Article

Glycine Propionyl-L-carnitine Modulates Lipid Peroxidation and Nitric Oxide in Human Subjects

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Abstract

Objective: To determine the efficacy of glycine propionyl-L-carnitine (GPLC) to decrease lipid peroxidation, elevate nitric oxide, and improve blood lipid profiles in human subjects. Methods: Thirty untrained, normolipidemic subjects performed eight weeks of supervised aerobic exercise while supplementing GPLC at one of two doses (1 or 3 grams daily of PLC + glycine) or placebo, following random assignment in a double-blind manner. Fasting blood samples were analyzed at rest for malondialdehyde, nitric oxide, and lipids before and after the intervention. Results: Malondialdehyde was decreased (p<0.05) from pre- to post-intervention with 1 g GPLC (1.08+/-0.24 vs. 0.69+/-0.25 micromol.L (-1)) and 3 g GPLC (0.94+/-0.18 vs. 0.66+/-0.17 micromol.L (-1)), but did not change statistically (p>0.05) with placebo (1.12+/-0.21 vs. 1.03+/-0.23 micromol.L (-1)). Nitric oxide was increased (p<0.05) from pre- to post-intervention with 3 g GPLC (21.34+/-2.27 vs. 29.46+/-3.61 micromol.L (-1)), but did not change statistically (p>0.05) with 1 g GPLC (23.22+/-4.13 vs. 26.24+/-4.32 micromol.L (-1)) or placebo (24.31+/-3.90 vs. 26.14+/-4.11 micromol.L (-1)). No main effects or interaction effects were noted for blood lipids (p>0.05). Conclusion: GPLC supplementation combined with eight weeks of aerobic exercise decreases lipid peroxidation and elevates nitric oxide, but does not further improve blood lipid profiles in normolipidemic subjects.

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... The novel ingredient Glycine Propionyl-L-Carnitine (GlycoCarn ® ) has been reported recently to improve repeated sprint cycle performance and reduce the blood lactate response to exercise when consumed in a single dosage of 4.5 grams [12]. We have also reported an increase in nitric oxide (measured as nitrate/nitrite) when subjects received GlycoCarn ® at a daily dosage of 4.5 grams for either four [13] or eight [14] weeks. Lastly, several antioxidant agents have been reported to decrease the oxidative stress response to exercise [15], and are believed to promote exercise recovery; hence, these are often included within some pre-workout supplements. ...
... However , even if this were the case, the main findings of no difference in performance measures may overshadow any potential effects for muscle pump. Our findings for no change in NOx with GlycoCarn ® refute our initial work, in which we have noted an increase in both resting [14] and stress-induced NOx [13]. The discrepancies in findings may be due to the fact that in the present design we simply provide a single serving of GlycoCarn ® prior to exercise, whereas our prior work involved four [13] or eight [14] weeks of GlycoCarn ® treatment. ...
... Our findings for no change in NOx with GlycoCarn ® refute our initial work, in which we have noted an increase in both resting [14] and stress-induced NOx [13]. The discrepancies in findings may be due to the fact that in the present design we simply provide a single serving of GlycoCarn ® prior to exercise, whereas our prior work involved four [13] or eight [14] weeks of GlycoCarn ® treatment. Likewise, our data are in opposition to the work of Jacobs and colleagues [12] who recently reported an improvement of 2.6-15% in high intensity cycle sprint performance with 4.5 grams of GlycoCarn ® compared to a placebo. ...
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We compared Glycine Propionyl-L-Carnitine (GlycoCarn(R)) and three different pre-workout nutritional supplements on measures of skeletal muscle oxygen saturation (StO2), blood nitrate/nitrite (NOx), lactate (HLa), malondialdehyde (MDA), and exercise performance in men. Using a randomized, double-blind, cross-over design, 19 resistance trained men performed tests of muscular power (bench press throws) and endurance (10 sets of bench press to muscular failure). A placebo, GlycoCarn(R), or one of three dietary supplements (SUPP1, SUPP2, SUPP3) was consumed prior to exercise, with one week separating conditions. Blood was collected before receiving the condition and immediately after exercise. StO2 was measured during the endurance test using Near Infrared Spectroscopy. Heart rate (HR) and rating of perceived exertion (RPE) were determined at the end of each set. A condition effect was noted for StO2 at the start of exercise (p = 0.02), with GlycoCarn(R) higher than SUPP2. A condition effect was also noted for StO2 at the end of exercise (p = 0.003), with SUPP1 lower than all other conditions. No statistically significant interaction, condition, or time effects were noted for NOx or MDA (p > 0.05); however, MDA decreased 13.7% with GlycoCarn(R) and increased in all other conditions. Only a time effect was noted for HLa (p < 0.0001), with values increasing from pre- to post-exercise. No effects were noted for HR, RPE, or for any exercise performance variables (p > 0.05); however, GlycoCarn(R) resulted in a statistically insignificant greater total volume load compared to the placebo (3.3%), SUPP1 (4.2%), SUPP2 (2.5%), and SUPP3 (4.6%). None of the products tested resulted in favorable changes in our chosen outcome measures, with the exception of GlycoCarn(R) in terms of higher StO2 at the start of exercise. GlycoCarn(R) resulted in a 13.7% decrease in MDA from pre- to post-exercise and yielded a non-significant but greater total volume load compared to all other conditions. These data indicate that 1) a single ingredient (GlycoCarn(R)) can provide similar practical benefit than finished products containing multiple ingredients, and 2) while we do not have data in relation to post-exercise recovery parameters, the tested products are ineffective in terms of increasing blood flow and improving acute upper body exercise performance.
... Recent studies assessed the effect of GPLC as a NO donor in sport exercise with different conclusions . First, Bloomer et al. [65] showed an increase in plasma NO metabolites (nitrate/nitrite) in active males after GPLC supplementation (4.5 g Á day -1 · 4 weeks). These findings were confirmed in the second study by the same research group. [66] However, contrary results were found in the third study published by Bloomer et al. [11] They showed that an acute dose (4.5 g) of GPLC did not increase NO markers. This controversy was attributed to the fact that in the latter study, [11] a single dose of GPLC was provided prior to exercise, whereas in the first two studies, GPLC was a ...
... This controversy was attributed to the fact that in the latter study, [11] a single dose of GPLC was provided prior to exercise, whereas in the first two studies, GPLC was administered for 4 and 8 weeks, respective- ly. [65,66] Nevertheless, an important limitation of the studies performed by Bloomer et al. [11,65,66] was the lack of evidence indicating some benefit of GPLC in exercise performance. Two recent studies assessed this issue showing different results. ...
... This controversy was attributed to the fact that in the latter study, [11] a single dose of GPLC was provided prior to exercise, whereas in the first two studies, GPLC was administered for 4 and 8 weeks, respective- ly. [65,66] Nevertheless, an important limitation of the studies performed by Bloomer et al. [11,65,66] was the lack of evidence indicating some benefit of GPLC in exercise performance. Two recent studies assessed this issue showing different results. ...
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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.
... These findings were confirmed in the second study by the same research group. [66] However, contrary results were found in the third study published by Bloomer et al. [11] They showed that an acute dose (4.5 g) of GPLC did not increase NO markers. This controversy was attributed to the fact that in the latter study, [11] a single dose of GPLC was provided prior to exercise, whereas in the first two studies, GPLC was administered for 4 and 8 weeks, respectively. ...
... This controversy was attributed to the fact that in the latter study, [11] a single dose of GPLC was provided prior to exercise, whereas in the first two studies, GPLC was administered for 4 and 8 weeks, respectively. [65,66] Nevertheless, an important limitation of the studies performed by Bloomer et al. [11,65,66] was the lack of evidence indicating some benefit of GPLC in exercise performance. Two recent studies assessed this issue showing different results. ...
... This controversy was attributed to the fact that in the latter study, [11] a single dose of GPLC was provided prior to exercise, whereas in the first two studies, GPLC was administered for 4 and 8 weeks, respectively. [65,66] Nevertheless, an important limitation of the studies performed by Bloomer et al. [11,65,66] was the lack of evidence indicating some benefit of GPLC in exercise performance. Two recent studies assessed this issue showing different results. ...
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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.
... 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%. ...
... Therefore it is suggested that an increase in plasma levels of Lcitrulline can also indicate an increase in NO synthesis (73). Accordingly, Liu et al (66) assessed plasma levels of L-citrulline after dietary L-arginine supplementation. They concluded that L-arginine did not increase levels of L-citrulline in comparison with a placebo. ...
... In Studies II and III of this thesis it was shown that inorganic nitrate supplementation did not alter heart rate response and blood lactate concentration during exercise tests. These results were consistent with other previous studies indicating that dietary L-arginine and inorganic nitrate have no effect on heart response and blood lactate during exercise (66,74,82,(84)(85)(86)(87)(88)(89). ...
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... It is created with the esterification of propionic acid and carnitine and has been used within dietary supplements as glycine propionyl-l-carnitine (GPLC). Both PLC [20][21][22] and GPLC [23] have been reported to improve physical function, with increased nitric oxide metabolites noted in studies using both PLC [24] and GPLC [25,26]. When considering carnitine supplementation, one should bear in mind that dosages listed typically include the total mass of the salt and that absorption characteristics differ with each carnitine form. ...
... We initially reported that oral intake of GPLC at a dosage of 4.5 g/day results in increased plasma nitric oxide, as measured by the metabolites nitrate/nitrite, in resistance-trained men following a 4-week intervention [25]. These findings have been further supported in previously sedentary men and women following an 8 week intervention of GPLC and aerobic exercise [26]. Similarly, postexercise plasma nitric oxide was increased in trained soccer players treated with 3 or 4 g of l-carnitine and fruit juice 1 h before a treadmill run to exhaustion [59]. ...
... The potential vasodilatory properties of carnitine may be one mechanism responsible for the increased muscle force output previously reported following carnitine supplementation [97]. This is partially supported by the findings of increased nitrate + nitrite in response to carnitine supplementation (in the form for GPLC) [25,26]. Furthermore, Spiering et al. observed reduced muscle oxygenation after upper arm occlusion in their treatment group supplemented with 2 g/day of LCLT for 23 days [100]. ...
... Surprisingly, the differences in NO concentrations between the studied time points in this study were nonsignificant but tended to increase (P = 0.07). Earlier studies in men indicated that administration of LC either through oral or parenteral routes provoked NO bioavailability (52,53). This discrepancy might be due to the differences in the dose (around 1 g/ram), frequency (single dose), and route of administration (IV) of LC treatment in this study compared to the aforementioned reports. ...
... This discrepancy might be due to the differences in the dose (around 1 g/ram), frequency (single dose), and route of administration (IV) of LC treatment in this study compared to the aforementioned reports. The selected dose might be insufficient to elevate the NO concentration, as 1 g of LC may be enough for exerting antioxidant capacity and protecting the cellular components against lipid peroxidation (53), as proposed by the obtained results; whereas, for the elevation of NO, LC should be administered at a dose of at least 3 g daily (52). Second, the role of LC in mitochondrial functions should be considered, through fatty acid transfer, energy production, and removal of excess acyl-CoA, promoting optimum cellular functions in the whole body organs including heart and testes (26,42,48). ...
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Heat stress (HS) diminishes the testicular antioxidant defense systems, which adversely affects the testicular blood perfusion. Improving the testicular hemodynamics during HS conditions is of great impact on the whole reproductive performance in rams. The current work aimed to evaluate the ameliorative effects of L-carnitine (LC) on the testicular blood flow and echotextures as well as on the total antioxidants (TAC) and nitric oxide (NO) concentrations in the serum during HS conditions in rams. Testicular blood flow was evaluated through scanning of the supra-testicular artery (STA) spectral patterns through pulsed Doppler ultrasonography [peak systolic velocity (PI), end-diastolic velocity (EDV), time average maximum velocity (TAMAX), resistive index (RI), and pulsatility index (PI)], while the echotexture assessment of testicular parenchyma was performed by a computerized software program. Moreover, TAC and NO concentrations were assayed colorimetrically using the spectrophotometer. There were significant decreases (P < 0.05) in values of PSV at 48 and 168 h (23.45±0.39 cm/s, 23.37±1.41 cm/s, respectively), and TAMAX at 1, 48, and 168 h (17.65±0.95 cm/s, 17.5±0.13 cm/s, 16.9±1.05 cm/s, respectively) after LC administration compared to just before administration (31.92±1.13 cm/s, 21.58±0.92 cm/s, respectively). Values of RI and PI of the examined STA significantly decreased, especially at 1 h for RI (0.45±0.02), and 1 and 48 h for PI (0.66±0.06, 0.65±0.05, respectively) after LC treatment to 0 h (0.55±0.03, 0.84±0.06, respectively). Whereas the EDV values didn’t show any significant (P < 0.05) changes in all the experimental time points. There were significant (P < 0.05) increases in the values of pixel intensity of the testicular parenchyma, especially at 1 and 168 h (78.71±2.50, 88.56±4.10, respectively) after LC administration, compared to just before administration (69.40±4.75). Serum NO levels tend to increase after administration LC administration (P = 0.07) concerning just before administration. While TAC values showed significant gradual increases and reached the highest values at 168 h (2.75±0.58 mM/L) after LC administration, compared to 0 h (1.12±0.05 mM/L). In conclusion, exogenous L-carnitine administration ameliorates testicular hemodynamic disruptions, as measured by spectral Doppler ultrasonography, via augmentation of the rams’ total antioxidant capacity under heat stress conditions.
