Oral arginine attenuates the growth hormone response to resistance exercise

[7:360]

Oral arginine attenuates the growth hormone response to resistance exercise
S. R. Collier, E. Collins, and J. A. Kanaley

Department of Exercise Science, Syracuse University, Syracuse, New York

Submitted 7 March 2006 ; accepted in final form 23 May 2006

This study investigated the combined effect of resistance exercise and arginine ingestion on spontaneous growth hormone (GH) release. Eight healthy male subjects were studied randomly on four separate occasions [placebo, arginine (Arg), placebo + exercise (Ex), arginine + exercise (Arg+Ex)]. Subjects had blood sampled every 10 min for 3.5 h. After baseline sampling (30 min), subjects ingested a 7-g dose of arginine or placebo (blinded, randomly assigned). On the exercise days, the subject performed 3 sets of 9 exercises, 10 repetitions at 80% one repetition maximum. Resting GH concentrations were similar on each study day. Integrated GH area under the curve was significantly higher on the Ex day (508.7 ? 169.6 min?ng/ml; P < 0.05) than on any of the other study days. Arg+Ex (260.5 ? 76.8 min?ng/ml) resulted in a greater response than the placebo day but not significantly greater than the Arg day. The GH half-life and half duration were not influenced by the stimulus administered. The GH secretory burst mass was larger, but not significantly, on the Arg, Ex, and Arg+Ex day than the placebo day. Endogenous GH production rate (Ex > Arg+Ex > Arg > placebo) was greater on the Ex and Arg+Ex day than on the placebo day (P < 0.05) but there were no differences between the Ex and Arg+Ex day. Oral arginine alone (7 g) stimulated GH release, but a greater GH response was seen with exercise alone. The combined effect of arginine before exercise attenuates the GH response. Autonegative feedback possibly causes a refractory period such that when the two stimuli are presented there will be suppression of the ****totrope.

[Trans_Isomer]

Interesting stuff, I have NOT looked at the complete full studies but heres another that seems to coincide with study above...



Oral arginine does not stimulate basal or augment exercise-induced GH
secretion in either young or old adults.

Marcell TJ, Taaffe DR, Hawkins SA, Tarpenning KM, Pyka G, Kohlmeier L, Wiswell RA, Marcus R.
Department of Exercise Science, University of Southern California, Los Angeles, USA. marcellt@grc.nia.nih.gov

BACKGROUND: Growth hormone (GH) helps maintain body composition and metabolism in adults. However, basal and peak GH decline with age. Exercise produces a physiologic GH response that is subnormal in elderly people. Arginine (Arg) infusion can augment GH secretion, but the efficacy of oral Arg to improve GH response to exercise has not been explored. We investigated whether oral Arg increases GH secretion in young and old people at rest and during exercise. METHODS: Twenty young (Y: 22.1 +/- 0.9 y; SEM) and 8 old (O: 68.5 +/- 2.1 y) male and female subjects underwent three different trials following determination of their one-repetition maximum strength (1-RM); exercise only (EO; 3 sets, 8-10 reps at 85% of 1-RM; on 12 separate resistive lifts), Arg only (5.0 g), or Arg + exercise. Blood samples were collected between successive lifts, and GH (ng x ml(-1)) was determined via RIA. RESULTS: In Y vs O: Basal GH secreted (area under the curve) was 543.6 +/- 84.0 vs 211.5 +/- 63.0. During EO, values were 986.6 +/- 156.6 and 517.8 +/- 85.5. Both were significantly lower in the older individuals (p < .05). Oral Arg alone did not result in any increase in GH secretion at rest (310.8 +/- 73.2 vs 262.9 +/- 141.2). When Arg was coadministered during exercise, GH release was not affected in either the young or old and appeared to be blunted in the young compared to the exercise only trial in the young. CONCLUSION: Based upon these findings, we concluded that oral Arg does not stimulate GH secretion and may impair GH release during resistive exercise.

PMID: 10496544 [PubMed - indexed for MEDLINE]

[INGENIUM]

here are the 2 most important quotes from this abstract...

