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Nitrates (N03-t in particular) are one of the new things in pre-workouts. Dangerous with cialis/pde-5?

Knight9

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On all cialis and pde-5 inhibitor rx's, it says do not take with nitrates. With cialis and such being as prevalent as it is in males and males in this endeavor..what kind of risks are we running if one doesn't realize this and ends up taking pre workouts with 500-1500mg of actual nitrates?

For example arginine Nitrate is 27% nitrate, so 2g of it in a pre workout yields 540mg. 3g would yield 810mg. There are about a dozen other nitrates with similar technology..some are 10% and others are up to 35%. Pre Jym X has 860mg (2g citrulline nitrate + 1g Betaine Nitrate).

Apparently taking nitrates with pde-5 can drop blood pressure dangerously low and result in fainting or even death. Is this an overexaggerated risk?
 

Alan1

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My n=1: I haven't experienced any discernable issues from taking a pde-5 product along with pre-workouts that contain nitrates. A few examples of some of my workout days lately:
-Scoop of BeetElite beetroot powder first thing in morning + 20mg cialis + pre-workout w/o nitrates + 1 serving of Purus Labs Noxygen, either the powder or gel caps (740mg and 500mg nitrate content per serving respectively I believe)
OR,
BeetElite + 20mg cialis plus serving of Unbound Unbent non-stim pre-workout (1500mg arginine nitrate and 1,500mg betaine nitrate) or CBum Thavage pre-workout (version with 2,000mg arginine nitrate), or Ryse Godzilla pre-workout (2,000mg of citrulline nitrate).

Of course I'm sure some of that is offset by the caffeine (260-350-ish mg) and other stims in a few of the pre's that I use. Even when I take the non-stim I'll often pop a cap of 200mg caffeine anhydrous.
 

Knight9

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While it's interesting and I'm glad to read the above, have you googled 'cialis and nitrates'?
 

Lumpi

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I seem to have problems (really intense headaches) even after eating to much nitrat containing salads. So I personally avoid these pre workout drinks. I also dropped drinking beet root juice in in general.
 

Alan1

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While it's interesting and I'm glad to read the above, have you googled 'cialis and nitrates'?
Oh for sure, definitely aware of the contraindication between nitrates and pde-5's. Which admittedly makes what I've been doing a bit risky and ill-advised. Frankly it'd probably be smart to simply do one or the other (cialis or nitrate pre) from now on. I do realize just because things have gone okay so far that doesn't mean the effects couldn't change for the worse at any point going forward. And ya' know, I'd really rather not be the recipient of a ProM Darwin award! ;)
 

Knight9

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Oh for sure, definitely aware of the contraindication between nitrates and pde-5's. Which admittedly makes what I've been doing a bit risky and ill-advised. Frankly it'd probably be smart to simply do one or the other (cialis or nitrate pre) from now on. I do realize just because things have gone okay so far that doesn't mean the effects couldn't change for the worse at any point going forward. And ya' know, I'd really rather not be the recipient of a ProM Darwin award! ;)
LOL.

My worry isn't just isolated to taking both pre workout though. Cialis is the 'weekend pill' and works for at least a good 24-36hrs while some nitrates claim to keep NO levels elevated for 8 hrs(I think I read this regarding red spinach)...it would be extremely easy to think you're taking them apart from eachother but they are still overlapping and potentially contraindicating.

Before thinking about this, I have taken 5-10mg cialis and nitrates a handful or two of times without realizing. Then, I lowered it to 5mg and was using a half dose of pre workout with nitrates and another half without...but the last week or so I completely cut them out and wanted to pose this question. I would love to have some people that really know how to break this down and evaluate it chime in here.
 

totalrecomp

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I do believe they are primarily warning against using pharma nitroglycerine sublingual pills used to treat angina and in-process hear attacks. I have NOT run into any issues with nitrates in supplements and foods and liberal pde-5 use and I have LOW BP and orthostatic hypotension to begin with.

If the interaction were with everyday nitrates they would be warning against eating deli meats and hotdogs with woody pills similar to no cheese with MAOI's.
 

Musclebound94

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I do believe they are primarily warning against using pharma nitroglycerine sublingual pills used to treat angina and in-process hear attacks. I have NOT run into any issues with nitrates in supplements and foods and liberal pde-5 use and I have LOW BP and orthostatic hypotension to begin with.

