Article

# Effect of glycine propionyl-L-carnitine on aerobic and anaerobic performance

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## Abstract

The purpose of this study was to evaluate the effect of glycine propionyl-L-carnitine (GPLC) supplementation and endurance training for 8 wk on aerobic- and anaerobic-exercise performance in healthy men and women (age 18-44 yr). Participants were randomly assigned to 1 of 3 groups: placebo (n=9), 1 g/d GPLC (n=11), or 3 g/d GPLC (n=12), in a double-blind fashion. Muscle carnitine (vastus lateralis), VO(2peak), exercise time to fatigue, anaerobic threshold, anaerobic power, and total work were measured at baseline and after an 8-wk aerobic-training program. There were no statistical differences (p> .05) between or within the 3 groups for any performance-related variable or muscle carnitine concentrations after 8 wk of supplementation and training. These results suggest that up to 3 g/d GPLC for 8 wk in conjunction with aerobic-exercise training is ineffective for increasing muscle carnitine content and has no significant effects on aerobic- or anaerobic-exercise performance.

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... The scores ranging from 9-14 points were obtained (Table 1), representing a minimum methodological quality of 60% and a maximum of 93.33%. Out of the 11 studies, three achieved acceptable methodological quality [14,15,20], two achieved good methodological quality [30,31], and the other six studies achieved very good quality [16,23,24,[32][33][34]. No study was excluded for not meeting the minimum quality threshold. ...
... Out of the 65 articles, 30 were eliminated for not using the double-blind design, 23 were eliminated for not having at least one outcome related to sports performance, and one was eliminated for not having clear information about the administration of supplementation. Therefore, 11 articles were finally included in the current systematic review [14][15][16]20,23,24,[30][31][32][33][34] (Figure 2). ...
... In all cases, both physically active and untrained participants were selected to carry out the studies. Out of those, only two of them selected professional participants [16,31], seven studies were carried out with recreational or amateur athletes [14,20,23,24,30,32,33], and two of them involved participants without any kind of previous training [15,34]. Nutrients 2021, 13, x FOR PEER REVIEW 8 of 22 ...
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l-Carnitine (l-C) and any of its forms (glycine-propionyl l-Carnitine (GPL-C) or l-Carnitine l-tartrate (l-CLT)) has been frequently recommended as a supplement to improve sports performance due to, among others, its role in fat metabolism and in maintaining the mitochondrial acetyl-CoA/CoA ratio. The main aim of the present systematic review was to determine the effects of oral l-C supplementation on moderate- (50–79% V˙O2 max) and high-intensity (≥80% V˙O2 max) exercise performance and to show the effective doses and ideal timing of its intake. A structured search was performed according to the PRISMA® statement and the PICOS guidelines in the Web of Science (WOS) and Scopus databases, including selected data obtained up to 24 October 2021. The search included studies where l-C or glycine-propionyl l-Carnitine (GPL-C) supplementation was compared with a placebo in an identical situation and tested its effects on high and/or low–moderate performance. The trials that used the supplementation of l-C together with additional supplements were eliminated. There were no applied filters on physical fitness level, race, or age of the participants. The methodological quality of studies was evaluated by the McMaster Critical Review Form. Of the 220 articles obtained, 11 were finally included in this systematic review. Six studies used l-C, while three studies used l-CLT, and two others combined the molecule propionyl l-Carnitine (PL-C) with GPL-C. Five studies analyzed chronic supplementation (4–24 weeks) and six studies used an acute administration (
... Oral supplementation with L -carnitine is used by endurance athletes to increase its content in skeletal muscle, increase fatty acid oxidation during exercise (Brass, & Hiatt, 1998), decrease toxic acyl groups (Peters et al., 2015;Stumpf et al., 1985), maintain the activity of pyruvate dehydrogenase (Brass, & Hiatt, 1998), preserve muscle glycogen, and delay muscular fatigue (Brass, & Hiatt, 1998;Smith, Fry, Tschume, & Bloomer, 2008;Wall et al., 2013). The increased use of fatty acids for energy production during prolonged exercise is beneficial to runners because it reduces muscle glycogen and thus increases aerobic capacity. ...
... To the best knowledge of the author of the present paper, several studies have studied the effect of L -carnitine with acute ingestion (Eizadi, Pourvaghar, Nazem, Eghdami, & Khorshidi, 2009;Kashef & Saei, 2017;Mojtaba et al., 2011;Vecchiet et al., 1990) and different supplementation periods (Greig et al., 1987;Smith et al., 2008;Wächter, Vogt, & Kreis, 2002); most of those studies focused on maximal oxygen consumption (VO 2max ) measurements on a cycle ergometer and conducted on healthy untrained subjects. However, no study has investigated the concentration of carnitine following a middle-distance race, such as 5000 m in endurance athletes. ...
... Greig et al. (1987) showed no significant changes in VO 2max between L -carnitine supplementation (2 g/day for 2-4 weeks) and placebo in healthy untrained subjects. Smith et al. (2008) showed no differences between or within groups in muscle (Vastus lateralis) carnitine content, time to fatigue, and anaerobic power in untrained men and women after eight weeks of L -carnitine supplementation (1 g/day, 3 g/day, or placebo). Kashef & Saei (2017) observed an increased VO 2max during testing to exhaustion (Bruce incremental exercise) following acute ingestion of 3 g of L -carnitine 90 min prior to testing compared to the placebo group in students. ...
Article
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This study was designed to determine the effect of oral supplementation with L-carnitine on the performance time in a 5000 m race. In addition, free fatty acid, blood carnitine, lactate, and glucose responses to the race following the supplementation period were measured. Twenty male trained-endurance athletes were randomly divided into two groups (L-carnitine, n = 10 (22.13 ± 2.66 yrs) or placebo, n = 10 (21.63 ± 2.23 yrs)). The study was performed with a randomized, double-blind, placebo-controlled parallel-group, in which participants ingested an L-carnitine supplement or a placebo 2 × 1.5 g/day for 3 weeks. Athletes completed a 5000 m race before and after the supplementation period. Blood samples were collected from each athlete before and after the race, preand post-supplementation to measure the physiological responses. Data showed that there were no differences in performance time before (p=0.624) and after (p=0.407) supplementation period between groups and within a group (p>0.05). No differences existed in physiological responses between groups after supplementation before beginning the race (p>0.05), except for the blood carnitine level, which was significantly higher in the L-carnitine than the placebo (P=0.001) group. After the finish of the race, however, data showed better physiological responses in response to L-carnitine supplementation compared to the placebo group (p<0.05). In conclusion, although L-carnitine supplementation increases blood carnitine concentration, it has no beneficial effect on performance time of 5000 m race probably due to the short duration of the race; it might also have no ergogenic effect.
... All publications that were included in the present systematic review were randomized controlled clinical trials in design and were published between 1998 and 2017. Nineteen studies were conducted in Asian populations [20,22,23,66e81], 13 in European populations [21,82e93], and others were conducted in Brazil [94,95], Australia [96], New Zealand [97] and USA [98]. One of the included studies used a cross-over design [72], while the others were parallel in design. ...
... The dose of L-carnitine that was used for supplementation ranged from 250 to 4000 mg/day, and 2000 mg/day was the most commonly dose which was used for intervention. In one of the studies [98], data was reported for two different doses, therefore two effect sizes were calculated. The highest dosage was used to calculate the overall effects, however both effect sizes were used in subgroup analysis based on intervention dose. ...
... The highest dosage was used to calculate the overall effects, however both effect sizes were used in subgroup analysis based on intervention dose. Nineteen trials used L-carnitine alone [20,22,23,66,67,69,71e73,75e77,79,81,84,90,91,93,94]; a number of trials used L-carnitine in combination with a low calorie diet [74,87,88] or exercise [78,80,82,83,89,95,96,98] and compared the intervention with low calorie diet or exercise; five trials used a combination of L-carnitine, low calorie diet and exercise [68,70,85,92,97] and compared the intervention with low-calorie diet and exercise; and two trials used a combination of L-carnitine, low calorie diet, exercise and weight loss drug [21,86] which was compared with low calorie diet, exercise and weight loss drug. Therefore, these co-interventions were also included in the control groups, and the only difference between two groups was in Lcarnitine supplementation. ...
Article
Background and aim Clinical evidence which investigated the effects of l-carnitine, a vitamin-like substance, on weight loss had led to inconsistent results. This study therefore aimed to examine the effect of l-carnitine supplementation on body weight and composition by including the maximum number of randomized controlled trials (RCTs) and to conduct a dose-response analysis, for the first time. Methods and results Online databases were searched up to January 2019. In total, 37 RCTs (with 2292 participants) were eligible. Meta-analysis showed that l-carnitine supplementation significantly decreased body weight [Weighted mean difference (WMD) = −1.21 kg, 95% confidence interval (CI): −1.73, −0.68; P < 0.001], body mass index (BMI) (WMD = −0.24 kg/m², 95% CI: −0.37, −0.10; P = 0.001), and fat mass (WMD = −2.08 kg, 95% CI: −3.44, −0.72; P = 0.003). No significant effect was seen for waist circumference (WC) and body fat percent. The meta-analysis of high-quality RCTs only confirmed the effect on body weight. A non-linear dose-response association was seen between l-carnitine supplementation and body weight reduction (P < 0.001) suggesting that ingestion of 2000 mg l-carnitine per day provides the maximum effect in adults. This association was not seen for BMI, WC and body fat percent. Conclusions l-carnitine supplementation provides a modest reducing effect on body weight, BMI and fat mass, especially among adults with overweight/obesity.
... In Study I of this thesis we saw that, despite enriching the diet of athletes with Larginine at different doses, no increase in NO markers measured as nitrate and nitrite (NOx) was found. As shown in Study IV, these results were in line with other previous studies in well-trained athletes which found no increase in plasma NO markers after dietary supplementation of L-arginine (66)(67). One explanation suggested for this effect is the low bioavailability of this amino acid in humans, since dietary L-arginine bioavailability is only about 30%. ...
... The energy and macronutrient composition of the three diets are shown in Table 2. No significant differences were found in participants' body mass over the duration of the study (CD, 67 Table 3. There was no significant difference in VO 2 or HR at any of the time points in the three trials. ...
