Coop's Corner #9: Nitrates

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Nitrates

Since the inception of the Thermolife lineup a few years ago, nitrates have been a popular ingredient sold in dietary supplements. They are claimed to increase nitric oxide (NO) and provide all-day pumps. But do they live up to the hype? Let's take a look.

Do Nitrates Increase NO?

The answer is a resounding yes. Most NO products seek to exploit the classic pathway:

Citrulline -> Arginine -> eNOS -> NO

Nitrates, conversely are free from the rate-limiting steps and enzymatic barriers that "slow down" the classic pathway (this is partly why arginine does not work for increasing NO). As such, nitrates serve as an "exogenous" source of nitric oxide:

NO3 (nitrate) -> NO2 (nitrite) -> NO

So nitrates will indeed increase NO, and they will do so in a manner more effective than arginine/citrulline in healthy populations [1].

This leads to the next question: will nitrates provide "all-day" pumps? Well, NO will induce venous pooling and pumps/vascularity, and the half-life of nitrate salts is up to 8 hours, so nitrates will provide "long-lasting pumps," not so much all-day.

Will nitrates enhance performance?

Mechanism #1 - Improved efficiency of oxygen consumption

Absolutely, and the data here is remarkable. The data from one trial shows that time to exhaustion is increased without any accompanying changes in metabolic biomarkers indicative of energetic stress (i.e. lactate), meaning that nitrates effectively enhance muscular efficiency [2]. This performance-enhancing effect is observed during low-intensity exercise (i.e. LISS cardio, high rep work) [3], moderate intensity exercise [5], and high intensity exercise (traditional weight training, HIIT, etc) [3, 4]. Of particular note, numerous studies have found that nitrates increase performance during intermittent, high intensity exercise bouts [4, 6]. Sound familiar? That's exactly what weight training is (HIIT too).

While we're briefly mentioning cardio, nitrates improve cardio performance as well, both for LISS (walking) and full-on running (MISS, HIIT) [7,8].

This makes nitrates the ideal performance-enhancing supplement for all conditions: cardio and lifting, of any intensity. You're missing out by not using this.

Mechanism #2 - Increasing calcium release from the sarcoplasmic reticulum

If you recall from our previous discussion of amentoflavone (http://anabolicminds.com/forum/supplements/255669-coops-corner-7-a.html), increasing calcium release in the muscle cell results in improved contractile force:

"The final trigger in muscle contraction is an increase in calcium in the muscle cell. This calcium is stored in an organelle known as the sarcoplasmic reticulum and is released in response to a neural stimulus. The calcium binds to key muscle proteins that result in contraction, and it has been shown that the more calcium released into the muscle cell, the more force is produced."


Amentoflavone acts on the ryanodine receptor, a receptor that lies downstream of another receptor in the muscle contraction cascade known as the dihydropyridine receptor (DHPR). Nitrates act on the DHPR to augment calcium release and increase muscle contractility, resulting in improved strength [16], an effect that has been documented in humans as well as the murine model [15, 16].

Of note, this may mean that combining nitrates and amentoflavone, which act on two separate portions of the calcium-release pathway, can create additive or possibly synergistic effects, depending on which step is limiting.

Bottom line: combine nitrates and amentoflavone. Both increase strength via complementary mechanisms.

Can nitrates directly increase muscle mass?

So we already established that nitrates increase NO/pumps/vascularity as well as performance via multiple mechanisms. These effects will indirectly result in muscle growth by pushing yourself harder and longer during training sessions. But can nitrates directly induce muscle growth?

Recent research has looked into NO as a possible method to induce myogenesis, and so far, the data is promising: nitrates may indeed be directly myogenic and aid in the muscle building process. Vasodilation via NO may increase MPS and mTOR activity in muscle cells [10, 11], and NO appears to play a direct role in the formation of new muscle cells [12-14]. This is fairly novel, because muscle typically grows via hypertrophy and myonuclear accretion from nearby satellite cells, and nitrates act directly on this pool of precursor satellite cells.

Which type of nitrate is best?

