Fasting-mimicking diet causes markers indicating reduced age and disease risk

https://www.nature.com/articles/s41467-024-45260-9

by gnabgib • 2 years ago

96 65 2 years ago

nature.com

oneepic• 2 years ago

decrease of 2.5 years in median biological age

Newbie q. This has to be mice-years, not human-years, correct?

ergonaught• 2 years ago

They are talking about humans, here.

bigethan• 2 years ago

Yep. The first words of the paper are “In mice…”

strken• 2 years ago

Interesting paper. Anyone know if there's a hint of a conflict of interest between the authors and Prolon? (Prolon being the FMD package they used)

pazimzadeh• 2 years ago

The experimental FMD was provided by L-Nutra Inc. USC has licensed intellectual property to L-Nutra that is under study in this research. As part of this license agreement, the University has the potential to receive royalty payments from L-Nutra.

V.D.L. and T.E.M., who have equity interest in L-Nutra, did not participate in the collection and analysis of the data.

One-hundred percent of V.D.L.’s equity will be assigned to charitable organizations and companies including the Create Cures Foundation. The remaining authors declare no competing interests.

It's not nothing..

biomcgary2• 2 years ago

This is a submarine research paper. They could have used a non-proprietary formulation with the same macro-ingredients but chose not to. This is NOT science that can be replicated. Nutrition studies are noisy enough as it is.

Very funny to see a closed source diet in an open access paper. It's open access because they paid the publisher, so it is a submarine ad.

000ooo000• 2 years ago

What's a submarine ad/research paper? Hard to search.. I get real submarines.

xk_id2• 2 years ago

They could have used a non-proprietary formulation with the same macro-ingredients but chose not to.

Do you have any idea how expensive it is to run high quality human trials, that meet all regulatory controls? It’s often not realistic without industry sponsors.

Also the diet is not closed source. The full list of ingredients/supplements being used has been published before in other papers they’ve sponsored.

I’ve written elsewhere on this submission about why this is actually a valuable contribution: https://news.ycombinator.com/item?id=39638556

qwerty45612710• 2 years ago

Hi fellow biohackers :-) I need an advice.

I happen to sincerely enjoy fasting and keto dieting. My preferred eating routine is almost exactly what Dr. Berg (don't worry, I know he's not a real doctor and don't follow him blindly, this is just a coincidence with my actual taste) considers perfect "healthy keto" with greens, OMAD and full water fasting days. I feel the best this way (also most energized and productive and sleep the best) and prefer keto snacks as a matter of taste. Except I normally add more proteins, more fruits + supplement some minerals and vitamins.

The problems are in ketosis my skin starts looking worse (kinda old and stressed, while it looks shiny great when I eat carbs) and my teeth become very sensitive (this feels really worrying to me). Any ideas why?

This can hardly be calcium or water deficiency - I get a lot of both, also all fat-soluble vitamins.

Another peculiar detail is I mostly mean junk food under "when I eat carbs". Even a junk food 99% carbs diet somehow seems better for my teeth and skin than any sort of keto and/or fasting.

AndrewKemendo2• 2 years ago

I made my own diet after fasting regularly for the last 11 years, finally landing at something like a loose OMAD comprised of what I call the pre-QME/late ice age diet:

Grass Fed Beef or other grazing megafauna ungulate (Bison, Caribou, Elk, Deer etc…) even better if you can just get a local grazed half cow - very low carbon and basically perfect nutrient balance your environment.

Sweet potato or other wild tubers

Peanuts and legumes

Fresh and dried Berries and stonefruit

This can be done way cheaper and more easily than it seems.

I have been the same weight and body fat (~10%) every day for the last two years when I initially adopted it. I walk between 3-8 miles per day and am exceptionally active, flexible, Sauna regularly etc…

Works for me

qwerty45612710• 2 years ago

Thanks, I'll give this a try.

The problem with sweet potatoes I would buy at my local groceries (I'm in the EU) is it often is crazy sweet (which I both dislike as a matter of taste and doubt being healthy) and juicing with maple-like syrup after I bake it. Should I better consume it raw? Or is this some sort of healthy non-sugar sweet like chicory syrup?

