as either systemic or myopathic. Secondary forms also are recognized. These are present in patients with renal tubular disorders, in which excretion of carnitine may be excessive, and in patients on hemodialysis. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading, in some patients, to carnitine depletion with a relative increase in esterified forms. Many studies have shown that LC supplementation leads to improvements in several complications seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia, normalizing the reduced carnitine palmitoyl transferase activity in red cells. Copyright 2003 by the National Kidney Foundation, Inc. Infusionsther Klin Ernahr. 1986 Dec;13(6):268-76. Related Articles, Links [Effect of L-carnitine on post-stress metabolism in surgical patients] [Article in German] Heller W, Musil HE, Gaebel G, Hempel V, Krug W, Kohn HJ. The positive influence of L-carnitine administration on postaggression metabolism was investigated. Clinical examinations were executed on three groups of patients K1, K2, K3). Comparable surgical operations like stomach- and intestinal- resections were performed on these groups of patients. During the first three days after operation a nutritional diet (parenteral, standardized hypocaloric) with (K2: 2 g; K3: 4g) and without L-carnitine (K1) was given. The effects of Lcarnitine administration were evaluated by the following parameters: free fatty acids (FFS), triglycerides (TG), beta-hydroxybutyric acid (beta-OH-BS), acetacetate (ACAC), blood sugar (BZ), insulin (INS), lactate (LAK), pyruvate (PYR), total protein (GE), cholinesterase (CHE), urea production rate (PU), nitrogen of alpha-aminogroups (alpha-AN), nitrogen balance (NB), catabolic index (KI), BUN-Creatinine-quotient (B/K), total carnitine (GC), free carnitine (FC), acetyl carnitine (AC) and also the ratio between acetyl carnitine and free carnitine (AC/FC) in serum and urine. The results show no statistical significance. But they could lead to the following conclusions: Carnitine obviously reduces the insulin resistance. But it does not influence the post-operative perturbation of glucose-utilization. Carnitine reinforces the utilization of long chain fatty acids and thus improves the energy conversion. Carnitine leads to an earlier positive nitrogen balance. By giving 4 g of carnitine a day, already after three days a repletion of tissue deposits is possible, and a dose dependence for carnitine administration exists for the utilization of long chain fatty acids and the repletion of tissue deposits. J Nutr. 2000 Feb;130(2):152-7. Related Articles, Links Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise. Hongu N, Sachan DS. Department of Nutrition and Agricultural Experiment Station, The University of Tennessee, Knoxville 37996-1900, USA. The effect of a combination of caffeine, carnitine and choline with or without exercise on changes in body weight, fat pad mass, serum leptin concentration and metabolic indices was determined in 20 male, 7-wk-old Sprague-Dawley rats. They were given free access to a nonpurified diet without or with caffeine, carnitine and choline at concentrations of 0.1, 5 and 11.5 g/kg diet, respectively. In a 2x2 factorial design, one-half of each dietary group was exercised, and the other half was sedentary. Body weight and food intake of all rats were measured every day for 28 d. Rats were killed and blood and tissue samples were collected and analyzed for biochemical markers. Food intake of the groups was not different, but the body weight was significantly reduced by exercise in both dietary groups. Fat pad weights and total lipids of epididymal, inguinal and perirenal regions were significantly reduced by the supplements as well as by exercise. Regardless of exercise, supplements significantly lowered triglycerides in serum but increased levels in skeletal muscle. Serum leptin concentrations were equally lowered by supplements and exercise. Serum leptin was correlated with body weight (r = 0.55, P< or =0.01), fat pad weight (r = 0.82, P< or =0.001) and serum glucose (r = 0.51, P< or =0.05). We conclude that the indices of body fat loss due to dietary supplements were similar to those due to mild exercise, and there were no interactive effects of the two variables. 1: J Nutr Sci Vitaminol (Tokyo). 2001 Dec;47(6):378-84. Related Articles, Links Effects of carnitine coingested caffeine on carnitine metabolism and endurance capacity in athletes. Cha YS, Choi SK, Suh H, Lee SN, Cho D, Li K. Department of Food and Nutritional Science, Chonbuk National University, Chonju, Korea. The purpose of this study was to examine whether caffeine (CAF), carnitine (CAR), or CAF+CAR mixture administration affects exercise endurance time via carnitine metabolism. Water (CON), CAF, CAR, or CAF+CAR mixture was administered to five male rugby athletes participating in this study by a randomized double-blind fashion who were made to ride a cycle ergometer for exercise. The CAF effect on exercise endurance time was small, but the CAR trial significantly increased the exercise endurance time compared with CON trial; a further CAF+CAR mixture trial had greater effects on the exercise endurance time than those of a CON, CAF, or CAR trial. A CAR or CAF+CAR mixed trial increased urinary nonesterified carnitine (NEC) and total carnitine (TCAR), but no changes were observed in acid-soluble acylcarnitine (ASAC) and acidinsoluble acylcarnitine (AIAC) excretion. A CAR or CAF+CAR mixed trial resulted in higher levels of plasma NEC, ASAC, and TCAR fractions than the CON and CAF trials did on exhaustion time. Total cholesterol, triglyceride, and free fatty acid in blood were significantly increased at exhaustion time, but they were not affected in the CAF or the CAR trial. These results suggest that carnitine ingestion could promote fat oxidation, resulting in higher endurance performance in athletes, and especially these ergogenic effects of carnitine coingested with caffeine may be greater than those of carnitine alone. Alzheimer Dis Assoc Disord. 1995 Fall;9(3):128-31. Related Articles, Links Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides. Bruno G, Scaccianoce S, Bonamini M, Patacchioli FR, Cesarino F, Grassini P, Sorrentino E, Angelucci L, Lenzi GL. Dipartimento di Scienze Neurologiche, Universita di Roma La Sapienza, Italy. Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer disease (AD) therapy. ALCAR seems to exert a number of central nervous system (CNS)-related effects, even though a clear pharmacological action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal fluid (CSF) and plasma biological correlates of ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly higher than the ones at baseline, reflecting a good penetration through the blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and their metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic hormone remained unchanged, beta-endorphins significantly decreased after treatment; plasma cortisol levels matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamicpituitary-adrenocortical (HPA) axis hyperactivity. At present, no clear explanation can be proposed for the specific mechanism of this action. