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BG5150 05-29-2005 12:30 PM

Nitric Oxide (Do I need it?)
Do I need NO? Should I take it separately, or blended withother stuff in one product?

Darkhorse 05-29-2005 01:14 PM

Depends on what you want...If you want an hour long pump then go ahead because that's all it's good for.

Nitric Oxide – what is it?

Nitric oxide is a colorless, free radical gas commonly found in tissues of all mammals (it’s also prepared commercially by passing air through an electric arc). Biologically, nitric oxide has been shown to be an important neuro-messenger in a number of vertebrate signal transduction processes. Nitric oxide is used in medical treatment; for example, nitroglycerin ameliorates the pain of angina by supplying nitric oxide to the blood vessels that supply the heart. The popular drug Viagra controls erection by regulating nitric oxide in the penile cartilage chamber.

The Research and the Claims

I don’t know where the marketers obtained their literature on nitric oxide. It looks like they are using the same journals as the companies selling Myostatin inhibitors – Alice in Wonderland. Although nitric oxide acts as a cell-to-cell communicator for certain metabolic functions, muscle growth is not one of them. After a review of the available literature I cannot find any research that remotely indicates increasing nitric oxide levels plays a part in increasing protein synthesis, contractile strength or any other biochemical pathway that may lead to increases in muscle mass.

For a company to claim their supplement increases “fast-twitch” muscle strength, the promoters must have instigated or funded some kind of research that involved biopsy procedures and histochemical analyses to extract, assesses and identify these particular muscle fibers from animals or humans, before and after supplementation. However, I could find no documentation (either on their web sites or via a literature scan) that details these findings, only the marketing claims. As far as I’m aware, there is zero scientific evidence supporting the notion that nitric oxide supplements increase “fast-twitch” muscle strength.

There also appears to be no evidence whatsoever that shows increasing nitric oxide levels enhances endurance, power output, and load capacity.

Arginine alpha-ketogluterate is the “active” ingredient reported by one company that sells this type of supplement. It is claimed that this compound increases and maintains a constantly high level of nitric oxide in muscle. Nitric oxide is synthesized within the body using the amino acid arginine, the energy cyclic substrate NADPH, and oxygen. Nitric oxide diffuses freely across membranes but it is a transient signaling molecule. Nitric oxide is by nature, a highly reactive gas that has an extremely short life – less than a few seconds. While there is a lot of research on the effects of nitric oxide, there is no research that shows supplementation with arginine alpha-ketogluterate increases or sustains nitric oxide levels in any human or animal organs.

Can you imagine, a supplement that “creates dramatic increases in muscle size, strength, endurance, power output, and load capacity”, but not a single study to support these claims. Nothing new here. Unfortunately, this is typical sports nutrition marketing bullshit. It's sad, misleading, and shows you just what these companies think of the intelligence level of their target market.

When new products burst onto the market, you the consumer can cut through the advertising hype quite easily. Simply ask the supplement company making the claims to "show you the research". A reference is a start, but the actual research study is particularly what your after. You want to see the study, the protocol, the outcome and the University at which the study was conducted. In the present case, you want to see a study showing were this supplement actually increased nitric oxide above a control group, and you want to see the data that demonstrates an increase in lean muscle mass, significantly more than the group without elevated nitric oxide levels.

The fact is, there is no science supporting any of the claims made for so-called nitric oxide supplements. There is no science showing they have any effect on nitric oxide levels and certainly no science showing in effects on muscle growth or increased performance.

Ask yourself why there is no research to support these companies’ wild claims. The simple answer is that research is expensive, make believe products are not. Research provides evidence, fraudulent supplement marketing only delivers hype. It’s far more financially rewarding to sell hype than to produce effective supplements backed by science.

One promoter of a nitric oxide supplement claims to have “brought creatine supplementation to the market” and that their supplement is “the perfected version of creatine”. I’m not sure which market is being referred to but creatine has been used as a supplement for over 40 years. And in NO way are nitric oxide supplements a “perfected version of creatine”. They are nothing like creatine. While creatine is backed by a wealth of research, nitric oxide supplements do not have a shred of scientific evidence that justifies their effectiveness as a bodybuilding supplements.

Bottom line, money spent on these products is money flushed down the toilet.

Read the Real Science
1. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 1992 6(12):3051-64.

2. Mayer B; Hemmens B. Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem Sci 1997 22(12):477-81.

3. Janabi N; Chabrier S; Tardieu M. Endogenous nitric oxide activates prostaglandin F2 alpha production in human microglial cells but not in astrocytes: a study of interactions between eicosanoids, nitric oxide, and superoxide anion (O2-) regulatory pathways. J Immunol 1996 1;157(5):2129-35.

4. Esposito C; Cozzolino A; Porta R; Mariniello L; Buommino E; Morelli F; Metafora V; Metafora S. Protein SV-IV promotes nitric oxide production not associated with apoptosis in murine macrophages. Eur J Cell Biol 2002 81(4):185-96.

