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Athletic Performance and Supplementation of Ornithine and Arginine By Jeff Gibberman and Ryan Kline Bastyr – Sports Nutrition, Spring 2012 1 Introduction It is well known that adequate protein and amino acids are necessary for the anabolic processes that occur as a result of athletic training and recovery. Research has been done to study the effect of various amino acids on human biochemistry to explore potential supplementation, ergogenic aids, that can ultimately increase athletic performance. Arginine and Ornithine are two amino acids that have been studies for their potential ability to have positive effects on athletic performance. Arginine is classified as a semi-essential or conditionally essential amino acid.1 This is due to a healthy body’s ability to synthesize arginine for its metabolic needs, thus only being essential in unusual circumstances like preterm infants that are unable to synthesize it endogenously. Arginine is also found naturally in a variety of foods including dairy products, oatmeal and nuts.1 Arginine is just one of the many molecular intermediates of the vast amount of bioactive reactions that occur in the body. Arginine as an ergogenic aid is linked with its roles as a nitric oxide precursor, nitrogen metabolism, synthesis of creatine, and hormone production.2 Nitric oxide (NO) plays an important role in the cardiovascular system as a regulator of vasodilatation. Vasodilation increases the supply of oxygenated and nutrient rich blood to muscle tissue, potentially increasing the efficiency of energy production in the muscle. Nitrogen metabolism via the urea cycle is important in maintaining nitrogen balance within the body. Creatine is an important compound that increases ATP synthesis in muscle. Ornithine is a an amino acid that is not required for DNA coding, and is not use in protein synthesis, rather it is an amino acid that plays a central role in the urea cycle.1 Ornithine is created in the body by the hydrolysis of arginine. Both ornithine and arginine are amino acids that play roles in the urea cycle. Ornithine, like Arginine, also plays a role in increased hormone production. Increased hormone production can lead to increased performance and has increased anabolic effects on the body. The following studies were selected to highlight the current research for use of both arginine and ornithine as ergogenic aids to increase athletic performance. Current Research In 2005 Collier et al. conducted a randomized double-blind study to determine the optimal oral dosage of arginine needed to affect the most significant increase in growth hormone (GH), as well as calculate a timeline for various doses to take effect.3 Blood samples were drawn from eight healthy young males over a period of five hours on four different occasions. Objectives were to determine the optimal oral 2 dosage amount and to assess the timeline of metabolic response of the arginine-dependent GH secretion. The trial consisted of four groups, differing only in arginine dosage (5g, 9g, 13g and 0g) which was ingested 30 minutes after blood sampling began. The statistical analysis was only conducted on six of the eight men due to GI distress at each dose in two of the subjects. The highest increase in blood GH concentration occurred ~60 minutes after arginine ingestion and began at ~30 minutes post ingestion. Peak GH levels increased 34% in subjects that consumed 5 g/day of arginine, and more than doubled when 9 g/day was ingested. GH levels showed a slight but insignificant increase when 13 g/d was consumed; however, an increased prevalence of a GI issues was noted. Collier et al. conducted a follow up study in 2006 that compared GH levels with arginine supplementation with and without exercise in eight healthy young men that were randomly selected from a qualifying survey done at Syracuse University.4 The subjects agreed participated in 3.5 hour lab evaluations one four separate occasions, subjects were also asked to not make any dietary changes. Blood was drawn every ten minutes to track GH levels. The supplemented dose was 7g of arginine. Collier et al. observed increased GH in both the exercise only and arginine only controls, with a greater hormone release in the exercise only control. One would assume that exercising and supplementing with arginine combined would have even greater effects on GH release, however when subjects both were supplemented with arginine and exercised, results showed a diminished GH release when compared to the exercise alone control. Collier et al. hypothesize that this result is due to an autonegative feedback that possibly causes a refractory period that suppress the release of GH hormone from the pituitary gland in the presence of two stimuli. Demura et al. conducted a study in 2010 consisting of ten healthy men that did not regularly participate in high intensity training partook in a double blind cross over study that measured the effects of oral ornithine ingestion on GH secretion after training.5 Oral dose of L-ornithine hydrochloride was adjusted to participant’s body weight at a ratio of 0.1 g per body mass. Blood was taken to measure serum ornithine and GH levels at a baseline before ingestion of ornithine, and performed a weight bearing exercise one hour after ingestion. Blood was taken 30 minutes after exercise for comparison analysis. Results of this study show that both serum ornithine and human GH were significantly increased in comparison to placebo. The study also noted that six out of the ten participants experienced GI discomfort such as stomachache and diarrhea related to the dose amount, thus concluding that more research is needed to be done in order to explore optimal dosing for avoiding these negative side effects while reaping the benefit of increased muscle anabolism activity via human GH. Demura et al. 3 hypothesized that previous studies that did not support their findings could have been due to varying dosage amounts and subjects that consisted of mainly body builders or weight lifters who routinely conducted high intensity strength training; inferring that the biological limit of enlarged muscle fibers in these well trained subjects marginalized the activity of anabolic processes. In 2010, Zajac et al. conducted a study to assess both arginine and ornithine supplementation and its role in anabolic activity.6 Subjects consisted of seventeen strength-trained young male athletes (weight lifters and body builders) and the study design was a double-blind and placebo-controlled study. The subjects were conditioned with a weight bearing exercise protocol for nine weeks before the supplementation period of the study. Subjects were also placed on a mixed isocaloric diet. The supplemented group was given 2,200 mg of L-ornithine 3,000 mg of L-arginine orally 2x daily. Blood samples were