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9498-502. Epub 2002 Jun 11. Related Articles, Links Comment in: Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9096-7. C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Thupari JN, Landree LE, Ronnett GV, Kuhajda FP. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. C75, a known inhibitor of fatty acid synthase is postulated to cause significant weight loss through decreased hypothalamic neuropeptide Y (NPY) production. Peripherally, C75, an alpha-methylene-gamma-butyrolactone, reduces adipose tissue and fatty liver, despite high levels of malonyl-CoA. To investigate this paradox, we studied the effect of C75 on fatty acid oxidation and energy production in diet-induced obese (DIO) mice and cellular models. Whole-animal calorimetry showed that C75-treated DIO mice had a 50% greater weight loss, and a 32.9% increased production of energy because of fatty acid oxidation, compared with paired-fed controls. Etomoxir, an inhibitor of carnitine Opalmitoyltransferase-1 (CPT-1), reversed the increased energy expenditure in DIO mice by inhibiting fatty acid oxidation. C75 treatment of rodent adipocytes and hepatocytes and human breast cancer cells increased fatty acid oxidation and ATP levels by increasing CPT-1 activity, even in the presence of elevated concentrations of malonyl-CoA. Studies in human cancer cells showed that C75 competed with malonyl-CoA, as measured by CPT-1 activity assays. Thus, C75 acts both centrally to reduce food intake and peripherally to increase fatty acid oxidation, leading to rapid and profound weight loss, loss of adipose mass, and resolution of fatty liver. The pharmacological stimulation of CPT-1 activity is a novel finding. The dual action of the C75 class of compounds as fatty acid synthase inhibitors and CPT-1 agonists has therapeutic implications in the treatment of obesity and type II diabetes. Mol Psychiatry. 2000 Nov;5(6):616-32. Related Articles, Links Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Pettegrew JW, Levine J, McClure RJ. Department of Psychiatry, School of Medicine, University of Pittsburgh, PA 15213, USA. [email protected] Acetyl-L-carnitine (ALCAR) contains carnitine and acetyl moieties, both of which have neurobiological properties. Carnitine is important in the betaoxidation of fatty acids and the acetyl moiety can be used to maintain acetyl-CoA levels. Other reported neurobiological effects of ALCAR include modulation of: (1) brain energy and phospholipid metabolism; (2) cellular macromolecules, including neurotrophic factors and neurohormones; (3) synaptic morphology; and (4) synaptic transmission of multiple neurotransmitters. Potential molecular mechanisms of ALCAR activity include: (1) acetylation of -NH2 and -OH functional groups in amino acids and N terminal amino acids in peptides and proteins resulting in modification of their structure, dynamics, function and turnover; and (2) acting as a molecular chaperone to larger molecules resulting in a change in the structure, molecular dynamics, and function of the larger molecule. ALCAR is reported in double-blind controlled studies to have beneficial effects in major depressive disorders and Alzheimer's disease (AD), both of which are highly prevalent in the geriatric population. Altern Med Rev. 1999 Dec;4(6):438-41. Related Articles, Links Acetyl-L-carnitine. [No authors listed] Acetyl-L-carnitine (ALC) is an ester of the trimethylated amino acid, L-carnitine, and is synthesized in the human brain, liver, and kidney by the enzyme ALCtransferase. Acetyl-L-carnitine facilitates the uptake of acetyl CoA into the mitochondria during fatty acid oxidation, enhances acetylcholine production, and stimulates protein and membrane phospholipid synthesis. ALC, similar in structure to acetylcholine, also exerts a cholinomimetic effect. Studies have shown that ALC may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, diabetic neuropathies, ischemia and reperfusion of the brain, and cognitive impairment of alcoholism. Metabolic changes induced by maximal exercise in human subjects following L-carnitine administration. Siliprandi N, Di Lisa F, Pieralisi G, Ripari P, Maccari F, Menabo R, Giamberardino MA, Vecchiet L. Istituto di Fisiopatologia Medica, Universita di Chieti, Italy. In double-blind cross-over experiments, ten moderately trained male subjects were submitted to two bouts of maximal cycle ergometer exercise separated by a 3 day interval. Each subject was randomly given either L-carnitine (2 g) or placebo orally 1 h before the beginning of each exercise session. At rest Lcarnitine supplementation resulted in an increase of plasma-free carnitine without a change in acid-soluble carnitine esters. Treatment with L-carnitine induced a significant post-exercise decrease of plasma lactate and pyruvate and a concurrent increase of acetylcarnitine. The determination of the individual carnitine esters in urine collected for 24 h after the placebo exercise trial revealed a decrease of acetyl carnitine and a parallel increase of a C4 carnitine ester, probably isobutyrylcarnitine. Conversely, acetylcarnitine was strongly increased and C4 compounds were almost suppressed in the L-carnitine loading trial. These results suggest that L-carnitine administration prior to high-intensity exercise stimulates pyruvate dehydrogenase activity, thus diverting pyruvate from lactate to acetylcarnitine formation. A knockout win for the supplements Supplementation with aspartate and asparagine produced some striking results. For example, after the week of supplementation, glycogen concentrations in the soleus muscles of the rest/amino acid rats were 59% higher than in those of the resting controls. Time to exhaustion while swimming at above lactate threshold intensity was also dramatically higher in the exhaustion/amino acid rats (68 minutes) than in the corresponding controls (41 minutes). Very interestingly, blood lactate levels at the end of the exhaustive exercise were significantly lower in the supplemented group, averaging just 8.6 mM per litre, compared with 11.3 in the non-supplemented rats (a 24% difference). In addition, the rate of glycogen degradation for the supplemented rats was 77% lower in the gastrocnemius (calf) muscles, 30% lower in the extensor digitorum longus muscles (running from the fibula to the toes) and a whopping 85% lower in the liver than for the controls. Overall, it was a knockout victory for aspartate and asparagine supplementation, with the amino acids producing longer endurance times, inducing more temperate blood lactate levels and promoting better conservation of precious glycogen. How did the two little amino acids actually produce such varied and impressively positive effects? Apparently, there exists within muscle cells a mechanism known as ‘the malate-aspartate shuttle’, whose purpose is to transport hydrogen ions from the cytoplasm of muscle cells into their mitochondria, where the hydrogens become involved in the aerobic production of a high-energy compound called ATP. Increased concentrations of aspartate and asparagine