Yes, an increase in resting HR makes sense intuitively (though I’ve not noticed a difference in the 6 to 10mg range)…
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Guywholikessleep, some things that help my cholesterol numbers are decreasing my intake of saturated fats, hydrogenated vegetable oils, and highly refined oils such as canola oil, corn oil, soybean oil, etc. Then, increasing my intake of extra virgin olive oil (cold pressed), cold pressed virgin avocado oil, and cold water fish such as salmon and sardines for the omega 3 oils. The supplement pantethine can also reduce LDL-C. Research clinical trials and you’ll likely find information on pantethine.
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My RHR pattern seems unmistakably correlated to my rapamycin intake. I take 10mg with a full grapefruit night before and one hour before on a two week cycle. Here’s my RHR pattern over the last 30 days.
Each sudden spike is a rapamycin day. RHR then gradually declines, regardless of my workout. Yesterday, for example, was a development (hard) day with heavy lifts at lunch, a swim in the afternoon and BJJ in the evening. Normally that would raise my RHR the following morning (today), but with rapamycin it seems that the entrainment to rapa drowns out training-based fluctuations. It’s actually confusing my recovery app, as there’s no way I should be at 88% recovered after a triple-workout day.
Before starting rapamycin, my RHR was in the 53 to 58 range (I’m naturally a power guy, not a cardio guy), but since then it’s in the 70s the week after a rapa dose, and in the high 60s as I’m getting closer to a trough. It took me a while to parse this out because of several heavy confounders (covid, plus my wife’s death) that also increase RHR and decrease HRV.
But given the two-week pattern that’s emerging, I’m getting increasingly convinced it’s the rapamycin. I’m going to increase my washout to 3 or 4 weeks this cycle and see what happens.
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Wow - thats a surprise and counterintuitive. I would expect the opposite. We “know” that Rapamycin helps the heart in many ways… and that lower Resting Heart rate is “usually” a good thing (and increased HRV). So I would have expected RHR to go down with rapamycin, not up.
By the way - do you see or track any changes in HRV (Heart Rate Variability) while on Rapamycin? Any correlation to changes?
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Yes, my HRV is correspondingly lower (worse).
I was surprised as well, which is why I initially sought other explanations. But the near-precise match between my rapamycin cycle and my RHR fluctuations has changed my mind.
It’s notable that my RHR seems to improve near the end of each 2-week cycle, suggesting that any negative impacts are transient–though there also seems to be a bit of a cumulative component. At 10mg + grapefruit the effective dose of 35mg is quite high, so I’m looking forward to seeing what a longer washout period does. Based on what I see, I may switch to a 3-week rapamycin cycle.
So - you’re using this to track RHR, etc. - right?
Anyone else tracking RHR and HRV and have any details they can report?
Yes, I’m a big fan of Joel Jamieson and Morpheus for recovery. I was actually an early beta tester, going back to Joel’s days training MMA fighters. At 50, most of my exercise programming revolves around managing recovery.
He has lots of useful articles at 8weeksout.com for anyone interested. Though they’re all oriented around performance rather than longevity, recovery acts as a bridge between those sometimes-conflicting spheres.
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My Oura data doesn’t show any correlation between rapamycin and RHR or HRV but 10mg with GFJ (if the ‘multiplier’ effect is real) is significantly higher than my current 6mg/week. I would be very surprised if an effective dose of 35mg doesn’t cause microcytosis. As the research paper up thread states it was a common side effect at 14mg/week.
As I’ve said elsewhere I dropped from 8mg last month as I felt even that was causing mild anaemia.
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@Boldi Interested to understand why you’re taking such an aggressive dosing strategy despite this data? What led you away from a 6 - 8mg/wk stand alone dose?
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That’s a good question. It was a combination of Blagosklonny and others moving to higher doses less frequently, an absence of more obvious side effects, and (if I’m honest) a slight non-rational discounting of the GFJ effect. I doubt I’d pop 35 mg of Rapamune, but 10mg plus grapefruit the night before and morning of seems less of a hill (and less expensive).
I do need to reconsider. Either drop the grapefruit, decrease the dose or increase the washout.
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I have read that although statins help lower cholesterol, they may actually INCREASE LP(a).
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I’m on the same jouney. I just had bloodwork done for the first time at age 40. Turns out I have FH, my apob 175 and ldl-p 3143 numbers are sky high. Otherwise I’m in great shape and health. Was just placed on Rosuvastatin and my doctor says that after a checkup in three months they will probably add a repatha because a statin alone wont get me to where i need to be.