XorNot3• 2 years ago

How much are you actually eating under this diet of yours, in terms of calories? It sounds entirely like you're not actually eating enough, and as soon as go back on carbs you're up around a sustainable number of calories per day.

The thermic effect (energy used in digestion) of protein is on the order of 20-30% of the stated calorie value. "Keto snacks" are probably not on the "high in fat" end of the spectrum (also what's your salt intake like under this?).

Get an app and start weighing / noting what you're eating and see if you're actually hitting a plausible number of calories (for comparison, I need about 11,000 kJ [2750 kcal] per day with moderate exercise and a high protein diet [150g a day target] to not lose weight).

qwerty45612710• 2 years ago

Isn't one supposed to loose weight when they don't eat enough calories to cover the work they do? I don't.

samplatt• 2 years ago

Blood test, my man. No sense asking people on the internet what you MIGHT be missing; get a test and find out for sure.

Posting this from Australia though where the test is cheap. YMMV.

rolisz• 2 years ago

Blood test for what exactly? I'm not OP, but last year I also had a health issue and after going to three doctors, eventually ChatGPT told me to do some tests and one of them was the thing I was deficient in.

ipaddr• 2 years ago

Oil pull for the teeth issue. The reason is the increased acid in your mouth.

qwerty45612710• 2 years ago

Nice clue. I'll try. But how does the acid get there in this case? For an isolated experiment condition I would even ask how can acid get into you mouth the days you don't eat anything at all and only drink water? Do you mean the very saliva is secreted more acidic? I thought the primary source of acid in the mouth are oral bacteria eating carbs remains and producing it.

nradov3• 2 years ago

This is bullshit. There is actually no "validated measure of biological age". We have no reliable biomarkers which can be used to measure changes in a person's expected lifespan based on an intervention. All the claims are highly suspect.

https://peterattiamd.com/richardmiller2/

There may be some health benefits to such a diet but they should focus on metrics with proven clinical relevance.

schaefer3• 2 years ago

Okay.

Here's the bio of the guy your calling bullshit on [1]...

Dr. Valter Longo is the Edna M. Jones Professor of Gerontology and Biological Sciences and Director of the Longevity Institute at the University of Southern California –Leonard Davis School of Gerontology, Los Angeles, one of the leading centers for research on aging and age-related disease. Dr. Longo is also the Director of the Longevity and Cancer Program at the IFOM Institute of Molecular Oncology in Milan, Italy.

What's your background in the field?

[1] https://www.valterlongo.com/biography/

nradov3• 2 years ago

Did you even read the article I linked? Appeal to authority is the lamest sort of argument.

rokkitmensch• 2 years ago

The droplet brigade appreciates your contribution to the credential-washing sense-making cartel's ideological bulwarks.

alchemist1e9• 2 years ago

Is 16/8 fasting-mimicking? and this says it’s good for you then?

Mistletoe• 2 years ago

FMD; a plant-based, low-calorie and low-protein 5-day lasting dietary intervention

Some people just called this college.

Dudhbbh33432• 2 years ago

Did they include details on the effects on LDL cholesterol and blood pressure?

It seems like most time-restricted diets have negative cardiovascular effects.

Slow_Hand• 2 years ago

Would you mind elaborating? I've been intermittent fasting daily for years now and while I'm generally in good health my physician has advised me to lower my LDL cholesterol which is far too high. I've been attributing this high LDL to a large amount of eggs and cheese in my diet, but if there are other potential factors contributing to my high LDL I'm all ears.

Dudhbbh33432• 2 years ago

The research generally shows consistent correlation between the number of meals eaten per day and good cardiovascular biomarkers like LDL and blood pressure, with a single meal per day being the worst.

For example: https://academic.oup.com/nutritionreviews/article/67/10/591/...

But for overall health, the results are more mixed.

schaefer3• 2 years ago

For what it's worth, the last author cited here, Valter Longo has a book called the longevity diet.

