Introduction
In endurance and resistance athletes, amino acids are among the most popular ergogenic supplements used to enhance performance. Apart from other amino acids, studies have suggested that arginine, alone or in combination with aspartate or other amino acids, may enhance performance, mediated by different pathways including enhanced secretion of endogenous growth hormone (hGH)1, its role in the synthesis of creatine2 and as a precursor in the production of nitric oxide (NO)3. The potential effect on hGH and NO might be most important from a performance enhancement point of view.
An enhanced secretion of hGH has been shown after infusion of arginine 4 but not after oral ingestion 5, 6. The influence on the production of NO might have a greater potential performance enhancing effect. Arginine is a precursor of the cell-signalling molecule NO, which is synthesised from arginine under the enzymatic control of nitric oxide synthase (NOS). NO is a signalling molecule that facilitates the dilation of blood vessels and decreases vascular resistance. It is hypothesised that the vasodilation effect of NO may increase the delivery and uptake of fuel substrates in the skeletal muscle 7.
Methods
A review of the literature was conducted by consulting the PubMed database and using the following keywords: “arginine”, “aspartate”, “performance” and “metabolism” in 2007. The references of these articles were scanned for further relevant publications.
Limitations
Arginine and aspartate have been used in studies alone or in combination with other substances, making data analysis complex. In addition, arginine has been administered intravenously or ingested orally.
Results
The combination of arginine with aspartate was the most often used supplement combination. Results are therefore presented separately for (1) arginine alone, (2) arginine with aspartate and (3) arginine and aspartate in combination with other substances. For each of those groups, effects on substrate metabolism, endocrine parameters and performance are cited.
(1) Arginine
Effects of arginine on metabolism and performance
In these studies, arginine was administered to subjects either orally or by intravenous infusion. The most common studies have investigated the effect of arginine on human growth hormone (hGH). Wideman et al. 4, showed that infused arginine appeared to affect endocrine parameters, especially hGH where increased concentrations were shown to be due to suppression of endogenous somatostatin secretion 8. Interestingly, during a marathon, an hGH increase has been shown after an oral intake of arginine aspartate 9, but not at rest 5, 6. However, the infusion of arginine had no effect on performance during cycling 10.
The effect on insulin concentration has also been investigated after the oral ingestion 5, 9, 11, 12 and after an infusion of arginine 10. In one study, the oral intake of arginine in combination with ornithine and lysine had no effect on the insulin concentration at rest 5. However, in another study, arginine aspartate resulted in a significant decrease in insulin concentration after exhaustive exercise 11, while in other studies no effect has been shown 9, 10, 12.
In yet other studies, the oral intake of arginine aspartate 9 or the infusion of arginine alone 4 led to a significant increase of both hGH and glucagon, which might explain the changes in concentration of free fatty acids (FFA), glucose and lactate during physical exercise 13.
In earlier studies, the oral administration of arginine aspartate in fasting, non-trained subjects, led to a significant increase in hGH 14, 15 and a significant increase in concentration of FFA 4 hours subsequent to ingestion 14. However, in more recently published studies with trained subjects, no effect on FFA, glucose and lactate were shown after the oral ingestion of arginine 9, 11, 16. However, Schaefer et al. 13 demonstrated a reduction in the exercise-induced increase in plasma lactate and ammonia after intravenous infusion of arginine. They found a close relationship between changes in lactate concentrations and citrulline and suggested that the blunted increase in lactate concentration was effected via the arginine NO pathway. It has been reported that the inhibition of NOS increased plasma lactate concentrations during exercise 17.
(2) Arginine aspartate
Effect of arginine aspartate on substrate metabolism
A variety of different parameters of metabolism were investigated in the studies scrutinised. This varied from determination of concentration of lactate 9, 11, 12, 18-20, glucose 9, 11, 12, pyruvate 9, 11, free fatty acids 9, 11, glycerol 9, 11, b-hydroxybutyrate 9, 11, ammonia 9, 21, creatine 12, creatine kinase 9, lactate dehydrogenase 9, urea 9, 11, 12, 19, uric acid 11, 12, ferritin 19 and plasma amino acids 9, 11 in response to arginine aspartate ingestion. Some of these studies showed a statistically significant change, specifically in lactate 18, 20, plasma amino acids 9, urea 11, 12 and ammonia 21 concentrations.