You want a nitrate salt, no beetroot extracts (which provide a fraction of the effective dose). Speaking in approximations regarding amino acid nitrates, 1 gram of amino acid nitrates should provide an ergogenic effect as per the data, with 2 grams probably being the optimal MAX dose. Taking more than this will probably be ergolytic due to the drop in BP.

As for the amino acid that is used, I'm partial to creatine or arginine nitrate.

I'd use creatine nitrate if I didn't have another source of creatine. By creating a salt, the creatine gains improved solubility and can be used even at < 3 grams to saturate creatine stores, in theory. So this can double up as a creatine and nitrate product if used at a high enough dose.

Arginine nitrate is my personal favorite because data shows arginine reduces nitrate tolerance [9]. It's unclear how big of an issue nitrate tolerance (or the phenomenon wherein nitrates' effects "wear off" with time) is for supplemental nitrates, but if you want to err on the side of caution and avoid tolerance formation, arginine nitrate is your best bet.

Of note, I also recommend vitamin C with nitrates for preventing gastric nitrosamine formation, and NAC can be used as well to potentiate the effects of nitrates.

Hope you enjoyed this week's spotlight. Stay tuned for episode #4 :)

References

1. Lundberg JO, et al. (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov.
2. Larsen, F. J., E. Weitzberg, J. O. Lundberg, and B. Ekblom. "Effects of Dietary Nitrate on Oxygen Cost during Exercise." Acta Physiologica 191.1 (2007): 59-66. Web.
3. Bailey, S. J., P. Winyard, A. Vanhatalo, J. R. Blackwell, F. J. Dimenna, D. P. Wilkerson, J. Tarr, N. Benjamin, and A. M. Jones. "Dietary Nitrate Supplementation Reduces the O2 Cost of Low-intensity Exercise and Enhances Tolerance to High-intensity Exercise in Humans." Journal of Applied Physiology 107.4 (2009): 1144-155. Web.
4. Larsen, Filip J., Eddie Weitzberg, Jon O. Lundberg, and Björn Ekblom. "Dietary Nitrate Reduces Maximal Oxygen Consumption While Maintaining Work Performance in Maximal Exercise." Free Radical Biology and Medicine 48.2 (2010): 342-47. Web.
5. Vanhatalo, A., S. J. Bailey, J. R. Blackwell, F. J. Dimenna, T. G. Pavey, D. P. Wilkerson, N. Benjamin, P. G. Winyard, and A. M. Jones. "Acute and Chronic Effects of Dietary Nitrate Supplementation on Blood Pressure and the Physiological Responses to Moderate-intensity and Incremental Exercise." AJP: Regulatory, Integrative and Comparative Physiology 299.4 (2010): R1121-1131. Web.
6. Wylie, Lee J., Magni Mohr, Peter Krustrup, Sarah R. Jackman, Georgios Ermιdis, James Kelly, Matthew I. Black, Stephen J. Bailey, Anni Vanhatalo, and Andrew M. Jones. "Dietary Nitrate Supplementation Improves Team Sport-specific Intense Intermittent Exercise Performance." European Journal of Applied Physiology 113.7 (2013): 1673-684. Web.
7. Murphy, Margaret, Katie Eliot, Rita M. Heuertz, and Edward Weiss. "Whole Beetroot Consumption Acutely Improves Running Performance." Journal of the Academy of Nutrition and Dietetics 112.4 (2012): 548-52. Web.
8. Lansley, K. E., P. G. Winyard, J. Fulford, A. Vanhatalo, S. J. Bailey, J. R. Blackwell, F. J. Dimenna, M. Gilchrist, N. Benjamin, and A. M. Jones. "Dietary Nitrate Supplementation Reduces the O2 Cost of Walking and Running: A Placebo-controlled Study." Journal of Applied Physiology 110.3 (2011): 591-600. Web.
9. MacAllister, R. (2000). Arginine and nitrate tolerance. Br J Pharmacol.
10. Lee, J. (2010). Effect of vasodilation on the response of muscle protein synthesis to insulin in aging. J Clin Endocrinol Metab.
11. Timmerman KL, et al. (2010). Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling. J Clin Endocrinol Metab.
12. Smith, L. W., J. D. Smith, and D. S. Criswell. "Involvement of Nitric Oxide Synthase in Skeletal Muscle Adaptation to Chronic Overload." Journal of Applied Physiology 92.5 (1985): 2005-011. Web.
13. Buono, Roberta, Chiara Vantaggiato, Viviana Pisa, Emanuele Azzoni, Maria Teresa Bassi, Silvia Brunelli, Clara Sciorati, and Emilio Clementi. "Nitric Oxide Sustains Long-Term Skeletal Muscle Regeneration by Regulating Fate of Satellite Cells Via Signaling Pathways Requiring Vangl2 and Cyclic GMP." Stem Cells 30.2 (2012): 197-209. Web.
14. Palma, Clara, and Emilio Clementi. "Nitric Oxide in Myogenesis and Therapeutic Muscle Repair." Molecular Neurobiology 46.3 (2012): 682-92. Web.
15. Bailey, S. J., J. Fulford, A. Vanhatalo, P. G. Winyard, J. R. Blackwell, F. J. Dimenna, D. P. Wilkerson, N. Benjamin, and A. M. Jones. "Dietary Nitrate Supplementation Enhances Muscle Contractile Efficiency during Knee-extensor Exercise in Humans." Journal of Applied Physiology 109.1 (2010): 135-48. Web.
16. Hernandez, A., T. A. Schiffer, N. Ivarsson, A. J. Cheng, J. D. Bruton, J. O. Lundberg, E. Weitzberg, and H. Westerblad. "Dietary Nitrate Increases Tetanic [Ca2 ]i and Contractile Force in Mouse Fast-twitch Muscle." The Journal of Physiology 590.15 (2012): 3575-583. Web.
 
