You may want to consider getting your apob way down.
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RPS
#19
It’s on the way down and still work in progress.
I suspect it would have been lower if the lab had used the blood I’d given the week before generating all the other great lipid data, rather than straight after going on holiday vacation where I enjoyed a lot of probably very unhealthy food!
Anyway, aiming for a lot lower by the time of my next test.
RPS
#20
Have started a new protocol that really tries to emphasise pulsing as many things as possible.
(Edit: please note the pharmaceuticals indicated at the bottom are taken every week not just in week 4. This was a last minute addition at the bottom as an afterthought for completeness).
I appreciate the negative effects that @desertshores and @Agetron have seen with high dose rapamycin (and subsequent positive ones of the 6mg per week variety) and having originally started out on 10-12mg fortnightly, and subsequently moved to 6mg weekly, (not noticing any particular effects) I have now moved to this 8+3+3mg over 3 days (hopefully not too long to induce mTor2 inhibition?) once every 4 weeks as an n=1 experiment to see if I notice any calorie restriction mimetic effects without having to do any 3 day fasts where I felt in the past I was losing too much muscle mass (my fat % as per DEXA hovers around 10% which probably explains the muscle mass loss when fasting).
If I feel no effects and it’s detrimental on other markers I will report back and go back to 6mg weekly.
Starting position is an Hba1c of 36mmol/mol or 5.4% which is completely unchanged from my pre Rapamycin days, and an ApoB of 0.85 which has been trending down since first measured pre Rapa at 1.62
All other biomarkers are in a good place.
Thanks to everyone here for all the pointers, especially @SilentWatcher @约瑟夫_拉维尔 @John_Hemming @desertshores @Agetron @DeStrider @adssx and @teumessian-fox
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@RPS, thank you for posting this plan. I appreciate you sharing your combinational approach; it looks really well thought out and interesting — definitely triggering some thought processes on my end!
Tongkat Ali: I’ve seen this recommended many times and it makes sense to consider it around weightlifting days due to its potential benefits in boosting testosterone and enhancing performance.
Ca-AKG: May I ask for the reasoning behind including it with weightlifting? Does it not activate the AMPK pathway, which is typically associated with catabolic rather than anabolic processes?
Also, the pulsed intake of Telmisartan/Bempedoic Acid + Ezetimibe within one week is very interesting. I’ve also pondered what the optimal combination might be for these compounds? Is the positioning within one week rather empirical, or are there some deeper considerations behind that choice?
Looking forward to hearing about your experience following this great strategy!
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@RPS I like how your mind works. Make sure you are clear on your goals. At 10% body fat you are at the low end. If you are not putting on muscle (if that is a goal) you should consider more protein and then more calories. If more muscle and slowing aging are in conflict, I’d add the muscle and then hold it while emphasizing the other goals. The key with muscle is to avoid falling so low that you lose the ability to get back what is lost in a “catabolic crisis” (illness, surgery, etc).
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RPS
#23
Firstly, sorry for the wrong impression, the daily pharmaceuticals are taken every week. It was just written at the bottom for completeness as an afterthought.
Interesting though that you think about even pulsing these. Maybe one to ponder about for the future though.
Re the Ca-AKG, I’ve been in 2 minds about this one having read somewhere that it is a useful weightlifting boost. I’m working my way through a 120 capsule bottle. Once done, if I don’t notice any drop off in performance I will drop it.
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RPS
#24
I’ve been doing the weight lifting for 35 years. My fat % has always been on the low side despite eating (what looks like) enormous amounts of food every day.
I feel strong; I’m close to all time personal bests on the strength side, but being 55 now I noticed a real dip in strength when fasting and I just want to maintain the current strength levels for as long as possible. (And who really wants to fast for 3 days anyway - it’s not my idea of fun!!)
(I’m now more wary about pushing it too heavy as injuries as a result have become all too frequent).