seem to enhance the activity of this shuttle. This could account for the improved performance associated with aspartate-asparagine supplementation, since the hydrogen ions – if left in the cytoplasm – could lower intracellular pH, interfere with the muscle-contraction process and heighten fatigue. As already mentioned, protein may play an important role as an energy substrate during sustained exercise. However, to provide energy the key amino acids which furnish energy during exercise (the branched-chain amino acids, aspartate, asparagines and glutamine) must first be converted into a compound that can readily enter the biochemical pathways associated with energy release. This process involves removing the nitrogen from the amino acids and passing it to other compounds via a process called transamination; once an amino acid has been transaminated, it exists as a ‘carbon skeleton’, which can be used for energy production. The importance of this process is demonstrated by the fact that muscles involved in heavy training adapt by increasing their concentrations of the enzymes which allow transamination to occur. As it turns out, aspartate and asparagines are transaminated readily inside muscle cells. This leads to the formation of oxaloacetic acid, which happens to be a key component of the ‘Krebs cycle’, a complex series of chemical reactions that ultimately generate huge quantities of usable energy (ATP) for muscle cells. Carbohydrate is also utilised to form Krebs cycle components, and the ability of the aspartate and asparagine derivative, oxaloacetic acid, to substitute for carbs in the Krebs cycle may well explain the lower glycogen degradation rates (and corresponding increased resistance to fatigue) in the amino acidsupplemented rats. To put it another way, less carbohydrate may have been needed to furnish the energy required for exercise in the supplemented rats, since aspartate and asparagine were being so helpful. This would also explain the higher lactate levels observed in the placebo rats: high rates of carbohydrate breakdown tend to produce high lactate concentrations, but the metabolism of aspartate and asparagine does not produce any lactate at all. The results of the Brazilian study are supported by a separate study which also examined the effects of aspartate and asparagine supplementation on muscle metabolism and exercise endurance(12). In this investigation, aspartate and asparagines increased the ability of muscles to spare glycogen – and heightened the capacity of muscles to break down fats for energy. In addition, time to exhaustion was about 40% longer with supplementation. Other research has indicated that even a single dose of aspartate can enhance fat oxidation during prolonged exercise(14). So should you give aspartate-asparagine supplementation a try? There has been limited human research in this field, but the results of the Brazilian study are certainly impressive. No side effects are associated with aspartate-asparagine supplementation, providing the supplements are obtained from a reputable supplier. Athletes who are interested in giving this potential ergogenic aid a go might like to start off with a short-term course of supplements, perhaps for two weeks, just to gain a feeling for how the amino acids influence their ability to perform prolonged workouts. Owen Anderson References 1. Journal of Clinical Investigation, vol 50, pp2703-2714, 1971 2. Journal of Applied Physiology, vol 93(2), pp499-504, 2002 3. Unpublished Master’s Thesis, Paulista State University, Institute of Biology, Rio Claro, Sao Paulo, 1998 4. Acta Physiologica Scandinavica, vol 133, pp115-121, 1988 5. Running Research News, vol 7(3), pp1, 5-7, 1991 6. Am J Physiol Endocrinol Metab, vol 281(2), ppE365-E374, 2001 7. Canadian Journal of Applied Physiology, vol 27(6), pp646-663, 2002 8. Exercise Physiology: Theory and Application to Fitness and Performance Boston: McGraw-Hill, 2001 9. Medicine and Science in Sports and Exercise, vol 19, ppS179-S190, 1987 10. Journal of Applied Physiology, vol 48, pp624-629, 1980 11. Biochemistry of Exercise IX, International Biochemistry of Exercise Conference. Champaign, Illinois: Human Kinetics Publishers, pp261-275, 1996 12. Physiology and Behavior, vol.57, pp367-371, 1995 13. International Journal of Sport Nutrition and Exercise Metabolism, vol 13, pp65-75, 2003 14. Physiology and Behavior, vol 54(1), pp7-12, 1993 Aspartic acid is a nonessential amino acid, which means that it is manufactured from other amino acids in the liver; it does not have to be obtained directly through the diet. Aspartic acid is very important in the urea cycle for the proper elimination of waste products from dietary protein. Poor control of the urea cycle may be related to symptoms such as chronic headache, fatigue, irritability, lack of concentration, mental confusion, and intolerances to various foods, particularly high protein foods. Deficiencies of a nonessential amino acid will not occur if a well-balanced diet is consumed because the intake of proper foods will allow the body to produce exactly the amount of amino acid required to function optimally. Aspartic acid has been used as mineral salts such as magnesium aspartate or potassium aspartate to help improve energy production in exercising muscles. Method of Action Aspartate and glutamate participate within the neurotransmitter family of substances. This family also includes acetylcholine, noradrenaline, and gamma-aminobutyric acid (GABA). Glutamate is one of the most important excitatory transmitters in the central nervous system in lower animals and may also be important in humans. Aspartate has been considered to be a neurotransmitter, whereas GABA and glycine are thought to be major inhibitory transmitters. Excitatory transmitters such as aspartate lead to depolarization of the nerves; on the other hand, inhibitory transmitters cause hyperpolarization, apparently by increasing the permeability within the nerve of potassium and chloride. Glutamate and aspartate are also very important in the tricarboxylic acid cycle (Kreb's cycle), from which most of the energy is produced by metabolism. Their reaction in this pathway is by what is called the malate-aspartate shuttle for the transportation of energy into the mitochondria. Recent studies in trained athletes indicate some advantage of using magnesium or potassium aspartate as mineral sources for improving aerobic competency during exercise. Minerals form a unique chelate with aspartic acid to form aspartates. Potassium and magnesium forms of the aspartates appear to be agents which enhance muscular work and aerobic competency. Doses of these mineral salts range between 500 and 2,000 mg per day. Thoroughly tested over several years in some of the most extreme athletic endurance contests, ANTI-FATIGUE CAPS has proven itself to be a valuable ally for endurance athletes, helping to remove excess fatigue-causing, performance-robbing ammonia. During endurance events, especially ultra marathons, your body produces ammonia, an unavoidable breakdown product of protein metabolism. Ammonia interferes with glycogen production, disrupting