Effects and Dosage of Arginine and AAKG: What's Myth and What's Reality?

The dietary supplement Arginine (L-arginine) or its variations like Arginine-alpha ketoglutarate (AAKG), which is a compound of L-Arginine and alpha ketoglutarate (keto-acid), remains a popular dietary supplement in the world of sports nutrition, for both endurance athletes and bodybuilders. This amino acid is associated with a number of key processes in the body, from hormone production to improving blood flow to working muscles. But what do scientific sources say about its actual effectiveness? Is it even worth supplementing?

What are arginine and alpha-ketoglutarate?

From a chemical perspective, arginine is a non-essential amino acid, meaning the human body can synthesize it on its own.

Alpha-ketoglutarate (α-ketoglutarate) is, from a chemical perspective, a keto-acid that is formed as an intermediate in the TCA cycle (Krebs cycle) – a metabolic pathway where cells convert nutrients into energy. It also participates in amino acid metabolism, as it can accept a nitrogen group from amino acids in reactions called transamination and be converted into, for example, glutamate.

AAKG vs. L-Arginine

Athletes often speculate that AAKG has better absorption and utilization; however, as we will show in the following paragraphs, it is completely irrelevant, and both forms are ineffective in oral administration, as the primary active substance is still L-Arginine.

What effects are attributed to arginine and in what doses?

Stimulation of growth hormone and insulin secretion

This idea is supported by two studies. Knopf et al. 1996, where adults were given an intravenous dose of 30g of arginine over 30 minutes, and an increase in growth hormone was observed. Infusions of amino acids such as ornithine or lysine can have the same effect. A second study by Dupre et al. 1698 found that blood infusion and oral administration of arginine can lead to increased insulin secretion. These two studies thus made arginine a popular dietary supplement among bodybuilders and other strength athletes.

However, the doses typically found in available supplements range only from 1-2g. Quality studies with robust methodology by Fogelholm, Naveri et al. 1993 and Lambert et al. 1993 specifically examined this dosage and did not demonstrate the effect of arginine on increased secretion of growth hormone or insulin.

It is also important to note that an increase in growth hormone levels can be achieved naturally through exercise alone. The effect we would gain from consuming a relatively large amount of arginine is still many times smaller than what we get from an hour of moderate-intensity exercise. Moreover, consuming large amounts of arginine causes significant digestive problems, and insulin secretion normally occurs with carbohydrate intake.

Production of nitric oxide (NO)

The second alleged benefit, why athletes supplement Arginine or AAKG, is increased production of nitric oxide (NO). Nitric oxide causes vasodilation (widening of blood vessels), which promotes higher blood flow and the delivery of more nutrients and oxygen to muscles, which can increase protein synthesis and improve muscle regeneration.

The effects of nitrate supplementation on reducing oxygen cost during exercise and improving endurance even during high-intensity exercise are excellently scientifically verified.

Theoretically, arginine supplementation could therefore have similar effects. There is some scientific evidence confirming that arginine supplementation can improve athletic performance, but unlike nitrates, Arginine has not been shown to have its effect related to changes in NO production. Bailey et al. (2010) confirmed an extension of time to exhaustion during cycling exercise and a reduction in oxygen cost during moderate-intensity cycling exercise with a dosage of 6 grams of arginine before a series of moderate and high-intensity exercises for three days. Buford and Koch (2004) observed an improvement in average power during repeated series of very intense (supramaximal) cycling ergometer exercise after participants consumed 6 g of arginine (in the form of glycine-arginine-alpha-ketocaproic acid) one hour before exercise.

Citrulline: A better alternative to arginine?

A far more suitable alternative to arginine is Citrulline (L-citrulline), as the body can convert it directly into arginine. According to current scientific data, L-Citrulline has a greater effect than L-Arginine alone, and moreover, it has no side effects, does not cause digestive problems (cramps and diarrhea) at the same doses, i.e., 6 grams, Viribay et al. 2022.

This scientific finding has thus made L-arginine an uninteresting dietary supplement for improving physical performance for both athletes and scientists.

Conclusion for athletes

Although arginine infusion in large doses can have anabolic effects, oral intake in typical doses of 1-2 g does not lead to increased secretion of human growth hormone or insulin. Increased insulin secretion can be achieved by carbohydrate intake, and a far greater increase in plasma growth hormone occurs during exercise than after very high doses of arginine or other amino acids.

Arginine can also be used by body tissues and blood vessel walls to produce nitric oxide (NO), but there is only limited evidence that arginine supplementation can increase athletic performance. It has not been proven that any potential effect would be related to changes in NO production. Moreover, L-citrulline is more effective in this regard.

From a practical point of view, arginine as a dietary supplement, whether in its pure form L-Arginine or a compound like AAKG, is completely ineffective and unnecessary for supporting physical performance or muscle building.

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Sources of information

1. Knopf, R.F., J.W. Conn, J.C. Floyd, Jr., S.S. Fajans, J.A. Rull, E.M. Guntsche, and C.A. Thiffault. 1966. The normal endocrine response to ingestion of protein and infusions of amino acids: Sequential secretion of insulin and growth hormone. Trans Assoc Am Physicians 79:312-321.
2. Dupre, J., J.D. Curtis, R.W. Waddell, and J.C. Beck. 1968. Alimentary factors in the endocrine response to administration of arginine in man. Lancet 2(7558):28-29.
3. Lambert, M.I., J.A. Hefer, R.P. Millar, and P.W. Macfarlane. 1993. Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders. Int J Sport Nutr 3(3):298-305.
4. Jeukendrup, A., & Gleeson, M. (2025). Sport nutrition (4th ed.). Human Kinetics.
   
5. Fogelholm, G.M., H.K. Naveri, K.T. Kiilavuori, and M.H. Harkonen. 1993. Low dose amino acid supplementation: No effects on serum growth hormone and
6. Bailey, S.J., P. Winyard, A. Vanhatalo, J.R. Blackwell, F.J. Dimenna, D.P. Wilkerson, and A.M. Jones. 2010. Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance. J Appl Physiol 109(5):1394-1403.
7. Buford, B.N., and A.J. Koch. 2004. Glycine-arginine-alpha-ketoisocaproic acid improves performance of repeated cycling sprints. Med Sci Sports Exerc 36(4):583-587.
8. Viribay, A., J. Fernández-Landa, A. Castañeda-Babarro, P.S. Collado, D. Fernández-Lázaro, and J. Mielgo-Ayuso. 2022. Effects of citrulline supplementation on different aerobic exercise performance outcomes: A systematic review and meta-analysis. Nutrients 14(17):3479.