What are the benefits of L-Arginine?

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With arginine, you can burn fat more easily while preserving muscle mass. Additionally, arginine can have a positive effect on the anabolic hormones testosterone, IGF-1, and growth hormone. See part 1 for the background on L-Arginine in: what is L-arginine?

Arginine as a fat burner

Arginine was found to work as a “fat burner” in overweight men with type II diabetes (1). The researchers put their subjects on a diet and had them train three times a week (strength and cardio). The group was divided in half, with one group receiving 8.3 grams of arginine and the other group receiving the same amount of a placebo. They chose this dosage because it was found to be the minimum effective amount in previous studies and is less than the 9 grams that was set as the upper limit to avoid stomach and intestinal problems.

Aside from the fact that the group using arginine achieved a greater decrease in waist circumference, there seemed to be no major differences in fat burning. However, there was a very important other difference. The fat-free mass remained unchanged only in the arginine group. In the group that received a placebo, weight loss also resulted in loss of muscle mass.

This latter is normal. A calorie-restricted diet causes the body to tap into reserves such as fat mass. Unfortunately, muscle mass is also a reserve, broken down into amino acids that can provide energy. The big challenge, especially for bodybuilders, is to burn fat without affecting hard-earned muscle mass. This research suggests that arginine could play a significant role in this.

Of course, the question remains to what extent the results in overweight people with type II diabetes are representative for healthy, less obese individuals. We have often seen that losing weight while preserving muscle mass is easier when there is a lot of body fat and relatively little muscle mass. However, we observed significant differences within a comparable group here.

The fat-burning effect of arginine has been demonstrated in studies with animals, but unfortunately, the fat-free mass was not examined (2). These were rats that were also overweight and had diabetes.

Arginine and growth hormone

Arginine can increase growth hormone at rest but limits the increase of growth hormone through training (14). Therefore, it is wise not to use arginine around the time of training.

There are many variables when it comes to muscle growth. Growth hormone is one of them (3). Growth hormone can increase significantly during training, and the levels that are normally present at rest can even increase by up to 800% in some cases (4-8). Basal levels of growth hormone increase when arginine is administered intravenously, as shown in two studies (9,10). In these studies, these values increased by 800% (in the case of men) to 2000% (in the case of women whose basal values are lower than those of men). This increase is attributed to the negative effect that arginine has on somatostatin (11) and the inhibitory effect that somatostatin has on growth hormone release (12,13). One might think that arginine and training would lead to an even greater increase. In one study where arginine was administered along with cardio, this was indeed the case (15). However, this study used 30 grams of arginine administered intravenously. As you read in part I, oral intake may present a different story due to breakdown. Those thirty grams would have to pass through the gastrointestinal tract, of which it has been shown that 9 grams already leads to complaints. So, you may wonder what happens with oral intake of acceptable amounts and the extent to which they eventually enter the bloodstream.

When American researchers tried exactly this in 2006, the results were indeed very different (14). Moreover, they used bodybuilders (aged 18-25), which makes the study somewhat more representative. They compared four situations:

• 7 grams of arginine on an empty stomach, no training
• 7 grams of arginine on an empty stomach half an hour before training (strength training including bench press, lat pulldown, and leg curls)
• Placebo, no training
• Training only

You can see the results in the image on the right. Arginine increases the amount of growth hormone at rest compared to the placebo. Training increases this even more, averaging about 500%. However, if you use arginine before training, you will see that the increase due to that training is limited. You can then naturally question which is more beneficial: more growth hormone at rest and less after training or vice versa? Instead, you may be better off trying to benefit from both. We see in the graph that the effect of the training lasts about 4 hours, but the decrease begins after 3 hours. We also see that it takes about half an hour after taking arginine for this effect to begin and that this effect lasts about 3 hours. So, you could choose not to use arginine between 3.5 hours before training and 2.5 hours after training, but use it outside of that window. The arginine should then not have a negative effect on growth hormone during training but should have a positive effect on growth hormone at rest.