I've worked through that book and done some rounds of FMD personally. Where FMD is defined as roughly 5 days of reduced calories. 400 calories from veggies, and 400 calories from healthy fats like olive oil.

After one of the rounds in particular, I felt amazing afterwords. I won't pretend to care about "longevity", but I really do think there's something to it when the author suggests that reduced calories kicks the body into a recovery cycle.

xyzelement• 2 years ago

This is maybe obvious but it sounds like pretty much anyone would feel amazing switching from the standard diet of processed crap and shitty carbs to vegies and healthy fats.

EG when I do "whole 30" a form of paleo I feel amazing even if I overeat in terms of cals - it's just much cleaner fuel for your body overall.

fbdab103• 2 years ago

I have done several fasts (longest 9 days), and low calorie dieting sounds more challenging than not eating. Once you get into the groove, it feels like you can continue not eating for a long time. Having to be perpetually hungry, but allowed to eat only the right things seems a recipe for failure.

Ballas• 2 years ago

The proposed diet - veg and fat - sounds like a form of keto. My experience with keto is that once your body is in ketosis, you also don't crave food; similar to fasting.

treflop• 2 years ago

Personally if I start eating less, my appetite also goes down.

But ngl, it’s real hard at first but if I can hold it together for a day or two, my body starts vibing with it or sumthin’ and I stop feeling hungry. It’s then real easy to eat less.

Funny thing is that I’m the opposite. I can’t do fasts. Impossible shit

riehwvfbk3• 2 years ago

I wonder how the people who have good experiences with fasting do it. For me, I get brutal headaches, walk around in a flu-like daze and can't think straight, oh any my ADHD turns up to 11. I think work would start wondering why I can't accomplish anything way before the 9 day mark.

binary132• 2 years ago

Traditional religious fasts like Lent are an extended period (40 days not counting Sundays in the case of Lent) of calorie restriction and yes being perpetually hungry. It's super doable, just not fun. Definitely causes a perspective shift though!

cmpalmer52• 2 years ago

A good example to use for how to read a paper. Make sure you get all the way to the end and see who sponsored the study, then re-read it in a new light. I was reading through the find out what they were eating. Turns out, they were eating Prolon meal packs which you can buy yourself for $175, which gets you five white boxes of snacks. One for each day of your ersatz fast.

echelon• 2 years ago

I was going to say that the best way to read a paper is to jump from abstract to the conclusion to quickly get a lay of the land before reading the figures and the methods. But in this case you found a really sneaky deal breaker.

The FMD is a plant-based diet designed to attain fasting-like effects on the serum levels of IGF-1, IGFBP-1, glucose, and ketone bodies while providing both macro- and micronutrients to minimize the burden of fasting and adverse effects. 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. All items to be consumed per day were individually boxed (Prolon) to allow the study participants to choose when to eat while avoiding accidentally consuming components of the following day.

They bought a fucking Nature paper.

Wild.

heisenzombie• 2 years ago

Well… Nature communications. But still.

xk_id2• 2 years ago

Please think before you judge. The company behind FMD has single handedly sponsored the largest body of empirical evidence in support of dietary interventions for ameliorating markers of ageing. They did so because they own the patent for their diet formulation. High quality human trials in this area wouldn’t have happened otherwise, because they are extremely expensive to run. We see this problem with other promising interventions that involve for example chemicals whose patent has expired: despite the imperative scientific need, nobody can afford to pay for the human trials.

Besides, the characteristics of the diet formulation are known and can be easily reproduced at home. Overall, this company has made valuable contributions.

In the last 50 years, the whole research industry has been forced by corporate-style management techniques, the financial environment and regulatory controls to become a servant to capitalism. So given the circumstances, this is the best possible outcome.

nonameiguess• 2 years ago

Galaxy-brained hackers and engineers need to learn how to inoculate themselves against premature excitement over this kind of thing. Listening over the years primarily to Eric Helms of Iron Culture, of all things, has given me a pretty good framework in which to look at research like this.

