zebit0
#124
I was looking to lower BP and started using 40mg then 80mg (for the PPAR activation). But I reduced to 40mg because I had transient low BP causing some light headedness.
My BP no longer measures above 133/85 (highest measure in last couple months) and usually is around 116/76. Likely had some additional improvement from 9mg Retatrutide weekly too. Stopped most supplements (beet root extract, magnesium, etc) related to BP.
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Yes. I had a similar problem. It is too effective. I’ve reduced my dose from Telmisartan 40 mg to 20 mg and my arms no longer fall asleep at night while I sleep.
A new medication recently approved which is a PPAR delta agonist is called Seladelpar. Studies are limited for now to primary biliary cholangitis but I’d be interested to see if it had similar performance enhancement effects to cardarine.
Cardarine cancer effects were always so unfortunate to me, it seems like such a promising molecule otherwise.
I did find this with more information on PPAR delta agonists including but not limited to Seladelpar:
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As I continue to explore drug combinations for my own possible future use, I post studies which I think might have general interest. And so I posted several interesting studies on the combination of telmisartan and pioglitazone in the pioglitazone thread, and I’m linking them here. There I also posted an extremely interesting study looking at the differential effects of telmisartan and pioglitazone on mTORC2 driven cell proliferation and migration.
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As pioglitazone has been associated with increased risk of bladder cancer, taking it concurrently with telmisartan might be of interest.
Telmisartan inhibits human urological cancer cell growth through early apoptosis
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Pioglitazone has been associated with increased risk of bone fractures. Telmisartan, being a partial PPAR-gamma agonist, might also be suspected to increase bone fracture risk. However as the mode of telmisartan activity differs significantly from pioglitazone, so there has been some interest in determining whether sartans such as telmisartan or losartan has any impact on the biology of bone health.
Effects of telmisartan and losartan treatments on bone turnover markers in patients with newly diagnosed stage I hypertension
“Neither telmisartan, despite its partial peroxisome proliferator-activated receptor-γ agonistic effect, nor losartan treatment had significant effects on bone turnover markers in newly diagnosed stage I hypertensive patients.”
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A_User
#131
What’s the reasoning behind the PPAR agonist hype, is this mechanistic speculation? I might’ve missed it.
I’m not so sure it’s possible to predict outcomes solely on e.g PPAR agonism, AMPK activation, or mTOR inihibition.
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Cardarine massively increased cardiovascular endurance, but it had cancer worries in trials and was abandoned before it was approved for human use. It seemed like a miracle drug and really want something like that without cancer issues to succeed.
You’re correct that it is hard to predict outcomes solely on isolated mechanisms. But if we can get something like cardarine without the risk that would be so damn good.
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A_User
#133
That’s very unlikely to happen because the more conditionals you add the less likely it becomes. It’s like a fractal once you zoom in you see more complexity that you need to research to even be sure of your previous conclusion.
If you ignore complexity for a moment and take it as given that the mechanism of action is that, it would automatically inherent the cancer causing issue as well. It’s not that simple so PPAR enjoyers don’t have to worry but I’m just saying.
If you really want to succeed in this area study mechanism with genetic support. That’s what you should spend your time on. Why? Those are natural randomized trials, which actually find outcomes, and genetic studies find the mechanisms for outcomes. If you think about it it makes sense.
Small multiple or single genetic changes in humans can cause or prevent disease, or change something else. It’s not selected by mate choice so it’s random, which fulfills the criteria of experimental studies (mendelian randomization they are called).
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LukeMV
#134
I actually looked into the cardiovascular endurance part but the human studies weren’t too convincing. I’ve taken it in the past but honestly, can’t remember if it helped my cardio fitness or not since it’s been so long. It seems to be the one major thing that really sets it apart from anything else is that it raises HDL, but does it even matter?
The cancer doses were very high but they didn’t test for it in lower doses in rats. Still, I am not convinced it’s a big concern, but I understand the hesitation regardless and admit it’s one of the reasons I haven’t used it again. Anecdotally, I used it a bunch and don’t have cancer.
Here is a AI response
Current human clinical studies on cardarine (GW501516), a PPARδ agonist, do not demonstrate improvement in cardiovascular fitness or exercise capacity in healthy individuals.
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Human trials with cardarine have focused on metabolic and lipid parameters(e.g., HDL increase, triglyceride reduction), not direct measures of cardiovascular fitness such as VO₂max or exercise performance. A randomized controlled trial in moderately overweight men showed improved lipid profiles and increased skeletal muscle fat oxidation, but did not assess or report changes in aerobic capacity or exercise endurance I 1, 2, 3.
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Preclinical animal studies suggest increased endurance in rodents, but these results have not been confirmed in human trials and cannot be directly extrapolated to clinical recommendations (Level II/III evidence) 4, 5.