In another study from 2010 among Powerlifters, strangely enough, the exact opposite was observed (16). In this study, levels of growth hormone (and IGF-1) were actually lower during rest after arginine intake, although not significantly (possibly due to chance). However, after training, these levels were higher than when training was done without supplementation. There are several possible explanations for this. As you saw in the image above, ornithine is a precursor of citrulline, which is a precursor of arginine. In addition to 6 grams of arginine, the powerlifters also received 2.2 grams of ornithine and 12mg of vitamin B12. It is possible that the ornithine ensured that more arginine ended up in the blood. However, this does not seem logical. Although the 2006 study did not show a dose-dependent effect because they only tried one dose, it seems more plausible that a higher dose would result in a higher effect.

In addition, it could be due to the way arginine is taken. They have divided it into taking it over two moments. Normally, you see that the so-called “first-pass” via the liver leads to more breakdown because it now takes place twice. This could mean that less arginine has entered the bloodstream depending on the effect of ornithine.

Finally, there is also the vitamin B12 as a new variable, which, like ornithine, is not explained. Throughout the report, the word B12 appears only once, namely in the description of the supplements they received. However, it is not explained why this choice was made, and subsequently, it is not addressed in the analysis of the results.

Arginine, ornithine, and citrulline are often found in pre- and post-workout supplements. Especially in pre-workouts for the “pump effect” as an NO Booster. In part I, you could read that it is questionable to what extent arginine has this effect on NO. In the event that you accept arginine as an NO Booster (or instead opt for citrulline or ornithine, which is converted into arginine in the body), you should question whether this added value is greater than the potential negative effect of the reduced increase in growth hormone. The conclusion is therefore that more research needs to be done to better understand the role of the various variables.

Arginine, testosterone, and IGF-1

“Arginine is necessary for the effectiveness of testosterone.” At least, according to a study from 2004 (17).

IGF-1 (insulin-like growth factor) was briefly mentioned earlier. Another important hormone for muscle growth is, of course, testosterone. When Spanish researchers in 2004 noticed that mice given arginine in their feed had more muscle mass than mice that did not receive it, they looked for the cause in the activity of testosterone and IGF-1 (17). The differences they saw in male mice were not seen in female mice (who naturally have less testosterone).

The fact that these changes were not associated with the decrease in the circulating levels of testosterone and that the dietary arginine restriction prevented the body weight gain induced by testosterone treatment of female mice fed the standard diet indicates that dietary arginine is required for the anabolic action of androgens.

A. Cremades, University of Murcia

When the researchers administered testosterone to both male and female mice, it turned out that in both cases, this did not result in more muscle mass when there was an arginine deficiency. Arginine thus appeared to be necessary for the action of testosterone. They attributed this to the influence of arginine on IGF-1, which in turn plays a role in the activity of testosterone.

Our results showing that arginine deficiency alters the expression of IGF1, IGFBP1 and IGF1R in the kidney and IGFBP1 in the liver support this possibility.

This effect of arginine would therefore have less impact on women because they naturally have less testosterone.

Summary of parts I and II

• Arginine may have a muscle-sparing effect during weight loss
• “Arginine can increase growth hormone at rest but limits the increase in growth hormone due to training.” Although this needs further investigation, it may be advisable not to use arginine a few hours before and after training.
• “Arginine is necessary for the effectiveness of testosterone.”

Conclusion of parts I and II: What is the use of arginine?

There are still many uncertainties surrounding arginine. The main ones concern the extent to which arginine actually leads to an increase in nitric oxide (NO). Arginine is broken down to a large extent before it reaches the bloodstream, and very large intakes to correct this result in stomach complaints. Therefore, it may be better to use citrulline and/or ornithine, which are converted into arginine in the body.

Other alleged benefits of arginine need to be further investigated. If arginine indeed makes “cutting” easier by limiting or even preventing muscle breakdown during weight loss, that would be fantastic. However, this needs to be studied in people (both men and women) without overweight and diabetes to see to what extent it offers the same benefits for “normal people”.