If the interaction were with everyday nitrates they would be warning against eating deli meats and hotdogs with woody pills similar to no cheese with MAOI's.
This is correct. The main concern with PDE-5 inhibitors is the systemic vasodilation that occurs from them. Add something like Nitro(commonly prescribed for cardiac patients and people with unstable angina) and you run the risk of dangerous hypotension causing a pronounced decrease in MAP( mean arterial pressure). This drops adequate perfusion to the brain, and well that's not a good time lol
 

Knight9

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That makes some sense except one of the very first people I remember using Nitrate in their product was Mike Arnold with his MA-Pump pre workout. I believe it was Sodium Nitrate and I also seem to remember him cautioning(or maybe even putting on the label or website) to not use with pde-5 inhibitors.

Believe me, if it were up to me I'd take 10-15mg daily and have 800-1200mg of total nitrates in my pre but I don't want to be stupid and or reckless with such a thing unless I am certain of the MOA and practicality of anything negative stemming from the use of both together.

I appreciate everyone's input and hope to read more.
 

LK3

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while it doesnt really answer your question. the most simple part of this seems to be know what you take and it does. maybe even some sort of limits or rational.

it also to me speaks loudly not to trying all sorts of new shit that people havent used for long periods of time.

statements like this form ME are absurdly ironic. things that are normal to me are unfathomable to most but dude, posts like this leave me scratching my head. sometimes its best to just do one drug or another.
 

Type-IIx

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As @Musclebound94 indicated, basically PDE-5 inhibitors & nitrates synergistically contribute to endothelial vasodilation, thereby promoting hypotension.

Thank you for making me think more deeply about this with your question, @Knight9 ; this post is partly self-serving because typing it up is helping me appreciate the mechanisms more deeply.

To delve a little more into how the mechanisms interact:

Endothelial cells function to prevent intravascular coagulation under normal conditions, yet promoting blood clotting and inflammation at sites of vessel damage. To achieve these opposite functions, endothelial cells secrete several proteins that regulate blood clotting, blood flow, and local immune responses. In response to endothelial cell activation, several important vasoactive molecules are released, including nitric oxide (NO).

L-arginine increases NO via nitric oxide synthase & synthetase enzyme activity (here, eNOS [endothelial nitric oxide synthase], the constitutive NOS isoform in the vascular endothelium).

NO released by endothelial cells functions largely via cyclic GMP. NO via guanylate cyclase yields GTP that yields cyclic GMP (cGMP).

There is another source of nitrates: dietary food sources. Here, nitrate (and nitrite) are physiologically recycled in blood & tissue to form NO, and serve as storage pools for NO bioactivity, complementing the aforementioned (eNOS-dependent) pathway. From this pool, a series of oxygen-independent and eNOS-independent single-electron transfer reactions occur, ultimately ⇒ vasodilation.

With respect to PDE-5 inhibitors:
PDE-5 breaks cGMP's phosphodiester bond, attenuating the PKG cascade (the signaling system involved in NO & cGMP synthesis). Thus, PDE-5 inhibitors abrogate (prevent) this breaking of the cGMP phosphodiester bond, increasing the synthesis of NO & cGMP.

In endothelial cells then, increased NO levels (by L-arginine, nitrates from food & PDE-5 inhibitors) ⇒ ↑↑vasodilation (greater than additively via ↑NO by different pathways; specifically, the eNOS -dependent [L-arginine] & -independent [dietary nitrates], with disinhibition of cGMP activity & the PKG cascade [PDE-5 inhibitor]) ⇒ hypotension

P.S., ARBs, ACE inhibitors, & β-antagonists (β blockers) further promote hypotension and are an additional consideration for those using them.
 

Lumpi

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So, would you guys say it's safe to take Arginine or in general pre workout drinks with vasodilating (NO) ingredients while on Nebivolol?
 

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So, would you guys say it's safe to take Arginine or in general pre workout drinks with vasodilating (NO) ingredients while on Nebivolol?
I think nebivolol in combination with these NO-increasing agents could be particularly unsafe: it is both a beta-blocker (anti-hypertensive) and additionally increases NO release.
 

Bobik

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I think nebivolol in combination with these NO-increasing agents could be particularly unsafe: it is both a beta-blocker (anti-hypertensive) and additionally increases NO release.
dangerous in the sense of hypotension?
 

Knight9

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The info below is from this link... https://examine.com/supplements/nitrate/

The optimal dosage of nitrate supplementation tends to be 0.1-0.2mmol/kg (or 6.4-12.8mg/kg), which is the range of:

  • 440-870mg for a 150lb person
  • 580-1,160mg for a 200lb person
  • 730-1,450mg for a 250lb person
Supplementation of nitrates via beetroot is equally feasible, and beetroot itself is dosed according to its nitrate content.

A randomized controlled trial noted that a single 2g dose of commercially available amaranth (red spinach) extract can increase nitrate levels for up to 8 hours.

-----------------------------------------------------------------------
Pre Jym X has Stoppani raving about how there are 860mg of Nitrates where most products you'd be lucky to find 500mg.

