Three Thoughts Update
As I reflect back on these almost 3 months of Rapamycin usage, three thoughts occur to me:
1. Low dose effectiveness?
I keep harkening back to my experience early on, where a single 1mg dose gave me a canker sore and seemed to shake up my system over night. Other effects seemed to mount in those early weeks, including reduced shoulder pain, improved gum health, and another canker sore.
What’s interesting to me is that all of this occurred on really low doses of 1mg/week, then 2mg/week, then 3mg/week. By week four I was seeing these changes.
I weigh around 185 lbs. and I’m shy of 50 years old. I wouldn’t have thought that such low doses would register in my biology at all, and yet they did.
This makes me wonder if low doses of rapamycin might actually be effective doses. More significantly, it makes me wonder if low doses of rapamycin might actually be more useful and more health-inducing than high doses.
Obviously this flies in the face of the research we’ve all read, where more is always better if you’re a mouse.
Several hypotheses might be that our systems are more sensitive to rapamycin, or that too much rapamycin creates some push-back in the body, or that it’s useful to give more time between MTOR regulation.
Another hypothesis would be as follows in item #2.
I’m certainly not advocating for low doses or suggesting that I know better than the experts researching these things. I just find it fascinating that low doses had a large impact on my heath very quickly, whereas a dose of 7mg seemed to be met by a giant “huh” by my body. Then again, who is to say what might be happening beneath the surface where I can’t see?
I’m tempted to return to low doses for a few weeks to see if anything changes. I’m also tempted to try one or two very high doses to see what I might feel, as I mention in #3 below.
2. Side effects as Purification?
As I think about my experience above, one explanation could be that my MTOR was out of control and rapamycin shocked it back into balance.
This would follow the overactive-MTOR1 theory of aging, which suggests that as we age our MTOR1 gets stuck in the ON position. Since deactivated MTOR1 engages cellular cleansing mechanisms, an overactive MTOR1 would keep one’s body from effectively cleaning up cellular damage.
So my thought, my curiosity, is that perhaps even those early small doses were enough to shock my MTOR1 into a level of cleansing that it had not done in a long time. In such a situation, I might imagine that there was a lot of cellular garbage that needed to be taken out.
Thus, I wonder if rapid rapamycin “side effects” like a canker sores, and rapid rapamycin “effects” like immediately improved gum health, might come from that sudden spring cleaning of the cells.
To my mind, I might liken this to a “purification effect” of rapamycin, or even a “purification hypothesis” of rapamycin usage. By this hypothesis, the longer you use rapamycin, the fewer effects you will see, because it is purifying your system. Early purification efforts will find lots of cellular garbage, so early effects will be strong. As the garbage is collected and removed, the system becomes more and more pure, or balanced, or as-intended, or whatever metaphor you want to use. Thus, even more rapamycin might not cause such side effects, and might not cause such obvious or immediate changes.
This also aligns with some of the research I’ve read on this page that suggests that mice that take rapamycin for only a period of time (I can’t recall the period, but let’s say 6 months) and then no longer receive rapamycin continue to have longevity effects and health effects for the rest of their lives.
One might imagine that once you get your cellular garbage cleaned up, it becomes easier for the body to maintain that state as it is not working against a backlog of garbage, but only has to deal with the new stuff.
It’s just an idea.
Also, I’m aware that it contradicts some of the ideas in the previous section, in the sense that it’s not that low doses are more effective than high doses, rather the early low doses were dealing with a high level of cellular garbage so they made a large immediate impact.
3. Really high dose?
This leads to my third thought. I’m beginning to wonder if I should take at least one really high dose.
The goals would be:
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To shock the system into some major cleaning, beyond what has been done by standard rapa dosing before.
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To potentially pass the blood-brain barrier at least once, which I read is more likely or more effective with higher doses.
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To see if high doses cause any immediate changes, good or bad, to my physiology.
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To approximate the very high doses that made a large impact on mice in some studies.
In the plan I’m formulating I would not take multiple high doses, I would take 2-3 weeks to allow for a reset before another rapamycin dose, and I would probably accomplish the high dose with grapefruit as a multiplier.
Therefore, I might take 4-6mg, once, with grapefruit 3 hours before and with the dose, and wait 3 weeks before another more regular dose.
Obviously my definition of “very high dose” is not an insane level. I think the most I would be comfortable with is 20-35mg. Since grapefruit can multiply the effective dose by 3.5-7x (by increasing bioavailability through improved absorption), that leaves me at the 4-6mg level.
I’m not set on it. Just something I’m thinking about.
Inevitably, I feel I’ll settle into something like 8 mg/14 days. A period of 10 days is 5 half-lives and therefore probably the right length of time for the average person to get rid of all the rapamycin in their body. Ten days is inconvenient when it comes to following a schedule, so I’ll probably stick with 14 days.
(Since 1mg of rapamycin had such an impact on my body early on, I’m counting even 0.5mg of rapamycin in my body as an effective dose. Therefore I’m not yet comfortable with a weekly dosing schedule. Since it’s by-weekly I figure the initial dose might as well pack a punch, even 8-10mg.)
My Partner and My Dog
My partner has finished her course of the anti-fungal. We now have a new device in the house, an in-shoe UV zapper with opaque bags for the shoes and a 15 minute timer. She’s dead set on not having this return.
With her course done, she took 4mg of rapa this week and got her period on day 2 or so after the dose. She said it was uncommonly light, but increased a bit after 4 days, which would have been rapa-dose-day 6. Recall she’s been taking roughly 1mg/week for the past 6-8 weeks.
Our dog is still happy as a clam. Still taking 3mg a week in some “Kong Easy Treat” which is a spray goo that she loves and which easily hides pills.
I took 7mg two weeks ago with no ill effects or obvious effects of any kind.
We’ll check back in a few weeks. Feedback, thoughts, and opinions are always welcome!