Fasting and autophagy — how long do you actually need to fast?

So I’ve been diving deep into the autophagy research rabbit hole and I’m getting really conflicting info about how long you actually need to fast to trigger meaningful autophagy. Some sources say 16 hours is enough, others say you need 24-48 hours or even longer.

I’ve been doing 18:6 IF for about 2 months now, mostly to help with the tiredness I was getting on semaglutide (which btw has helped a lot). But now I’m wondering if I should push to longer fasts occasionally if cellular cleanup is really the goal here.

Does anyone have experience with this? Like have you noticed differences between shorter daily fasts vs doing longer 36-48 hour fasts once a week or something? I know autophagy is hard to measure without actually like… taking tissue samples lol… but curious if people have noticed differences in how they feel, skin quality, inflammation markers, anything like that.

Also I’m wondering if being on a GLP-1 changes anything since we’re already in a caloric deficit most of the time anyway. Does that give us any advantage or does the fasting window itself matter more than overall calorie restriction?

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4 Comments

  1. From what I’ve read, autophagy really starts ramping up around the 24 hour mark and peaks somewhere between 48-72 hours. The 16-18 hour fasts definitely have metabolic benefits but they’re probably not giving you maximum autophagy.

    That said, I do think the GLP-1s might give us some advantage here since there’s research showing that fasting-mimicking diets can trigger similar pathways to actual fasting. When you’re on semaglutide and barely eating anyway, your body might be getting some of those signals even if you’re technically eating every day.

    I personally do 18:6 most days and then one 42-hour fast per month. The longer fasts definitely make me feel like I’ve hit some kind of reset button, hard to describe but my brain feels clearer after.

  2. I’ve experimented with both and honestly the longer fasts are ROUGH for me, especially while on tirzepatide. Like I already don’t want to eat most of the time, but going past 24 hours I start feeling weak and spacey.

    My functional medicine doc told me that for women especially, super long fasts can actually be stressful on the system and might not be worth it. She suggested 16-18 hours daily is plenty for cellular benefits without the cortisol spike. Idk if that’s true for everyone but it resonated with me. I’ve stuck with 17:7 for 6 months now and my skin has never looked better tbh.

  3. MitoMike is right about the 24+ hour thing. There was a study I came across (I think it was in mice though) showing that autophagy markers really don’t get significant until you’re past 24 hours. But here’s the thing – we don’t really know how much autophagy is optimal or necessary for humans.

    The daily 16-18 hour fasts are probably giving you plenty of benefits in terms of insulin sensitivity, inflammation reduction, etc. even if max autophagy isn’t happening. And those benefits are well documented.

    If you want to experiment with longer fasts, maybe try one 36-hour fast and see how you feel? Just make sure you’re getting electrolytes. Being on a GLP-1 might actually make it easier since you won’t be fighting hunger the whole time.

  4. def agree with jessika about the gender differences, this is real. I pushed myself to do 48 hour fasts twice a month for like 3 months and my cycle got weird and I was exhausted all the time. Backed off to 18:6 daily and feel so much better.

    Also worth mentioning that exercise might trigger some similar pathways? My trainer said that’s why HIIT and resistance training are good for longevity stuff. So if you’re working out regularly you might already be getting cellular cleanup benefits without needing to fast for days on end.

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