Afi140

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Nice as usual man.
 
paula

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So c4 as creatine nitrate and high volume arginine nitrate for pre workout, intra amino iv.
 

test112

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What's the practical difference between an amino acid bonded to nitrate (creatine nitrate, arginine nitrate, leucine nitrate, etc.) versus both the amino acid and the nitrate as separate forms/salts?
 
LeanEngineer

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I love NO boosters! Good article here.
 
Driven2lift

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Informative as always Coop!
 

iddqd

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thanks for the writeup, great read as always!
two follow up questions:

how does NAC work here?

and on a side note, i've been wondering for a while... i've read several times now that we don't actually have enough blood to supply everything in our bodies at once at any given time. if that is correct, then why is it a good idea to induce this 'venous pooling' etc thing for an extended period of time? if it simply increased 'turnover' and thus supply with fresh blood i would understand, but do we trigger some low-level blood building effect in response or anything? because i'd imagine constantly supplying brain & organs and only directing to muscle on demand will do more for me in the long run. i assume my premise is generally flawed somehow because no one ever discusses it?
 

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What's the practical difference between an amino acid bonded to nitrate (creatine nitrate, arginine nitrate, leucine nitrate, etc.) versus both the amino acid and the nitrate as separate forms/salts?
They can't exist as separate salts. A salt, in this case the negative anion nitrate, will need a positive ion to maintain electroneutrality. That's where the AAs come in.

thanks for the writeup, great read as always!
two follow up questions:

how does NAC work here?

and on a side note, i've been wondering for a while... i've read several times now that we don't actually have enough blood to supply everything in our bodies at once at any given time. if that is correct, then why is it a good idea to induce this 'venous pooling' etc thing for an extended period of time? if it simply increased 'turnover' and thus supply with fresh blood i would understand, but do we trigger some low-level blood building effect in response or anything? because i'd imagine constantly supplying brain & organs and only directing to muscle on demand will do more for me in the long run. i assume my premise is generally flawed somehow because no one ever discusses it?
NAC recycles nitrates in the body, further prolonging their halflife.

We always have enough blood at any one time. Bloodflow is selective based on metabolic demand. Nitrates preferentially induce vasodilation in hypoxic tissues (tissues with not enough bloodflow/oxygen), so they actually fix the issue you're talking about. This isn't an issue at rest, but it's one of the reasons you fatigue during exercise...and nitrates reverse this.
 

test112

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They can't exist as separate salts. A salt, in this case the negative anion nitrate, will need a positive ion to maintain electroneutrality. That's where the AAs come in.
I mean is there any difference in function between arginine nitrate and, say, L-arginine + some other nitrate source?