Endogenous GH production rate (Ex > Arg+Ex > Arg > placebo) was greater on the Ex and Arg+Ex day than on the placebo day

endogenous GH production was GREATER on the exercise only day than on the EX + ARG day...

Oral arginine alone (7 g) stimulated GH release, but a greater GH response was seen with exercise alone

AND exercise alone stimulated a greater GH response than arginine alone...

this only supports my belief that arginine has no significant effect on GH

[Vipersg123]

i've been saying this for a while.

[in10city]

i've been saying this for a while.

So have I

http://forum.bodybuilding.com/search...&starteronly=0

[Dr.Dave1]

Interesting stuff

Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):46-51.
Effects of L-arginine supplementation on exercise metabolism.
McConell GK.


PURPOSE OF REVIEW: To describe the influence of acute and chronic administration of L-arginine on metabolism at rest and during exercise. RECENT FINDINGS: There has been substantial examination of the effect of infusion and ingestion of L-arginine at rest. It has been clearly demonstrated that L-arginine administration improves endothelial function in various disease states. In addition, L-arginine infusion at rest increases plasma insulin, growth hormone, glucagon, catecholamines and prolactin. Such hormonal changes affect metabolism. There has, however, been very little examination of the effect of increases in L-arginine availability during exercise. This is important to study as there is preliminary evidence that L-arginine infusion, probably via increases in nitric oxide (NO), alters skeletal-muscle metabolism during exercise. There is a need for further research, especially to understand the mechanisms of how L-arginine affects exercise metabolism and also to determine whether the hormonal responses that occur in response to L-arginine at rest are also present to some extent during exercise. SUMMARY: This line of research may have important therapeutic implications as there are indications that L-arginine augments the effects of exercise training on insulin sensitivity and capillary growth in muscles.

PMID: 17143054 [PubMed - in process]

The article did not comment on the affect of arginine on GH during exercise only on the affect at rest, the following is an excerpt from that portion

L-Arginine infusion at rest increases plasma insulin, glucagon, growth hormone, prolactin and adrenaline (epinephrine) and noradrenaline (norepinephrine) concentrations [13?15]. Intravenous infusion of several different amino acids stimulates insulin secretion, with L-arginine being the most potent . . . In aerobically trained individuals at rest, there appears to be diminished arginine-stimulated insulin secretion but not arginine-stimulated increases in plasma glucagon and growth hormone [18].

Supplementation at rest (e.g. before bed) might be a different story . . .

[Trans_Isomer]

Interesting stuff



The article did not comment on the affect of arginine on GH during exercise only on the affect at rest, the following is an excerpt from that portion

Supplementation at rest (e.g. before bed) might be a different story . . .

Dr. Dave, don't you think it's odd that in your posted article statement that arginine increased insulin AND the counter-regulatory hormones as well? The counter-regulatory hormones are usually either up when insulin is down or when insulin is up they are down, they act opposite of each other. The counter-regulatory ones are classified 'catabolic' in that they initiate lipolysis (especially norepinephrine/noradrenaline/growth hormone) along with other catabolic processes to increase energy availability while anabolic hormones like insulin halt lipolysis and conserve energy rather than make it available. It seems odd that it would increase all those hormone secretions rather than just either the anabolic (insulin) or catabolic (counter-regulatorys).

[Dr.Dave1]

Dr. Dave, don't you think it's odd that in your posted article statement that arginine increased insulin AND the counter-regulatory hormones as well? The counter-regulatory hormones are usually either up when insulin is down or when insulin is up they are down, they act opposite of each other. The counter-regulatory ones are classified 'catabolic' in that they initiate lipolysis (especially norepinephrine/noradrenaline/growth hormone) along with other catabolic processes to increase energy availability while anabolic hormones like insulin halt lipolysis and conserve energy rather than make it available. It seems odd that it would increase all those hormone secretions rather than just either the anabolic (insulin) or catabolic (counter-regulatorys).

yes I do. Specifically, the fact that it would raise both insulin and glucagon seemed very questionable. I finished a more indepth read of the article after my post . . . as I just skimmed it at first. My opinion is that it is not very well written. It seems kind of sloppily thrown together (not to say I would do better . . . just not a great piece of scientific literature). That being said I'm not ready to totally discount all use of arginine . . . yet

[in10city]

Another point to note is the delivery method(s) used in the studies - Intravenous (infusion) vs. Oral.

