Doses and Schedules of Rapamycin for Longevity - Blagosklonny

[curt504]

Hi all re high LDL vs CHD risk vs studies… Tnx for asks and contradictions. Lots of fuzziness and per person variabilities in this area.

• (My views) Finally major Med Magazines authors are finally writing that some percent of studies even Mag peer reviewed are non-reproducable or Statistical math trickery was used to find a small benefit.

• There are alot of past studies on LDL/Statins/CHD risk. How many are “directed out come”?

• We pay $$ to go to confs every yr and take the latest from the on stage folks who study and find the faults in past studies etc. I can’t in the 1st person discuss one study vs another. I filtered and posted the summary of what I heard from the stage (Denver Low carb 2023, Boca FL low carb 2023)

• We are all responsible for coming to our own conclusions re best path for our health. I certainly respect anyones views that may contradict what I have summarized.

• I apologize for not giving URLs to latest or best structured CHD / statin / LDL studies…

• I can recommend as money and time well spent going to the Feb +/- Boca Raton FL Metabolic Health conf and March ish Denver Metabolic Health conf. I see the same speakers at San Diego in a month I think. Seen similar speakers at KetoCon but I’m less keen on public facing confs. I prefer Researchers/MDs in the audience focused.

• Other threads mention some here are experiencing Poly-Pharma. Well that describes my kitchen sink protocol which I’m certain some percent for me; is counter protuctive and some not good or bad. All I can do is blood test and body scan. So far I havent given myself cancer, artharitis, pre mature death, knocked my hair out etc. I have decent blood tests and very good calcium.

I’m looking at that Millionaire anti aging self experimenter (??) and trying to figure what age tests he’s been taking. Since there’s a bunch of age tests some better then others. I don’t have personal data on my effective age or rate of aging (??). Lance Hitchings (a youtuber) is starting an insiders group so I should be hooking into my missing tests of effective age vs chronological and the latest metric; “rate of aging”. That Millionaire’s rate of aging is 0.71, his $$$ has successfully puts him as lowest ager on his website. Good for him!!!

My practice; test test test including multi-calcium tests and look for changes good vs bad, then possibly make changes.

Wishing all well, Curt

[AlexKChen]

It’s way more than artery/heart calcium. It’s also glycation/average glucose levels and oxidative stress. Glucose and cholesterol synergize in a really bad way.

High lipids are less obviously problematic if your oxidative stress and glucose are low (but we are uncertain - it’s still unclear if this is risk-free). And it may depend on whether the lipids are oleic acid.

BTW I often wonder if rebound effect when eating too much WHILE rapamycin levels are low is a problem (+justifies carrying emergency rapamycin+metformin around when traveling). Metformin, at least, could be theoretically helpful for suppressing glycative damage from glucose spikes

[AnUser]

Practically, it’s all ApoB. Impossible to develop ASCVD at neonatal/child apoB levels. Optimizing other things for this is just rearranging decks on the titanic.

[AlexKChen]

So how do MUFAs/PUFAs affect ApoB counts, especially if one nut-binges on 2400 calories at once? [and I do nut-binge frequently]…

I sometimes have LDL of 97 and HDL of 60. Which isn’t terrible but could be better, but otoh it’s better than having high glucose… (eating more nuts means more calories and higher LDL, but if it means less glycation/glucose, then I wonder if this is a tradeoff worth making whose results are simply not observable in data seen in any other model organism simply because NONE of the commonly studied model organisms suffer from arteriosclerosis at the same rates as humans [though they may suffer from effects of high-lipid consumption in other ways - and humans will suffer arteriosclerosis on top of it])

Mammals, at least, are WAY better at dealing with excess lipids (like my epic 2500 calorie almond binges) than invertebrate models of aging are

[curt504]

@AlexChen, Please search youtube for high oxalate foods, high oxalate nuts. IMHO oxalates in your almond diet have many negative consequences.

I’m concerned for the folks given bad advice and drink almond milk, eat nuts, eat alot of spinach, sweet potatoes on the basis of such items are good for you. Sally Norton wrote a book; Toxic Superfoods, recently out. We read it, now take its advice. We cut out all oxalate sources as well as most other plants. Occasional asparagus, squash.

Oxalate toxicity/poisoning mimics many other chronic problems. Aches, pains, sniffles, rough skin etc.

Hear you re binges!!! Its a challenge keeping foods in check. I used to eat nuts frequently too. Bananas like a monkey! 50% of why CGM wearers say they wear a CGM is to be a food cop. It gamifies what we eat. – Just a sec; Lemme check my glucose. - Whew 80, glad that low sugar chocolate nibble didn’t get noticed… :> :> :>

Only a thought; read Toxic Superfoods, get a month or 2 of a CGM, it may help with nut binges.