... Two recent studies assessed this issue showing different results. Smith et al. [67] showed that ingestion of 3 g Á day -1 of GPLC for 8 weeks did not enhance peak power, mean power or total work during a 30-second Wingate test. In contrast, Jacobs et al. [54] indicated that only one dose of GPLC (4.5 g) 90 minutes before performing a test consisting of five 10-second Wingate cycle sprints separated by 1-minute of active recovery periods, significantly improved peak power (~5.2%) and reduced power decrement (~5.2%) through sprints, compared with placebo. ...
Article
... Transport of carnitine into skeletal muscle is performed against a considerable concentration gradient (>100-fold) [37][38][39] through a high affinity, saturable, Na + -dependent, active transport process [40]. Because of this, the majority of early investigations reported no significant increase in muscle carnitine content [39,[41][42][43], even when provided for relatively long periods, such as 3 [39] or 6 [9] months. ...
... As mentioned previously, this lack of carnitine transport into skeletal muscle can be improved through insulin-dependent mechanisms. By failing to stimulate the insulin cascade, many of these early studies also failed to increase muscle carnitine content, thus not observing any changes in substrate utilization [39,[41][42][43][88][89][90]. Interestingly a study carried out in male vegetarians who supplemented for 12 weeks at 2 g/day without instructed coingestion of carbohydrate observed significant increases to skeletal muscle carnitine content; however, this increase did not result in any differences in P max , VO 2max , or muscle phosphocreatine, lactate, or glycogen alterations after a cycling bout at 75% VO 2max for 1 h [91]. ...
... Consequently, many are led to believe that carnitine ingestion will increase the concentration of endogenous carnitine, thereby increasing lipid metabolism and decrease adipose reserves. To date, the majority of the data continues to suggest that carnitine supplementation does not markedly affect muscle carnitine content [647][648][649], fat metabolism [648,650,651], exercise performance [648,649,652,653], or weight loss in overweight [650,654], obese [651,655,656] or trained subjects [657]. For example, Burrus and investigators [658] had ten cyclists ingest combinations of carbohydrate and carnitine while completing a 40-min ride at 65% VO 2 peak before completing an exhaustion ride at 85% VO 2 Peak. ...
... Consequently, many are led to believe that carnitine ingestion will increase the concentration of endogenous carnitine, thereby increasing lipid metabolism and decrease adipose reserves. To date, the majority of the data continues to suggest that carnitine supplementation does not markedly affect muscle carnitine content [647][648][649], fat metabolism [648,650,651], exercise performance [648,649,652,653], or weight loss in overweight [650,654], obese [651,655,656] or trained subjects [657]. For example, Burrus and investigators [658] had ten cyclists ingest combinations of carbohydrate and carnitine while completing a 40-min ride at 65% VO 2 peak before completing an exhaustion ride at 85% VO 2 Peak. ...
Article
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Background: Sports nutrition is a constantly evolving field with hundreds of research papers published annually. In the year 2017 alone, 2082 articles were published under the key words 'sport nutrition'. Consequently, staying current with the relevant literature is often difficult. Methods: This paper is an ongoing update of the sports nutrition review article originally published as the lead paper to launch the Journal of the International Society of Sports Nutrition in 2004 and updated in 2010. It presents a well-referenced overview of the current state of the science related to optimization of training and performance enhancement through exercise training and nutrition. Notably, due to the accelerated pace and size at which the literature base in this research area grows, the topics discussed will focus on muscle hypertrophy and performance enhancement. As such, this paper provides an overview of: 1.) How ergogenic aids and dietary supplements are defined in terms of governmental regulation and oversight; 2.) How dietary supplements are legally regulated in the United States; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of nutritional approaches to augment skeletal muscle hypertrophy and the potential ergogenic value of various dietary and supplemental approaches. Conclusions: This updated review is to provide ISSN members and individuals interested in sports nutrition with information that can be implemented in educational, research or practical settings and serve as a foundational basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.
... Over the years, a number of studies have been conducted on the effects of L-carnitine supplementation on fat metabolism, exercise capacity and body composition. The overwhelming conclusions of L-carnitine research indicates that L-carnitine supplementation does not affect muscle carnitine content [375], fat metabolism, aerobic-or anaerobic-exercise performance [375], and/ or weight loss in overweight or trained subjects [376,377]. Despite the fact that L-carnitine has been shown apparently ineffective as a supplement, the research on L-carnitine has shifted to another category revolving around hypoxic stress and oxidative stress. ...
... Over the years, a number of studies have been conducted on the effects of L-carnitine supplementation on fat metabolism, exercise capacity and body composition. The overwhelming conclusions of L-carnitine research indicates that L-carnitine supplementation does not affect muscle carnitine content [375], fat metabolism, aerobic-or anaerobic-exercise performance [375], and/ or weight loss in overweight or trained subjects [376,377]. Despite the fact that L-carnitine has been shown apparently ineffective as a supplement, the research on L-carnitine has shifted to another category revolving around hypoxic stress and oxidative stress. ...
Article
Full-text available
Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients.
... Because of its function in converting fat into energy, LC is a popular substance among athletes as a potential ergogenic aid (Kim et al., 2015). Propionyl-L-Carnitine (1 g/day or 3 g/day) did not increase aerobic or anaerobic exercise performance in 32 healthy people in an 8-week study (Smith et al., 2008). In a study examining the effects of LC supplementation on plasma and skeletal muscle carnitine concentrations and physical performance in 16 vegetarian and 8 omnivorous male volunteers, the plasma carnitine levels in vegetarians were 10% lower at baseline than those of omnivores. ...
Article
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Carnitine is a conditionally necessary vitamin that aids in energy creation and fatty acid metabolism. Its bioavailability is higher in vegetarians than in meat-eaters. Deficits in carnitine transporters occur because of genetic mutations or in conjunction with other illnesses. Carnitine shortage can arise in health issues and diseases—including hypoglycaemia, heart disease, starvation, cirrhosis, and ageing—because of abnormalities in carnitine control. The physiologically active form of L-carnitine supports immunological function in diabetic patients. Carnitine has been demonstrated to be effective in the treatment of Alzheimer’s disease, several painful neuropathies, and other conditions. It has been used as a dietary supplement for the treatment of heart disease, and it also aids in the treatment of obesity and reduces blood glucose levels. Therefore, L-carnitine shows the potential to eliminate the influences of fatigue in COVID-19, and its consumption is recommended in future clinical trials to estimate its efficacy and safety. This review focused on carnitine and its effect on tissues, covering the biosynthesis, metabolism, bioavailability, biological actions, and its effects on various body systems and COVID-19.
... aerobik ve anaerobik egzersiz performansını etkilemediğine dair ortak bir görüş bulunmaktadır.(122). Bunun tam tersi olarak ise, L-karnitinin direkt etkisinin kas glikojenlerinin kullanımını desteklemesi ve yağ asidi oksidasyonunu artırması şeklinde olduğu konusunda da diğer bir ortak bir görüş olmaktadır(123,124).Glutamin vücut proteinlerinin önemli bir parçası olup, aminoasitler, nükleotidler, nükleik asitler, amino şekerler ve diğer bir takım biyolojik olarak önemli role sahip moleküllerin sentezinde önemli role sahip olan elzem olmayan bir aminoasittir(125). ...
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... Nutritional deficiencies have been reported to induce alterations in brain neurochemistry in conjunction with various psychological disorders or fatigue (59), which highlights the role of nutrition in fatigue induced by exercise (60). Leucine supplementation reduced inflammatory reactions and muscle pain following intensive exercise (61) and a supplement that included glycine improved exercise performance and reduced oxidative stress (62). In addition, peptides from Pseudosciaena crocea prolonged exhaustive swimming time in mice and exhibited notable anti-fatigue effects (23). ...
Article
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Fatigue is a common and serious health problem, and various dietary interventions have previously been employed to ameliorate fatigue. The aim of the current study was to investigate the anti‑fatigue effects of Danish porcine placenta (DPP) and its major dipeptides, including leucine‑glycine (LG) and glycine‑leucine (GL). The anti‑fatigue effects of orally administered DPP, LG and GL were determined using a treadmill exercise test and a forced swimming test (FST) in mice. Additionally, the anti‑inflammatory effects of DPP, LG and GL were investigated in activated splenocytes. The results demonstrated that oral treatment of mice with DPP, LG and GL increased the time to exhaustion during treadmill exercise. Furthermore, DPP, LG and GL enhanced the levels of dopamine, brain‑derived neurotrophic factor and phosphorylated-extracellular signal‑regulated kinase in the brains of mice with treadmill exercise‑induced exhaustive fatigue, and decreased levels of certain proinflammatory cytokines in the serum and spleen, as determined by ELISA and western blot analysis. Following treadmill exercise, commercial kits were employed to demonstrate that DPP, LG and GL reduced the levels of lactate dehydrogenase, lactate, creatine kinase, blood urea nitrogen, alanine transaminase and aspartate transaminase in the muscle and/or serum of mice. In addition, DPP, LG and GL enhanced the muscle and liver glycogen levels, catalase activity in the liver and serum superoxide dismutase activity. DPP, LG and GL also increased the proliferation of splenocytes and inhibited proinflammatory cytokine production by reducing the activation of caspase‑1 and nuclear factor‑κB in activated splenocytes, as determined by MTT assays, ELISA and western blotting, respectively. Furthermore, DPP, LG and GL reduced immobility time in the FST in mice. In conclusion, DPP may limit intensive exercise‑induced fatigue by increasing dopaminergic systems and inhibiting inflammatory responses.
... Two recent studies assessed this issue showing different results. Smith et al. [67] showed that ingestion of 3 g Á day -1 of GPLC for 8 weeks did not enhance peak power, mean power or total work during a 30-second Wingate test. In contrast, Jacobs et al. [54] indicated that only one dose of GPLC (4.5 g) 90 minutes before performing a test consisting of five 10-second Wingate cycle sprints separated by 1-minute of active recovery periods, significantly improved peak power (~5.2%) and reduced power decrement (~5.2%) through sprints, compared with placebo. ...
Article
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Dietary L-citrulline malate supplements may increase levels of nitric oxide (NO) metabolites, although this response has not been related to an improvement in athletic performance. NO plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. L-Arginine is the main precursor of NO via nitric oxide synthase (NOS) activity. Additionally, L-citrulline has been indicated to be a second NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. The importance of L-citrulline as an ergogenic support derives from the fact that L-citrulline is not subject to pre-systemic elimination and, consequently, could be a more efficient way to elevate extracellular levels of L-arginine by itself. L-Citrulline malate can develop beneficial effects on the elimination of NH(3) in the course of recovery from exhaustive muscular exercise and also as an effective precursor of L-arginine and creatine. Dietary supplementation with L-citrulline alone does not improve exercise performance. The ergogenic response of L-citrulline or L-arginine supplements depends on the training status of the subjects. Studies involving untrained or moderately healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly-trained subjects were supplemented, no positive effect on performance was indicated.