optimal energy output. The higher your blood ammonia level, the less available glycogen, and the poorer your performance will be. ANTI-FATIGUE CAPS is a one-of-a-kind product combining three wellknown ammonia-scavenging nutrients, a potent arsenal for the removal of accumulated performance-robbing ammonia. Additionally, you'll get more consistent energy from the conversion and increased production of oxaloacetate (a key substrate), and support in the prevention of muscle tissue catabolism from effective, nonammonia producing glutamine replenishment. Lastly, because the aspartate component is chelated to magnesium and potassium, you also receive additional support for the prevention of cramping. ANTI-FATIGUE CAPS has been the "secret weapon" of many endurance athletes; it's time to make it yours! Asparagine General Information Asparagine help prevent nervous system from becoming overexcited, or overlyrelaxed. It is a nonessential amino acid manufactured from other amino acids in the liver. Asparagine is a vital component in the metabolism of toxic ammonia in the body, and having the proper levels of Asparagine, stimulates the kidneys and liver so they can perform their functions. This amino acid is found mainly in meats. - - - - - - - - - - - - Back to Top - - - - - - - - - - - Asparagine Uses & Scientific Evidence For Asparagine supplements are most often taken when illness effects the proper functioning metabolism and waste elimination functions. When those functions do not operate properly, the result is a buildup of nitrogen-containing toxic metabolites which can lead to confusion, headaches, depression, irritability, and in extreme cases, psychosis. L-asparaginase is an enzyme that helps convert Asparagine to aspartic acid. This is important because tumor cells need Asparagine to thrive and grow. Once the L-Asparaginase converts the Asparagine to aspartic acid though, the tumor cells will die. Healthy cells are not affected in this way. - - - - - - - - - - - - Back to Top - - - - - - - - - - - Asparagine Dosage Information Amino acid supplements prefaced by the letter L, such as L-Asparagine, are more similar to the amino acids in the body than those that start with the letter D, with the exception of D-L phenylalanine, which treats chronic pain. Asparagine supplementation is not necessary unless illness has affected the metabolism and waste elimination function. If you need Asparagine supplements, it is advised that you do so under the care of your physician. - - - - - - - - - - - - Back to Top - - - - - - - - - - - - Asparagine Safety & Interaction Information Having low levels of Asparagine can be the result of an inadequate diet which can end up affecting waste elimination. There are no known side effects associated with long term use of Asparagine. Ann Pharmacother. 1992 Jul-Aug;26(7-8):935-7. Related Articles, Links Comment in: Ann Pharmacother. 1994 Jul-Aug;28(7-8):973. N,N dimethylglycine and L-carnitine as performance enhancers in athletes. Tonda ME, Hart LL. School of Pharmacy, University of California, San Francisco 94143. Publication Types: Clinical Trial Randomized Controlled Trial Review Review, Tutorial PMID: 1380344 [PubMed - indexed for MEDLINE] J Sports Sci. 1999 May;17(5):387-95. Related Articles, Links Muscular soreness following prolonged intermittent high-intensity shuttle running. Thompson D, Nicholas CW, Williams C. Department of Physical Education, Sports Science and Recreation Management, Loughborough University, UK. The aim of this study was to examine the impact of prolonged intermittent highintensity shuttle running on soreness and markers of muscle damage. Sixteen males took part in the study, half of whom were assigned to a running group and half to a resting control group. The exercise protocol involved 90 min of intermittent shuttle running and walking (Loughborough Intermittent Shuttle Test: LIST), reflecting the activity pattern found in multiple-sprint sports such as soccer. Immediately after exercise, there was a significant increase (P < 0.05) in serum activities of creatine kinase and aspartate aminotransferase, and values remained above baseline for 48 h (P < 0.05). Median peak activities of creatine kinase and aspartate aminotransferase occurred 24 h post-exercise and were 774 and 43 U x l(-1), respectively. The intensity of general muscle soreness, and in the specific muscles investigated, was greater than baseline for 72 h after the shuttle test (P < 0.05), peaking 24-48 h post-exercise (P < 0.05). Muscle soreness was not correlated with either creatine kinase or aspartate aminotransferase activity. Soreness was most frequently reported in the hamstrings. Neither soreness nor serum enzyme activity changed in the controls over the 4 day observation period. It appears that unaccustomed performance of prolonged intermittent shuttle running produces a significant increase in both soreness and markers of muscle damage. Biochim Biophys Acta. 1990 Apr 23;1034(1):17-21. Related Articles, Links Physiol Behav. 1995 Feb;57(2):367-71. Related Articles, Links Effect of aspartate, asparagine, and carnitine supplementation in the diet on metabolism of skeletal muscle during a moderate exercise. Lancha AH Jr, Recco MB, Abdalla DS, Curi R. Physical Education School, Biodynamic Department, Sao Paulo University, Brasil. The present study examined the effect of diet supplementation of oxaloacetate precursors (aspartate and asparagine) and carnitine on muscle metabolism and exercise endurance. The results suggest that the diet supplementation increased the capacity of the muscle to utilize FFA and spare glycogen. Time to exhaustion was about 40% longer in the experimental group compared to the control, which received commercial diet only. These findings suggest that oxaloacetate may be important to determine the time to exhaustion during a prolonged and moderate exercise. Drugs Exp Clin Res. 1999;25(4):167-71. Related Articles, Links Plasma and urine carnitine concentrations in well-trained athletes at rest and after exercise. Influence of L-carnitine intake. Nuesch R, Rossetto M, Martina B. Department of Internal Medicine, University Hospital, Basel, Switzerland. L-carnitine is essential to cellular energy production mainly because of its acyland acetyl-carrier properties. Athletes commonly take L-carnitine, which is thought to improve exercise performance. There are no reports on carnitine plasma concentrations and carnitine excretion in short-duration maximal exercise in well-trained athletes taking this substance. We measured plasma and urine carnitine concentrations before and 10 min after maximal treadmill ergometry in nine well-trained sportsmen with and without oral supplementation with 1 g Lcarnitine. In athletes without L-carnitine intake, plasma free carnitine concentration decreased significantly from 45.2 +/- 5.3 to 41.6 +/- 5.0 mumol/l (mean +/- SD, p < 0.001) 10 min after exercise compared with baseline. In athletes with oral L-carnitine supplementation, plasma free carnitine concentration at baseline was 71.3 +/- 10.2 mumol/l and did not change after maximal exercise (71.8 mumol/l +/- 10.7 mumol/l). The elevated plasma concentration of free carnitine without decrease after maximal exercise in welltrained athletes taking L-carnitine could be important in view of the newly postulated direct vascular effects of L-carnitine in improving skeletal muscle performance. Urology. 