Nothing earth shattering or novel, but good bathroom reading for some relaxing literature. Single author review.
Angiotensin Receptor Blockers Are Not Just for Hypertension Anymore
Click link inside for the free article.
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Angiotensin-Receptor Blockers and the Risk of Alzheimer´s Disease: A Meta-analysis
“Ten studies (1 RCT, 2 case-control and 7 cohort studies) met the inclusion criteria. When all observational studies (9) were analyzed, ARB use was associated with a reduced risk of incident AD (HR 0.72, 95% CI: 0.58-0.88, p<0.001). In the only RCT, decrease in the incidence of AD was also significant (HR= 0.31, 95% CI: 0.14-0.68).”
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That’s an impressive hazard ratio for the single RCT. My cumulative view is that TM is proving to be a robust geroprotective for many people, perhaps one belonging to the top tier.
I’m not sure. To my eyes olmesartan is looking better and better. Super low AE (in some studies lower than TM), more effective in lowering dementia risk (than TM) and notably (to me) lower ACM (compared to TM which barely - if at all - affected it). I’m not saying it’s a slam dunk case, but something to keep an eye on if we’re looking for drugs that can really move the needle healthwise. TM is good, but possibly olmesartan is the one. To be continued. YMMV.
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I previously took Olmesartan but switched to Telmisartan because it crosses the BBB.
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And yet, olmesartan outperformed telmisartan (and every other sartan) in lowering the risk of dementia, per the study Antoine posted:
And by quite a margin. I have long since given up treating the crossing of BBB as definitive proof that some molecule or other has no impact on the brain perhaps by indirect means.
Again, I’m not claiming that olmesartan is superior to telmisartan, just that the weight of evidence is slowly shifting and it’s worth re-examining one’s stack. I do that all the time. I look at each drug and supplement I take and regularly ask: is it still in my stack for a good reason, can better be had, is this optimal and so on. Telmisartan is what I take, but I’m keeping an eye out for olmesartan and keep reading the literature as it rolls in.
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Interesting article by Saavedra, but perhaps too optimistic about ARBs than than the evidence suggests. Summarizer: “This is a useful compendium of the pleiotropic pharmacology of ARBs, and the core idea — that RAS dysregulation contributes to diverse pathology — is well-supported. But the leap from “ARBs do interesting things in cell cultures and rodents” to “ARBs should be used for Alzheimer’s, depression, and menopause” needs much more clinical trial evidence than currently exists. The review is better as a research roadmap than as clinical guidance.“
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Now you know that isn’t a fair statement - that olmesartan outperformed the other meds. At least based on what you quoted.
They weren’t compared to each other and the confidence intervals are overlapping - and not by just a little bit.
I do seem to remember there was one situation where olmesartan did outperform talmisartan but not in the data you quoted.
Look at table S4 “Adjusted Hazard Ratios for Dementia Risk Across Individual ARBs”. So this is within class of ARBs. Irbesartan was the reference (based on neutrality in previous studies), and olmesartan stood out for significance (p value >0.001). Within ARBs using Irb as reference (AHR 1.00) Olme was 0.55 Telmi 0.94 (NS). And the CI on Olme was 0.43-0.71, whereas Telmi was completely outside the Olme range 0.84-1.05.
For ACM see table S9 and the within class (ARBs) numbers - again Olme was the lowest 0.64 vs Telmi 0.91. And the CI were non overlapping with Olme 0.56-0.74 and Telmi 0.85-0.97.
Keeping in mind we are dealing with decent size cohorts, not a handful of subjects.
After all this time, 40 or 80 for longevity? 
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I don’t know that the thresholds are well understood for broader benefits. Taking 80 mg/day, the mean reduction in systolic blood pressure is approximately 12–13 mmHg and diastolic blood pressure is ~ 7–8 mmHg. For many, the limiting factor will be their baseline BP. A person with high normal BP can likely take a full 80 mg dose and still have adequate, perhaps optimal BP. That is my situation. A person with mid-normal or lower baseline BP will have to see if they can maintain adequate BP with 40 mg or 20 mg. Many normotensive people are reporting doing well and actually improving their BP profile taking either 20 or 40 mg/day. I do very well, with no dizziness or other symptoms with a mean BP of 104/62. Empirical. No hard formula and your minimums may vary.
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For anyone taking Telmisartan, preferably at 80 mg’s or above, look into cold exposure. I find they couple incredibly well, mood is vastly enhanced with their synergy. Gemini gave several rationales, perhaps this is relevant:
Shifting the Telmisartan BAT Engine into Gear
This is the most fascinating cellular synergy. Telmisartan upregulates UCP1 and alters fat-pad macrophages to “prime” your white fat tissue, turning it into metabolically active beige fat. However, without a physical stimulus, those newly created beige mitochondria are like a high-performance sports car sitting in neutral.
The Cold Shower Correction: Cold exposure is the physical key that turns that engine on. The cold activates the newly formed UCP1 channels to start aggressively burning those cleared fats to generate heat. Instead of your body feeling sluggish from telmisartan’s nutrient-clearing process, the cold exposure forces your body to cleanly consume that fuel for thermogenesis, completely optimizing your full-body energy expenditure.
Having just started taking cold showers, I am quite befuddled as the lack of attention to cold exposure for health- and lifespan promotion. We shower anyway, so why not optimise its effects on our physiology. Rhonda Patrick has a good overview of the literature.
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If you are going to do this for a while you should get a scan done and another after doing this for a few months.
Cold showers are not how you do CE (cold exposure). Back when the CRSociety website was active, we had a years long exploration of CE as a rival to CR (calorie restriction). CE can be an incredible longevity tool. There is a long list of interventions which increase BAT, but CE is the most reliable. If you want to do real CE, cold showers (or cold plunges) are not it (or only a tiny part for beginners), for real CE you need much longer exposure, on the order of hours. To do that in practical terms, you use a cold vest. There is a variety of designs, several available on Amazon, or make your own. It involves inserting ice packs into a specially constructed vest with the ice packs hitting key areas, such as trapezoids where BAT generation is most activated. You increase the time you wear the vest gradually, starting with a few minutes. Eventually you get it long enough to get substantial benefits.
Re: telmisartan and BAT, I am not familiar with this interaction, but I’m very familiar with CE, so I thought I’d chime in 
FWIW, I’ve mentioned CE as a longevity intervention in seversl threads here, but indeed it’s a topic almost never discussed on the site - strange, considering CE can rival CR for longevity. But of course, pharmaceuticals are more the focus here - it’s in the name 
!
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did you mean trapezius muscle/area? as I’m not familiar with a trapezoid area in human body, real question btw,
Sorry, yes, that’s what I meant, somehow my fingers went geometric😅.
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Thanks
I didn’t know about that. That is something I might try. For some reason, perhaps because I spent my youth in cold country and most of my adult life in the desert, I am very tolerant of heat and cold, but I’m not into cold showers.
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Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes
https://www.kidney-international.org/article/S0085-2538(16)30590-7/fulltext
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This is a very complex paper. I’m still digesting it. Thanks.
This really is a very nice paper looking at the kidney protection afforded by telmisartan vs enalapril so, you are looking at class effects ARBs vs ACEi (in diabetics). What’s very nice is that it is not a short term trial, but five years 
- and it’s randomly assigned, prospective, multicenter, double blind with 250 subjects. Telmisartan was the ARB and it was at a dose of 80mg (so, you are looking at max effects dose), while enalapril was at 20mg. Primary endpoint was GFR with several secondary endpoints. It’s also a very old trial and somehow it escaped my attention. Enjoy!
Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy
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