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Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org)
Journal of the International Society of Sports Nutrition©. A National Library of Congress Indexed Journal. ISSN # 1550-2783
The Ergogenic Potential of Arginine
Bill I Campbell, Paul M. La Bounty, Mike Roberts
Exercise and Sport Nutrition Laboratory, Baylor University, Waco, TX. Address correspondence
to William_I_Campbell@baylor.edu
Received November 9, 2004 /Accepted December 28, 2004/Published (online)
ABSTRACT
Arginine is a conditionally essential amino acid that is involved in protein synthesis, the
detoxification of ammonia, and its conversion to glucose as well as being catabolized to produce
energy. In addition to these physiological functions, arginine has been purported to have ergogenic
potential. Athletes have taken arginine for three main reasons: 1) its role in the secretion of
endogenous growth hormone; 2) its involvement in the synthesis of creatine; 3) its role in
augmenting nitric oxide. These aspects of arginine supplementation will be discussed as well as a
review of clinical investigations involving exercise performance and arginine ingestion. Journal of
the International Society of Sports Nutrition. 1(2):35-38, 2004
Key Words: sports supplements, sports nutrition, amino acids, nitric oxide
INTRODUCTION
Arginine is a basic amino acid and is
classified as a conditionally essential amino
acid. The typical dietary intake of arginine
is 3.5 to 5 grams daily 1
. One of the main
functions of arginine is its participation in
protein synthesis 2,3
. Also, arginine is
involved in a number of other roles in the
body such as the detoxification of ammonia
formed during the nitrogen catabolism of
amino acids via the formation of urea 1
; its
potential to be converted to glucose (hence
its classification as a glycogenic amino
acid); and its ability to be catabolized to
produce energy 1
. Arginine is utilized by a
number of metabolic pathways that produce
a variety of biologically active compounds
such as nitric oxide, creatine, agmatine,
glutamate, polyamines, ornithine, and
citrulline 2,3
.
In addition to these physiological functions,
arginine has been purported to have
ergogenic potential. Athletes have taken
arginine for three main reasons: 1) its role in
the secretion of endogenous growth
hormone 4
; 2) its involvement in the
synthesis of creatine; 3) its role in
augmenting nitric oxide. The focus of this
review will be to investigate these various
ergogenic possibilities and to examine the
investigations that have looked at arginine
supplementation and exercise performance.
ARGININE AND GROWTH
HORMONE
It is well documented that the infusion of
arginine stimulated growth hormone
secretion from the anterior pituitary 5-7
. This
increase in growth hormone secretion from
arginine infusion has been attributed to the
suppression of endogenous somatostatin
secretion 8
. The amounts of arginine infused
to elicit the growth hormone response
ranged from 12 grams to 30 grams. The
clinical investigations of oral consumption
of arginine and its impact on growth
hormone release are not in agreement.
When arginine (1.2g) was ingested along
with the amino acid lysine (1.2g) in young
Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org) 36
males, peak plasma growth hormone
concentrations increased 8-fold at 90
minutes post-ingestion 9
. However, when
arginine and lysine were ingested alone at
the same doses, there was no corresponding
increase in plasma growth hormone.
Suminiski and associates 10
reported that the
ingestion of arginine (1.5g) and lysine (1.5g)
resulted in a 2.7-fold increase in plasma
growth hormone concentrations in resistance
trained males. Colombani et al. 11
supplemented marathon runners with 15g
arginine aspartate for 14 days before a
marathon run. On the day of the marathon,
blood samples were taken shortly before the
run, after 31km, at the end of the run, and
after a recovery period of two hours. The
researchers found that growth hormone
concentrations were elevated during a
marathon run to a greater degree than
exercise would elicit alone.
Other studies using either resistance trained
or physically active individuals showed no
increases in plasma growth hormone
concentrations following arginine
supplementation. When resistance trained
males consumed approximately 8 grams of
arginine daily for 17 days there was no
associated changes in growth hormone
concentrations 12
. Similarly, Lambert et al.
13
gave male bodybuilders 1.2g of arginine
and 1.2g of lysine. This supplementation
did not induce a statistically significant
increase in serum growth hormone
concentrations over a 3 hour period. In a
recent review, Chromiak and Antonio 4
highlighted several factors that appear to
modify the growth hormone response to
amino acid administration. These include
training status, age, sex, diet, and time since
last meal. Also, the growth hormone
response to amino acid ingestion may be
reduced in exercise-trained individuals 4
.