... ALCAR can upregulate levels of Nrf2 and the antioxidants glutathione (GSH) and heme oxygenase 1 (HO-1) and can decrease markers of oxidative stress (13)(14)(15)(16)(17). A number of human trials (non-ALS) that tested supplementation with LC (18)(19)(20)(21)(22)(23)(24)(25) or PLC (26)(27)(28)(29) reported lowered blood biomarkers of oxidative stress. In trials with ALCAR supplementation, the effect was less clear (30,31). ...
... Carnitine supplements are typically taken orally but have been administered by intramuscular or intravenous injections. The clinical trial showing some possible benefit of ALCAR in PALS used 1000 mg ALCAR by mouth three times per day (55); similar total daily doses of LC (7,67,88) and PLC (26)(27)(28)69) have been used in other human clinical trials. The optimal dosage or form of carnitine for use in ALS is not clear; however, it is unlikely that individual doses over 1000 mg will lead to greater absorption (89,90). ...
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https://www.tandfonline.com/doi/full/10.1080/21678421.2020.1726565
... In fact, all published studies in this area indicate that oral administration of arginine in dosages tolerated by the gastrointestinal system are not effective in producing endothelium-dependent vasodilation or in elevating NO levels345. It has been demonstrated that short term administration of an oral carnitine compound, glycine propionyl- L-carnitine (GPLC), produces significantly elevated levels of nitric oxide metabolites at rest in both sedentary and trained persons [6,7]. Increased nitric oxide activity has also been demonstrated in resistance trained persons with reactive hyperaemia testing, an assessment used in clinical settings that, to some degree, simulates the physical stresses encountered during very intense exercise such as resistance training [7]. ...
... The only food supplement shown to directly affect the production of NO is GPLC. It has been shown that 28 d GPLC at 4.5 g/d produces significantly elevated levels of nitrites and nitrates [6,7]. Acute supplementation at 4.5 g resulted in significant improvements in cycling power output [8], but in the current study long-term supplementation of GPLC at that daily intake was not associated with power enhancement. ...
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It has been demonstrated that acute GPLC supplementation produces enhanced anaerobic work capacity with reduced lactate production in resistance trained males. However, it is not known what effects chronic GPLC supplementation has on anaerobic performances or lactate clearance. The purpose of this study was to examine the long-term effects of different dosages of GPLC supplementation on repeated high intensity stationary cycle sprint performance. Forty-five resistance trained men participated in a double-blind, controlled research study. All subjects completed two testing sessions, seven days apart, 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. Following completion of the second test session, the 45 subjects were randomly assigned to receive 1.5 g, 3.0 g, or 4.5 g GPLC per day for a 28 day period. Subjects completed a third test session following the four weeks of GPLC supplementation using the same testing protocol. Values of peak power (PP), mean power (MP) and percent decrement of power (DEC) were determined per bout and standardized relative to body mass. Heart rate (HR) and blood lactate (LAC) were measured prior to, during and following the five sprint bouts. There were no significant effects of condition or significant interaction effects detected for PP and MP. However, results indicated that sprint bouts three, four and five produced 2 - 5% lower values of PP and 3 - 7% lower values of MP with GPLC at 3.0 or 4.5 g per day as compared to baseline values. Conversely, 1.5 g GPLC produced 3 - 6% higher values of PP and 2 -5% higher values of MP compared with PL baseline values. Values of DEC were significantly greater (15-20%) greater across the five sprint bouts with 3.0 g or 4.5 g GPLC, but the 1.5 g GPLC supplementation produced DEC values -5%, -3%, +4%, +5%, and +2% different from the baseline PL values. The 1.5 g group displayed a statistically significant 24% reduction in net lactate accumulation per unit power output (p < 0.05). The effects of GPLC supplementation on anaerobic work capacity and lactate accumulation appear to be dosage dependent. Four weeks of GPLC supplementation at 3.0 and 4.5 g/day resulted in reduced mean values of power output with greater rates of DEC compared with baseline while 1.5 g/day produced higher mean values of MP and PP with modest increases of DEC. Supplementation of 1.5 g/day also produced a significantly lower rate of lactate accumulation per unit power output compared with 3.0 and 4.5 g/day. In conclusion, GPLC appears to be a useful dietary supplement to enhance anaerobic work capacity and potentially sport performance, but apparently the dosage must be determined specific to the intensity and duration of exercise.
... In the total 4.5 g/d dosage of GPLC, the actual PLC content was equal to 3 g and the glycine content was equal to 1044 mg (the remainder of the capsule consisted primarily of cellulose). The short term (8–9 week) safety of GPLC supplementation at the dosage provided (4.5 g/d) was established in our initial work [18], where we noted no adverse changes in subjects' complete blood count or blood chemistry panel data. Capsules were manufactured by Jarrow Formulas (Los Angeles, CA), were identical in appearance, and were provided to subjects in unlabeled bottles every two weeks. ...
... While the fitness industry is inundated with advertisements for such products, the scientific data are scant. We have recently demonstrated an increase in plasma NOx in healthy sedentary subjects following oral treatment with a novel carnitine agent, glycine propionyl-L-carnitine (GPLC; [18]). This finding extends recent work of Lofreddo et al. [19] who reported an increase in blood NOx in response to 6 grams per day of PLC given via IV infusion to patients with peripheral arterial disease. ...
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We have recently demonstrated that oral intake of glycine propionyl-L-carnitine (GPLC) increases plasma nitrate/nitrite (NOx), a surrogate measure of nitric oxide production. However, these findings were observed at rest, and in previously sedentary subjects. In the present study, we sought to determine the impact of oral GPLC on plasma NOx at rest and in response to a period of reactive hyperemia in resistance trained men. Using a double blind, crossover design, 15 healthy men (24 +/- 4 years) were assigned to GPLC (3 g/d PLC + 1044 mg glycine) and a placebo in random order, for a four-week period, with a two-week washout between condition assignment. Blood samples were taken from subjects at rest and at 0, 3, and 10 minutes following an ischemia-reperfusion protocol (six minutes of upper arm cuff occlusion at 200 mmHg followed by rapid reperfusion with cuff removal). Blood samples were taken from a forearm vein from the same arm used for the protocol and analyzed for total nitrate/nitrite. Data are presented as mean +/- SEM. A condition main effect (p = 0.0008) was noted for NOx, with higher values in subjects when using GPLC (45.6 +/- 2.8 mumol.L-1) compared to placebo (34.9 +/- 1.2 mumol.L-1). No time main effect was noted (p = 0.7099), although values increased approximately 12% from rest (37.7 +/- 2.7 mumol.L-1) to a peak at 10 minutes post protocol (42.3 +/- 3.3 mumol.L-1). The interaction effect was not significant (p = 0.8809), although paired time contrasts revealed higher values for GPLC compared to placebo at 3 (48.2 +/- 6.7 vs. 34.9 +/- 2.4 mumol.L-1; p = 0.033) and 10 (48.8 +/- 5.9 vs. 35.7 +/- 2.1 mumol.L-1; p = 0.036) minutes post protocol, with non-statistically significant differences noted at rest (41.8 +/- 4.5 vs. 33.6 +/- 2.5 mumol.L-1; p = 0.189) and at 0 minutes (43.6 +/- 5.1 vs. 35.4 +/- 2.7 mumol.L-1; p = 0.187) post protocol. An analysis by subject (collapsed across time) indicated that 11 of the 15 subjects experienced an increase in NOx with GPLC treatment. These findings indicate that short-term oral GPLC supplementation can increase NOx in resistance trained men. However, as with many dietary supplements, there exist both "responders" and "non-responders" to treatment. Future work may focus on the mechanisms for the discrepancy in response to GPLC supplementation for purposes of NOx elevation.
... Carnitine is produced naturally in the body from the amino acids lysine and methionine and the form of L-carnitine (L-Ca) is considered a biologically active substance. Its vital role is an essential co-factor in transporting long-chain fatty acids to the inner membrane of mitochondria (lipids metabolism) and thus in energy production as well as improve neuronal metabolism which helps in the treatment of certain diseases such as Alzheimer's, obesity, diabetes and heart disease (Bloomer et al., 2009) . Due to the multiple benefits of CoQ10 and L-Ca, the potential therapeutic advantages and the ease of synthesis, whether by biological or chemical methods, have made it one of the special substances of high demand in the market along with other compounds such as alpha lipoic acid, vitamin C and vitamin E (Golbidi et al., 2011;Shukla and Dubey, 2018). ...
... CoQ10 is well known as a super-vitamin (vitamin Q) that exhibits potent antioxidant ability, free radical scavenger, helps regenerating of vitamin E, supports healthy energy levels, improves health in case of many disease (Varela-López et al., 2016). Furthermore, L-carnitine (L-Ca) exhibits potent antioxidant ability, free radical scavenger, helps in energies body, and the treatment of certain diseases (Bloomer et al., 2009). ...
... The main role of PLC is that helps the body to produce energy. Furthermore, PLC is known to decrease lipid peroxidation or the process wherein lipid membranes are attacked by free radicals, causing cellular damage [3,34]. Also helps increase the production of nitric oxide, which promotes blood circulation and regulates blood pressure [2]. ...
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The purpose of this study was to perform a systematic review and summarize the current literature regarding L-carnitine and the potential role of sports especially in distance athletes. L-carnitine is a naturally occurring compound that plays an important role in mitochondrial β-oxidation. The main role of L-carnitine is to promote weight loss by increasing calorie expenditure. Also, L-carnitine plays an important role on recovery from strenuous exercise and may help to achieve quicker recovery and reduce muscle soreness. Finally, the results indicate that there is uncertainty in regards to how L-carnitine helps athletic performance. There are only three studies in the literature showing beneficial effects of L-carnitine on performance of athletes. On the contrary, three other studies have shown no effect of L-carnitine on performance.
... Table 2A summary of studies on potential protective effects of L-carnitine against muscular I/R injury. [72] Resistancetrained men Muscle GPLC 4.5 g/day for 4 weeks Blood lactate, MDA, F2-iso, H2O2, xanthine oxidase activity, hypoxanthine, total and oxidized glutathione, and trolox-equivalent antioxidant capacity assessment Oral GPLC supplementation does not attenuate the increase in these biomarkers ...
Article
Ischemia-reperfusion (I/R) injury plays important role in morbidity and mortality in several pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, and circulatory arrest. An imbalance in metabolic supply and tissue's demand during ischemia results in profound tissue hypoxia and microvascular dysfunction. Subsequently, reperfusion further results in activation of immune responses and cell death programs. l-carnitine and its derivatives have been administered to improve tolerance against I/R injury in various tissues. Anti-ischemic properties of l-carnitine and its derivative in neuromuscular organs will be reviewed here at the light of pertinent results from basic and clinical researches. All available in vitro and in vivo studies, patents, clinical trials, and meeting abstracts in English language that examined the protective effects of l-carnitine against I/R induced injury in neuromuscular organs were reviewed. Materials were obtained by searching ELSEVIER, web of knowledge, PubMed, Scopus, clinical trials, and Cochrane database of systematic reviews. Although animal studies on central nervous system and some human studies on muscular system were in favors of effects of l-carnitine against I/R injury, however, more clinical trials are needed to clarify the clinical importance of l-carnitine as a treatment option to manage I/R-induced injury of neuromuscular system. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
... In this respect, CoQ10 has antioxidant potential and acts as a free radical scavenger that can improve animal health status (Varela-López et al., 2016). In addition, LC has the same antioxidants potential as CoQ10 (Bloomer et al., 2009), and can increase body energy balance. In ruminants, animals expose to very stressful periods during pregnancy and lactation due to high levels of oxidative damage, so they want to consume more enzymatic and non-enzymatic antioxidants (Castillo et al., 2005). ...