2004 Apr;63(4):641-6. Related Articles, Links Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Andrological Operative Unit, Headquarters of Societa Italiana di Studi di Medicina della Riproduzione, Bologna, Italy. OBJECTIVES: To To compare testosterone undecanoate versus propionyl-Lcarnitine plus acetyl-L-carnitine and placebo in the treatment of male aging symptoms. METHODS: A total of 120 patients were randomized into three groups. The mean patient age was 66 years (range 60 to 74). Group 1 was given testosterone undecanoate 160 mg/day, the second group was given propionyl-Lcarnitine 2 g/day plus acetyl-L-carnitine 2 g/day. The third group was given a placebo (starch). Drugs and placebo were given for 6 months. The assessed variables were total prostate-specific antigen, prostate volume, peak systolic velocity, end-diastolic velocity, resistive index of cavernosal penile arteries, nocturnal penile tumescence, total and free testosterone, prolactin, luteinizing hormone, International Index of Erectile Function score, Depression Melancholia Scale score, fatigue scale score, and incidence of side effects. The assessment was performed at intervals before, during, and after therapy. RESULTS: Testosterone and carnitines significantly improved the peak systolic velocity, end-diastolic velocity, resistive index, nocturnal penile tumescence, International Index of Erectile Function score, Depression Melancholia Scale score, and fatigue scale score. Carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and International Index of Erectile Function score. Testosterone significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone; carnitines did not. No drug significantly modified prostate-specific antigen or prolactin. Carnitines and testosterone proved effective for as long as they were administered, with suspension provoking a reversal to baseline values. Only the group 1 prostate volume proved significantly greater than baseline 6 months after testosterone suspension. Placebo administration proved ineffective. Negligible side effects emerged. CONCLUSIONS: Testosterone and, especially, carnitines proved to be active drugs for the therapy of symptoms associated with male aging. Psychosom Med. 2004 Mar-Apr;66(2):276-82. Related Articles, Links Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Vermeulen RC, Scholte HR. Research Center Amsterdam, Amsterdam, Netherlands. [email protected] OBJECTIVES: We compared the effects of acetylcarnitine, propionylcarnitine and both compounds on the symptoms of chronic fatigue syndrome (CFS). METHODS: In an open, randomized fashion we compared 2 g/d acetyl-Lcarnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 CFS patients during 24 weeks. Effects were rated by clinical global impression of change. Secondary endpoints were the Multidimensional Fatigue Inventory, McGill Pain Questionnaire, and the Stroop attention concentration test. Scores were assessed 8 weeks before treatment; at randomization; after 8, 16, and 24 weeks of treatment; and 2 weeks later. RESULTS: Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels correlated with clinical improvement. CONCLUSIONS: Acetylcarnitine and propionylcarnitine showed beneficial effect on fatigue and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue. J Neurol Sci. 2004 Mar 15;218(1-2):103-8. Related Articles, Links Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C. Department of Neurological Sciences, University of Rome "La Sapienza", viale dell' Universita 30, Rome 00185, Italy. Treatment with acetyl L-carnitine (ALCAR) has been shown to improve fatigue in patients with chronic fatigue syndrome, but there have been no trials on the effect of ALCAR for treating fatigue in multiple sclerosis (MS). To compare the efficacy of ALCAR with that of amantadine, one of the drugs most widely used to treat MS-related fatigue, 36 MS patients presenting fatigue were enrolled in a randomised, double-blind, crossover study. Patients were treated for 3 months with either amantadine (100 mg twice daily) or ALCAR (1 g twice daily). After a 3-month washout period, they crossed over to the alternative treatment for 3 months. Patients were rated at baseline and every 3 months according to the Fatigue Severity Scale (FSS), the primary endpoint of the study. Secondary outcome variables were: Fatigue Impact Scale (FIS), Beck Depression Inventory (BDI) and Social Experience Checklist (SEC). Six patients withdrew from the study because of adverse reactions (five on amantadine and one on ALCAR). Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale (p = 0.039). There were no significant effects for any of the secondary outcome variables. The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue. Med Sci Sports Exerc. 2001 Sep;33(9):1415-22. Related Articles, Links Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease. Barker GA, Green S, Askew CD, Green AA, Walker PJ. School of Human Movement Studies, Queensland University of Technology, Brisbane, Australia. BACKGROUND: Supplementation with propionyl-L-carnitine (PLC) may be of use in improving the exercise capacity of people with peripheral arterial disease. METHODS: After a 2-wk exercise familiarization phase, seven subjects displaying intermittent claudication were studied over a 12-wk period consisting of three 4-wk phases, baseline (B), supplementation (S), and placebo (P). PLC was supplemented at 2 g x d(-1), and subjects were blinded to the order of supplementation. Unilateral calf strength and endurance were assessed weekly. Walking performance was assessed at the end of each phase using an incremental protocol, during which respiratory gases were collected. RESULTS: Although there was not a significant increase in maximal walking time ( approximately 14%) in the whole group, walking time improved to a greater extent than the individual baseline coefficient of variation in four of the seven subjects. The changes in walking performance were correlated with changes in the respiratory exchange ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end of S. Changes in calf strength from B to S were modestly related to changes in walking performance (r = 0.56). No improvements in calf endurance were detected throughout the study. CONCLUSIONS: These preliminary data suggest that, in addition to walking performance, muscle strength can be increased in PAD patients after 4 wk of supplementation with propionyl-Lcarnitine. Am J Med. 2001 Jun 1;110(8):616-22. Related Articles, Links Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Hiatt WR, Regensteiner JG, Creager MA, Hirsch AT, Cooke JP, Olin JW, Gorbunov GN, Isner J, Lukjanov YV, Tsitsiashvili MS, Zabelskaya TF, Amato A. Department of Medicine, Section of Vascular Medicine, Divisions of Geriatrics and Cardiology, University of Colorado Health Sciences Center, Denver 80203, USA. PURPOSE: We tested the