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Cardarine is not approved for human use due to concerns about serious adverse effects, including increased cancer risk in preclinical data I 6, 4.
| Evidence Source |
Study Population |
Outcome on Cardiovascular Fitness |
Clinical Evidence |
| GW501516 RCT |
Healthy overweight men |
No effect measured/reported |
No improvement in fitness 1
|
| Metabolic studies |
Healthy volunteers |
Improved lipid profile only |
No fitness change 3
|
| Animal studies |
Rodents |
Increased endurance |
Not validated in humans 4
|
Conclusion:
There is no high-quality human evidence supporting the use of cardarine to improve cardiovascular fitness. Its use is not recommended due to lack of efficacy data for fitness and potential safety risks.
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Oldie but goodie.
Effect of telmisartan on cholesterol levels in patients with hypertension - Saga Telmisartan Aggressive Research (STAR)
The effect of telmisartan on glucose and lipid metabolism in nondiabetic, insulin-resistant subjects
Meanwhile this is worthwhile in common combinations of statin (here: rosuvastatin), ezetimibe and telmisartan.
Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial
https://onlinelibrary.wiley.com/doi/full/10.1111/jch.14778
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DrT
#136
Following a cardiac ablation 2 years ago, my BP has remained stubbornly high. I have been on a beta blocker but this has the unwanted effect of slowing my heart rate.
I was considering switching to Telmisartan to lower the BP without lowering the heart rate. At the same time, I might benefit from the other effects of Telmisartan such as a reduction in total cholesterol.
One complication is that Telmisartan increases insulin sensitivity and mine is already pretty sensitive. My insulin level is usually <2.0. Possibly it’s so low that Telmisartan won’t lower it anymore, but I don’t want to become hypo glycaemic.
Any comments appreciated.
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Is it possible to be overly insulin sensitive? I haven’t heard of this.
Telmisartan at 40mg will be very unlikely to affect insulin sensitivity. Telmisartan’s non-BP related effects only begin at 80mg and more realistically at 120-160mg. I don’t think there would be much harm in trying 40-80mg.
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RobTuck
#138
With respect to insulin sensitivity, increased sensitivity translates into more precise metabolic control, not necessarily lower BG. When we lose sensitivity, our metabolic system becomes less responsive. In any event, telmisartan’s effect on insulin sensitivity is not high in the best case and has leveled off to a practical plateau at 80 mg/day.
With respect to telmisartan’s primary effect on BP, and its impacts on cardiovascular remodeling and lipids, all of the dose/response curves begin to flatten at ~80 mg/day. For example, receptor saturation for AT₁ is 90-95% at 80 mg/day. Interestingly, most of the non-BP benefits are not significant at the 40 mg/day level but also begin to flatten out at 80 mg/day.
Telmisartan demonstrates a family of non-linear dose/response curves which, together, offer good reasons why the maximum dose is set at 80 mg/day, although making a 100 mg tablet might have been more optimal.
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DrT
#139
Thanks for the thoughtful replies. Out of an abundance of caution I’ll start out with 20mg/day and see how I go.
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RobTuck
#140
One good study on that low dose found, after correcting for placebo effect, telmisartan 20 mg yields reductions of approximately 6–8 mmHg systolic and 6 mmHg diastolic.PMC+15
At that dose, none of the other potential benefits have been observed. At any dose, some people experience a mild dizziness the first day or two which is one of two reasons why taking your dose before bed is often recommended.
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I have wondered this because a few months ago my fasting glucose tested at 70 and my insulin was below the detection threshold. It has been 2.3-2.6 since then.
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Wow, that’s pretty extreme, lol. Any idea what is responsible? Genes, lifestyle, supps, meds?
I think I was legally dead.
… I will check my records
Edit: @CronosTempi records checked. I was not dead.
7mg of reta a week (not a big deal for me), 0.5mg of cagrilintide a week, 5mg dapagliflozin, 2IU HGH, some aromasin, 500IU HCG every 3 days, a dose of testosterone that will remain private, 5mg ezetimibe, 180 bempedoic acid, 5 mg rosuvastatin every 3 days, 1200 NAC, 20mg telmisartin, 5 mg nebivolol, 250mg ashwaganda, 1000mg curcumin, 32IU oxytocin nasal spray, 1mg thymosin alpha 1, some trazodone, some T3, fish oil, multivitamin. Assorted other supplements that probably don’t do much of anything.
The cagrilintide was the only thing truly out of the ordinary. Simultanous reta + tirz + dapa have not done that to me on other panels. You would think the HGH would have been a minor issue, but no.
I do eat very clean, but I don’t watch carbs at all.
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