... Those findings are particularly notable as GPLC is the first and only nutritional supplement product proven to increase NO synthesis. Smith and associates [30] reported findings related to a group of previously inactive persons, who for eight weeks performed stationary cycling and/or walking with GPLC supplementation. Study participants were randomized to receive placebo, 1 or 3 g GPLC per day. ...
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Recent research has indicated that short term administration of glycine propionyl-L-carnitine (GPLC) significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperaemia. However, no scientific evidence exists that suggests such supplementation enhances exercise performance in healthy, trained individuals. The purpose of this study was to examine the effects of GPLC on the performance of repeated high intensity stationary cycle sprints with limited recovery periods in resistance trained male subjects. In a double-blind, placebo-controlled, cross-over design, twenty-four male resistance trained subjects (25.2 ± 3.6 years) participated in two test sessions separated by one week. Testing was performed 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL), in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Peak (PP) and mean values (MP) of sprint power output and percent decrement of power (DEC) were determined per bout and standardized relative to body masss. Heart rate (HR) and blood lactate (LAC) were measured prior to, during and following the five sprint bouts. Significant main effects (p < 0.001) were observed for sprint bout order in values of PP, MP, DEC, and HR. There were significant main effects detected for condition in PP and MP (p < 0.05), with values across the five sprint bouts 2.6 – 15% greater with GPLC. Significant statistical interactions were detected between bout order and condition for both PP and MP (p < 0.05). There was a significant main effect of condition for LAC, LAC values 15.7% lower 4 min post-exercise with GPLC (p = 0.09) and with GPLC resulting in 16.2% less LAC at 14 min post-exercise (p < 0.05). These findings indicate that short-term oral supplementation of GPLC can enhance peak power production in resistance trained males with significantly less LAC accumulation.
... Two recent studies assessed this issue showing different results. Smith et al. [67] showed that ingestion of 3 g Á day -1 of GPLC for 8 weeks did not enhance peak power, mean power or total work during a 30-second Wingate test. In contrast, Jacobs et al. [54] indicated that only one dose of GPLC (4.5 g) 90 minutes before performing a test consisting of five 10-second Wingate cycle sprints separated by 1-minute of active recovery periods, significantly improved peak power (~5.2%) and reduced power decrement (~5.2%) through sprints, compared with placebo. ...
Article
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Nitric oxide (NO) has led a revolution in physiology and pharmacology research during the last two decades. This labile molecule plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. Currently, it is known that NO synthesis occurs via at least two physiological pathways: NO synthase (NOS) dependent and NOS independent. In the former, L-arginine is the main precursor. It is widely recognized that this amino acid is oxidized to NO by the action of the NOS enzymes. Additionally, L-citrulline has been indicated to be a secondary NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. Nitrate and nitrite are the main substrates to produce NO via the NOS-independent pathway. These anions can be reduced in vivo to NO and other bioactive nitrogen oxides. Other molecules, such as the dietary supplement glycine propionyl-L-carnitine (GPLC), have also been suggested to increase levels of NO, although the physiological mechanisms remain to be elucidated. The interest in all these molecules has increased in many fields of research. In relation with exercise physiology, it has been suggested that an increase in NO production may enhance oxygen and nutrient delivery to active muscles, thus improving tolerance to physical exercise and recovery mechanisms. Several studies using NO donors have assessed this hypothesis in a healthy, trained population. However, the conclusions from these studies showed several discrepancies. While some reported that dietary supplementation with NO donors induced benefits in exercise performance, others did not find any positive effect. In this regard, training status of the subjects seems to be an important factor linked to the ergogenic effect of NO supplementation. Studies involving untrained or moderately trained healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly trained subjects were supplemented, no positive effect on performance was indicated. In addition, all this evidence is mainly based on a young male population. Further research in elderly and female subjects is needed to determine whether NO supplements can induce benefit in exercise capacity when the NO metabolism is impaired by age and/or estrogen status.
... All of these can potentially improve physical performance during high-intensity exercise. Besides, recent studies demonstrated that short term administration of glycine propionyl-L-carnitine (GPLC) significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperemia [28][29][30], and can also enhance exercise performance in healthy, trained individuals [28]. Carnosine is synthesized in skeletal muscle from L-histidine and A-alanine amino acids [22]. ...
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In metabolomics, biomarker discovery is a highly data driven process and requires sophisticated computational methods for the search and prioritization of novel and unforeseen biomarkers in data, typically gathered in preclinical or clinical studies. In particular, the discovery of biomarker candidates from longitudinal cohort studies is crucial for kinetic analysis to better understand complex metabolic processes in the organism during physical activity. In this work we introduce a novel computational strategy that allows to identify and study kinetic changes of putative biomarkers using targeted MS/MS profiling data from time series cohort studies or other cross-over designs. We propose a prioritization model with the objective of classifying biomarker candidates according to their discriminatory ability and couple this discovery step with a novel network-based approach to visualize, review and interpret key metabolites and their dynamic interactions within the network. The application of our method on longitudinal stress test data revealed a panel of metabolic signatures, i.e., lactate, alanine, glycine and the short-chain fatty acids C2 and C3 in trained and physically fit persons during bicycle exercise. We propose a new computational method for the discovery of new signatures in dynamic metabolic profiling data which revealed known and unexpected candidate biomarkers in physical activity. Many of them could be verified and confirmed by literature. Our computational approach is freely available as R package termed BiomarkeR under LGPL via CRAN http://cran.r-project.org/web/packages/BiomarkeR/.
... The effect of exercise performance improvement by L-ornithine hydrochloride ingestion may not be expected in the case of the present relatively brief, high-intensity exercise. Many previous studies have reported the effects of amino acid ingestion on improving performance, but a variety of exercise types were used (Smith et al., 2008; Zoeller et al., 2007; de Araujo et al., 2006; Norton and Layman. 2006). ...
Article
L-Ornithine has an important role in ammonia metabolism via the urea cycle. This study aimed to examine the effect of L-ornithine hydrochloride ingestion on performance during incremental exhaustive ergometer bicycle exercise and ammonia metabolism during and after exercise. In all, 14 healthy young adults (age: 22.2±1.0 years, height: 173.5±4.6 cm, body mass: 72.5±12.5 kg) who trained regularly conducted incremental exhaustive ergometer bicycle exercises after -ornithine hydrochloride supplementation (0.1 g/kg, body mass) and placebo conditions with a cross-over design. The exercise time (sec) of the incremental ergometer exercise, exercise intensity at exhaustion (watt), maximal oxygen uptake (ml per kg per min), maximal heart rate (beats per min) and the following serum parameters were measured before ingestion, 1 h after ingestion, just after exhaustion and 15 min after exhaustion: ornithine, ammonia, urea, lactic acid and glutamate. All indices on maximal aerobic capacity showed insignificant differences between both the conditions. Plasma ammonia concentrations just after exhaustion and at 15 min after exhaustion were significantly more with ornithine ingestion than with placebo. Plasma glutamate concentrations were significantly higher after exhaustion with ornithine ingestion than with placebo. It was suggested that, although the ingestion of L-ornithine hydrochloride before the exercise cannot be expected to improve performance, it does increase the ability to buffer ammonia, both during and after exercise.
... Finally, GPLC (a novel form of carnitine) supplementation with exercise has been shown to elevate NO levels in human subjects. Besides, decreasing oxidative stress, GPLC supplementation was associated with normalization/enhancement of circulating NO levels [34]. ...
Carnitines are involved in mitochondrial transport of fatty acids and are of critical importance for maintaining normal mitochondrial function. This review summarizes recent experimental and clinical studies showing that mitochondrial dysfunction secondary to a disruption of carnitine homeostasis may play a role in decreased NO signaling and the development of endothelial dysfunction. Future challenges include development of agents that can positively modulate L-carnitine homeostasis which may have high therapeutic potential.
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Abstract Sport nutrition is a constantly evolving field with literally thousands of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper presents a well-referenced overview of the current state of the science related to how to optimize training through nutrition. More specifically, this article discusses: 1.) how to evaluate the scientific merit of nutritional supplements; 2.) general nutritional strategies to optimize performance and enhance recovery; and, 3.) our current understanding of the available science behind weight gain, weight loss, and performance enhancement supplements. Our hope is that ISSN members find this review useful in their daily practice and consultation with their clients.
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The global proliferation of sports nutrition brands is emblematic of the size of consumers seeking enhancements through this class of ingestible products. However, a nearly ubiquitous theme of commonality is shared by these products: the compositions are often close to identical, differing only by amount and description, with ancillary alterations in flavor or packaging. How many branched chain amino acid or whey protein compositions can be birthed? The future of sports nutrition will continue to witness the penetration of multinational (food, beverage, and pharma) brands entering the fray through acquisition, and patent filings, which may foster a generic storm or heightened innovation. What remains most compelling is the opportunity for true innovation and pioneering to disrupt the highly duplicative sports nutrition product landscape. Such adventurous excursions may include systematic research/innovation programs that provide novelty, compelling proof of concept, and “real-world” utility; implementation of research methods that provide direct, inferential insights into the bioavailability and metabolism of bioactives; and novel protein/amino nitrogen sources that mimic the biological effects of whey protein.
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Competitive sport on high levels is far from being healthy. Strenuous physical activity on the way to the medal is far from being physiologic. In fact, we have now ways and means to evaluate the immediate muscle damage and the accumulation of metabolic products causing pain and other physical phenomena by which the body notifies us about this suffering. It is important to find ways and means to decrease body discomfort or to reduce the tissue damage, and to avoid exercise stress-related health risks. On the other hand, from the medical point of view we have to provide athletes with adequate nutrients and energy for the maintenance of homeostasis. Doing this, the question is, what is the border between doping and preventive medicine? Energetic and nutritional needs of athletes are higher than those of sedentary people. Where is the border between adequate nutritional supplementation aimed at maintenance of appropriate body composition, energy stores, and body mass on one hand and nutritional overload for the improvement of athletic performance in elite athletes on the other hand? Very often, there are possible links between “supplements or ergogenic compounds” and the endocrine-metabolic system.