5. Eckmann L; Laurent F; Langford TD; Hetsko ML; Smith JR; Kagnoff MF; Gillin FD. Nitric oxide production by human intestinal epithelial cells and competition for arginine as potential determinants of host defense against the lumen-dwelling pathogen Giardia lamblia. J Immunol 2000 1;164(3):1478-87.

6. Kelly RA; Smith TW. Nitric oxide and nitrovasodilators: similarities, differences, and interactions. Am J Cardiol 1996 30;77(13):2C-7C.

7. Stryer L. Biochemistry 4th Ed. Freeman & Co. 1997.

Frontline 05-29-2005 01:19 PM

Ditto to what 0311 said, I found most of them are just good for a nice pump and some mental focus (depending on the brand). Other than that the research shows they don't do much.

Darkhorse 05-29-2005 01:57 PM

It doesn't take much to get a pump from working out. When dealing with muscle hypertrophy, your goal is to cause microtrama to your muscles. This in turn creates the pump. You don't need useless supplements like no2 to cause that. Herein lies the problem. Most people like the get an extra pump to feel bigger than they actually are. It only lasts for 45 or so minutes at best. Now assuming you want to use the no2 for nutrient delivery, which you don't need, then your muscles are only getting fed for a half hour roughly provided your postworkout nutrition is adaquate enough.

So, why waste all that money for nutrient delivery (no2) that your body naturally produces after a moderate bout of resistance training anyway? Why not instead buy extra protein, creatine, even bcaa's and let your body take care of the delivery naturally?

Darkhorse 05-29-2005 02:06 PM

Part 1
The Real Secret

Here’s where things get real interesting. You may want to be seated for this, because I’m about to blow the lid off the whole deal.

Arginine is the amino acid known to be the most potent insulin secretagogue, meaning that it causes insulin release from the pancreas (4). Now this is of critical importance, because insulin itself stimulates vasodilation and blood flow (2), and this occurs via elevations in nitric oxide synthesis (27).

So arginine stimulates insulin, and insulin stimulates nitric oxide. Nitric oxide causes vasodilation and increased blood flow. Hmmm… Combining this info with what the scientific literature tells us, we can see that much of arginine’s vasodilatory effect can be attributed to insulin secretion!

In fact, one study examined the extent of this very effect, and the results are shocking. Researchers infused the standard 30 grams of arginine with or without blocking insulin release from the pancreas (15). As usual, the massive arginine infusion increased blood flow. But, when insulin release was blocked, blood flow decreased by 77%!

When the latter experiment was repeated with an insulin infusion, blood flow was completely restored! So, over three-quarters of the increased blood flow response was caused by insulin. While not all arginine-induced blood flow can be attributed to insulin, you must remember that these studies use the equivalent of over 40 grams orally ingested arginine, which isn't even possible to tolerate.

The Revised Theory:

Arginine -> Insulin -> Nitric Oxide -> Vasodilation -> Nutrient Delivery -> Muscle Growth and Strength

You have to wonder if the companies who produce these supplements knew this when they began to market them. If they did, then they intentionally swindled people. If they didn’t, then they clearly didn’t have any idea what they were asking people to put into their bodies. Either way, it’s lose-lose for them.

To make things worse, AKG is being shown to play a role in stimulating insulin secretion (23), suggesting that companies may have indeed been trying to pull the wool over our eyes the whole time.

While this addition may seem beneficial, you have to remember that we still have no real evidence even suggesting that any of these products work at reasonable doses. And don't forget, an increase in insulin levels (and therefore blood flow) is all too easy to obtain without NO products.

Why would we use arginine to stimulate blood flow when we can get direct effects by manipulating insulin? In Part II of this article, I'll tell you how to do that without arginine supplements. The good news is, you're probably already doing it!


• Arginine blood flow stimulators ("nitric-oxide" or "NO2" supplements) have been shown to increase vasodilation, but only in unfed people receiving enormous doses through an IV.

• Oral arginine supplementation doesn't affect blood flow.

• A dose as low as 10 grams has been associated with gastric upset when consumed orally. This dose has no significant effect on glycogen storage, even if it didn't cause diarrhea.

• Time release arginine is supposed to lead to a "perpetual pump" effect. New studies have shown this not to be the case.

• NO2 was shown to have no effect compared to a placebo on body composition or muscle strength.

• It's not possible for us to consume high enough levels of arginine to effectively increase nitric oxide levels.

• Copycat NO2 products are no better than the original supplement. In fact, those that contain glycocyamine should be avoided because of potential health concerns.

• If you think these products work for you, then you'd better look into the placebo effect.

• Arginine might temporarily elevate growth hormone levels, but only if you're able to take unrealistic doses. There's little evidence to support that this short term increase in GH would do anything for your physique anyway.

• In one study, arginine aspartate was shown to increase prolactin by an average of 75%. Prolactin is associated with decreased Testosterone levels.

• Five grams of arginine consumed during resistance exercise was shown to decrease normal exercise-induced GH output.

