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Supplements discussion on nitric oxide, within the Bodybuilding Forum; does nitric oxide live up to the hype?...


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Old 01-14-2006, 08:04 AM   #1
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does nitric oxide live up to the hype?
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Old 01-14-2006, 10:57 AM   #2
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I like it, I use Nitrix and it works well. For me, NO is more of a psychological thing. Feeling the pump and listening to Metal helps get me focused. BUT it's not necessary and you don't really need it if you stick to creatine. If you have some extra money I say try it.

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Old 01-14-2006, 11:26 AM   #3
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I posted a lot of good articles here:

http://www.bodybuilding.net/suppleme...ed-it-549.html

I personally don't believe they're worth it. According to science, aside from citrulline malate, akg and the like aren't worth it. Make sure to really read the link I provided above so you can make an informed decision.

However, I recommend supplementing something like citrulline malate. It's relatively cheap and helps you get that last rep.

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Old 01-14-2006, 11:27 AM   #4
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By: Karl Hoffman at http://www.scivation.com/?pageID=26

Citrulline malate (CM) is a combination of two compounds that occur naturally in the human body. Malate is an intermediate in the so-called tricarboxylic acid cycle (TCA). ATP, which the body uses as a source of energy, is produced via the TCA when oxygen is abundant. (In reality, no ATP is produced directly from the TCA, although this statement is often heard. Rather, reduced coenzymes, NADH, are used to generate ATP in electron transport chain powered oxidative phosphorylation.) This is so called aerobic energy production.

Tricarboxylic acid cycle (TCA) at a glance. Each kind of major fuel is converted to acetyl groups, which are handled by attachment to a particular coenzyme known as coenzyme A. Ultimately ATP is produced from NADH generated by the TCA.

Malate is dehydrogenated in the TCA cycle to oxaloacetate, the concentration of which is one of the most critical controls of the rate of aerobic ATP production. During prolonged aerobic activity, and in patients suffering from malate deficiency, malate becomes depleted and the TCA is unable to produce ATP fast enough to meet the demands of working muscle. One classic disease characterized by malate deficiency is fibromyalgia. When patients suffering with this disease are given malate, their energy levels improve dramatically (1).

Not only patients suffering from malate deficiency benefit from malate supplementation. As mentioned above, strenuous, prolonged aerobic activity depletes the body’s malate stores. One recent study looked at the effects of CM supplementation in 18 otherwise healthy men who complained of easy fatigability. (2) The subjects were administered 6 gm/day of CM for 15 days. To quote from the results of the study,

"CM ingestion resulted in a significant reduction in the sensation of fatigue, a 34% increase in the rate of oxidative ATP production during exercise, and a 20% increase in the rate of phosphocreatine recovery after exercise, indicating a larger contribution of oxidative ATP synthesis to energy production… The expansion of the TCA intermediate pool [through malate supplementation] can therefore be regarded as a means of attaining higher rates of aerobic energy production, in agreement with our results showing that malate supplementation promotes a greater contribution of aerobic ATP production to total energy production. These results suggest that this hyperactivation of aerobic ATP production coupled to a reduction in anaerobic energy supply may contribute to the reduction in fatigue sensation reported by the subjects."So not only were objective measures of energy production increased, but the study participants felt a subjective improvement in energy levels as well.

Thus far we have only addressed the role of malate in enhancing ATP production during aerobic metabolism. What about citrulline? Citrulline is a non-essential amino acid produced from glutamine in the body. Citrulline is involved in the so-called urea cycle, which is responsible for the removal of excess nitrogen from the breakdown of amino acids. Were excessive levels of nitrogen to accumulate in the body, ammonia toxicity would develop. Besides stimulating hepatic ureogenesis , citrulline also promotes the renal reabsorption of bicarbonates. The latter acts as a buffer against lactic acidosis, which also helps to stave off fatigue. In fact there has been some debate over the years whether citrulline or malate is primarily responsible of prolonging endurance (3). The consensus now seems to be that the two compounds work in concert, with malate maintaining TCA intermediates and allowing for increased ATP production, and citrulline buffering against lactic acid and ammonia buildup.

So we have seen that citrulline malate seems to be a worthwhile adjunct to any supplement protocol, especially where aerobic performance and fatigue resistance are important.
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Old 01-14-2006, 11:54 AM   #5
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Quote:
Originally Posted by 0311
I posted a lot of good articles here:

http://www.bodybuilding.net/suppleme...ed-it-549.html

However, I recommend supplementing something like citrulline malate. It's relatively cheap and helps you get that last rep.
for some odd reason the link is just sending me back to the main page and not to the supplement section. could you re-post or quote it. I would also like to know what the cheaper version of citrulline malate is.
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Old 01-14-2006, 12:25 PM   #6
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Quote:
I would also like to know what the cheaper version of citrulline malate is.
I was referring to something like Bulk Nut's brand vs. something like MAN's brand, ect..