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As usual, the alphabet throws together a mixture of supplements with different levels of popularity and scientific support. Part 20 covers some rarely reported, studied and/or little used supplements in sport: glycine, histidine and inosine. The majority of human studies of supplementation with the essential amino acid histidine has involved clinical work. In terms of athletic performance, there is current interest in supplementation strategies to increase muscle content of the histidine-containing dipeptide (HCD), carnosine. Despite some interest in the use of a chicken breast extract (CBEX) described in this article, most of the focus in this area involves β-alanine supplementation (covered in part 5). There was some interest in inosine as an ergogenic aid in the 1990s but it appears not to have been studied since then. Meanwhile, there appears little role for glycine supplementation in sport although some interest in glycine-containing compounds is possible. β-Hydroxymethyl β-butyrate (HMB) is much more well known, with marketing usually targeting bodybuilders.
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(Received 31 October, 2009 ; Accepted 10 March, 2010)AbstractBackground and purpose: Many athletes adopt nutritional manipulations to improve their performance. Among the substances generally consumed is carnitine (L-trimethyl-3-hydroxy-ammoniobutanoate) which has been used by athletes as an ergogenic aid, due to its role in the transport of long-chain fatty acids across mitochondrial membranes. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widely used in various sporting fields to provide a boost to the recommended daily allowance. The aim of this study is to investigate the effects of acute L-carnitine administration on ventilatory breakpoint, an exercise performance during incremental exercise.Materials and methods: This study was double-blind, randomized and crossover in design. The subjects were 12 randomly selected active male physical education students, 21.75±0.64 years old, with a mean body mass index (BMI) of 23.7±0.94kg/m2, divided into 2 groups. They received orally either 2g of L-carnitine dissolved in 200 ml of water, plus 6 drops of lemon juice or a placebo (6 ml lemon juice dissolved in 200 ml of water) 90 minutes before they began to exercise on a treadmill. They performed a modified protocol of Conconi test to exhaustion. One-way analysis of variance with repeated measurements was used for data analysis.Results: The results showed that exercise performance improved in LC group (2980±155 meter) compared with placebo group (2331±51 meter). Furthermore, no significant difference was found in ventilatory breakpoint between the two groups.Conclusion: This finding indicates that administration of L- Carnitine, 90 minutes prior to exercise may improve performance; despite the ventilatory breakpoint as one of the anaerobic system indices that had no effect. J Mazand Univ Med Sci 2009; 19(73): 43-50 (Persian).
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Competitive sport and strenuous physical activity make demands on our body above the usual physiological range. Measurable muscle damage and accumulation of metabolic products cause pain and other effects that can be demonstrated. From the medical point of view we have to provide athletes with adequate nutrients and energy for the maintenance of homeostasis and to cover their higher energetic and nutritional needs as compared to sedentary people. Some athletes may need supplements to replace essential nutrients missing from their regular (especially if unbalanced) diet, or to restore special needs, such as fluids and salts, while exercising in extreme climatic conditions. Overload of additives is frequent in both professional and amateur athletes. Very often, the proposed mechanism for the rationale of using these additives, 'supplements' or 'ergogenic compounds', is related to their possible effect on the endocrine-metabolic system, in many cases without solid evidence-based research. Yet it needs to be remembered that there is still disagreement on what are the required physiological needs of athletes for amino acids and other supplements. Different surveys on the use of supplements report that 40-60% of athletes take food additives, and the numbers are rapidly increasing. A more alarming fact is that about 50% of the recommendations to use these supplements come from non-professional people. Since some additives may change the endocrine and metabolic homeostasis in an unexpected way--as an extreme example of close to 50 deaths reported from the use of L-tryptophan supplements--it is important to study carefully the effects of additives given to athletes, and to increase awareness of the lack of knowledge in this field.
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A double-blind crossover field study was performed to investigate the effects of acute L-carnitine supplementation on metabolism and performance of endurance-trained athletes during and after a marathon run. Seven male subjects were given supplements of 2 g L-carnitine 2 h before the start of a marathon run and again after 20 km of the run. The plasma concentration of metabolites and hormones was analysed 1 h before, immediately after and 1 h after the run, as well as the next morning after the run. In addition, the respiratory exchange ratio (R) was determined before and at the end of the run, and a submaximal performance test was completed on a treadmill the morning after the run. The administration of L-carnitine was associated with a significant increase in the plasma concentration of all analysed carnitine fractions (i.e. free carnitine, short-chain acylcarnitine, long-chain acylcarnitine, total acid soluble carnitine, total carnitine) but caused no significant change in marathon running time, in R, in the plasma concentrations of carbohydrate metabolites (glucose, lactate, pyruvate), of fat metabolites (free fatty acids, glycerol, -hydroxybutyrate), of hormones (insulin, glucagon, cortisol), and of enzyme activities (creatine kinase, lactate dehydrogenase). Moreover, there was no difference in the result of the submaximal performance test the morning after the run. In conclusion, acute administration of L-carnitine did not affect the metabolism or improve the physical performance of the endurance-trained athletes during the run and did not alter their recovery.
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The effects of a 9-week aerobic interval training program on anaerobic intermittent performance were investigated. Intermittent work consisted of four repeat 30-sec maximal efforts on a cycle ergometer (Wingate test) with 3-min recovery intervals. Thirteen men trained 3 days a week on the cycle ergometer, completing 3-min work-to-rest intervals and progressing from 5 to 10 reps. Relative and absolute values of aerobic power increased significantly for the training group (p < .05). No significant change was observed for the control group (n = 11). The training group demonstrated significant increases in the four anaerobic variables of short-term peak power (SPP), short-term anaerobic capacity (SAC), intermediate-term peak power (IPP), and total work (TW), and across the four 30-sec maximal repeats for anaerobic performance (T1-T4) (p < .05). Greater percentages of increase occurred for IPP and TW, especially during Repeats 3 and 4. The control group only demonstrated a significant increase in SPP for Repeat 3. These data suggest that the type of interval training program used in the study increased aerobic power and also enhanced performance in repeated high intensity, short duration work.
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We examined the influence of L-carnitine L-tartrate (LCLT) on markers of purine catabolism, free radical formation, and muscle tissue disruption after squat exercise. With the use of a balanced, crossover design (1 wk washout), 10 resistance-trained men consumed a placebo or LCLT supplement (2 g L-carnitine/day) for 3 wk before obtaining blood samples on six consecutive days (D1 to D6). Blood was also sampled before and after a squat protocol (5 sets, 15-20 repetitions) on D2. Muscle tissue disruption at the midthigh was assessed using magnetic resonance imaging (MRI) before exercise and on D3 and D6. Exercise-induced increases in plasma markers of purine catabolism (hypoxanthine, xanthine oxidase, and serum uric acid) and circulating cytosolic proteins (myoglobin, fatty acid-binding protein, and creatine kinase) were significantly (P < or = 0.05) attenuated by LCLT. Exercise-induced increases in plasma malondialdehyde returned to resting values sooner during LCLT compared with placebo. The amount of muscle disruption from MRI scans during LCLT was 41-45% of the placebo area. These data indicate that LCLT supplementation is effective in assisting recovery from high-repetition squat exercise.
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Increasing skeletal muscle carnitine content may alleviate the decline in muscle fat oxidation seen during intense exercise. Studies to date, however, have failed to increase muscle carnitine content, in healthy humans, by dietary or intravenous L-carnitine administration. We hypothesized that insulin could augment Na+-dependent skeletal muscle carnitine transport. On two randomized visits, eight healthy men underwent 5 h of intravenous L-carnitine infusion with serum insulin maintained at fasting (7.4+/-0.4 mIU*l(-1)) or physiologically high (149.2+/-6.9 mIU*l(-1)) concentrations. The combination of hypercarnitinemia (approximately 500 micromol*l(-1)) and hyperinsulinemia increased muscle total carnitine (TC) content from 22.0 +/- 0.9 to 24.7 +/- 1.4 mmol*(kg dm)(-1) (P<0.05) and was associated with a 2.3 +/- 0.3-fold increase in carnitine transporter protein (OCTN2) mRNA expression (P<0.05). Hypercarnitinemia in the presence of a fasting insulin concentration had no effect on either of these parameters. This study demonstrates that insulin can acutely increase muscle TC content in humans during hypercarnitinemia, which is associated with an increase in OCTN2 transcription. These novel findings may be of importance to the regulation of muscle fat oxidation during exercise, particularly in obesity and type 2 diabetes where it is known to be impaired.
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Glycine, a non-essential amino acid, has been found to protect against oxidative stress in several pathological situations, and it is required for the biosynthesis of structural proteins such as elastin. As hypertension is a disease in which free radicals and large vessel elasticity are involved, this article will examine the possible mechanisms by which glycine may protect against high blood pressure. The addition of glycine to the diet reduces high blood pressure in a rat model of the metabolic syndrome. Also, glycine supplemented to the low protein diet of rat dams during pregnancy has a beneficial effect on blood pressure in their offspring. The mechanism by which glycine decreases high blood pressure can be attributed to its participation in the reduction of the generation of free radicals, increasing the availability of nitric oxide. In addition, as glycine is required for a number of critical metabolic pathways, such as the synthesis of the structural proteins collagen and elastin, the perturbation of these leads to impaired elastin formation in the aorta. This involves changes in the aorta's elastic properties, which would contribute to the development of hypertension. The use of glycine to lower high blood pressure could have a significant clinical impact in patients with the metabolic syndrome and with limited resources. On the other hand, more studies are needed to explore the beneficial effect of glycine in other models of hypertension and to investigate possible side-effects of treatment with glycine.
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Maintaining hyperinsulinemia (approximately 150 mU/l) during steady-state hypercarnitinemia (approximately 550 micromol/l) increases skeletal muscle total carnitine (TC) content by approximately 15% within 5 h. The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through L-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits (study A), eight men ingested 3 g/day L-carnitine followed by 4 x 500-ml solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day L-carnitine followed by 2 x 500 ml of either Con or CHO for 2 wk (study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con (P < 0.001) and in a lower plasma TC concentration throughout the CHO visit (P < 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 +/- 10.7 vs. 212.1 +/- 17.2 mg; P < 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 +/- 18.0 to 281.0 +/- 35.0 mg; P < 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 +/- 9.2 to 166.8 +/- 17.3 mg after 3 days (P < 0.01), which was less than during the Con trial (P < 0.01), and it remained lower over the course of the study (P < 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.
