Video explaining potential testosterone increasing mechanism of Tadalafil, with visuals

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Tadalafil: Erectile Dysfunction Cure? Testosterone Booster? Non-Responders? [Study 147-154 Analysis]
View: https://www.youtube.com/watch?v=Nmi3hR9aA80


Interesting video explaining the actual mechanisms of Tadalafil, Nitric Oxide inhibiting Calcium uptake of cells and accelerated Potassium release from cells, and the mechanism for potential increased Testosterone production effect of Tadalafil. There is graphics of molecules and timestamps.

At 8:11 he explains the mechanism of how Tadalafil inhibits calcium influx into cells and into some non-cell structure in muscles, and also accelerates release of potassium, leading to relaxation of the cells, which allows for vasodilation.

At 15:52 the mechanism for potential Testosterone production increase of Tadalafil.

He also says Testosterone itself can increase Nitric Oxide production. Not sure if this is true. At 13:40 min

At 36:11 he goes through a graph from a study that shows Tadalafil significantly decreases Estrogen and significantly increases insulin levels. Though he says the study is not that good because there was no placebo group.

------------------------------------------------------------------

On the topic of Nitric Oxide. I heard that the nose produces nitric oxide when nose breathing, allegedly to act as a disinfectant of the air inhaled through the nose.
If this is true, could Nitric Oxide act as a systemic anti-microbial? Maybe the anti-microbial effects would outweigh it's negative effects? Maybe a non-chronic, periodical acute increases of Nitric Oxide could clear the body of some pathogens. Maybe pathogens are worse for the body than the Nitric Oxide amount required to kill them. I guess that would depend on how effective it is as an antimicrobial and in what amounts to make an educated guess if it is positive or not.
 
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Nokoni

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I started taking tadalafil for urological issues, which resulted in substantial improvements. But I also quickly noticed all kinds of other benefits, firstly and most notably just feeling better overall. Started some research and found the following study, called PDE5 Inhibitors in Non-Urological Conditions, which is from 2009: PDE5 inhibitors in non-urological conditions - PubMed.

From the abstract: "Importantly, accumulating data show that the therapeutic potential extends to the cardiovascular, gastrointestinal, cutaneous and nervous system and that these agents may be beneficial in a multitude of conditions such as Raynaud's phenomenon, heart failure, essential hypertension and stroke. PDE5 inhibitors are a conceptually attractive therapeutic class of agents with pleiotropic effects."

Such evidence suggests that PDE5 levels may rise with aging, thereby inducing a variety of problems, and that reducing those levels might therefore restore a more youthful phenotype. I couldn't find any direct evidence for that theory, although I did run across some hints that it may be true. In any event, I'm extremely happy to have found it (courtesy of this forum, btw) and will take it from now on. I have the full study if anyone wants me to upload it. (Alternatively just use Sci-Hub.) I've attached a graphic from the article.
 

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TruffleGnocchi
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Interesting, thanks for sharing.
I wonder if the beneficial effect on the nervous system is from increased blood flow to the nervous tissue, or something else like the effect on calcium and potassium flow
Recently I've started taking 5-10mg of tadalafil when I feel uncomfortable from taking modafinil and more glucose doesn't help, makes more more relaxed sitting on the chair while maintaining benefits of modafinil, probably blood pressure
 
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TruffleGnocchi
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If possible can some admin please correct my original post. I just realized that what I said is not true, the video does not say tadalafil increases nitric oxide. So when I said that tadalafil's effects are "via nitric oxide", it is not true, it does not affect the NO concentration in the body.

I would like to remove this line exactly:
I know nitric oxide is bad in Ray Peat's view and there are already posts about estrogen reduction. But still

And change this line:
At 8:11 min, he explains the mechanism of how Tadalafil, via nitric oxide, inhibits calcium influx into cells and into some non-cell structure in muscles, and also accelerates release of potassium, leading to relaxation of the cells, which allows for vasodilation.

To this:
At 8:11 min, he explains the mechanism of how Tadalafil inhibits calcium influx into cells and into some non-cell structure in muscles, and also accelerates release of potassium, leading to relaxation of the cells, which allows for vasodilation.