(Assuming that we temporarily disregard the function of whatever the nitrate is bonded to)
 

mr.cooper69

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I mean is there any difference in function between arginine nitrate and, say, L-arginine + some other nitrate source?

(Assuming that we temporarily disregard the function of whatever the nitrate is bonded to)
Nope
 
braskibra

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They can't exist as separate salts. A salt, in this case the negative anion nitrate, will need a positive ion to maintain electroneutrality. That's where the AAs come in.

NAC recycles nitrates in the body, further prolonging their halflife.

We always have enough blood at any one time. Bloodflow is selective based on metabolic demand. Nitrates preferentially induce vasodilation in hypoxic tissues (tissues with not enough bloodflow/oxygen), so they actually fix the issue you're talking about. This isn't an issue at rest, but it's one of the reasons you fatigue during exercise...and nitrates reverse this.
Coop, then couldn't this negatively impact muscle growth in the long term as fatigue and metabolite build up from hypoxia is one of the mechanisms of growth
 

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Cool, thanks. My curiosity stems from whether or not it's disproportionately costly to produce or source bonded amino nitrates versus just blending non-bonded components with the same constituents, if they had the same effect.

I have some HV on the way; keen to try it out.
 
JudoJosh

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Good stuff as always
 
schizm

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CoopMD in the house, great stuff as usual sir :)
 
braskibra

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im still unsure of nitrates place in a resistance training regime. I've used nitrates (pumpbol) in the past and I'm not sure if I notice much of a difference.


To elaborate on my earlier point, I would like to see some studies with nitrates and a resistance training program, I doubt it would have an appreciable effect on tissue hypertrophy. It could potentially increase hypertrophy for someone training at high intensity % RM because it may augment maximal voluntary contraction but it could "potentially" be detrimental for someone training with intensity techniques (drop sets,BFR) and sub-maximally.


Metabolic Stress is an important pathway to muscle growth:
"Metabolic stress (i.e. accumulation of metabolites during exercise) has been reported as being equally as important as mechanical tension, if not more, for the induction of muscle growth [9, 12, 28, 31, 46]. "


"It has been theorised that exercise-induced metabolic stress mediates muscle hypertrophy via a number of mechanisms, including elevated systemic hormone production [25], increased fast-twitch fibre recruitment [6, 7], cell swelling [26], muscle damage [31, 48] and increased production of ROS [13, 27, 31, 49], all of which are thought to mediate muscle protein signalling and/or satellite cell proliferation for the induction of muscle growth."

Nitrates
"It has been reported that leakage of protons through the inner mitochondrial membrane is reduced following NO3 - supplementation, thereby improving mitochondrial P/O and reducing the O2 cost of exercise [28]"


"These effects, along with less accumulation of ADP and Pi, metabolites which are inked to fatigue, seem to enhance exercise tolerance in healthy individuals."

peace out boiiiiis
 

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Coop, then couldn't this negatively impact muscle growth in the long term as fatigue and metabolite build up from hypoxia is one of the mechanisms of growth
Nah, to the contrary it appears NO is myogenic (see 1st post). The occlusion theory is more based on build-up of other metabolites like adenosine and straight H+
 

mr.cooper69

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im still unsure of nitrates place in a resistance training regime. I've used nitrates (pumpbol) in the past and I'm not sure if I notice much of a difference.


To elaborate on my earlier point, I would like to see some studies with nitrates and a resistance training program, I doubt it would have an appreciable effect on tissue hypertrophy. It could potentially increase hypertrophy for someone training at high intensity % RM because it may augment maximal voluntary contraction but it could "potentially" be detrimental for someone training with intensity techniques (drop sets,BFR) and sub-maximally.


Metabolic Stress is an important pathway to muscle growth:
"Metabolic stress (i.e. accumulation of metabolites during exercise) has been reported as being equally as important as mechanical tension, if not more, for the induction of muscle growth [9, 12, 28, 31, 46]. "


"It has been theorised that exercise-induced metabolic stress mediates muscle hypertrophy via a number of mechanisms, including elevated systemic hormone production [25], increased fast-twitch fibre recruitment [6, 7], cell swelling [26], muscle damage [31, 48] and increased production of ROS [13, 27, 31, 49], all of which are thought to mediate muscle protein signalling and/or satellite cell proliferation for the induction of muscle growth."