hypothesis that propionyl-L-carnitine would improve peak walking time in patients with claudication. Secondary aims of the study were to evaluate the effects of propionyl-L-carnitine on claudication onset time, functional status, and safety. SUBJECTS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 155 patients with disabling claudication from the United States (n = 72) or Russia (n = 83) received either placebo or propionyl-L-carnitine (2g/day orally) for 6 months. Subjects were evaluated at baseline and 3 and 6 months after randomization with a graded treadmill protocol at a constant speed of 2 miles per hour, beginning at 0% grade, with increments in the grade of 2% every 2 minutes until maximal symptoms of claudication forced cessation of exercise. Questionnaires were used to determine changes in functional status. RESULTS: At baseline, peak walking time was 331 +/- 171 seconds in the placebo group and 331 +/- 187 seconds in the propionyl-Lcarnitine group. After 6 months of treatment, subjects randomly assigned to propionyl-L-carnitine increased their peak walking time by 162 +/- 222 seconds (a 54% increase) as compared with an improvement of 75 +/- 191 seconds (a 25% increase) for those on placebo (P <0.001). Similar improvements were observed for claudication onset time. Propionyl-L-carnitine treatment significantly improved walking distance and walking speed (by the Walking Impairment Questionnaire), and enhanced physical role functioning, reduced bodily pain, and resulted in a better health transition score (by the Medical Outcome Study SF-36 Questionnaire). The incidence of adverse events and study discontinuations were similar in the two treatment groups. CONCLUSIONS: Propionyl-L-carnitine safely improved treadmill exercise performance and enhanced functional status in patients with claudication. Cardiovasc Drugs Ther. 1998 Jul;12(3):291-9. Related Articles, Links Acute and chronic effects of propionyl-L-carnitine on the hemodynamics, exercise capacity, and hormones in patients with congestive heart failure. Anand I, Chandrashekhan Y, De Giuli F, Pasini E, Mazzoletti A, Confortini R, Ferrari R. VA Medical Center, Minneapolis, Minnesota, USA. Carnitine is an important cofactor in the intermediary metabolism of the heart, and carnitine deficiency is associated with congestive heart failure. We therefore studied the effects of acute (IV bolus, 30 mg/kg body weight) and chronic administration (1.5 mg/d for 1 month) of propionyl-L-carnitine on hemodynamics, hormone levels, ventricular function, exercise capacity, and peak oxygen consumption in 30 patients with chronic congestive heart failure (NYHA II-III, mean EF 29.5 +/- 7%) in a phase II, parallel, single-blind, randomized, and placebo-controlled study. Acute administration of propionyl-L-carnitine caused a significant reduction in pulmonary artery and pulmonary wedge pressures at both day 1 (P < 0.001) and day 30 (P < 0.05) of the study but no other hemodynamics changes. Hormone levels did not change following acute administration of the drug. Chronic administration of propionyl-L-carnitine increased peak oxygen consumption by 45% (from 16.0 +/- 3 to 23.5 +/- 2 mL/kg/min, P +/- 0.001), exercise time by 21% (from 8.1 +/- 0.5 to 9.8 +/- 0.4 minutes, P < 0.01), and peak exercise heart rate by 12% (P < 0.01). These changes were concomitant with a reduction of pulmonary artery pressure. In the treated group, there was a slight, but significant (P < 0.01), reduction in left ventricular dimensions. Hemodynamics and hormones measured after 1 month of oral therapy remained unchanged, except for a fall in pulmonary artery pressures, with a nonsignificant trend towards a fall in filling pressures and plasma norepinephrine. The chronic changes in the propionyl-L-carnitine group were seen at 15 days of treatment, and no further changes in these parameters were seen at 1 month. We conclude that propionyl-L-carnitine increases exercise capacity and reduces ventricular size in patients with congestive heart failure. The drug has no significant effects on hemodynamics or neurohormone levels. The use of a single-blind design reduces the impact of the positive finding on exercise capacity. Muscle Nerve. 1997 Sep;20(9):1115-20. Related Articles, Links Changes in skeletal muscle histology and metabolism in patients undergoing exercise deconditioning: effect of propionyl-L-carnitine. Brevetti G, Fanin M, De Amicis V, Carrozzo R, Di Lello F, Martone VD, Angelini C. Department of Medicine, University Federico II of Naples, Italy. To define the skeletal muscle abnormalities in patients undergoing exercise deconditioning and evaluate the metabolic effect of propionyl-L-carnitine (PLC), muscle biopsies were obtained from 28 patients with effort angina and 31 control subjects. Coronary artery disease patients received either placebo (n = 12), PLC (1.5 g i.v. followed by infusion of 1 mg/kg/min for 30 min, n = 10), or L-carnitine (1 g i.v. followed by infusion of 0.65 mg/kg/min for 30 min, n = 6) for 2 days. Exercise deconditioned patients treated with placebo showed normal muscle content of total carnitine and glycogen, and decrease in percentage of type 1 fibers (P < 0.01) and in the activity of citrate synthase (P < 0.05), succinate dehydrogenase (P < 0.05), and cytochrome oxidase (P < 0.05), as compared to controls. Both PLC and L-carnitine did not modify muscle fiber composition or enzyme activities, but significantly increased muscle levels of total carnitine by 42% and 31%, respectively (P < 0.05). Moreover, PLC significantly increased glycogen muscle content (P < 0.01), while the equimolar dose of L-carnitine did not. This effect, probably due to the anaplerotic activity of the propionic group of PLC, suggests that this drug may be effective in improving energy metabolism of muscles with impaired oxidative capacity. Am J Physiol. 1994 Aug;267(2 Pt 2):H455-61. Related Articles, Links Contrasting effects of propionate and propionyl-L-carnitine on energy-linked processes in ischemic hearts. Di Lisa F, Menabo R, Barbato R, Siliprandi N. Dipartimento di Chimica Biologica, Universita di Padua, Italy. Propionyl-L-carnitine, unlike L-carnitine, is known to improve myocardial function and metabolism altered during the course of ischemia-reperfusion. In this study, the effect of propionyl-L-carnitine has been compared with that of propionate and carnitine on the performance of rat hearts perfused with a glucosecontaining medium either under normoxia, ischemia, or postischemic reperfusion. In the postischemic phase, contractile parameters were partially restored both in the control and in the propionate plus carnitine-treated hearts, were markedly impaired by propionate, and were fully recovered by propionyl-L-carnitine. In addition, propionyl-L-carnitine, but not propionate, reduced the functional decay of mitochondria prepared from the ischemic hearts. Even in normoxic conditions propionate, unlike propionyl-L-carnitine, caused a drastic reduction of free CoA and L-carnitine. The concomitant increase in lactate production and decrease in ATP content might be explained by the inhibition of pyruvate dehydrogenase caused by the accumulation of propionyl-CoA. Indeed, when pyruvate was the only oxidizable substrate, propionate induced a gradual decrease in developed pressure, which was largely prevented by L-carnitine. The protective effect of propionyl-L-carnitine may be a consequence of the anaplerotic utilization of propionate in the presence of an optimal amount of ATP and free L-carnitine. Int J Sport Nutr Exerc Metab. 