These authors concluded that the practice of
consuming specific amino acids, including
arginine, during or after exercise does not
appear to be effective 4
.
ARGININE AND CREATINE
Another possible ergogenic potential of
arginine is its role in the synthesis of
creatine. Arginine, glycine, and methionine
are the three amino acids involved in the
synthesis of creatine. Creatine has been
shown to increase muscular strength 14
and
muscle fiber size 15
. In addition, creatine
supplementation enhances performance in
swimming, all out cycling, sprinting,
repeated jumping, and resistance training 16
.
It is worth noting that these improvements in
muscle function and exercise performance
were the result of creatine supplementation.
A question to be asked is whether an
increase in dietary or supplemental arginine
results in an increase in creatine stores to the
levels observed where there was
performance enhancement. Do to the fact
that the rate limiting step in the synthesis of
creatine from arginine and glycine is the
formation of guanidinoacetate by the
enzyme arginine:glycine amidino-transferase
(AGAT) 17
and not arginine concentration;
furthered by the fact that dietary creatine
ingestion downregulates AGAT 18
, it is
unlikely that additional arginine ingestion
leads to increases in creatine concentration
needed to improve performance. Rather, the
most likely method of increasing
performance from increases in creatine
stores is from supplemental creatine or
increasing dietary creatine.
ARGININE AND NITRIC OXIDE
Arginine is a precursor of the cell-signaling
molecule nitric oxide (NO). NO acts as a
signaling molecule to facilitate the dilation
of blood vessels and decrease vascular
resistance. NO is synthesized from arginine
under the enzymatic control of nitric oxide
synthase (NOS). There are three NOS
isoforms, endothelial cell NOS (eNOS),
neuronal NOS (nNOS), and inducible NOS
(iNOS). Skeletal muscle expresses all three
forms of NOS, with nNOS predominating.
Muscle functions regulated by NO or related
molecules include force production
Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org) 37
(excitation-contraction coupling),
autoregulation of blood flow, myocyte
differentiation, respiration, and glucose
homeostasis 19
. Contractile activity greatly
increases NO production in the muscle, and
this is likely due to elevated intracellular
calcium 20
. One of the main effects of NO
on skeletal muscle metabolism is to increase
the delivery and uptake of fuel substrates via
its vasodilating effects 21
. Even though
arginine augments nitric oxide production,
there is still no clear evidence that this
synthesis of nitric oxide results in
improvements in exercise performance in
healthy individuals.
ARGININE AND EXERCISE
PERFORMANCE
With all of the aforementioned effects that
arginine possesses in relation to ergogenic
potential, it would seem plausible that
supplementing with arginine would improve
exercise performance and body composition.
There is scant evidence that this is the case
in humans, and the available data is
conflicting. When male weight trainers on a
hypocaloric diet ingested approximately 8
grams of arginine daily, there were no
positive influences on muscle function
(biceps/quadriceps isokinetic assessments)
or body composition 12
. Conversely, when
untrained males were given 3 grams of
arginine daily for 15 days and underwent a
test retest protocol evaluating resistance to
muscular fatigue (by quadriceps isokinetic
dynamometry), there was a significant
resistance to muscular fatigue 22
.
Unfortunately, the investigators did not
utilize a double-blinded protocol nor was
there a placebo or control group.
In addition to the studies conducted on
healthy subjects, there are also several
studies investigating the effects of oral
arginine supplementation in subjects with
cardiovascular issues 23-25
. Subjects with
congestive heart failure ingested 9 grams of
arginine daily for 7 days. At the end of the
supplementation period, the authors
concluded that in patients with chronic
stable congestive heart failure,
supplementation with a moderate dose of
arginine resulted in a prolonged exercise
duration as compared to placebo 23
. In
patients with healed myocardial infarction,
investigators 24
supplemented the
participants with 6 grams of arginine for 3
days. After only 3 days of such
supplementation, the authors concluded that
oral arginine supplementation had a
beneficial effect on exercise capacity in
patients with stable angina.
Nagaya, et al. 25
studied the effects of oral
supplementation of arginine on exercise
capacity in patients with pulmonary
hypertension. Cardiorespiratory exercise
tests were performed to measure peak
oxygen consumption. The supplementation
protocol required that each treated subject
consume 1.5 g of arginine per 10 kg of body
weight per day for 7 days. A significant
increase in peak oxygen consumption was
observed. A possible mechanism to describe
this increase in performance is the role that
arginine has in augmenting nitric oxide. An
increase in nitric oxide bioavailability results
in coronary vessel vasodilatation and flow,
which in turn may positively influence
coronary perfusion.