Nitrates
"It has been reported that leakage of protons through the inner mitochondrial membrane is reduced following NO3 - supplementation, thereby improving mitochondrial P/O and reducing the O2 cost of exercise [28]"


"These effects, along with less accumulation of ADP and Pi, metabolites which are inked to fatigue, seem to enhance exercise tolerance in healthy individuals."

peace out boiiiiis
All this is showing is that energy efficiency is increased. Metabolic byproduct build-up is an extremely new and unproven theory; whereas we know for a fact that tension and time under tension, which will both be enhanced with nitrates, induce hypertrophy.

As an analogy, would you weight train in the 30-40 rep range and maximize waste product build up for muscle growth? Or would you stick to 6-12 reps and maximize tension at the expense of waste product creation? Obviously the latter, which is a tried and true stimulus.
 
JudoJosh

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braskibra, where are those quotes from? Links would be appreciated
 
PhoenixMuscle

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Great post, that's quite a wealth of information there. I never took the time to look so in depth on nitrates (although, before coming to this forum I've been inclined to do further research due to wanting to switch to creatine nitrate). Makes me that much more anxious to try HV as it would be my first "pump" product.
 

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So is a nitrate a nitrate? Would PN be just as good a choice compared to the creatine and arginine?
 
Driven2lift

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So is a nitrate a nitrate? Would PN be just as good a choice compared to the creatine and arginine?
In terms of nitrate effectiveness, yes. As long as the amount of nitrate is the same the salt it is bound to is relatively unimportant.

His reference for creatine/arginine was because of the separate benefits they bring to the equation. Unless you form s tolerance that would require more arginine as he discussed, the nitrate itself should be just as effective.
 
abformulations

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Great info
 
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In terms of nitrate effectiveness, yes. As long as the amount of nitrate is the same the salt it is bound to is relatively unimportant.

His reference for creatine/arginine was because of the separate benefits they bring to the equation. Unless you form s tolerance that would require more arginine as he discussed, the nitrate itself should be just as effective.
Bingo. I also know Coop prefers those two to KNO3 because he doesn't see the need for supplementing potassium like that vs. supplementing creatine and arginine (arginine specifically for nitrate tolerance).
 
Auslifter

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Always loved Agrinine Nitrate ever since jack3d micro first came out, i was hooked on that for pumps. until i discovered craze lol and started to disregard pumps for energy and focus. later adding TMG Nitrates (Max Pump) alongside it, made for the best stack ever :) miss dem days.. but now we go HV and Frenzy ;) lol until TechNO comes along of course, or when i decide to import Target A2.

there needs to be an enitre sub forum for coop lol. pure coop corners and discussion threads on different ingredients.
 

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Always loved Agrinine Nitrate ever since jack3d micro first came out, i was hooked on that for pumps. until i discovered craze lol and started to disregard pumps for energy and focus. later adding TMG Nitrates (Max Pump) alongside it, made for the best stack ever :) miss dem days.. but now we go HV and Frenzy ;) lol until TechNO comes along of course, or when i decide to import Target A2.

there needs to be an enitre sub forum for coop lol. pure coop corners and discussion threads on different ingredients.
This. I read several logs on yok3d+max pump and the pumps were supposedly unheard of
 
Segansational

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Nice info, and particularly interested in the potential synergy with amentoflavone.
 
braskibra

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All this is showing is that energy efficiency is increased. Metabolic byproduct build-up is an extremely new and unproven theory; whereas we know for a fact that tension and time under tension, which will both be enhanced with nitrates, induce hypertrophy.
As an analogy, would you weight train in the 30-40 rep range and maximize waste product build up for muscle growth? Or would you stick to 6-12 reps and maximize tension at the expense of waste product creation? Obviously the latter, which is a tried and true stimulus.
1.) That's pretty much irrelevant to the conversation, any rationale program is going to utilize both. There is no OR scenario, its both. The concept of diminishing returns proves both are useful. As far as discussing the "metabolic theory" it is not mutually exclusive from TUT and tension, i.e you can't speak about the impacts of metabolic stress and not accept a certain amount of mechanical tension.