Effect on lactate concentration
A statistically significant decrease in the concentration of lactate has been shown at submaximal exercise intensities 18, 20 after the ingestion of arginine. Burtscher et al. demonstrated a statistically significant decrease in lactate concentration when cycling at 100W (2.0 ± 0.7 mmol × l-1 to 1.4 ± 0.5 mmol× l-1, p=0.001) and at 150W (2.8 ± 0.8 mmol× l-1 to 2.0 ± 0.9 mmol× l-1, p<0.001) 20.
In the study of Gremion et al., athletes had to run on a treadmill at 100W, 200W, 300W and 400W until exhaustion 18. At 100W, no statistically significant difference could be shown. At 200W, in the group who ingested arginine aspartate, the concentration of lactate was 2.97 mmol× l-1 compared to 3.53 mmol× l-1 in a supplemented control group (p=0.01). At 300W, the supplemented athletes had a lactate concentration of 6.57 mmol× l-1 compared to 7.08 mmol× l-1 in the control group (p=0.05). Similarly, at 400W, the athletes who supplemented with arginine aspartate had a significantly lower concentration of lactate (9.47 mmol× l-1 compared to 10.02 mmol× l-1; p=0.05). After 5 min and 20 min of rest, lactate concentration was not significantly different between groups. Several other studies, however, have shown no effect of arginine aspartate supplementation on concentration of lactate. Specifically, in the studies of Abel et al. 19, Colombani et al. 9, Denis et al. 21 and Schmid et al. 12 there were no changes in lactate concentration as a result of supplementation.
Reduction of concentration of plasma amino acids
Colombani et al. showed in their study with marathon runners that the concentration of plasma amino acids was significantly reduced after a marathon run (2,938 μmol × l-1 versus 2,095 μmol × l-1; p<0.05) in athletes who had supplemented for two weeks with 15g arginine aspartate daily 9. In the placebo group, the total sum of amino acids dropped from 3,170 μmol × l-1 to 2,301 μmol × l-1; p<0.05) 9. In another study of Colombani et al. with body builders, the concentration of arginine decreased significantly from 78.7 ± 10.1 μmol × l-1 before the resistance programme to 54.0 ± 3.4 μmol × l-1 2 h after the exercise (p=0.04) 11. In the placebo group, arginine decreased from 57.6 ± 8.6 μmol × l-1 to 49.3 ± 4.8 μmol × l-1 2h after the exercise (p=0.04). A decrease of arginine must be rated as a negative effect when the effect on performance enhancement is considered.
Reduction of concentration of urea
In the study of Colombani et al. 11 with body builders, an intense resistance exercise programme decreased the concentration of urea statistically significantly from 5.80 ± 0.35 mmol × l-1 before the exercise to 5.63 ± 0.31 mmol × l-1 2 h after the exercise (p=0.05).
In the placebo group, urea decreased from 5.15 ± 0.47 mmol × l-1 to 5.03 ± 0.32 mmol × l-1 2 h after the exercise (p=0.05) 11.
Reduction of concentration of ammonia
Denis et al. showed that the concentration of blood ammonia (b[NH4+]) was significantly reduced in an endurance exercise bout after the administration of 5g arginine aspartate for 10 days 21. The exercise was performed at 80% VO2max for 45 min on a cycle ergometer (57 ± 9 μmol × l-1 versus 62 ± 7 μmol × l-1 in a placebo group; p<0.05).