CONCLUSION
Arginine’s involvement as a precursor of
creatine and its potential to increase
endogenous growth hormone makes it a
popular supplement among those who wish
to improve their physical performance. The
choice to supplement with arginine is also
based on sound physiologic theory.
However, there is currently little scientific
evidence available to support such claims
promoting and increase in functional
capacity in healthy, athletic participants.
Among those with cardiovascular issues
(congestive heart failure, healed myocardial
infarction, and pulmonary hypertension)
there does seem to be some rational for
ingesting arginine (3-9g/day) for an
improvement in physical performance.
Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org) 38
These improvements may be accounted for
via arginine’s role as a precursor to nitric
oxide. More research is needed to evaluate
the role of arginine supplementation on
exercise performance and training
adaptations in healthy and diseased
populations before any conclusions can be
drawn.
REFERENCES
1. PDR for Nutritional Supplements, Montvale, NJ: Thompson PDR.; 2001
2. Tong BC, Barbul, A. Cellular and physiological effects of arginine. Mini Reviews in Medicinal Chemistry 2004;4(8):823-32.
3. Wu G, Morris SM. Arginine metabolism: nitric oxide and beyond. Biochem. J. 1998;336:1-17.
4. Chromiak JA, Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 2002;18(7/8):657-661.
5. Merimee TJ, Rabinowitz D, Riggs L, et al. Plasma growth hormone after arginine infusion. Clinical experiences. N Engl J Med
1967;276(8):434-9.
6. Merimee TJ, Rabinowitz D, Fineberg SE. Arginine-initiated release of human growth hormone. Factors modifying the
response in normal man. N Engl J Med 1969;280(26):1434-8.
7. Hembree WC, Ross GT. Arginine infusion and growth-hormone secretion. Lancet 1969;1(7584):52.
8. Alba-Roth J, Muller OA, Schopohl J, et al. Arginine stimulates growth hormone secretion by suppressing endogenous
somatostatin secretion. J Clin Endocrinol Metab 1988;67(6):1186-9.
9. Isidori A, Lo Monaco A, Cappa M. A study of growth hormone release in man after oral administration of amino acids. Curr
Med Res Opin 1981;7(7):475-81.
10. Suminiski RR, Robertson RJ, Goss FL, et al. Acute effect of amino acid ingestion and resistance exercise on plasma growth
hormone concentration in young men. Int J Sport Nutr 1997;7:48-60.
11. Colombani PC, Bitzi R, Frey-Rindova P, Frey W, et al. Chronic arginine aspartate supplementation in runners reduces total
plasma amino acid level at rest and during a marathon run. Eur J Nutr 1999;38:263-70.
12. Walberg-Rankin J, Hawkins C, et al. The effect of oral arginine during energy restriction in male weight trainers. J Strength
Cond Res 1994;8(3):170-7.
13. Lambert MI, Hefer JA, Millar RP, Macfarlane PW. Failure of commercial oral amino acid supplements to increase serum
growth hormone concentrations in male bodybuilders. Int J Sport Nutr 1993;3:298.
14. Vandenberghe k, Goris M, Van Hecke P, Van Leemputte M, et al. Long-term creatine intake is beneficial to muscle
performance and pharmacokinetic considerations. J Appl Physiol 1997;83:2055-2063.
15. Volek JS, Duncan ND, Mazzetti SA, Putukian M. Performance and muscle fiber adaptations to creatine supplementation and
heavy resistance training. Med Sci Sports Exerc 1999;31:1147-1156.
16. Juhn MS, Tarnopolsky M. Oral creatine supplementation and athletic performance: A critical review. Clin J Sport Med
1998;8:286-297.
17. Walker JB. Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 1979;50:177-242.
18. Stead LM, Au KP, Jacobs RL, Brosnan ME, et al. Methylation demand and homocysteine metabolism: effects of dietary
provision of creatine and guanidineacetate. Am J Physiol 2001;281:E1095-E1100.
19. Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev 2001;81(1):209-237.
20. Kobzik L, Reid MB, Bredt DS, Stamler JS. Nitric-oxide in skeletal muscle. Nature 1994;372(6506):546-548.
21. Wolin MS, Hintze TH, Shen W, Hohazzabh KM, et al. Involvement of reactive oxygen and nitrogen species in signaling
mechanisms that control tissue respiration in muscle. Biochem Sos Trans 1997;25(3):934-939.
