L-arginine: examining common myths

A lot of beliefs have formed around L-arginine, which go from advertising to forums and back. Some of them are based on real biochemical facts, but draw too bold conclusions from them. The editors selected the most common myths about arginine and verified each one with research data.

Myths about NO and "pump"

Myth 1: “More arginine always means more nitric oxide.” Arginine is a substrate for NO synthase, but the relationship is not linear. The “arginine paradox” actually describes effects of extracellular arginine despite intracellular concentrations that should already saturate the enzyme. It is not the name for a simple absence of response, and does not establish a reliable benefit from supplements in healthy athletes.

In addition, most of the oral dose is broken down by arginase in the intestine and liver before entering the systemic circulation. A systematic review by Álvares et al. (2011) found that in most studies in healthy humans, supplementation did not significantly increase markers of NO synthesis.

Myth 2: "Feeling a pump proves that arginine works." Fullness of muscles during training occurs primarily due to the accumulation of metabolites, fluid displacement and natural working hyperemia. It appears even without any additives, and its intensity strongly depends on the volume, number of repetitions and rest between sets.

The subjective feeling is easily enhanced by the anticipation effect, especially if there is caffeine in the pre-workout complex. Without a placebo control, it is impossible to say how much of the "pump" is due to arginine. And most importantly, even a real increase in blood flow does not guarantee a better result.

Myth 3: "Arginine is the best NO booster." It is preceded by at least two alternatives in terms of strength of evidence: dietary nitrates, which have the largest evidence base for endurance performance, and L-citrulline, which is more effective at increasing plasma arginine levels (Schwedhelm et al., 2008).

Myths about hormones and muscles

Myth 4: "Arginine increases growth hormone and therefore builds muscle." Intravenous arginine does stimulate GH secretion and is used in endocrinological diagnostics. Oral doses can also modestly increase resting GH, as shown by Collier et al (2005).

However, in another study by the same group (Collier et al., 2006), arginine before resistance training attenuated the natural release of GH that occurs in response to exercise. That is, "additional growth hormone for training" turned out to be the opposite of what the advertisement promises.

In addition, short-term growth hormone fluctuations within physiological values ​​are not a reliable predictor of hypertrophy. Muscle growth is primarily determined by mechanical stress, sufficient protein and energy, not a few-minute peak of GH.

Myth 5: "Arginine increases testosterone." The editors did not find convincing human studies that would show an increase in testosterone in healthy men after taking arginine. Such claims are usually based on animal data or on confounding with other effects of NO.

The myth of "natural Viagra"

Myth 6: "Arginine is a natural substitute for potency drugs." Erection really depends on nitric oxide and cGMP, so the connection with arginine has a biological logic. There are small clinical trials of arginine in erectile dysfunction, particularly of vascular origin, with mixed results.

However, the effect, even if present, is much weaker and less predictable than that of registered medicinal products. Positioning arginine as an "equivalent alternative" is incorrect.

More dangerous: Erectile dysfunction is often an early marker of cardiovascular disease. A person who "treats" it with arginine without examination may miss an important signal about the state of the vessels.

In addition, "male" complexes with arginine in a number of countries were repeatedly found to be falsified - with undeclared analogues of sildenafil or tadalafil. In combination with nitrates, it creates a real threat to life.

Myths about safety and formulations

Myth 7: "Arginine is found in food, so it's safe in any amount." Large single doses often cause diarrhea and bloating; as reviewed by Grimble (2007), the risk increases dramatically at single doses above 9–10 g. For healthy adults, the Shao and Hathcock (2008) risk assessment established an observed safe level of 20 g per day—but this is not a formal upper limit or a guarantee of safety for every healthy adult.

For people after a heart attack, data from the VINTAGE MI trial (Schulman et al., 2006) showed no benefit and more deaths in the arginine group. People with hypotension and those taking nitrates or PDE-5 inhibitors also need caution.

Myth 8: “Special forms are absorbed many times better.” AAKG, ethyl ester and proprietary mixtures are often marketed on this basis. Independent human evidence showing superiority over an equivalent amount of ordinary arginine is very limited.

In practice, however, such forms often contain less arginine per gram of product than the free base or hydrochloride. The buyer pays more for a lower content of the active substance.

Myth 9: "Arginine is doping or, conversely, a 'legal steroid'." Arginine is not on the WADA Prohibited List and is not an anabolic steroid. At the same time, the name "legal steroid" is pure marketing: arginine has neither a hormonal nor a pronounced anabolic effect.

Why myths are so durable

Myths about arginine are based on a combination of several factors. First, the real scientific basis: the role of nitric oxide in vasodilation was recognized by the Nobel Prize in 1998, and this adds credibility to the marketing claims.

Secondly, transferring data from one group to another. Positive results in patients with endothelial dysfunction or in intravenous tests are automatically transferred to healthy athletes taking the pills.

Thirdly, there is a strong effect of expectation and subjective feelings. "Pump", a rush of energy from caffeine in the same complex, motivation from a new purchase - all this can easily be attributed to arginine.

Fourth, the rarity of independent studies with large samples. When data is scarce, the information space is dominated by the loud statements of manufacturers rather than the careful conclusions of systematic reviews.

Editorial conclusions

Most of the popular claims about arginine—from “more NO” to “growth hormone for muscle”—are not supported by studies in healthy athletes. Biochemical logic here does not coincide with clinical results.

Arginine is neither a doping agent nor a "legal steroid" nor an equivalent substitute for potency drugs. It is relatively safe for healthy people in moderate doses, but has real limitations for certain groups.

For a deeper understanding of the topic, we recommend the materials "L-arginine: what it is and how it works", "The benefits of L-arginine for athletes: the evidence base" and "Who should not take L-arginine".

References

1. Álvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Med. 2011;41(3):233–248.
2. Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51–59.
3. Collier SR, Casey DP, Kanaley JA. Growth hormone responses to varying doses of oral arginine. Growth Horm IGF Res. 2005;15(2):136–139.
4. Collier SR, Collins E, Kanaley JA. Oral arginine attenuates the growth hormone response to resistance exercise. J Appl Physiol. 2006;101(3):848–852.
5. Grimble GK. Adverse gastrointestinal effects of arginine and related amino acids. J Nutr. 2007;137(6 Suppl 2):1693S–1701S.
6. Shao A, Hathcock JN. Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regul Toxicol Pharmacol. 2008;50(3):376–399.
7. Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: the VINTAGE MI randomized clinical trial. JAMA. 2006;295(1):58–64.
8. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List. Montreal: WADA (чинна редакція).