Creatine Nitrate, any good?

[NO HYPE]

Taking a baby asprin (<81 mg) every day has been demonstrated conclusively to enhance vasodilation, but no one is claiming that an asprin-creatine combo would result in better results than creatine mono.

Are you seriously comparing the pharmacokinetics of asprin, with a mere terminal half-life of 0.4 to 2.1 hours [1], to that of nitrates?

[1] J Clin Pharmacol. 1995 Dec ;35 (12):1181-6 8750369

[chefwaffles]

creatine mono>all other creatines. dont fall for the hype of new age creatine. mono is the oldest, most widely tested and proven to work.

[NO HYPE]

creatine mono>all other creatines.

False.

[neuron]

Are you seriously comparing the pharmacokinetics of asprin, with a mere terminal half-life of 0.4 to 2.1 hours [1], to that of nitrates?

[1] J Clin Pharmacol. 1995 Dec ;35 (12):1181-6 8750369

There is a difference between a clearance half-life and a biological half-life.

Asprin inhibits platelet and endothelial COX.

Inhibting platelet COX results in less thromboxane A2 (a vasoconstrictor) for 10-13 days - i.e. the life of the platelet (biological half-life).

Endothelial cells can regenerate COX (asprin forms a suicidal covalent linkage with COX), which allows it to re-produce prostanoids and prostacyclin (vasodilators) within a few hours.

The end result is vasodilation.

This is why physicians recommend baby asprin to patients at risk.

[neuron]

False.

You have no evidence to the contrary.

[tylerdurden92]

seems like everyday some company comes out with some revolutionary creatine, but some of the best creatine supplements I have tried, like size on, still use creatine monohydrate...

[swiftknight]

On my way to CVS now

rofl

Man I wish I was smart as No Hype or Neuron.

[NO HYPE]

which allows it to re-produce prostanoids and prostacyclin (vasodilators) within a few hours. The end result is vasodilation.

"The results we report here, strongly support the view that ISDN promotes release of prostacyclin and PGF2 alpha from the lung and inhibit PGE2 production. These prostanoids may be responsible for the concomittant platelet reactivity lowering, thus providing a basis for understanding how ISDN might relieve myocardial ischemia favoring prostanoid-mediated vasodilation and inhibition of platelet reactivity."

Prostaglandins Leukot Med. 1984 Dec;16(3):333-46.
Evidence for isosorbide dinitrate (ISDN) promoting effect on prostacyclin release by the lung and prostacyclin implication in ISDN-induced inhibition of platelet aggregation in humans

This is why physicians recommend baby asprin to patients at risk.

Physicians also advocate the clinical use of organic nitrates for coronary artery disease and congestive heart failure.

[NO HYPE]

You have no evidence to the contrary.

Obviously I have no evidence within the literature, as it does not exist [seeing how creatine nitrate is still in it's infancy]. However, I can still put two & two together [in addition to my anecdotal evidence]. Creatine nitrate effectively enhances vasodilation to a noticeable degree. Creatine monohydrate does not.

[WheyBeastly]

neuron and NO HYPE, please store all of your intelligence onto a hard drive, and mail that to me. Thanks.

[brudman]

Obviously I have no evidence within the literature, as it does not exist [seeing how creatine nitrate is still in it's infancy]. However, I can still put two & two together [in addition to my anecdotal evidence]. Creatine nitrate effectively enhances vasodilation to a noticeable degree. Creatine monohydrate does not.

While you've established that creatine nitrate enhances vasodilation and monohydrate does not, is there any literature that you know of that clarifies whether Creatine Nitrate is as efficient as mono in terms of intramuscular PCr?

Not trying to take you on here...just trying to choose my next creatine product wisely

[NO HYPE]

neuron and NO HYPE, please store all of your intelligence onto a hard drive, and mail that to me. Thanks.

lol

Seriously though, I have learned much through neuron's degree of knowledge. His knowledge is accredited, mine however, is not.

[NO HYPE]

is there any literature that you know of that clarifies whether Creatine Nitrate is as efficient as mono in terms of intramuscular PCr?

