Hungry Fat Cells Could Someday Starve Cancer

165 pointsposted 4 days ago
by mrtnmrtn
(ucsf.edu)

54 Comments

sejje

4 days ago

> Nguyen moved to UT Austin to start his own lab in January 2024 but passed away suddenly in November before he could finish the final experiments. The paper, of which he is the first author, is dedicated to him.

That's sad. I hope someone picks up the torch. The research sounds very promising.

sigmoid10

4 days ago

The thing is, this is not really new. People have been pushing this metabolic theory of cancer for a long time now and even used it to propose things like cold therapy or ketogenic diets as a treatment option, despite the fact that we have very little evidence that any of this stuff really works. It is still refreshing to see people target cancer from a theory-first standpoint instead of the usual empirical tactics, but the theoretical foundation of cancer science simply isn't that good. Clinicians also aren't slow to adapt or scared to experiment with these new approaches, because everyone would jump immediately on those fancy low-invasive supplement treatments when the alternative is certain death. But you can't game the final survivability statistics, now matter how reasonable your theory sounds or how well founded it is.

adrian_b

3 days ago

I do not remember "evidence that any of this stuff really works" about curing an existing cancer, but there was rather strong evidence in large-scale studies with various lab animals, in which a mutagen agent created tumors when they were fed normally, but no tumors appeared when they were malnourished, either by eating a reduced amount of protein, or by eating the normal amount of protein, but with a bad amino-acid profile.

Both forms of malnutrition would diminish the capacity of synthesizing proteins, which would affect mainly a fast-growing organ, like the tumors. Presumably this slowed down the growth of the tumors, allowing time for the immune system to react and suppress them in their incipient form.

Unfortunately, malnutrition as a prophylactic measure does not really work, as it enhances the risk of other diseases, even if it might lower the risk of cancer.

The method described in the parent article might have better chances, but it seems likely to work only with a cancer that has been discovered very early.

sigmoid10

3 days ago

Yes, this is exactly what theory-first approaches look like. And no, there is no data that any of this really works in humans. If it was about curing cancer in mice that were genetically engineered to have cancer in the first place, of course we'd already be there. But it isn't and we aren't.

__natty__

4 days ago

And he was only 35. Rest in peace.

edwardtay

4 days ago

The metabolic competition angle is fascinating - it's elegant how this leverages the body's own resource allocation rather than trying to poison cancer cells directly.

A few questions about the mechanism:

1. How selective is this approach? Cancer cells are notoriously heterogeneous - do different cancer types or subtypes respond differently to this metabolic pressure?

2. The cold exposure converting white to beige fat is interesting, but what about the feasibility for actual patients? Sustained cold exposure seems difficult to maintain for someone already dealing with cancer treatment.

3. Has anyone looked at whether this could work synergistically with existing metabolic therapies like metformin or ketogenic diets? The metabolic stress combined with nutrient competition could be powerful.

4. What's the risk of adaptive resistance? Cancer cells are remarkably good at finding alternative metabolic pathways when stressed.

RIP to Nguyen - it's heartbreaking when promising researchers pass before seeing their work come to fruition. Hope the team continues this line of investigation.

Dumblydorr

4 days ago

It’s CRISPR and injection changing their fat cells, not cold exposure. They theorized something in cold exposure modulated energy and fat, they found genes and tested which one works best via crispr, the ucp1

mettamage

4 days ago

For the curious among us, here are articles related to cold exposure in mice and cancer [1, 2, 3]. I briefly skimmed it but seems like a somewhat plausible idea in the realm of: if it doesn’t hurt you, it can perhaps benefit you.

Also, I think in some cases you can pair it with the Wim Hof Method to make short extreme cold exposure more bearable. I don’t know what the interaction is with norepinephrine though as doing the WHM, one releases a lot of it [4] (I was part of this experiment as a participant so remember the paper quite well). Note, I am not claiming the WHM may help with suppressing cancer, I am simply claiming that it is my experience that performing the WHM makes cold exposure a bit more comfortable. I suspect this is because tons of norepinephrine goes through your body.