"effects of two volume/ intensity-matched resistance exercise protocols (3–5 sets of 10 reps at 75 % 1RM), with the only difference being that one protocol included a 30-s rest period in the midway point of each set to try and reduce the degree of metabolic build-up, whereas the other did not. Results showed blood lactate concentrations to be significantly higher following the without-rest protocol relative to the with-rest protocol. Additionally, following 12 weeks of training, the without rest regimen was found to significantly increase muscle cross-sectional area (CSA), whereas no such differences were observed following the with-rest protocol, indicating a direct link between metabolic stress and muscle hypertrophy."

"The principal novel finding of this study was that dietary nitrate supplementation reduced muscle metabolic perturbation"


2.) Nitrates most likely do NOT improve maximal force production, or force production over a series of 50 muscle contractions

Given that no statistically significant time effects were obtained over the supplementation period for any of the force or 31P data, the BR and PL data were averaged over time[ (2.5 h, 5 days and 15 days). An illustration of the mean force profile for BR and PL over the 50 contractions is presented in Fig. 3 for the full 6.6 s contraction. The mean force generation values of the entire 6.6 s contraction are presented in Table 5. No significant BR effect was found relative to PL for the peak contraction, mean of the final five contractions, mean over all contractions or fatigue index (P > 0.05 for all comparisons). No significant difference for any of the force parameters was found between the supplementation conditions (BR and PL) and the control condition (P > 0.05 for all comparisons).

"The present study indicated that NO3 - supplementation, which increased the circulating NO substrate, NO2 -, resulted in no significant attenuation of maximum skeletal muscle force output. "

3.) Nitrates probably reduce force output in submaximal exercise
"The majority of studies examining force output in isolated muscle fibres have indicated a depressive effect of NO [9, 27, 39, 41]. "

4.) No offense, but if we are talking unproven's, how about nitrates promoting hypertrophy or effects on body comp? There isn't one study using nitrates with a resistance training regime. Now we are speaking on a conceptual basis, well it does x so it should do y. Should being the key.


5.)In addition, in the real world, most people taking nitrates are ingesting them in conjunction with caffeine. And when they do the results have not been fantastic:

"There was no effect of BJ supplementation when used alone (–0.4%, p = 0.6 compared with CONT) or when combined with caffeine (–0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg−1 BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50–60 min by ∼3%–4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study."

"nonsignificant TTE improvements were observed on BR+C compared with BR and PLA+C alone, respectively."
BR=beetroot C=caffeine


6.) Lastly, nitrates in my opinion, are only "super" beneficial to novices or at best moderately trained individuals. Once you reach a certain degree of training status, the effects are much less noticeable. (along with most other things)

"In contrast to observations in moderately trained subjects intake of BR juice had no effect on VO(2) kinetics and performance in elite cyclists.

"Acute ingestion of dietary nitrate may not represent an effective strategy for reducing the oxygen cost of submaximal exercise or for enhancing endurance exercise performance in highly trained cross-country skiers."


Right now I would say if you want the effects of greater TUT etc, then 10 cent caffeine tab will do the trick via neural drive and reduced m. subjective pain.
 

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We will have to agree to disagree. I have seen every study you just linked, and the reason the studies go both ways is because nitrates are so well-studied. The scales are, to me, unquestionably tipped in favor of utilizing nitrates, and I will continue to do so. To point 1, this is a given since there is a correlation between stress and workout intensity. And while you can't have stress without tension, you can certainly emphasize one over the other. I have numerous studies that oppose point 2 and only a few in favor of your point. Point 3 needs some context, and it's likely not relevant in vivo since we're talking about NO in circulation, not bathing skeletal muscle in NO which is a known muscle relaxant. Point 4 is fair, it was just conjecture. Point 5 I just flat out don't agree with based on one study, and point 6 is again cherry-picked amidst the overall body of data. Just my 2 cents