Seven healthy young male adults were subjected to a total of 56 tests to ascertain the effects of L-carnitine (L-C) and a placebo (P) on ventilation, OZ intake $(\dot V_{o_2 } )$ , CO2 output, heart rate, blood pressure and serum lactic acid, non-esterified fatty acid, glycerol and glucose during strenuous and aerobic/anaerobic threshold-level treadmill exercise. The tests were made in conditions of normoxia (02=20.9%) and hypoxia (O2=13.0%, equivalent to 3,500 m above sea level). The only clear difference was in the respiratory quotient (RQ = 0.883, SD 0.025 vs 0.904, SD 0.035) after L-C and P administration respectively (P<0.01), under normal oxygenation and 0.861, SD 0.052 following L-C vs 0.926, SD 0.040 after P (P<0.01) in acute hypoxia at $\dot V_{o_2 }$ levels around the anaerobic threshold. The lower RQ values of the L-C-treated subjects during hypoxia indicate a lower rate of carbohydrate transformation.
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Sprint (S, n=12) and endurance (E, n=14) training were performed independently and concurrently (C, n=6) for eight weeks to determine adaptive responses to each and their capability. Group S trained three days per week performing six 100m and six 50m sprints at 95 percent maximum speed. Group E ran continuously for 30 minutes at 85 percent HRmax three days per week. Group C trained six days per week, alternating days of sprint and endurance training. Group S improved (p<0.05) 50m and 100m sprint times (2.5 and 4.5 percent, respectively), 30-second run distance (2.5 percent), showed no change (p>0 .05) in 30-minute run distance or [latin capital V with dot above]O2 max, and decreased (p<0.05) average power output 20.9 percent during the 30- to 45-second interval of a 60-second continuous jump test (CJT) Group E improved (p<0.05) 30-minute run distance (12.6 percent), [latin capital V with dot above]O2, max (5.9 percent), and sprint performance (2.2 percent in 50m, 2.5 percent in 100m), but showed no change (p>0.05) in 30-second run distance. Group C showed (p<0.05) improvements of similar magnitude to group E in [latin capital V with dot above]O2, max (7.5 percent) and 30-minute run distance 9.9 percent), and to Group S in 50m (2.4 percent) and l00m (3.5 percent) times and 30-second run distance (3.5 percent). All groups decreased (p<0.05) average power output during the 45- to 60-second interval of the GO-second CJT. Our result sug gest that optimum improvements in performance are specific to the mode of training (sprint or endurance) and are independent of concurrent performance of both modes of exercise. (C) 1988 National Strength and Conditioning Association
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The effects of dietary L-carnitine supplementation on lactate (LA-) accumulation following anaerobic exercise were examined by assessing blood LA- concentration before and after an intense 600-m sprint in 26 elite male runners (age 20.9 +/- 2.4 yrs) who ingested either 2 g per day of L-carnitine or a placebo for 21 days in a double-blind, crossover study. A 7-day washout period occurred at the end of the first treatment. Statistical analyses revealed no significant differences in either preexercise or postexercise blood LA- after ingestion of L-carnitine vs. placebo. In addition, subjects who received L-carnitine last did not have significantly different postexercise blood LA- levels than those who received carnitine first. Likewise, those ingesting the placebo last did not have significantly different postexercise blood LA- values than those receiving it first. Moreover, since exercise times under either treatment did not differ significantly, the apparent inability of carnitine supplementation to affect this indicator of fatigue was likely not due to differences in exertion. Thus it is concluded that supplementation of L-carnitine as provided in this study had no effect on LA- accumulation during maximal anaerobic exercise. (C) 1997 National Strength and Conditioning Association
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The effects of L-carnitine on respiratory chain enzymes in muscle of long distance runners were studied in 14 athletes. These subjects received placebo or L-carnitine (2 g orally b.i.d.) during a 4-week period of training. Athletes receiving L-carnitine showed a significant increase (p < 0.01) in the activities of rotenone-sensitive NADH cytochrome c reductase, succinate cytochrome c reductase and cytochrome oxidase. In contrast, succinate dehydrogenase and citrate synthase were unchanged. No significant changes were observed after placebo administration. The levels of both total and free carnitine from athletes receiving placebo were significantly decreased (p < 0.01) after treatment. By contrast, total and free carnitine levels were markedly increased (p < 0.01) after supplementation with L-carnitine. Our results suggest that L-carnitine induces an increase of the respiratory chain enzyme activities in muscle, probably by mechanisms involving mitochondrial DNA.
Carnitine has a potential effect on exercise capacity due to its role in the transport of long-chain fatty acids into the mitochondria for beta-oxidation, the export of acyl-coenzyme A compounds from mitochondria and the activation of branched-chain amino acid oxidation in the muscle. We studied the effect of carnitine supplementation on palmitate oxidation, maximal exercise capacity and nitrogen balance in rats. Daily carnitine supplementation (500 mg.kg-1 body mass for 6 weeks) was given to 30 rats, 15 of which were on an otherwise carnitine-free diet (group I) and 15 pair-fed with a conventional pellet diet (group II). A control group (group III, n = 6) was fed ad libitum the pellet diet. Palmitate oxidation was measured by collecting 14CO2 after an intraperitoneal injection of [1-14C]palmitate and exercise capacity by swimming to exhaustion. After carnitine supplementation carnitine concentrations in serum were supranormal [group I, total 150.8 (SD 48.5), free 78.9 (SD 18.4); group II, total 170.9 (SD 27.9), free 115.8 (SD 24.6) mumol.l-1] and liver carnitine concentrations were normal in both groups [group I, total 1.6 (SD 0.3), free 1.2 (SD 0.2); group II, total 1.3 (SD 0.3), free 0.9 (SD 0.2) mumol.g-1 dry mass]. In muscle carnitine concentrations were normal in group I [total 3.8 (SD 1.2), free 3.2 (SD 1.0) mumol.g-1 dry mass] and increased in group II [total 6.6 (SD 0.5), free 4.9 (SD 0.9) mumol.g-1 dry mass].(ABSTRACT TRUNCATED AT 250 WORDS)
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An investigation on the therapeutic effect of L-carnitine was performed at three different centres and included two hundred patients, 40 to 65 years of age, with exercise-induced stable angina. In one hundred randomly selected patients the drug was administered orally in daily doses of 2 g in addition to the already instituted therapy, and the effect studied over a 6-month period. Compared with the control group, these patients showed a significant reduction in the number of premature ventricular contractions (PVC) at rest, as well as an increased tolerance during ergometric cycle exercise as demonstrated by an increased maximal cardiac frequency, increased maximal systolic arterial blood pressure and therefore also increased double cardiac product and reduced ST-segment depression during maximal effort. This was accompanied by improvement in cardiac function and resultant performance, as shown by an increase in the number of patients belonging to class I of the NYHA classification and a reduction in the consumption of cardioactive drugs. Laboratory analysis showed an improvement in plasma lipid levels. The authors conclude, after having discussed the particular metabolic mechanisms, that L-carnitine undoubtedly represents an interesting therapeutic drug for patients with exercise-induced stable angina.
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Efficient utilization of fatty acids to sustain prolonged physical efforts is thought to be dependent on the carnitine shuttle of muscle. A study has been carried out in 24 athletes (13 long-distance runners and 11 sprinters). These subjects received placebo or L-carnitine (1 g/orally b.i.d.) during a 6-month period of training. In endurance athletes, training induced lowering of total and free muscle carnitine. Increase of esterified muscle carnitine was also observed. Post-exertional overflow of acetylcarnitine and long-chain acylcarnitine, as well as reduction of the free fraction was also noticed in the blood. Fasting plasma carnitine levels, however, were not affected in carnitine-treated athletes at rest. These changes were likely related with the significantly increased urinary excretion of esterified and total carnitine which occurred after physical exercise. In the sprinters only, a decrease in free and total carnitine of muscle was detected after training. Both these potentially unfavorable effects were prevented by oral administration of L-carnitine. Our data suggest that training in endurance athletes, and to a lesser extent, in sprinters, is associated with a decrease in free and total carnitine of muscle, due to an increased overflow of short-chain carnitine esters in urine.
Article
In animals carnitine is formed from proteic lysine through a complex set of reactions, leading to deoxycarnitine, the immediate precursor of carnitine in all tissues. However the last stage, hydroxylation of deoxycarnitine to carnitine, is restricted to liver, brain and, in humans, kidney (1). Therefore other tissues can export deoxycarnitine via the blood stream to these hydroxylating tissues, but for their own endogenous carnitine depend either on the return and import of the newly synthesized compound or on an adequate dietary supply.
The effects of L-carnitine administration on maximal exercise capacity were studied in a double-blind, cross-over trial on ten moderately trained young men. A quantity of 2 g of L-carnitine or a placebo were administered orally in random order to these subjects 1 h before they began exercise on a cycle ergometer. Exercise intensity was increased by 50-W increments every 3 min until they became exhausted. After 72-h recovery, the same exercise regime was repeated but this time the subjects, who had previously received L-carnitine, were now given the placebo and vice versa. The results showed that at the maximal exercise intensity, treatment with L-carnitine significantly increased both maximal oxygen uptake, and power output. Moreover, at similar exercise intensities in the L-carnitine trial oxygen uptake, carbon dioxide production, pulmonary ventilation and plasma lactate were reduced. It is concluded that under these experimental conditions pretreatment with L-carnitine favoured aerobic processes resulting in a more efficient performance. Possible mechanisms producing this effect are discussed.
Seven healthy young male adults were subjected to a total of 56 tests to ascertain the effects of L-carnitine (L-C) and a placebo (P) on ventilation, O2 intake (VO2), CO2 output, heart rate, blood pressure and serum lactic acid, non-esterified fatty acid, glycerol and glucose during strenuous and aerobic/anaerobic threshold-level treadmill exercise. The tests were made in conditions of normoxia (O2 = 20.9%) and hypoxia (O2 = 13.0%, equivalent to 3,500 m above sea level). The only clear difference was in the respiratory quotient (RQ = 0.883, SD 0.025 vs 0.904, SD 0.035) after L-C and P administration respectively (P less than 0.01), under normal oxygenation and 0.861, SD 0.052 following L-C vs 0.926, SD 0.040 after P (P less than 0.01) in acute hypoxia at VO2 levels around the anaerobic threshold. The lower RQ values of the L-C-treated subjects during hypoxia indicate a lower rate of carbohydrate transformation.
