Thought this was interesting (article and firewalled paper)

“The results support past trials which also suggest fasting requires several days before it becomes more useful than simply reducing calorie intake. Most proteins return to baseline the moment a person starts to eat again, which suggests that biological changes from fasting need to be sustained for a certain amount of time to reap long-term health benefits.”

“ Here we show that a 7-day water-only fast leads to an average weight loss of 5.7 kg (±0.8 kg) among 12 volunteers (5 women, 7 men). We demonstrate nine distinct proteomic response profiles, with systemic changes evident only after 3 days of complete calorie restriction”

“ The fasting signature is strongly enriched for extracellular matrix proteins from various body sites, demonstrating profound non-metabolic adaptions, including extreme changes in the brain-specific extracellular matrix protein tenascin-R.”

https://www.nature.com/articles/s42255-024-01008-9

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I’m sure I’m not alone in learning with the 5 day Prolon FMD (and other fasting) Longo says the good stuff happens after day 3.

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It would be really interesting to do the same type of study on rapamycin users dosing at different levels (e.g. 5mg once per week, 10mg once per week, 15mg once per week) to see how similar or different the biological effects are. I suspect the impact is very similar in many ways.

when done properly and under medical supervision, fasting is thought to offer a range of health benefits to people – but those benefits may not occur in shorter or more intermittent fasts, recent research shows.

A study by researchers in Europe and the UK found it took more than three days for all major organs to change protein production in ways that could predict better health in participants undertaking a seven-day water-only fast.

These changes were consistent across all 12 healthy participants (five women and seven men), who had their blood taken before, during, and after the week of fasting.

“For the first time, we’re able to see what’s happening on a molecular level across the body when we fast,” explains Claudia Langenberg, an epidemiologist from Queen Mary University of London.

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I hate to say it, but if the benefits are similar, I’d rather take Rapamycin than fast for several days.

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There are certainly downsides to fasting, i.e. muscle wasting.

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I always fast when I take rapamycin, which is only about once a quarter, since I’m only 39 and in good health, so I prefer to err on the side of a conservative intervention. I don’t start counting a fast until 6 hours after my last meal, to give things time to return to baseline, and I fast for 24 hours or so before taking rapamycin, then continue to fast for another 24 or as long as I can take it.

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Fasting Mimicking Diet studies show no loss of muscle during a 5-day FMD despite some fat loss (500-1000 kcal a day). Mostly the weight loss is water and poop (bowels empty out over 5 days). I found the muscle retention to be true for me (as far as I could tell) although I did lift weights while I was doing the 5-day FMD. The main benefit was a significant turn down of my already low chronic inflammation. I had zero body aches for 1.5 months afterwards. The effect didnt last longer than that (a gradual reemergence for another 1.5 months) but I don’t mind repeating periodically.

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I’ve never been able to make it 5 days but have done multiple 48 hour fasts and I’ve never experienced any strength loss.

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What’s your source on this? I just looked at four of Longo’s human FMD studies, and none of them assessed even lean mass, let alone muscle.

And if he did somewhere measure muscle mass pre- and post-FMD, I don’t think it would mean anything: even DEXA lacks the precision to measure lean mass changes over a few months, let alone five days.

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So even if I did find studies showing evidence you wouldn’t believe it? Why bother asking?

Well here is one study that i found with a 5 mins search on google.

“ MD but not FMD cycles caused loss of lean body mass.”

https://www.nature.com/articles/s44324-023-00002-1

This is consistent with what I’ve heard Dr Longo say and what Dr Antoun told me on my interview with him. Unlike most health span interventions, you can just try FMD to see for yourself. My personal experience was very good. I will repeat after my Christmas feast this year.

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@Joseph_Lavelle Do you have your own recipe of ingredients for FMD or using Prolon?

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I buy the prolon kit so far. I got my latest on a Black Friday sale so it wasn’t too bad. I hope to make time to create a homemade version. Do share if you find a good recipe.