• The positive benefits of oral arginine supplementation can only be achieved through doses higher than the human body can handle. And most (but not all) of this effect is mediated by insulin. So if you want to have blood flow increases equivalent to a huge IV arginine infusion, just manipulate insulin through other means (which will be discussed in the next article.)

About the Author

David J. Barr is a Doctoral student at the prestigious University of Texas Medical Branch amino acid metabolism lab, which is almost single handedly responsible for our pre and post-workout nutrition information. An accomplished varsity strength coach, he has certifications with the NSCA and USA Track and Field. In addition to his work for NASA at the Johnson Space Center, David’s research has involved everything from the cellular basis of muscle breakdown to work on critically ill catabolic patients. He can be contacted at

Darkhorse 05-29-2005 02:07 PM

Part 2
This specific product had several studies performed on it, and they were presented at the International Society of Sports Nutrition conference in the summer of 2004. While the findings do not yet come from peer reviewed publications, they yield important information about the efficacy, or lack thereof, of this supplement.

The first study examined the blood levels of arginine and "time released arginine" (following a four gram supplementation with each) to determine whether the latter enhanced the duration of elevated blood arginine levels (18). The reasoning for this study is due to the claim that NO2 has time-release technology, resulting in "perpetual pumps."

Unfortunately for the company, blood arginine levels were nearly all quite similar, and at times 30% lower, in the time-release trial compared to the pure arginine trial! The reason for the lower levels of the former group remains elusive, but could be due to a decreased absorption by the gut, an increased uptake by tissues, or a half dozen other fates for arginine (see 4). Not surprisingly, there was nothing resembling a "time release" effect.

The second study of interest evaluated the effects of NO2 on body composition, muscle strength and endurance (8). For eight weeks, subjects took either 12 grams of NO2 or placebo and underwent a resistance training protocol. At the end of the time period, subjects between groups had no differences in either muscle mass or body fat percentage.

Interestingly, the NO2 group threw an average of 19 pounds onto their bench 1RM, while the placebo group added less than a six pound mean. Does it seem strange to anyone else that this supplement alone supposedly added an average of more than 13 pounds to bench press 1RM over placebo without a concomitant change in muscle mass? This would indicate that the changes are strictly neural in origin, which gets quite complicated and goes beyond the scope of this article.

I'll briefly mention that while nitric oxide itself can have a negative effect on the force of muscle contraction (25), this effect has yet to be shown in humans, and doesn’t warrant serious consideration for our purposes. More importantly, all of the scientific evidence indicates that it's not even possible for us to consume high enough levels of arginine to effectively increase nitric oxide levels! Since this unpublished study is already gracing the advertisements for this supplement, we need to examine the results in a little more detail.

If the subjects in the above study were untrained, they would all add a significant amount of strength without changes in muscle mass within the first several weeks of working out. In this case, these rapid neural adaptations would be expected in both groups, but wouldn't explain how arginine seemingly tripled the improvement in the nervous system activation.

However, since the subjects were in fact trained, the situation is even more puzzling. Unlike novice trainees, strength increases in trained individuals tend to be more a result of muscle growth, which means that there should've been some changes in lean body mass accompanying the other gains. There wasn't.

I would've been impressed, albeit skeptical, by a three or four pound gain over the placebo group on bench press 1RM, but an average of 13 pounds?! Looking at it another way, this means an average gain of two and a half pounds on bench 1RM each week, and this progress is maintained for a whole eight weeks on the same program!

If this trend continued for all exercises, which it presumably does, everyone with these results could easily become a competitive powerlifter. Although such improvements might be theoretically possible, you must remember that these fantastic results were achieved on a training program and diet that normally leads to a mere six pound addition to bench press. Furthermore, to have such incredible strength gains throughout every muscle group, without even the slightest trend for improved muscle growth, demands questioning.

Considering the other research which showed no effect on blood flow and no time release effect, the results just don’t fit. Whether it be improper group selection, outliers in the data, or measurement error, the results presented remain questionable.

With my objective experience as a strength coach, researcher and bodybuilder, I don't believe these results to be possible. Having said that, this article is merely intended to give you the facts that you won’t get anywhere else, and allow you make up your own mind.

Let’s sum of the results of this study and others:

• One group used oral arginine in this study, but oral arginine supplementation doesn't affect blood flow.

• The arginine group used "time release" arginine, but so-called time release arginine is not actually time released.

• The trained individuals in the NO2 group got stronger without increasing muscle growth, but trained individuals get stronger mostly due to muscle growth.

• The training program and diet alone yielded a six pound increase in bench 1RM, yet four grams of NO2 taken three times a day tripled strength gains on the same program.

In short, something just isn't right.

Darkhorse 05-29-2005 02:34 PM

I love watching the 18 year old kids over at Bulk all debating over which no2 is the best. You get at least one or two a day. I'd take the time to post all this info but I really don't care :( if they waste their money or not. If I did I'd be posting this three times a day.

BG5150 05-29-2005 02:43 PM

Thank you VERY much for all of that.

I guess I'll stick to my creatine and protein for now.

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