I am very excited about the future of longevity interventions such as rational rapamycin combinations. Thought this could be a good place to debate optimal longevity protocols. So here is my current protocol that I use as a 44 year old male.
5mg siromus rapamycin weekly with grapefruit
juice and 1 hr sauna before dosing with rapa.
500mg metformin with 0.2mg voglibose combo pill day of and 2 days post treatment.
Acarbose 50-100mg lunch and dinner daily. I do not eat breakfast so the voglibose takes care of any carbs in my morning coffee.
20mg lithium daily and 1-2 tsp glycine with 2 scoops of ultima electrolyte during sauna.
Tonal 2-4 days per week and peloton other days. Sauna after for 30-90 minutes given schedule.
I really noticed a benefit from combining sauna with rapamycin and would love to hear if anyone else has experienced something similar.
Hi - I sauna after workouts frequently, but have not considered actively tying it into my rapamycin use. Interesting idea - I’ll try to watch and see if I notice a difference if I sauna on the same days.
The Ki of lithium for GSK3 is pretty high at 2mM so a larger dose is probably required. I have not checked serum levels since the dose is very low compared to the lithium dose used for psychiatric indications. Would be nice to know what the levels are though.
My IR sauna gets up to about 145F so I usually warm it up to 120-130 then do a peloton ride or tonal workout. I finish with the sauna for 30-90 minutes.
I am not convinced that sauna triggers the mTOR pathway to a significant degree when compared to what a high leucine protein rich meal yield in pathway activation. My rationale is that the sauna induces pretty significant dehydration which hopefully aids with transport and uptake of the rapamycin due to osmotic fluid equilibration from digestive track to serum since so much fluid and salt is being excreted in my sweat. I am a person that significantly perspires in the sauna and often lose 5+ lbs. Combining grapefruit juice with rapamycin and sauna feels way better to me than taking rapamycin alone at the same dose.
I was referring to the Ki which is defined as 50% of the max inhibitory concentration not the plasma concentration target. Most small molecules have Ki values in the single digit nM concentration range which is 6 orders of magnitude lower than Li for its gsk3 binding site. Its a good metric for ranking molecules by potency. So lithium never reaches a high enough concentration for complete pathway inhibition which is probably good given the necessity for gsk3 pathway activity.
I read a paper which talked about Lithium operating in an indirect manner as well. They were doing in vitro tests in the 25mcmol-2.5mcmol range.
There is no really solid data on exactly what concentration to target, but clearly you want to stay out of the range which might cause renal issues. If I am getting 100mcmol from 5mg per day, you might be able to get 400mcmol from 20mg which is coming close to that 600mcmol threshold, but it probably isn’t a straight line relationship between dose and concentration.