We have an outcome we care about. That is, we want to live longer. We have a proposed intervention. Eat some proprietary diet. How do you study, scientifically, whether undergoing this intervention will produce the desired outcome? The gold standard way to know for sure is you run this. You take a broad sample of all humans on the planet, cutting across races, congenital conditions, metabolic phenotypes and what not, divide them randomly into two groups, feed one whatever else they might normally eat, and feed one this diet, and see who lives longer.

Clearly, we can't achieve this standard. This is the basic reason quantum physics is so much more settled than nutrition science. We can easily produce and mess with hundreds of quadrillions of photons and electrons a day in labs across the globe and measure exactly what happens to them. It would take centuries and no such thing as ethics boards to do this with humans.

So instead we typically end up with a few other options. One is epidemological studies. Collect lots of data over the decades and survey how people ate. See how long they lived. Try to find patterns in that data. Not a bad idea in principle, but survey data like this is often unreliable and this can't work for a new proposed intervention in which no past humans did this.

Now we get down to mechanistic studies. Okay, we can't see directly if doing something will make you live long. Let's see if doing it will change some other quantity we can measure that other research has suggested maybe correlates with longer life. It's getting iffier, but if it's the best we can do, so be it.

Then we get to the bottom of the barrel. That is mechanistic studies but not even conducted on humans. Let's do something to mice instead and see how biochemical markers change in the short term.

It's a long way from that to demonstrating with any kind of reasonable assurance that doing this to a randomly-selected human will produce the outcome we actually care about.

Funnily enough, Eric has chimed in on this so much largely because his research is in muscle hypertrophy, and for a long time, exercise science simply hadn't been doing work for long enough to answer questions we cared about, like feed one person 30g of whey within 30 minutes of lifting, let another eat normally, otherwise they train and eat the same, will one have measurably more muscle in ten years? As we've gotten that data, we've found that no, we can't find any difference. But a lot of people thought for a long time that it would make a difference. Why? Because we had mechanistic studies. We could measure muscle protein synthesis in the hours following lifting and see that the rate at which it occurred was higher if you ate a fast-absorbing protein within some limited time window after a workout. Sufficiently decent logic suggested that would lead to your body actually building more muscle. Well, it turns out no.

It's interesting in general to see how sport outcomes have so drastically improved over the past few decades compared to health and to think about some of the reasons that might happen. At least one seems like athletes and teams have been trying various different training, lifestyle, and game-time strategies for decades and measuring what actually happens in terms of the outcome they truly care about. Will they run faster, jump higher, lift greater weights, and win more?. That can be tested in a reasonable amount of time and you have plenty of willing participants who will try anything and actually comply. All of the people doing it are otherwise pretty similar and trying to accomplish the same thing.

Health, in contrast, is just much harder to study. We're never going to have the time, resources, ethical, practical, or political ability to tweak one variable at a time in otherwise identical populations, wait 90 years, see if one lives longer, then do it again until we find something that works. Most likely, we will never have real answers to a question like if I eat a particular diet for the next year or next decade, will I live longer?

And remember when the comments get filled with "I did this and felt so great," whether it be for fasting, carnivore, keto, anything that severely restricts what you eat and is, in practice, a somewhat less principle ad hoc version of an elimination diet, that some proportion of the population is always out there living with some kind of food allergy or sensitivity they're not aware of. When they do any kind of restriction, some of them are going to eliminate whatever it was that was giving them a problem. Ergo, they suddenly find they feel much better. When you do this for real, under the supervision of a dietician, you reintroduce what you eliminated until you find what the problem actually was. On the Internet, you conclude this must be a magic diet that any person on the planet would benefit from over the full course of an entire lifetime. At least be aware of the logical leaps you are making and how warranted they truly are.

meristohm3• 2 years ago

Your last point is especially useful. It was thanks to a comment on HN that prompted me to try an elimination diet, which has helped me pay more attention to how I feel after I eat specific foods, giving me the actual control I wanted, rather than a fleeting sense of control.

Fasting-mimicking diet causes markers indicating reduced age and disease risk

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