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Old 08-17-2009, 06:11 AM   #11
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and More...

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!

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.

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.)

Stay tuned for Part II, coming tomorrow to T-Nation!

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

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