Fasting-mimicking diet clinical trial led to 2.5 years of reduced biological aging, 12.5 years increase I max life expectancy if done for 20 years

I’m out and not in a place where i can easily pull these up, bit of memory serves me correctly theres a good deal of research on fasting. The benefits off the top of my head are autophagy and growth hormone stimulation after a certain point (two days?), and caloric restriction as well. I listened to a lot of interviews with Dr Fung of toronto who is a huge proponent and practitioner of this, in part because he’s had thousands of patients fast under his care, and partially because he focuses on renal health and i have a solitary kidney.

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How are those cycles defined for us humans?

5 days each. (Extra characters)

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“Our results do not support activation of AMPK/PGC-1a by fasting in human muscle… Human data is not consistent with benefits of fasting on muscle mitochondria.”

Hmmmmm. Perhaps the issue is studied fasts are too short? A 5 day fast is my next project when I get brave enough to try it.

The big advantage of the fasting mimicking protocol vs extended fasting is the reported lack of lean tissue loss in the FMD. They provide just enough carbs and glycerol to spare lean tissue while at the same time allowing for ketosis, autophagy and fat loss.

Unfortunately, it’s expensive and I’m not a fan of the powdered soups :nauseated_face:. I have experimented many times over the last 6 or 7 years with the Prolon product, splitting boxes and replacing some of the soups with other foods to save money and make it more palatable. Every time I’ve done that, the replacement foods tasted better, but I felt worse and didn’t lose nearly as much body fat (and also lost muscle), according to visual inspection and my bioelectrical impedance scale. I suspect it was because I kept calories constant but lowered carbs and increased fat (mistakenly thinking it would work even better).


Did you try resistance training during the fast?

Theres a whole group of people who lift fasted and that seems to work for them. I can usually lift easily (normally on OMAD having not eaten for 22hours), and can list 1-2 days into a water fast, but days 3-4 i feel pretty weak (meaning i can still lift 50% of my 1 rep max which is pretty decent weight, but probably not 75%).

Theres a whole group of people who do ultramarathons fasted, including a small group of angry Type-1 diabetics who do ultramarathons on five day water fasts (with I believe roughly seven units of slow acting insulin daily). In 2021 my daughter and I did the Grand Canyon rim-to-rim with basically only a jar of peanut butter and we really moved (we had other food on us but didn’t eat it — always safety first), but by the fourth day (the final rim climb) we we’re really dragging. I don’t see how these five day water fast ultramarathoners do it.

I do four-day water fasts every 1.5 months, and have been considering adding a two-day fast every week (5-2 with ad libitum feeding the rest of the week focused on heavy protein) but 1) i’m afraid of stressing my body out too much (some is good; a lot is bad) and 2) i don’t want to lose muscle mass, and 3) I’m not sure autophagy will really kick in within the two days so what am i doing other than calorie restriction?

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Thanks for sharing.

Have you done Dexa to make sure your bone mineral density is good?

Re not wanting to overdo it. You could also consider sandwiching your fast with lower protein diet days before and after the actual fast - if the goal you were seeking with potentially longer fasts was eg longer period of mTOR down, IGF-1 down, etc.

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A couple of times I did resistance training during the FMD, but it just made me more hungry and miserable. Since resistance training causes micro-damage to the muscle fibers, which then get stronger/bigger during the repair process, it would seem counter-productive to do resistance training during a fast, when you have little or no protein or resources for that repair process. This is presumably why Prolon specifically recommends against any kind of significant exercise during the FMD protocol (walking or gentle Yoga, for instance, is ok). The studies they’ve published back up the lean-tissue-sparing results of the FMD. I haven’t looked for studies with other kinds of fasting along with resistance training (vs no resistance training) and lean mass, but that would be interesting to see.

Don’t know about studies here either. I do remember that Peter Attia’s fasting protocol has resistance training during the fast to counteract risks of muscle loss.

Perhaps: Since autophagy is happening there are some building blocks available (and perhaps it even helps increase autophagy in other tissues)… not sure.

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Yes, that’s something I’ve actually wondered about, too, but the increased hunger from resistance training was a killer for me (it’s already hard enough). BUT, now that I have a GLP-1 agonist to play with (Rybelsus tablets), this could conceivably be a game-changer for making fasting that much easier because of the appetite-suppressant effect. The main thing I wonder about is if the uptick in insulin from GLP agonism could counteract some of the autophagy. Question would be is if there really is any considerable real-world, clinically significant uptick of insulin during fasting or FMD protocol combined with GLP agonist.

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Ive never done a dexa, but ive had probably 10 CT scans in the past five years with good view of my ribs, spine, and pelvis, so not sure if i can repurpose these to “approximate” a dexa’s quantification; i see the radiologist notes on “normal age related spinal deterioration in vertebrates 4 and 5” but i was assumed this is very normal. I really only started heavy lifting last year January and with it started eating heavily animal protein so I’m looking forward to see if I’m making my 4&5 worse with heavy deadlifts and squats (i recently squatted 335 pounds and im hoping for 400 in December), making them more dense, or no change. I started fasts three years ago so if it shows up in a CT scan we would have already seen this effect.