[Dr.Dave1]

an article pointing to the ineffectiveness of chronic use of arginine in athletes . . .

Int J Sports Med. 2005 Jun;26(5):344-9. Links
Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled study.
Abel T, Knechtle B, Perret C, Eser P, von Arx P, Knecht H.


The intake of arginine aspartate has been shown to increase anabolic hormones like human growth hormone (hGH) and glucagon. The aim of our study was to investigate whether daily intake of two different dosages of arginine asparate during four weeks affects selected parameters of overtraining syndrome like performance, metabolic and endocrine parameters. Thirty male endurance-trained athletes were included in a randomized, double-blind, placebo-controlled study and divided into three groups. During four weeks, they ingested either arginine aspartate with a high concentration (H) of 5.7 g arginine and 8.7 g aspartate, with a low concentration (L) of 2.8 g arginine and 2.2 g aspartate or placebo (P).VO(2)peak and time to exhaustion were determined on a cycling ergometer in an incremental exercise test before and after supplementation. Before and after each incremental exercise test, concentrations of hGH, glucagon, testosterone, cortisol, ferritine, lactate, and urea were measured. Compared to placebo, no significant differences on endurance performance (VO(2)peak, time to exhaustion), endocrine (concentration of hGH, glucagon, cortisol, and testosterone) and metabolic parameters (concentration of lactate, ferritine, and urea) were found after chronic arginine aspartate supplementation. The chronic intake of arginine asparate during four weeks by male endurance athletes showed independent of dosage no influence on performance, selected metabolic or endocrine parameters. Consequently, there seems to be no apparent reason why the supplementation of arginine aspartate should be an effective ergogenic aid. The practice of using arginine aspartate as potential ergogenics should be critically reevaluated. Further investigations with higher dosage and extended supplementation periods should be performed.

[Trans_Isomer]

yes I do. Specifically, the fact that it would raise both insulin and glucagon seemed very questionable. I finished a more indepth read of the article after my post . . . as I just skimmed it at first. My opinion is that it is not very well written. It seems kind of sloppily thrown together (not to say I would do better . . . just not a great piece of scientific literature). That being said I'm not ready to totally discount all use of arginine . . . yet

Yep, glad I wasn't the only one who noticed that, lol. Good point on the glucagon as well as it is DIRECTLY opposite that of insulin in action, increasing blood glucose versus lowering it.

[Trans_Isomer]

Interesting study as well that isn't directly about arginine but rather nitric oxide in relation to the sarcoplasmic reticulum and calcium ion inhibition...

Nitric oxide impairs Ca2+ activation and slows cross-bridge cycling kinetics in skeletal muscle.

Heunks LM, Cody MJ, Geiger PC, Dekhuijzen PN, Sieck GC.

Department of Pulmonary Diseases, University Hospital Nijmegen, 6500 HB Nijmegen, The Netherlands.

The effects of the nitric oxide (NO) donor spermine NONOate (Sp-NO, 1.0 mM) on cross-bridge recruitment and cross-bridge cycling kinetics were studied in permeabilized rabbit psoas muscle fibers. Fibers were activated at various Ca2+ concentrations (pCa, negative logarithm of Ca2+ concentration), and the pCa at which force was maximal (pCa 4.0) and approximately 50% of maximal (pCa50 5.6) were determined. Fiber stiffness was determined using 1-kHz sinusoidal length perturbations, and the fraction of cross bridges in the force-generating state was estimated by the ratio of stiffness during maximal (pCa 4.0) and submaximal (pCa 5.6) Ca2+ activation to stiffness during rigor (at pCa 4.0). Cross-bridge cycling kinetics were evaluated by measuring the rate constant for force redevelopment after quick release (by 15% of optimal fiber length, L(o)) and restretch of the fiber to L(o). Exposing fibers to Sp-NO for 10 min reduced force and the fraction of cross bridges in the force-generating state at maximal and submaximal (pCa50) Ca2+ activation. However, the effects of Sp-NO were more pronounced during submaximal Ca2+ activation. Sp-NO also reduced the rate constant for force redevelopment but only during submaximal Ca2+ activation. We conclude that Sp-NO reduces Ca2+ sensitivity by decreasing the number of cross bridges in the strongly bound state and also impairs cross-bridge cycling kinetics during submaximal activation.