In the field of growth hormone, more research needs to be done under equal conditions so that arginine can be compared with arginine instead of a mixture containing ornithine. It would also be nice to confirm the effect of arginine on (the effectiveness of) testosterone. However, these are all studies trying to demonstrate the effect of one substance on another. Very interesting for science, but ultimately we just want to know what it does for us. So, I come back to the point that studies like those conducted among the “diabetic overweight” should be conducted more frequently and on a larger scale. This should primarily focus on the effect on actual results in: Muscle mass and fat mass, but also on muscle strength and endurance.

References

1. Lucotti P1, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti P. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E906-12. Epub 2006 Jun 13.
2. Fu WJ1, Haynes TE, Kohli R, Hu J, Shi W, Spencer TE, Carroll RJ, Meininger CJ, Wu G. Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats.J Nutr. 2005 Apr;135(4):714-21.
3. Chromiak J and Antonio J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 18: 657–661, 2002.
4. Kanaley JA, Weatherup-Dentes MM, Jaynes EB, and Hartman ML. Obesity attenuates the growth hormone response to exercise. J Clin Endocrinol Metab 84: 3156–3161, 1999.
5. Kanaley JA, Weltman JY, Pieper KS, Weltman A, and Hartman ML. Cortisol and growth hormone responses to exercise at different times of day. J Clin Endocrinol Metab 86: 2881–2889, 2001.
6. Pritzlaff CJ, Wideman L, Weltman JY, Abbott RD, Gutgesell ME, Hartman ML, Veldhuis JD, and Weltman A. Impact of acute exercise intensity on pulsatile growth hormone release in men. J Appl Physiol 87:498–504, 1999.
7. Weltman JY, Weltman A, van der Heijden M, Janssen Y, Metzger D, Veldhuis JD, Keizer HA, and Rogol AD. Effect of intensity of exercise on 24-hour growth hormone release. Med Sci Sports Exerc 26: S37, 1994.
8. Wideman L, Weltman JY, Shah N, Story S, Veldhuis JD, and Weltman A. Effects of gender on exercise-induced growth hormone release. J Appl Physiol 87: 1154–1162, 1999.
9. Alba-Roth J, Muller O, Schopohl J, and Werder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab 67: 1186–1189, 1988.
10. Merimee T, Rabinowitz D, and Fineberg S. Arginine-initiated release of human growth hormone. Factors modifying the response in normal man. N Engl J Med 280, 1969.
11. Ghigo E, Arvat E, Vanelte F, Nicolosi M, Boffano G, Procopio M, Bellone J, Maccario M, Mazza E, and Camanni F. Arginine reinstates the somatotrope responsiveness to intermittent growth hormone-releasing hormone administration in normal adults. Neuroendocrinology 54: 291–294, 1991.
12. Casanueva FF, Villanueva L, Cabranes JA, Cebazas-Cerrato J, and Fernandez-Cruz A. Cholinergic mediation of growth hormone secretion elicited by arginine, clonidine, and physical exercise in man. J Clin Endocrinol Metab 59: 526–534, 1984.
13. Thompson DL, Weltman JY, Rogol AD, Metzger DL, Veldhuis JD, and Weltman A. Cholinergic and opioid involvement in release of growth hormone during exercise and recovery. J Appl Physiol 75: 870–878, 1993.
14. S. R. Collier, E. Collins, and J. A. Kanaley. Oral arginine attenuates the growth hormone response to resistance exercise. Journal of Applied PhysiologySeptember 2006 vol. 101no. 3 848-852
15. Wideman L, Weltman J, Patrie J, Bowers C, Shah N, Story S, Veldhuis J, and Weltman A. Synergy of L-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise.Am J Physiol Regul Integr Comp Physiol 279: R1467–R1477, 2000.
16. Zajac A1, 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 Apr;24(4):1082-90.
17. Cremades A1, Ruzafa C, Monserrat F, López-Contreras AJ, Peñafiel R.Influence of dietary arginine on the anabolic effects of androgens.J Endocrinol. 2004 Nov;183(2):343-51.