Once saturated, there will be absolutely no difference in the cellular capacity of intramuscular PCr concentrations [wether it's creatine nitrate or creatine monohydrate].

[brudman]

Once saturated, there will be absolutely no difference in the cellular capacity of intramuscular PCr concentrations [wether it's creatine nitrate or creatine monohydrate].

I gotcha. How about literature on how much Creatine Nitrate is required to achieve saturation vs creatine monohydrate? The reason I ask is because Neuron said that creatine nitrate is a salt and readily dissociates upon ingestion. If that's the case, would the additive effect be the same as taking creatine monohydrate and the nitrate separately?

[NasGhost]

I gotcha. How about literature on how much Creatine Nitrate is required to achieve saturation vs creatine monohydrate? The reason I ask is because Neuron said that creatine nitrate is a salt and readily dissociates upon ingestion. If that's the case, would the additive effect be the same as taking creatine monohydrate and the nitrate separately?

Im not sure you would want to take that much creatine nitrate; you would want to add another creatine to i think.

[apsnutrition]

seems like everyday some company comes out with some revolutionary creatine, but some of the best creatine supplements I have tried, like size on, still use creatine monohydrate...

I have to agree with NO HYPE from a REAL WORLD perspective.when testing products before we decide to use them we consider the science for sure but if there is a preponderance of evidence that it clearly elicits an effect on a majority of test subjects then (even if by a secondary pathway)it is strongly considered.I don't think there is any question creatine nitrate is superior to mono based solely on real world feedback.I am speaking with the patent holder in a couple of hours and will see if he can provide me with the science to put this one to bed and post it.thermolife claims it bolsters the assimilation/effectiveness of anything taken with it.If so,wouldn't this hold true for creatine?Not challenging neuron as he clearly knows what he is talking about but no hype is right CN is superior in the gym.Everyone who has taken both can confirm this.

[NO HYPE]

How about literature on how much Creatine Nitrate is required to achieve saturation vs creatine monohydrate?

As previously mentioned, there is no evidence for creatine nitrate within the literature, as it does not exist [seeing how creatine nitrate is still in it's infancy].

The reason I ask is because Neuron said that creatine nitrate is a salt and readily dissociates upon ingestion. If that's the case, would the additive effect be the same as taking creatine monohydrate and the nitrate separately?

The solubility of monohydrate reflects it’s absorption limit. The organically-bonded nitrate moiety increases the water-solubility of creatine, which elicits a faster absorption time and a second absorption method.

Passive diffusion requires water solubility i.e. existence in anionin form in aqueus solution. This is why water soluble forms of Creatine like nitrate and HCl exhibit much faster absorption and better AUC compared to the non-soluble anhydrous/monohydrate that is only absorbed through active transportation channels.

The main advantage is the perfect water solubility which gives a faster absorption time and a second absorption method (passive diffusion due to osmosis+active transportation VS the active transportation only of mono), giving superior PKs and much less GI issues that have arised from the bolus/osmotic imbalance mono might create.

[neuron]

The solubility of monohydrate reflects it’s absorption limit. The organically-bonded nitrate moiety increases the water-solubility of creatine, which elicits a faster absorption time and a second absorption method.

Creatine nitrate is a salt. When ingested, it becomes ionized into its respective components (creatine, nitrate) - exactly the same as any other salt, be it creatine HCl or otherwise.

[neuron]

Obviously I have no evidence within the literature, as it does not exist [seeing how creatine nitrate is still in it's infancy]. However, I can still put two & two together [in addition to my anecdotal evidence]. Creatine nitrate effectively enhances vasodilation to a noticeable degree. Creatine monohydrate does not.

Creatines modality has nothing to do with vasodilation, so it's a completely moot point.

[neuron]

If that's the case, would the additive effect be the same as taking creatine monohydrate and the nitrate separately?

Yes.

[neuron]

"The results we report here, strongly support the view that ISDN promotes release of prostacyclin and PGF2 alpha from the lung and inhibit PGE2 production. These prostanoids may be responsible for the concomittant platelet reactivity lowering, thus providing a basis for understanding how ISDN might relieve myocardial ischemia favoring prostanoid-mediated vasodilation and inhibition of platelet reactivity."