22. Santos RS, Pacheco MTT, Martins RABL, Villaverde AB, et al. Study of the effect of oral administration of L-arginine on
muscular performance in healthy volunteers: an isokinetic study. Isokinetics and Exercise Science 2002;10(3):153-158.
23. Bednarz B, Jaxa-Chamiec T, Gebalska J, Herba K, et al. L-arginine supplementation prolongs duration of exercise in
congestive heart failure. Polish Heart Journal 2004;60(4):348-353
24. Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients
with stable angina pectoris. Am J Cardiol 1997;80(3):331-333.
25. Nagaya N, Uematsu M, Oya H, Sato N, et al. Short-term oral administration of L-arginine improves hemodynamics and
exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 2001;163:887-891.

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The ergogenic potential of arginine

  • 1. Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org) Journal of the International Society of Sports Nutrition©. A National Library of Congress Indexed Journal. ISSN # 1550-2783 The Ergogenic Potential of Arginine Bill I Campbell, Paul M. La Bounty, Mike Roberts Exercise and Sport Nutrition Laboratory, Baylor University, Waco, TX. Address correspondence to William_I_Campbell@baylor.edu Received November 9, 2004 /Accepted December 28, 2004/Published (online) ABSTRACT Arginine is a conditionally essential amino acid that is involved in protein synthesis, the detoxification of ammonia, and its conversion to glucose as well as being catabolized to produce energy. In addition to these physiological functions, arginine has been purported to have ergogenic potential. Athletes have taken arginine for three main reasons: 1) its role in the secretion of endogenous growth hormone; 2) its involvement in the synthesis of creatine; 3) its role in augmenting nitric oxide. These aspects of arginine supplementation will be discussed as well as a review of clinical investigations involving exercise performance and arginine ingestion. Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004 Key Words: sports supplements, sports nutrition, amino acids, nitric oxide INTRODUCTION Arginine is a basic amino acid and is classified as a conditionally essential amino acid. The typical dietary intake of arginine is 3.5 to 5 grams daily 1 . One of the main functions of arginine is its participation in protein synthesis 2,3 . Also, arginine is involved in a number of other roles in the body such as the detoxification of ammonia formed during the nitrogen catabolism of amino acids via the formation of urea 1 ; its potential to be converted to glucose (hence its classification as a glycogenic amino acid); and its ability to be catabolized to produce energy 1 . Arginine is utilized by a number of metabolic pathways that produce a variety of biologically active compounds such as nitric oxide, creatine, agmatine, glutamate, polyamines, ornithine, and citrulline 2,3 . In addition to these physiological functions, arginine has been purported to have ergogenic potential. Athletes have taken arginine for three main reasons: 1) its role in the secretion of endogenous growth hormone 4 ; 2) its involvement in the synthesis of creatine; 3) its role in augmenting nitric oxide. The focus of this review will be to investigate these various ergogenic possibilities and to examine the investigations that have looked at arginine supplementation and exercise performance. ARGININE AND GROWTH HORMONE It is well documented that the infusion of arginine stimulated growth hormone secretion from the anterior pituitary 5-7 . This increase in growth hormone secretion from arginine infusion has been attributed to the suppression of endogenous somatostatin secretion 8 . The amounts of arginine infused to elicit the growth hormone response ranged from 12 grams to 30 grams. The clinical investigations of oral consumption of arginine and its impact on growth hormone release are not in agreement. When arginine (1.2g) was ingested along with the amino acid lysine (1.2g) in young
  • 2. Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org) 36 males, peak plasma growth hormone concentrations increased 8-fold at 90 minutes post-ingestion 9 . However, when arginine and lysine were ingested alone at the same doses, there was no corresponding increase in plasma growth hormone. Suminiski and associates 10 reported that the ingestion of arginine (1.5g) and lysine (1.5g) resulted in a 2.7-fold increase in plasma growth hormone concentrations in resistance trained males. Colombani et al. 11 supplemented marathon runners with 15g arginine aspartate for 14 days before a marathon run. On the day of the marathon, blood samples were taken shortly before the run, after 31km, at the end of the run, and after a recovery period of two hours. The researchers found that growth hormone concentrations were elevated during a marathon run to a greater degree than exercise would elicit alone. Other studies using either resistance trained or physically active individuals showed no increases in plasma growth hormone concentrations following arginine supplementation. When resistance trained males consumed approximately 8 grams of arginine daily for 17 days there was no associated changes in growth hormone concentrations 12 . Similarly, Lambert et al. 13 gave male bodybuilders 1.2g of arginine and 1.2g of lysine. This supplementation did not induce a statistically significant increase in serum growth hormone concentrations over a 3 hour period. In a recent review, Chromiak and Antonio 4 highlighted several factors that appear to modify the growth hormone response to amino acid administration. These include training status, age, sex, diet, and time since last meal. Also, the growth hormone response to amino acid ingestion may be reduced in exercise-trained individuals 4 . These authors concluded that the practice of