Thanks in advance. I think this is important to not misinform people
 

Ras

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If possible can some admin please correct my original post. I just realized that what I said is not true, the video does not say tadalafil increases nitric oxide. So when I said that tadalafil's effects are "via nitric oxide", it is not true, it does not affect the NO concentration in the body.

I would like to remove this line exactly:
I know nitric oxide is bad in Ray Peat's view and there are already posts about estrogen reduction. But still

And change this line:
At 8:11 min, he explains the mechanism of how Tadalafil, via nitric oxide, inhibits calcium influx into cells and into some non-cell structure in muscles, and also accelerates release of potassium, leading to relaxation of the cells, which allows for vasodilation.

To this:
At 8:11 min, he explains the mechanism of how Tadalafil inhibits calcium influx into cells and into some non-cell structure in muscles, and also accelerates release of potassium, leading to relaxation of the cells, which allows for vasodilation.

Thanks in advance. I think this is important to not misinform people
Could @Blossom or @charlie help with this?
 
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I started taking tadalafil for urological issues, which resulted in substantial improvements. But I also quickly noticed all kinds of other benefits, firstly and most notably just feeling better overall. Started some research and found the following study, called PDE5 Inhibitors in Non-Urological Conditions, which is from 2009: PDE5 inhibitors in non-urological conditions - PubMed.

From the abstract: "Importantly, accumulating data show that the therapeutic potential extends to the cardiovascular, gastrointestinal, cutaneous and nervous system and that these agents may be beneficial in a multitude of conditions such as Raynaud's phenomenon, heart failure, essential hypertension and stroke. PDE5 inhibitors are a conceptually attractive therapeutic class of agents with pleiotropic effects."

Such evidence suggests that PDE5 levels may rise with aging, thereby inducing a variety of problems, and that reducing those levels might therefore restore a more youthful phenotype. I couldn't find any direct evidence for that theory, although I did run across some hints that it may be true. In any event, I'm extremely happy to have found it (courtesy of this forum, btw) and will take it from now on. I have the full study if anyone wants me to upload it. (Alternatively just use Sci-Hub.) I've attached a graphic from the article.
Would you mind telling us about your dosing and what is improving for you? Thank you so much.
 

Nokoni

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Would you mind telling us about your dosing and what is improving for you? Thank you so much.
Well it's been a while and I've moved on, but I'll try my best. As for dosing I don't remember the numbers but I was using a typical prescription dose for chronic use at first. Since that was working well I increased it over time to double or triple that and continued to experience benefits, but it seemed that I was possibly experiencing some hearing loss. I believe I then looked into that as a possible side effect and learned that ototoxicity was indeed a possible side effect. Again, operating from memory so I'm no longer sure. You might want to investigate that a bit. Anyhow I discovered an alternative PDE-5 inhibitor so I moved on from tadalafil. More about the alternative below.

As for benefits, the most notable was a significant improvement in urological problems. Less urgency, fewer nighttime interruptions, less dribbling, stronger stream, more complete emptying. In other words, really substantial improvement in every way, urologically. And also more lead in the pencil, obviously. Other benefits are hazier since they were more subtle and it's been so long, but I do remember just feeling better, so probably some neurological benefit. Some other stuff also but I just no longer remember. But that ototoxicity.

The alternative I found is a more natural substance, I think actually produced in the body, at least in small quantities, and that is pyroglutamic acid (PGA). Not sure how I discovered it, but the Wikipedia article had as the last sentence of their article a brief reference to this study: "A Multi-Biochemical and In Silico Study on Anti-Enzymatic Actions of Pyroglutamic Acid against PDE-5, ACE, and Urease", https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770154/. The study says that PGA is almost as strong as the pharmaceuticals in inhibiting PDE-5, almost as strong as the pharmaceuticals at inhibiting ACE, and that it also inhibits urease, so potentially reducing ammonia and kidney stones as well. The first time I ever heard of it was in Haidut's product Magnoil, which uses magnesium pidolate, and pidolate is another name for PGA.

So I'm using PGA now and enjoying all the same benefits, and maybe avoiding aggravating the hearing loss. I buy it from Amazon in bulk, I take 1/4 teaspoon per day currently, and, since it's highly acidic, I buffer it with 1/8 teaspoon of baking soda. I also have a bunch of studies from pubmed that I identified and to some of which I added a brief note. I'll create another post to share those.
 