On day 4 of our WHM training we were walking 2.5 hours to the top of some Polish ski resort near Wim’s house. It was -7 degrees Celsius. We had shoes on and shorts. No one got frostbite (24 people in total did it, 2 groups of 12 - a few weeks apart). There were 2 research doctors with us (though they were capable doctors as they needed to apply oxygen to one person almost, as he took the training on day 3 really far as we were encouraged to by the doctors and Wim - ultimately it wasn’t needed. Just before they rushed to apply it he started breathing himself again and regained consciousness).

[1] https://www.nature.com/articles/s41586-022-05030-3

[2] https://news.ki.se/cool-room-temperature-inhibited-cancer-gr...

[3] https://www.nature.com/articles/s41392-022-01284-5

[4] https://www.pnas.org/doi/10.1073/pnas.1322174111

manmal

4 days ago

Why would someone do this to themselves? Such a trip doesn’t sound like a lot of fun. Wouldn’t long term sauna have similar effects and be way less straining on the cardiovascular system?

mettamage

a day ago

Don't know, haven't looked into it. Do you have any sources I could start reading on?

UniverseHacker

4 days ago

This is fascinating and sounds really promising.

However, this article also seems to imply that frequent cold exposure that converts your own white fat cells into beige fat cells could be effective at both treating and preventing cancer.

They state without explanation that cold therapy cannot be done by cancer patients, but I don’t see why not. I take an ice bath every morning as it helps with my mental health, and its really not that shocking or difficult when you’re used to it as the very adaptation they’re talking about here eventually makes it easy to tolerate cold- your body adapts to be able to keep you warm. I can and do still do it when I’m sick, fatigued, or slept poorly.

Moreover, before modern climate controlled environments and low cost warm clothing humans naturally experienced cold a lot more often and were probably already cold adapted, even in warm climates. Could modern heating systems be predisposing us to cancer by making our metabolism work abnormally?

OutOfHere

4 days ago

The problem with chronic cold exposure is that it makes one very hungry, a lot hungrier than usual, with the compensatory calorie consumption risking negating the intended benefit.

brandall10

4 days ago

Hunger, like cold exposure, is an uncomfortable but transient signal. In many cases it peaks and subsides without requiring immediate action, especially once the body adapts.

Anecdotally, my first 72-hour fast was revealing. Around the 48-hour mark my body aggressively signaled hunger, esp. for sugary foods. By the third day, however, hunger largely subsided, and at break I wasn’t hungry at all. For the following week the usual sugary suspects in my life went untouched. Subsequent 72-hour fasts were far more manageable, suggesting at least some component of adaptation.

My understanding is that this ability to adapt exists because intermittent hunger and cold were regular aspects of human life for much of our history, particularly in environments without reliable food access (pre-agrarian) or thermal protection.

ricardonunez

4 days ago

I have similar findings. I fast regularly and take cold showers. Another thing is one meal days are far easier after you do it couple of times. You don’t even think about food which is harder if you have two to three meals per day.

Edit: for those wanting to try this lifestyle, everybody is different. do your own research before jumping into regular fasting or even cold showers. Max time without food I did was 6 days, since then t it he max is 72 hours. Do blood work regularly and if you drink coffee be aware that caffeine withdraws are painful.

gametorch

4 days ago

> Another thing is one meal days are far easier after you do it couple of times.

It's mind-boggling to me that multiple "one meal" days don't incidentally happen to everyone over the course of a year.

I would think most people have those days where they skip breakfast and lunch due to some or other exigency and only get to eat dinner.

