5 ms·

Does this lend credence to the rumored idea that putting the body into ketosis (or perhaps ketoacidosis) could actually have tumor fighting effects?

actually_a_dog 5y ago
There is some evidence that a ketogenic diet might be of benefit to cancer patients: > In KDs, the 4:1 ratio of high fat to low carbohydrates mimics the metabolic effects of starvation (Figure 2). These diets slow cancer by inhibiting insulin/IGF and downstream intracellular signaling pathways, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR). Ketogenic diets also amplify adenosine monophosphate—activated protein kinase (AMPK), which inhibits aerobic glycolysis and suppresses tumor proliferation, invasion, and migration. Mouse models of metastatic cancer show that exogenous ketones themselves have direct cytotoxic effects on tumor viability.5 β-hydroxybutyrate can modify chromatin by binding to and thereby inhibiting histone deacetylase, ultimately repressing transcription and curbing cancer cell proliferation (Figure 1). [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ This same article also mentions that a ketogenic diet can promote weight gain in cancer patients, which is a concern because frequently such patients lose weight as a result of both their disease and the treatment for it. Although not a scientific paper, there is some suggestion in [1] that both fasting and keto can have benefits in terms of making chemotherapy both more tolerable and effective. The suggestion here is that driving down insulin and blood sugar may be the mechanism, which seems naively to mean it effectively "starves out" the cancer. Note however that both keto and fasting act on the insulin/IGF, AMPK and mTOR pathways, so there is a moderately large web of cellular/biological interactions to untangle here. As a side note, the insulin/IGF, AMPK, and mTOR pathways are frequently implicated in animal studies of general longevity as well. We don't know the extent to which this stuff transfers over to humans, but, if you're a mouse, we can extend your life dramatically by playing around with these metabolic pathways. --- [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ [1]: https://www.curetoday.com/view/early-evidence-shows-fasting-keto-diet-may-make-chemo-and-some-other-cancrer-treatments-more-effective-and-easier-to-tolerate https://www.curetoday.com/view/early-evidence-shows-fasting-...
daniel_iversen 5y ago
I think potentially so. There was a podcast episode with Tim Ferris or/and Kevin Rose once (maybe this one? [1]) where they talked about research from/with Valter Longo on this (and it’s likely in his book too). Also in Michael Mosley’s book “Fast 800” he talks about how once you’ve fasted for 12 hours your body triggers the “metabolic switch” and autophagy happens where your body starts dissolving/eating(?) unhealthy cells which are then later regenerated! [1] https://podcast.kevinrose.com/guests/dr-valter-longo/ https://podcast.kevinrose.com/guests/dr-valter-longo/
- heymijo 5y ago
  The 12 hours is a guess. IPeter Attia has talked about this. We just don’t know when autophagy kicks in in humans as we have no direct measurements or bio markers to measure yet. I forget how they measure it in animals but I believe it results in animals no longer being among the living.
- tacon 5y ago
  This second episode with Dom D'Agostino discusses potential cancer treatments with the ketogenic diet: https://tim.blog/2018/06/05/the-tim-ferriss-show-transcripts-dom-dagostino-the-power-of-the-ketogenic-diet/ https://tim.blog/2018/06/05/the-tim-ferriss-show-transcripts...
deleted 5y ago
[deleted]
failwhaleshark 5y ago
It makes intuitive sense that people who are overweight / too well-feed get more cancers than people who are subsistence farmers and don't get quite enough to eat. The evidence is the rate of cancers between countries. I would examine if keto / severe calorie restriction kills more precancerous and cancerous cells through stress. It's probably best to start calorie restriction before acquiring cancer to keep the population of precancerous down.
- puchatek 5y ago
  That's hardly evidence. You have to control for all the other things that differ between developed and undeveloped countries. Since this is difficult you could at the very least find 1000 farmers in an undeveloped country and feed them 100g of fat a day I'm addition to what they eat, then monitor their health for a few decades. Then we'd know better
- MrBuddyCasino 5y ago
  Don't you simply have more cells that can turn into cancer when you're fat? More tickets for the cancer lottery? As you usually loose weight on keto, maybe that explains the protective effect?
  - failwhaleshark 5y ago
    Not exactly. Fat cells primarily increase in volume in response to lipogenesis. One of the primary hypotheses behind chemotherapy is to halt all cell division to let stress kill off more cancerous cells than healthy ones. The idea being that cancerous cells are more fragile than healthy ones, even though they proliferate faster and don't execute programmed cell death themselves as readily.
nabla9 5y ago
No. The mechanism described absolutely not. The paper starts with the fact that tumor acidosis promotes disease progression through a stimulation of fatty acid metabolism in cancer cells. Instead of blocking fatty acids, they test a hypothesis that excess uptake of specific fatty acid could have antitumor effects.
fpoling 5y ago
In Mongolia especially in rural area local people eat only meat/fat from horses, sheep and camels and drink heavy fermented horse milk. They do not eat any fruits or vegetables (it is hard to grow those in a semi-desert). They also avoid fish even when it is plenty in nearby rivers or lakes. Mongolia is on top of the charts regarding death from liver and other cancers and from heart decease. So I very much doubt that keto-diet has a protection against cancer. On the other hand the life expectancy both absolute and conditional at a particular age of Mongolians either matches or within 2-3 years of that of Indians who eat mostly vegetarian diet. So if Mongolian have high prevalence of cancers, then they must have less prevalences of other deceases. So if keto diet has any protection, then it is against those other deceases, but not for cancer and heart ones.