Prostaglandins Leukot Med. 1984 Dec;16(3):333-46.
Evidence for isosorbide dinitrate (ISDN) promoting effect on prostacyclin release by the lung and prostacyclin implication in ISDN-induced inhibition of platelet aggregation in humans





Physicians also advocate the clinical use of organic nitrates for coronary artery disease and congestive heart failure.

No physician in his right mind would suggest non-pharmaceutical 'nitrates' for congestive heart failure. ACE inhibitors and diuretics are the drugs of choice for CHF.

Furthermore, what does that have to do with the point I was making above (biological half-life versus clearance half-life)?

[SwolenONE]

for what its worth, i was not only impressed with the pumps on c-bol, but ten fold was impressed on the strength gains on c-bol. This, to me, showed me creatine nitrate does in fact seem to be a better option than creatine monohydrate.

[Adjusting]

for what its worth, i was not only impressed with the pumps on c-bol, but ten fold was impressed on the strength gains on c-bol. This, to me, showed me creatine nitrate does in fact seem to be a better option than creatine monohydrate.

Well you can't exactly discount the orotic acid which could have had an effect on your strength.

[michael3435]

Well you can't exactly discount the orotic acid which could have had an effect on your strength.

It can't be just the orotic acid. I had extreme strength increases on c-bol. MAN clout didn't do it like this did.

[Adjusting]

It can't be just the orotic acid. I had extreme strength increases on c-bol. MAN clout didn't do it like this did.

Some of it is just bound to be coincidence. I didn't gain massive strength on c-bol and never have on a nitrate formula. Pumps are wicked but no dramatic gains.

[michael3435]

Some of it is just bound to be coincidence. I didn't gain massive strength on c-bol and never have on a nitrate formula. Pumps are wicked but no dramatic gains.

i was actually very sensitive to the nitrates (got headaches very easily). with my strength going up so much and having not seen the results from the other ingredients on other occasions, i think it would be safe to say its the nitrates.

[EricTheRed]

IFS






in for science

[freak111]

Tim,

You need to make a supplement book you're a genius along with Neuron!

Is it that P-Bol is the only supplement product that offers Creatine Nit. ? Also what are the most beneficial dosing with Crea-Nitrate? In this matter do you think all other Creatine are useless and uneffective such as Kre-Alkalyn, CEE/AKG or whatever exist and even Creapure Mono?

Thanks!

False.

[NO HYPE]

Why should he start out with plain ol' mono, when he can recieve better results from creatine nitrate?

Nitrates don't enhance the physiological effects of creatine.

As mentioned previously, This was never implied. I feel that my comments were rather obvious from the start, and in no way pertained to an alteration in the pharmacodynamics of creatine. How does the statement "he can recieve better results from creatine nitrate" imply that the physiological effects of creatine itself will be altered? Again, I am well aware of the fact that intramuscular PCr concentrations will be identical following saturation however, nitrates will elicit enhanced vasodilatory/absorption mechanisms.

Creatines modality has nothing to do with vasodilation.

We have established this well-known fact already.

so it's a completely moot point.

Completely moot point? Not quite. Once again [seeing how creatine's modality was never in question in the first place], If you take the clinically-validated physiological effects of creatine and combine them with the clinically-validated physiological effects of nitrate-enhanced vasodilation/absorption, do you honestly feel that the endpoint [multifaceted] results would not exceed the original elicited benefits?

Are you implying that creatine nitrate does not elicit more beneficial physiological benefits than monohydrate?

The nitrate moiety has physiological effects that are unrelated to the effects of creatine

This fact was blantantly obvious from the start, and I'm not sure how you came to the conclusion that I was implying notions to the contrary.

If it somehow enhanced intracellular storage, or increased phosphate donation, then it would be considered better than regular creatine. It doesn't.

Once again, I never implied that the pharmacodynamics of creatine would be altered however, how do the added physiological benefits of enhanced vasodilation/absorbtion, fail to add to the physiological benefits of creatine?

