Todd
#79
@约瑟夫_拉维尔 Thank you for your reply.
I get the value-added benefits of nasal breathing. I’m already a fan. Thanks to your podcast and my snoring problem, incorporating mouth taping at sleep and nasal breathing at exercise has been life-changing… literally. I’ve been surprised at what a big difference it has made on so many levels.
Where I’m unclear is the value-added benefits of low-dose Tadalafil if one has incorporated the full suite of nasal breathing practices into their life already.
Stated another way, we’re all clear about the risks of polypharmacy. We may not be able to define or quantify the risks, but it’s clear that undefined risks exist whenever we add a med to our stack.
That polypharmacy risk results in a general policy of trying to minimize additions to my stack to minimize that risk, and only add something when the researched benefits point toward a reasonably clear expected benefit.
I can see the expected benefit of low-dose tadalafil reasonably clearly, but all roads point toward nitric oxide increase as the key actor in this game. NO is the lynchpin that is driving the bus (at least, that’s my admittedly non-expert read of the material).
Given the research subjects weren’t parsed for nasal breathers vs. mouth breathers, I’m not seeing any way to know how applicable the research results are to nasal breathers who are already taking in much higher than average NO relative to the study population.
Does disciplined nasal breathing provide a comparably similar benefit? Is there still value-add for low-dose tadalafil above and beyond disciplined nasal breathing?
I dunno…
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FWIW: I ordered a lifetime supply of both tadalafil (Cialis) and sildenafil (Viagra) from India. 
They are dirt cheap from India so it didn’t seem worthwhile to pay more for shipping than the product, so I ordered a large amount of both.
I thought that tadalafil might be the better option but after a little more research, I found that the half-life of tadalafil is ~17,5 hrs which would cause a worrying amount of accumulation if taken daily.
I took tadalafil daily for about two weeks before I knew what the half-life was. Then I started taking tadalafil every other day. Then I started plugging this routine into the drug half-life calculator and I could see that this would still result in a high amount of tadalafil in my system over a few weeks. This is when I decided to take sildenafil instead.
Sildenafil has a terminal half-life of about 4 hours, so a dose of sildenafil would essentially be eliminated in 24 hours.
So now I take sildenafil 6 days a week taking one day off to prevent an accumulation.
My experience is that I had no side effects from Sildenafil, but I had some with tadalafil.
In addition of course sildenafil was used in the study, so for now, I will be sticking with sildenafil.
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LukeMV
#81
Perhaps take an even lower dose of Tadalafil to accommodate a daily dosing schedule? I do 2.5mg per day, although Sildenafil is also a good option
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@Todd Awesome! I wish I knew the answer to your question. I hope someone here can provide some information.
What I was told by Beth Shirley (pharmacist) was that tadalafil and the like do not help create NO but keep NO from dissipating / being removed. So, if a person has low NO as seen via vascular issues (such as ED), then these drugs would be helpful. They also seem to help with BPH in some way.
Beth also said that our ability to make NO decreases as we get older so we should fix our oral biome and eat nitrates to get NO that way. Since NO is so important, I take tadalafil to get as much help as I can get.
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Todd
#83
Thank you both Desert Shores and Joseph Lavelle. Those are both helpful distinctions (half life of tadalafil vs. sildenafil, and tadafil acting to reduce NO dissipation vs.nasal breathing adding NO).
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Interesting. Did you see any references to studies? I’d like to investigate this claim.
I like this quote:
I told my wife about the benefits of Tadalifil.
But she found it hard to swallow. 
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Thanks.
This paper says…“ increased abdominal lean mass”. Is this referring to larger organs? What would have gotten larger in the abdomen?
Is the amount of tadalafil used in the test tube study possible in a person from the dosing of 5mg (or 20mg) per day? “Exposure of C2C12 cells upon increasing tadalafil concentrations (10-7 to 10-6 M)…”
Conclusions: Daily tadalafil improved lean mass content in non-obese men probably via enhanced insulin secretion, estradiol reduction, and improvement of endothelial function in vivo. The in vitro increased myogenin and androgen receptor protein expression in skeletal muscle cells suggests a translational action of phosphodiesterase type-5 on this receptor.
I think the study is looking only at abdominal lean mass via Dexa. I’m confused about what got larger in the abdomen. But it suggests muscle building could be augmented via higher insulin (a growth factor), lower estrogen (less conversion from testosterone?), and better blood flow.
Did I understand that correctly?