Effect of arginine aspartate on endocrine parameters
Several different endocrine parameters have been determined. Insulin 9, 11, 12, hGH 9, 11, 12, 19, testosterone 19, ACTH 11, cortisol 9, 11, 19, and glucagon 9, 11, 19 have all been determined in response to arginine aspartate supplementation. An effect has been shown for hGH 9, glucagon 9 and insulin 11. For example, Colombani et al. could demonstrate that in marathon runners the concentration of hGH and glucagon was significantly increased after a marathon in those athletes who had supplemented for two weeks with 15g arginine aspartate daily 9. In another study of Colombani et al. with body builders, an intense resistance exercise programme resulted in a decreased concentration of insulin from 10.23 ± 1.49 μU × ml-1 before the exercise to 6.27 ± 0.99 μU × ml-1 2h after the exercise (p=0.02) [11]. In the placebo group, insulin decreased from 14.67 ± 3.33 μU × ml-1 to 7.57 ± 0.66 μU × ml-1 2 h after the exercise (p=0.02) 11.
Effect of arginine aspartate on performance
In six studies with endurance trained athletes, different parameters concerning performance have been investigated (Table 1). Some studies have determined changes in VO2max 18, 19, measured time to exhaustion in an incremental test 19 or race time in field studies 9, 12. In the study of Gremion et al., in an incremental treadmill test to exhaustion, VO2max showed a significant increase from 52.7 ml × min-1 × kg-1 to 56.5 ml × min-1 × kg-1 (p<0.05) after supplementation with 5g arginine aspartate taken orally 18. However, in the study of Abel et al., VO2max was directly measured on a cycle ergometer and showed no statistically significant increase (p<0.05) 19. Cross country skiers in the study of Schmid et al. finished 36km of cross country skiing significantly faster (198 ± 22.2 min versus 219 ± 21.9 min; p<0.01) after supplementation with 3 x 1g of arginine aspartate taken orally 12. However, in two other studies, neither an effect on measured VO2max 19 nor on race performance in a marathon 9 could be shown. In the study of Colombani et al. 9, running time for a marathon was not changed after supplementation with arginine aspartate and in the study of Abel et al. 19, time to exhaustion in an incremental cycling test was not enhanced as a result of supplementation.
Impressive effects on the performance of endurance exercise have been reported after a prolonged intake of arginine aspartate in earlier studies 12, 22. However, these studies often utilised questionable test procedures to evaluate the influence of arginine aspartate on performance. Most published reports on humans were based on studies of small numbers of subjects. Aspartate, a precursor of oxaloacetate, has been reported to increase the utilisation of FFA and to spare muscle glycogen 23. In addition, it has been suggested that aspartate increases the peripheral clearance of ammonia 21 resulting in delayed muscle fatigue and increased endurance performance. It has been suggested that aspartate may lead to improved endurance performance 23-26 by reducing muscle fatigue and increasing calculated VO2max 18. Reported increases in concentration of FFA 26 and a decrease in lactate concentration 18, 26 could explain the improvement in performance 12, 26.
On the other hand, other studies have found no improvement in performance after supplementation with aspartate 27, 28. No effects on ammonia and lactate concentrations were demonstrated in a double-blind study 29. These inconsistencies may be explained by the different test protocols applied, the different training states of athletes and the different dosages of aspartate. Overall, the evidence suggests that aspartate has at least equal ergogenic advantages in healthy athletes as arginine, although evidence for both is marginal.
Discussion
It has been suggested that arginine alone or in combination with aspartate improves physical performance by means of their effects on substrate metabolism and endocrine parameters. However, it has been shown that the effects on metabolism and endocrine parameters are limited. In addition, effects on performance are also marginal.
Arginine, aspartate or combinations
The question remains whether arginine, aspartate or the combination thereof, leads to possible changes in metabolism and performance. Studies have been performed to assess the effects of aspartate 24, 26, 29, arginine 4-6, 13, 16, 30-32 or arginine aspartate 9, 11, 12, 21. Others used potassium or magnesium aspartate 12, 24, 26, 33, arginine aspartate in combination with carnitine 23 or arginine and lysine for supplementation 6, 16. In addition, the dosages for arginine aspartate varied from 3g 12, 20, 5g 18, 21 or 5.7g arginine and 8.7g aspartate 19 to as high as 15g 9, 11. In addition, combinations with daily 7g 24 to 10g potassium or magnesium aspartate 26, 150mg aspartate per kg body mass 29, 2.4g 6 or 132mg arginine-lysine per kg fat-free body mass and 1g arginine, ornithine and lysine 5 have been used.
