Fasting-mimicking diet causes markers indicating reduced age and disease risk(nature.com)
nature.com
Fasting-mimicking diet causes markers indicating reduced age and disease risk
https://www.nature.com/articles/s41467-024-45260-9
70 comments
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.
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.
> 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.
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.
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.
And they would have published the results of these trials even if they didn't support the company's business model, I'm sure. And they certainly wouldn't cherry-pick results.
In other words, this science is almost certainly bunk.
In other words, this science is almost certainly bunk.
Negative results very very rarely get published in academia either. They sure don't help you get tenure.
I guess that makes OK that nature just MSM'ed itself (reference to mainstream media slowly dying as they're now doing anything for clicks and sponsors).
Well… Nature communications. But still.
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.
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.
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.
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.
Your body is switching to ketosis. You can read about it a lot and it's literally called keto-flu by the keto diet community :) If you want to ease the transition, you should first get into ketosis, but not fasting yet(so still eating but not carbs), and after ket-flu is gone then try fasting.
From my experience all that comes from shock to the body. You are simply not used to it. It gets better over repeated attempts.
Also for the headache - do you still drink caffeine? Brutal headaches usually come from caffeine withdrawal(if you normally drink it but stop during fasting). If that is the case you need first to drop caffeine slowly lowering your daily dosage so the headaches won't happen.
This kind of has me wondering if this is actually good for the body. Ketosis is not without downsides. Alcohol actually acts much the same way in someone completely not used to it. Interesting to hear that it's not just me, and the people who do this all the time also suffer.
So the idea is to ignore the body's defense mechanism in order to... what? Lose weight? Feel good about having suffered through this? I guess I'm trying to figure out the upside. Like lowered social inhibition with alcohol :)
So the idea is to ignore the body's defense mechanism in order to... what? Lose weight? Feel good about having suffered through this? I guess I'm trying to figure out the upside. Like lowered social inhibition with alcohol :)
Frequent MCT oil servings starting pre-fast (continuing through the fast until post-fast) shortens the time spent in "keto flu" by a lot (works for me).
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
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
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!
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.
I played around with intermittent fasting in the early stages of covid lockdown because I was gaining weight being inside all the time.
I would frequently be in ketosis before breaking fast per the urine strips - despite not intentionally limiting carbs at all.
It was an interesting experiment but after having a kid I found it tough to keep the routine. I was in amazing shape for a little while though
I would frequently be in ketosis before breaking fast per the urine strips - despite not intentionally limiting carbs at all.
It was an interesting experiment but after having a kid I found it tough to keep the routine. I was in amazing shape for a little while though
When adhering to if+keto well lines up with a period where social pressures don't compel me to eat, it's not terribly hard to go 2 or 3 days without eating just by not eating until I feel hungry.
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.
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.
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.
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.
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
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
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?
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?
I dice and microwave sweet potatoes, after I do the same for the beetroot (which takes a bit longer to cook). Added jicama recently (diced, uncooked), and in combination with sprouted legumes (cooked, or raw if just lentils), apple, cabbage, nutritional yeast, vinegar and olive oil, it was delicious. That's not a strict recipe, just an example of a recent breakfast/lunch.
No just bake them in the oven. That sweetness is natural hence the “sweet” potato. My daughter likes to eat them skins and all
No need for any additions in my opinion but some folks like to add an oil of some kind. If you’re not into butter then beef lard is really nice etc…
No need for any additions in my opinion but some folks like to add an oil of some kind. If you’re not into butter then beef lard is really nice etc…
I like to oven-roast thin slices of sweet potato, and then freeze them. They're great right out of the freezer: a little chewy and a little sweet. No seasoning, just a little olive oil. Have to flip them partway through though, and open the oven a couple times to let the moisture out so they don't steam.
Isn't beef lard (as well as butter if the butter had been stored in a freezer, as well as egg yolks if baked to the point they are not liquid anymore) dangerously rich in oxysterols?
AFAIK cholesterol (famously abundant in animal fats) gets oxydized into various particularly dangerous forms (which easily pass the blood-brain barrier and actively clog blood vessels) during baking and during freezing.
AFAIK cholesterol (famously abundant in animal fats) gets oxydized into various particularly dangerous forms (which easily pass the blood-brain barrier and actively clog blood vessels) during baking and during freezing.