2003 Mar;13(1):65-75. Related Articles, Links Effect of aspartate and asparagine supplementation on fatigue determinants in intense exercise. Marquezi ML, Roschel HA, dos Santa Costa A, Sawada LA, Lancha AH Jr. Laboratory of Experimental Nutrition and Metabolism Applied to Physical Exercise in the Physical Education and Sport School at Sao Paulo University, Brazil CEP 05508-900, Sao Paulo, Brazil. PURPOSE: This study evaluated the effect of aspartate (ASP) and asparagine (ASG) supplementation on fatigue determinants in Wistar rats exercised to exhaustion by swimming. METHODS: The animals were tested for anaerobic threshold (AT) determination and then supplemented with 350 mM ASP + 400 mM ASG x day(-1) (AA group, n = 16) or 2 ml x day(-1) of distillated water (PLC group, n = 16) for 7 days. On the 7th day of supplementation, the animals were divided into 4 new groups and killed at rest (RAA, n = 8; RPLC, n = 8), or immediately after the swimming exercise to exhaustion (EAA, n = 8; EPLC, n = 8). R: No significant differences were observed between amino acids and placebo rest groups for muscle and liver glycogen, blood glucose, lactate, alanine, and glutamine concentrations. However, in the exhaustion groups, the EAA group showed higher exercise time (68.37 +/- 25.42 x 41.12 +/- 13.82 min, p <.05) and lower blood lactate concentration (8.57 +/- 1.92 x 11.28 +/- 2.61 mmol x L(-1), p <.05) than the EPLC group. Moreover, the ASP+ASG supplementation decreased the rate of glycogen degradation of gastrocnemius (1.00 +/- 0.51 x 3.43 +/- 0.99 microg x 100 mg of tissue sample(-1) x min(-1), extensor digitorius longus (5.70 +/- 2.35 x 8.11 +/- 3.97 microg. 100 mg of tissue sample(-1) x min(-1) and liver (0.51 +/- 0.34 x 3.37 +/- 2.31 microg x 100 mg of tissue sample(-1) x min(-1) for EAA. Conclusion: These results suggest that ASP+ASG supplementation may increase the contribution of oxidative metabolism in energy production and delay fatigue during exercise performed above the AT. Biochim Biophys Acta. 1990 Apr 23;1034(1):17-21. Related Articles, Links Metabolic changes induced by maximal exercise in human subjects following L-carnitine administration. Siliprandi N, Di Lisa F, Pieralisi G, Ripari P, Maccari F, Menabo R, Giamberardino MA, Vecchiet L. Istituto di Fisiopatologia Medica, Universita di Chieti, Italy. In double-blind cross-over experiments, ten moderately trained male subjects were submitted to two bouts of maximal cycle ergometer exercise separated by a 3 day interval. Each subject was randomly given either L-carnitine (2 g) or placebo orally 1 h before the beginning of each exercise session. At rest Lcarnitine supplementation resulted in an increase of plasma-free carnitine without a change in acid-soluble carnitine esters. Treatment with L-carnitine induced a significant post-exercise decrease of plasma lactate and pyruvate and a concurrent increase of acetylcarnitine. The determination of the individual carnitine esters in urine collected for 24 h after the placebo exercise trial revealed a decrease of acetyl carnitine and a parallel increase of a C4 carnitine ester, probably isobutyrylcarnitine. Conversely, acetylcarnitine was strongly increased and C4 compounds were almost suppressed in the L-carnitine loading trial. These results suggest that L-carnitine administration prior to high-intensity exercise stimulates pyruvate dehydrogenase activity, thus diverting pyruvate from lactate to acetylcarnitine formation. Propionyl-L-carnitine-mediated improvement in contractile function of rat hearts oxidizing acetoacetate. Russell RR 3rd, Mommessin JI, Taegtmeyer H. Division of Cardiology, University of Texas Houston Medical School, Houston 77030. Prior evidence has suggested that propionyl-L-carnitine improves function in ischemic hearts by providing carnitine for dissipation of acyl-CoA derivatives and propionate for enrichment of the citric acid cycle. Because contractile failure in hearts oxidizing ketone bodies is due to sequestration of free coenzyme A, which can be reversed by the addition of anaplerotic substrates that enrich the citric acid cycle, experiments were performed to determine whether the addition of propionyl-L-carnitine (2 mM) can improve performance in working rat hearts utilizing acetoacetate (7.5 mM). Whereas the addition of propionyl-L-carnitine to acetoacetate resulted in a sustained improvement in the work output of the heart, the addition of propionate (2 mM) or L-carnitine (2 mM) alone to acetoacetate had negligible effects on contractile function. Propionyl-L-carnitine increased the uptake of acetoacetate by 130%, whereas beta-hydroxybutyrate release was minimal and unchanged compared with other groups. These observations show that rates of acetoacetate oxidation are increased commensurate with increased contractile function. Tissue metabolite data indicate that the utilization of propionyl-L-carnitine did not lead to accumulation of citric acid cycle intermediates in the span from citrate to 2-oxoglutarate but to an increase in the tissue content of malate. The results show that addition of propionyl-L-carnitine in hearts oxidizing acetoacetate results in improved mechanical performance that is comparable to the mechanical performance of hearts perfused with glucose as the only substrate. This improvement is most likely conferred by anaplerosis, as suggested by enhanced rates of acetoacetate utilization and citric acid flux. Urology. 2004 Apr;63(4):641-6. Related Articles, Links Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood, and fatigue associated with male aging. Cavallini G, Caracciolo S, Vitali G, Modenini F, Biagiotti G. Andrological Operative Unit, Headquarters of Societa Italiana di Studi di Medicina della Riproduzione, Bologna, Italy. OBJECTIVES: To To compare testosterone undecanoate versus propionyl-Lcarnitine plus acetyl-L-carnitine and placebo in the treatment of male aging symptoms. METHODS: A total of 120 patients were randomized into three groups. The mean patient age was 66 years (range 60 to 74). Group 1 was given testosterone undecanoate 160 mg/day, the second group was given propionyl-Lcarnitine 2 g/day plus acetyl-L-carnitine 2 g/day. The third group was given a placebo (starch). Drugs and placebo were given for 6 months. The assessed variables were total prostate-specific antigen, prostate volume, peak systolic velocity, end-diastolic velocity, resistive index of cavernosal penile arteries, nocturnal penile tumescence, total and free testosterone, prolactin, luteinizing hormone, International Index of Erectile Function score, Depression Melancholia Scale score, fatigue scale score, and incidence of side effects. The assessment was performed at intervals before, during, and after therapy. RESULTS: Testosterone and carnitines significantly improved the peak systolic velocity, end-diastolic velocity, resistive index, nocturnal penile tumescence, International Index of Erectile Function score, Depression Melancholia Scale score, and fatigue scale score. Carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and International Index of Erectile Function score. Testosterone significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone; carnitines did not. No drug significantly modified prostate-specific antigen or prolactin. Carnitines and testosterone proved effective for as long as they were administered, with suspension provoking a reversal to baseline values. Only the group 1 prostate volume proved significantly greater than baseline 6 months after testosterone suspension. Placebo administration proved ineffective. Negligible side effects emerged. CONCLUSIONS: Testosterone and, especially, carnitines proved to be active drugs for the therapy of symptoms associated with male aging. Neuroendocrinology. 