Just had the thought that a natural corollary of Matt Kaeberlain’s “cure deficiencies first”, is “cycle all supplements and pharma”.
The logic would be: many drugs have side effects because they cause deficiencies. We know about lots of these, but there are also likely to be many unknowns.
So statins may effect CoQ10, ezetimibe may effect Omega3 absorption, metformin … B12 etc etc.
We can of course try to compensate directly. But that only counters known side effects. Would a better strategy be to assume that there are likely to be side effects/deficiencies that we haven’t identified yet, so we should cycle all interventions.
So we should look to treat say Apo b, or high Hba1c through as many strategies as possible cycling them on and off. Otherwise, my argument goes, with any chronic/long term intervention, we run the risk of creating deficiencies - precisely the thing Kaeberlain says we should focus on as a priority.
My bias is to avoid long term dosing of anything, so i may be simply finding some logic support my biases. The counter argument would be, i guess - that this strategy risks missing optimal targets. Also introducing any new drug intervention risks a major side effect reaction?
I do some cycling of some of my meds on an alternating day basis. Just those that may be ‘troublesome’ in their risk:benefit ratio, such as aspirin, colchicine, statin (when I eventually migrate over to rosuvastatin) etc.
In order to ‘qualify’ for alternating day basis the med must have a sufficiently long half life or have scientific evidence that the effect is still present when dosed e.o.d
One problem I had was remembering what I did yesterday (don’t think it’s Alzheimer’s) so I made a peg board to remind me where I got up to with my meds.
Although I think we should recognise a daily cycle, certain micronutrients such as Copper, Selenium and Boron really are needed at a steady state.
Rapamycin is an obvious candidate for cycling. I also cycle other things when there is a good reason, but I think this depends entirely on what the substance is.
I don’t separate out pharma and supplements from other inputs such as food. Food is, however, cycled both by fasting and by eating at specific times. Exercise is cycled to some extent.
I do think some things require long term inputs/dosing, but cycling should be considered for any intervention.
I was thinking more: cycling substitute interventions. So say, a statin for 6 months followed by 6 months of ezetimibe + policosanol each year. Assuming you can reach target apo b, that “feels” less risky than permanent use of either one (if there are no immediate side effects from any of the drugs).
Ditto Metformin and acarbose.
I think yes we should cycle for several reasons but the biggest reason is the one you mentioned:
Use as few as possible powerful drugs with significant side effects. The only way to get off a drug is to find out if you still need it. Of course if you haven’t done anything to correct the problem through lifestyle then the only alternative is switching between drugs to trade side effects. And some issues for some people cannot be resolved via lifestyle so a plan to switch periodically makes sense. Plus you might find a better (less side effects) way to solve the problem with some experimentation.
I know this conversation is very old but I was thinking about cycling and my search here yielded this topic.
I was wondering if anyone else was cycling day to day like me.
Rapamycin clearly has an anti anabolic effect which lasts 3-4 days due to its long half life. So I have devised a completely different drug/supplement intake, diet and exercise regime for those 4 days followed by the anabolic phase. The problem with a weekly dose is that I find 3 days is not enough for the anabolic recovery so I extended it to every 10 days and maybe will change to every 14 days with 10 days anabolic phase as some take it every 2 weeks.
Using AI, the multiple interventions I personally undertake ( mitochondrial interventions, muscle interventions, immune boosters or suppression like colchicine, protein intake and even intense exercise red light therapy) all come under the spotlight as counterproductive during the 4 day Rapamycin phase.
What’s everyone’s experience with these short cycles?
For me make sense, but as a longevity approach who knows? I personally, after read above paper, intent to do 2 or 3 weekly cicle and 2 or 3 bi weekly then, start againt, until news paper corrobore or not this…
These are all exceptions to the rule. It’s rare for interventions to cause deficiencies. In any case, if you take a multivitamin that covers all the bases, you’re largely protected against any such potential exceptions.
You’re missing the fact that not taking something is also risky. If something is beneficial for you for 6 months, why wouldn’t it be beneficial for you to take longer? If it’s actually overall beneficial for you for 6 months despite having some downsides, then it’s most certainly more risky and harmful for you to stop taking it than to continue taking it.
Note that things that are harmful for you usually cause harm very soon so you should either minimize the harm or accept it, if you think the benefit outweigh the harm. In case of statins reducing CoQ10, the logical thing to do is to simply take CoQ10 whenever you take statins, to minimize that downside.If your cholesterol is high without statins that can likely be good for you overall.
I’ve said before that cycling generally makes no sense for most interventions unless in specific cases like e.g. rapamycin. If something is good for you, why would you stop taking it for long periods? That’s opportunity cost. For the large majority of interventions, if you only take them half the time, you only get half the benefits.Sure, you also get half the harm, but if it’s overall harmful you probably shouldn’t be taking them in the first place.
That doesn’t make sense. You’re acting like rapamycin just does one thing, and like that one thing reaches maximal effect when done occasionally with long breaks inbetween. It’s not that simple. One of the strongest argument against your statement is all the animal studies that use daily rapamycin and show large benefits, or the calorie restriction studies showing benefits, but calorie restriction basically reduces mTOR chronically every day.
There are some studies showing benefits of more intermittent rapamycin and taking unusually long breaks is not a bad idea for people that want to be very conservative on the doses, but they are likely paying opportunity cost for that.
John can speak for himself but I understood him to refer to the mtorc1 (tissue growth) vs mtorc2 (immune system) differential effects. This is the idea that rapamycin turns down mtorc1 rapidly but only for as long as rapamycin continues to be taken. And mtorc2 is not turned down unless rapamycin is taken continuously. To get the autophagy benefit of rapamycin without turning down the immune system (I don’t need to avoid organ transplant rejection) we take rapamycin intermittently (let rapamycin get to zero in body before next dose). Has the science progressed beyond this framework?
Yes, that’s the general idea with cycling rapamycin by taking it weekly. However, John takes rapamycin something like once a month IIRC and the original poster was giving examples of cycling statins for 6 months on and 6 months off. So I don’t think he was talking about the mTORc1 mTORc2 effects specifically.
My thought was that John was probably talking about rapamycin acting mainly through increasing mitophagy (if I’m wrong on that guess please correct me John) and then thinking once a month is frequent enough to be close to maximizing those effects, which is why he takes it only once a month.
My comment refers to the fact that even if rapamycin were to mainly act through increased mitophagy and that effect would be maximized at a frequency of once a month (both of which I don’t agree with) that still doesn’t mean that once a month is the optimal cycling frequency for rapamycin, because rapamycin acts on more things than mitophagy and those other things may have maximal benefits at frequencies quite different than what is best for mitophagy.