If it was an ester then one could make the argument that the combination would effect the pharmacokinetics of creatine, but it's not; creatine nitrate is a salt and readily dissociates upon ingestion - as if they were two compounds ingested separately (an additive effect).

When ingested, it becomes ionized into its respective components (creatine, nitrate) - exactly the same as any other salt, be it creatine HCl or otherwise.

So are you suggesting that because C-BOL/creatine nitrate is a salt and readily dissociates upon ingestion, that the solubility of creatine nitrate is not enhanced? In terms of Bane's comments, are you suggesting that faster absorption/enhanced concentration versus time curve with the added benefit of a second absorption mechanism [passive diffusion due to osmosis+active transportation vs. the singular active transportation mechanism of mono], are incorrect and do not positively alter the pharmacokinetics of monohydrate?

Originally posted by Bane:
Passive diffusion requires water solubility i.e. existence in anionin form in aqueous solution. This is why water soluble forms of Creatine like nitrate and HCl exhibit much faster absorption and better AUC compared to the non-soluble anhydrous/monohydrate that is only absorbed through active transportation channels. The main advantage is the perfect water solubility which gives a faster absorption time and a second absorption method (passive diffusion due to osmosis+active transportation VS the active transportation only of mono)

The two have never been tested head-to-head so it's only a guess on your part that creatine nitrate would be better than creatine mono.

so combining two seemingly benefical compounds together doesn't necessarily equate to a synergistic, or even additive, conclusion.

Obviously I have no evidence within the literature, as it does not exist [seeing how creatine nitrate is still in it's infancy]. However, I can still put two & two together [in addition to my anecdotal evidence]. Creatine nitrate effectively enhances vasodilation to a noticeable degree. Creatine monohydrate does not.

Taking a baby asprin (<81 mg) every day has been demonstrated conclusively to enhance vasodilation, but no one is claiming that an asprin-creatine combo would result in better results than creatine mono.

Has baby aspirin been found to increase athletic performance [as nitrates have]? Does baby aspirin assist intestinal co-ingested nutrient absorption?

Originally posted by Bane:
Nitrates have been used in the pharmaceutical industry for decades to induce direct and fast vasodilation. They do this by directly binding to the blood vessel NO receptor. This creates a powerful vasodilating effect which actually helps with nutrient absorption and distribution and increases athletic performance(3).

Organic nitrates have also a great use in pharmacy as a permeation enhancer. That means that they increase intestinal absorption of not only the bonded molecule but ALL nutrients co ingested. They are even able to allow absorption of large macromolecules as insulin(4,5,6)!

[NO HYPE]

Physicians also advocate the clinical use of organic nitrates for coronary artery disease and congestive heart failure.

No physician in his right mind would suggest non-pharmaceutical 'nitrates' for congestive heart failure. ACE inhibitors and diuretics are the drugs of choice for CHF.

Am J Cardiol. 2004 Dec 1;94(11):1465-8.
Bitar F, Akhter MW, Khan S, Singh H, Elkayam U.
Heart Failure Program, Division of Cardiovascular Medicine, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA
Survey of the use of organic nitrates for the treatment of chronic congestive heart failure in the United States.

A survey of members of the Heart Failure Society of America revealed that despite their lack of approval by the United States Food and Drug Administration, nitrates are widely used in patients with chronic congestive heart failure (CHF). Most members reported using nitrates in patients with ischemic (90%) and nonischemic (81%) causes of chronic CHF, especially those with symptomatic CHF (43% reported using nitrates in >50% of their patients with ischemic and 25% with nonischemic causes). Ninety-six percent reported using nitrates to reduce symptoms, 74% for hemodynamic improvement, 65% for better exercise tolerance, and only 14% for left ventricular reversed remodeling. Nitrates were always combined with hydralazine in 25% of patients and occasionally combined with hydralazine in 67%.



Cardiovasc Drugs Ther. 1994 Jun;8(3):501-7.
Dupuis J. Montreal Heart Institute, Québec, Canada.
Nitrates in congestive heart failure.

