Good god yes, haha. Why do you even need to ask? What we really want to know is the effects on lifespan and also the healthspan/pathophysiology.
I think the dosing stuff is as clear as we can make it. The question of how it translates to humans is the question. And I guess none of us are really experts in the Marmoset model, the typical progression of OA or aging in that model. That’s where Alex’s expertise would be most insightful.
I am much younger (39) but had an episode similar to this. It turned out to be a viral infection (parvovirus). Just horrible joint pain, stiff everywhere. I only realised because my kids both got very weirdly rosy red cheeks, and some of their classmates had the same. Some ChatGPT later, and I realised that it’s parvovirus - nicknamed “apple cheek disease”, and in adult the symptoms including sudden joint pain. Took ~2 months to fully resolve.
Could be. There also may be other viruses that attack the joints.
My symptoms didn’t improve until I started back on rapamycin, whereas the Mayo online bit suggests parovirus resolves on its own – a general statement, though, and we all know individual differences vary widely. Everolimus worked on flu virus in Joan Mannick’s study, so that could be the case with parovirus and rapamycin – it may just be that nobody’s thought to try it yet.
You got parovirus when your kids brought it home from school, but otherwise it’s rare in adults, so I’m still leaning toward magnesium in my case. Whatever it was, rapamycin is taking care of it for now. Will it come back when I take my next break?
I’m an N=1, but one of my primary motivations for starting Rapamycin was my osteoarthritis was becoming debilitating to the point that it was becoming difficult to continue exercise. After 6 months of Rapa my OA was materially improved, but not gone. At that point I added senolytics (100 mg D+1200 mg Q). I started the senolytics intensively at first (once every 3 weeks for 3 rounds over a couple months) then extended the time between doses progressively after that until now I’m on a maintenance program of once per quarter. The reason for the intensive treatment was two pending endurance events that would have been difficult with the OA. Again, N=1, but my OA fell off a cliff to where it’s all but gone now at age 64.
Rapamycin is a senomorphic, and D+Q is a senolytic. One of the causes/correlations of some forms of OA is a high concentration of senescent cells in the joint tissue and chronic inflammaging.
So anyway, this conclusion is incongruent with my understanding and personal experience, but again, I’m an N=1.
Regarding your first question, I take the D+Q between once-per-week Rapa doses - usually exactly in the middle to give Rapa a chance to tail off through multiple half-lifes while still allowing a little time in the week for D+Q to tail off before the next Rapa dose.
With that said, there’s no science or research supporting that dosing regimen. I just made it up because it was intuitively appealing. But I’m not aware of any research saying the dosing should be separated or combined. I just decided to do it that way to minimize polypharmacy risks.
Regarding your second question, I’m not aware of any research to support your intended protocol. There is a reason D and Q are combined - their effects complement each other for the most effective treatment.
The research on Fisetin alone and Quercetin alone is mixed and not convincing. I personally wouldn’t bother. However, I found the research quite compelling when the two are combined.
I would encourage you to fully examine the published research before committing to a protocol. I’m unclear why anyone would choose a Fisetin-only protocol given the ITP results and other conflicting research.
Todd, I’m thinking about the Mayo Clinic fisetin protocol. Without looking around longer than I’d like, I can’t tell you where I copied this, but it originated from Mayo, not me:
“The Mayo Protocol consists of taking 20 mg/kg body weight of oral fisetin on two consecutive days and repeating the same dose, one month later.”
and
“New Mayo Protocol - 20 mg/kg/day (this is equivalent to around 1,800mg per day for an average 180lb person) for 3 consecutive days, resting one month, then repeating this procedure of 3 days on, one month off for 5 months total. This is a substantial increase over their previous protocol of 2 days on, one month off for only 2 months, showing Fisetin is safe and effective at even higher doses than previously known.”
I also recall reading somewhere that quercetin’s slightly more complex molecular structure could blunt the effects of fisetin’s simpler structure, when taken together. However, I have seen other opinions that quercetin would enhance fisetin.
Opinions, opinions. I do plan on using them together.
I’m trying to avoid Desatinib because it is generally not recommended for transplant recipients (I have transplanted kidney) due to its immunosuppressive and nephrotoxic potential, especially in those with reduced renal reserve. And I understand that there’s no research in using only Q instead of D+ Q. So, most likely I’ll go with Fisetin protocol b rescues it is not known to be nephrotoxic and may be better tolerated in transplant patients. Fisetin unfortunately is not well researched. The 20 mg/kg once monthly fisetin protocol is based on mouse-to-human extrapolation and has been used in pilot studies and self-experiments.
I had a similar situation with a very rapid onset right before starting rapa at the end of 2022. I thought I had broken my hand. I was told it was de Quervain tenosynovitis and is common in women over 50. During that time period I had been driving a stick shift about 100-200 miles 5-6 days per week for work. I was never X-Ray’d though and the discomfort is in my left hand as well although to a lesser degree so I’m leaning toward it possibly being osteoarthritis. It’s pretty mild and I don’t require any interventions but your situation makes me think should probably get an X-ray at this point. Thanks for sharing your experience.
My pain became milder after I stopped all supplements besides D3/K2 and reduced magnesium to once/day dose. Today is my Fisetin day - will watch what happens.