NO supplement study 2010

[Will Brink]

The three NO formulas used in this study were big name products. As expected, they did nadda.

Comparison of pre-workout nitric oxide stimulating dietary supplements on skeletal muscle oxygen saturation, blood nitrate/nitrite, lipid peroxidation, and upper body exercise performance in resistance trained men

Richard J Bloomer1 email, Tyler M Farney1 email, John F Trepanowski1 email, Cameron G McCarthy1 email, Robert E Canale1 email and Brian K Schilling2

Journal of the International Society of Sports Nutrition 2010, 7:16doi:10.1186/1550-2783-7-16


Abstract

Background

We compared Glycine Propionyl-L-Carnitine (GlycoCarn®) and three different pre-workout nutritional supplements on measures of skeletal muscle oxygen saturation (StO2), blood nitrate/nitrite (NOx), lactate (HLa), malondialdehyde (MDA), and exercise performance in men.

Methods

Using a randomized, double-blind, cross-over design, 19 resistance trained men performed tests of muscular power (bench press throws) and endurance (10 sets of bench press to muscular failure). A placebo, GlycoCarn®, or one of three dietary supplements (SUPP1, SUPP2, SUPP3) was consumed prior to exercise, with one week separating conditions. Blood was collected before receiving the condition and immediately after exercise. StO2 was measured during the endurance test using Near Infrared Spectroscopy. Heart rate (HR) and rating of perceived exertion (RPE) were determined at the end of each set.

Results

A condition effect was noted for StO2 at the start of exercise (p = 0.02), with GlycoCarn® higher than SUPP2. A condition effect was also noted for StO2 at the end of exercise (p = 0.003), with SUPP1 lower than all other conditions. No statistically significant interaction, condition, or time effects were noted for NOx or MDA (p > 0.05); however, MDA decreased 13.7% with GlycoCarn® and increased in all other conditions. Only a time effect was noted for HLa (p < 0.0001), with values increasing from pre- to post-exercise. No effects were noted for HR, RPE, or for any exercise performance variables (p > 0.05); however, GlycoCarn® resulted in a statistically insignificant greater total volume load compared to the placebo (3.3%), SUPP1 (4.2%), SUPP2 (2.5%), and SUPP3 (4.6%).

Conclusion

None of the products tested resulted in favorable changes in our chosen outcome measures, with the exception of GlycoCarn® in terms of higher StO2 at the start of exercise. GlycoCarn® resulted in a 13.7% decrease in MDA from pre- to post-exercise and yielded a non-significant but greater total volume load compared to all other conditions. These data indicate that 1) a single ingredient (GlycoCarn®) can provide similar practical benefit than finished products containing multiple ingredients, and 2) while we do not have data in relation to post-exercise recovery parameters, the tested products are ineffective in terms of increasing blood flow and improving acute upper body exercise performance.

Full study:

http://www.jissn.com/content/7/1/16#B2

[apex23]

Thanks for the posting. People should read this before blowing their hard earned cash.

[daywalker72]

but if these preworkout products have a placebo effect or give you more energy to push harder then go for it

[MikeS]

Seems like a solid study....apart from the fact it was funded by Sigma-Tau Health Science who happen to hold a patent for http://www.google.com/patents/about?id=MkoRAAAAEBAJ&dq=%236703042 and sell Glycocarn http://www.glycocarn.com/

The study even says the companies 'representatives' had involvement in the study.

I'm not doubting the results but I dont like these sorts of studies where the company who has a financial interest in the results pay for the study....maybe I'm too skeptical

[MikeS]

I'm sure if muscletech or gaspari wanted to they could pay for a study to show their supplements 'work'..

[Will Brink]

Seems like a solid study....apart from the fact it was funded by Sigma-Tau Health Science who happen to hold a patent for http://www.google.com/patents/about?id=MkoRAAAAEBAJ&dq=%236703042 and sell Glycocarn http://www.glycocarn.com/

The study even says the companies 'representatives' had involvement in the study.