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The present study aimed to investigate the effect of Coenzyme Q10 (CoQ10) and L-carnitine (LC) on the reproductive performance, milk production, and health status of lactating cows. Multiparous Friesian cows (n=21) with 2-4 parities at late pregnancy were divided into three groups (7 in each). Cows in the first group were fed a basal ration (control, G1), while those in G2 and G3 were fed the same diet and received an oral dose of 1.5 mg CoQ10 and 100 mg LC per kg BW, respectively. Treatment lasted for 30 d prepartum to 120 d postpartum. Results show that LC increased (P<0.05) daily milk yield, body weight of dams and their calves at calving, serum total proteins, albumin, globulin, glucose, total lipids, total cholesterol, triglycerides, triiodothyronine (T3), insulin-like growth factor-I (IGF-I), insulin, glutathione (GSH), and superoxide dismutase (SOD) activity, erythrocyte, and leukocyte counts, as well as hemoglobin and packed cell volume (PCV) concentration. On the other hand, placental drop, uterine involution, days to cervical closer, postpartum 1st estrus interval, service period and the number of services/conception, days open, calving interval, serum cortisol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were decreased (P<0.05) by LC treatment. Treatment of CoQ10 followed the beneficial effects of LC treatment on most parameters studied. In conclusion, oral pre-and post-partum administration of LC (100 mg/kg BW) may use as a useful tool for improving milk production and reproductive efficiencies, energy metabolism, and antioxidant status of lactating cows during the early postpartum period
... The primary purpose of this L-carnitine is to create energy in the body generally. It also decreases the peroxidation of lipids, in which the free radicals generally attack the lipid membrane, which results in the damaging of cells [19]. The other major function of propionyl L-carnitine is to generate nitric oxide in the body, which helps maintain blood pressure and ensures the proper supply of blood to the muscles [20]. ...
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L-carnitine, an amino acid derivative, is naturally synthesized in human bodies in very few amounts and can also be taken as a dietary supplement. This amino acid derivative is very popular among various medical drugs and in gym dietary nutrients. In addition, it plays an intense role in brain functioning, in the generation of energy, known to provide more oxygen for muscles and improve stamina, strength, and power. Besides its various applications, several myths are reported but do not have adequate scientific evidence to date. This review aims to investigate the effects of L-Carnitine as a drug and the myths related to it. This paper contains significant facts about L-Carnitine, i.e., its benefits, side effects, and myths. It will give a clear idea about L-Carnitine and its applications. This review paper discussed the characteristics of L-carnitine, which finds vast applications and benefits. This review paper has also discussed the most recent finding of L-Carnitine promoting atherosclerosis by way of trimethylamine N-oxide Meta organismal pathway along with its solution on trial bases. L-Carnitine has many applications in the clinic and personalized medicine; hence, it has an excellent scope for future works, which requires the trials of its applications on a large scale.
... While these hypotheses are interesting, there exists no evidence that such events take place, at least as applied to human subjects consuming oral dietary supplements purported to increase nitric oxide. Even for dietary ingredients reported to result in measurable increases in plasma nitrate/nitrite, such as glycine propionyl-L-carnitine [23,24], additional studies which include functional, rather than just biochemical outcomes, are needed. Without such studies, there is no way of knowing what, if any, physiological effect an increase in circulating nitrate/nitrite has within an in vivo system. ...
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Betaine, beetroot juice, and supplemental nitrate have recently been reported to improve certain aspects of exercise performance, which may be mechanistically linked to increased nitric oxide. The purpose of the present study was to investigate the effect of betaine supplementation on plasma nitrate/nitrite, a surrogate marker or nitric oxide, in exercise-trained men. We used three different study designs (acute intake of betaine at 1.25 and 5.00 grams, chronic intake of betaine at 2.5 grams per day for 14 days, and chronic [6 grams of betaine per day for 7 days] followed by acute intake [6 grams]), all involving exercise-trained men, to investigate the effects of orally ingested betaine on plasma nitrate/nitrite. Blood samples were collected before and at 30, 60, 90, and 120 min after ingestion of 1.25 and 5.00 grams of betaine (Study 1); before and after 14 days of betaine supplementation at a dosage of 2.5 grams (Study 2); and before and after 7 days of betaine supplementation at a dosage of 6 grams, followed by acute ingestion of 6 grams and blood measures at 30 and 60 min post ingestion (Study 3). In Study 1, nitrate/nitrite was relatively unaffected and no statistically significant interaction (p = 0.99), dosage (p = 0.69), or time (p = 0.91) effects were noted. Similar findings were noted in Study 2, with no statistically significant interaction (p = 0.57), condition (p = 0.98), or pre/post intervention (p = 0.17) effects noted for nitrate/nitrite. In Study 3, no statistically significant changes were noted in nitrate/nitrite between collection times (p = 0.97). Our data indicate that acute or chronic ingestion of betaine by healthy, exercise-trained men does not impact plasma nitrate/nitrite. These findings suggest that other mechanisms aside from increasing circulating nitric oxide are likely responsible for any performance enhancing effect of betaine supplementation.
... Although this was unexpected because of the relatively short half-life of the molecule, it is possible that chronic use of the gel (7 days in this study) may have led to elevated levels of nitrate/nitrite. In a similar manner, we have noted an approximate 38% increase in resting levels of nitrate/nitrite when providing men and women the dietary supplement glycine propionyl Lcarnitine at a dosage of 4.5 gÁd 21 for 8 weeks, in conjunction with an aerobic exercise program (7). ...
Article
Nitric oxide dietary supplements are popular within the sport community. Our recent work involving the oral intake of 2-nitrooxy ethyl 2-amino 3-methylbutanoate demonstrated an approximately 6.7% increase in circulating nitrate/nitrite. However, no measures of exercise performance were obtained. The present study used a topical form of this molecule to determine the impact on exercise performance and blood nitrate/nitrite. Fourteen resistance trained men (24 ± 1 years old) reported to the laboratory on 2 occasions to undergo exercise testing, which consisted of arm curl isometric force and muscular endurance (3 sets to fatigue using 80, 65, and 50% of 1 repetition maximum [1RM]: total of 9 sets). The gel (2-nitrooxy ethyl 2-amino 3-methylbutanoate; mixed in tea tree oil) or placebo (tea tree oil) was applied topically by the subjects for 7 days before each test day, with 7-10 days separating the randomly ordered conditions. Blood samples, arm circumference, and perceived "muscle pump" were taken before and immediately after exercise on both test days. The heart rate and perceived exertion were measured after each set. No statistically significant differences were noted between conditions for performance variables (p > 0.05). However, when using a load of 50% of 1RM, 6.2% more repetitions were performed when using the gel as compared with when using the placebo; 19.9% more repetitions were performed by 8 subjects noted to be "responders" to gel treatment. Blood lactate and muscle pump significantly increased with exercise (p < 0.0001) but were not different between conditions (p > 0.05). Minimal change was noted in nitrate/nitrite, and the heart rate and perceived exertion were nearly identical between conditions (p > 0.05). These findings indicate that 2-nitrooxy ethyl 2-amino 3-methylbutanoate gel has a modest (6.2%), nonstatistically significant effect on exercise performance, in particular when using a load of 50% 1RM-with greater benefit noted in selected individuals. Studies inclusive of a larger sample size are needed to extend these initial findings.
... In patients with peripheral arterial disease, decreased levels of plasma NO x augment after repeated administration of propionyl-L-carnitine, and the plasma concentrations of the oxidative stress biomarker 8hydroxy-2-deoxy-2-deoxyguanosine and plasma NO x are inversely correlated (Loffredo et al. 2007). Plasma NO x of healthy subjects is increased following oral treatment with glycine propionyl-L-carnitine (Bloomer et al. 2009). The physiological mechanisms leading to an increased systemic availability of NO described in the above studies after administration of carnitine and its esters remain to be elucidated. ...
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This study investigated the protective effect of two nitric oxide synthase inhibitors N(omega)-Nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.p.) and aminoguanidine (AG, 400 mg/kg i.p.), and an antioxidant acetyl-L-carnitine (ALC, 250 mg/kg i.p., once daily for five days) against radiation-induced damage in Wistar rats. Blood samples were collected 6 hrs after whole-body irradiation with 8 Gy. Plasma concentrations of nitrite+nitrate (NOx) and malondialdehyde (MDA) were measured by high-performance liquid chromatography. A single injection of L-NAME one hour before exposure effectively prevented the radiation-induced elevation of plasma NO(x) and it reduced 2.6-fold the risk for death during the subsequent 30-day period. Pretreatment with ALC prevented the radiation-induced increase in plasma MDA and it had similar effect on mortality as L-NAME did. Presumably due to its short half-life, the partially iNOS-selective inhibitor and antioxidant AG given in a single dose before exposure did not attenuate MDA and NO(x) and it failed to significantly improve the 30-day survival. In conclusion, pretreatment with both the nonspecific NOS inhibitor L-NAME and the antioxidant ALC markedly reduce mortality to radiation sickness in rats. The radioprotective effect may be directly related to effective attenuation of the radiation-induced elevation of NO production by L-NAME and of oxidative stress by ALC.
... It transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so they can be broken down through beta-oxidation to acetyl CoA to obtain usable energy via the citric acid cycle. L-carnitine, the biologically active form, has also been found to increase nitric oxide production when combined with aerobic exercise (Bloomer et al., 2009). This relaxes the smooth muscles of the blood vessels, causing them to widen, allowing more blood to flow through. ...
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Good nutrition and strenuous exercise are the two pillars of sports performance. Feeding stimulates protein synthesis and, in combination with resistance exercise, induces muscle hypertrophy and strength. A very important macronutrient of this equation is protein. Athletes need high protein doses to stimulate muscle protein synthesis over muscle protein breakdown, and therefore, a positive muscle protein balance. A well-chosen nutrition plan should be based on ingredients made from whole foods and provide the needed protein. But, there are times when athletes choose to use protein supplements. High-quality supplemental protein, such as milk-based protein, whey and casein, help in maintenance or building of muscle mass, and the recovery process after effort. This article will discuss the need for high amounts of protein in enhancing muscle mass and performance , the quality of protein, the most used amino acid supplements, and the security for athletes in using increased quantities of protein and amino acids. The latest information found in scientific journals was analyzed, and the results of this paper will be helpful for athletes and sport specialists regarding optimal protein and amino acid intake in order to enhance sports performance and maintain the athletes' health. Rezumat Nutriţia adecvată şi antrenamentele fizice sunt cei doi piloni ai performanţei sportive. Hrana stimulează sinteza proteică şi, în combinaţie cu exerciţiile de rezistenţă, induce creşterea masei musculare şi a forţei musculare. Un macronutrient foarte important este în această ecuaţie proteina. Atleţii au nevoie de un aport crescut de proteine pentru stimularea sintezei proteinelor musculare peste catabolismul proteic şi, astfel, pentru a avea o balanţă pozitivă a proteinelor musculare. Un plan nutriţional bine ales trebuie să cuprindă alimente integrale, care să furnizeze toate proteinele necesare, calitativ şi cantitativ, dependent de particularităţile metabolice ale fiecărui sportiv şi de tipul de sport practicat. În anumite situaţii este necesară şi se recomandă utilizarea de suplimente proteice. Astfel de suplimente de înaltă calitate, cum ar fi proteinele din lapte, zer şi cazeină, ajută la menţinerea sau la construirea masei musculare în perioadele de efort fizic intens şi facilitează recuperarea după efort. În acest articol se va discuta şi sublinia necesitatea unui aport ridicat de proteine pentru creşterea masei musculare şi a performanţei sportive, calitatea proteinelor furnizate, dar şi suplimentele de aminoacizi recomandate, care pot fi utilizate în siguranţă de către sportivi. Acest articol sumarizează cele mai recente informaţii furnizate de articolele ştiinţifice din domeniu şi oferă date impor-tante sportivilor şi specialiştilor din sport cu privire la aportul optim de proteine şi aminoacizi, în vederea creşterii performanţei sportive, asigurând totodată menţinerea sănătăţii sportivilor.
... Therefore, it is possible that LC could increase serum NO in PV patients by augmenting the expression of NO synthase. In confirmation of this study's results, intake of 3 g/day of glycine propionyl-L-carnitine in healthy adults for eight weeks resulted in an elevation of serum NO levels [26]. ...