1993 Jun;57(6):985-90. Related Articles, Links Effect of different chronic intermittent stressors and acetyl-lcarnitine on hypothalamic beta-endorphin and GnRH and on plasma testosterone levels in male rats. Bidzinska B, Petraglia F, Angioni S, Genazzani AD, Criscuolo M, Ficarra G, Gallinelli A, Trentini GP, Genazzani AR. Department of Endocrinology, Medical School of Wroclaw, Poland. Chronic stress affects the reproductive function by modifying the neuroendocrine homeostasis. The aim of the present study was to clarify the neuroendocrine and the gonadal changes following chronic intermittent stress in male rats and the action of a neuroactive drug, acetyl-l-carnitine (ALC). The effect of two different stressors, cold water swimming or ether, on central beta-endorphin (beta-EP) and GnRH contents, and on plasma testosterone levels was investigated. In addition, the response to an acute stress in chronically stressed rats, treated or untreated with ALC (10 mg/day/rat p.o.), was evaluated. The stressors were applied twice a day for 10 days, and rats were killed before, during and after the last stress session. Mediobasal hypothalamus (MBH) beta-EP and GnRH contents, and plasma testosterone levels were evaluated by radioimmunoassay. The following results were obtained: (1) both chronic swimming and ether stress caused a decrease in hypothalamic beta-EP contents; (2) MBH GnRH contents increased after chronic swimming stress but not after ether stress; (3) chronic swimming stress induced a twofold decrease in plasma testosterone levels, while no changes were observed after ether stress; (4) the treatment with ALC prevented the decrease in plasma testosterone levels after chronic swimming stress, and (5) acute stress in chronically stressed animals caused an increase in MBH-beta-EP. The present data showed that chronic swimming stress reduces the reproductive capacity and impairs the capacity to respond to the acute stress and that ALC modulates the hormonal changes to physical stress and prevents the antireproductive effect of chronic cold swimming. Fertil Steril. 1981 Aug;36(2):214-8. Related Articles, Links Carnitine and acylcarnitines in semen from azoospermic patients. Lewin LM, Shalev DP, Weissenberg R, Soffer Y. Carnitine and its short-chain acyl esters were assayed in semen from normospermic and azoospermic men. Extremely low concentrations of free carnitine and acylcarnitine were found in semen from patients with obstructive azoospermia where the ejaculate was primarily of prostatis origin, and low values were also obtained in obstruction of the vas deferens, where the epididymal contents were not ejaculated. Semen from patients whose azoospermia was caused by testicular dysfunction had low acylcarnitine concentrations and normal levels of free carnitine in most cases, but a group of patients with severe testicular failure (including cases of Klinefelter syndrome and cryptorchidism) had low semen free carnitine concentrations. Whereas treatment with human chorionic gonadotropin increased serum testosterone levels in azoospermic patients, it did not increase the free carnitine concentration in semen, although it increased the proportion of carnitine found in acylcarnitines. Horm Metab Res. 1990 Dec;22(12):622-6. Related Articles, Links The effect of L-acetylcarnitine on some reproductive functions in the oligoasthenospermic rat. Palmero S, Leone M, Prati M, Costa M, Messeni Leone M, Fugassa E, De Cecco L. Istituto di Fisiologia Generale, Universita di Genova, Italy. The effect of L-acetylcarnitine (LAC) on some parameters of male reproductive function was studied on rats made oligoasthenospermic with dibromochloropropane (DBCP). DBCP depresses sperm count and motility. After one injection of the drug, LAC induces a recovery of both sperm count and motility but after two injections it is ineffective. This effect is also shown visually by microscopic examination of seminiferous tubules. Among the enzymatic activities evaluated as biochemical markers of testicular function both lactate dehydrogenase and NADPH-cytochrome P 450-reductase increased significantly (P less than 0.05) after treatment with LAC in normal rats. LAC also stimulates testosterone production. It is suggested that LAC may affect testicular function. J Pharmacol Exp Ther. 1999 Feb;288(2):509-15. Related Articles, Links Effects of ethanol treatment on epididymal secretory products and sperm maturation in albino rats. Srikanth V, Malini T, Arunakaran J, Govindarajulu P, Balasubramanian K. Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India. Alcoholics are often associated with fertility disturbances with low sperm count and impaired sperm motility. Spermatozoa attains forward motility and fertilizing capacity during their transit through the epididymis. Epididymal secretory products form a suitable microenvironment, which favors sperm maturation. To study the effects of ethanol on epididymal sperm maturation, ethanol (3 g/kg body weight as 25%, v/v) was given by gastric intubation twice daily for 30 days, and in another group, rats given treatment for 30 days were withdrawn of treatment for a further period of 30 days to assess the reversibility of ethanol-induced changes. Serum and epididymidal testosterone and dihydrotestosterone (DHT), epididymidal tissue and sperm carnitine, acetyl carnitine, glycerylphosphoryl choline (GPC), and sialic acid were studied along with epididymidal sperm count and cauda epididymidal sperm motility. Ethanol treatment significantly reduced the epididymal tissue/sperm carnitine, acetyl carnitine, GPC, and sialic acid, suggesting its adverse effect on these secretory products. Impaired cauda epididymidal sperm motility and fertility (in vivo) of ethanol-treated rats imply the defective sperm maturation. All these changes were reverted back to normalcy after withdrawal of ethanol treatment, indicating the transient effects of ethanol. In conclusion, it is evident that ethanol has an adverse effect on sperm maturation, which may be affected due to the decrease in serum/epididymal testosterone and DHT level and epididymal secretory products.