News to me, so I went looking for more. This PubMed paper seems to back up what you've raised[0]:
Conclusive Remarks As a final point, it appears important to stress that, although the majority of experimental studies have challenged cells or tissues with individual oxysterols, in the living organism oxysterols are present as mixtures, whether of endogenous or of exogenous origin. Like many other molecules with biochemical and/or pharmacological effects, oxysterols interact with one another in such a way as to modulate the effect of such mixtures. Quenching reactions among different components of oxysterol mixtures have been reported with regard to the role of oxysterols in atherosclerosis [46] and IBD progression [39].
Complex interactions of oxysterols likely occur in vivo, thus in vitro results concerning biochemical properties of pathologic amounts of individual oxysterols must be carefully weighed up and, where possible, accompanied and/or followed by analogous experiments with biologically compatible oxysterol mixtures.
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757713/
Conclusive Remarks As a final point, it appears important to stress that, although the majority of experimental studies have challenged cells or tissues with individual oxysterols, in the living organism oxysterols are present as mixtures, whether of endogenous or of exogenous origin. Like many other molecules with biochemical and/or pharmacological effects, oxysterols interact with one another in such a way as to modulate the effect of such mixtures. Quenching reactions among different components of oxysterol mixtures have been reported with regard to the role of oxysterols in atherosclerosis [46] and IBD progression [39].
Complex interactions of oxysterols likely occur in vivo, thus in vitro results concerning biochemical properties of pathologic amounts of individual oxysterols must be carefully weighed up and, where possible, accompanied and/or followed by analogous experiments with biologically compatible oxysterol mixtures.
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757713/
Let me add a list of relevant links. I just hope this won't hit some filter as there are too many :-) I haven't read all of them, let alone thoroughly, but these are relevant research papers on the important subject we raised.
[01] https://onlinelibrary.wiley.com/doi/abs/10.1002/jsfa.2740550...
[02] https://www.sciencedirect.com/science/article/abs/pii/S01406...
[03] https://www.academia.edu/80933160/High_Total_and_Cardiovascu...
[04] https://www.nature.com/articles/493S2a
[05] https://onlinelibrary.wiley.com/doi/abs/10.1002/jsfa.2740550...
[06] https://www.nature.com/articles/493S2a
[07] https://www.tandfonline.com/doi/abs/10.1080/07315724.1994.10...
[08] https://pubmed.ncbi.nlm.nih.gov/27561087/
[09] https://www.sciencedirect.com/science/article/pii/B978012823...
[10] https://pubmed.ncbi.nlm.nih.gov/24656052/
[11] https://pubmed.ncbi.nlm.nih.gov/12531208/
[12] https://pubmed.ncbi.nlm.nih.gov/25305550/
[13] https://pubmed.ncbi.nlm.nih.gov/21388551/
[14] https://www.cambridge.org/core/journals/british-journal-of-n...
[15] http://researcherslinks.com/current-issues/Effect-of-High-Di...
[16] https://www.researchgate.net/publication/335421256_Biologica...
[17] https://pubmed.ncbi.nlm.nih.gov/11768237/
[18] https://pubmed.ncbi.nlm.nih.gov/10718625/
[19] https://pubmed.ncbi.nlm.nih.gov/20870006/
[20] https://europepmc.org/article/agr/ind21989519
[21] https://onlinelibrary.wiley.com/doi/abs/10.1002/jsfa.2740550...
[22] https://pubmed.ncbi.nlm.nih.gov/4036336/
[23] https://europepmc.org/article/agr/ind21989519
[24] https://cadiresearch.org/topic/diet-indian/animal-and-vegtab...
[25] https://www.jcpconline.org/article.asp?issn=2250-3528%3Byear...
[26] https://onlinelibrary.wiley.com/doi/abs/10.1002/978111853416...
[27] https://onlinelibrary.wiley.com/doi/abs/10.1002/978111853416...
[28] https://www.meneerspoor.nl/uploads/1/7/4/7/17471559/butter_p...
[39] https://pubmed.ncbi.nlm.nih.gov/27561087/
[30] https://www.researchgate.net/publication/26523948_Cholestero...
[31] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931501/
[32] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121705/
[01] https://onlinelibrary.wiley.com/doi/abs/10.1002/jsfa.2740550...
[02] https://www.sciencedirect.com/science/article/abs/pii/S01406...
[03] https://www.academia.edu/80933160/High_Total_and_Cardiovascu...
[04] https://www.nature.com/articles/493S2a
[05] https://onlinelibrary.wiley.com/doi/abs/10.1002/jsfa.2740550...
[06] https://www.nature.com/articles/493S2a
[07] https://www.tandfonline.com/doi/abs/10.1080/07315724.1994.10...
[08] https://pubmed.ncbi.nlm.nih.gov/27561087/
[09] https://www.sciencedirect.com/science/article/pii/B978012823...
