From the lens of the mTOR model -- if you just eat a lot of food all the time, mTOR is constantly agonized and your body consistently operates in anabolic mode. Periods of fasting (either explicit through hours/days without eating, or implicit through low calorie diets, or synthetic via metformin or rapamycin) allow your body to enter catabolic mode and tear down aggregated and misfolded proteins. Recent Noble Prize winner Yoshinori Otsumi discovered autophagy does that specifically. [1, 2]
As a SWE/EE I tend to look at things through that lens, and it seems like most processes in the body are AC coupled. DC signals tend to get filtered out and not recognized properly. Lower calorie diets and fasting convert mTOR agonism from a DC signal to an AC signal and it's the periodic alternation of modes that keeps you healthy. Periods where you can tear down the broken and periods where you can rebuild.
Another example, people look at stress hormone cortisol as leading to central adiposity in the context of insulin resistance. This is fundamentally backwards - cortisol is a potent insulin antagonist, it's a catabolic hormone that prevents insulin secretion, disrupts insulin signaling and mobilizes stored fat. The problem is when it's constantly elevated (DC signal) it stops working, and the opposite happens.
mTOR inhibition also modulates the immune system and suppresses hyperimmunity. This reduces inflammation (via Hypoxia-indidible factor 1-alpha / HIF1A and several downstream processes). Which explains why metformin reduces inflammation too. Even more interesting is that inhibition of mTOR in the AMPK-mTOR-HIF1A pathway makes vaccines significantly less effective.
I walk first thing in the morning before eating. So that’s fasting exercise. It’s definitely pulled down my pain levels enough that I’m putting off medical intervention for now. I do need to go in anyway because I want to see where my A1Cs are. I was flirting with the lower edge of the danger zone a few years ago.
My first quibble is: honestly an 8 hour window for eating is pretty large, that's like, late breakfast, lunch and dinner. Is that fasting? It seems like kind of a normal eating schedule.
My first thought when I read something like this is "why would it be severely detrimental" and the first response is "the kind of people who are overweight are the ones who are going to be trying new diets to lose weight, and being overweight in the first place is severely detrimental to lifespan." Controlling for that, there may be something further confounding, for instance.
People skip breakfast all the time, and skipping breakfast leads to a 60% increase cancer risk. Peter Attia has a writeup on this [1]. Turns out, the people who skip breakfast are far less health conscious. People who skipped breakfast were 3X as likely to smoke. As he says, 'health and lifestyle characteristics between groups can either mask or exaggerate the association between frequency of breakfast consumption and mortality.'
I'd be very surprised if a kinda normal ish eating schedule led to a materially worse outcome when properly controlled. But proper control is damn near impossible in nutrition studies.
>My first quibble is: honestly an 8 hour window for eating is pretty large, that's like, late breakfast, lunch and dinner. Is that fasting? It seems like kind of a normal eating schedule.
Even worse, they define, "time-restricted eating" as being up to 12 hours!
>Time-restricted eating, a type of intermittent fasting, involves limiting the hours for eating to a specific number of hours each day, which may range from a 4- to 12-hour time window in 24 hours.
Thanks for the insight - especially that bit about skipping breakfast. I've seen that kind of silly conclusion from poorly controlled data in studies in my field, apparently I am blind to it in other fields.
Fasting increases nitric oxide levels. Maybe that's bad for people with existing cardiovascular issues? Probably the same people who would try intermittent fasting- it's a relatively bigger population. Of course you have to balance that against complications from being overweight.
Nitric oxide actually dilates your blood vessels, reduces blood pressure and improves cardiovascular outcomes. [1] Water fasting for a couple of days brings your systolic and diastolic numbers waaaaay down over 10 days.
> The average reduction in blood pressure was 37/13 mm Hg, with the greatest decrease being observed for subjects with the most severe hypertension. [2]
It's probably just a poor job of controlling variables in the study.
As a SWE/EE I tend to look at things through that lens, and it seems like most processes in the body are AC coupled. DC signals tend to get filtered out and not recognized properly. Lower calorie diets and fasting convert mTOR agonism from a DC signal to an AC signal and it's the periodic alternation of modes that keeps you healthy. Periods where you can tear down the broken and periods where you can rebuild.
Another example, people look at stress hormone cortisol as leading to central adiposity in the context of insulin resistance. This is fundamentally backwards - cortisol is a potent insulin antagonist, it's a catabolic hormone that prevents insulin secretion, disrupts insulin signaling and mobilizes stored fat. The problem is when it's constantly elevated (DC signal) it stops working, and the opposite happens.
mTOR inhibition also modulates the immune system and suppresses hyperimmunity. This reduces inflammation (via Hypoxia-indidible factor 1-alpha / HIF1A and several downstream processes). Which explains why metformin reduces inflammation too. Even more interesting is that inhibition of mTOR in the AMPK-mTOR-HIF1A pathway makes vaccines significantly less effective.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329718/
[2] https://www.nobelprize.org/prizes/medicine/2016/press-releas...