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Background and Objective: Pemphigus Vulgaris (PV) is an autoimmune disease with a high oxidative stress level. L-Carnitine (LC)
... Oral intake of GPLC at a dosage of 4.5 grams per day results in increased plasma NO 3 -+ NO 3 -. This has been reported in previously sedentary men and women following an eight week intervention (Bloomer et al., 2009) and in resistance trained men following a four week intervention (Bloomer et al., 2007). The mechanism of action for this apparent increase in NO • with PLC and GPLC appears mediated by a decrease in NADPH oxidase activation (Pignatelli et al., 2003). ...
Article
p class="jbls-body"> Nitric oxide (NO<sup>∙</sup>) is an important signaling molecule that has received considerable attention in recent years for its beneficial impact on a variety of health related outcomes. The effects range from improving various aspects of circulatory health to aiding exercise performance. Although NO<sup>∙</sup> is produced naturally within the body, methods have been proposed to increase circulating NO<sup>∙</sup> within humans. Most notably, the performance of regular exercise, the use of pharmaceutical agents, and the use of nutritional ingredients has been studied. A newly developed molecule known as 2 nitrooxy ethyl 2 amino 3 methylbutanoate (VEEN™) is now being studied as a next generation NO<sup>∙</sup> agent. This paper discusses the importance of NO<sup>∙</sup> in human health, with a particular focus on methods to increase NO<sup>∙</sup>. Attention is given to VEEN™, highlighting the studies performed to date using this molecule. </p
... 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/.
Article
Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions. PLC has been demonstrated to replenish the intermediates of the tricarboxylic acid cycle by the propionyl-CoA moiety, a greater affinity for the sarcolemmal carrier, peripheral vasodilator activity, a greater positive inotropism, and more rapid entry into myocytes. Most studies of the therapeutic use of PLC are focused on the prevention and treatment of ischemic heart disease, congestive heart failure, hypertrophic heart disease, and peripheral arterial disease. ALC and PLC are considered well tolerated without significant side-effects. A number of therapeutic effects possibly come from the interaction of carnitine and its derivatives with the elements of cellular membranes.
Article
Objective(s) Diabetic patients with hypertension are at a high risk of cardiovascular complications. The present study made an attempt to determine the effect of oral L-carnitine supplementation on blood pressure in patients with type 2 diabetes mellitus (T2DM). Materials and methods In this randomized, double-blind, placebo-controlled trial, 70 patients with T2DM at the age range of 41 to 75 years were randomly allocated to two groups: L-carnitin group (LG) (n = 35) receiving 1000 mg/day L-carnitin, and placebo group (PG) (n =35) receiving 1000 mg/day wheat starch as placebo for 12 weeks. The systolic and diastolic blood pressures, mean arterial blood pressure and pulse pressure were examined before and after the intervention. Results Sixty-four participants completed the study. At the end of the study period, LG compared with the PG, showed no significant difference in SBP (-1.14±2.45 mmHg vs. -2.42±2.79 mmHg), DBP (-3.2±1.94 mmHg vs. -6±2.30 mmHg), MAP (-2.51±1.84 mmHg vs. -4.80±2.11 mmHg) and PP (2.05±2.23 mmHg vs. 3.57±2.73 mmHg). Conclusion The oral supplementation of L-carnitine 1000 mg/day fails to affect blood pressure after 12 weeks of treatment in diabetes patients. *This was a randomized, controlled clinical trial (RCT) which was registered 28 October 2017 in the Iranian Registry of Clinical Trials (http://www.irct.ir, identifer: IRCT2017100936681N1).
Article
Adenosine monophosphate-activated protein kinase (AMPK) has a crucial role in neuroprotection. It phosphorylates serine/threonine kinase (Akt) Substrate inhibiting the inflammatory responses induced by the nuclear factor-κB (NF-κB). Exposure to chromium VI dust among workers has been reported and induced brain injury, as the absorption of chromium through the nasal membrane has been found to deliver it directly to the brain. The study aimed to investigate the influence of administration of L-carnitine or/and Co Q10 as theraputic agents against potassium dichromate (PD)-induced brain injury via AMPK/AKT/NF-κβ signaling pathway. Brain injury was induced by PD intranasally as a single dose of 2 mg/kg, 24 h latter rats received L-carnitine (100 mg/kg; orally), Co Q10 (50 mg/kg; orally) and L-carnitine (50 mg/kg; orally) + Co Q10 (25 mg/kg; orally) respectively for 3 days. Locomotor activity was assessed before and at the end of the experiment, then, biochemical and histopathological investigations were assessed in brain homogenate. The exposure of rats to PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in GSH serum contents with an increase in brain contents of TNF-α, IL-6, and NF-kβ and reduced AMPK and AKT brain contents as compared to the control group. Treatment with L-carnitine + Co Q10 ameliorated cognitive impairment and oxidative stress, decreased the brain contents of inflammatory mediators; TNF-α, IL-6, and NF-κβ elevated AMPK and AKT, as compared to each drug. Also, L-carnitine + Co Q10 administration restored morphological changes as degenerated neurons and necrosis. L-carnitine + Co Q10 play important role in AMPK/AKT/NF-κβ pathway that responsible for their antioxidant and anti-inflammatory effects against PD-induced brain injury in rats.
Article
Nitric oxide dietary supplements are extremely popular within the sport and bodybuilding community. Most products contain l-arginine, for which there is no direct evidence that oral L-arginine increases circulating nitric oxide or blood flow. A new molecule (2-[nitrooxy]thyl 2-amino-3-methylbutanoate) is being marketed as a sport supplement for purposes of delivering "real nitric oxide" to the circulation. In the present study, we measured the acute effects of this supplement on blood nitrate/nitrite and hemodynamic variables. Ten resistance trained men (26 ± 4 years old; 8 ± 6 years of resistance exercise training) reported to the laboratory in random order after a 10-hour overnight fast on 2 occasions separated by 1 week and were provided the supplement (2-[nitrooxy]ethyl 2-amino-3-methylbutanoate) or placebo. Heart rate and blood pressure were recorded, and venous blood samples were collected before and at 5, 15, 30, and 60 minutes after complete breakdown of the supplement (5 minutes post intake) or placebo. Blood samples were assayed for plasma nitrate/nitrite. No interaction (p = 0.99), condition (p = 0.18), or time (p = 0.98) effects were noted for plasma nitrate/nitrite, with values remaining nearly identical across time for placebo (∼27 μmol·L(-1)) and increasing a maximum of ∼6.7% (from 32.9 to 35.1 μmol·L(-1)) at the 15-minute collection period for the supplement. In regards to hemodynamic variables, no interaction, condition, or time effects were noted for heart rate, systolic, or diastolic blood pressure (p > 0.05), with values near identical between conditions and virtually unchanged across time. These findings indicate that 2-(nitrooxy)ethyl 2-amino-3-methylbutanoate has a small effect on increasing circulating nitrate/nitrite and does not cause any change in hemodynamic variables within the 1 hour postingestion period in a sample of resistance trained men.
Article
Carnitine is an essential metabolite that is absorbed from the diet and synthesized in the kidney, liver, and brain. It ferries fatty acids across the mitochondrial membrane to undergo β-oxidation. Carnitine has been studied as a therapy or protective agent for many neurological diseases and neurotoxicity (e.g., prolonged anesthetic exposure-induced developmental neurotoxicity in preclinical models). Preclinical and clinical data support the notion that carnitine or acetyl carnitine may improve a patient's quality of life through increased mitochondrial respiration, release of neurotransmitters, and global gene expression changes, showing the potential of carnitine beyond its approved use to treat primary and secondary carnitine deficiency. In this review, we summarize the beneficial effects of carnitine or acetyl carnitine on the central nervous system, highlighting protective effects against neurotoxicity-induced damage caused by various chemicals and encouraging a thorough evaluation of carnitine use as a therapy for patients suffering from neurotoxicant exposure.
Article
Objective Several trials investigated the efficacy of L-carnitine administration on markers of inflammation and indicators of oxidative stress; however, their findings are controversial. The aim of this study was to conduct a comprehensive meta-analysis and a critical review, which would analyze all randomized controlled trials (RCTs) in order to determine the effects of L-carnitine supplementation on inflammatory markers and oxidative stress. Methods An electronic search was performed using Scopus, Cochrane Library, PubMed, Google scholar and Web of Science databases on publications from 1990 up to May 2020. Human RCTs conducted in healthy subjects or participants with certain disorders which investigating the efficacy of L-carnitine supplementation compared to control (placebo, usual treatment or no intervention) on inflammation and oxidative markers were included. Data were pooled applying a random-effects model and as the overall effect size, weighted mean difference (WMD) was presented. Between heterogeneity among studies was computed using Cochran’s Q test and I-square (I2). Quality of studies assessed using the Jadad scale. Dose-response analysis was measured using meta-regression. The funnel plot, as well as the Egger’s regression test was applied to determine the publication bias. Results 44 trials (reported 49 effect sizes for different outcomes of interest) met the inclusion criteria for this meta-analysis. According to the findings, L-carnitine supplementation resulted in a significant reduction in C-reactive protein (CRP) (WMD: -0.10; 95% CI: -0.14, -0.06), interleukin 6 (IL-6) (WMD: -1.87; 95% CI: -2.80, -0.95), tumor necrosis factor-α (TNF-α) levels (WMD: -1.43; 95% CI: -2.03, -0.84), and malondialdehyde (MDA) (WMD: -0.47; 95% CI: -0.76, -0.18) levels, while there was a significant increase in superoxide dismutase (SOD) (WMD: 2.14; 95% CI: 1.02, 3.25). However, no significant effects of L-carnitine on glutathione peroxidase (GPx) (WMD: 0.02; 95% CI: -0.01, 0.05) and total antioxidant capacity (TAC) (WMD: 0.14; 95% CI: -0.05, 0.33) were found. Conclusions L-carnitine supplementation was associated with lowering of CRP, IL-6, TNF-α, and MDA, and increasing SOD levels, but did not affect other inflammatory and oxidative stress biomarkers.
Article
The inflammatory response to vigorous exercise ranges from the mild symptoms of delayed-onset muscle soreness to debilitating injuries affecting soft tissue, joint, and bone. Although there is a great deal of information available on the inflammatory response to exercise in human athletes, less information is available regarding the inflammatory response to exercise in young horses undergoing training for racing careers. Here, we assessed the cytokine response to exercise in a group of young Thoroughbred racehorses during their initial training. Because there is interest in nonpharmacologic approaches to control or ameliorate exercise-induced inflammation, we also examined the anti-inflammatory effect of a nutritional supplement fed to half of the horses undergoing training. Twenty-five Thoroughbred horses aged 2 years were followed through their initial race training. Peripheral blood samples were collected at various times during the exercise for the quantitation of lactic acid, oxidative stress, and inflammatory cytokine gene expression. There was an intensity-dependent effect of exercise on lactate, malondialdehyde, and proinflammatory cytokine gene expression. Although training itself was associated with an overall reduction in inflammatory markers, horses receiving the supplement exhibited further reductions in their indicators of inflammation. As such, this study provides novel evidence of nutritional supplementation reducing postexercise inflammation.
Article
Glycine propionyl l-carnitine (GPLC) is a propionyl ester of carnitine that includes an additional glycine component. The present study evaluated hepatoprotective effect of GPLC in D-Galactosamine (D-GalN) induced fulminant hepatic failure. Rats were intraperitonially administerd D-GalN (700mg/kg BW). GPLC was given as a pre-treatment (35mg/kgBW/day) for one month followed by a single dose of D-GalN on the 31st day. D-GalN administration resulted in increased mortality and serum ALT and AST activities. These increases were significantly attenuated by GPLC. D-GalN treatment increased hepatic lipid peroxidation and a decrease in reduced glutathione content was observed. GPLC pre-treatment significantly decreased lipid peroxidation and augmented the level of GSH. D-GalN increased the circulating level of TNF-α and ATM-Kinase and MAP-Kinase protein expression. GPLC supplementation prevented the increase in serum TNF-α and ATM-Kinase and MAP-Kinase protein expression. D-GalN treatment increased the level of Bax and Caspase-3 m-RNA while as a decline was observed in BCL2 m-RNA. GPLC prevented the increase in Caspase-3 and BAX m-RNA and at the same time augmented the expression of Bcl2 m-RNA. Our findings suggest that GPLC alleviates D-GalN induced liver injury by strengthening antioxidative defense system and reducing apoptotic signalling pathways.