I went down the rabbit hole on cholesteral and heart health and can say the most recent podcast with Peter Attia and Tom Dayspring is very informative regarding the most up to date treatments for lowering apo b. All of peter attia’s interviews regarding heart health are worth listning to and will greatly inform you for how to speak with your physician
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@Maveric78 Yes, I did. I took a 6 week rapa vacation. During that time my HR gradually decreased to the low to mid 60s, which is still 8 to 10bpm higher than it had been before starting rapamycin. But the 2 week HR pattern/cycle in my screenshot above broke very noticeably.
I restarted end of July. I’ve only had two cycles since the rapa vacation, one at 7mg an hour after a whole grapefruit, the next at 8mg + g. My HR is again inching up, but I’m particularly overtrained right now so it’s difficult to say. The clear-cut HR cycle hasn’t re-started yet.
My current take-away from this is to confirm in my own mind the need for periodic rapa vacations. Something along the lines of 6 months on, 6 weeks off, repeat. Plus to keep a bit lower. I don’t intend to go above 8mg + g once every two weeks.
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One interesting twist from my last blood test is that my testosterone is quite high, with total T above the normal range. I’m happy with that, but it’s surprising at age 50 with no TRT, etc. It would also suggest that stress isn’t the cause of my higher heart rate or lower HRV, since stress tends to decrease T.
I do get a lot of sunlight, sauna and exercise.
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Thanks for the update. Your testosterone data looks promising.
@Agetron ‘s recent data shows that GFJ can multiply blood levels >3 times so your original 10mg might actually have been the equivalent of >50…
I’m interested to know who here is taking over 10mg per week of actual Rapamune (powders have lower bio availability) without GFJ.
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I have been taking powder rapamycin with coconut oil in my coffee since Dec 2021. I had been training 11 weeks for a sprint triathlon event that I competed in late July. I took 6mg/per week for the first 6 weeks of training and 5 weeks off rapamycin before the event. I felt ok training with rapamycin but it does impact my sleep for a few days. Rapamcin doesn’t seem to impact my resting HR.
During the 5 weeks off Rapamycin:
- Resting HR (taken upon waking) decreased from 50 to 42 bpm.
- Recovery rate from hard workouts subjectively seemed much easier than I have experienced over the past 20 years
Race Results:
- Improved finish time by 4 minutes over the last time I did the triathlon 3 years ago in 2019 (86 minutes to 82 minutes)
- Improved finish rank also - 65th of 180 m/f finishers. 2019 rank was 122 of 230 m/f finishers.
I had an annual physical 2 days before the triathlon. BS and Cholesterol were slightly improved and in the normal range. I also had a testosterone test done for the first time to establish a baseline. My results are very similar to Boldi’s. At age 67 I thought it odd to have such high levels.
I was surprised at the improved results given I have not done any races or hard training since 2019 and expected to be pretty gassed. I am 3 years older also. I will consider doing the same type of on/off rapamycin dosing when training for similar endurance events in the future.
Note - 17 days after the event, my morning resting HR is back to 50. I still workout but the de-training effect is pretty rapid. I will go back on rapamycin in a few weeks for 6 weeks and take another break from it.
Note - There were only 9 m/f competitors in my 65 and above age group out of 165 total racers. Where is everybody? Playing pickle-ball? 
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@Bettywhitetest that’s fantastic, and interesting info–thank you for sharing!
One thing I should add. If the increased HR really is due to lower MCV (I exchanged emails with Matt Kaeberlein and he agreed this could be the mechanism) then a full rapamycin vacation would have to be close to 120 days to fully change over red blood cells. I don’t want to go that long.
But a question that’s come to my mind since then is that if rapamycin shrinks MCV, then I wonder whether it has similar effects to training at altitude, where the body compensates for lower oxygen delivery (lower MCV) by increasing the number of red blood cells? But I’m just spit-balling at this point…
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I was thinking along the same lines that endurance training under rapamycin could be similar to training at altitude. I wasn’t thinking to the direct effect of lower MCV (mean corpuscular volume) and just the generalized training effect and recovery being enhanced in some way.
I am not even close to doing the endurance training hours you put in weekly. Training for the much shorter sprint triathlon is about as hard as I push it. I generally do 5k races here and there but am active daily with strength training, and hobbies like hiking and downhill skiing. My guess is rapamycin had some impact on recovery at my training level - I typically would be pretty beat after a race and I barely felt any impact this time.
Please update us on how your resting HR and recovery from over training does as you reintroduce rapamycin into your schedule.
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