It is difficult to directly compare the results of these studies due to the non-uniformity of the study protocols. However, it appears that the combined supplementation might induce synergistic effects. Specifically, arginine may primarily reduce production of lactic acid by the inhibition of glycolysis, and aspartate may favour oxidation of free fatty acids 26.
However, in other studies, no influence on performance or substrate oxidation was found after treatment with aspartate and/or arginine 9, 11, 13, 16. Studies that evaluated the combined effects of a prolonged intake of arginine and aspartate and showed beneficial effects on endurance performance have not been well controlled 12, 22.
In contrast, well controlled studies by Colombani et al. 9, 11 and Abel et al. 19 reported no obvious benefits on metabolism and performance after chronic supplementation with arginine aspartate.
Effect on performance
In some studies, an endurance exercise protocol was performed 9, 12, 19, 21, 24, 34, whereas in others a resistance exercise protocol was followed 5, 6, 11, 13, 16, making the assessment of performance difficult. In the 6 studies with endurance protocols, only Schmid et al. 12 and Ahlborg et al. 24 found an enhanced performance. In the 5 studies with the resistance protocol, the effect on performance was not investigated, or no effect on performance was found.
Effect on metabolic parameters
Metabolites, mainly of carbohydrate and fat metabolism, have been measured during exercise 4, 9, 11, at rest 5, 6 or after exhaustive exercise 19. The change in fat and carbohydrate metabolism is likely to be due to aspartate 34 and the changes in hormone concentrations to arginine 4, 9. Apart from endocrine changes, aspartate seems to increase blood ferritin concentrations 35, while arginine plays an important role in the urea cycle in reducing hyperammonia in the plasma and increasing serum urea concentration 13, 35.
Effect on endurance performance
Two earlier studies 12, 18 showed an improvement in physical exercise performance following supplementation, whereas two more recent studies 9, 19 demonstrated no effect on performance. Since the speed at which the lactate threshold occurs is the best physiological predictor of distance running performance 36, it would be expected that the lactate threshold will increase subsequent to supplementation if there was any impact on performance. However, this has not been investigated in these studies.
Effect on VO2max
In the study of Abel et al. 19, VO2max was directly measured on a cycle ergometer and showed no significant increase as a result of supplementation, but in the study of Gremion et al. 18, the calculated VO2max in an incremental treadmill test until exhaustion showed a significant increase. However, VO2max, in contrast to speed at lactate threshold, is not a good predictor of performance 37, 38. Rather, as shown by Grant et al. in their study with runners, the velocity at lactate threshold is the best single predictor for running speed over 3km 38.
Conclusions
No absolute conclusions can be drawn from this review of the literature on effects of arginine aspartate on metabolism and performance. On the one hand, older studies show, in some cases, positive effects on parameters of metabolism and performance as a result of supplementation, but more recent studies - performed as randomized, double-blind and placebo-controlled trials - suggest no specific effects on various metabolic parameters and performance. Dosages and exercise protocols from earlier studies are not comparable with recent studies.
The effects on metabolic and endocrine parameters do not suggest the potential for improvement in athletic performance. Although the intravenous infusion of arginine appeared to influence hGH, intense physical exercise has the same effect. The positive effect on performance shown in earlier studies has not been demonstrated in recent studies, performed as randomised, double-blind and placebo-controlled trials, with larger subject numbers.
Address for correspondence:
Dr Beat Knechtle, Facharzt FMH für Allgemeinmedizin, Haggenhaldenstr 12, CH-9014 St. Gallen, Switzerland
Tel.: +41 71 534 01 31
Fax: +41 71 534 01 31
Email:beat.knechtle@hispeed.ch
Website: www.beatknechtle.ch
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