Article
This study was undertaken to determine the effects of L-carnitine addition to the diet during submaximal exercise in endurance-trained humans. Ten subjects (VO2max: 62 ml.kg-1.min-1) performed a control test (C) (45 min of cycling at 66% of VO2max) followed by 60 min of recovery in a sitting position. Each subject repeated this trial after 28 days of placebo (P) and L-carnitine (L-C) treatment (double-blinded cross-over design). The dose of each treatment was 2 g/day. There were no differences between the C and P tests. The respiratory quotient was lower (p less than 0.05) with treatment than with P or C during exercise. In addition, oxygen uptake, heart rate, blood glycerol, and resting plasma free fatty acid concentrations presented a nonsignificant trend toward higher values in L-C than in the C or P groups. These observations suggest an increased lipid utilization by muscle during exercise in the L-C-treated group. This effect has further possibilities for improving performance during submaximal exercise.
Article
Reperfusion of isolated rabbit heart after 60 min of ischaemia resulted in poor recovery of mechanical function, release of reduced (GSH) and oxidized glutathione (GSSG), reduction of tissue GSH/GSSG ratio and shift of cellular thiol redox state toward oxidation, suggesting the occurrence of oxidative stress. Pretreatment of the isolated heart with propionyl-L-carnitine (10(-7) M) improved the functional recovery of the myocardium, reduced GSH and GSSG release and attenuated the accumulation of tissue GSSG. This effect was specific for propionyl-L-carnitine as L-carnitine and propionic acid did not modify myocardial damage.
Article
Excess CO2 is generated when lactate is increased during exercise because its [H+] is buffered primarily by HCO-3 (22 ml for each meq of lactic acid). We developed a method to detect the anaerobic threshold (AT), using computerized regression analysis of the slopes of the CO2 uptake (VCO2) vs. O2 uptake (VO2) plot, which detects the beginning of the excess CO2 output generated from the buffering of [H+], termed the V-slope method. From incremental exercise tests on 10 subjects, the point of excess CO2 output (AT) predicted closely the lactate and HCO-3 thresholds. The mean gas exchange AT was found to correspond to a small increment of lactate above the mathematically defined lactate threshold [0.50 +/- 0.34 (SD) meq/l] and not to differ significantly from the estimated HCO-3 threshold. The mean VO2 at AT computed by the V-slope analysis did not differ significantly from the mean value determined by a panel of six experienced reviewers using traditional visual methods, but the AT could be more reliably determined by the V-slope method. The respiratory compensation point, detected separately by examining the minute ventilation vs. VCO2 plot, was consistently higher than the AT (2.51 +/- 0.42 vs. 1.83 +/- 0.30 l/min of VO2). This method for determining the AT has significant advantages over others that depend on regular breathing pattern and respiratory chemosensitivity.
Article
Acute effects of l-carnitine (vials of 1 g endovenous) were recorded in a group of elite athletes (17 swimmers) by a prospective double-blind placebo-controlled trial and cross over. Significant changes were registered after l-carnitine injection, compared to placebo, for FFA, triglycerides, lactic acid after exercise, evoked muscular potential, 90 to 120 minutes after injection. The authors explain these changes by the increase of free carnitine, which permits a larger quantity of FFA to enter the mitochondria and to be more extensively used as energy source.
Changes in the main physiological parameters and circulating indicators of carbohydrate, protein, lipid (and ketone body) metabolism were measured in ten exercising subjects before L-carnitine (L-carn) loading, after 4 weeks of daily loading with 2 g L-carn, and 6-8 weeks after terminating L-carn administration. Measurements were made on venous blood samples collected during each experiment at fixed time intervals over an initial rest of 45 min, 60 min bicycle exercise performed near 50% VO2max and 120 min recovery. Free and total plasma carnitine levels reached a plateau corresponding to an average rise of 25% for both fractions, 9-10 days after the beginning of the L-carn diet. These levels returned to their initial values 6-8 weeks after cessation of the supply. Generally L-carn supplementation did not significantly modify the physiological parameters and circulating metabolites. No distinct increase of the relative participation of endogenous lipids in the fuel supply of prolonged submaximal exercise was observed. In normal human subjects the increased demand for fatty acid oxidation resulting from exercise seems to be adequately supported by endogenous levels of carnitine.
Two trials were conducted to investigate the effects of L-carnitine supplementation upon maximum and submaximum exercise capacity. Two groups of healthy, untrained subjects were studied in double-blind cross-over trails. Oral supplementation of 2 g per day L-carnitine was used for 2 weeks in the first trial and the same dose but for 4 weeks in the second trial. Maximum and submaximum exercise capacity were assessed during a continuous progressive cycle ergometer exercise test performed at 70 rpm. In trial 1, plasma concentrations of lactate and beta-hydroxybutyrate were measured pre- and post-exercise. In trial 2, pre- and post-exercise plasma lactate were measured. The results of treatment with L-carnitine demonstrated no significant changes in maximum oxygen uptake (VO2max) or in maximum heart rate. In trial 1, there was a small improvement in submaximal performance as evidenced by a decrease in the heart-rate response to a work-load requiring 50% of VO2max. The more extensive trial 2 did not reproduce the significant result obtained in trial 1, that is, there was no significant decrease in heart rate at any given submaximal exercise intensity, under carnitine-supplemented conditions. Plasma metabolic concentrations were unchanged following L-carnitine, in both trials. It is concluded, that in contrast to other reports, carnitine supplementation may be of little benefit to exercise performance since the observed effects were small and inconsistent.
l-Carnitine (l-c), a well known physiological carrier across the inner mitochondrial membrane of activated long chain fatty acids and acceptor of acyl groups from acyl-CoA, has been recently synthesised industrially. This has made it possible to study the effects ofl-c loading (4 g·d−1 by mouth over a period of 2 weeks) on the aerobic and anaerobic performance of 6 long distance competitive walkers. As a result of the treatment: 1) mean total, free and esterified seruml-c both at rest and shortly after completing a 120 min walk at about 65% of the individual maximal aerobic power$$(\dot V_{O_{2\max } } )$$ were significantly increased; 2)$$V_{O_{2\max } }$$ increased 6%, from 54.5±3.7 (S.D.) to 57.8±47 mlO2·kg−1·min−1 (P<0.02); 3) blood lactate concentration (Lab ) as a consequence of short bouts of repeated exercise (series of 10, 15 and 20 jumps off both feet on a force platform) was unchanged; 4) heart rate, pulmonary ventilation, oxygen consumption, and respiratory quotient in the same conditions as for 1) were unchanged. It is concluded that, in trained athletes, as a consequence ofl-c loading$$\dot V_{O_{2\max } }$$ is slightly but significantly raised, probably as a result of an activation of substrate flow through the TCA cycle, whereas the lipid contribution to metabolism in prolonged submaximal exercise remains unchanged.
Article
Carnitine was detected at the beginning of this century, but it was nearly forgotten among biochemists until its importance in fatty acid metabolism was established 50 years later. In the last 30 years, interest in the metabolism and functions of carnitine has steadily increased. Carnitine is synthesized in most eucaryotic organisms, although a few insects (and most likely some newborn animals) require it as a nutritional factor (vitamin BT). Carnitine biosynthesis is initiated by methylation of lysine. The trimethyllysine formed is subsequently converted to butyrobetaine in all tissues; the butyrobetaine is finally hydroxylated to carnitine in the liver and, in some animals, in the kidneys (see Fig. 1). It is released from these tissues and is then actively taken up by all other tissues. The turnover of carnitine in the body is slow, and the regulation of its synthesis is still incompletely understood. Microorganisms (e.g., in the intestine) can metabolize carnitine to trimethylamine, dehydrocarnitine (beta-keto-gamma-trimethylaminobutyric acid), betaine, and possibly to trimethylaminoacetone. In some insects carnitine can be converted to methylcholine, presumably with trimethylaminoacetone as an intermediate (see Fig. 3). In mammals the unphysiological isomer (+) carnitine is converted to trimethylaminoacetone. The natural isomer (-)carnitine is excreted unchanged in the urine, and it is still uncertain if it is degraded in mammalian tissues at all (Fig. 2). The only firmly established function of carnitine is its function as a carrier of activated fatty acids and activated acetate across the inner mitochondrial membrane. Two acyl-CoA:carnitine acyltransferases with overlapping chain-length specificities have been isolated: one acetyltransferase taking part in the transport of acetyl and short-chain acyl groups and one palmitoyltransferase taking part in the transport of long-chain acyl groups. An additional octanoyltransferase has been isolated from liver peroxisomes. Although a carnitine translocase that allows carnitine and acylcarnitine to penetrate the inner mitochondrial membrane has been deduced from functional studies (see Fig. 5), this translocase has not been isolated as a protein separate from the acyltransferases. Carnitine acetyltransferase and carnitine octanoyltransferase are also found in the peroxisomes. In these organelles the enzymes may be important in the transfer of acyl groups, which are produced by the peroxisomal beta-oxidation enzymes, to the mitochondria for oxidation in the citric acid cycle. The carnitine-dependent transport of activated fatty acids across the mitochondrial membrane is a regulated process. Malonyl-CoA inh
Article
The effects of L-carnitine (900mg, p.o. daily) on exercise performance were studied in 12 patients with stable effort angina using a multistage treadmill exercise test. Exercise tests were performed at the end of the placebo period and after 4 and 12 weeks of carnitine therapy. While 12 patients experienced angina during treadmill tests in the placebo period, 2 patients were free of angina after treatment with carnitine. The mean exercise time was 11.4±0.7min (mean±SE) in the placebo period. This increased significantly to 12.2±0.5min (p<0.05) after 4 weeks and 12.8±0.5min (p<0.01) after 12 weeks of treatment with carnitine. The time required for 1mm ST depression to occur was 6.4±0.9min in the placebo period. This increased significantly to 7.6±0.9min (p<0.01) after 4 weeks and 8.8±1.0min after 12 weeks of treatment with carnitine. There was significantly less ST segment depression during the same exercise load after 12 weeks of treatment as compared with that in the placebo period (p<0.05). The heart rate and the pressure rate product at the same work load showed no significant difference among the 3 testing periods. The results of this study suggest that L-carnitine may improve exercise tolerance in patients with effort angina.