Wishing all well, curt

[AlexKChen]

Inhibiting mineral (ESPECIALLY CALCIUM) absorption is a good thing.

IDK if oxalates are problematic in other ways

[AnUser]

Your LDL is in the 50th percentile, it’s not good if only the 5th percentile does not develop ASCVD, as evident by the fact that a 0 positive calcium scan is extremely rare in higher chronological ages (advanced disease). Easiest way IMO is just try a low dose rosuvastatin at that LDL (for example three times a week / 1 mg). And test apoB relatively frequently until its stable. Not medical advice.

[AlexKChen]

Yeah, maybe I should just get some off of unitedpharmacies.md …

Why rosuvastatin over other statins? https://dir.indiamart.com/search.mp?ss=rosuvastatin&prdsrc=1&stype=attr=1|attrS&res=RC3 seems annoying

https://www.unitedpharmacies.md/Simvastatin-Mylan-Simvastatin.html seems easiest and cheapest to get

My LDL used to be in the 60s all the time (up to late 2020) but suddenly shifted to the 90s in 2021 and hasn’t budged since.

I know people on the keto diet who have scary-high ApoB. Luckily I avoid animal food.

Zoledronate seems hard to get damnit

[AnUser]

It isn’t lipophilic so it has a harder time crossing the blood-brain barrier. Cholesterol synthesis in the brain is closed from the rest of the body. Speculatively reducing brain desmosterol might be bad for cognition in the long run. The point of the statins is to prevent atherosclerosis in the heart and elsewhere, not specifically the brain.

Genetic variation with chronological age is probably why, you could upload genome data in 23andme to Nebula and check your polygenic risk score (percentiles) for apoB etc. Also LDL is not perfectly correlated with apoB, that could be lower. But the important thing is apoB number.

[scta123]

I would first try ezetimib (as independent therapy / usually is used in combination with statins). It is reducing the (re)uptake of cholesterol in gut and it works mostly non systemic which is IMO better than starting statins first (which have quite a lot possible side effects). You can use ezetimib intermittently every other day. If it is not working well enough you can add for example rosuvastatin in the days in between as @AnUser suggests. I agree after researching statins that rosuvastatin might be a better option over other statins. This is also not medical advice.

[AlexKChen]

Okay thanks for all the advice! My PRS for apoB is fine.

Are spikes in apoB almost as important as just fasting apoB?

[AnUser]

I don’t know anything about spiking apoB, technically if it’s just short, it wont do as much damage as if it was longer. ApoB compounds risk over time, that’s where the effect is. But that’s a question for Allan Sniderman or Thomas Dayspring.

[Ericross2]

If “G6 / G7” comment referred to the continuous glucose monitor, my limited understanding (from my daughter’s CGM usage and my monitoring it in real-time) is that the G6 is bigger and older, but is set up (and FDA approved) to wirelessly interact with the insulin pumps. The G7 isn’t yet approved to interact with the insulin pump (although I believe this is coming soon); this could be part of what is considered “better” about the G6 although you may not need that capability. I believe the G6 is bigger simply because the electronic components are several years older, not that it has less functionality. I’m sure the software has been very slightly updated but given the general coding-laziness of medical device companies, I can’t imagine a serious functionality overhaul was done other than user-interface; even the app is minimal and less impressive than what my daughter has coded for iPhone apps. I

f I recall what we were told, the actual sensors (the wire you insert into your skin) are the same so they should be equivalent (please check this: we were told this by the trainer PA/RN, but could be wrong). Also understand that these units are installed in different locations on the same person each time (to minimize scarring) and each person has slightly different skin, and the insertion process is “easy” but clearly subject to variability, so some sensor variability is expected: we were told there is a 20% error normally, meaning if you have a blood glucose reading of 120 it could be 76 or 144: the trend is considered more accurate (and useful for diabetics). That being said, I assume errors decrease with smaller blood glucose numbers so the errors must be tighter at 120 than they are telling us (76 to 145 is a big difference while 200 to 300 isn’t that much of an actionable difference — you need more insulin!). I’d again check this because that is what we were told. However, these things are VERY cool tech and certainly would tell you a lot about your metabolism, particularly when combined with instantaneous continuous heart rate and maybe pulse/blood pressure. I understand there is a blood glucose/ketone CGM in the works as well.

[John_Hemming]

I am not diabetic and monitor glucose to know what makes it work better. However, I do see what is said in places such as the reddit Dexcom forum which is where I saw comments about the G7 being less reliable.

I have used G6 and G7. G7 did flatline quite a bit when I was drinking alcohol. Freestyle went low, but not as low.

I don’t know, however. I don’t fingerstick to test against it because that is also unreliable (I did do it a couple of times in early 2022, but I only used two sessions in 2022 I let someone else have my third.).