Data
Aim: Evaluation of the role of Glycine Propionyl L-Carnitine (GPLC) in ameliorating D-Galactosamine (D-GalN) induced oxidative stress in male wistar rats. Methods: Our current study included the treatment of male wistar rats with GPLC and D-GalN. Animals were given a pretreatment of GPLC for two months at a dose of 35mg/kgBW/day after which a single dose of D-GalN (700 mg/kgBW) was administered (ip). Another group was administered with D-GalN alone. Hepatic biochemical markers of oxidative stress (ALP,AST,ALT, γ-GT ,GSH,MDA,SOD,CAT and TNF-α) were monitored after the administration of D-GalN at 0 hr, 24 hr and 48 hr in all the groups,. Results: ALP, AST, ALT and γ-GT levels in control group were measured to be 70.51 ± 1.31, 66.83 ± 1.93, 72.65 ± 1.92 and 8.90 ± 0.83 and when compared with D-GalN treated (alone) group gave P < 0.001. Similarly GSH, MDA, SOD, CAT and TNF-α pool in control group were measured to be 46. when compared with D-GalN treated group gave P < 0.001.On the other hand GPLC, when administered simultaneously with D-GalN, showed a significant protection against D-GalN induced damage as the values of biochemical markers when compared to the D-GalN group gave P < 0.001. Conclusion: GPLC is able to prevent the lipid peroxidation by ROS. Dietary supplement of GPLC could prove to be a better neutraceutical having antioxidant role against hepatotoxicants. Moreover it maintains the redox potential inside a cell due to its radical scavenging action thereby maintaining a healthy state of an individual.
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The findings of trials investigating the effect of L-carnitine administration on glycemic control are controversial. This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of L-carnitine intake on glycemic control. Two authors independently searched electronic databases including MEDLINE, EMBASE, Cochrane Library, Web of Science, PubMed and Google scholar from 1990 until February 2019, in order to find relevant RCTs. 37 studies with 44 effect sizes met the inclusion criteria and were eligible for the meta-analysis. L-carnitine supplementation resulted in a significant reduction in fasting plasma glucose (FPG) (WMD: -4.57; 95 % CI: -6.88, -2.25), insulin (WMD: -1.21; 95 % CI: -1.85, -0.57), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.67; 95 % CI: -0.90, -0.44) and HbA1C concentrations (WMD: -0.30; 95 % CI: -0.47, -0.13). L-Carnitine supplementation significantly reduced FPG, insulin, HOMA-IR, and HbA1c levels.
Chapter
The primary factors that affect exercise performance capacity include an individual’s genetic endowment, the quality of training, and effective coaching (see Fig. 19.1). Beyond these factors, nutrition plays a critical role in optimizing performance capacity. In order for athletes to perform well, their training and diet must be optimal. If athletes do not train enough or have an inadequate diet, their performance may be decreased [1]. On the other hand, if athletes train too much, without a sufficient diet, they may be susceptible to becoming overtrained (see Fig. 19.2).
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(Purpose):Studies of L-carnitine in healthy athletic populations have yielded equivocal results. Further scientific based knowledge is needed to clarify the ability of L-carnitine to improve exercise capacity and expedite the recovery process by reducing oxidative stress. This study aimed to examine the 9-week effects of L-carnitine supplementation on exercise performance, anaerobic capacity, and exercise-induced oxidative stress markers in resistance-trained males. [Methods]: In a double-blind, randomized, and placebo controlled treatment, 23 men (age, 25±2y; weight, 81.2±8.31 kg; body fat, 17.1±5.9%) ingested either a placebo (2 g/d, n=11) or L-carnitine (2 g/d, n=12) for 9 weeks in conjunction with resistance training. Primary outcome measurements were analyzed at baseline and at weeks 3, 6, and 9. Participants underwent a similar resistance training (4 d/w, upper/lower body split) for a 9-week period. Two-way ANOVA with repeated measures was used for statistical analysis. [Results]: There were significant increases in bench press lifting volume at wk-6 (146 kg, 95% CI 21.1, 272) and wk-9 (245 kg, 95% CI 127, 362) with L-carnitine. A similar trend was observed for leg press. In the L-carnitine group, at wk-9, there were significant increases in mean power (63.4 W, 95% CI 32.0, 94.8) and peak power (239 W, 95% CI 86.6, 392), reduction in post-exercise blood lactate levels (-1.60 mmol/L, 95% CI-2.44,-0.75) and beneficial changes in total antioxidant capacity (0.18 mmol/L, 95% CI 0.07, 0.28). [Conclusion]: L-carnitine supplementation enhances exercise performance while attenuating blood lactate and oxidative stress responses to resistance training.
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[Purpose] Studies of L-carnitine in healthy athletic populations have yielded equivocal results. Further scientific-based knowledge is needed to clarify the ability of L-carnitine to improve exercise capacity and expedite the recovery process by reducing oxidative stress. This study aimed to examine the 9-week effects of L-carnitine supplementation on exercise performance, anaerobic capacity, and exercise-induced oxidative stress markers in resistance-trained males. [Methods] In a double-blind, randomized, and placebo-controlled treatment, 23 men (age, 25±2y; weight, 81.2±8.31 kg; body fat, 17.1±5.9%) ingested either a placebo (2 g/d, n=11) or L-carnitine (2 g/d, n=12) for 9 weeks in conjunction with resistance training. Primary outcome measurements were analyzed at baseline and at weeks 3, 6, and 9. Participants underwent a similar resistance training (4 d/w, upper/lower body split) for a 9-week period. Two-way ANOVA with repeated measures was used for statistical analysis. [Results] There were significant increases in bench press lifting volume at wk-6 (146 kg, 95% CI 21.1, 272) and wk-9 (245 kg, 95% CI 127, 362) with L-carnitine. A similar trend was observed for leg press.In the L-carnitine group, at wk-9, there were significant increases in mean power (63.4 W, 95% CI 32.0, 94.8) and peak power (239 W, 95% CI 86.6, 392), reduction in post-exercise blood lactate levels (-1.60 mmol/L, 95% CI 2.44, -0.75) and beneficial changes in total antioxidant capacity (0.18 mmol/L, 95% CI 0.07, 0.28). [Conclusion] L-carnitine supplementation enhances exercise performance while attenuating blood lactate and oxidative stress responses to resistance training. [Key words] strength, lactate, antioxidant
Article
Full-text available
Purpose] Studies of L-carnitine in healthy athletic populations have yielded equivocal results. Further scientific based knowledge is needed to clarify the ability of L-carnitine to improve exercise capacity and expedite the recovery process by reducing oxidative stress. This study aimed to examine the 9-week effects of L-carnitine supplementation on exercise performance, anaerobic capacity, and exercise-induced oxidative stress markers in resistance-trained males. [Methods] In a double-blind, randomized, and placebo controlled treatment, 23 men (age, 25±2y; weight, 81.2±8.31 kg; body fat, 17.1±5.9%) ingested either a placebo (2 g/d, n=11) or L-carnitine (2 g/d, n=12) for 9 weeks in conjunction with resistance training. Primary outcome measurements were analyzed at baseline and at weeks 3, 6, and 9. Participants underwent a similar resistance training (4 d/w, upper/lower body split) for a 9-week period. Two-way ANOVA with repeated measures was used for statistical analysis. [Results] There were significant increases in bench press lifting volume at wk-6 (146 kg, 95% CI 21.1, 272) and wk-9 (245 kg, 95% CI 127, 362) with L-carnitine. A similar trend was observed for leg press. In the L-car-nitine group, at wk-9, there were significant increases in mean power (63.4 W, 95% CI 32.0, 94.8) and peak power (239 W, 95% CI 86.6, 392), reduction in post-exercise blood lactate levels (-1.60 mmol/L, 95% CI-2.44,-0.75) and beneficial changes in total antioxidant capacity (0.18 mmol/L, 95% CI 0.07, 0.28). [Conclusion] L-carnitine supplementation enhances exercise performance while attenuating blood lactate and oxidative stress responses to resistance training.
Article
Full-text available
Purpose] Studies of L-carnitine in healthy athletic populations have yielded equivocal results. Further scientific based knowledge is needed to clarify the ability of L-carnitine to improve exercise capacity and expedite the recovery process by reducing oxidative stress. This study aimed to examine the 9-week effects of L-carnitine supplementation on exercise performance, anaerobic capacity, and exercise-induced oxidative stress markers in resistance-trained males. [Methods] In a double-blind, randomized, and placebo controlled treatment, 23 men (age, 25±2y; weight, 81.2±8.31 kg; body fat, 17.1±5.9%) ingested either a placebo (2 g/d, n=11) or L-carnitine (2 g/d, n=12) for 9 weeks in conjunction with resistance training. Primary outcome measurements were analyzed at baseline and at weeks 3, 6, and 9. Participants underwent a similar resistance training (4 d/w, upper/lower body split) for a 9-week period. Two-way ANOVA with repeated measures was used for statistical analysis. [Results] There were significant increases in bench press lifting volume at wk-6 (146 kg, 95% CI 21.1, 272) and wk-9 (245 kg, 95% CI 127, 362) with L-carnitine. A similar trend was observed for leg press. In the L-car-nitine group, at wk-9, there were significant increases in mean power (63.4 W, 95% CI 32.0, 94.8) and peak power (239 W, 95% CI 86.6, 392), reduction in post-exercise blood lactate levels (-1.60 mmol/L, 95% CI-2.44,-0.75) and beneficial changes in total antioxidant capacity (0.18 mmol/L, 95% CI 0.07, 0.28). [Conclusion] L-carnitine supplementation enhances exercise performance while attenuating blood lactate and oxidative stress responses to resistance training.
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Background The findings of trials investigating the effects of carnitine administration on serum lipids are inconsistent. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to summarize the existing evidence and find which the effects of carnitine supplementation on serum lipids are. Methods Two authors independently searched electronic databases including MEDLINE, EMBASE, Cochrane Library, and Web of Science from inception until February 2019, in order to find relevant RCTs. The quality of selected RCTs was evaluated using the Cochrane Collaboration risk of bias tool. Cochrane’s Q test and I-square (I2) statistic were used to determine the heterogeneity across included trials. Weight mean difference (SMD) and 95% CI between two intervention groups were used to determine pooled effect sizes. Results Out of 686 potential papers selected based on keywords, 43 studies met the inclusion criteria and were eligible for the meta-analysis. The pooled results indicated that L-carnitine administration led to a significant decrease in triglycerides (WMD: -4.08; 95% CI: -7.59, -0.58), total cholesterol (WMD: -7.75; 95% CI: -11.23, -4.28) and LDL-cholesterol concentrations (WMD: -4.67; 95% CI: -7.03, -2.30), and a significant increase in HDL-cholesterol levels (WMD: 1.01; 95% CI: 0.28, 1.74). L-carnitine supplementation did not influence VLDL-cholesterol concentrations. Conclusions This meta-analysis demonstrated that carnitine administration significantly reduced triglycerides, total cholesterol and LDL-cholesterol levels, and significantly increased HDL-cholesterol levels, but did not affect VLDL-cholesterol levels.
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L-Propionylcarnitine, a propionyl ester of L-carnitine, increases the intracellular pool of L-carnitine. It exhibits a high affinity for the enzyme carnitine acetyltransferase (CAT) and, thus, is readily converted into propionyl-coenzyme A and free carnitine. It has been reported that L-propionylcarnitine possesses a protective action against heart ischemia–reperfusion injury; however, the antioxidant mechanism is not yet clear. L-Propionylcarnitine might reduce the hydroxyl radical production in the Fenton system, by chelating the iron required for the generation of hydroxyl radicals. To obtain a better insight into the antiradical mechanism of L-propionylcarnitine, the present research analyzed the superoxide scavenging capacity of L-propionylcarnitine and its effect on linoleic acid peroxidation. In addition, the effect of L-propionylcarnitine against DNA cleavage was estimated using pBR322 plasmid. We found that L-propionylcarnitine showed a dose-dependent free-radical scavenging activity. In fact, it was able to scavenge superoxide anion, to inhibit the lipoperoxidation of linoleic acid, and to protect pBR322 DNA from cleavage induced by H2O2 UV-photolysis.
