PDE5 - The Elephant in the Room ?

[The Dude]

So we know that cGMP allows an erection to occur, and PDE5 is responsible for turning it off.

The fact that PDE5 inhibitors (Cialis,Viagra,Levitra) are a spectacular financial success has two big implications:

1 - everyone who finds that PDE5 inhibitors work - which is roughly two-thirds of those who try them - must have no problem producing nitric oxide and cGMP, otherwise it would not work.

2 - The fact that PDE5 inhibitors solve the problem for most older guys, indicates that PDE5 production increases as we age.

I've done a lot of web searching and amazingly, cannot find any discussion on the latter point, which seems to me a very big issue.

This is likely due to:

A - The current difficulty of searching for anything having to do with the issue. There seem to be thousands, maybe millions of bot-generated web pages that have a sentence or two of medical research on PDE5, followed by " Buy at best price at Joe's Safe Online Pharmacy dot com !! ".

B - The vast billions of dollars at stake seems to have the medical researchers tight lipped on anything having to do with PDE5, beyond the Wikipedia description.

So, I was curious if anyone on this board has read any discussions about why and how the PDE5 production increases as we age ?

Thanks !

 

[Gene Devine]

Freaking wonderful post!!!

This is why Excel Male is going to be the single destination site for men's health; due to posts and questions like this!

I've done a ton of research into PDE5i's and why NO decreases as we age and all that I can surmise is that, like all other hormonal loops, they slow down and adverse reaction happens...it's just part of aging.

It's like saying why does the enzyme Aromatase increase as we age...it just does as it's part of the aging clock built into our bodies?

Answer to it all: It's part of growing old and slowly dying.

It's why we have found that replacing Testosterone levels that deplete as we age has wonderful anti aging effects on men...we can slow that clock down!

TRT is just one pathway to anti aging; PDE5i's are another, as is DEHA, Pregnenolone and HGH supplementation all a part of replacing what our bodies stop producing as we age.

Keep something in mind, our bodies from a physiological perspective are not much different then when we lived in caves. We are designed to dye at about 35 to 40 years of age just after our ability to procreate...but thanks to advanced medical science, better food and overall dedication to our health, we live longer.

Diseases that once were a menace to society...today are just a pill away from a cure.

Our bodies work on a clock and it's simple; procreate and then die.

But science has figured out how to halt some of this and things like PDE5i's that increase NO by suppressing the PDE5i enzyme is just one example.

Funny thing, many of these findings when conducting drug trials are purely by accident.

Thanks again for a great post Dude!

 

[The Dude]

Aha! I had to go to the legal documents for the lawsuit over Viagra by Pfizer against Teva from 2011. There I found statements of fact that are carefully checked for accuracy, because Pfizer do not want their decision thrown out over a technicality. Here are the quotes:

To initially relax the smooth muscle tissue, which in turn sets off the chain reaction, the nervous system reacts to sexual stimuli by producing nitric oxide.
This nitric oxide reacts with guanylate cyclase, an enzyme, producing cyclic guanosine monophosphate ("cGMP").
cGMP can be inhibited, however, by another enzyme, PDE5. Thus, if there is too much PDE5, cGMP can be inhibited and the whole process of smooth
muscle tissue relaxation can be thwarted.
This is where Viagra comes in, when an individual's ED is caused by this imbalance in PDE5 and cGMP.
The way Viagra works, then, is to inhibit excess PDE5 so that cGMP can work the way that it is supposed to.

There was a footnote to this:

ED has many causes, both psychological and physical. In regard to physical causes, when ED is not the result of by any particular physical injury to the body, such as paralysis or certain lower back injuries, then it is often caused by an imbalance at the cellular level between PDE5 and cGMP.
In this type of case, Viagra is effective.

Yes, it is true that clogged arteries (and other conditions) can cause insufficient nitric oxide in the system, and those people with those conditions would see benefit from nitric oxide generating supplements.

However, it is clear that Pfizer's research indicates that most ED is due to excess PDE5 - not a lack of nitric oxide.

In fact, those who have a lack of nitric oxide do not benefit from PDE5 inhibitors, because they are not producing cGMP, so it does not matter whether PDE5 is inhibited or not.

And, in fact, a significant minority (something like 30-40% IIRC) do not benefit from Viagra or Cialis, precisely because they are not generating enough nitric oxide.

But - for those who do respond to Viagra and Cialis, then it seems clear that their problem is excess PDE5 - we see this confirmed by Pfizer themselves.

So, why has there been so little mention of the problem of excess PDE5 - including its origin and prevention ?

I think there are two possible reasons:

1 - Viagra and Cialis are big business world-wide. They are sold for $20 and wholesale for $0.30. There is a big motivation to just sell people pills, rather than do anything to prevent the condition (this is also true of many other conditions).

2 - If there is research into the origin of the condition of excess PDE5, then it is undoubtedly being done very quietly, so that whoever comes up with a treatment can patent it.

(NOTE: This does not mean that there are not many benefits to increasing nitric oxide, but simply to say that in the case of ED, if Viagra or Cialis work, then the problem is excess PDE5, not insufficient nitric oxide.)

 

[Tom Larabee]

Great read and yes I do suspect someone is looking into excess PDE5 deep under cover in order to patent the treatment whatever they determine it is.