Article
This study investigated the effects of L-carnitine supplementation on muscle carnitine and glycogen content during submaximal exercise (EX). Triglycerides were evaluated by a fat feeding (90 g fat) and 3 h later subjects cycled for 60 min at 70% VO2max (CON). Muscle biopsies were obtained preexercise and after 30 and 60 min of EX. Blood samples were taken prior to and every 15 min of exercise. Subjects randomly completed two additional trials following 7 and 14 d of carnitine supplementation (6 g.d-1). During one of the two trials, subjects received 2000 units of heparin 15 min prior to EX to elevate FFA (CNhep); no heparin was administered during the other trial (CN). There were no differences in VO2, respiratory exchange ratio, heart rate, or g.min-1 of CHO and fat oxidized among the three trials. At rest serum total acid soluble (TASC) and free (FC) carnitine increased with supplementation (TASC; CON, 71.3 +/- 2.9; CN, 92.8 +/- 5.4; CNhep, 109.8 +/- 3.5 mumol.l-1) (FC; CON, 44.1 +/- 2.7; CN, 66.1 +/- 5.3; CNhep, 77.1 +/- 4.1 mumol.l-1). During EX, TASC remained stable, while FC decreased and short-chain acylcarnitine (SCAC) increased (P < 0.05). Muscle carnitine concentration at rest was unaffected by supplementation. During EX, muscle TASC did not change, FC decreased, and SCAC increased significantly in all three trials. Pre-EX and post-EX muscle glycogens were not different. Increased availability of serum carnitine does not result in an increase in muscle carnitine content nor does it alter lipid oxidation. It appears that there is an adequate amount of carnitine present within the mitochondria to support lipid oxidation.
Article
This study examined the effects of 14 days of L-carnitine supplementation on muscle and blood carnitine fractions, and muscle and blood lactate concentrations, during high-intensity sprint cycling exercise. Eight subjects performed three experimental trials: control I (CON I, Day 0), control II (CON II, Day 14), and L-carnitine (L-CN, Day 28). Each trial consisted of a 4-min ride at 90% VO2max, followed by a rest period of 20 min, and then five repeated 1-min rides at 115% VO2max (2 min rest between each). Following CON II, all subjects began dietary supplementation of L-carnitine for a period of 14 days (4 g/day). Plasma total acid soluble and free carnitine concentrations were significantly higher (p < .05) at all time points following supplementation. L-carnitine supplementation had no significant effect on muscle carnitine content and thus could not alter lactate accumulation during exercise.
Article
To examine the effects of L-carnitine supplementation on short high-intensity exercise, twenty male collegiate swimmers completed two trials separated by seven days. Each trial consisted of five 91.4 m (100 yd) swims with a two minute rest interval between each bout. Following the first trial subjects were evenly and randomly assigned to either an L-carnitine (LC) group or a placebo (PL) group. The LC group ingested 2 grams L-carnitine in a citrus drink twice daily for 7 days, while the PL group received only the citrus drink during the same time period. Performance times were recorded for each repeat during both trials. Blood samples (5 ml) were obtained from an antecubital vein 1 minute following the interval set. Blood pH, base excess (BE), lactate (LA), carnitine and carnitine fractions were measured. Total serum carnitine was significantly (p < 0.05) elevated (75.9 +/- 2.0 vs. 106.4 +/- 3.5 mumol.l-1) in the LC group following treatment, while the PL group was unchanged (79.5 +/- 2.8 vs. 77.6 +/- 5.3 mumol.l-1). Free and short-chain serum carnitine fractions were also increased (p < 0.05) in the LC group, but were not altered in the PL group. No differences in performance times were observed between trials or between groups. Blood pH, LA and BE revealed a similar response in both groups during each trial. Despite the elevation in serum L-carnitine and carnitine fractions, these results indicate that L-carnitine supplementation does not provide an ergogenic benefit during repeated bouts of high-intensity anaerobic exercise in highly trained swimmers.
Article
The effects of L-carnitine on the pyruvate dehydrogenase (PDH) complex and carnitine palmitoyl transferase (CPT) were studied in muscle of 16 long-distance runners (LDR). These subjects received placebo or L-carnitine (2 g orally) during a 4-week period of training. Athletes receiving L-carnitine showed a dramatic increase (P < 0.001) in the PDH complex activities. By contrast, the levels of CPT, both 1 and 2, were unchanged. No significant changes were observed after placebo administration. We previously reported [Huertas R. et al., Biochem. Biophys. Res. Commun. 188 (1992) 102-107] that L-carnitine induces an increase in the activities of complexes I, III and IV of the respiratory chain in muscle of LDR. Taken together, our data suggest that the improvement in (maximal oxygen consumption) VO2max observed in LDR after L-carnitine administration is based on these biochemical findings.
Article
Plasma carnitine "insufficiency," (plasma esterified carnitine to free carnitine ratio above 0.25) was found in 21 of 48 (43.8%) patients with mitochondrial myopathy, of whom 4 also showed both total and free carnitine deficiencies in plasma. In addition, plasma levels of SCAC and LCAC were higher in patients with mitochondrial myopathy than in controls (P < 0.001 and P < 0.01, respectively). Patients diagnosed as having plasma carnitine insufficiency or deficiency were treated with L-carnitine (50-200 mg/kg per day in four daily doses). Muscle weakness improved in 19 of 20 patients, failure to thrive in 4 of 8, encephalopathy in 1 of 9, and cardiomyopathy in 8 of 8 patients. Plasma carnitine "insufficiency" provides an additional clue to the diagnosis of mitochondrial myopathy and an indication for L-carnitine therapy.
Article
Carnitine plays a central role in fatty acid (FA) metabolism. It transports long-chain fatty acids into mitochondria for β-oxidation. Carnitine also modulates the metabolism of coenzyme-A (CoA). Several rationales have been forwarded in support of the potential ergogenic effects of oral carnitine supplementation. However the following arguments derived from established scientific observations may be forwarded: (i) carnitine supplementation neither enhances FA oxidation in vivo nor spares glycogen or postpones fatigue during exercise. Carnitine supplementation does not unequivocally improve performance of athletes; (ii) carnitine supplementation does not reduce body fat or help to lose weight; (iii) in vivo pyruvate dehydrogenase complex (PDC) is fully active already after a few seconds of intense exercise. Carnitine supplementation induces no further activation of PDC in vivo; (iv) despite an increased acetyl-CoA/free CoA ratio, PDC is not depressed during exercise in vivo and therefore supplementary carnitine has no effect on lactate accumulation; (v) carnitine supplementation per se does not affect the maximal oxygen uptake (V̇O2max); (vi) during exercise there is a redistribution of free carnitine and acylcarnitines in the muscle but there is no loss of total carnitine. Athletes are not at risk for carnitine deficiency and do not have an increased need for carnitine. Although there are some theoretical points favouring potential ergogenic effects of carnitine supplementation, there is currently no scientific basis for healthy individuals or athletes to use carnitine supplementation to improve exercise performance.
Article
The aim of this study was to test the hypothesis that individual differences in the response of maximal O(2) uptake (VO(2max)) to a standardized training program are characterized by familial aggregation. A total of 481 sedentary adult Caucasians from 98 two-generation families was exercise trained for 20 wk and was tested for VO(2max) on a cycle ergometer twice before and twice after the training program. The mean increase in VO(2max) reached approximately 400 ml/min, but there was considerable heterogeneity in responsiveness, with some individuals experiencing little or no gain, whereas others gained >1.0 l/min. An ANOVA revealed that there was 2.5 times more variance between families than within families in the VO(2max) response variance. With the use of a model-fitting procedure, the most parsimonious models yielded a maximal heritability estimate of 47% for the VO(2max) response, which was adjusted for age and sex with a maternal transmission of 28% in one of the models. We conclude that the trainability of VO(2max) is highly familial and includes a significant genetic component.
Article
This study was performed to identify a target population of claudicants for propionyl-L-carnitine treatment. Previous studies suggest that the efficacy of propionyl-L-carnitine in intermittent claudication is greater in patients with severe functional impairment than in those with mild walking disability. After run-in, 485 claudicant patients were randomized to placebo or propionyl-L-carnitine (1 g bid, p.o.) and then stratified on the basis of maximal walking distance (cutoff point 250 m) and maximal walking distance variability (cutoff point 25%). Treatment lasted 12 months. Walking capacity was assessed by treadmill and quality of life by a questionnaire exploring various aspects of daily life. In the target population, that is, patients who at baseline walked < or = 250 m and showed a maximal walking distance variability < or = 25%, per-protocol analysis showed that the effect of propinyl-L-carnitine was significantly greater than that with placebo for both maximal walking distance and initial claudication distance (ICD). In the intention-to-treat population, maximal walking distance increased by 62 +/- 14% on propionyl-L-carnitine and by 46 +/- 9% (p < 0.05) on placebo, while no difference between treatments was observed for ICD. The beneficial effect of propionyl-L-carnitine was confirmed when data of the target population were pooled with those of patients who at baseline walked < or = 250 m and showed a > 25% maximal walking distance < 50% variability. Actually, maximal walking distance increased by 98 +/- 16% in the propionyl-L-carnitine group and by only 54 +/- 10% in the placebo group (p < 0.01). The corresponding values for ICD were 99 +/- 21% and 51 +/- 8% (p < 0.05). For patients with baseline maximal walking distance > 250 m, no difference between treatments was observed. Claudicants with maximal walking distance < or = 250 m benefited from the use of propionyl-L-carnitine, with improvement in walking distance and quality of life. However, patients with mild functional impairment (i.e., walking distance > 250 m) showed no response to propionyl-L-carnitine.
Article
For many decades researchers did not consider that there were any differences between the genders in the metabolic response to exercise. As a result, nutritional recommendations and exercise training prescriptions have not considered the potential for gender specific responses. More recently, we and others have demonstrated that females oxidize proportionately more lipid and less carbohydrate during endurance exercise as compared to males. The oxidation of amino acids is similarly lower in females as compared to males during exercise. These gender differences are partially mediated by a higher estrogen concentration in females. Specific areas where there are gender differences in nutritional/supplement recommendations include carbohydrate (CHO) nutrition, protein requirements and creatine (CRM) supplementation. We have shown that females do not carbohydrate load in response to an increase in dietary carbohydrate when expressed as a percentage of total energy intake (i.e., 55-75%), however if they consume >8 g CHOxkg(-1)xd(-1), they show similar increases as compared to males. Top sport male and female athletes require somewhat more dietary protein as compared to sedentary persons. The maximal increase is approximately 100% for elite male athletes and approximately 50-60% for elite female athletes. Fortunately, most athletes habitually consume this level of protein intake. We have recently demonstrated that females show a lesser increase in lean body mass following acute CRM loading as compared to males. Females also did not show reductions in protein breakdown in response to CRM loading, whereas males did. In the future I expect that there will be further research from which gender specific nutritional/supplement recommendations can be made.