[10] https://pubmed.ncbi.nlm.nih.gov/24656052/
[11] https://pubmed.ncbi.nlm.nih.gov/12531208/
[12] https://pubmed.ncbi.nlm.nih.gov/25305550/
[13] https://pubmed.ncbi.nlm.nih.gov/21388551/
[14] https://www.cambridge.org/core/journals/british-journal-of-n...
[15] http://researcherslinks.com/current-issues/Effect-of-High-Di...
[16] https://www.researchgate.net/publication/335421256_Biologica...
[17] https://pubmed.ncbi.nlm.nih.gov/11768237/
[18] https://pubmed.ncbi.nlm.nih.gov/10718625/
[19] https://pubmed.ncbi.nlm.nih.gov/20870006/
[20] https://europepmc.org/article/agr/ind21989519
[21] https://onlinelibrary.wiley.com/doi/abs/10.1002/jsfa.2740550...
[22] https://pubmed.ncbi.nlm.nih.gov/4036336/
[23] https://europepmc.org/article/agr/ind21989519
[24] https://cadiresearch.org/topic/diet-indian/animal-and-vegtab...
[25] https://www.jcpconline.org/article.asp?issn=2250-3528%3Byear...
[26] https://onlinelibrary.wiley.com/doi/abs/10.1002/978111853416...
[27] https://onlinelibrary.wiley.com/doi/abs/10.1002/978111853416...
[28] https://www.meneerspoor.nl/uploads/1/7/4/7/17471559/butter_p...
[39] https://pubmed.ncbi.nlm.nih.gov/27561087/
[30] https://www.researchgate.net/publication/26523948_Cholestero...
[31] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931501/
[32] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121705/
If you are concerned about glycemic index, try boiling them for 30 mins.
https://www.healthline.com/nutrition/sweet-potato-glycemic-i...
https://www.healthline.com/nutrition/sweet-potato-glycemic-i...
Glycemic index is kinda retro already :-) Insulinemic index is what's interesting. Sadly, for overwhelming majority of foods, it is very hard to find.
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).
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).
Isn't one supposed to loose weight when they don't eat enough calories to cover the work they do? I don't.
The punchline here is that you're complaining of a specific problem while being very vague about what exactly it is you're doing: no one's going to be able to give you a good answer. But I'd suggest if you don't know quantities and calories (and types), then you don't have enough data to self-diagnose the problem. Good scientists keep accurate notes.
I just tried to be concise. So my question was if somebody could guess a way how carbs deficiency or OMAD can harm teeth and skin health.
I could share my whole menu of low-carb foods I eat every dinner and you would see that sounds like a Robin O'Bobin's dinner, certainly more calories than necessary. Would you count your calories precisely when it's just obvious you over-eat (incl. caloric-dense fatty meats, cheeses and oils, also supplement digestive enzymes) but don't have any concerns about weight?
Sure, I also experimented with severe caloric restriction and water fasting - these made me feel surprisingly energized, high-stamina and physically-performant, notably without loosing weight (this still puzzles me). But I don't find this very relevant because that was a different story, separated by time and by some time of a carbs-rich diet which caused swift recovery.
Both had the same ill effect on skin and teeth.
I even have a hypothesis of my own: perhaps that is insufficient endogenesis of hyaluronate which needs glucose as its pre-precursor.
And Mistral suggests this indeed is a good clue:
«However, a very low carbohydrate diet can potentially impact the health of various tissues in the body that rely on hyaluronic acid for their structure and function. For example, a low carbohydrate diet can lead to decreased skin hydration and elasticity, joint pain, and dry eyes due to changes in the hyaluronic acid content of these tissues.»
What I am going to try the next is hyaluronate supplementation or intense glucosamine supplementation (as moderate glucosamine supplementation didn't help).
I could share my whole menu of low-carb foods I eat every dinner and you would see that sounds like a Robin O'Bobin's dinner, certainly more calories than necessary. Would you count your calories precisely when it's just obvious you over-eat (incl. caloric-dense fatty meats, cheeses and oils, also supplement digestive enzymes) but don't have any concerns about weight?
Sure, I also experimented with severe caloric restriction and water fasting - these made me feel surprisingly energized, high-stamina and physically-performant, notably without loosing weight (this still puzzles me). But I don't find this very relevant because that was a different story, separated by time and by some time of a carbs-rich diet which caused swift recovery.
Both had the same ill effect on skin and teeth.
I even have a hypothesis of my own: perhaps that is insufficient endogenesis of hyaluronate which needs glucose as its pre-precursor.