SoftTalker

4 days ago

I only eat breakfast intentionally, as I am not really hungry in the mornings. But as I understand it, it's better to get your calories earlier in the day than late, so I make myself eat in the morning.

ricardonunez

3 days ago

I am testing it at the moment. I read that cortisol levels raise after 14 hours or so of no food. So I decided to eat breakfast about 13 hours to see if there's any changes on my mood. I do find it that I get less cranky. Another thing, this year during mother's day I had a huge brunch, so I didn't eat anything else that day, and it worked fine for 24 hours, the problem is that I felt in comma after eating that much which is one of the reason I stopped eating lunch, I don't like to crash; what to eat solves that partially, but I still fine some slow down after eating breakfast.

anonzzzies

4 days ago

When calory restricting I do this too: I am actually never hungry before 11 am while I get up at 5 am always but I force myself (at 8) and don't need anything else the rest of the day because of it.

hyperman1

4 days ago

You scare me. After life dishing out one of its lessens, I decided to get some fundamentals in order, and for me that includes 3 meals a day, with the family. Things have to get really disastrous to not get breakfast, and I don't think my kid skipped breakfast ever. Each his own, of course, but I wonder what happens in your life that this is semi normal?

gametorch

4 days ago

I have a morning routine. Usually I go for a walk and read for an hour before doing anything else. But I almost never eat breakfast. I'm just not hungry in the morning.

By midday I'm on an adventure. Some days, it takes me in a direction where it makes more sense to skip lunch than to stop and have it.

When I'm hungry and it's convenient, I eat. When I'm not, I don't.

It's almost never the case that I'm hungry for a meal three times a day.

robocat

3 days ago

> if you drink coffee be aware that caffeine withdraws are painful.

I've successfully used caffeine pills (e.g. some NoDoz brand products) for coffee replacement to avoid withdrawal symptoms.

Specifically I used caffeine pills to give up coffee. I found it easy to taper down caffeine usage to zero by using a standardised dose size.

Additionally pills are a habit change which helps me stick with a plan. I have tapered down using instant coffee but I found that was a little harder to police myself.

Fire-Dragon-DoL

4 days ago

I cannot work when I don't eat, I'm unable to think properly. I'm not sure how people manage fasting

adrian_b

3 days ago

When you do not eat, you are not permanently hungry, at least not when you are accustomed to this. This is similarly like when you feel that you must immediately use the restroom, but when that not happens the sensation disappears and it may come back only one hour or two later.

What is funny is that, at least for me, the sensation of hunger is strongly conditioned by whether there really exists a possibility to satisfy it.

I eat 2 meals per day and during the time between them I am not hungry, and if I were hungry that would be futile, because I intentionally do not keep in my home any kind of food that can be eaten instantly, but only raw ingredients that I must cook before eating.

After I cook my next meal, I have to be patient and wait some time for the food to cool down. During that time, I become suddenly very hungry and like you say, I find it difficult to continue to work at the computer or at whatever I was doing, as my thought shifts to the food I am waiting to eat.

In the past, when I kept food that could be eaten at any time, without preparation, I became frequently hungry and it was hard to resist to the temptation of having a snack.

UniverseHacker

3 days ago

Some people never seem to be able to think clearly or focus while fasting, independently of any feelings of hunger. There is likely some biological variability here, but it could also be due to metabolic problems that are making it hard to provide the brain with energy during a fast. In some cases the fasting itself can help treat that, and it may get better over time.

UniverseHacker

3 days ago

People respond differently to fasting, some are never able to do focused knowledge work during a fast, others can’t at first but can once their bodies get used to fasting. Others can immediately focus better right from the beginning. There is a lot of individual variation.

Fire-Dragon-DoL

3 days ago

I literally cannot sleep if hungry. I wake up in the middle of the night if I had dinner and went to bed at midnight. My trick is to eat one apple right before sleep, then I wake up not hungry and can sleep well.

sowbug

4 days ago

If you can handle the body's switchover to ketosis, the rest of the fast is relatively easy.

Fire-Dragon-DoL

4 days ago

I did that before, my breath becomes horrible when that happens, but it's way more manageable. Is there a way to activate ketosis before starting the fasting? That seems like it could solve my problem

sowbug

4 days ago

Ketosis is your body using fat as an energy source when glucose isn't readily available. So if you deprive yourself of dietary glucose (carbs, simple sugars, etc), but keep eating fat and protein, you'll enter ketosis while eating as much sustenance as you want. Use ketone strips to tell when it happens.

