The three musketeer amino acids.

In case of supplementation for supporting sports performance, these three amino acids certainly deserve attention: arginine, ornithine and citrulline. These three are structurally and functionally related, let’s say cousins. Research about the use of amino acid has not been conclusive. This is due to the difference in the variables involve in the different tests: age of the subjects, level of training, dosage of amino acids, duration of administration, mode of administration (IV or oral), timing of administration, which exercises test is chosen, etc. But then; we are looking for a marginal gain only and we have been using amino acid supplementation since a long time, mainly to support fat loss (1)

Arginine is probably the most well-known of the three amino acids, used in the 1980’s and 1990’s as a growth hormone releasing amino acid and as an ammonia scavenger (2)

Arginine in IV form or in a high dose orally, stimulates the secretion of the anabolic hormone somatotropin, better known as growth hormone or HGH.  (3)

It is hard to say if a high peak in growth hormone secretion will directly lead to increased sports performances, but there are reasons to assume it might help.

Recent research has shown that arginine also might have a direct effect on muscle protein synthesis via mTOR.

Arginine is also involved in the detoxification of ammonia, a metabolite of very high intensity exercise and the breakdown of proteins (the locker room fragrance). Ammonia has a negative effect on neuronal functioning and coordination.(4)

Arginine is also necessary for the synthesis of creatine-phosphate in the muscle.

Arginine also affects NO production and might be improving vasodilatation (more blood flow to the muscles) but is mainly useful for cardiac patients.

Another positive effect of arginine is its stimulating effect on immune function. The recent Covid-19 situation once again stressed the importance of a well-functioning immune system.

The limitation for the use of arginine is that it works better when one is a female, older or untrained.

Arginine has been studied well and the most used forms are L-arginine or arginine-aspartate (aspartic acid is another amino acid with reported to have ammonia-lowering effects as well). (5)

This why it is used in ammonia-detoxification in case of liver dysfunction leading to brain problems by ammonia.

Ornithine is related to arginine.

Like arginine, ornithine also stimulates the secretion of growth hormone.(6)

It is known to increase work capacity and reduce fatigue. (7) . Ornithine reduces stress markers like cortisol and improves sleep quality as well. (8). Both arginine and ornithine are used to speed up the recovery of burns and of wound healing.

Ornithine is often used in the form of ornithine-keto-glutarate or OKG

Citrulline is rather new as a focus of interest, thanks to its capacity to increase NO and vasodilatation. Most likely that’s is why it was hailed as being “the natural Viagra”. Natural, because one of the main sources of citrulline is ….. water melon. Now it is somewhat impractical and counterproductive to eat enough watermelon to create a Viagra-like effect.

One of the things have you do sometimes as an athlete: competing who can eat the most watermelon

The effects of citrulline (in capsule or powder form) overlap with the effect of arginine and ornithine. (9,10,11)

Citrulline has been studied for a long time for its anti-fatigue effects. The most used form is citrulline-malate (malic acid is a natural organic acid (apples) and can be found in the citric acid cycle as well).

In order for these amino acids to be effective one needs dosages into the grams, ranging from 5- 10 gram per day.

1 Takeda, K; Takemasa,T : An Overview of Ornithine, Arginine and Citrulline in Exercise and Sports Nutrition; in: Nutrition and Enhanced Sports Performance, 2013, Chapter 43, pg.423-439,  DOI:

2 Schaefer, a; Piquard, F; Geny, B; Doutreleau, S; Lampert, E; Mettauer, B; Lonsdorfer, J:  L-Arginine Reduces Exercise-Induced Increase in Plasma Lactate and Ammonia; Int J Sports Med 2002; 23: pg.403–407.

3 Collier, S.R; Casey, D.P;  Kanaley, J.A: Growth hormone responses to varying doses of oral arginine; Growth Hormone & IGF Research 15 (2005) pg. 136–139.

4 Banister E.W; Cameron B.J; Exercise-induced hyperammonemia: peripheral and central effects. Int J Sports Med 1990;11 (Suppl 2) pg. 129-142.

5 Zak, R.B;  Camic, C.L; Hill, E.C; Monaghan, M.M; Kovacs,A.J;  Wright, G.A: Acute effects of an arginine-based supplement on neuromuscular, ventilatory, and metabolic fatigue thresholds during cycle ergometry; Appl. Physiol. Nutr. Metab. 40: 1–7 (2015)

6 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; Advances in Bioscience and Biotechnology, 2010, 1, pg. 7-11.

7 Suginoa, T; Shiraia, T; Kajimotoa, Y; Kajimoto, O:  L-Ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism; Nutrition Research 28 (2008) ,pg.738–743.

8 Miyake, M; Kirisako, T; Kokubo, T; Miura, Y;  Morishita, K; Okamura, H;  Tsuda, A:  Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers; Nutrition Journal 2014, 13: 53

9 Trexler,E.T; Persky, A.M; Ryan, E.D; Schwartz, T.D; Stoner, L;  Smith‑Ryan, A.E:  Acute Effects of Citrulline Supplementation on High‑Intensity Strength and Power Performance: A Systematic Review and Meta‑Analysis; Sports Medicine,

10 Bendahan, D;  Mattei, J.P; Ghattas, B;  Confort-Gouny, S; Le Guern, M.E; Cozzone, P.J:    Citrulline/malate promotes aerobic energy production in human exercising muscle; Br J Sports Med 2002; 36: pg.282–289

11 Kiyici, F;  Eroglu, H; Fazil Kishali, N; Burmaoglu, G: The Effect of Citrulline/Malate on Blood Lactate Levels in Intensive Exercise; Biochem Genet. DOI 10.1007/s10528


    1. Hello Juan, thanks for your questions

      For me, trusted brands are brands that put on the label what is in there, in quality and quantity, not more, not less, but also try not to put too much binders, fillers, and other additives into their capsules and tablets. To be honest, I prefer powders or make capsules myself.

      Trusted brands mainly depend where you live. Brands from the therapeutic market are more reliable that brands from the fitness, body-building or performance /muscle-gain market, which are, too often, intentially or not, contaminated with substances that are on the doping list.

      I often advise Solgar or PureBulk. There is little consensus about when to take amino acids, since there are many variables like which one, dosage, absorption, interference with each other’s uptake, kind of training, etc. Most explanations seem plausible, be it before, during or right after training (the uptake is fast since it’s small and simple molecule)

      For sake of simplicity and practicality, I prefer athletes taking supplements right after the workout, avoiding stomach problems and athletes having the peace of mind. I don’t think in the long run it will make a lot of difference, but if you doubt: use Henk’s golden rule: “when in doubt, choose both”

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