The ketogenic diet improves healthspan and memory in aging mice | Hacker News Reader

The ketogenic diet improves healthspan and memory in aging mice

medicalxpress.com

47 pointsPaulHoule34 comments

Be careful because there exists significant evidence against the ketogenic diet. For example:

Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis (2021) (PMID: 33558457)

> increased β-OHB levels and SIRT7 expression, decreased mitochondrial biogenesis, and increased cardiac fibrosis were detected in human atrial fibrillation heart tissues. Our results highlighted the unknown detrimental effects of KDs

Ketogenic diet induces p53-dependent cellular senescence in multiple organs (2024) (PMID: 38758782)

> Mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD.

As per PMC11100565, a cycled KD avoids the senescence issue:

> Both an alternate-day and an alternate-week IKD have been reported to improve health parameters over a continuous KD in different murine models (10, 64), while a third study using a 3-day/week IKD reported attenuated improvements relative to continuous KD (74).

Contrast this with the recent HN submission that found that a high fat diet altered mice microbiome and created changes in the signaling pathways in the brain related to anxiety:

High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats https://news.ycombinator.com/item?id=40801181

May depend what kind of fat it is.

My one one rat experience was trying keto years back and having my glycogen reserves bottom out and my body had not switched to ketone body metabolism so I was thoroughly spaced when I was chairing a critical meeting where we had 20 members vote one way, 20 members vote the other way with one in the bathroom. Fortunately a friend helped delay a remote until the person got back from the bathroom who voted the way we wanted.

It seemed like a win at the time but it was the first of many votes like that that revealed our organization was non-viable.

What a weird non sequitur that was

Perhaps the commenter is still spaced out by their diet.

If its gut biome, its probably both hereditary and envirnomental and going to suffer from way too many convolutional variables.

Although the value of fecal transplants will probably rocket if you can isolate biomes which thrive in tge current.dietary environment.

> the brain related to anxiety

anxiety likely may produce some healthy behaviour reaction: animal starts running/hunting/escaping more, which may increase health indicators. Many humans start overeating, which is bad.

Story from my life: when I was in some stressful life situation, I exercised much more driving my anxiety/fear in that direction, and got the best fitness results in my life.

Anecdotally, everyone I know who has been on a keto diet always complained about brain fog and memory problems.

It is normal that you bonk when you start and run out of glycogen. Your body adapts after a few days.

Yes, everyone goes through the initial sluggishness getting into keto, but this only lasts a few days to a week and can be dealt with via exogenous ketones. One of the biggest benefits for me in keto was consistent even energy. It eliminated the post-lunch lethargy and gave me consistent energy throughout the day. I almost felt like I needed to sleep a bit less when I was on it. I'm not sure if that was better sleep or actually needing less sleep but my energy was great when I was doing keto.

As long as I’m weight lifting consistently, I have no post-lunch lethargy. If I pause for a few days, I almost pass out after lunch. This is consistent. Must be related to the glucose-insulin response

People really need to test whether they are actually making enough ketones.

That's temporary though. That's not from the keto diet directly, it's from your body adapting to the keto diet. After a few weeks, that goes away entirely. It's commonly refered to as "keto flu".

Also, yes to brain fog, but I've never heard of memory problems. It's really just feeling low-energy.

there is also internet belief that this happens because of lack of electrolytes, and can be mitigated by adding nutrition additions.

I could not find their definition of a high-fat diet. Anecdotally I have often heard researchers of ketogenic diets complain that in animal studies "high-fat diets" typically contain high amounts of sugar as well, and thus do not induce a low-insulin state as we see in ketogenic diets.

From memory, the study I linked used 40ish percent fat as the high fat diet, so not keto by any means.

One also needs to be aware of the actual fatty acid profile of the lab feed used. The researchers may not even know (or be aware of the possible differences) until asked to track down what the specific feed was.

“Animal fat” that is highly unsaturated because it was from pigs fed polyunsatured seed meal byproduct, is going to have different health effects from the more saturated fat from a ruminant like a cow, which typically resist PUFA accumulation. Even breed and time of year will affect the fatty acid contents, so to be sure you always have to test. In this case, looks like the fat was a crisco (pig lard, maby), coconut oil (highly saturated) and corn oil (highly unsaturated) blend.

