#1

I am curious about how the community here thinks about their diet while on rapamycin (especially the day of and following a dose).

It is known that rapa causes slight glucose intolerance, which means that simple carbs and sugars should be out of the picture (unless there are interventions to help with this such as acarbose).

It is also known that rapa use can cause hyperlipidemia. So it may be safer to use monounsaturated fatty acids such as olive oil and supplement with fish oil. (Perhaps it makes sense to take statins or ezetimbe while on this?)

Now proteins — well they activate mTOR while, rapa blocks mTOR. Does this mean there can be potential negative interactions? Surely protein may blunt some effects of rapa? I think it might make sense to reduce BCAAs at least (if we are to extrapolate Dudley Lamming’s research). In an old interview with David Sabatini, he had seemed to suggest that because mTOR is inhibited, protein should not make a big difference. ON the positive side, in case there are interactions, higher protein diets could potentially counteract side-effects by activating mtorc2 and may be sensible to take after a couple days on rapa? It’s all puzzling to me.

Right now, I just make sure to take a lot of fiber before food, because this would slow the absorption of all these foods and arguably reduce any negative interactions. I previously used to take rapa occassionally in combination with a fast. So, I realized that I had never thought of rapa’s interactions with food much. Now, I have access to rapa and everolimus after almost a year, and I’m trying to figure out how I use it — I want to take it more frequently this time around, but I don’t see myself fasting every week, for example.

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#2

The million dollar question, what offsets or turns on the benefits during the Rapa process - eat or fast, exercise or rest? (In the mice study it’s unclear to there diet and exercise regimen)

Personally, I do a long zone 2 fasted run on rapa day followed by a ketogenic meals (high fat, low protein and no carbs) for 1-3 days. Day 4-6- strength training while loading higher protein, lower fat and moderate to lower complex carbs in veggies and fiber (no starch or sugars) . Day 7 rest and cycle back into ketogenic diet.

Any recommendations would be greatly appreciated!

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#3

I like your strategy. Zone 2 and rapa may be synergistic w.r.t. mitophagy, and after having exercised, our bodies may be a bit better at glucose disposal.

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#4

KFISH, Your plan sounds interesting. Do you mind sharing exactly what your meals consist of for days 1-3 and days 4-6? I need some new meal plans.

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#5

I am on my 3rd week of Rapacan (Sirolimus). I took 4 mg with a shot of Walnut Oil in Mushroom coffee with Coconut Milk. I understand we want to take with fats to improve Rapa absorption. I also took a double shot of grapefruit juice, to slow the metabolism of Rapa. I understand this may result in 5X-15X the blood concentration, and prolong the action. I am ramping up each week, adding 1 mg. The first week at 2 mg, I did an FMD for 5 days. Lots of avocado, lettuce, and other veggies. Gazpacho soup worked great to fill me up for hours. Given that FMD also activates AMPK and inhibits mTOR, I strongly believe this will deliver the deepest Autophagy and lengthen the duration of Rapamycin effects. However, I do not do FMDs more than 1x per month, and I am on vacation this week and home with my young kids. I ate Tabouli, Hummus, Carrots for lunch. Tonight I had a few chicken wings olives and more tabouli. I suspect that Paleo Keto Mediterranean would be good diets, but we need to restrict protein to minimize the mTOR activation and Autophagy inhibition. Limiting simple carbs and processed foods seems prudent. Think about refueling the body with minerals and vitamins it needs to increase NAD+, SIRT Activation, and maximize Autophagy.

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#6

I will re-emphasize a food which I believe will be highly synergistic with Rapamycin: Mushrooms. Many mushrooms contains high levels of Spermidine, a polyamine which has similar effects like Rapamycin on Autophagy activation. Mushroom also contains Ergothioneine, a potential dual activator of SIRT1 and SIRT6. Another underappreciated mushroom nutrient is Trehalose, which also activates Autophagy, but appears to do so independent of mTOR. So Trehalose activates Autophagy via seperate MoA than Rapamycin, and in theory would be more synergistic and effective, than excessive mTOR inhibition and minimize risk of side effects such as immunosuppression.

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#7

Spermidine and trehalose are almost definitely not going to activate autophagy to any significant degree in humans when ingested, because of their poor bioavailability.

#8

Could be. The problem in all these cases is that it is often not the molecule itself that achieves an effect, but some downstream metabolite, and you don’t always need to absorb the molecule itself to achieve an effect. Many drugs, food, or food components (like fiber), are not absorbed by the gut at all, but instead modulate the gut biome, which in turn generates molecule(s) which are absorbed and have health impacts. Many drugs work in part or in whole by modifying the gut. One has to be specific when saying something is or is not bioavailable, is it present in and impacts the digestive system, present in blood, achieves tissue penetration, crosses the blood brain barrier, remains unaltered at a given stage etc.

Judging the impact of any such molecule, including spermidine is best done not by determining some mechanistic feature (like “bioavailability”), but according to the “black box” model. Feed the animal/human X at one end, and look at the outcome at the other. It’s fun, good and scientifically productive to speculate what happens inside the box, but often the practicality dictates, “what matters is that it works (or not), not how”. If it’s not bioavailable, but it works, does that matter?

There’s always the danger of getting so wedded to some model of how things supposedly work, that it blinds us to reality. There’s the old anecdote, of how a team of distiguished Prussian scientists carefully examined a bumblebee and declared that according to scientific principles, it cannot fly. The bumblebee flew anyway, but the scientists disqualified it, so there :grin:.

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#9

This would be a good way to think about them IF they work. But this is not such a case. There are no studies that show that oral spermidine or trehalose increase autophagy in humans in vivo so people are basing their hope that they increase autophagy on in vitro studies. When all you have is in vitro studies indicating that spermidine or trehalose increase autophagy, but they are not bioavailable, then it’s illogical to expect any increase in autohpagy from ingesting them. If spermidine and trehalose actually worked at increasing autophagy after ingestion, but we just didn’t know how because they weren’t bioavailable, then yes it would be reasonable to expect some metabolites to be having the effect, or the effect to be very indirect. Point is, we don’t have such evidence at all.

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#10

Rectal route I say. This way there will be no trehalase and no glucose spikes, and trehalose is small enough and soluble enough to be absorbed.