Arginine (free, salt, ester)
syn. 2-amino-5-guanidinopentanoic acid syn. L-arginine (salt)
Arginine is a common dietary amino acid. It is classified as a conditionally essential amino acid, which means that while the body is normally capable of manufacturing enough to meet its metabolic needs, under certain conditions (such as protein malnutrition, burns, infection, rapid development, and hyperammonemia) arginine must be supplied in the diet.134 It is also classified as a glycogenic amino acid, which means that it can be converted to glucose when energy demands require it. Similar to all of the 20 common amino acids, one of the most basic roles of arginine is as a building block for the synthesis of new proteins. It is also necessary for the biosynthesis of urea, which removes ammonia (a cell toxin) from the body.
Arginine has a diverse set of additional biological activities, some of direct interest for athletic performance.135 For one, it is necessary for the production of nitric oxide. Nitric oxide is a potent vasodilator, relaxing the blood vessels and assisting blood flow and nutrient delivery. Arginine is also involved in the stimulation of the growth hormone axis. It is specifically believed to suppress a hormone called somatostatin, which acts to inhibit growth hormone release. Arginine is also involved with the synthesis of creatine phosphate, an important constituent of the muscle energy cycle. Because of the known involvement of arginine in these biological processes, it has been the subject of athletic supplementation for many years.
As a supplement, arginine is usually supplied as a free form amino acid (pure arginine), an arginine salt, or an ester. The most common arginine products include arginine hydrochloride, arginine aspartate, di-arginine malate, and arginine ethyl ester. These compounds likely have varying solubility, absorption, and distribution properties, but are all regarded as delivering utilizable arginine to the body. Studies examining the potential performance enhancing properties of arginine and its various salts have thus far yielded inconsistent results. More research is needed to determine the potential value of arginine as a performance-enhancing supplement.
Arginine is promoted to increase growth hormone levels and nitric oxide production, and support improvements in muscle mass, strength, and athletic performance.
This ingredient has been shown to improve performance in placebo-controlled studies with untrained individuals. It has a Clinical Support Rating of 4 (3/5).
The growth hormone elevating properties of oral arginine supplementation have been well documented. For example, one commonly cited study examined the effects of arginine supplementation on a group of healthy young men.136 A single dose of 7 g was taken both at rest and prior to exercise. The study demonstrated an approximate 115% increase in GH levels when arginine was taken at rest. Hormone levels peaked approximately 1 hour after ingestion, and remained elevated for 2-3 hours. When the dose was taken immediately before resistance exercise, however, the combination resulted in an inhibition of the normal exercise induced peak in GH secretion.
The growth hormone response to arginine also appears to be a dose dependant phenomenon. We see this in a study that examined varying doses of oral arginine (5 g, 9 g, and 13 g) on the GH response in a group of healthy adult men.137 The study found that the highest peaks in GH level occurred with the 5 g and 9 g doses. The response with the 13 g dose was deemed insignificant. Why the higher dose of arginine failed to produce the same positive response remains unknown.
The effects of regular arginine supplementation on exercise performance have been less conclusive. One study in support of arginine supplementation examined the effect of a 3 g daily dose on exercise performance in a group of healthy untrained men.138 The supplement was taken for a period of 15 days. The approximately 2-week loading period of L-arginine (at a modest dosage) resulted in an 8.5% increase in muscle endurance during training (isokinetic knee extension resistance to fatigue).
Another study looked at the effects of 1 g of arginine daily (combined with 1 g of L-ornithine, another amino acid) for five weeks by a group of healthy untrained adult men.139 All were subject to a progressive resistance training program at the same time. Those subjects taking the arginine/ornithine supplement noticed statically significant improvements in total and lean body mass compared to placebo. The supplemented subjects also noticed less tissue damage, as evident by lower levels of urinary hydroxyproline. Given the combined use of L-ornithine, however, we cannot conclusively attribute the benefits to arginine supplementation.
In contradiction to these results, another placebo-controlled study examined four weeks of arginine aspartate supplementation by a group of young male endurance athletes.140 Both low dose and high dose groups were used for the study, which consumed arginine aspartate in a dose equivalent to 2.8 g and 5.7 g of free arginine per day. Neither dose produced significant differences in peak oxygen consumption, time to exhaustion, or hormone levels (growth hormone, testosterone, cortisol, glucagon) compared to placebo.
The effects of arginine supplementation on nitric oxide production and blood flow following exercise were also examined in two placebo-controlled studies, without supporting results. The first examined a 6 g daily dose of arginine, which was taken for three days.141 The supplementation failed to produce a statistically significant increase in nitric oxide production during a cycle exercise test compared to placebo. There was also no change in peak or average muscle power. The second study looked more closely at blood flow parameters of resistance exercise after the ingestion of a single 7 g dose of arginine.142 Supplementation failed to produce a statistically significant improvement in forearm blood flow.
With regard to the vasodilation (“pump”) effect of arginine, studies suggest this might actually be a counterproductive goal unless additional amino acids are also consumed. One such study involved subjecting a group of healthy volunteers to a bout of lower body resistance exercise, with or without an arterial balloon catheter to maintain blood flow at the pre-exercise state (inhibiting the pump effect).143 The study demonstrated a significant improvement in muscle protein synthesis and amino acid influx/efflux balance when blood flow was reduced. It is speculated that an enhanced blood flow may increase the gradient between the serum and intracellular space, actually drawing amino acids out of the cells. If arginine is to be taken before training for an enhanced pump effect, a complete blend of essential and non-essential amino acids should also be provided, to help ensure this results in muscle nutrient delivery and not depletion.
Whether the inconsistent results concerning the effects of arginine on exercise performance are due to individual variances, study methodological difficulties, or a true absence of consistent ergogenic benefits remains unclear. Further study is needed to determine the potential role of arginine in sport supplementation.
Arginine has been widely used as a stand-alone supplement. The feedback on this supplement has been very mixed. To being with, the use of arginine as a vasodilator has been very popular in recent years. I believe the fact that this effect has not been clinically validated underlines the methodological difficulties with many clinical studies, not an absence of effect. Indeed, I believe that had the subject of this empirical review been the general use of arginine products to enhance the pump effect, it would rate as consistently positive (4/5). As it stands, however, the overall use of arginine products to increase muscle mass,strength, or performance, whether the side focus is pump enhancement or GH elevation, are less consistent, and roughly balanced between positive and negative experiences. Arginine has an Empirical Evidence Rating of 3 (3/5).
Based on clinical studies, a dosage of 3-9 g per day (free arginine, arginine hydrochloride) is recommended. Equivalent doses of di-arginine malate and arginine ethyl ester have not been established.
It is generally advised to limit intake to 8-12 weeks, followed by equal time off, as it is believed that chronic use of arginine products may upregulate the arginase enzyme, reducing nitric oxide production and the supplement’s efficacy.
When taken before training to stimulate vasodilation (“pump”), it is advised to also consume protein or a mixture of essential and non-essential amino acids. When taken for its effect on growth hormone secretion, arginine should not be taken before exercise.
Side Effects / Safety:
Arginine was well tolerated during all clinical studies with healthy subjects, with no significant side effects reported.