Publication Types:

* In Vitro
* Research Support, Non-U.S. Gov't
* Research Support, U.S. Gov't, P.H.S.


PMID: 11641366 [PubMed - indexed for MEDLINE]

FULL STUDY: http://jap.physiology.org/cgi/content/full/91/5/2233

[Dr.Dave1]

A study on AAKG in "trained men"

1: Nutrition. 2006 Sep;22(9):872-81. Links
Pharmacokinetics, safety, and effects on exercise performance of l-arginine alpha-ketoglutarate in trained adult men.
Campbell B, Roberts M, Kerksick C, Wilborn C, Marcello B, Taylor L, Nassar E, Leutholtz B, Bowden R, Rasmussen C, Greenwood M, Kreider R.


OBJECTIVE: We evaluated the pharmacokinetics, safety, and efficacy of l-arginine alpha-ketoglutarate (AAKG) in trained adult men. METHODS: Subjects participated in two studies that employed a randomized, double-blind, controlled design. In study 1, 10 healthy men (30-50 y old) fasted for 8 h and then ingested 4 g of time-released or non-timed-released AAKG. Blood samples were taken for 8 h after AAKG ingestion to assess the pharmacokinetic profile of l-arginine. After 1 wk the alternative supplement was ingested. In study 2, which was placebo controlled, 35 resistance-trained adult men (30-50 y old) were randomly assigned to ingest 4 g of AAKG (three times a day, i.e., 12 g daily, n = 20) or placebo (n = 15). Participants performed 4 d of periodized resistance training per week for 8 wk. At 0, 4, and 8 wk of supplementation the following tests were performed: clinical blood markers, one repetition maximum bench press, isokinetic quadriceps muscle endurance, anaerobic power, aerobic capacity, total body water, body composition, and psychometric parameters tests. Data were analyzed by repeated measures analysis of variance. RESULTS: In study 1, significant differences were observed in plasma arginine levels in subjects taking non-timed-release and timed-release AAKG. In study 2, significant differences were observed in the AAKG group (P < 0.05) for 1RM bench press, Wingate peak power, blood glucose, and plasma arginine. No significant differences were observed between groups in body composition, total body water, isokinetic quadriceps muscle endurance, or aerobic capacity. CONCLUSION: AAKG supplementation appeared to be safe and well tolerated, and positively influenced 1RM bench press and Wingate peak power performance. AAKG did not influence body composition or aerobic capacity.

PMID: 16928472 [PubMed - in process]

quote on change in 1 RM

The analysis of 1RM bench press (Fig. 2) over 8 wk showed a significant difference between groups (AAKG 8.82 +/- 7.33 versus PLA 2.67 +/- 9.11 kg, P = 0.03).

So, it might help with strength . . .

[Trans_Isomer]

A study on AAKG in "trained men"

quote on change in 1 RM
So, it might help with strength . . .

Yep saw that one awhile ago... strength change but NOT body composition change... perhaps arginine influences the nervous system/motor unit control with more specificity than it does directly with the skeletal musculature.

BUT they used A-AKG, not just arginine, and AKG (alphaketoglutaric acid) itself does have some beneficial properties so perhaps it was just the AKG and NOT anything with the arginine as indicated by the above studies...

[Dr.Dave1]

Yep saw that one awhile ago... strength change but NOT body composition change... perhaps arginine influences the nervous system/motor unit control with more specificity than it does directly with the skeletal musculature.

BUT they used A-AKG, not just arginine, and AKG (alphaketoglutaric acid) itself does have some beneficial properties so perhaps it was just the AKG and NOT anything with the arginine as indicated by the above studies...

good point, it would have been nice if they had a controlled for that by adding another group

[Dr.Dave1]

another one supporting oral arginine increasing GH release . . . in rats atleast

Authors de Castro Barbosa T. Lourenco Poyares L. Fabres Machado U. Nunes MT.
Title Chronic oral administration of arginine induces GH gene expression and insulin resistance.
Source Life Sciences. 79(15):1444-9, 2006 Sep 5.



