#1

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Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk

Nature Comms, * Published: 20 February 2024

Star cast that combines profs like Valter Longo and Morgan Levine…:

In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that ***3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss.

Nearly identical findings resulted from a second clinical study (NCT04150159).

Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.

Wow, just three cycles of FMD…

Haven’t read the paper yet, what are people’s thoughts?

Full Open access paper:
https://www.nature.com/articles/s41467-024-45260-9

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#2

And they did some modeling (not sure how much to believe in it, but interesting if directionally right, for someone one just does 3 times a year in their analysis):

This reduction in biological age is reflected in the extension of life expectancy estimates at age 70, assuming 3 FMD cycles annually starting at age 50 (Fig. S6B).

While the estimated mean life expectancy differs by about 5 years, the predicted maximum life expectancy differs by 12 years.

#3

I didn’t read the paper but I presume they only looked at surrogate markers not actual healthspan? Sure the markers can improve in the short but what will the effect of such a diet be in the long run, will it cause frailty and/or deficiencies?

#4

I suppose the idea is that short fasts (12-24 hours) do not trigger autophagy enough, and a FMD is more tolerable for holding an extended fast (5 days) that would trigger autophagy. 5 days is a long time but I now have a 1-week rapa holiday every 5th week which I could use for this effort. Thanks for posting.

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#5

If you take a rapamycin holiday you should indulge not vast, otherwise there is no point in taking the holiday if you are going to suppress mtor another way

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#6

I read the paper…it’s using their proprietary plant based diet from Prolon (a company associated with USC). Not trying to discredit it, just pointing it out. It’s soup mixes, plant based crackers, bars and some supplements. No coffee, alcohol, etc. Herbal teas provided as well.
The 1st day of the FMD is 4600 kJ or 1100 calories. Days 2-5 are only 3000 kJ or only ~720 calories.
You’re not starving but definitely fasting.

Day 1 of the FMD supplies ~4600 kJ (11% protein, 46% fat, and 43% carbohydrate), whereas days 2 to 5 provide ~3000 kJ (9% protein, 44% fat, and 47% carbohydrate) per day. The FMD provided by L-Nutra to this study participants comprises proprietary formulations belonging to USC and L-Nutra (www.prolonfmd.com) of vegetable-based soups, energy bars, energy drinks, chip snacks, tea, and a supplement providing high levels of minerals, vitamins, and essential fatty acids34.

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#7

You can do FMD with avocados and some powdered greens for an easy no cook approach. But you can cook your own meals too. Many tips in Valter Longo’s book and countless recipes online.

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#8

Having done many 5 day water fasts and 2 FMDs, I can definitely say that I find water only fasts easier. I felt so weak on the FMD both times I completed it. My body responds better on an all or nothing basis it seems.

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#9

I also find nothing to be easier than a little. But after 3 days I’d kill for some dry cat food. I’ve never gotten past 3 days on just water.

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#10

The third day is the hardest. If you get trough day 3 you can go on for days. At least in my case. I haven’t done this in decades, but in my twenties and early thirties I did several prolonged fasts with a friend. It is not hard to go on when endorphins kick in. Few times I did it in a spa (very german spa to be exact!) but few times I did it at home and I could even cook food for others and not feel hunger.
But I am conflicted about fasts now in other ways. I would like to try FMD but recently I was in hospital and I could not eat for few days and I lost almost all muscles I trained very hard for the past few months. And would every FMD cycle do that? I know they say it increases lean body mass, but does it? I guess I will need to try…

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#11

Does anyone think of rapamycin as lazy man’s fasting?

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#12

It sure is fasting mimetic :laughing:
But real fasting is also about control and suffering and getting trough it and other psychological effects beyond physiology.

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#13

I tried it once. Day 3 was the worst, closely followed by days 1,2,4 and 5

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#14

The longest I went was 9 days I believe, or 11 probably… it was a 14 days in a german spa, paid a great deal to be starving, but after a certain point maybe day around day 5 or 6 I felt like I can go forever, the hunger was really suppressed. But I rarely feel hungry to the point of starving. Maybe I have naturally high GLP-1.

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#15

That reminds me, i once managed about 21 days on a very restricted diet in an Ayurvedic retreat in Sri Lanka (all the other clients were large German women).