None of the links I post work here today for some reason so I'll cut and paste.

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.
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Old 01-14-2006, 12:25 PM   #7
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The Real Secret Part 1

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!

Summary

• 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 DBMuscle@Hotmail.com.
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Old 01-14-2006, 12:26 PM   #8
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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.
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Old 01-14-2006, 12:28 PM   #9
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Last two articles courtesy of T-Nation. It's title has the word SCAM in it. I cannot remember.
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Old 01-14-2006, 12:42 PM   #10
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Consumer Alert: The NO2/Arginine Scam
by David Barr



The Biggest Scam in Supplement History

Take a look at the history of nutritional supplements and you'll find many scams and cons. It's easy to spot these swindles in hindsight; it's a little tougher to identify them during their market peaks. Well, there's a scam going on right now, a big one. In fact, it's growing even bigger as I write this. Are you falling for it? Are you being suckered by bad science and questionable marketing tactics?

Let's cut to the chase: the biggest scam on the market right now is arginine blood flow stimulators. You may know these by the terms "nitric-oxide stimulators" or "NO2 supplements."

Wait, you already knew these supplements were worthless? And you think you already know what the scam is? Doubtfully. Because I'm about to reveal the real con behind these supplements. In this Consumer Alert, I’ll not only blow the lid off of the whole scam, but I’ll also reveal to you a better hemodilator that's been proven for years to increase blood flow, aid in recovery, and stimulate muscle protein synthesis.

This article covers the science showing why arginine products don’t stand up to their claims, but the rabbit hole goes much deeper than that. Hang on Alice, you’re in for a wild ride.


Why Arginine? Why Now?

Why are so many supplement companies focusing on arginine? Well, now that prohormones are banned, companies are scrambling to throw out the next big supplement to keep them in business. If nothing truly groundbreaking is within their grasp, they'll come out with a worthless supplement supported by dubious science. Want to know what's really pathetic? If this garbage supplement makes some money, other companies will rip off the bad idea and market their own versions, regardless of whether or not the supplement works!

Are the copycats and knockoffs, with their additional bells and whistles, better? No. In fact, some sleazy manufacturers are even including potentially harmful substances like glycocyamine in their products!

This copycat movement was really noticeable at the recent Olympia Expo, where only variations on two products seemed to exist: creatine and nitric oxide stimulators. While readers may be aware of the inherent risks of creatine wannabes from our Consumer Report on Dangerous Creatine, recent evidence demonstrates how nitric oxide stimulators can be considered the greatest con since ENRON. Let's dig into the evidence.


Hemodilators: Theory and Practice

The hemodilator (or blood vessel dilator) products saturating the market are purported to stimulate blood flow and subsequently enhance nutrient delivery to muscles, resulting in increased size and strength. As you may know, these products contain little more than the amino acid arginine, something that's been on the supplement market for years and years. Basically, arginine supplementation is claimed to stimulate the synthesis of the hemodilator nitric oxide (NO) in our blood vessels.

The existing theory looks like this:

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

Now there’s nothing inherently wrong with arginine. In fact, it’s an important amino acid. It’s just not the amino acid to really help your gains — more on that later.

New research has been revealed since the first T-Nation article on these types of supplements was published. Now we can focus on that which is directly applicable to us: studies on healthy adults.


Sick Over Arginine

The whole hemodilator theory is relatively simple. Arginine is the precursor for NO synthesis and it's been shown that high dose arginine infusion directly into the bloodstream can lead to vasodilation in healthy fasted humans (17). Unfortunately, high doses can lead to decreases in total body water and sodium (4). And even a dose as low as 10 grams has been associated with gastric upset when consumed orally (26,14).

Researchers involved in a third study demonstrating oral arginine-induced GI distress actually had to reduce the quantity originally given so the trials could be completed effectively (29). Despite the reduction to seven grams an hour for three hours (for a 200 pound man), the researchers reported: "All of our subjects reported mild intestinal cramping and diarrhea that lasted for approximately five hours."

But wait, it gets worse! This arginine dose still had no significant effect on glycogen storage following exercise (29)! Because oral arginine only has 70% bioavailability, and up to 50% of this can be broken down to ornithine, taking arginine tablets or powder is impractical for research (6, 9). This is why arginine is usually infused directly into the blood via peripheral IV for scientific studies, and even then an impractical dose of 30 grams of this amino acid is common.