I'm not doubting the results but I dont like these sorts of studies where the company who has a financial interest in the results pay for the study....maybe I'm too skeptical

Skeptical is good. That's where issues of methodology, reproducibility, author conflict of interest statements, location of study, etc, etc all come into play. Stay skeptical my friend. ;)

[Will Brink]

but if these preworkout products have a placebo effect or give you more energy to push harder then go for it

It's your $$$ dude, so what ever make ya happy. :hypno:

http://i23.photobucket.com/albums/b374/willbrink/Placebo.jpg

[MikeS]

Any independant data research using a similar methodology?



Not that I think the results will be different...

["Rodz"]

I'm sure if muscletech or gaspari wanted to they could pay for a study to show their supplements 'work'..


64565767467% better than any other supp

[BavarianMaximus]

Thanks for the posting. People should read this before blowing their hard earned cash.

We should look into the ingredients. The active ingredient are sugar, creatin, coffein and arginin. You can buy creatine, coffein and arginin very cheap. Why should anyone buy an expensive product like superpump? The reason is advertising.

I used some NO supplements, but without a satisfactory.

[Bryan Hildebrand]

will, what was your primary purpose for posting this "study"?

[BiggTexx]

the tested products are ineffective in terms of increasing blood flow and improving acute upper body exercise performance.



What do you think about this possibility Will, sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway through inhibition of type 5 phosphodiesterase. NO-cGMP pathway causes smooth muscle relaxation and induces vasodilation. Some have reported that taking small doses 10mg) of sildenafil citrate before training work great to stimulate nitric oxide.

[Will Brink]

What do you think about this possibility Will, sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway through inhibition of type 5 phosphodiesterase. NO-cGMP pathway causes smooth muscle relaxation and induces vasodilation. Some have reported that taking small doses 10mg) of sildenafil citrate before training work great to stimulate nitric oxide.

But to what end? An improved pump? Is that actually going to increase contractile fibers or just make you look cool in the gym? I have always considered the entire "pump" category of supps fools gold anyway.

Also see:

http://forums.rxmuscle.com/showthread.php?t=40707&highlight=nitrix+oxide

[BiggTexx]

But to what end? An improved pump? Is that actually going to increase contractile fibers or just make you look cool in the gym? I have always considered the entire "pump" category of supps fools gold anyway.


Increased vasodilation= increased flow of nutrients to the muscle? That could mean increased recovery. In fact Science Daily has an article about how Olympic cyclists athletes have improved cardiac output at high altitudes as much as 45% in a study published in JAP.

http://www.sciencedaily.com/releases/2006/06/060624120556.htm

No doubt Sildenafil citrate's benefit of causing vasodilation would benefit a bodybuilder the day of the big show. Certainly more effective that the No2 supplements that have not been shown to be effective.

[Will Brink]

Increased vasodilation= increased flow of nutrients to the muscle?

Possible, but blood flow is not a limiting factor to getting nutrients, etc to muscles.


That could mean increased recovery. In fact Science Daily has an article about how Olympic cyclists athletes have improved cardiac output at high altitudes as much as 45% in a study published in JAP.

But that's do to changes in Red Blood Cell Volume, improved 02 utilization, etc. It's a different physiological effect.


No doubt Sildenafil citrate's benefit of causing vasodilation would benefit a bodybuilder the day of the big show. Certainly more effective that the No2 supplements that have not been shown to be effective.

No doubt, but that's starting from zero... Might be useful day of the show. I have not gotten feedback from anyone doing it for workouts myself. Personally, would need to see some real data on endpoints that matter; increased LBM, strength, etc, to get interested in such a thing. And what to do with that boner you end up sporting in the gym??!! :hypno:

[BiggTexx]

PNo doubt, but that's starting from zero... Might be useful day of the show. I have not gotten feedback from anyone doing it for workouts myself. Personally, would need to see some real data on endpoints that matter; increased LBM, strength, etc, to get interested in such a thing. And what to do with that boner you end up sporting in the gym??!! :hypno:

I know several BB's using it for training and shows. I think it was in the news that several pro-baseball players were using it in their training too. However, I don't think we are going to see studies done one it because it is a prescription substance being used for athletic gains. It will never be prescribed or allowed by the FDA to be prescribed for this purpose.