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It would be abdominal musculature (which also would include muscles in the back through the same region), not the organs getting bigger, in regard to the increase in lean mass.
It seemed like the results were best with the 5 mg/day rather than the occasional use of 20 mg, but I don’t have the full paper to fully review this.
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LukeMV
#90
If you have an X/Twitter account, you’ll be able to see all the replies to his own tweets where he sites references
LukeMV
#92
I might just have to suck it up and deal with stuffy nose and some GERD on 2.5mg until they hopefully go away. I had stopped it three weeks ago but I can’t help but feel I’m missing out by not taking it anymore.
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tj_long
#93
I stopped using tadalafil, too many side effects. Worsened acid reflux and constant stuffy nose, which also caused waking up at night. These symptoms persisted even with a 2.5 mg dose.
I didn’t notice any benefits while exercising; on the contrary, the stuffy nose raised my heart rate.
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Thanks for this. Yes seems like the 5 mg daily is the win. Interesting mention in this paper, of another paper showing decreased epicardial fat with sildenafil.
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I have a lifetime supply of tadalafil and sildenafil because they were so cheap (from India, of course).
I have tried both over several weeks. After taking tadalafil daily for some time, I was starting to feel a little off, funky, as it were.
Then, I decided to do some research using the half-life calculator. Because the mean half-life (t1/2) of tadalafil is 17.5 hours, it accumulates over a few days to an unacceptable level. Instead of trying to find a protocol for how many days on or off or when to skip a day, I decided to switch to sildenafil, which has a shorter half-life. Median half-life of ~4 hours. This means some of the sildenafil is in your system for most of the day—no accumulation when taken daily, according to the half-life calculator.
In addition, sildenafil was used in the study to show life-extension probability.
There is no reason to think tadalafil is superior.
“Sildenafil’s selectivity for PDE5 over other phosphodiesterases is well-documented. It is approximately 4,000-fold more selective for PDE5 compared to PDE3, which is involved in cardiac contractility, and about 10-fold more selective for PDE5 compared to PDE6, which is found in the retina and involved in the phototransduction pathway.”
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In the paper posted above, the Dexa calculated lean mass (or more accurately fat-free mass) increased by 0.3% in the 5 mg daily tadalafil group, which perhaps is statistically significant, but is almost certainly not clinically significant, given that “The lean body mass evaluated by DEXA includes skeletal muscle mass, viscera, and fluids, which have similar radiological density.”* So it could all be water, and even if it’s muscle or other lean tissue, it’s really not much tissue almost certainly within Dexa’s margin of error. The small reduction in android fat mass is more interesting to me since Dexa measurement of fat mass is more reliable.
Is this the reference that Greg Mushen is using to claim that tadalafil is “scientifically proven to double muscle growth?” It’s hard to take anyone seriously that uses the words “scientifically proven” and thinks that anything that doubles muscle growth would not be exploited by the bodybuilding community. By the way tadalafil is used by gear heads but it’s an adjunct to powerful steroids.
For the record, I do think that tadalafil has potential as a longevity drug, mostly because of its vascular benefits and this is reflected in improved endothelial function measured in this study. However, the authors note a correlation between improved endothelial function and increased insulin and decreased estradiol serum levels. From what we know about these hormones and their impact on longevity, I’m not sure we want them moving in these directions. Any thoughts?
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There is nothing in the paper you cited that indicates to me that tadalafil is superior to sildenafil.
From the paper you cited.
“Studies in men with type-2 diabetes (T2D) confirmed that chronic sildenafil administration was able to reduce epicardial adipose tissue and in a murine diabetic model regulated visceral adiposity by shifting adipose tissue cell composition toward a less inflamed profile [11]. No data on possible effects of PDE5 inhibitors on lean mass in humans have been described yet.”
“Chronic treatment with sildenafil in
a mouse model of diet-induced insulin resistance caused a
significant improvement in energy expenditure and insulin
sensitivity [24]. In animal models, chronic sildenafil
improved cardiac performance [25] and reduced interstitial
cardiac fibrosis [26]. In men with T2D, Fiore et al.
demonstrated that daily sildenafil improved WC and
epicardial fat, and demonstrated that this occurred by regulation of miR22 release and SIRT1.[11] Also Ramirez
et al. demonstrated that chronic sildenafil administration in
overweight men with pre-diabetes enhanced insulin sensitivity and improved markers of endothelial function”
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You meant to reply to @ageless64 …
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