In fact, one study compared infusions and oral dosing. The researchers found that six grams of arginine had no effect via either route of administration, while it took a 30 gram infusion to cause vasodilation (6). So, it takes a 30 gram IV dose to get results. If we were to get these results from an oral dose, we’d have to take 43 grams because only 70% of it is bioavailable (i.e. 30 / .7 = 43).

Now if 10 grams can cause gastric upset, then the 43 gram oral dose (with bioavailability taken into account) makes me more than a little uneasy.


Arginine: A No Go for NO

If you think that this lack of effect is an isolated incident, other studies investigating high oral doses of arginine and NO induced blood flow have shown no effect when 21 grams (7 g 3x/d) were used (1). Two additional studies where 20 grams per day were taken for 28 days also showed no effects (11,12).

At first, this complete lack of effect was a little surprising considering that arginine is the precursor for nitric oxide synthesis. But upon closer inspection, natural arginine levels are far in excess of what should activate the enzyme responsible for NO production — an effect known as the arginine paradox (21).

In yet another study, a six day, arginine free diet had no effect on nitric oxide synthesis. This indicates that arginine isn't limiting for NO production, and its regulation is far more complicated than supplement companies would have us believe (9).

Of course, the whole rested and fasted thing doesn’t apply to you, so let’s see what happened when exercise was involved. This next noteworthy study used 10 grams of arginine along with 70 grams of carbohydrates in subjects who either performed resistance training or cycling exercise (26). The results? There were no changes in blood flow or glucose uptake compared to placebo, regardless of which mode of exercise was used. This is significant because it directly contradicts the claims of the supplement manufacturers.

For those who are more skeptical, or perhaps just brainwashed by flashy advertising, you’re probably not happy with studies using pure arginine. Oh no, it has to be special arginine, like the ones used in the popular products, before you’ll believe any results. Fine, let's look into the science and crack that nut.


The Acid Test

While it’s important to understand the evidence behind normal arginine supplementation, many would argue that it doesn’t apply to the original nitric oxide-stimulating supplement, NO2. This is because the aforementioned product contains arginine alpha-ketoglutarate, not simply arginine. The theory is that alpha ketoglutarate (AKG) somehow makes this supplement "work." Okay, that’s cool, let’s see what science has to say.



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.


But Wait, I Thought I Felt Something! :eek:

I’m sure some people are reading this and thinking, "But I know these products work because I’ve taken them and feel their effects!" While these perceived effects are potent, I submit to you that based on the scientific evidence, this is merely a result of the placebo effect.

The placebo effect is when someone uses an inert substance, which should produce no effect, yet somehow still experiences an effect. This occurs frequently when pharmaceutical companies test a new drug. They give one group the real drug and another group an inert sugar pill. Interestingly, the group receiving the sugar pill often has a series of side effects like dry mouth, headaches, dizziness, adding ten pounds to their bench, etc. — all caused by their own minds!

One famous research analysis calculated the placebo effect to account for 75% of a drug’s effect, although this exact figure remains controversial (19). It’s amazing what dogma we can succumb to in the face of contrary reason and evidence, merely because we want to believe something. This belief, desire and trust all seem to work at the neurological level of the brain (10). This indicates that it’s more than a matter of a few people being tricked by unscrupulous companies.

Unfortunately, the situation is even worse when it comes to sports supplements because of our expectations. Hundreds of advertisements with spectacular claims, combined with our incredibly strong desire to believe that these supplements work, often defeat our poor psyches. I call this a directed placebo effect, because we have not only a simple belief in what the supplement is supposed to do, but a powerful desire to believe in its effectiveness.

What can make our desire to believe in these products even stronger is the very fact that we've already purchased them! After all, recognizing that a product doesn’t work is like admitting that we were duped — something no one wants to do. Hey, I've fallen into this trap too in the past. We're all susceptible.

Even if you still believe in the products in question, you’ll now be aware of this powerful psychological effect.


But What About Growth Hormone Release?

In response to this rather damning article, some companies will scrounge up data showing that arginine can elevate growth hormone levels. While we’ve known for the past decade that this applies only to huge doses infused into the bloodstream, many people will be unaware of this trick.

Now, there's evidence that ingesting 22 grams per day (in a 200 pound man) of arginine aspartate increased nocturnal growth hormone output (5). The peak GH output during sleep was increased by an average of 60%. Unfortunately, only five subjects were studied and one of them had four times the peak output of the others. Without that one oddball subject, the average peak was cut in half! (Again, these are just peak measurements, not total levels.)

Also of note, prolactin increased by an average of 75%. This hormone is associated with decreased Testosterone (7)! What’s really scary is that a mere five grams of arginine consumed during exercise actually decreased the resistance exercise-induced increase in GH output (24)!

The bottom line is that you can forget about arginine and GH stimulation, despite what the advertisements try to tell you.
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