I appreciate the discussion
 
JudoJosh

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hmmm... seems like a good dissertation topic to me ;)
 
braskibra

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We will have to agree to disagree. I have seen every study you just linked, and the reason the studies go both ways is because nitrates are so well-studied. The scales are, to me, unquestionably tipped in favor of utilizing nitrates, and I will continue to do so. To point 1, this is a given since there is a correlation between stress and workout intensity. And while you can't have stress without tension, you can certainly emphasize one over the other. I have numerous studies that oppose point 2 and only a few in favor of your point. Point 3 needs some context, and it's likely not relevant in vivo since we're talking about NO in circulation, not bathing skeletal muscle in NO which is a known muscle relaxant. Point 4 is fair, it was just conjecture. Point 5 I just flat out don't agree with based on one study, and point 6 is again cherry-picked amidst the overall body of data. Just my 2 cents

I appreciate the discussion
I appreciate it as well, I am not against nitrates, I hope they prove to be beneficial in regards to hypertrophy etc. I am sure this matter will be taken care of soon as there is a ton of data being published on the topic.

I do have one question, why risk a PDE inhibitor with nitrates in the high volume formula when they are clearly contraindicated in the medical community (organic+PDE)? Are you concerned about someone getting a hypotensive reaction with high dose inorganic nitrate + PDE?

Unless you feel the reduction in BP is gradual enough(peak reduction generally considered at 2-3 hours) and amento is a very very mild PDE inhibitor . Or you know something I don't (most likely)
 
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Any update on the patent rejection and if it ended up going through after the last review?
 

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I appreciate it as well, I am not against nitrates, I hope they prove to be beneficial in regards to hypertrophy etc. I am sure this matter will be taken care of soon as there is a ton of data being published on the topic.

I do have one question, why risk a PDE inhibitor with nitrates in the high volume formula when they are clearly contraindicated in the medical community (organic+PDE)? Are you concerned about someone getting a hypotensive reaction with high dose inorganic nitrate + PDE?

Unless you feel the reduction in BP is gradual enough(peak reduction generally considered at 2-3 hours) and amento is a very very mild PDE inhibitor . Or you know something I don't (most likely)
You are correct, peak BP reduction from nitrates occurs at 3 hours. I would never combine clinical PDE5 inhibitors with nitrates, but as far as amentoflavone goes, it acts chiefly through cAMP (PDE1-4), hence its inclusion in norcodrene. Its lowest affinity is for PDE5, and it's certainly not on a level to induce BP drops like, say, sildenafil. Even though PDE5i + nitrate is synergistic in lowering BP, the rule always applies that the dose makes the poison: and the dose of amentoflavone simply isn't enough given its potency relative to clinical drugs.
 
braskibra

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You are correct, peak BP reduction from nitrates occurs at 3 hours. I would never combine clinical PDE5 inhibitors with nitrates, but as far as amentoflavone goes, it acts chiefly through cAMP (PDE1-4), hence its inclusion in norcodrene. Its lowest affinity is for PDE5, and it's certainly not on a level to induce BP drops like, say, sildenafil. Even though [I]PDE5i + nitrate is synergistic[/I] in lowering BP,the rule always applies that the dose makes the poison: and the dose of amentoflavone simply isn't enough given its potency relative to clinical drugs.
Did you test this?
 
braskibra

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Of course. I'm actually usually the first tester for anything, and use objective measures like BP cuff, pulse, orthostatics, glucometer, etc
Cool I'm assuming pre, intra, and post exercise bp because u know what ur doing

In my opinion (which is worth about 2cents), considering the dearth of evidence on inorganic nitrates and pde inhibitors and their interactions i guess i dont understand the risk:reward ratio for combining them (even mild) and then adding another proposed vasodilator on top of that in rutaecarpine. To me it just seems unnecessary considering arginine nitrate is already a potent vasodilator itself . And I'm sure many people will combine norco and amentoflavone with hv which will increase the dosage of AF substantially and without any data we are left with guessing the safety of their combined use ( or taking your word for it).

But that's why PES pays u the big bucks and ur the BMOC, your the formulator and a helluva good one at that and I'm not

Reps on r/c in the morning
Sorry for being a headache I promise I'm not the supp police, if its any condolences I do quite like select and IV.