Why do you think so many research chem shops sell PDE5 Inhibitors? I certainly don't know any BB's who can't get a boner and know of no one who can get one using 10mgs.;)

[BiggTexx]

Saraiva KL, Silva AK, Wanderley MI, De Araújo AA, De Souza JR, Peixoto CA. Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion. Int J Exp Pathol. 2009 Aug;90(4):454-62.

Abstract

The phosphodiesterase type 5 (PDE5) inhibitor, Sildenafil, is a novel, oral treatment approach for pulmonary hypertension. As Leydig cells present PDE5, this study was conducted to investigate the effects of the chronic treatment with Sildenafil (25 mg/kg) on male Swiss Webster mice steroidogenesis. After a 4-week long experimental design, Leydig cells were analysed by morphological and immunocytochemical procedures. Serum testosterone was assayed by radioimmunoassay. Leydig cells presented noteworthy ultrastructural alterations, such as a vesicular smooth endoplasmic reticulum, large vacuoles scattered through the cytoplasm, enlarged mitochondria with discontinue cristaes and whorle membranes with vesicles at the periphery, which are typical characteristics of an activated steroid-secreting cell. Important immunocytochemical labelling for steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme and testosterone were detected in isolated Leydig cells. In addition, Sildenafil-treated mice showed significant increased levels of total testosterone. The results obtained in the present study are consistent with the hypothesis that the accumulation of cyclic guanosine monophosphate by PDE5 inhibition could be involved in the androgen biosynthesis stimulation. Important clinical implications of hormonal disorders should be taken into account for patients with pulmonary hypertension.


After a four-week long experimental design, Leydig cells (these are in the testes) were analyzed by microscope. Sildenafil-treated mice showed significant increased levels of total testosterone. So not only does this stuff give you boner, it also increases plasma testosterone. :)

[Will Brink]

I know several BB's using it for training and shows. I think it was in the news that several pro-baseball players were using it in their training too. However, I don't think we are going to see studies done one it because it is a prescription substance being used for athletic gains. It will never be prescribed or allowed by the FDA to be prescribed for this purpose.

There's plenty of other reasons to research those effects that would be applicable to athletes. If there's $$$ to be made due to finding another use for the drug, research may get done.


Why do you think so many research chem shops sell PDE5 Inhibitors? I certainly don't know any BB's who can't get a boner and know of no one who can get one using 10mgs.;)

I get a boner on no mg, so....but seriously, maybe I'll ask my docs friends for some samples. ;)

[Will Brink]

After a four-week long experimental design, Leydig cells (these are in the testes) were analyzed by microscope. Sildenafil-treated mice showed significant increased levels of total testosterone. So not only does this stuff give you boner, it also increases plasma testosterone. :)

May increase T. It's an interesting finding, but in vivo in humans would get my interest up much more personally, and whether it's physiologically relevant (vs statistically significant) rise in T (see my article on T Boosters (http://www.brinkzone.com/articles/the-facts-on-testosterone-boosting-supplements/) for example) to cause actual changes in bodycomp is what matters end of the day. I hope there's a followup to this study done in humans using realistic doses.

[Will Brink]

Saraiva KL, Silva AK, Wanderley MI, De Araújo AA, De Souza JR, Peixoto CA. Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion. Int J Exp Pathol. 2009 Aug;90(4):454-62.

Abstract

The phosphodiesterase type 5 (PDE5) inhibitor, Sildenafil, is a novel, oral treatment approach for pulmonary hypertension. As Leydig cells present PDE5, this study was conducted to investigate the effects of the chronic treatment with Sildenafil (25 mg/kg) on male Swiss Webster mice steroidogenesis. After a 4-week long experimental design, Leydig cells were analysed by morphological and immunocytochemical procedures. Serum testosterone was assayed by radioimmunoassay. Leydig cells presented noteworthy ultrastructural alterations, such as a vesicular smooth endoplasmic reticulum, large vacuoles scattered through the cytoplasm, enlarged mitochondria with discontinue cristaes and whorle membranes with vesicles at the periphery, which are typical characteristics of an activated steroid-secreting cell. Important immunocytochemical labelling for steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme and testosterone were detected in isolated Leydig cells. In addition, Sildenafil-treated mice showed significant increased levels of total testosterone. The results obtained in the present study are consistent with the hypothesis that the accumulation of cyclic guanosine monophosphate by PDE5 inhibition could be involved in the androgen biosynthesis stimulation. Important clinical implications of hormonal disorders should be taken into account for patients with pulmonary hypertension.