Also, the guy selling the Nitrate technology has indicated a range of 400-800mg as a beginning and upper end dosing. Not sure if he is being extra cautious with recommendations or something else.



I would personally love to create a Pre-workout with 1100-1250mg Nitrates but I am very cautious of evaluating the issues cialis or viagra might have while active in the system.

@Type-IIx , I really appreciate your post but did you come to any kind of recommended conclusion regarding this?
 

Type-IIx

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@Type-IIx , I really appreciate your post but did you come to any kind of recommended conclusion regarding this?

Oh yes, good point.

In conclusion, due to the synergistic effects by acting via different pathways and on different components of the L-arginine-NO pathway, eNOS pathways, etc. my conservative recommendation is avoiding the combination of any of these supplements or drugs in any amount.

Dose/response is sure to be individual - NO is so highly labile (subject to change)- and even likely to vary depending on factors that could vary from dose to dose and from day to day.

Besides, these pathways are not fully characterized: e.g., L-citrulline is gaining a lot of attention because of its effects on performance especially in combination with L-arginine - and yet, the L-arginine concentrations seem unlikely to be a relevant factor in any ergogenic effect because the Km of the enzyme for L-arginine is in the micromolar range while the concentration for L-arginine in the relevant cells is in the millimolar range, thus under physiologic conditions, NOS is already saturated with its L-arginine substrate (i.e., L-arginine would not be expected to be rate-limiting for this enzyme). Yet, L-citrulline (a precursor to L-arginine that increases its bioavailability) is absolutely performance enhancing (and moreso with L-citrulline + L-arginine ingestion).

There are a great number of unanswered questions, and certainly no actual understanding of dose/response with the combination of these agents (hence the advisory to simply NOT combine them on product labels).
Personally, I don't use any of these agents. I am interested in L-citrulline conceptually, but would absolutely not combine these.
 

Knight9

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I am interested in L-citrulline conceptually, but would absolutely not combine these.

Which?
L Citrulline and L-Arginine?
L citrulline, L Arginine and Nitrates?
Nitrates and PDE-5i?
All of the above?



Do you take anything for pre-workout or performance?
 

Mike Arnold

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That makes some sense except one of the very first people I remember using Nitrate in their product was Mike Arnold with his MA-Pump pre workout. I believe it was Sodium Nitrate and I also seem to remember him cautioning(or maybe even putting on the label or website) to not use with pde-5 inhibitors.

Believe me, if it were up to me I'd take 10-15mg daily and have 800-1200mg of total nitrates in my pre but I don't want to be stupid and or reckless with such a thing unless I am certain of the MOA and practicality of anything negative stemming from the use of both together.

I appreciate everyone's input and hope to read more.
Combining them could be potentially dangerous, but most people aren't going to use high enough doses of nitrates to be problematic. A much bigger risk would be combining Cialis with prescription nitrites, such as nitroglycerin, etc. A nitrate must first convert to nitrite before becoming active, so we have both a conversion and a dosage barrier protecting us from dangerously low BP. At some point, if the nitrate dose got high enough, it would indeed become dangerous, but that would normally require much higher doses than what we see in pump products. This is not to say that we shouldn't exercise caution...because we should, but I've seen many use a nitrate product at the same time Cialis is still active and there were no issues. Prescription nitrites and Cialis is a completely different story. Even nitrites alone can be dangerous. Just a few extra tabs of nitroglycerin and the person could run into serious issues, but the lethal dose can vary quite a bit. It could be as low as 200 mg and as high as 1,200 mg+, so for bodybuilding purposes, it's good to just stay away from nitrites altogether.

As far as bodybuilding is concerned, rather than attempting to max out the pump via blood vessel expansion alone, it would be safer and more effective to take a more holistic approach. For example, using nitric oxide boosters in combination with products that increase overall blood volume, such as certain forms of stabilized glycerin (HydroPrime, etc.). You'll get better results and it'll be safer.
 

TrippplePPP

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For what its worth I use low dose 12.5mg metoprolol daily and have juiced beets and ate a lot of spinach over the years. I knew beets lower blood pressure so I would juice it all the time and it definitely lower BP by a good 10-20 systolic for me. I didn't realize spinach had such nitrates until recently bought a gigantic bad of it and tried to nail it down in a week. I was getting dizzy from eating meals made with it. It made me realize some of my anxiety at work over the years was from using spinach in my morning smoothie when I would run out of kale. I would get all anxious and feel shitty and not know why. Understanding the above about nitrates in food made me avoid certain foods yet also use some for my benefit in controlled way. I haven't died from this but have floored myself with veggie juice and meals pre and post metoprolol use.
 

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