And Mistral suggests this indeed is a good clue:
«However, a very low carbohydrate diet can potentially impact the health of various tissues in the body that rely on hyaluronic acid for their structure and function. For example, a low carbohydrate diet can lead to decreased skin hydration and elasticity, joint pain, and dry eyes due to changes in the hyaluronic acid content of these tissues.»
What I am going to try the next is hyaluronate supplementation or intense glucosamine supplementation (as moderate glucosamine supplementation didn't help).
To cut to the chase: depending on what you're doing, and what you're eating, are you getting enough Vitamin C to ward off scurvy? Because going into deficit would initially mess with both skin and teeth. Modern cereal products tend to be heavily vitamin fortified, so it won't happen in that context.
You're complaining of what sounds like a nutritional deficit, so what you eat - precisely - is in fact incredibly important to the question, as is how long you've been maintaining any one set of menu choices. And then since time is a factor, quantity matters too - it is not equivalent to binge on something one week and then go 3 weeks completely cutting it out, for example.
You're complaining of what sounds like a nutritional deficit, so what you eat - precisely - is in fact incredibly important to the question, as is how long you've been maintaining any one set of menu choices. And then since time is a factor, quantity matters too - it is not equivalent to binge on something one week and then go 3 weeks completely cutting it out, for example.
Good point. Thank you. Indeed this looks like a deficiency. But I suspect deficiency in the very carbs to be the cause of the problem and am curious whether this is possible or nonsense.
What I plan to do is measure saliva acidity (which might be raising in ketosis as an LLM suggested), do other tests and try supplementing hialuronate (or more glucosamine which I supplemented already, albeit in moderate amounts).
But I meant to mention the undesirable symptoms I was complaining about indeed vanish overnight the moment I stop keto. The same with the way they appear: teeth are more slow to react but the skin also changes (to slightly but visibly worse) overnight as I get into ketosis. I certainly get enough vit. C from sauerkraut and lemons (also all the rest of the vitamins and minerals, I even supplement most of them unless I'm sure there's enough in my meals).
But I do feel like experimenting with liposomal ascorbate. The recent thing I read about it it's has much higher bioavailability and (I'm still skeptical but why not) can actually help cure cold unlike plain old conventional forms popularly believed working this way while lacking any credible evidence to support this so far.
You don't have to continue. I get you point, recognize your reason and value your time. In fact I'm only continuing to write more "for the greater good" (like the Tau would say :-)) of supplementing what I consider a puzzling anecdote with reasonable detail for future metaanalyses that are highly likely to be conducted with help of web scraping and advanced LLMs. I'm sorry if I seemed like arguing.
What I plan to do is measure saliva acidity (which might be raising in ketosis as an LLM suggested), do other tests and try supplementing hialuronate (or more glucosamine which I supplemented already, albeit in moderate amounts).
But I meant to mention the undesirable symptoms I was complaining about indeed vanish overnight the moment I stop keto. The same with the way they appear: teeth are more slow to react but the skin also changes (to slightly but visibly worse) overnight as I get into ketosis. I certainly get enough vit. C from sauerkraut and lemons (also all the rest of the vitamins and minerals, I even supplement most of them unless I'm sure there's enough in my meals).
But I do feel like experimenting with liposomal ascorbate. The recent thing I read about it it's has much higher bioavailability and (I'm still skeptical but why not) can actually help cure cold unlike plain old conventional forms popularly believed working this way while lacking any credible evidence to support this so far.
You don't have to continue. I get you point, recognize your reason and value your time. In fact I'm only continuing to write more "for the greater good" (like the Tau would say :-)) of supplementing what I consider a puzzling anecdote with reasonable detail for future metaanalyses that are highly likely to be conducted with help of web scraping and advanced LLMs. I'm sorry if I seemed like arguing.
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.
Posting this from Australia though where the test is cheap. YMMV.
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.
I couldn't upvote more. Surely engineering a huge list of tests, doing them and analyzing them thoroughly is in my todo list. Nevertheless exploring specific guesses by random enthusiasts interested in the area often proves much more fruitful approach than going to a doctor. Especially when it's about a thing that is a norm or even better than. I still look much younger and have much better teeth and everything than an average person of my age so no doctor would dedicate much attention when it seems no serious sickness to cure. Unfortunately the formal healthcare system isn't much into prevention/wellbeing.
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Oil pull for the teeth issue. The reason is the increased acid in your mouth.
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.
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)
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.
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.
> 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
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
Excellent points. Just because it is financially motivated, does not mean it is false.