Nokoni

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Pyroglutamic Acid
- Activates GABA, acetylcholine, and causes mild sedation. Pyroglutamic acid administration modifies the electrocorticogram and increases the release of acetylcholine and GABA from the guinea-pig cerebral cortex - PubMed
- Pyroglutamic acid improves the age associated memory impairment, Pyroglutamic acid improves the age associated memory impairment - PubMed
- L-Pyroglutamic acid protects rat cortical neurons against sodium glutamate-induced injury, L-pyroglutamic acid protects rat cortical neurons against sodium glutamate-induced injury - PubMed
- A new endogenous anxiolytic agent: L-pyroglutamic acid, A new endogenous anxiolytic agent: L-pyroglutamic acid - PubMed
- Anti-diabetic effect of pyroglutamic acid in type 2 diabetic Goto-Kakizaki rats and KK-Ay mice, Anti-diabetic effect of pyroglutamic acid in type 2 diabetic Goto-Kakizaki rats and KK-Ay mice - PubMed
- Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice, Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice - PubMed
- Pyroglutamic acid improves learning and memory capacities in old rats, Pyroglutamic acid improves learning and memory capacities in old rats - PubMed
- Virucidal hand treatments for prevention of rhinovirus infection, Virucidal hand treatments for prevention of rhinovirus infection - PubMed, "salicylic acid and pyroglutamic acid have potent virucidal activity for the rhinoviruses that persists for several hours after application to the hands."
- The central vascular and metabolic effects of pyroglutamic acid, [The central vascular and metabolic effects of pyroglutamic acid] - PubMed, "The ability of pyroglutamic acid, a cyclic glutamic acid derivative, to increase cerebral blood flow, to decrease the resistance of brain vessels, and to relax the isolated grafts of cerebral arteries has been demonstrated. Pyroglutamic acid markedly stimulated brain metabolism: increased glucose uptake and utilization by cerebral tissues and decreased brain lactate dehydrogenase activity."
 
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Messages
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Well it's been a while and I've moved on, but I'll try my best. As for dosing I don't remember the numbers but I was using a typical prescription dose for chronic use at first. Since that was working well I increased it over time to double or triple that and continued to experience benefits, but it seemed that I was possibly experiencing some hearing loss. I believe I then looked into that as a possible side effect and learned that ototoxicity was indeed a possible side effect. Again, operating from memory so I'm no longer sure. You might want to investigate that a bit. Anyhow I discovered an alternative PDE-5 inhibitor so I moved on from tadalafil. More about the alternative below.

As for benefits, the most notable was a significant improvement in urological problems. Less urgency, fewer nighttime interruptions, less dribbling, stronger stream, more complete emptying. In other words, really substantial improvement in every way, urologically. And also more lead in the pencil, obviously. Other benefits are hazier since they were more subtle and it's been so long, but I do remember just feeling better, so probably some neurological benefit. Some other stuff also but I just no longer remember. But that ototoxicity.

The alternative I found is a more natural substance, I think actually produced in the body, at least in small quantities, and that is pyroglutamic acid (PGA). Not sure how I discovered it, but the Wikipedia article had as the last sentence of their article a brief reference to this study: "A Multi-Biochemical and In Silico Study on Anti-Enzymatic Actions of Pyroglutamic Acid against PDE-5, ACE, and Urease", https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770154/. The study says that PGA is almost as strong as the pharmaceuticals in inhibiting PDE-5, almost as strong as the pharmaceuticals at inhibiting ACE, and that it also inhibits urease, so potentially reducing ammonia and kidney stones as well. The first time I ever heard of it was in Haidut's product Magnoil, which uses magnesium pidolate, and pidolate is another name for PGA.

So I'm using PGA now and enjoying all the same benefits, and maybe avoiding aggravating the hearing loss. I buy it from Amazon in bulk, I take 1/4 teaspoon per day currently, and, since it's highly acidic, I buffer it with 1/8 teaspoon of baking soda. I also have a bunch of studies from pubmed that I identified and to some of which I added a brief note. I'll create another post to share those.
Super, thank you SO MUCH for this detailed account.
 

Nokoni

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EMF Mitigation - Flush Niacin - Big 5 Minerals

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