I use a fitbit for heart rate and I must admit it is nice seeing the glucose and HR figures together. You can to some extent spot the switch from parasympathetic to sypmathetic mode (particularly at night).

I think the error is normally more like 10%, but whatever the error it I find it really useful information.

[Olafurpall]

Oxalate toxicity/poisoning mimics many other chronic problems. Aches, pains, sniffles, rough skin etc.

Please provide peer reviewed evidence for this claim. Not that I have looked into it, but I have never seen any good evidence of dietary oxalate being harmful other than by being able to form kidney stones. The only people I have heard say oxalate is toxic and can cause a lot of harm other than kidney stones are people that don’t know much about biology and often get their information from dubious non-scientific sources.

[curt504]

Hi Olaurpall and others.

Its easy to google oxalate toxicity, symptoms. Its been an inconvenient truth so really hasn’t gotten much up take or dissemination in the clinic or foodie groups… ;( This recent author has sever sensitivity herself so packaged it all up:

Sally Norton; Toxic super foods. on amazon. We read it, removed offending vegetables and our gut aches went away… ;( Which lead to removing most vegetables for me sadly.

Removing oxalates was just a side effect of increasing protein to retain muscle, avoid sarcopenia, per many current practitioners including Dr Gabriel Lyons, 1.6gr/body kg/day. FYI Beef is 30% protein.

My ability to eat volume has dropped (for some reason) and to get in my min 138gr protein/day I had to remove things that took up space like vegetables, salads etc. It a problem for me on TRE time restricted eating, my lower volume per eating session, and needing 138gr x 3x (30% protein) meat per day, AND a hiatal hernia that really slows me down swallowing when including alot of water to wash stuff down. I can squeeze but a bite of asparagus, krout etc down plus my meat. On low-carb out went sweat potatoes, cashews etc. So oxalates have gone to near zero. I miss the salted roasted cashews!!! Almond milk has big risks re oxalates.

I’m on the kitchen sink pills protocol and make up for any minor nutrient loss. My other studies of nutrition finds the nutrient density of store bought vegetables is quite low and suspect the nutrition tables today for vegetables is way high. I’m planning on taking the spectracile micro nutrient panel as a circle back on my whole diet, pills included.

My comments that vegetables are not without their own risks, side effects, and issues is also in play with all of these nutricals, protocols. My wife (got 1/2 way through Chinese medicine school) beats me over the head with my kitchen sink list; nothing comes free, all foods, pills, nutricals are “drugs” and have costs. That truth doesn’t even consider drug (nutrical) interactions!!! :<

Its skull exploding complicated. IE the U shape benefit curve (often its also per the individual, gender, weight) thats in play for many of these nutricals.

I’m just plodding along like everyone here.

Good luck to all, curt

[dominus]

I’m not trying to stalk you but I saw that you had a calcium score of zero in June 2022. Did you have a higher score prior to taking rapa?

Also is the 36 to 38mg of rapa in this comment calculated due to drinking grapefruit juice?

Thanks

[Agetron]

Hey Dominus - not a problem… stalk away… hahaha.

Correct in June 2022 I had a score of zero - see below.

I have been on rapamycin for 2 years at that point. It was my first Coronary Calcium Scan ever - I did it as a results of those on this site recommending it to know what is going on. I turned 65 years in late April. I eat steak every other day, whole milk , cheese lots of satruated fats. No issue - I even have hereditary high LDL-C 140 average – familial hypercholesterolemia. Still good.

No doubt my veins have opened and are enlarged since on rapamycin. Varicose veins have diminished and not progressed. There is some speculation that rapamycin might be able to reduce atherosclerosis… there needs to be trials. I can feel and hear my blood pulsing throughout my body since on rapamycin. We know it does improve the heart’s left ventricle function - so who knows. More research needed.

And yes the 36-38 ng/mL was my c-max in my system of 6mg rapmycin with one fresh squeezed Red Grapefruit…GFJ. attached with my Labcorp test of 9mg with GFJ - I got a high 6-7 times increase in the dose.

[Agetron]

Again - much more needs to be tested, but results are encouraging for stopping the advance of atheroscleurosis. Maybe more?

Link: Rapamycin: A Bacteria-Derived Immunosuppressant That Has Anti-atherosclerotic Effects and Its Clinical Application - PMC

“Rapamycin inhibits the formation and development of atherosclerosis (AS) by promoting vasorelaxation, inhibiting monocyte recruitment, inhibiting VSMCs de-differentiation, reducing inflammatory immune response, decreasing foam cell formation, inhibiting platelet activation, enhancing autophagy, and inhibiting senescence and apoptosis.”

[John_Hemming]

I think Atherosclerosis is partially senescence driven. Hence you would expect Rapamycin to help.