It was very protein and calorie restricted, but not fasting. Looking back i wonder whether there were any long term benefits. By the end I felt and looked about 10 years younger.

9 days is very impressive . I feel that hunger tolerance can be trained, but I’ve no real evidence other than personal experience (i used to be awful, now I’m less awful). How did you feel after 9 days?

And is there any data pointing to optimum age to fast?

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#16

Yes, Germans and their self punishing character :sweat_smile:

Well I know I had this euphoric feeling during the last days of fasting. It felt like I can do anything. I felt powerful and it was a good feeling. I also remember that I had great skin. I did it in my late twenties, early thirties almost two decades ago. I don’t think I was concerned with any anti-aging effect or was I? For sure there are longterm benefits of fasting, Valter Longo has written a lot about it, probably Luigi Fontana too. Valter Longo is a big proponent of fasting as a cure for many aliments even as adjuvant therapy for cancer. This points to any age I would imagine. When I got interested in longevity few years back, Valter Longo was one of the first books I read. I haven’t done much research into the subject later.
Now I take rapamycin.

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#17

I do a three day water fast every 2 months. Is there a considerable advantage in fasting for 5 instead of 3 days, even when done less frequently? Not interested in the « mimicking diet » as water fasting is just fine for me.

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#18

So if I’m reading this correctly, the founders of Prolon (from Valter Lingo’s lab) say if you buy their Prolon packaged food and follow the Prolon FMD for five days every month for 20 years, their revenues will grow spectacularly? …errr, I meant to say “your longevity will increase dramatically”? (Maybe I’m being a touch unfair)

I am a believer in fasting. If autophagy is a longevity/protective mechanism (clean out the crap, including misfolded tau proteins, cancer cells, etc) then fasting is a huge benefit. I do a four-day fast every (roughly) 1.5 months. I had done a few fasts many years ago in a desperate attempt to lose weight, and doctors told me i was destroying my metabolism; yet another example of how the conventional wisdom didn’t quite capture the truth. I assume we are all able to fast, except a small number of us who cant regulate our metabolism: I’ve been reading about these die-hard type-1 diabetes ultramarathoners who fast for days while on ultramarathons and they seem fine; for the rest of us with working beta islets, theoretically we should be fine. (Not medical advice!)

I picked four days somewhat arbitrarily: i want to hit autophagy so two days seemed too short of a period, and if h to ree days is good, shouldn’t another say be better? — i think day 2 is the hardest, then day 3, and day four is easier. I also want to preserve muscle, and even though i know fasting wastes muscle, i want to minimize it. So i settled on four days. Ive done longer, but I’m also not sure i could fit a seven day fast regularly into my life. If you believe this would be a game-changer, I’m all ears: show me the data and I’m willing to try.

I’m also making the assumption that a four-day water fast is roughly equivalent to a five day FMD.

I feel fantastic after i stop fasting, but it just might be because fasting sucks while you’re doing it. I feel like small injuries appear to heal noticeably faster during a fast, like minor lifting injuries/etc. i would guess (again, no personal lab tests to back this up) that for me, my fasting has done far more for me than my dietary changes) perhaps outside of eliminating non-whole foods), which is a bit funny to me given the massive tribalism i see surrounding diets.

I’d love a 12.5% life extension from fasting, especially if i can push my healthspan solidly into my 90s and ideally beyond with strenuous exercise and lifting (again: im not a muscle-clad adonis, but have very good strength/power while not really looking “swol” at all). I dint see highly muscular beasts hitting their 90’s but maybe they didn’t exist before now?

#19

Just throwing my experience in: Two weeks ago I completed a fasting mimicking diet cycle following Longo’s Longevity Diet book.

I did not buy the Prolon meal package but simply ate a bunch of vegetables and a bit of olive oil and a few walnuts and almonds. It was very manageable — I was not hungry at any point, though I did tire more easily.

After the fast was over, I went back to the gym. Though I definitely got somewhat weaker (strength training), I was pleasantly surprised that it wasn’t very much.

In other words, the muscle loss seemed to be limited. I did lose fat, and I did have some other benefits (reduced patches of skin inflammation that’s been following me for years). I’ll definitely repeat the diet in anothe few months’ time.

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#20

Interested to hear what benefits does fasting gives over rapamycin. I have done short fasts in recent years but would love to hear that rapa gives similar benefits