The breath thing is unavoidable as far as I know.

UniverseHacker

3 days ago

Apologies in advance for the pedantic response, but the human body can generally make enough glucose from protein to keep you out of ketosis. You usually have to restrict both protein and fat to reliably induce ketosis. You can confirm this for yourself with ketone test strips. Most dieters on so called ketogenic diets are not actually in ketosis.

Even more surprising is that fermentable fibers get converted into short chain fats by bacteria in the gut that are ultimately metabolized as ketones, so a diet high in those can induce ketosis even with a high carb diet. Some herbivore animals are always in ketosis, and some carnivores are almost never in ketosis unless they are starving and can’t find protein.

user

3 days ago

[deleted]

UniverseHacker

4 days ago

Ultimately, regardless of how one feels, you need to (will) maintain calorie balance in the long term, and cold exposure requires a higher calorie intake.

brandall10

4 days ago

For sure, but my point is that increased hunger doesn’t automatically negate the benefit via overeating; people often adapt through modest adjustment instead.

More generally, it seems inconsistent to assume someone can voluntarily tolerate significant cold discomfort while being unable to manage similar degrees of hunger discomfort.

louthy

4 days ago

I also found that after my first 3 day fast I was able to deal with hunger much better. I used to get irritable when hungry and now I realise I can just tolerate it without any real downside — even years after my last fast.

It’s like my brain has retrained itself to ‘just get over it’. It was quite something

deepsun

4 days ago

I read blockade survivors diaries, they all say it's easy to get used to hunger, but not to cold.

anonzzzies

4 days ago

After about 24 hours I don't notice anymore. I just finished a 2 week fast on only water, tea and supplements. I hardly notice when I focus on something else (work/hobby). When I stop focusing I get sleepy instead of hungry. Cold I have not managed; I come from a cold country and I really really hate any type of cold; I like 30C+ high humidity as a baseline, under that, I am cold and uncomfortable. I did try to view them the same and tried to meditate through it, but, unlike fasting, I cannot ignore the continues suffering that is cold while fasting is almost pleasant (makes me sharper).

UniverseHacker

4 days ago

If white fat converts to beige fat, it is going to be burning a lot more calories, so you ultimately would have to eat more to maintain a stable body weight. It’s not clear to me that this would negate the benefit.

If it does negate the benefit than that would suggest that the entire benefit from the beige fat is from putting the body in a calorie deficit, and you would then expect the exact same effectiveness from calorie restriction. A quick search shows that there does seem to be an anti cancer therapeutic benefit from calorie restriction, so this seems at least plausible.

So this raises the research question of if increasing calorie intake to keep weight stable completely negates the anti-cancer benefits of increased beige fat or not. I’m curious if that has been investigated yet.

blensor

4 days ago

I recently saw a video discussing fasting effects on cancer.

In the past it seems the consensus was that since cancer cells need more fuel than regular cells, starving them is beneficial in combating it.

But recently it has been discovered that some cancers can grow better with ketones.

So it seems that some cancers benefit from fasting while others are starved from fasting.

bratwurst3000

4 days ago

in all respect sorry this is wrong. this is a broad misinformation. It can enhance but also supresse cancer dependig of soo much we dont know yet enough to know if fasting is beneficial or dangerous.

https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.5577

edit:// and the article has imho nothinh to do with autophagy. Its about beige fat cells eating stuff away from cancer not autophagy wich happened in the innercell. And if you go into caloric deficit you could burn away those beige fat cells that "heal" the cancer.

UniverseHacker

4 days ago

The paper you posted is just a review on autophagy and cancer that doesn’t contradict anything I stated. It is a mistake to conflate autophagy, calorie restriction, and cold exposure as necessarily biologically identical, which your comment seems to imply.