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I’m one who almost cries if I have to delay my morning almond milk latte to get labs done, but I’ve done aprox 12 rounds of Prolon (have not done one in a year), and truly, day 3 is brutal, but other than that, the only hard thing is not wanting those god forsaking soups. The thing I’m mostly excited about after finishing is my latte, and not much else… and this is from someone who can not fast for 24 hours. I have not actually noticed any difference in my labs, fwiw, but I am still a believer it’s helping in ways I can’t see… at least that is my hope! My goal is to start rapa in the coming months!


Systemic proteome adaptions to 7-day complete caloric restriction in humans

Nature Metabolism

We demonstrate nine distinct proteomic response profiles, with systemic changes evident only after 3 days of complete calorie restriction based on in-depth characterization of the temporal trajectories of ~3,000 plasma proteins measured before, daily during, and after fasting. The multi-organ response to complete caloric restriction shows distinct effects of fasting duration and weight loss and is remarkably conserved across volunteers with >1,000 significantly responding proteins. 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. Using proteogenomic approaches, we estimate the health consequences for 212 proteins that change during fasting across ~500 outcomes and identified putative beneficial (SWAP70 and rheumatoid arthritis or HYOU1 and heart disease), as well as adverse effects. Our results advance our understanding of prolonged fasting in humans beyond a merely energy-centric adaptions towards a systemic response that can inform targeted therapeutic modulation.


I’d like to see a study like this looking at proteome adaptations over a week, after 2 or 3 days of significant rapamycin use, and a comparison between the results of that to this study.


Great idea. Perhaps email the team and suggest it?

Should be low cost and since they already have all the content formed, the test machinery up and running, might not need a new grant at all and they will likely get another high impact paper.

We could probably also help them find Rapa curious people who have never taken Rapa and who could be the test subjects if they need that type of population.

If they say that they have no funding we could ask how much they need and perhaps we could crowdsource a bit here on the forum and see if eg AgeLess and Healthspan and Matt K / Peter A communities/network could chip in

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Its very easy (and cheap) to replicate the Prolon diet and actually improve on it because you can use less processed food. I’ve done it once - having reverse engineered prolon, and mainly using a home made minestrone soup. Its relatively easy to stick to for a few days, but not enjoyable by any stretch

I’ll dig out the protocol.


This is my take on the Prolon diet:

A fasting-mimicking diet (FMD) is low in calories, sugars and proteins, but includes relatively high levels of plant based complex carbohydrates and healthy fats.
5 Days is the target – “autophagy” starts from day 3
Day 1 = 1100 Calories
Day 2-5 = 717 Calories

Here’s a daily menu overview

  1. An omega 3 tablet
  2. Soup x 3 portions (300ml each)
  3. Avo + Mozzarella Salad
  4. Fast Bar
  5. Glycerine Drink
    • Drinks = herbal tea + water as much as you like!


Fast Bar recipe is here:

Miso Soup: Miso paste 10g, spring onions x 2, tomatoes x 4 cherry, shiitake mushrooms 8g dried, parsley, chillies. We had this for breakfast

Minestrone: Fry 4 rashers of smoky bacon with garlic and 2 x shallots. Add 2 x tins of chopped tomatoes, 1 litre of quality chicken stock, 2 x tins of cannellini, parsley. + 5grams of grated parmesan! We had this for lunch and supper. [this makes about 7 x 300ml portions – enough for 3.5 days!]

Avo Salad – Half an avo + quarter of a mozzarella + 5cherry toms + basil + 2.5g of olive oil

Glycerine Drink – add 5ml of glycerine to a pint of water


Was this assuming 3 fasts per year x 5 days for 20 years? So 300 days of eating soup for 12 years life extension payback? Not a bad ROI


I’m really impressed with FMD. Some points I was unaware of:

  • "No loss of Lean body mass retention. " (well, not stat-sig at least).
  • Reduced abdominal fat vs mediteranean. Ie 25d eat what you usually do, 5 days Prolon vs 30 day Med.
  • (in mice) It improved inflammatory bowel vs a water fast made it worse

FMD vs Med: Fasting mimicking diet cycles versus a Mediterranean diet and cardiometabolic risk in overweight and obese hypertensive subjects: a randomized clinical trial | npj Metabolic Health and Disease
The FMD group gained 0.1 lbs lean mass, while losing 7.8 lbs after 4 months of 25 / 5 - std diet / FMD. That’s truly incredible!

Based on this, I dont see a good reason not to do these Prolon or roll-your-own FMD more regularly. And it provides a great reason to do FMD instead of water fasting (preserve your lean mass).

Next someone needs to trial what effect adding a rapa dose on day 1 or 2 has on the outcomes :smiley:

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