High and Low Dose of L-Arginine Equally Ineffective in Promoting Nitric Oxide Synthesis in Young Active Men at Rest - GH and IGF-1 Response Negligible.

Image 1: Arginine based first generation
"nitric oxide booster", such as BSN's
NO-Xplode still have a huge fanbase
"No NO from l-arginine", you probably remember this or similar headlines from a few years ago, when the first studies seemed to indicate that l-arginine, the main "working" ingredient in all the (over-)hyped nitric oxide (NO) boosters that had become an integral part of the line-up of each and every major supplement producer was found not to increase the amount of nitric oxide in their consumers' bloodstream. Although these results stand in stark contrast to the early studies using intravenous infusion of l-arginine, which established the myth of the NO and growth hormone boosting effects of 2-amino-5-guanidinovaleric acid (l-arginine),  a 2007 study by Malinauskas et al. (Malinauskas. 2007) found that 8% of the male student athletes who participated in their survey were still interested in the ingestion of l-arginine containing supplements. Thus, it does not come as a surprise that - even with the rise of the so-called 2nd generation pre-workout products - the classic, l-arginine based products such as NO XPlode, SuperPump and Co. still have a huge fanbase, the majority of whose members, asked about why they are taking the respective product, will certainly answer "for the pump".

A very recent study by Scott C. Forbes and Gordon J. Bell , published in the Journal of Appl. Physiol. Nutr. Metab. (Forbes. 2011), is yet only the latest in series of investigations, which puts into question, how much of a placebo effect may be involved in the real-world observations of "enormous pumps and vasolidation" many consumers of l-arginine based preworkout products report. 14 weight training (4 sessions per week) male participants, who had been free from other nutritional supplements for at least 12 weeks participated in the study. In a double-blind repeated measure design with 3 testing conditions (baseline, placebo/l-arginine, l-arginine/placebo) that were separated by 7 days, the subjects received either high or low dose (0.075 (low) or 0.150g/kg (high)) l-arginine or placebo (flour) solved in 500ml of water after a 10 hour fast. Interestingly,
plasma concentrations significantly increased (p < 0.05) to a similar level [+178% and +204%] above resting values, respectively)at all time points in both the low- and high-dose conditions, while there was no change in the placebo condition over time.
Or, in other words, there was a tight regulation of maximal l-arginine levels in the plasma of the subjects, either via decreased absorption or increased metabolism of the orally ingested l-arginine (it is estimated that with increasing doses >40% of the ingested arginine is degraded by the small intestine). 
Apart from the issue of gastro-intestinal distress, simply increasing the dosage will thus not further increase the availability of arginine in the blood stream, which at the concentration that were observed in this study also failed to induce "a significant main effect for insulin (p < 0.05)". Previous studies using intravenously administered arginine had shown increased insulin secretion and, in some cases, onset hypoglycemia. In absence of these insulinogenic effects, however, there were also
no significant difference over time or between conditions for GH (Fig. 3), IGF-1 (Fig. 4), or glucose, (p > 0.05);
all that, despite the fact that the area under the curve (iAUC), a measure for the total amount of l-arginine that was taken up and metabolized by the subjects, did in fact reveal "a significant difference between the L-arginine conditions and placebo and between the high and low relative doses." With regard to the nitric oxide production, this dose dependent increase in plasma arginine levels turned out to be useless, or in fact counterproductive, as contrary to expectation the  area under the curve (iAUC) "for NOx with the high relative dose was significantly lower than that for the low dose of L-arginine" - a clear sign that "overuse" of large amounts l-arginine could diminishes the already negligible on nitric oxide production at rest.

Before totally discarding arginine, however, I suggest you tune in to tomorrow's episode of Super Human Radio. In the 2nd installment of the "Amino Acids for Super Humans" series, I will provide further insights into what we really know about arginine and its "metabolic children" ornithine and citrulline and how they may effect how you look, feel and perform in and outside the gym.
Disclaimer:The information provided on this website is for informational purposes only. It is by no means intended as professional medical advice. Do not use any of the agents or freely available dietary supplements mentioned on this website without further consultation with your medical practitioner.