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From what I can glean on the Prolon website, it just seems to be Mediterranean style soups with some healthy carbs on the side, smoothies and some supplements. That is what we eat most of the time anyway. My wife makes soups always from scratch frequently with just organic vegetables from the market. Lentils, kale, celery, leeks, lots of garlic in our diet, EVOO. Also, eat Kirkland wild caught salmon couple times a week. Other things from scratch are made up of quinoa, farro, freekeh, barley, brown rice. Not all together of course, just rotating in various dishes. Tonight we’re just splitting a can of Nuri spiced sardines and homemade sourdough (50/50 whole wheat/bread flour). We don’t buy store bread. I don’t know what other people really eat when they go back on “regular” diet. I usually have a smoothie for lunch (blueberries, strawberry, organic or grass fed whey protein, 5 defenders mushroom powder, milk + lifeway organic kefir or just water) and a handful of walnuts or almonds. Breakfast is egg or ancient grains cereal, granola (both organic) with blueberries. Very rarely eat red meat (couple times a year maybe), but chicken, turkey, occasional other fish. Sometimes we’ll just have a large salad for dinner. Almost no added salt to anything we eat. Maybe I don’t understand the nature of the Prolon diet. Is it the 5 day frequency of the components? Sometimes we’ll do that in winter especially. I should make a log of daily diet to compare.

I’m always prepared to have my views changed by new evidence.

Ah — thanks. Well, two things. First, this was a four-month trial with repeated 5-day FMD cycles: your OP seemed to say they had measured it over a 5-day cycle, which does seem to be impossible to do due to lack of precision of the instruments.

Second, they used a Tanita bioimpedance scale to measure lean mass: far from the best way to assess it, though better than calipers in most cases.

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We use many recipes from these books.

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It’s among others about ratio fats: carbs: protein, and of course amount (and sort of) carbs and protein (the latter is very low). It’s detailed in several papers. With the Cron-O-Meter it is not that difficult to try to replicate that with whole foods, rather than using the bars and soups of the Prolon kit. I’ve used that kit about 6-8 times in the past, but as I mentioned it didn’t give me the ‘results’ a water fast did give me, neither a rise in ketones. But then I’m a (very) small-framed female, so I can imagine this may be different for males/people with more lean/fat mass. I’d say in fact it would be a bit unexpected that as a ~86lbs female, I would eat the same amount of food as a 180lbs male and reap similar results - to name but an example. But still the Prolon kit doesn’t differentiate.

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That’s a very stupid and misleading headline.

That looks like a false interpretation of the study. You wouldn’t say resistance exercise isn’t beneficial for building muscle because protein synthesis is only elevated for a short while and goes back to baseline several days after you trained the muscle. Resistance exercise needs to be done on a regular basis consistently for long periods until the effects start to show. The same is most certainly true for fasting.

Well don’t hold back…tell us what you really think.

I’m no expert but I understood this to mean something different than your analogy to resistance training. I understood it to mean, to modify your analogy, that you’d have to lift weights for 3 hours to turn on muscle protein synthesis. If the lifted for less than 3 hours, you’d get other benefits but not MPS.

So fasting, according to the paper, is useful for a variety of benefits but the some of the benefits the study pointed to you do not get without a prolonged fast…long enough to turn it on and then hold it on for a while to accumulate benefit.

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Good point. What I was mainly criticizing is the notion that you might not get benefits with shorter term fasting just because they didn’t see changes in the following days. Using a training analogy, that’s like saying resistance training doesn’t make your muscles bigger because you trained your muscles and didn’t see any measurable muscle growth three days later. You would see some increased protein synthesis in the following days in the trained muscle if you did resistance training but you won’t see any muscle growth. To see the muscle growth you need to train regularly for weeks or months. For fasting, I think it is similar in that maybe some effects you would see immediately, but other effects would take months to show up to a significant degree. The main takeaway from the article IMO is that there may be some short term effects that don’t become apparent unless you fast for quite long (3 days or so), which is interesting.

What I’m more interested in with respect to fasting, is not the effect you see in the first days that goes back to normal shortly after the fast, but the long term effects on your baseline state. In the case of exercise, nobody really cares about what effect it has in the few days after doing it, because you’re not going to transform your body and health with a single exercise session. What’s really important is the effects it has over the long run when done regularly. I think the same applies to fasting. I wish someone would do a study with different fasting regimens to see the effects after 6 months or so, and would measure some important markers, like baseline autophagy with tissue biopsy. Problem is, it would be hard to do while keeping calories and body weight constant.

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Agreed. Hard to separate benefits from fasting ve calorie control/ reduction but I’d bet there is a benefit from occasional long term (3+ days water fasting) fasting to turn on programs that otherwise would never turn on. Too much long term fasting would not be great for muscle or fitness maintenance, so the balancing act is key. Or maybe a fasting mimicking diet works well enough to replace the 3 day water fast without the muscle loss (they say).

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