Rilmenidine vs Telmisartan or other BP meds for Longevity

[adssx]

Yes beta blockers might be good for some specific indications, for instance, arrhythmias. However, for essential hypertension and for neuroprotection, they’re not recommended as of today.

[sunshine4]

After being on Telmisartan 80 for another month and a half after writing this, I definitely feel a positive affect on my body composition. I do take other stuff like rapa/jardiance known to affect fat loss, so it could be synergy or other compounds. But since being on Telmisartan 80, I’ve noticed some fat loss.

I don’t know what else I will add to get my BP where I want it. I have light CKD so its IMO I’ve read its even better for me to lower my readings. The thing about this is, I take high dose melatonin which can have a blood pressure lowering affect, but my readings at night after the Telmisartan 80 are dead at the hypotension line (Is it 90/60?), with all I take. Its just that because I take caffeine and dont have the best diet and even smoke intermittently (hopefully that doesn’t take away my rapamycin.news pass) my day time blood pressure can get to the 120 systolic level which I want down.

adding 5/10 of amlodipine at night might push that hypotension over the edge

[DeStrider]

Honestly, the risk of hypotension seems to be bigger than the risk of being at 120 which is 5 over the 115 target. I wouldn’t do anything else except stop smoking! Have you tried a nicotine patch?

Don’t worry, we won’t revoke your Rapamycin pass.

[sunshine4]

Thanks

I’m not addicted. Only smoke about 4 cigs a day, maybe with my coffee or after a meal, or after a long day to think. Actually only started in my mid 40s recently after not smoking most my life (so hopefully it won’t catch up as soon for me as everyone else if it does)

Its kind of a “quality of life” thing. Some people just like the action of it. I know I have to give it up soon though!

[adssx]

Utilizing genetics and proteomics to assess the role of antihypertensive drugs in human longevity and the underlying pathways: a Mendelian randomization study 2024

After correcting for multiple testing, genetically proxied beta-blockers (BBs), calcium channel blockers (CCBs) and vasodilators were related to longer life years (BBs: 2.03, 95% CI 0.78 to 3.28 per 5-mmHg reduction in SBP, CCBs: 3.40, 95% CI 1.47 to 5.33, and vasodilators: 2.92, 95% CI 1.08 to 4.77). The beneficial effects of BBs and CCBs were more obvious in men.

ACEi and ARBs are vasodilators.

Integrated metabolomics analysis reveals mechanistic insights into variability in blood pressure response to thiazide diuretics and beta blockers 2024

Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to β-blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). […] This might provide a possible step forward in personalizing antihypertensive therapy by identifying patients expected to have robust BP-lowering effects from these drugs.

[DeStrider]

Effects of ARBs and ACEI on the immune system.

The immunomodulatory effects of antihypertensive therapy: A review

http://www.sciencedirect.com/science/article/pii/S075333222200676X

[sunshine4]

Does Telmisartan have immunosuppressant properties? I was looking for answers on my week long cough (though I’m taking a lot of other stuff that could affect it). This looked old but a bit concerning

Telmisartan (MPKB)

Telmisartan, an ARB, is an extreme immunosuppressant by means of being a strongly active antagonist of VDRs

My in-silico work showed Telmisartan totally shuts off the VDR and is therefore highly immunosuppressive.

Trevor Marshall, PhD (personal communication to research team)

Due to differences in molecular structure, each ARB is shown to have significantly different properties when interacting with the nuclear receptors in the immune cells. For example: where Telmisartan will quickly and completely suppress immune function, frequent dosing of olmesartan medoxomil (which is an agonist of VDRs) over a prolonged period allows recovery of immune function via activation of the vitamin D receptor.

[Davin8r]

@sunshine4

My in-silico work showed Telmisartan totally shuts off the VDR and is therefore highly immunosuppressive.

Trevor Marshall, PhD (personal communication to research team)

That web page looks very “sketchy”. If telmisartan were an “extreme immunosuppressant”, wouldn’t we know it by now? It’s been on the market for 26 years.

[Virilius]

All the other miracle drugs have already been badmouthed on other conspiracy sites so they had to pick a new one to stand out.

[sunshine4]

Yes, I didn’t see anything else suggesting telmisartan had a negative role in immune function

What concerning is that stuff is literally the first thing that shows on google for “telmisartan - immune system” for me.

I think I’ve noticed a couple longer colds recently. But I take so much stuff it’s hard to pinpoint what causes what (or if it’s dosage related). I think I’ve seen a bit of conflicting stuff on high dose statin usage which I do too… (I take high dose statins/ezetimibe - jardiance - acarbose - rapa and a lot of different supplements)

I don’t even know if the longer colds are indicative of negative immune function necessarily either. Maybe elements can not be the best for colds necessarily, but still better for overall immune health

[DeStrider]

Telmisartan does have an immunosuppressive function. I posted it above in the link. It affects the VDR (vitamin D receptor) which affects the immune system. Also:

Telmisartan was shown to inhibit the expression of the potassium channel proteins Kv1.3 and KCa3.1 and thus to block the increase in calcium ion influx. As a consequence, this inhibits the activation and proliferation of T lymphocytes by blocking calcineurin and NF-AT-dependent pathways [87], [88], [94].

However, the above is from a Chinese study done in Kazakh, so I’m skeptical.

