@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.
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).
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.
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.
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.
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.
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.
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.”
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?
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”
https://www.youtube.com/watch?v=r8DSpOd0NZc
Professor Phillips has suggested that the studies may not be that accurate because DEXA can’t tell the difference between water and muscle… so he’s a doubter.
We don’t know. “Tadalafil is generally safe when used as directed.”
To be clear, I think that tadalafil probably has the same life-extension properties as sildenafil, as they are in the same drug class. But, because of the long half-life of tadalafil compared to sildenafil, the proper dosing is more problematic.
Dose-Dependent Adverse Events of tadalafil:
Headache
Dyspepsia (indigestion)
Back pain
Myalgia (muscle pain)
These side effects tend to decrease in incidence with longer treatment duration ([1]).
“Cardiovascular Risks
Hypotension-Related Events
Risk of hypotension-related treatment-emergent adverse events (TEAEs) is low, ranging from 0.6-1.5% in placebo-controlled studies ([2]).
Increased risk observed only in ED patients not receiving concomitant antihypertensive medications.
No significant increase in risk for patients taking antihypertensive medications alongside tadalafil.
Major Adverse Cardiovascular Events (MACE)
Incidence of MACE ranges from 0.0-1.0% across all indications in placebo-controlled studies ([2]).
No significant difference in MACE risk between tadalafil and placebo, regardless of concomitant antihypertensive medication use.
Specific Organ Systems
Visual Effects
Potential increased risk of non-arteritic ischemic optic neuropathy (NAION), though the magnitude of risk is small ([3]).
Higher doses of sildenafil (100mg) are more associated with visual disorders than tadalafil ([4]).
Auditory Concerns
Possibility of sensorineural hearing loss remains uncertain ([3]).”