Arginine (Arg) presents a potent growth hormone (GH) releasing activity. In vivo and in vitro studies carried out in our laboratory have demonstrated that acute treatment with Arg also increases GH gene expression. Taking into account the recognizable diabetogenic role of GH and that [/b]Arg increases insulin release[/b], this study aimed at evaluating the effects of oral chronic administration of Arg on GH gene expression, by Northern blotting analysis, and on the insulin sensitivity, by means of the Insulin Tolerance Test (ITT), blood glucose decay rate (kitt) and insulin plasma concentration. We demonstrated that rats that consumed Arg ( approximately 35 mg/day) in drinking water, during 4 weeks, presented an increase in GH mRNA content (p < 0.01), a decreased peripheral response to insulin, as shown by the reduced blood glucose decay rate (p < 0.05), and a higher insulin plasma concentration (p < 0.01) than control group. Arg treatment did not modify the animals' food and water intake, while it decreased the heart rate and the arterial blood pressure compared to control group (p < 0.05). According to the results presented herein we conclude that chronic oral administration of arginine increases GH gene expression and induces insulin resistance. The arterial blood pressure decrease has already been pointed out in the literature, and seems to occur in response to the dilating effect of nitric oxide generated from Arg, as well as from NO generation in central and peripheral neuronal populations that express NOS and are involved in the autonomic regulation of the cardiac function.

[Trans_Isomer]

chronic oral administration of arginine increases GH gene expression and induces insulin resistance

Yikes...

[oldmanmarley]

What jumped out at me the most from that first study is that the subjects did 10 reps of 80% of 1RM. Using the benchpress as a guide, my 1RM is around 225, and there's no way I'm getting 180 for 10 reps. Also it wasn't in good detail at all. It doesn't even say whether the exercise took place within the 3.5 hour window in which they were testing them. I'd like to see the full study. There's something fishy about it.

[Dr.Dave1]

chronic oral administration of arginine increases GH gene expression and induces insulin resistance

Yikes...

yay diabetes


Not totally related . . . . But while we are on the topic of arginine my memory was jogged regarding an old thread . . . http://forum.bodybuilding.com/showthread.php?t=750704
Basically it looked at restricting blood flow to muscles during exercise (opposite of arginine) and the beneficial affects associated with this . . .

[Trans_Isomer]

yay diabetes


Not totally related . . . . But while we are on the topic of arginine my memory was jogged regarding an old thread . . . http://forum.bodybuilding.com/showthread.php?t=750704
Basically it looked at restricting blood flow to muscles during exercise (opposite of arginine) and the beneficial affects associated with this . . .

Yep that is some interesting stuff, vascular blockage actually leading to BETTER muscle hypertrophy/strength... maybe vasoCONstriction is the way to go... you tried this out yet Dr. Dave?

[Dr.Dave1]

Yep that is some interesting stuff, vascular blockage actually leading to BETTER muscle hypertrophy/strength... maybe vasoCONstriction is the way to go... you tried this out yet Dr. Dave?

nah, I figured I would let you give it a go and take all the credit

[5Six]

yay diabetes


Not totally related . . . . But while we are on the topic of arginine my memory was jogged regarding an old thread . . . http://forum.bodybuilding.com/showthread.php?t=750704
Basically it looked at restricting blood flow to muscles during exercise (opposite of arginine) and the beneficial affects associated with this . . .

Well, I wouldn't say diabetes exactly But in general, that is how the how type II diabetes works.

There is some very interesting stuff here. Thanks for the info everyone!

[Dr.Dave1]

Well, I wouldn't say diabetes exactly But in general, that is how the how type II diabetes works.

There is some very interesting stuff here. Thanks for the info everyone!

yes to clarify I was referring to insulin resistance leading to type II DM . . . it's stretch and probably not a serious threat to most but it is worth noting

[5Six]

yes to clarify I was referring to insulin resistance leading to type II DM . . . it's stretch and probably not a serious threat to most but it is worth noting

Something that interesting to note to say the least.