After a four-week long experimental design, Leydig cells (these are in the testes) were analyzed by microscope. Sildenafil-treated mice showed significant increased levels of total testosterone. So not only does this stuff give you boner, it also increases plasma testosterone. :)

More recent:

Am J Physiol Endocrinol Metab. (javascript:AL_get(this,%20'jour',%20'Am%20J%20Phy siol%20Endocrinol%20Metab.');) 2010 Oct;299(4):E544-50. Epub 2010 Jul 27.
Sildenafil treatment in vivo stimulates Leydig cell steroidogenesis via the cAMP/cGMP signaling pathway.

Andric SA (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Andric%20SA%22%5BAuthor%5D), Janjic MM (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Janjic%20MM%22%5BAuthor%5D), Stojkov NJ (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Stojkov%20NJ%22%5BAuthor%5D), Kostic TS (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kostic%20TS%22%5BAuthor%5D).
Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
Abstract

Sildenafil citrate (Viagra), a cGMP-selective phosphodiesterase (PDE) inhibitor, is widely used to treat erectile dysfunction and pulmonary arterial hypertension. In contrast to its well established action on erectile dysfunction, little is known on the action of sildenafil on cGMP/cAMP signaling and testicular steroidogenesis. This study was designed to assess the effects of prolonged sildenafil treatment on NO synthase-dependent signaling and steroidogenic function of rat Leydig cells. Male adult rats were treated with Viagra (1.25 mg/kg body wt) daily for 30 days. In our studies, serum testosterone and ex vivo testosterone production significantly increased in sildenafil-treated animals. Human chorionic gonadotropin-stimulated testosterone production and cAMP accumulation were also significantly higher in Leydig cells obtained from sildenafil-treated rats. The expression of soluble guanylyl cyclase (GUCY1) subunits (Gucy1a1, Gucy1b1) significantly increased; cAMP-specific Pde4a, cGMP-specific Pde6c, and dual Pde1c and Nos2 were inhibited and expression of Nos3, protein kinase G1 (Pkg1), and Pde5 remained unchanged. Treatment of purified Leydig cells with NO donor caused a dose-dependent increase in both testosterone and cGMP production. Testosterone and cGMP production was significantly higher in Leydig cells obtained from sildenafil-treated animals. The stimulatory effect of NO donor was significantly enhanced by saturating concentrations of hCG in both Leydig cells obtained from control and sildenafil-treated animals. Occurrence of mature steroidogenic acute regulatory protein also increased in sildenafil treated animals in accord with increased cAMP and cGMP production. In summary, inhibition of PDE activity during prolonged sildenafil treatment increased serum testosterone level and Leydig cells' steroidogenic capacity by coordinated stimulatory action on cAMP and cGMP signaling pathway.

[MR. BMJ]

J Nutr. 2010 Dec 29.
Bolus Arginine Supplementation Affects neither Muscle Blood Flow nor Muscle Protein Synthesis in Young Men at Rest or After Resistance Exercise.