Article
Long-term administration of high oral doses of L-carnitine on the skeletal muscle composition and the physical performance has not been studied in humans. Eight healthy male adults were treated with 2 x 2 g of L-carnitine per day for 3 months. Muscle biopsies and exercise tests were performed before, immediately after, and 2 months after the treatment. Exercise tests were performed using a bicycle ergometer for 10 min at 20%, 40%, and 60% of the individual maximal workload (P(max)), respectively, until exhaustion. There were no significant differences between V(O(2)max), RER(max), and P(max) between the three time points investigated. At submaximal intensities, the only difference to the pretreatment values was a 5% increase in V(O(2)) at 20% and 40% of P(max) 2 months after the cessation of the treatment. The total carnitine content in the skeletal muscle was 4.10 +/- 0.82 micromol/g before, 4.79 +/- 1.19 micromol/g immediately after, and 4.19 +/- 0.61 micromol/g wet weight 2 months after the treatment (no significant difference). Activities of the two mitochondrial enzymes citrate synthase and cytochrome oxidase, as well as the skeletal muscle fiber composition also remained unaffected by the administration of L-carnitine. Long-term oral treatment of healthy adults with L-carnitine is not associated with a significant increase in the muscle carnitine content, mitochondrial proliferation, or physical performance. Beneficial effects of the long-term treatment with L-carnitine on the physical performance of healthy adults cannot be explained by an increase in the carnitine muscle stores.
Article
Despite an abundance of literature describing the basic mechanisms of action of L-carnitine metabolism, there remains some uncertainty regarding the effects of oral L-carnitine supplementation on in vivo fatty acid oxidation in normal subjects under normal conditions. It is well known that L-carnitine normalizes the metabolism of long-chain fatty acids in cases of carnitine deficiency. However, it has not yet been shown that L-carnitine influences the metabolism of long-chain fatty acids in subjects without disturbances in fatty acid metabolism. Therefore, we investigated the effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation by measuring 1-[(13)C] palmitic acid oxidation in healthy subjects before and after L-carnitine supplementation (3 x 1 g/d for 10 days). We observed a significant increase in (13)CO(2) exhalation. This is the first investigation to conclusively demonstrate that oral L-carnitine supplementation results in an increase in long-chain fatty acid oxidation in vivo in subjects without L-carnitine deficiency or without prolonged fatty acid metabolism.
Article
We used a combined tracer technique with the stable isotopes 13C and 15N to gain further insight into the metabolic changes that accompany supplementation of L-carnitine. The aim of the present study was to investigate whether L-carnitine supplementation can influence fat oxidation, protein turnover, body composition, and weight development in slightly overweight subjects. Twelve volunteers received an individual regular diet either without or with L-carnitine supplementation of 3 g/d for 10 days. Protein turnover and fat oxidation were investigated after administration of [15N]glycine and an [U-13C]algae lipid mixture. The 15N- and 13C-enrichment in urine and breath were measured by isotope ratio mass spectrometry. Body fat mass (BFM), total body water (TBW), and lean body mass (LBM) were calculated by using bioelectric impedance analysis. L-carnitine supplementation led to a significant increase in 13C-fat oxidation (15.8% v 19.3%; P = .021) whereas protein synthesis and breakdown rates (3.7 and 3.4 g/kg/d, respectively) remained unchanged, indicating that the increased dietary fat oxidation in slightly overweight subjects was not accompanied by protein catabolism.
Article
A strategy for detection of carnitine and acylcarnitines is introduced. This versatile system has four components: (1) isolation by protein precipitation/desalting and cation-exchange solid-phase extraction, (2) derivatization of carnitine and acylcarnitines with pentafluorophenacyl trifluoromethanesulfonate, (3) sequential ion-exchange/reversed-phase chromatography using a single non-end-capped C8 column, and (4) detection of carnitine and acylcarnitine pentafluorophenacyl esters using an ion trap mass spectrometer. Recovery of carnitine and acylcarnitines from the isolation procedure is 77-85%. Derivatization is rapid and complete with no evidence of acylcarnitine hydrolysis. Sequential ion-exchange/reversed-phase HPLC results in separation of reagent byproducts from derivatized carnitine and acylcarnitines, followed by reversed-phase separation of carnitine and acylcarnitine pentafluorophenacyl esters. Detection by MS/MS is highly selective, with carnitine pentafluorophenacyl ester yielding a strong product ion at m/z 311 and acylcarnitine pentafluorophenacyl ester fragmentation yielding two product ions: (1) loss of m/z 59 and (2) generation of an ion at m/z 293. To demonstrate this analytical strategy, phosphate buffered serum albumin was spiked with carnitine and 15 acylcarnitines and analyzed using the described protein precipitation/desalting and cation-exchange solid-phase extraction isolation, derivatization with pentafluorophenacyl trifluoromethanesulfonate, chromatography using the sequential ion-exchange/reversed-phase chromatography HPLC system, and detection by MS and MS/MS. Successful application of this strategy to the quantification of carnitine and acetylcarnitine in rat liver is shown.
Article
This investigation estimated the amount of variance in voluntary in vivo muscle performance that can be explained by relative myosin heavy chain (MHC) isoform expression. The role of the relative expression of these proteins in relation to in vitro force and velocity performance is well understood, but the in vivo model is less clear. Twenty-two men and women (mean +/- SD age, 27 +/- 6 years) performed isometric knee extensor actions in which peak force and rate of force development (RFD) were measured. The results of regression analysis showed that the inclusion of MHC IIb explained a significant (19.9%, p < 0.05) amount of variance in relative peak force (adjusted for muscle mass) and 14.1% of the variance in the first half of the rise phase of the force-time curve (RFD(0-50%)) (p < 0.1). The addition of MHC I into this model explained a significant (p < 0.05) amount of variance above that accounted for by MHC IIb in RFD (45.4%), RFD(0-50%) (50.8%), and RFD(50-100%) (second half of the rise phase of the force-time curve) (37.4%). Since the percentage of MHC IIb is reduced rather quickly with training, these data suggest that peak force may also be affected quickly by training. The percentage of MHC I has a longer course for change with training; therefore, it may be inferred that the greatest changes in RFD variables will likely occur during a longer course.
Article
The purpose of this investigation was to determine the effects of 3 wk of L-carnitine L-tartrate (LCLT) supplementation and post-resistance-exercise (RE) feeding on hormonal and androgen receptor (AR) responses. Ten resistance-trained men (mean+/-SD: age, 22+/-1 yr; mass, 86.3+/-15.3 kg; height, 181+/-11 cm) supplemented with LCLT (equivalent to 2 g of L-carnitine per day) or placebo (PL) for 21 d, provided muscle biopsies for AR determinations, then performed two RE protocols: one followed by water intake, and one followed by feeding (8 kcal.kg body mass, consisting of 56% carbohydrate, 16% protein, and 28% fat). RE protocols were randomized and included serial blood draws and a 1-h post-RE biopsy. After a 7-d washout period, subjects crossed over, and all experimental procedures were repeated. LCLT supplementation upregulated (P<0.05) preexercise AR content compared with PL (12.9+/-5.9 vs 11.2+/-4.0 au, respectively). RE increased (P<0.05) AR content compared with pre-RE values in the PL trial only. Post-RE feeding significantly increased AR content compared with baseline and water trials for both LCLT and PL. Serum total testosterone concentrations were suppressed (P<0.05) during feeding trials with respect to corresponding water and pre-RE values. Luteinizing hormone demonstrated subtle, yet significant changes in response to feeding and LCLT. In summary, these data demonstrated that: 1) feeding after RE increased AR content, which may result in increased testosterone uptake, and thus enhanced luteinizing hormone secretion via feedback mechanisms; and 2) LCLT supplementation upregulated AR content, which may promote recovery from RE.
Article
Both regular physical exercise and carnitine supplementation exert a role in energy metabolism and may improve endurance capacity. We investigated whether a combination of long-term carnitine ingestion and exercise training reveals any interactive effects on cytosolic fatty acid-binding protein (FABPc) expression and beta-hydroxyacyl CoA dehydrogenase (beta-HAD) activity in human skeletal muscle. Twenty-eight untrained healthy males randomly divided into four experimental groups: a placebo (CON; n = 7), exercise training (ET; n = 7, 40 min session(-1), five times per week at 60% VO2max), carnitine supplementation (CS; n = 7, 4 g day(-1)), and exercise training and carnitine supplementation (CT; n = 7). Before and after 6-week treatment, muscle biopsy samples were taken from the vastus lateralis. Nonesterified carnitine and acid-soluble acylcarnitine concentrations were increased in CT (P < 0.05), and serum triacylglycerol concentration was elevated almost twofold in ET and CT (P < 0.05). No interactive effects in FABPc expression were shown from any of treatment groups. Although FABPc increased by 54% in ET compared to CON, it failed to reach statistical significance. In addition, there was no change in FABPc expression from any of experimental groups. Similar trends with FABPc contents were demonstrated in beta-HAD activity. It is concluded that the combination of exercise training and L-carnitine supplementation does not augment in FABPc expression and beta-HAD activity in human skeletal muscle indicating that combined treatment does not exert additive effect in fat metabolism. Thus L-carnitine supplementation would be unlikely to be associated with the enhanced exercise performance.
Sports nutrition: A practice manual for professionals
• M Dunford
Dunford, M. (2006). Sports nutrition: A practice manual for professionals (4th ed.). Chicago: The American Dietetic Association.
Is glycine effective against elevated blood pressure? Current Opinion in Clinical Nutrition and Metabolic Care
• M E Hafidi
• I Perez
• G Banos
Hafidi, M.E., Perez, I., & Banos, G. (2006). Is glycine effective against elevated blood pressure? Current Opinion in Clinical Nutrition and Metabolic Care, 9, 26-31.
Influence of L-carnitine administration on maximal physical exercise
• L Vecchiet
• F Di Lisa
• G Pieralisi
• P Ripari
• R Menabò
• M A Giamberardino
• N Siliprandi
Vecchiet, L., Di Lisa, F., Pieralisi, G., Ripari, P., Menabò, R., Giamberardino, M.A., & Siliprandi, N. (1990). Influence of L-carnitine administration on maximal physical exercise. European Journal of Applied Physiology, 61, 486-490.