Good clinical study, though on a very small group, shows that an early TRE schedule will increase autophagy compared to a normal full-day schedule. Unfortunately, they didn’t also look at the later TRE schedule, so it’s hard to know if it’s the timing or the limited eating window that’s causing it. Still, it’s good to have a bit more evidence to show that you don’t have to stop eating completely for 42 hours to get any autophagy at all. Some other interesting results, too.
FYI, this wasn’t a low carb or very low carb study. Results in some areas might have been even more notable with a very low carb diet dropping insulin even further.
PaulL
(You've tried everything else; why not try bacon?)
#2
Here’s Mike Mutzel’s on the topic of autophagy. Some interesting stuff in there:
I read through it, and there are some unproven assumptions, i.e. it says, “eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.”
I’d say there’s no question about the glucose and lipids - intermittent fasting achieves this for many people. “Circadian clock gene expression” - yeah, okay… - could be. But the noted changes in the autophagy-related stuff are underwhelming, to say the least. They’re talking about people fasting for 18 hours a day, and 18 hours isn’t much more than getting the stomach empty and having the small intestine mostly emptied out (the small intestine doesn’t empty out all at once, it gradually becomes what we’d call really empty). There is the ‘post-absorptive phase’ (as Dr. Fung calls it) yet to come, glycogen depletion yet to go through, and the lion’s share of the decrease in insulin and increase in glucagon yet to be obtained, as well as the supression of mTOR and the activation of AMPK - which, under favorable conditions, really only get going during the second day of fasting.
Totally agree - I have to think that’s true. Eating very low carb should put one ahead of the game with glycogen depletion. Still - what’s really going to happen as far as autophagy within 18 hours? It reminds me of some of Dr. Longo’s stuff ("Fast Mimicking Diet’ et al) which is really tenuous as far as autophagy, if not just outright wishful thinking; and a few of the references involve Longo. mTOR, AMPK, insulin and glucagon are the big players as far as the upregulation of autophagy due to nutrient deprivation, and the big gains there occur over days of fasting.
Those weren’t assumptions. Those were the conclusions from their testing. Yes, it was a very small test group, but those were the results of the blood tests they did on people at the end of the fasting period compared to those who weren’t fasting.
I don’t see them arguing that this doesn’t happen, that autophagy won’t continue to increase. They’re simply saying that in people doing eTRE that there’s a 22% increase compared to people who are eating on a regular schedule.
Apparently a 22% increase according to this study.
I love for them to repeat this with a larger group and also compare later TRE (which is more common) with the eTRE and regular 12-hour eating.
Yes they were assumptions - the researchers know that what they observe in the blood does not translate on a linear basis to the actual number of autophagosomes, lysosomes, etc., and that’s why they said, " may also increase autophagy." They’re being careful to be factually correct.
It’s not nearly that simple. Look at the chart they gave:
Only 1 of the 5 had a meaningful increase, to start with. So do we divide by 5 and average it out to 4.4%? There is also the matter of nonlinearity and that to an extent they would be trying to work things backwards (if they really asserted increased autophagy rather than just saying “may increase”). It’s like Longo’s ‘FMD’ study and the p62 protein (also known as SQSTM1). While it’s true that when increased autophagy is present, p62 levels rise, that does not automatically mean that higher p62 means increased autophagy.
A lot of our newly-made proteins are messed up, like 30% or more (surprised me):
It’s the the ubiquitin–proteasome system that takes care of most the newer and shorter-lived proteins that are screwed up, not autophagy. p62 is involved, but this is proteasomes at work, not autophagy, and as far as I can tell, Longo et al just glossed this over, pretending to an extent that it was autophagy occurring (while eating the ‘FMD’ calories and nutrients).
The same thing applies to LC3A - it does not, by itself, get us to autophagy. The LC3s do matter - they make parts of the membranes of autophagosomes - but while the stage may be being set for increased autophagy (and I do think that operates late in the first day and into the second day of fasting) in no way does an observed increase in one thing (LC3A expression, in this case) mean the same percentage increase in the number of autophagosomes.
In the Mike Mutzel video that Paul posted, he says human autophagy was observed to be 30% higher after 72 hours of fasting. That’s much more in line with the majority of studies that I’ve seen, and with comparisons of humans and other mammals, as imperfect as those may be.
- could be. But the noted changes in the autophagy-related stuff are underwhelming, to say the least. They’re talking about people fasting for 18 hours a day, and 18 hours isn’t much more than getting the stomach empty and having the small intestine mostly emptied out (the small intestine doesn’t empty out all at once, it gradually becomes what we’d call really empty). There is the ‘post-absorptive phase’ (as Dr. Fung calls it) yet to come, glycogen depletion yet to go through, and the lion’s share of the decrease in insulin and increase in glucagon yet to be obtained, as well as the supression of mTOR and the activation of AMPK - which, under favorable conditions, really only get going during the second day of fasting.