Tang JE, Lysecki PJ, Manolakos JJ, Macdonald MJ, Tarnopolsky MA, Phillips SM.
Department of Kinesiology, Exercise Metabolism Research Group, McMaster University, Hamilton, ON L8S 4K1, Canada.
Abstract
The aim of this study was to investigate the ergogenic potential of arginine on NO synthesis, muscle blood flow, and skeletal muscle protein synthesis (MPS). Eight healthy young men (22.1 ± 2.6 y, 1.79 ± 0.06 m, 76.6 ± 6.2 kg; mean ± SD) participated in 2 trials where they performed a bout of unilateral leg resistance exercise and ingested a drink containing either 10 g essential amino acids with 10 g l-arginine (ARG) or an isonitrogenous control (CON). Femoral artery blood flow of both the nonexercised and exercised leg was measured continuously using pulsed-wave Doppler ultrasound, while rates of mixed and myofibrillar MPS were determined using a primed continuous infusion of l-[ring-(13)C(6)] or l-[ring-(2)H(5)]phenylalanine. The plasma arginine concentration increased 300% during the ARG trial but not during the CON trial (P < 0.001). Plasma nitrate, nitrite, and endothelin-1, all markers of NO synthesis, did not change during either the ARG or CON trial. Plasma growth hormone increased to a greater degree after exercise in the ARG trial than CON trial (P < 0.05). Femoral artery blood flow increased 270% above basal in the exercised leg (P < 0.001) but not in the nonexercised leg, with no differences between the ARG and CON trials. Mixed and myofibrillar MPS were both greater in the exercised leg compared with the nonexercised leg (P < 0.001), but did not differ between the ARG and CON treatments. We conclude that an oral bolus (10 g) of arginine does not increase NO synthesis or muscle blood flow. Furthermore, arginine does not enhance mixed or myofibrillar MPS either at rest or after resistance exercise beyond that achieved by feeding alone.

[Will Brink]

J Nutr. 2010 Dec 29.
Bolus Arginine Supplementation Affects neither Muscle Blood Flow nor Muscle Protein Synthesis in Young Men at Rest or After Resistance Exercise.

.

Shocking....not! :whistle:

[luke_b21]

In addition to the blood flow and testosterone effects mentioned, there is also evidence that arginine/NO may improve glucose uptake by skeletal muscle. However, the group that has done most of this work recently showed that insulin is increased by arginine, and that is likely what is responsible.

Effect of L-Arginine Infusion on Glucose Disposal during Exercise in Humans.
Linden KC, Wadley GD, Garnham AP, McConell GK.

Abstract
PURPOSE: We have previously shown that local infusion of a nitric oxide synthase (NOS) inhibitor attenuates increases in leg glucose uptake during exercise in humans. We have also shown that infusion of the NOS substrate, L-arginine (L-Arg), increases glucose clearance, although the mechanisms involved were not determined. A potential mechanism for NO-mediated glucose disposal is via interactions with NOS and the energy sensor AMP-activated protein kinase (AMPK). The aim of this study was to determine the mechanism(s) by which L-Arg infusion increases glucose disposal during exercise in humans by examining total NOS activity and AMPK signaling.

RESULTS: L-Arg increased the glucose rate of disappearance and glucose clearance rate during exercise, however this was accompanied by a 150% increase in plasma insulin concentration from 65-75 min (P<0.05) that remained significantly elevated until 90 min of exercise. Skeletal muscle AMPK signaling, nNOSμ phosphorylation by AMPK and total NOS activity increased to a similar extent in the two trials.

CONCLUSION: The increase in glucose disposal following L-Arg infusion during exercise is likely due to the significantly higher plasma insulin concentration.

[luke_b21]

HOWEVER, in respect to blood flow, there is also substantial data showing that reduced blood flow is good for strength and muscle gains. Just look up Kaatsu or vascular occlusion training. So maybe there is something to "the pump."

But I agree that pre-workout supplements are a little benefit beyond the stimulants. Arginine may have some benefit, but as far as using it pre-workout for a better "pump," I think its probably bogus.

[adpolice]

Personally i used nitrates once which increase blood flow..the result?After 15 minutes i got so pumped i couldn't continue my workout..The question is even if there are compounds that increase no production what does this mean to the bber who want to gain muscle or to the lifter who wants more strength,my opinion nothing..It is just the feel effect and especially the stimulants that made those NOpreworkout supplents so popular

[meowcat]

All this research is great but how about our own experience and instincts...
I for one did great when i first started using NO products years ago..i did'nt gain any muscle directly from them but the pumps and muscle fibre recruitment i experienced then from it took me to a new level in training.
They're not as effective on me now as they were then but still i use NO products occasionally and get a good feeling workout from them.
just my two cents.