/rant
 
Synapsin

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Cool I'm assuming pre, intra, and post exercise bp because u know what ur doing

In my opinion (which is worth about 2cents), considering the dearth of evidence on inorganic nitrates and pde inhibitors and their interactions i guess i dont understand the risk:reward ratio for combining them (even mild) and then adding another proposed vasodilator on top of that in rutaecarpine. To me it just seems unnecessary considering arginine nitrate is already a potent vasodilator itself . And I'm sure many people will combine norco and amentoflavone with hv which will increase the dosage of AF substantially and without any data we are left with guessing the safety of their combined use ( or taking your word for it).

But that's why PES pays u the big bucks and ur the BMOC, your the formulator and a helluva good one at that and I'm not

Reps on r/c in the morning
Sorry for being a headache I promise I'm not the supp police, if its any condolences I do quite like select and IV.

/rant
This is a null point. Amentoflavone has an extremely mild PDEi 5 effect when you consider its affinity, not to mention comparing inorganic nitrates to organic nitrates is not the best course of action here. On top of that, we use different vasodilators because of the pathways they use. There is zero health concerns with combining Norcodrene and Amentoflavone.
 
braskibra

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This is a null point. Amentoflavone has an extremely mild PDEi 5 effect when you consider its affinity, not to mention comparing inorganic nitrates to organic nitrates is not the best course of action here. On top of that, we use different vasodilators because of the pathways they use. There is zero health concerns with combining Norcodrene and Amentoflavone.
Exactly! There is no comparison! Organic nitrates and PDE are contraindicated, we KNOW that, we have data that shows how they interact. We DON'T KNOW anything about how inorganic nitrates and PDE's interact period. Seems irresponsible at best to put them in a formula together, despite how "mild" you are essentially guessing amentoflavone is in vivo. In addition you have Rutaecarpine, another ingredient which, from your website, is responsible for:

"potentiation of the cGMP pathway [11-14]. The action on the cGMP pathway complemented perfectly with AmentoMAX, making these two ingredients a real 1-2 punch."

That's 3 ingredients interacting with cGMP, with the combined potential to cause excessive levels of cGMP

Without any data on half-life, without any data in humans, without any data on possibly synergism, im not sure how you label that as "zero" concerns but to each his own i guess.

regardless of our apparent disagreement in this manner have a happy thanksgiving
 
Danes

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I have 3 bottles of AmentoFlavone and i have some questions:

Whats the best dosage: (tried 120mg)
Can it be taken everyday and does it need to be cycled?
When is it best time to take it? 30min prior workout, 1 hour or....?
 

ma70

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I have 3 bottles of AmentoFlavone and i have some questions:

Whats the best dosage: (tried 120mg)
Can it be taken everyday and does it need to be cycled?
When is it best time to take it? 30min prior workout, 1 hour or....?
If taken every day, I think it needs to be cycled 8 on-4 off. If taken for workouts only (around 4 workouts per week), I believe it is up to 12 weeks of usage, followed by 4 off.

30 mins pre-workout.
 
Danes

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If taken every day, I think it needs to be cycled 8 on-4 off. If taken for workouts only (around 4 workouts per week), I believe it is up to 12 weeks of usage, followed by 4 off.

30 mins pre-workout.
Thank you very much.
Lol i tought i wrote in amento thread.. sorry
 
kbayne

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I have 3 bottles of AmentoFlavone and i have some questions: Whats the best dosage: (tried 120mg) Can it be taken everyday and does it need to be cycled? When is it best time to take it? 30min prior workout, 1 hour or....?
I would dose 80-100mg per day. Dose ~30 minute pre-workout on workout days and either in the morning or spread out on off days if you plan to dose on off days.

Everyday dosing will increase weight/fat loss. Dose on workout days only if you're only focused on strength/performance.

Everyday dosing: 8 weeks on followed by 4 weeks off.

Workout days only: 12 weeks on followed by 4 off.
 
Danes

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I would dose 80-100mg per day. Dose ~30 minute pre-workout on workout days and either in the morning or spread out on off days if you plan to dose on off days.

Everyday dosing will increase weight/fat loss. Dose on workout days only if you're only focused on strength/performance.

Everyday dosing: 8 weeks on followed by 4 weeks off.

Workout days only: 12 weeks on followed by 4 off.
Thank you :)
 

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