consuming specific amino acids, including arginine, during or after exercise does not appear to be effective 4 . ARGININE AND CREATINE Another possible ergogenic potential of arginine is its role in the synthesis of creatine. Arginine, glycine, and methionine are the three amino acids involved in the synthesis of creatine. Creatine has been shown to increase muscular strength 14 and muscle fiber size 15 . In addition, creatine supplementation enhances performance in swimming, all out cycling, sprinting, repeated jumping, and resistance training 16 . It is worth noting that these improvements in muscle function and exercise performance were the result of creatine supplementation. A question to be asked is whether an increase in dietary or supplemental arginine results in an increase in creatine stores to the levels observed where there was performance enhancement. Do to the fact that the rate limiting step in the synthesis of creatine from arginine and glycine is the formation of guanidinoacetate by the enzyme arginine:glycine amidino-transferase (AGAT) 17 and not arginine concentration; furthered by the fact that dietary creatine ingestion downregulates AGAT 18 , it is unlikely that additional arginine ingestion leads to increases in creatine concentration needed to improve performance. Rather, the most likely method of increasing performance from increases in creatine stores is from supplemental creatine or increasing dietary creatine. ARGININE AND NITRIC OXIDE Arginine is a precursor of the cell-signaling molecule nitric oxide (NO). NO acts as a signaling molecule to facilitate the dilation of blood vessels and decrease vascular resistance. NO is synthesized from arginine under the enzymatic control of nitric oxide synthase (NOS). There are three NOS isoforms, endothelial cell NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). Skeletal muscle expresses all three forms of NOS, with nNOS predominating. Muscle functions regulated by NO or related molecules include force production
  • 3. Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org) 37 (excitation-contraction coupling), autoregulation of blood flow, myocyte differentiation, respiration, and glucose homeostasis 19 . Contractile activity greatly increases NO production in the muscle, and this is likely due to elevated intracellular calcium 20 . One of the main effects of NO on skeletal muscle metabolism is to increase the delivery and uptake of fuel substrates via its vasodilating effects 21 . Even though arginine augments nitric oxide production, there is still no clear evidence that this synthesis of nitric oxide results in improvements in exercise performance in healthy individuals. ARGININE AND EXERCISE PERFORMANCE With all of the aforementioned effects that arginine possesses in relation to ergogenic potential, it would seem plausible that supplementing with arginine would improve exercise performance and body composition. There is scant evidence that this is the case in humans, and the available data is conflicting. When male weight trainers on a hypocaloric diet ingested approximately 8 grams of arginine daily, there were no positive influences on muscle function (biceps/quadriceps isokinetic assessments) or body composition 12 . Conversely, when untrained males were given 3 grams of arginine daily for 15 days and underwent a test retest protocol evaluating resistance to muscular fatigue (by quadriceps isokinetic dynamometry), there was a significant resistance to muscular fatigue 22 . Unfortunately, the investigators did not utilize a double-blinded protocol nor was there a placebo or control group. In addition to the studies conducted on healthy subjects, there are also several studies investigating the effects of oral arginine supplementation in subjects with cardiovascular issues 23-25 . Subjects with congestive heart failure ingested 9 grams of arginine daily for 7 days. At the end of the supplementation period, the authors concluded that in patients with chronic stable congestive heart failure, supplementation with a moderate dose of arginine resulted in a prolonged exercise duration as compared to placebo 23 . In patients with healed myocardial infarction, investigators 24 supplemented the participants with 6 grams of arginine for 3 days. After only 3 days of such supplementation, the authors concluded that oral arginine supplementation had a beneficial effect on exercise capacity in patients with stable angina. Nagaya, et al. 25 studied the effects of oral supplementation of arginine on exercise capacity in patients with pulmonary hypertension. Cardiorespiratory exercise tests were performed to measure peak oxygen consumption. The supplementation protocol required that each treated subject consume 1.5 g of arginine per 10 kg of body weight per day for 7 days. A significant increase in peak oxygen consumption was observed. A possible mechanism to describe this increase in performance is the role that arginine has in augmenting nitric oxide. An increase in nitric oxide bioavailability results in coronary vessel vasodilatation and flow, which in turn may positively influence coronary perfusion. CONCLUSION Arginine’s involvement as a precursor of creatine and its potential to increase endogenous growth hormone makes it a popular supplement among those who wish to improve their physical performance. The choice to supplement with arginine is also based on sound physiologic theory. However, there is currently little scientific evidence available to support such claims promoting and increase in functional capacity in healthy, athletic participants. Among those with cardiovascular issues (congestive heart failure, healed myocardial infarction, and pulmonary hypertension) there does seem to be some rational for ingesting arginine (3-9g/day) for an improvement in physical performance.