[DRP7]

A study on AAKG in "trained men"

quote on change in 1 RM
So, it might help with strength . . .

apparently the participants in this study did NOT take arginine / AAKG immediately pre-workout.

I think it can be very useful to supplement arginine but NOT immediately pre-workout because this specific condition may attenuate exercise-induced GH release.

[DRP7]

yay diabetes


Not totally related . . . . But while we are on the topic of arginine my memory was jogged regarding an old thread . . . http://forum.bodybuilding.com/showthread.php?t=750704
Basically it looked at restricting blood flow to muscles during exercise (opposite of arginine) and the beneficial affects associated with this . . .

of course is relative ischemia a very srrong stimulus for cellular metabolic adaptations, and a very strong inductor for neovascularisation.
but you should be aware of two things:

1.) the studies that were cited above have used only "low resistance" training or exercises performed at 50% 1RM. Of course, you will have great difficulties to create "ischemia-like" conditions (=local acidosis due to lactate) in muscle tissue during such low exercise intensity. if you then exogenously / artificially reduce the blood flow to the muscles with e.g. a cuff you can amplify the metabolic adaptation of the muscle to low-intensity exercise.

2.) during high-intensity training, i.e. training at a very high % 1RM and doing as many repetions until you feel a "burning" in your msucles, you will get an "ischemia-like" condition in the trained muscle. moreover, if you make very slow reps or even isometric exercises, you will induce an endogenous "occlusion" of supplying vessels and there you will have again your "ischemia".

because this is a transent mechanical compression of vessels due to muscle contractions, arginine won't and can't attenuate this effect by its own vasodialting properties.

these are exactely the resons why it is so incredibly improtant to push oneself to the limit during each and every set and exercise. if you don'T feel the burn and the pain, your strength and size gains will be suboptimal. period!

best regards


david

[Dr.Dave1]

of course is relative ischemia a very srrong stimulus for cellular metabolic adaptations, and a very strong inductor for neovascularisation.
but you should be aware of two things:

1.) the studies that were cited above have used only "low resistance" training or exercises performed at 50% 1RM. Of course, you will have great difficulties to create "ischemia-like" conditions (=local acidosis due to lactate) in muscle tissue during such low exercise intensity. if you then exogenously / artificially reduce the blood flow to the muscles with e.g. a cuff you can amplify the metabolic adaptation of the muscle to low-intensity exercise.

2.) during high-intensity training, i.e. training at a very high % 1RM and doing as many repetions until you feel a "burning" in your msucles, you will get an "ischemia-like" condition in the trained muscle. moreover, if you make very slow reps or even isometric exercises, you will induce an endogenous "occlusion" of supplying vessels and there you will have again your "ischemia".

because this is a transent mechanical compression of vessels due to muscle contractions, arginine won't and can't attenuate this effect by its own vasodialting properties.

these are exactely the resons why it is so incredibly improtant to push oneself to the limit during each and every set and exercise. if you don'T feel the burn and the pain, your strength and size gains will be suboptimal. period!

best regards


david

Just to clarify I am not advocating that method, I brought it up for discussion sake and I definitely appreciate your input Dr. P as you make some very good points. I definitely agree that forcing your muscles to adapt to harsh conditions and pushing yourself hard in the gym are key to success.
However, I am not 100% convinced that you would not see increased results with the occlusion method and high resistance training (again I do not advocate this). It's possible that vasodilation is good in that it enables us to lift longer before we feel the burn but bad in that it does not stress our muscles as much therefore not forcing us to adapt (of course this can probably be overcome if you always push yourself)

[Dr.Dave1]

chronic oral administration of arginine increases GH gene expression and induces insulin resistance

Yikes...

one thing that totally skipped my mind is that growth hormone itself induces insulin resistance so if arginine is increasing growth hormone then you will be increasing insulin resistance via growth hormone.

[5Six]

one thing that totally skipped my mind is that growth hormone itself induces insulin resistance so if arginine is increasing growth hormone then you will be increasing insulin resistance via growth hormone.

Ah good point. That is something that I never thought 'bout.

[deadforaminute]

this thread scares me... so should we be taking it? is it dangerous? or just not worth it?