taken at rest, two minutes after strength exercise protocol, and again one hour after exercise to assess anabolic biomarkers such as GH, cortisol, testosterone and insulin levels. There was no change in body mass in either group over the study period. Subject groups were measured at a baseline then completed an additional three weeks of training before final assessment for comparison to baseline of placebo and supplemented group. Zajac et al. observed that arginine and ornithine supplementation increased GH and insulin-like growth factor-1 (IGF-1) levels. They also found that lower insulin-like growth factor binding proftein-3 (IGFBP-3) levels, which they hypothesized, may be due to increased IGF-1 availability in tissue. The relationship between these 3 biomarkers, GH/IGF-1/IGFBP-3, favor the anabolic state and the authors conclude that arginine and ornithine supplementation may provide benefits during strength training in conditioned athletes. In 2010 a double-blind crossover study was conducted by Bailey et al. that consisted of nine healthy middle aged men were supplemented with 6 g of arginine beverage one hour before completing a series of moderate and intense exercise bouts.7 Subjects were required to report to the laboratory on seven occasions over a four- to five- week period, and were supplemented according to current arginine pharmacokinetics protocol. Blood pressure was taken at rest before exercise, pulmonary gas exchange and ventilation were measure continuously along with hearth rate, and blood samples were taken during and after exercise. Subjects’ baselines were assessed during the first visit, and then were randomly assigned to a control group for three days of supplementation of either placebo drink or commercially available L-arginine product (ARK 1). Subject diets remained unchanged from their regular diets and were required to keep food journals throughout the study. Bailey et al. observed increased indexes of nitric oxide (NO) synthesis, reduced steady-state VO2 during moderate-intensity exercise and 4 reduced VO2 slow component. Subjects also experienced a slower time to task failure during severeintensity exercise. The authors conclude that arginine supplementation increases plasma NO, reduce systolic blood pressure, and improves exercise efficiency and tolerance in healthy middle aged men. Although the mechanisms for increased stamina are unknown, the authors hypothesized that the increase was most likely due to increased oxygen supply to muscle and direct effects on muscle contractile efficiency and/or mitochondrial function. Professional Opinion We believe that based on the current research that the usefulness of arginine and ornithine supplementation can be beneficial for specific individuals. Timing, method of supplementation, dosage, aerobic vs. anaerobic, health of the individual, age, and level of training are all factors that need to be taken into consideration for using arginine and ornithine as ergogenic aids. As noted by Demura et al., previous studies that found no significant release of GH from arginine supplementation could have been due to insufficient dosage amounts and the fact that subjects studied consisted mainly body builders or weight lifters who routinely conducted high intensity strength training.5 Demura et al. further hypothesized that diminished return related to the biological limit of enlarged muscle fibers in these well trained subjects. Based on these observations, we can infer that arginine supplementation may have amplified effects in deconditioned or intermediate athletes when compared to highly trained athletes. Both exercise and arginine supplementation alone increased the release of GH.4 Ironically, arginine supplementation coupled with exercise induced decreased GH levels when compared to the exercise alone, thus we would recommend supplementing with arginine for the purpose of increased GH levels to enhance recovery several hours after exercise or on off days. Side Effects & Concerns A high dose of arginine, 13g, caused GI distress in all but one of eight subjects in the Collier et al. study. Therefore, high doses of arginine can have negative effects on GI functioning. Six out of the ten subjects from the study by Demura et al. also experienced GI discomfort such as stomachache and diarrhea at a dose ratio of 0.1 g per body mass. 5 Conclusion The optimal dose for arginine supplementation to increase GH levels without exercise seems to peak at ~9 grams since only marginal increases were observed at a higher does along increased GI distress, thus incremental GH levels can be expected to result from oral arginine doses up to ~9 grams.3 As noted in the study by Collier et al., arginine supplementation before exercise resulted in diminished release of GH after weight bearing exercise when compared to the exercise alone control.4 Therefore, it seems best to take arginine apart from exercise to attain both its positive effects of increased GH release and increased nitric oxide production. Arginine supplementation with ornithine appears to have a positive effect of increasing GH release.6 Ornithine supplementation by itself also appears to have a positive effect on increasing GH levels in the body.5 Arginine supplementation also increases NO production (a vasodilator) which can aid in the anabolic process by increasing the profusion of nutrient rich blood to tissue, allowing for optimal recovery.7 In summary, oral supplementation of arginine and ornithine do have physiological effects that can enhance performance and recovery in athletes. 6 References 1. Sareen G., Jack S. James G. Advanced Nutrition and Human Metabolism. 5th ed. Belmont, CA: Wadsworth; 2009, 2005. 2. Wikipedia free online encyclopedia. Available at: http://en.wikipedia.org/wiki/Arginine http://en.wikipedia.org/wiki/Nitric_oxide http://en.wikipedia.org/wiki/Vasodilation http://en.wikipedia.org/wiki/Creatine 3. Callier S, Casey D, Kanaley J. Growth hormone responses to varying doses of oral arginine. Growth Horm IGF Res 2005;15:136-139. 4. Collier S, Collins E, Kanaley J. Oral arginine attenuates the growth hormone response to resistance exercise. J Appl Physiol 2006;101:848-852. 5. Demura S, Yamada T, Yamaji S, Komatsu M, Morishita K. The effect of L-ornithine hydrochloride ingestion on human growth hormone secretion after strength training. Adv Biosci Biotechnol 2010;1:7-11. 6. Zajac A, Poprzecki S, Zebrowska A, Chalimoniuk M, Langfort J. Arginine and ornithine supplementation increases growth hormone and insulin-like growth factor-1 serum levels after heavy-resistance exercise in strength-trained athletes. J Strength Cond Res 2010;24,4:10831090. 7. Bailey S, Winyard P, Vanhatalo A, et al. Acute L-arginine supplementation reduces the O2 cost of moderate-intensity excersize and enhances high-intensity excersize tolerance. J Appl Physiol 2010;109:1394-1403. 7