Rilmenidine vs Telmisartan or other BP meds for Longevity

Effects of ARBs and ACEI on the immune system. The immunomodulatory effects of antihypertensive therapy: A review http://www.sciencedirect.com/science/article/pii/S075333222200676X

[Davin8r]

Anything that is anti-inflammatory is technically immunomodulatory/immunosuppressive (which is a good thing in the setting of overly active inflammation), but that’s a far cry from it suppressing the immune system to the extent of raising risk of infections or cancer in a human population to a clinically relevant extent. I haven’t seen any evidence of that in the drug’s 26 years on the market. All the BP meds in that article have anti-inflammatory properties. I skimmed the whole article and didn’t see anything about human research showing increased risk of infections.

On the other hand, ACEi are known to often cause a chronic cough, and so can ARBs (although less common than ACEi).

[DeStrider]

Yes. Exactly. When I saw it reduced cytokines and inflammation, I thought that was a good thing. Although it is technically immunosuppressive.

[sunshine4]

Good. I didn’t want to have to get off it, or blame it. Its probably been my favorite drug so far.

I feel its helping me transform physically without much diet/exercise change
Ive been hitting my bp targets recently
Its very good for CKD in the papers Ive read (I have light CKD)
Ive read it has synergy with my statin - simvastatin in certain aspects
I think its helped other blood work
I think actually my libido has been good on it (Ive read it helps with energy)
And to boot, at least so far, when you take the 80 at night (and blood pressure medicine is often taken then), it has a strong sedative affect that works for me as another sleeping pill (hopefully that continues even as my body gets accustomed to it after many months)

[globaltraveler]

I’ve been taking a small dose of Rilmenidine for a while now. It’s been around for years, mainly Europe I think, so has been proven. Don’t know why USA isn’t really selling it, but I’ve had good experience with www.buyrilmenidine.com recently (previously bought from a way more expensive place so pleased I found this site).
My bloods have been good, monitoring regularly and lost weight. I do have a good exercise routine and keep off nasty foods which of course will help. That study published by the professor in the U.K. on rilmenidine and animals made me think this might be beneficial to more than humans, like pets may benefit as well?
In any case thought I’d share in case it’s helpful to others.

[ageless64]

I’ve started telmisartan and went from 40 mg daily to 40 morning and again at night, but it’s only bringing my BP down into the mid 120s systolic, although that’s pretty stable across the day and night as measured by Aktiia.

So I’ll probably need to add something thing else to my stack. I’m 65, caucasian, and fit (VO2 max: 58, Dexa: 18% BF) and have replaced salt with a sodium/potassium mix (20/80%). Perhaps related is a high resting heart rate, in the 70s when I’m on a beta blocker (propranolol) or 80s if not. I’m an experienced mediator but don’t do it much anymore. Paradoxically, when I do mediate, my heart rate increases like 5 beats!

To complicate things further, my eGFR is low, mid 60s to 80s, although albumin/creatinine urine ratio is good at 0.3 mg/mmol.

So I’m leaning to adding either rilmenidine, although the longevity data on this seems to be limited to one worm study and it’s expensive, or something like amlodipine, discussed by @DrFraser and @adssx below:

@DrFraser

Indeed - unless there is a reason against this in an individual patient, once I get to 40 mg of Telmisartan, the amlodipine is next for exactly that reason then indapamide as third agent. The side effects usually occur once pushing higher dose on amlodipine, and I generally don’t go beyond 5 mg.

@adssx

most hypertension guidelines say that “antihypertensive medication should start with SPCs to ensure more rapid, effective BP-lowering” (source). SPC means “single pill combination” such as telmisartan/amlodipine. For instance, the 2023 European guidelines say: “Initiation of therapy with a two-drug combination is recommended for most hypertensive patients. Preferred combinations should comprise a RAS blocker (either an ACE inhibitor or an ARB) with a CCB or Thiazide/Thiazide-like diuretic. Other combinations of the five major drug classes can be used.”

Thoughts?

[DrFraser]

In general terms, the benefits to super tight management of BP go down with age and risks go up. It however sounds like your are 65 going on 50, rather than most of of my ER patients who are 40 and look like they are 65.
I’d first thing not be overly excited about letting it sit in the 120’s - however, if really going for optimal, add a dose of something you tolerate well is reasonable. Propranolol is a bit of nasty drug, but a long acting beta blocker could be an option - but I’d generally favor a tiny dose like 2.5 mg of Amlodipine and be pretty happy with goaling in the upper 110’s or low 120’s and not push harder on that.
I obviously don’t know all your medical history, but in general terms with a generic patient in this situation, that would be my usual approach.

[Jonas]

Can you elaborate on the risk? Thanks

[DrFraser]

Risks are that as people get older, than have more postural hypotension, even with no meds. Pretty much, all the BP meds make this worse. This increases rate of syncope (fainting) and trauma - along with the population being more frail and more likely to bleed in their head or fracture bones at that age.
Risk of other underlying conditions resulting in more hypotension than desired go up with age (e.g. acute renal injury, sepsis).
Risk of organ dysfunction due to BP meds, primarily renal injury also goes up with age.
Then on the other side - the benefits of targeting lower BP’s seems less beneficial as people get older.
So ultimately the risk/benefit ratio looks a little different, and caution is required.

[Jonas]

Same with my mom and so we had to increase it to 80mg, her doc said Telmisartan is weak ARB so we also had to add 5mg amlodipine.