  • 4. Journal of the International Society of Sports Nutrition. 1(2):35-38, 2004. (www.sportsnutritionsociety.org) 38 These improvements may be accounted for via arginine’s role as a precursor to nitric oxide. More research is needed to evaluate the role of arginine supplementation on exercise performance and training adaptations in healthy and diseased populations before any conclusions can be drawn. REFERENCES 1. PDR for Nutritional Supplements, Montvale, NJ: Thompson PDR.; 2001 2. Tong BC, Barbul, A. Cellular and physiological effects of arginine. Mini Reviews in Medicinal Chemistry 2004;4(8):823-32. 3. Wu G, Morris SM. Arginine metabolism: nitric oxide and beyond. Biochem. J. 1998;336:1-17. 4. Chromiak JA, Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 2002;18(7/8):657-661. 5. Merimee TJ, Rabinowitz D, Riggs L, et al. Plasma growth hormone after arginine infusion. Clinical experiences. N Engl J Med 1967;276(8):434-9. 6. Merimee TJ, Rabinowitz D, Fineberg SE. Arginine-initiated release of human growth hormone. Factors modifying the response in normal man. N Engl J Med 1969;280(26):1434-8. 7. Hembree WC, Ross GT. Arginine infusion and growth-hormone secretion. Lancet 1969;1(7584):52. 8. Alba-Roth J, Muller OA, Schopohl J, et al. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab 1988;67(6):1186-9. 9. Isidori A, Lo Monaco A, Cappa M. A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin 1981;7(7):475-81. 10. Suminiski RR, Robertson RJ, Goss FL, et al. Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int J Sport Nutr 1997;7:48-60. 11. Colombani PC, Bitzi R, Frey-Rindova P, Frey W, et al. Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run. Eur J Nutr 1999;38:263-70. 12. Walberg-Rankin J, Hawkins C, et al. The effect of oral arginine during energy restriction in male weight trainers. J Strength Cond Res 1994;8(3):170-7. 13. Lambert MI, Hefer JA, Millar RP, Macfarlane PW. Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male bodybuilders. Int J Sport Nutr 1993;3:298. 14. Vandenberghe k, Goris M, Van Hecke P, Van Leemputte M, et al. Long-term creatine intake is beneficial to muscle performance and pharmacokinetic considerations. J Appl Physiol 1997;83:2055-2063. 15. Volek JS, Duncan ND, Mazzetti SA, Putukian M. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc 1999;31:1147-1156. 16. Juhn MS, Tarnopolsky M. Oral creatine supplementation and athletic performance: A critical review. Clin J Sport Med 1998;8:286-297. 17. Walker JB. Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 1979;50:177-242. 18. Stead LM, Au KP, Jacobs RL, Brosnan ME, et al. Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidineacetate. Am J Physiol 2001;281:E1095-E1100. 19. Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev 2001;81(1):209-237. 20. Kobzik L, Reid MB, Bredt DS, Stamler JS. Nitric-oxide in skeletal muscle. Nature 1994;372(6506):546-548. 21. Wolin MS, Hintze TH, Shen W, Hohazzabh KM, et al. Involvement of reactive oxygen and nitrogen species in signaling mechanisms that control tissue respiration in muscle. Biochem Sos Trans 1997;25(3):934-939. 22. Santos RS, Pacheco MTT, Martins RABL, Villaverde AB, et al. Study of the effect of oral administration of L-arginine on muscular performance in healthy volunteers: an isokinetic study. Isokinetics and Exercise Science 2002;10(3):153-158. 23. Bednarz B, Jaxa-Chamiec T, Gebalska J, Herba K, et al. L-arginine supplementation prolongs duration of exercise in congestive heart failure. Polish Heart Journal 2004;60(4):348-353 24. Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol 1997;80(3):331-333. 25. Nagaya N, Uematsu M, Oya H, Sato N, et al. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 2001;163:887-891.