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NO Supp's Part IV: NO Supplements, Training Age & Supraphysiological NO Spikes

Quick Hit Summary

In Part IV of our NO Supplement Series we briefly examine if ones training age (ie – experience) may influence their "muscle pump" response to NO Supplements. A quick review of the literature indicates that well trained athletes are even less likely than untrained athletes with respect to manufacturer claims on these supplements. Ditto for chronic users of the supplement. In addition, we examine the question, "Are spiking NO levels beyond that which a healthy exercising individual does on their own even desirable?" In answering the latter question, outrageous spikes in NO opens up a whole can of worms that one is best to avoid! Don't worry though; in healthy individuals NO production is very tightly controlled. This is one of the reasons why most supplements fail to have any significant effect on giving you the "ultimate muscle pump" often claimed by supplement manufacturers.

A Review of Where We've Been

So far we've discussed the in's and out's of the NO Supplements; covering everything from basic NO physiology to the effects of the NO amino acids in isolation, or as part of propriety blended "NO Boosting" supplements. In case you missed any of the articles, I recommend checking them out.

  • Nitric Oxide Supp's Part I – Understanding the Key Players
  • Nitric Oxide Supp's Part II – Let's "Pump You Up"… or Not?
  • NO Supp's Part III – The "Everything But The Kitchen Sink" NO Supplements
  • NO Supp's Part IV – Training Age & Supraphysiological NO Spikes
  • Still to Come: NO Supp's Part V – True Potential Benefits of Citrulline Supplementation
  • Still to Come: NO Supp's Part VI – True Potential Benefits of Arginine Supplementation

In Part IV of this series we look to tie up a few loose ends in regards to these purported muscle pumping supplements. Namely, our focus changes slightly and we examine if training status affect one's response to NO Boosting Supplements and if extreme spikes of NO are even desirable.

Does Training Status Alter One's Response to NO Boosting Supplements?

While I have listed a few studies showing increased muscle blood volume and/or NOx production (see Part II and Part III), I have been careful to mention that these are mostly observed in "recreationally" active individuals; NOT well trained athletes (The one exception to this was the acute study carried out by Alvares et al.1 which involved individuals with a mean resistance training age of 5.9 years and one of the semi-chronic GPLC studies which gave men with a mean resistance training age of 8 years 4.5g for 28 days2). As one's training age/capacity increases, the likelihood of them seeing any positive effects related to NO production post supplementation decreases. This was best summed up by Bescos et al. in their comprehensive 2012 review of studies which directly examined NO related supplements on human performance in healthy individuals….

"With some of the benefits linked with NO donors [ie – supplements] have been shown in moderately trained subjects, in well trained athletes, scientific data that show the effect of these supplements is low….in part, to the positive effect of exercise in the regulation of NO metabolism. While short term training rapidly increases NO bioactivity, if training is maintained, the short term functional adaptation is succeeded by NO-dependent structural changes leading to arterial remodeling and structural normalization of shear [stress]… Structural remodeling and consequent normalization of shear obviates the need for ongoing functional dilation, including enhanced NO dilator system function. The conclusion that we can extract is that training performed by competitive athletes has a greater effect on improving the NO system compared with NO supplementation…3

Are Outrageous NO Spikes Beyond That Normally Induced by Exercise Even Desirable?

Figure 1. Reactions of peroxynitrite leading to either apoptotic or necrotic cell death. Image Source8

Thus far, the supplement industry has strongly purported the myth that “more is better” with respect to spiking NO levels during/post workout. However, does this even make sense? As seen in the GPLC study conducted by Jacobs et al (Part III of this series), too much of a pump makes it harder for one to move, thus limiting athletic performance.4 Let’s look at a few other potential reasons as to why one would want to avoid NO spikes beyond that which a normal healthy exercising human body can naturally create on its own (ie – supraphysiological levels)…

  • Increased workload by the heart in order to maintain blood pressure. Think about it, the heart has to be able to pump oxygen to the brain. If one increases vasodialation, without a parallel increase in blood flow, we'll get light headed and pass out in order to maintain oxygen delivery to the brain…. Not cool if this happens while bench pressing or squatting (although look at the great "muscle pump" you had prior to passing out, right !?). To prevent this scenario, the heart must work harder, pumping more blood per unit time in order to maintain blood pressure.
  • Decreased muscle contraction force capabilities. In-vitro evidence indicates that elevated NO levels, including its byproducts such as peroxynitrite (NO + O2- <—> ONOO-), may actually decrease the ability of a muscle to contract.56
  • Oxidative stress, beyond that which is healthy and required, related to excessive ONOO- production. Multiple lines of research have linked this molecule to cardiovascular, cancer, neuro-degenerative and various autoimmune diseases via the mechanisms depicted in Figure 1.7

Now before everyone gets paranoid that increasing NO will lead to the problems discussed above, I must stress the fact that NO production is VERY CLOSELY regulated in the human body due to potentially dangerous reasons mentioned above; "over-production" of NO does not happen in healthy individuals, regardless of if they are taking Muscle Pump supplements or not while exercising. Thus, my use of the word "supraphysiological levels" in the preceding paragraph refers to "NO Spikes beyond that which a normal healthy exerciser is capable of producing."