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We studied the effect of administering glycine, a non-essential amino acid, on serum and tissue lipids in experimental hepatotoxic Wistar rats. All the rats were fed standard pellet diet. Hepatotoxicity was induced by administering ethanol (7.9 g kg(-1)) for 30 days by intragastric intubation. Control rats were given isocaloric glucose solution. Glycine was subsequently administered at a dose of 0.6 g kg(-1) every day by intragastric intubation for the next 30 days. Average body weight gain at the end of the total experimental period of 60 days was significantly lower in rats supplemented with alcohol, but improved on glycine treatment. Feeding alcohol significantly elevated the levels of cholesterol, phospholipids, free fatty acids and triglycerides in the serum, liver and brain as compared with those of the control rats. Subsequent glycine supplementation to alcohol-fed rats significantly lowered the serum and tissue lipid levels to near those of the control rats. Microscopic examination of alcohol-treated rat liver showed inflammatory cell infiltrates and fatty changes, which were alleviated on treatment with glycine. Alcohol-treated rat brain demonstrated edema, which was significantly lowered on treatment with glycine. In conclusion, this study shows that oral administration of glycine to alcohol-supplemented rats markedly reduced the accumulation of cholesterol, phospholipids, free fatty acids and triglycerides in the circulation, liver and brain, which was associated with a reversal of steatosis in the liver and edema in the brain.
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Hyperhomocysteinemia (Hhcy) has been associated with pathological and stressful conditions and is a risk factor for cardiovascular disease (CVD). The aim of this study was to evaluate the correlation between plasma homocysteine (hcy) and lipid peroxidation in patient with CVD. This study was carried out on 40 patients with CVD as well as 15 healthy volunteers of comparable age and gender as control group. The patients were divided into 2 groups as follows: group I, included 20 patients with acute myocardial infarction and group II, included 20 patients with atherosclerotic coronary artery disease with no evidence of previous myocardial infarction. Plasma hcy, nitric oxide (NO) and malondialdhyde (MDA) [as index of lipid peroxidation] were measured in all groups. In addition serum total-cholesterol, HDL, LDL and triglycerides were evaluated. Results obtained showed that, there was a significant elevation in the levels of plasma hcy, NO and MDA in groups I and II as compared to control group. There was a strong positive correlation between plasma hcy and MDA (r = 0.59, p < 0.001). Also NO was positively correlated with both hcy (r = 0.49, p < 0.001) and MDA (r = 0.51, p < 0.001). Serum total cholesterol, LDL, and triglycerids were also significantly elevated while serum HDL was significantly decreased in groups I and II as compared to control group. It can be concluded that, hyperhomocysteinemia is a possible factor in free radical generation and therefore cardiovascular diseases.
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We studied the effect of administering glycine on tissue lipid peroxidation and enzymic and non-enzymic antioxidants in experimental hepatotoxic Wistar rats. Hepatotoxicity was induced by administering ethanol for 30 days by intragastric intubation. Glycine administered at a dose of 0.6 g kg(-1) body weight for 30 days significantly inhibited the severe oxidative stress as evidenced by the decreased levels of liver and brain thiobarbituric acid reactive substances (TBARS) and hydroperoxides compared to control. The activities of enzymic and non-enzymic antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in the liver and brain were significantly elevated on glycine supplementation as compared to the untreated alcohol fed rats. The levels of serum vitamin E and vitamin C were also increased to near normal levels on glycine treatment. Microscopic examination of alcohol treated rat liver showed inflammatory cell infiltrates and fatty changes, which were alleviated on treatment with glycine. Alcohol treated rat brain demonstrated oedma, which was significantly lowered on treatment with glycine. Thus our study shows that administering glycine to alcohol supplemented rats, markedly reduced the oxidative stress and elevated the enzymic and non-enzymic antioxidants in the liver and brain, which a was associated with a reversal of hepatic steatosis and cerebral oedma.
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We studied the effect of glycine supplementation on lipid peroxidation and antioxidants in the erythrocyte membrane, plasma and hepatocytes of rats with alcohol-induced hepatotoxicity. Administering ethanol (20%) for 60 days to male Wistar rats resulted in significantly elevated levels of erythrocyte membrane, plasma and hepatocyte thiobarbituric acid reactive substances (TBARS) as compared with those of the experimental control rats. Decreased activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) were also observed on alcohol supplementation as compared with those of the experimental control rats. Glycine was administered at a dose of 0.6 g kg(-1) body weight to rats with alcohol-induced liver injury, which significantly decreased the levels of TBARS and significantly elevated the activities of SOD, CAT, GSH, GPx and GR in the erythrocyte membrane, plasma and hepatocytes as compared to that of untreated alcohol supplemented rats. Thus, our data indicate that supplementation with glycine offers protection against free radical-mediated oxidative stress in the erythrocyte membrane, plasma and hepatocytes of animals with alcohol-induced liver injury.
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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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Exercise training improves arterial compliance due to increases in blood flow to skeletal muscle during repeated bouts of daily exercise. The effect of resuming training on arterial stiffness in previously well-trained subjects is poorly documented. Hence, the purpose of this study was to determine the vascular effects induced by return to exercise in highly trained cyclists. Pulse wave velocity (PWV), an index of arterial stiffness, was assessed at rest and during constant moderate-intensity cycle exercises before and after 16 weeks of endurance training. The impact of daily exercise on the concentration of nitric oxide (NO) measured as nitrate in plasma was examined at rest and during maximal exercise before and after the training period. At rest, PWV was significantly lower in the subjects after a training session (6.4 +/- 0.4 vs. 8.1 +/- 0.4 m x s(-1), p < 0.05). During constant exercise, PWV was significantly and positively correlated with increases in blood pressure. The increased PWV induced by exercise was, however, significantly lower after training (9.8 +/- 0.6 vs. 11.4 +/- 0.6 m x s(-1), p < 0.05). After the training program, nitrate plasma levels at rest were higher. During the maximal test, the plasma nitrate concentration was increased in the subjects studied before the training period, but not after. These results show that resumption of chronic endurance training rapidly induces adaptive changes in arterial stiffness and NO release that may contribute to improved physical fitness in athletes.
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The exposure to hypobaric hypoxia increased lipid peroxidation (as indicated by thiobarbituric acid-reactive substances [TBARS] in rat brain. Plasma lactate/pyruvate ratio was used as a marker of hypoxia. We compared the protective effect of -tocopherol with the effect of l-carnitine or phosphocreatine. Rats pretreated with -tocopherol, l-carnitine, or phosphocreatine had lower TBARS levels after the exposure to hypobaric hypoxia. However, lactate/pyruvate ratio was improved only in rats pretreated with l-carnitine or phosphocreatine. We conclude from our data that, contrary to -tocopherol, protective effects of l-carnitine and phosphocreatine administrations are due to their regulation of metabolic reactions during hypobaric hypoxia rather than to their scavenger activity.
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An experimental model was developed to investigate some metabolic effects of strenuous exercise in hypoxic muscle tissue of human volunteers. The incidence of carnitine supplementation was studied, assuming as marker the thiobarbituric acid reaction products analysed in plasma samples collected during the course of the protocol programme. Propionyl-L-carnitine appears to antagonize in a significant degree the damaging effects of muscle fatigue combined with hypoxic status. Under these conditions the detoxifying role played by propionyl-L-carnitine, previously reported in various tissues and in other pathological conditions, appears to be relevant, although further studies are needed to elucidate the pharmacodynamics of this molecule.
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Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure. We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis. Thirty-eight patients received up to six months of L-carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions. In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal, and plasma acyl levels were elevated. Post-dialysis plasma free and total carnitine concentrations were also subnormal. Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo. There were no significant changes observed in plasma triglycerides, HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups. We conclude that carnitine metabolism is altered in uremia. Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles.
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The effects of the supplementation of methionine (Met), cystine (Cys), and glycine (Gly) to soybean protein or casein on serum and liver lipid levels were studied in rats. Rats were fed cholesterol-free diets containing 25% soybean protein or casein supplemented with 0.75% Met, 2.5% Gly, or a combination of these two for 4 weeks. The addition of Met to soybean protein caused a significant increase in serum cholesterol and this was slightly ameliorated when Gly was given simultaneously. In rats fed casein diets, serum cholesterol tended to decrease when Gly, or Met and Gly were added. A simultaneous supplementation of Met and Gly to casein resulted in a reduction of hepatic cholesterol. Cystine added at the 0.6% level did not cause demonstrable changes in lipid concentrations except for a drop in serum triglyceride of the casein group. When 2.0% Gly was added to cholesterol-enriched diets containing 20% protein, serum cholesterol decreased significantly only when the protein source was casein and the level attained was comparable to that observed in rats fed soybean protein. Liver cholesterol was also markedly decreased by the addition of Gly to casein. The results suggest a possible role of Gly in the regulation of serum cholesterol levels by dietary protein.
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Vitamin status may be related to serum lipid-lipoprotein levels. We tested this hypothesis in a group of 270 healthy elderly men and women over 60 years of age. Vitamin status was determined from dietary intakes and biochemical analysis of plasma. Fasting lipid profile included triglycerides, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C). Correlations have been adjusted by partial correlation for age, physical activity, body mass index, and alcohol consumption. Neither vitamin E intake nor ascorbic acid intake nor ascorbic acid plasma levels correlated with any lipids measured. HDL-C levels did not correlate with any vitamin parameters. In men, vitamin A blood levels correlated with LDL-C, triglyceride, and total cholesterol levels. In women, total cholesterol levels correlated inversely with thiamine and riboflavin blood status and with dietary intake of vitamins B6, D, and niacin. LDL-C plasma values were also inversely correlated with both intake and plasma vitamin D levels and intakes of riboflavin and vitamin B12 in women.
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We have characterized the extent and the phenotype of total and proliferating cell population of aortic plaques in aged rabbits receiving a long-term low-dose cholesterol hyperlipemic diet, which represents an experimental model of atherosclerosis. For nine months, rabbits received the hypercholesterolemic diet alone or in addition to a treatment with propionyl-L-carnitine (PLC), a derivative of carnitine, an intramitochondrial carrier of fatty acids present in most cell types. We observed that, in both PLC-treated and control hyperlipemic rabbits, the ratio between proliferating macrophage-derived and smooth muscle cells was 2:1. PLC in addition to the hypercholesterolemic diet induced a marked lowering of plasma triglycerides, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) triglycerides, while plasma cholesterol was slightly and transiently reduced. Moreover, PLC-treated hyperlipemic rabbits exhibited a reduction of plaque thickness and extent, a slight but significant reduction of the percentage of macrophage-derived cells as compared to control hyperlipemic animals and a reduction of the number of both proliferating macrophage- and smooth muscle cell-derived foam cells. Finally, both proliferating and non-proliferating plaque cells expressed large amounts of macrophage colony-stimulating factor protein, in particular macrophage-derived foam cells. These results indicate that a modification of plasma lipemic pattern obtained by a long-term oral administration of PLC was associated with a decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions.
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It has been reported that acetyl-L-carnitine (AcCn) can reduce the degenerative processes in the central nervous system of rats, modify the fluidity of membranes and decrease the accumulation of lipofuscins in neurones. In light of these considerations we have assayed the in vitro effect of acetyl-L-carnitine on spontaneous and induced lipoperoxidation in rat skeletal muscle; in addition, the effect of AcCn on XD/XO ratio was evaluated. The presence of AcCn (10-40 mM) in incubation medium significantly reduced MDA and conjugated diene formation in rat skeletal muscle; moreover, a significant decrease in induced MDA levels was observed when microsomal preparation where incubated in the presence of 10-40 mM AcCn. Since a significant reduction of XO activity was detected in the presence of 10-80 mM AcCn, the reduced lipid peroxidation by AcCn seems to be due to an inhibition of XO activity.
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The widely used TBA assay for lipid peroxidation was modified to minimize artefactual oxidative degradation of lipids during the assay. Formation of the TBA-MDA condensation product was studied with and without exclusion of oxygen, and the concentration effect of BHT addition was examined. Oxygen was depleted from the reaction mixture by extensive argon gassing. Exclusion of oxygen resulted in decreased TBARS production in plasma but not in standard solutions. High BHT concentrations resulted in a similar effect. At concentrations higher than 3 mmol/l BHT exclusion of oxygen had no additional effect. By measuring n-butanol extracts in a multititer plate reader this modified method was made suitable as a preliminary screening assay of human body fluids for lipid peroxidation.