I was only raising questions this research and discussion made me curious about, not making any concrete claims.

Although the idea of calorie restriction as a cancer treatment is something still actively debated and researched, I personally doubt it is very useful, or likely to be the main mechanism here in the connection between beige fat and cancer, but it is a possibility to at least be ruled out experimentally in the context of the comment I replied to, which is why I mentioned it anyways. One major concern with calorie restriction in humans but not rodents is that it shuts down your metabolism by limiting t3 thyroid hormone production whereas cold exposure ramps up metabolism by uncoupling mitochondria to produce heat. You are correct that the body can shut down processes and systems that might be important for fighting cancer, in response to calorie restriction.

I am a researcher that studies metabolism, and actually think the prominent focus on fasting and calorie restriction as a potential medical cure-all has been mostly a dead end, that people were mistakenly led down largely as a result of these fundamental differences between rodent and human metabolism.

bratwurst3000

4 days ago

you are right now I better understand what you meant.

That was the part that confused me.

"If it does negate the benefit than that would suggest that the entire benefit from the beige fat is from putting the body in a calorie deficit, and you would then expect the exact same effectiveness from calorie restriction"

As far as I understood the paper its beige fat that can eat away food from cancer and not white fat. And afaik calorie restriction doesnt augment beige fat. My error was thinking you meant calorie restriction while having white fat but you meant with beige fat? And yes this makes sense.

And I thinked autophagy because this is the main "thing" happenkng while fasting which is not burning body fuel

thanks for the answer

UniverseHacker

4 days ago

The comment you quoted was me paraphrasing what I saw as the implied idea that I was reading into the comment I was replying to. It's not what I personally suspect is going on here at all, but I can't dismiss it out of hand.

Yes, autophagy does ramp up during fasting, but it's just one of a number of different physiological changes that occur during fasting.

dustbunny

4 days ago

How do you create/store the ice?

UniverseHacker

3 days ago

I have an inflatable ice tub from costco, and a large aquarium chiller. There is no literal ice involved, just a tub of water that is just above freezing temps. You can buy regular bags of ice and put them in a bathtub full of water, but that is a hassle and expensive to do frequently.

dustbunny

3 days ago

So do you keep it chilled 24/7 or do you turn it on manually or with a timer?

cadamsdotcom

4 days ago

Hold one sec while I vibecode an ice recipe SaaS website, only charging $10/mo for all the ice recipes you can handle!

cathyreisenwitz

4 days ago

"Fat cells have many advantages... They are easy to obtain from patients." LOL. Also, we'll see if that's still true once everyone is on Ozempic.

semessier

4 days ago

triggering the cold signal artificially might be an approach

fnord77

4 days ago

> implanted in mice

every time

OutOfHere

4 days ago

[flagged]

gavinray

4 days ago

  > I can't wait to be downvoted for sharing something useful, which pretty much is par for the course on this site, i.e. altogether shallow people voting only on the basis of what they already believe in.
I think you're getting downvoted more on the basis of making claims without providing credible evidence.

If you really wanted to fend off the downvotes, I probably would have linked at least a handful of well-designed studies with outcomes supporting your claims.

Also, Occam's Razor would suggest that if it truly worked, surely the very smart people trying to solve this problem would have known about + adopted it.

OutOfHere

4 days ago

> Also, Occam's Razor would suggest that if it truly worked, surely the very smart people trying to solve this problem would have known about + adopted it.

Please save me from such nonsense. Only naive people believe that. Informed people know that nothing is pursued by big corporations if there isn't big money in it. And there isn't since it's a cheap common product produced around the world.

As a further example, mRNA tech was intentionally rejected, ignored, and not developed for decades. Meanwhile, the false beta-amyloid theory of Alzheimers was purused for over a decade even though it was very clear informed people that it's a dumb theory. People are not as smart as you think they are, not even close.

As for the studies, PMID 27980600 and DOI 10.1016/j.hermed.2024.100875 are a fair start, although the latter is paywalled.