Bottom Line

In Part IV of of our look at NO supplements we tackle a few remaining questions, namely does one's training age/capacity affect the "muscle pumping" effect often claimed by manufactures? The answer to this question appears to be "yes", with those of higher trained athletes being less likely to experience an effect vs. novices. In addition, we also examined if outrageous spikes in NO, beyond that which a healthy individual is normally capable of producing while exercising is even desirable. As with most things, supraphysiological spikes in NO production could lead to excessive drops in blood pressure, excessive oxidative stress and even decreases in contractile force. Don't worry though, the healthy human body tightly monitors its production pretty closely, preventing these things from ever becoming issues.

After reading through the first few installments of this series, you're probably getting pretty leery of NO Supplements and ready to trash all arginine/citrulline based supplements. However, don't go "throwing out the baby out with the bathwater" and totally ditch any thought of ever purchasing supplements containing the NO amino acids (arginine, citrillune, ornithine) – THESE AMINO ACIDS DO HAVE POTENTIAL PERFORMANCE & HEALTH BENEFITS; Just not for the reasons stated on the labels of your favorite "NO Boosting" Supplements.

Have I caught your interest? Curious as to what their beneficial effects are for hard training individuals? If so, be sure to catch a future installment in CasePerformance's series on the NO Amino Acids!


1 Alvares TS, Conte CA, Paschoalin VM, Silva JT, Meirelles Cde M, Bhambhani YN, Gomes PS.Acute l-arginine supplementation increases muscle blood volume but not strength performance. Appl Physiol Nutr Metab. 2012 Feb;37(1):115-26. Epub 2012 Jan 17

2 Bloomer RJ, Smith WA, Fisher-Wellman KH. Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men. J Int Soc Sports Nutr. 2007 Dec 3;4:22.

3 Bescós R, Sureda A, Tur JA, Pons A. The effect of nitric-oxide-related supplements on human performance. Sports Med. 2012 Feb 1;42(2):99-117.

4 Jacobs PL, Goldstein ER. Long-term glycine propionyl-l-carnitine supplemention and paradoxical effects on repeated anaerobic sprint performance. Int Soc Sports Nutr. 2010 Oct 28;7:35.

5 Lamb GD, Westerblad H.Acute effects of reactive oxygen and nitrogen species on the contractile function of skeletal muscle. J Physiol. 2011 May 1;589(Pt 9):2119-27. Epub 2010 Nov 1.

6 Dutka TL, Mollica JP, Lamb GD. Differential effects of peroxynitrite on contractile protein properties in fast- and slow-twitch skeletal muscle fibers of rat. J Appl Physiol. 2011 Mar;110(3):705-16. Epub 2010 Oct 28.

7 Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007 Jan;87(1):315-424.

8 Erica Novo and Maurizio Parola. Reactions of peroxynitrite leading to either apoptotic or necrotic cell death. 2008. Novo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Image accessed Oct 13, 2012 from: http://en.wikipedia.org/wiki/File:Reactions_of_peroxynitrite_leading_to_either_apoptotic_or_necrotic_cell_death.jpg

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Written on October 22, 2012 by Sean Casey
Last Updated: July 04, 2013

This information is not intended to take the place of medical advice.Please check with your health care providers prior to starting any new dietary or exercise program. CasePerformance is not responsible for the outcome of any decision made based off the information presented in this article.

About the Author: Sean Casey is a graduate of the University of Wisconsin-Madison with degrees in both Nutritional Science-Dietetics and Kinesiology-Exercise Physiology. Sean graduated academically as one of the top students in both the Nutritional Science and Kinesiology departments.
Field Experience: During college, Sean was active with the UW-Badgers Strength and Conditioning Department. He has also spent time as an intern physical preparation coach at the International Performance Institute in Bradenton, FL. He also spent time as an intern and later worked at Athletes Performance in Tempe, AZ. While at these locations he had the opportunity to train football, soccer, baseball, golf and tennis athletes. Sean is also active in the field of sports nutrition where he has consulted with a wide variety of organizations including both elite (NFL’s Jacksonville Jaguars) and amateur athletic teams. His nutrition consultation services are avalable by clicking on the Nutrition Consultation tab.