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It has been reported that cumulative carnitine losses through dialysis membranes may worsen hyperlipidemia during long-term hemodialysis. However, carnitine supplementation has not shown a consistent beneficial response. We undertook the present study to determine if there is any hypolipidemic effect of L-carnitine on Greek dialysis patients in concert with the dialysate buffer composition (acetate or bicarbonate). A total of 28 patients (16 male, 12 female), mean age 43 years (range 21-61), with end-stage renal disease on maintenance hemodialysis for a mean period of 25 months (range 7-84) were studied. The dialysis schedule was 4 h, 3 times/week using cuprophane hollow-fiber dialyzers and acetate (n = 14) or bicarbonate (n = 14) dialysate. In all patients L-carnitine (5 mg/kg body weight) was infused intravenously 3 times/week at the end of each hemodialysis session. Blood samples for carnitine and lipid determinations were obtained before treatment, and 3 and 6 months following treatment. Even though L-carnitine did not modify most of the serum lipid levels, a significant decrease in serum triglycerides was evident in the whole group of patients (from 225 +/- 76 to 201 +/- 75 mg/dl, p = 0.03). Furthermore, L-carnitine could decrease serum triglycerides only in hypertriglyceridemic patients (from 260 +/- 64 to 226 +/- 82 mg/dl, p < 0.05). L-Carnitine resulted in a reduction of serum triglycerides in both patients on bicarbonate and on acetate dialysis, while there were no significant differences in the changes of lipid parameters after L-carnitine between the two groups of hemodialysis patients. We conclude that relatively low doses of L-carnitine supplementation could contribute to the management of some hypertriglyceridemic hemodialysis patients.
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This review focuses on the regulation of myocardial fatty acids and glucose metabolism is physiological and pathological conditions, and the role of L-carnitine and of its derivative, propionyl-L-carnitine. Fatty acids are the major oxidation fuel for the heart, while glucose and lactate provide the remaining need. Fatty acids in cytoplasm are transformed to long-chain acyl-CoA and transferred into the mitochondrial matrix by the action of three carnitine dependent enzymes to produce acetyl-CoA through the β-oxidaton pathway. Another source of mitochondrial acetyl-CoA is from the oxidation of carbohydrates. The pyruvate dehydrogenase (PDH) complex, the key irreversible rate limiting step in carbohydrate oxidation, is modulated by the intra-mitochondrial ratio acetyl-CoA/CoA. An increased ratio results in the inhibition of PDH activity. A decreased ratio can relieve the inhibition of PDH as shown by the transfer of acetyl groups from acetyl-CoA to carnitine, forming acetylcarnitine, a reaction catalyzed by carnitine acetyl-transferase. This activity of L-carnitine in the modulation of the intramitochondrial acety-CoA/CoA ratio affects glucose oxidation. Myocardial substrate metabolism during ischemia is dependent upon the severity of ischemia. A very severe reduction of blood flow causes a decrease of substrate flux through PDH. When perfusion is only partially reduced there is an increase in the rate of glycolysis and a switch from lactate uptake to lactate production. Tissue levels of acyl-CoA and long-chain acylcarnitine increase with important functional consequences on cell membranes. During reperfusion fatty acids oxidation quickly recovers as the prevailing source of energy, while pyruvate oxidation is inhibited. A considerable body of experimental evidence suggests that L-carnitine exert a protective effect in in vitro and in vivo models of heart ischemia and hypertrophy. Clinical trials confirm these beneficial effects although controversial results are observed. The actions of L-carnitine and propionyl-L-carnitine cannot be explained as exclusively dependent on the stimulation of fatty acid oxidation but rather on a marked increase in glucose oxidation, via a relief of PDH inhibition caused by the elevated acetyl-CoA/CoA ratio. Enhanced pyruvate flux through PDH is beneficial for the cardial cells since less pyruvate is converted to lactate, a metabolic step resulting in the acidification of the intracellular compartment. In addition, L-carnitine decreases tissue levels of acyl moieties, a mechanism particularly important in the ischemic phase.
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Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. In westernized societies, it is the underlying cause of about 50% of all deaths. Epidemiological studies have revealed several important environmental and genetic risk factors associated with atherosclerosis. Progress in defining the cellular and molecular interactions involved, however, has been hindered by the disease's aetiological complexity. Over the past decade, the availability of new investigative tools, including genetically modified mouse models of disease, has resulted in a clearer understanding of the molecular mechanisms that connect altered cholesterol metabolism and other risk factors to the development of atherosclerotic plaque. It is now clear that atherosclerosis is not simply an inevitable degenerative consequence of ageing, but rather a chronic inflammatory condition that can be converted into an acute clinical event by plaque rupture and thrombosis.
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The study investigated the influence of L-carnitine on the formation of malondialdehyde, an indicator of lipid peroxidation, in isolated Langendorff rat hearts. Earlier investigations of hemodynamic parameters and the recovery of ATP and creatine phosphate, carried out by means of 31P-NMR spectroscopy, had demonstrated that, depending on the composition of the perfusates (content of glucose, fatty acids, and carnitine), quite strong differences may occur in the reperfusion period after ischemia. In order to determine a possible relationship between these differences and the addition of carnitine, the study investigated whether carnitine penetrated into the tissue during the experiments, and whether it was able to reduce the concentration of detrimental substances. The concentrations of free and total carnitine as well as the malondialdehyde content as an indicator of ischemia/reperfusion damage were determined in different parts of the cardiac tissue as follows: After the Langendorff-experiments the hearts were dissected, homogenized and reconditioned; then carnitine and malondialdehyde were determined. The study included 63 hearts, which were divided into 8 different perfusion groups. Carnitine concentrations in heart tissue perfused with L-carnitine were much higher than those of the controls. Since exogenous L-carnitine and formed esters could be found in the tissue after the experiment, they must have permeated the cellular membrane rapidly. The concentrations of malondialdehyde behaved in an inverted way; as expected they were lower in carnitine-perfused hearts. The favourable effects of L-carnitine, expressed both by improved cardiac dynamics and ATP and CrP recovery in the reperfusion period, are obviously due to the fact that L-carnitine reduces ischemic damage.
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The purpose of this investigation was to examine the effects of ingestion of L-CARNIPURE (L-carnitine L-tartrate [LCLT]) on alterations in a complete blood cell profile and in circulating metabolic enzymes. Using a balanced, placebo (P), cross-over design (1 week washout), 10 healthy, active men volunteered and acted as their own control taking either a P or LCLT supplement (3 g.day(-1)) for 3 weeks. Postabsorptive morning blood samples were obtained both before and after 21 days of P and LCLT supplementation. Serum samples were analyzed for clinical chemistries including a complete chemistry panel with markers of liver and renal function along with various minerals and electrolytes. In addition, whole blood was analyzed for a complete blood count with differential. It was determined that there were no statistically significant differences between the LCLT and the placebo conditions for any of the variables examined. The results of this study suggest that LCLT, when used as a dietary supplement, has no adverse effects on metabolic and hematological safety variables in normally healthy men.
Article
Cardiomyopathy induced by Adriamycin (ADR) is a cause of congestive heart failure. Recently, it has been suggested that ADR inhibits the carnitine palmitoyltransferase system (CPT I) and consequently the transport of long-chain fatty acids across mitochondrial membranes. This study was devised to ascertain how ADR affects serum lipid and fatty acid metabolism in rats given ADR with and without L-carnitine supplementation. Male Sprague-Dawley rats were divided into four groups. The first group was the control. The second group was given intraperitoneal injections of ADR (5 mg/kg) twice a week over a period of 2 wk. The third group received the same dose of ADR plus L-carnitine (200 mg/kg). The fourth group was injected with L-carnitine only. Serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol) and fatty acid levels were determined on the first, eighth, and 15th d after injection of ADR. ADR caused an increase of serum total cholesterol, triglyceride, and LDL cholesterol compared with the control group. HDL cholesterol was similar between two groups. Similarly, total fatty acids, especially C16-C18 fatty acids, were significantly elevated after injection of ADR. Striking reduction in these substances was observed when L-carnitine was added (p < 0.05). This study is the first report regarding the reversal effect of L-carnitine in connection with FFA profiles (C6-C18) in the serum of ADR-induced cardiomyopathic rats. This study also supports the view that ADR causes cardiomyopathy because it interferes with fatty acid metabolism, and we hypothesize that there is a possible protective effect of L-carnitine.
Article
Our group has previously shown that human umbilical vein endothelial cells exposed to smokers' serum decreased nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) activity in the presence of increased eNOS expression. In the present study, we examined whether these observations extended to human coronary artery endothelial cells (HCAECs). In addition, the role of reactive oxygen species in the observed alterations was examined. HCAECs were incubated with serum from 10 nonsmokers and 15 smokers for 12 hours with or without the addition of either polyethylene glycol-superoxide dismutase (PEG-SOD, 300 U/mL), PEG-SOD+PEG-catalase (1000 U/mL), chelerythrine (3 micromol/L), or tetrahydrobiopterin (20 micromol/L). At the end of incubation, NO, eNOS protein, and eNOS activity were measured from the same culture. HCAECs incubated with smokers' serum alone showed significantly lower NO production (P<0.05) and eNOS activity (P<0.005) but higher eNOS expression (P<0.005) compared with nonsmokers. In smokers, addition of PEG-SOD, PEG-SOD+PEG-catalase, or tetrahydrobiopterin significantly (P<0.05) improved NO levels and eNOS activity. Interestingly, in the same smokers, a significant decrease in eNOS expression was only seen with the addition of PEG-SOD+PEG-catalase (P<0.05) and treatment with PEG-SOD alone insignificantly increased eNOS expression. The present study indicates that in vitro, HCAECs show similar changes in NO biosynthesis as human umbilical vein endothelial cells when exposed to smokers' serum and also confirms that oxidative stress plays a central role in smoking-mediated dysfunction of NO biosynthesis in endothelial cells. Furthermore, these data support other studies suggesting a role for hydrogen peroxide in the upregulation of eNOS.
Article
A previous study has demonstrated that L-carnitine reduces plasma lipoprotein(a) (Lp[a]) levels in patients with hypercholesterolemia. To test a tolerable Lp(a)-reducing agent in diabetic patients, we assessed the effect of a dietary supplementation of L-carnitine on plasma lipid levels, particularly Lp(a), of patients with type 2 diabetes mellitus (DM) and hypercholesterolemia. In this 6-month, randomized, double-masked, placebo-controlled clinical trial, patients were enrolled, assessed, and followed up at the Diabetic and Metabolic Diseases Center of the Department of Internal Medicine and Therapeutics at the University of Pavia, Pavia, Italy. All study patients had newly diagnosed type 2 DM that was managed through dietary restriction alone throughout the study, as well as hypercholesterolemia. Patients were randomized to 1 of 2 groups. One group received L-carnitine, one 1-g tablet BID. The other group received a corresponding placebo. We assessed body mass index, fasting plasma glucose, postprandial plasma glucose, glycosylated hemoglobin, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B, and Lp(a) at baseline and at 1, 3, and 6 months of treatment. This study included 94 patients. The treatment group included 24 men and 22 women (mean [SD] age, 52 [6] years). The placebo group included 23 men and 25 women (mean [SD] age, 50 [7] years). The baseline characteristics of the groups did not differ significantly. The mean (SD) body weight, height, and body mass index were 78.2 (5.8) kg, 1.70 (0.04) m, and 27.3 (2.5) kg/m(2), respectively, in the L-carnitine group and 77.6 (6.4) kg, 1.71 (0.05) m, and 26.8 (2.2) kg/m(2), respectively, in the placebo group. In the treatment group, Lp(a) was significantly reduced at 3 and 6 months compared with baseline (P < 0.05) and P < 0.01, respectively). We observed a significant improvement after 6 months (P < 0.05) in the Lp(a) value in patients taking L-carnitine compared with those taking placebo. Between-group differences in other variables did not reach a level of significance at months 3 and 6. No drug-related adverse events were reported or observed. In this preliminary study, after 3 and 6 months, L-carnitine significantly lowered the plasma Lp(a) level compared with placebo in selected hypercholesterolemic patients with newly diagnosed type 2 DM.
Article
The relative importance of mechanisms relevant to smoking-induced vascular injury is poorly understood. Cigarette smoke is a source of free radicals but also results in cellular activation and consequent generation of free radicals in vivo. Here we consider several approaches to estimating the consequences of free radical generation in vivo, using measurements of modified lipids, proteins, and DNA. Smoking appears to result in elevation of several biomarkers of oxidant stress, some in a dose-related fashion. There is also some evidence that disordered endothelial function in smokers may be partly attributable to oxidant stress. Other effects of smoking on hemostatic activation, sympathoadrenal function, and lipoprotein structure and function may also be modulated by smoking-induced oxidant stress. The emergence and application of rational quantitatively reliable indexes of oxidant stress in vivo is likely to elucidate the relative contribution of oxidant stress to smoking-induced vascular injury.
