Thread by @mkaeberlein

Genuinely surprised at the response this Tweet is getting and how many folks were unaware of the data showing caloric restriction is not universally beneficial. Many people assume these diet interventions have no risk, which is obviously false /1

https://twitter.com/mkaeberlein/status/1438965248204042243

I’m not trying to bash caloric restriction/intermittent fasting/time restricted feeding. The science is important, and I think many people obtain health benefits. Although those who would probably benefit most are least likely to actually practice them IMO /2

I would suggest that the risk profile for diet interventions is significantly higher than commonly appreciated, including adverse psychological effects. The impact of individual genetic and environmental context is not understood /3

The disconnect I struggle with is that we often think of drugs as much riskier than they are and dietary interventions as less risky than they are /4

I think it’s interesting to consider the actual relative risk/reward ratio of something like low dose rapamycin taken once each week compared to intermittent fasting. If you are scared by rapamycin, substitute metformin. The point is the same /5

The perception is that the drug is much riskier, but I’m not convinced that’s true. Personally, I’d *guess* that the likelihood of adverse events is higher in the IF group. Benefits in people are also better established for IF given the lack of data for the drug /6

My point here is to try to step away from your preconceived notions and consider the actual biology. Why would you think that periodic inhibition of mTOR from rapamycin (e.g. 1x/wk) is riskier than periodic inhibition of mTOR from IF? /7

*Probably* IF inhibits mTOR more than low dose rapamycin and does a bunch of other stuff, some of which might be good, some of which might be bad. Both have nasty side effects if taken to extremes /8

It’s not obvious whether the risk/reward favors fasting or low dose rapamycin at this point. My intuition is that it favors rapamycin, but I admit a bias away from restricting myself from good food /9

I also don’t know which individuals will benefit and which will be harmed, which is why I try hard to stay away from making recommendations about what other people should do 10/10