Nitrates are commonly used in the therapy of congestive heart failure (CHF). They exert beneficial hemodynamic effects by decreasing left ventricular filling pressure and systemic vascular resistance while modestly improving cardiac output. The improvement in left ventricular function caused by nitrates is the result of combined reduction in outflow resistance and mitral regurgitation, while decreased pericardial constraint and subendocardial ischemia may also contribute to the process. With continuous nitrate administration, complete arterial tolerance develops, while venous tolerance appears to be only partial. The major mechanism of tolerance is loss of vascular smooth muscle sensitivity to nitrates. An increase in total blood volume occurring during the first few hours of an acute administration may partly contribute to tolerance. The importance of reflex neurohumoral activation is controversial; although it may contribute to tolerance in CHF, its role does not appear to be major. Chronic continuous nitrate therapy in CHF improves submaximal and maximal exercise tolerance. In combination therapy with hydralazine, isosorbide dinitrate reduces mortality, although to a lesser extent than the angiotensin converting enzyme inhibitor enalapril. Intravenous or sublingual nitrates are first-line agents in the therapy of acute pulmonary edema. In severe CHF, refractory to standard medical therapy, a short course of intravenous nitroglycerin, with or without inotropic agents, can help break the vicious spiral of CHF. Because tolerance occurs without nitrate-free intervals and until an optimal schedule of administration is determined, it makes good sense to include a nightly nitrate-free interval when prescribing nitrates for CHF in order to maintain maximal benefit during the hours of activity.



J Am Coll Cardiol. 1995 Dec;26(7):1575-80.
Gogia H, Mehra A, Parikh S, Raman M, Ajit-Uppal J, Johnson JV, Elkayam U.
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
Prevention of tolerance to hemodynamic effects of nitrates with concomitant use of hydralazine in patients with chronic heart failure.

OBJECTIVES: This study was designed to determine the effect of oral hydralazine on the development of nitrate tolerance in patients with chronic congestive heart failure. BACKGROUND: Early development of nitrate tolerance with either continuous administration of intravenous or topical nitrate preparations or frequent dosing of oral nitrates leads to significant attenuation of nitrate-mediated hemodynamic and anti-ischemic effects. In recent animal experiments, prevention of nitroglycerin-induced hemodynamic tolerance with a concomitant use of hydralazine was demonstrated. This finding may have important clinical relevance. METHODS: Twenty-eight patients with chronic heart failure due to left ventricular systolic dysfunction were randomized to receive either a continuous infusion (24 h) of nitroglycerin alone (group I, 14 patients) or concomitantly with oral hydralazine (75 mg four times a day [group II, 14 patients]). The effect of nitroglycerin in each group was evaluated by analysis of variance for repeated measures. The power of the analysis to detect a 5.4-mm Hg (20%) change in mean pulmonary artery wedge pressure was 90%. RESULTS: Baseline hemodynamic variables as well as the initial hemodynamic response to nitroglycerin were comparable in both groups. Compared with the initial response to nitroglycerin, a significant attenuation of effect was found in group I at 24 h in mean (+/- SE) pulmonary artery pressure (27 +/- 4% vs. 10 +/- 3%, p < 0.05) and mean pulmonary artery wedge pressure (40 +/- 4% vs. 16 +/- 4%, p < 0.05). In group II, conversely, oral hydralazine prevented nitroglycerin-induced hemodynamic tolerance and resulted in a persistent effect on mean pulmonary artery and wedge pressures throughout the study period (31 +/- 3% vs. 27 +/- 4%, p = 0.13 and 37 +/- 4% vs. 34 +/- 6%, p = 0.40, respectively). In addition, the initial effect on blood pressure was attenuated at 24 h in group I (5 +/- 2% vs. 12 +/- 3%, p < 0.05) but not in group II (15 +/- 3% vs. 17 +/- 2%, p = 0.46). CONCLUSIONS: In patients with chronic heart failure due to left ventricular systolic dysfunction, the concomitant use of oral hydralazine prevents early development of nitrate tolerance and results in a persistent nitrate-mediated hemodynamic effect on systemic and pulmonary artery and left ventricular filling pressures. These data may support the concurrent use of hydralazine in patients with heart failure treated with organic nitrates.