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@RPS Awesome. To avoid injuries I do 3 things in the gym:
(1) I back off (stop the exercise immediately for the day or skip an exercise for a day) if I feel a muscle or tendon is “not right”
(2) I start with a warmup set for every muscle group
(3) I go for high reps to failure. I NEVER do a weight that I can’t lift 10 times in a set when fresh. A 30 rep set is not unusual but I aim for 15-20 reps.
I’m not going for max strength or max muscle size. I just want high stimulus to my body.
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RPS
#26
Goals are simple - remain fully functioning in body and mind for as long as possible.
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RPS
#27
I’ve always really enjoyed trying to push the 1rep max personal bests and I know I need to get away from this now to avoid the injuries.
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I have “normal” systolic BP in the morning (120) and “elevated” (130) during the day. I am considering including telmisartan into my regimen and have found consistent studies showing that Telmisartan activates AMPK and Telmisartan Suppresses mTOR Activation. With that, I am tending to try a small dosage of telmisartan on my “AMPK days” (aerobic exercise + resting days after aerobic exercise) - constantly monitoring all parameters.
Any critiques on this idea? 
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RPS
#29
Interesting.
On that basis I might try 80mg on AMPK days and 40mg on the others.
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It’s almost a no-brainer for anybody older, few downsides and it may be one of the best preventative medicines you can take. I have taken it for almost a year. It has stabilized my daytime BP to between 100-100 systolic and 50 to 60 diastolic.
I have felt no dizziness etc.
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Thank you for your opinion - appreciate it.
I am continuing to study telmisartan. In light of my interest in health levels of testosterone (and considering tongkat ali as supp), I am very concerned about the effect of testosterone on benign prostatic hyperplasia (BPH). In this regard, it is interesting to see: Telmisartan alone or in combination with pioglitazone prevented the development of testosterone-induced prostatic hyperplasia.
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I think BPH is driven by splicing variations. One driver of splicing variations is (cytosolic) acetyl-CoA levels
https://www.nature.com/articles/emm201032
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On the upstream there is DHT which causes the prostate to enlargen.
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On top of my previous link about Telmisartan->AMPK->preventing BPH, there’s another study - Metformin: A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation showing:
“The occurrence of benign prostate hyperplasia (BPH) is related to disrupted sex steroid hormones, and metformin (Met) has shown clinical responses in sex steroid hormone-related gynecological diseases. However, it’s unclear if Met exerts an antiproliferative effect on BPH via sex steroid hormones. Our clinical study showed that alongside prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. Elevated dihydrotestosterone (DHT), a major contributor to this dysregulation, was significantly positively correlated with the clinical characteristics of BPH patients. Activation of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) by Met restored the balance of dysregulated sex steroid hormones and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated Yes-associated protein (YAP1)-TEA domain transcription factor (TEAD4) heterodimers. Met’s antiproliferative effects were blocked by an AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicate that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation”
AMPK activation could be key here. When AMPK is active, it helps keep cell growth in check and promotes healthy metabolism by regulating energy balance and enhancing cellular repair processes. Specifically, AMPK activation can reduce the effects of DHT by limiting the formation of AR-YAP1-TEAD4 complexes, which are crucial for DHT-driven cell proliferation. This regulatory role of AMPK might also prevent the splicing variations driven by altered acetyl-CoA levels that @John_Hemming mentioned. By ensuring adequate AMPK activation, we could potentially maintain healthier splicing patterns and cellular functions (MTOR days vs AMPK days)
In short, boosting AMPK, possibly with Metformin, Berberine, or Quercetin, might be a way to tackle BPH by regulating hormone effects and splicing patterns.
Would love to hear your thoughts!
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p.s. @John_Hemming, how activated AMPK increases acetyl-COA:
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AMPK triggers fatty acid breakdown → beta-oxidation → producing acetyl-COA
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glucose breakdown → AMPK increases uptake and breakdown of glucose to pyruvate → pyruvate converted to acetyl-CoA by pyruvate dehydrogenase
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blocking acetyl-CoA carboxylase → AMPK inhibits ACC, preventing conversion of acetyl-COA to malonyl-COA
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There are lots of things that end up.with more acetyl-CoA