On a related note, on the labels of food you buy, the types of fat listed can be wildly different from what is actually in the food, simply because there is so much variation it’s not economical to test that much. Food items from smaller producers can also just use a generic label provided by the FDA, rather than actually testing themselves.

A high-fat diet and ketogenic diet are NOT synonymous. Keto is high-fat but high-fat is not keto.

That source study is here: https://www.cell.com/cell-reports-medicine/fulltext/S2666-37...

Also they seemed to show a lifespan change with caloric reduction. The same wasn't seen (at least in at the same level) in humans.

Are mice and human nutritional needs similar enough to draw any useful conclusions here? Genuine question.

As I understand it, it's a beta test at best. It's mostly for scientists to prove it's safe ethical and worth the money of moving forward to test on humans, more than evidence of the underlining hypothesis. It is to be taken with a grain of salt. If it's working for you now keep doing it, if you're not doing it don't feel pressured to do it, just keep an eye out.

Usually that's what I hear from the bio/fitness PHDs breaking down studies on nutrition/drug effects for fitness/nutrition.

The conclusion of the paper is the title. Extrapolating out from it to conclusions about humans should be regarded as just that, an extrapolation until tested otherwise.

I think this is obviously a both yes and no answer.

Yes in that we are both mammals, and we have similar bodies given our common ancestors.

No in that even different humans have different responses to diets, so why should mammalian cousins be enlightening on medical issues.

Science is complicated and everything is a question of scope and ability to test. It’s certainly used information, but should probably be replicated and then experimented with by humans.

no, of course not, we've been using them in experiments just for shits and giggles

https://en.wikipedia.org/wiki/Laboratory_mouse#Limitations

"Overall, mice and humans share virtually the same set of genes. Almost every gene found in one species so far has been found in a closely related form in the other. Of the approximately 4,000 genes that have been studied, less than 10 are found in one species but not in the other." https://www.genome.gov/10001345/importance-of-mouse-genome

Alert the influencers and grifters everyone, there's a fresh small-sample-size study to peddle. Use code yourdailydietguru to sign up and get 20% off your first order of the worlds first ketogenic cereal.

Purely observance and subjective personal experience. I find the best results for myself are when I stay closer to ruminant meat and eggs as my primary nutrition sources. I tend to feel various forms of ill when I have wheat and legumes (depending on processing).

For most, I've seen the best results when people stay closer to minimally processed foods in general. Paleo, keto, vegetarian, can all be either minimally processed or include in-group junk foods. Personally, I think it's the junk food, excessive sugar and seed oil consumption that most do best without. It's hard to do, and harder still the more restrictive of a diet you may be getting the best results from. Especially when interacting with social queues and food around you.

Mice aren't people. Small sample size- sounds like they used only 8 mice?

This obsession with extreme diets is a very American phenomenon. The human body will adapt to any diet that's given, it matters very little in practice. Just eat sensibly and listen to your body. That's pretty much it. Queue the hucksters and grifters who say "avoid X!", while they themselves are on high doses of rHGH, TRT, AAS, etc

I agree that for most people a regular diet is probably just fine, and the right choice.

However, it takes very little looking to see that there is interest in keto in the UK, for example: https://www.bhf.org.uk/informationsupport/heart-matters-maga...

The vast, vast majority of people I know in real life (in the US, in case it is not obvious) have exactly zero interest in any kind of extreme diet. The ones that do tend to be louder, which you may mistake as implying it is a commonly held belief.

I think most people can handle most diets. I do think that there are influences from things like excess sugar, seed oil and highly processed foods. These are things that are generally hard to study en-masse and take a lot of time. Observational studies are more difficult to get anything convincing from in general. Not to mention differences that take place over generations, like experienced in some cat feeding experiments.

"Food" has changed so much in the past 150 years and more around 100 years ago then the history of man before it. Humans are also incredibly adaptive, and experience disease in different ways altogether.

Reply on news.ycombinator.com