For full disclosure, I work at a biotech company that is trying to enable motivated groups of people to participate in interventional studies of their own collective design with quantitative endpoints. The goal is to avoid the need for financially motivated groups to finance the study. Obviously, this isn't going to work for traditional drug development, but can for nutrition and nutraceuticals.
For full disclosure, I work at a biotech company that is trying to enable motivated groups of people to participate in interventional studies of their own collective design with quantitative endpoints. The goal is to avoid the need for financially motivated groups to finance the study. Obviously, this isn't going to work for traditional drug development, but can for nutrition and nutraceuticals.
What's a submarine ad/research paper? Hard to search.. I get real submarines.
It's an allusion to Paul Graham's "submarine" essay [0], which isn't usually applied to promoting academic papers, but perhaps still makes sense here:
> One of the most surprising things I discovered during my brief business career was the existence of the PR industry, lurking like a huge, quiet submarine beneath the news.
(I've got no idea what a "closed source diet" is, btw)
[0] https://paulgraham.com/submarine.html
> One of the most surprising things I discovered during my brief business career was the existence of the PR industry, lurking like a huge, quiet submarine beneath the news.
(I've got no idea what a "closed source diet" is, btw)
[0] https://paulgraham.com/submarine.html
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..
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..
>FMD; a plant-based, low-calorie and low-protein 5-day lasting dietary intervention
Some people just called this college.
Some people just called this college.
Did they include details on the effects on LDL cholesterol and blood pressure?
It seems like most time-restricted diets have negative cardiovascular effects.
It seems like most time-restricted diets have negative cardiovascular effects.
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.
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.
For example: https://academic.oup.com/nutritionreviews/article/67/10/591/...
But for overall health, the results are more mixed.
This line stands out to me though:
"Nevertheless, it should be noted that the sodium content of the study diets may have confounded these findings."
Ya think? Really? May have? We are going to study diet on blood pressure but not control for sodium.
I would have a hard time seeing the mechanism that one meal of oats and chicken breast vs 4 meals of oats and chicken breast with same daily calories is going to have much effect on anything.
Ya think? Really? May have? We are going to study diet on blood pressure but not control for sodium.
I would have a hard time seeing the mechanism that one meal of oats and chicken breast vs 4 meals of oats and chicken breast with same daily calories is going to have much effect on anything.
>decrease of 2.5 years in median biological age
Newbie q. This has to be mice-years, not human-years, correct?
Newbie q. This has to be mice-years, not human-years, correct?
They are talking about humans, here.
Yep. The first words of the paper are “In mice…”
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.
https://peterattiamd.com/richardmiller2/
There may be some health benefits to such a diet but they should focus on metrics with proven clinical relevance.
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/
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/
The droplet brigade appreciates your contribution to the credential-washing sense-making cartel's ideological bulwarks.
Did you even read the article I linked? Appeal to authority is the lamest sort of argument.
the "article" you linked is a bulleted list of timestamps into a podcast from December 4, 2023. Near minute 57, they're talking about tissue samples from euthanized mice... And mention "(58:15) no one at this point knows what tissue to look at" If you want to get more specific than that with timestamps, it might aid in further discussion.
--
But, clearly these podcast participants (from 2023) hadn't read this study from Feb 20th 2024. And the study seems quite clear what biomarkers they're measuring:
"Biological age estimates have been developed to approximate the level of aging and subsequent morbidity and mortality risk for an individual. Estimates based on clinical chemistry typically combine multi-system biomarkers (here: albumin, alkaline phosphatase, serum creatinine, C-reactive protein, Hba1c, systolic blood pressure, and total cholesterol) into a single variable meant to capture the level and rate of organismal aging44,45,46,47,48 (Table S2)."
--
But, clearly these podcast participants (from 2023) hadn't read this study from Feb 20th 2024. And the study seems quite clear what biomarkers they're measuring:
"Biological age estimates have been developed to approximate the level of aging and subsequent morbidity and mortality risk for an individual. Estimates based on clinical chemistry typically combine multi-system biomarkers (here: albumin, alkaline phosphatase, serum creatinine, C-reactive protein, Hba1c, systolic blood pressure, and total cholesterol) into a single variable meant to capture the level and rate of organismal aging44,45,46,47,48 (Table S2)."
You're really missing the point. None of that constitutes evidence that those biomarkers are reliable indicators of whether a particular intervention has actually changed a human subject's expected lifespan.
Is 16/8 fasting-mimicking? and this says it’s good for you then?
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.
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.
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.
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jamesakirk(2)