Article
Studies in athletes have shown that carnitine supplementation may foster exercise performance. As reported in the majority of studies, an increase in maximal oxygen consumption and a lowering of the respiratory quotient indicate that dietary carnitine has the potential to stimulate lipid metabolism. Treatment with L-carnitine also has been shown to induce a significant postexercise decrease in plasma lactate, which is formed and used continuously under fully aerobic conditions. Data from preliminary studies have indicated that L-carnitine supplementation can attenuate the deleterious effects of hypoxic training and speed up recovery from exercise stress. Recent data have indicated that L-carnitine plays a decisive role in the prevention of cellular damage and favorably affects recovery from exercise stress. Uptake of L-carnitine by blood cells may induce at least three mechanisms: 1) stimulation of hematopoiesis, 2) a dose-dependent inhibition of collagen-induced platelet aggregation, and 3) the prevention of programmed cell death in immune cells. As recently shown, carnitine has direct effects in regulation of gene expression (i.e., carnitine-acyltransferases) and may also exert effects via modulating intracellular fatty acid concentration. Thus there is evidence for a beneficial effect of L-carnitine supplementation in training, competition, and recovery from strenuous exercise and in regenerative athletics.
Article
This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an "oxidative response to inflammation" model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.
Article
The aim of this study was to evaluate the effects of L-carnitine supplementation on serum triglyceride and total cholesterol levels in streptozotocin (STZ)-induced diabetic rats. Thirty-two male Wistar rats were divided into diabetic and diabetic-L-carnitine-supplemented groups. Diabetes was induced by injection of a single dose of streptozotocin (40 mg/kg, intraperitoneally) in citrate buffer. L-Carnitine was supplemented by IM injection of 100 mg/kg per day for 10 days. Serum glucose, triglyceride and total cholesterol levels were determined at days 0, 5 and 10. Rats receiving L-carnitine had lower triglyceride levels at both days 5 and 10 (P < 0.05). Total cholesterol levels in the carnitine-supplemented group were lower, but statistical significance was achieved only at day 10 (P < 0.05). These results suggest that L-carnitine exhibits hypotriglyceridemic and hypocholesterolemic effects in streptozotocin-induced diabetic rats. Clinical trials of L-carnitine supplementation on patients with diabetes induced hyperlipidemia must be further evaluated.
Article
We designed this study to investigate the effects of oral L-carnitine administration on fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and lipid parameters in patients with diabetes mellitus type II. The effect of L-carnitine on FPG and lipid parameters was investigated in 22 male and 13 female type II diabetic patients; the mean age +/- s.d. was 51.3 +/- 3.7 y. The patients were randomly allocated to two groups (L-carnitine and placebo group) and 1 g of L-carnitine or of placebo was given orally three times a day for a period of 12 weeks. FPG in the L-carnitine group decreased significantly from 143 +/- 35 to 130 +/- 33 mg/dl (P = 0.03), and we observed a significant increase of triglycerides (TG) from 196+/-61 to 233+/-12 mg/dl (P = 0.05), of Apo A1 from 94 +/- 20 to 103 +/- 23 mg/dl (P = 0.02), and of Apo B100 from 98 +/- 18 to 108 +/- 22 mg/dl (P = 0.02) after 12 weeks of treatment. There was no significant change in LDL-C, HDL-C, HbA1C, LP(a) or total cholesterol. L-Carnitine significantly lowers FPG but increases fasting triglyceride in type II diabetic patients.
Article
Fatty acid oxidation is predominantly a mitochondrial event, which is enhanced by dietary choline and carnitine supplementation resulting in extra reactive oxygen species (ROS) load. The objective was to assess oxidative stress level by thiobarbituric acid reactive substances [TBARS] in choline and carnitine supplemented healthy women before and after mild exercise. Nineteen free-living women completed the placebo control study in which choline and/or L-carnitine was orally taken for 21 days. Anthropometric measurements, dietary recall, exercise routine and blood samples were analyzed to determine body composition, nutrients intake, distance walked and biochemical markers related to oxidative stress. TBARS were significantly lower in the groups supplemented with choline, carnitine or both and the mild exercise (walking) was not a deterrent in this effect of the supplements. Serum vitamin A and E concentrations were higher in the supplemented groups even though the consumption of these nutrients was not different among the groups. Choline and carnitine supplementation lowers lipid peroxidation, and promotes conservation of retinol and alpha-tocopherol in free-living women.
Article
The association between oxidative stress and cardiovascular diseases is a widely accepted fact today. Generally, men have a higher risk of cardiovascular incidents and mortality from acute myocardial infarction and strokes. We have examined sport-associated circannual rhythms of oxidant and antioxidant processes by measuring plasma LPO, erythrocyte SOD, CAT, Gpx activity and plasma hormonal status in both sedentary and long-term trained men and women. We have shown seasonal variations in both oxidant and antioxidant status in all examined groups. The largest difference was observed in the oxidant status between sedentary men and women during autumn and winter, which is considered a period of high coronary risk for men. Sport decreased LPO in trained men in autumn, while the same effect in trained women was shifted towards summer. These data state that regular, long-term physical exercise training induces adaptive responses that confer protection against oxidative stress, as well as the beneficial effect of exercise with regard to season, particularly in men during a period of high coronary risk (autumn and winter, respectively) and in women during summer.
Article
L-carnitine plays an important regulatory role in the mitochondrial transport of long-chain free fatty acids. In this study, the antioxidant activity of L-carnitine was investigated as in vitro. The antioxidant properties of the L-carnitine were evaluated by using different antioxidant assays such as 1, 1-diphenyl-2-picryl-hydrazyl free radical (DPPH.) scavenging, total antioxidant activity, reducing power, superoxide anion radical scavenging, hydrogen peroxide scavenging and metal chelating activities. Total antioxidant activity was measured according to ferric thiocyanate method. alpha-tocopherol and trolox, a water-soluble analogue of tocopherol, were used as the reference antioxidant compounds. At the concentrations of 15, 30 and 45 microg/mL, l-carnitine showed 94.6%, 95.4% and 97.1% inhibition on lipid peroxidation of linoleic acid emulsion, respectively. On the other hand, 45 microg/mL of standard antioxidant such as alpha-tocopherol and trolox indicated an inhibition of 88.8% and 86.2% on peroxidation of linoleic acid emulsion, respectively. In addition, L-carnitine had an effective DPPH. scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, total reducing power and metal chelating on ferrous ions activities. Also, those various antioxidant activities were compared to alpha-tocopherol and trolox as references antioxidants.
Article
Lipoprotein(a) [Lp(a)] concentration is generally related to coronary artery disease (CAD) and cerebrovascular disease. However, at present, few interventions are available to lower Lp(a) concentrations. We investigated the effects of l-carnitine, co-administered with simvastatin, on hyper-Lp(a) in patients with type 2 diabetes mellitus. We conducted an open, randomised, parallel-group study, in one investigational center (University hospital). Fifty-two patients with type 2 diabetes mellitus, a triglyceride serum levels <400mg/dL (<4.5 mmol/L), and Lp(a) serum levels >20mg/dL (0.71 mmol/L) were randomised to receive simvastatin alone (n=26) or simvastatin plus l-carnitine (n=26) for 60 days. Simvastatin was administered, in both groups, at a dosage of 20 mg/day, while l-carnitine was administered at a dosage of 2g/day once daily. Both treatments were given orally. Serum levels of triglycerides, total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol (total cholesterol minus HDL cholesterol), apolipoprotein B, and Lp(a) were measured at baseline and 60 days after starting treatment. No difference in time by groups (simvastatin and simvastatin plus l-carnitine) were observed in the reduction of LDL cholesterol, non-HDL cholesterol, and apoB serum levels. On the other hand, Lp(a) serum levels increase from baseline to 60 days in the simvastatin group alone versus a significant decrease in the combination group. Our findings provide support for a possible role of combined treatment with l-carnitine and simvastatin in lowering Lp(a) serum levels in patients with type 2 diabetes mellitus than with simvastatin alone. Our results strongly suggest that l-carnitine may have a role among lipid-lowering strategies.
Article
The purpose of this investigation was to measure the oxidative stress response to similarly matched work bouts of squat and sprint exercise. Twelve anaerobically trained men performed six 10-s sprints and, on a separate occasion, repeated barbell squats to approximately equal the amount of work performed during the sprints. Blood lactate, heart rate, and perceived exertion was measured before and following each exercise bout. Muscle soreness, muscle force, and creatine kinase activity was determined preexercise and through 48 h of recovery. Desmin cytoskeletal protein was determined via muscle biopsy of the vastus lateralis before and at 24 h following each exercise. Plasma protein carbonyls (PC) and malondialdehyde (MDA) were measured as biomarkers of oxidative stress. Heart rate and perceived exertion was not different between exercise sessions (P > 0.05), although lactate was higher following sprinting compared with squatting (P = 0.002). Muscle soreness was greater for squatting than sprinting (P = 0.003) and reached a peak immediately postexercise for both sessions (P = 0.0003). Muscle force was unaffected by either exercise session (P > 0.05), and creatine kinase activity was elevated to a similar extent following both sessions. Desmin-negative fibers were virtually nonexistent after either exercise bout, indicating no loss of this cytoskeletal protein. Neither PC nor MDA was affected by the exercise (P > 0.05). These results suggest that in anaerobically trained men, the oxidative stress and muscle injury response to similarly matched anaerobic exercise bouts is minimal, and not different between exercise modes. Furthermore, when compared with previous literature on untrained subjects, the response is significantly attenuated, possibly because of adaptations occurring as a result of chronic, strenuous anaerobic training.
Article
The objective of this study was to investigate the effects of 12 weeks of standard cardiac rehabilitation on endothelial function, oxidative stress, and antioxidant defenses in patients with coronary artery disease. Twelve weeks of endurance exercise training led to an improvement in endothelial function as measured by brachial artery flow-mediated dilation (7.9% at baseline vs 11.1% at 12 weeks). Exercise training resulted in increased plasma nitrite and nitrate levels, increased plasma superoxide dismutase activity, and decreased oxidative stress.
Article
This study was designed to ascertain whether regular exercise may attenuate lipid peroxidation in adolescents with Down's syndrome. Thirty-one male adolescents with Down's syndrome performed a 12-week training program, 3 days/week at a work intensity of 60-75% of peak heart rate (HRmax=194.5-[0.56 age]). Plasmatic malondialdehyde (MDA) was determined by high performance liquid chromatography (HPLC). When compared to baseline, MDA content was decreased significantly. Regular exercise significantly decreased lipoperoxidation in Down's syndrome.
Article
NO (nitric oxide), formed in the vascular endothelium and derived from a biochemical reaction catalysed by eNOS (endothelial NO synthase), appears to play a role in exercise-induced dilation of blood vessels supplying cardiac and skeletal muscle. Endothelium-dependent, NO-mediated vasodilation is augmented by exercise training. Increases in eNOS gene transcription, eNOS mRNA stability and eNOS protein translation appear to contribute to increased NO formation and, consequently, enhanced NO-mediated vasodilation after training. Enhanced endothelial NO formation may also have a role(s) in the prevention and management of atherosclerosis because several steps in the atherosclerotic disease process are inhibited by NO. A growing body of work suggests that exercise training, perhaps via increased capacity for NO formation, retards atherosclerosis. This has significant implications for human health, given that atherosclerosis is the leading killer in Western society.
Article
Both cigarette smoking and strenuous physical work are associated with increased oxidative stress, which is implicated in the pathogenesis of cardiovascular disease. No study to date has measured oxidative stress in response to graded exercise in cigarette smokers. We compared oxidative stress biomarkers before and after strenuous exercise (Bruce treadmill protocol) in 14 cigarette smokers and 15 nonsmokers of similar age (24+/-6 years) and fitness status. Plasma protein carbonyls (PC), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) were measured pre- and postexercise. Smoking status (p<.01) and time (p<.01) effects were noted for PC with values higher for smokers than nonsmokers and increasing from pre- to postexercise (52% vs. 25%, respectively). The smoking statusxtime interaction for PC approached statistical significance (p=.07). The change in PC from pre- to postexercise was positively correlated with the number of cigarettes smoked per day (r=.5782, p=.03). A smoking statusxtime interaction was noted for MDA (p<.01), with values increasing 37% from pre- (0.6140+/-0.0708 micromol/L) to postexercise (0.8440+/-0.0687 micromol/L) for smokers and remaining relatively unchanged for nonsmokers (from 0.7664+/-0.0901 to 0.7419+/-0.0776 micromol/L). 8-OHdG was unaffected by smoking status (p=.43) or exercise (p=.40). These findings indicate that young cigarette smokers experience an exaggerated oxidative stress response to strenuous physical work, compared with nonsmokers of similar age. These results highlight yet another detrimental impact of cigarette smoking on human health. Future investigations should focus on older, more established smokers.