actually_a_dog 5y ago

There is some evidence that a ketogenic diet might be of benefit to cancer patients: > In KDs, the 4:1 ratio of high fat to low carbohydrates mimics the metabolic effects of starvation (Figure 2). These diets slow cancer by inhibiting insulin/IGF and downstream intracellular signaling pathways, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR). Ketogenic diets also amplify adenosine monophosphate—activated protein kinase (AMPK), which inhibits aerobic glycolysis and suppresses tumor proliferation, invasion, and migration. Mouse models of metastatic cancer show that exogenous ketones themselves have direct cytotoxic effects on tumor viability.5 β-hydroxybutyrate can modify chromatin by binding to and thereby inhibiting histone deacetylase, ultimately repressing transcription and curbing cancer cell proliferation (Figure 1). [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ This same article also mentions that a ketogenic diet can promote weight gain in cancer patients, which is a concern because frequently such patients lose weight as a result of both their disease and the treatment for it. Although not a scientific paper, there is some suggestion in [1] that both fasting and keto can have benefits in terms of making chemotherapy both more tolerable and effective. The suggestion here is that driving down insulin and blood sugar may be the mechanism, which seems naively to mean it effectively "starves out" the cancer. Note however that both keto and fasting act on the insulin/IGF, AMPK and mTOR pathways, so there is a moderately large web of cellular/biological interactions to untangle here. As a side note, the insulin/IGF, AMPK, and mTOR pathways are frequently implicated in animal studies of general longevity as well. We don't know the extent to which this stuff transfers over to humans, but, if you're a mouse, we can extend your life dramatically by playing around with these metabolic pathways. --- [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ [1]: https://www.curetoday.com/view/early-evidence-shows-fasting-keto-diet-may-make-chemo-and-some-other-cancrer-treatments-more-effective-and-easier-to-tolerate https://www.curetoday.com/view/early-evidence-shows-fasting-...

daniel_iversen 5y ago

I think potentially so. There was a podcast episode with Tim Ferris or/and Kevin Rose once (maybe this one? [1]) where they talked about research from/with Valter Longo on this (and it’s likely in his book too). Also in Michael Mosley’s book “Fast 800” he talks about how once you’ve fasted for 12 hours your body triggers the “metabolic switch” and autophagy happens where your body starts dissolving/eating(?) unhealthy cells which are then later regenerated! [1] https://podcast.kevinrose.com/guests/dr-valter-longo/ https://podcast.kevinrose.com/guests/dr-valter-longo/

heymijo 5y ago
The 12 hours is a guess. IPeter Attia has talked about this. We just don’t know when autophagy kicks in in humans as we have no direct measurements or bio markers to measure yet. I forget how they measure it in animals but I believe it results in animals no longer being among the living.
tacon 5y ago
This second episode with Dom D'Agostino discusses potential cancer treatments with the ketogenic diet: https://tim.blog/2018/06/05/the-tim-ferriss-show-transcripts-dom-dagostino-the-power-of-the-ketogenic-diet/ https://tim.blog/2018/06/05/the-tim-ferriss-show-transcripts...

deleted 5y ago

[deleted]

failwhaleshark 5y ago

It makes intuitive sense that people who are overweight / too well-feed get more cancers than people who are subsistence farmers and don't get quite enough to eat. The evidence is the rate of cancers between countries. I would examine if keto / severe calorie restriction kills more precancerous and cancerous cells through stress. It's probably best to start calorie restriction before acquiring cancer to keep the population of precancerous down.

puchatek 5y ago
That's hardly evidence. You have to control for all the other things that differ between developed and undeveloped countries. Since this is difficult you could at the very least find 1000 farmers in an undeveloped country and feed them 100g of fat a day I'm addition to what they eat, then monitor their health for a few decades. Then we'd know better
MrBuddyCasino 5y ago
Don't you simply have more cells that can turn into cancer when you're fat? More tickets for the cancer lottery? As you usually loose weight on keto, maybe that explains the protective effect?
- failwhaleshark 5y ago
  Not exactly. Fat cells primarily increase in volume in response to lipogenesis. One of the primary hypotheses behind chemotherapy is to halt all cell division to let stress kill off more cancerous cells than healthy ones. The idea being that cancerous cells are more fragile than healthy ones, even though they proliferate faster and don't execute programmed cell death themselves as readily.

nabla9 5y ago

No. The mechanism described absolutely not. The paper starts with the fact that tumor acidosis promotes disease progression through a stimulation of fatty acid metabolism in cancer cells. Instead of blocking fatty acids, they test a hypothesis that excess uptake of specific fatty acid could have antitumor effects.

fpoling 5y ago

In Mongolia especially in rural area local people eat only meat/fat from horses, sheep and camels and drink heavy fermented horse milk. They do not eat any fruits or vegetables (it is hard to grow those in a semi-desert). They also avoid fish even when it is plenty in nearby rivers or lakes. Mongolia is on top of the charts regarding death from liver and other cancers and from heart decease. So I very much doubt that keto-diet has a protection against cancer. On the other hand the life expectancy both absolute and conditional at a particular age of Mongolians either matches or within 2-3 years of that of Indians who eat mostly vegetarian diet. So if Mongolian have high prevalence of cancers, then they must have less prevalences of other deceases. So if keto diet has any protection, then it is against those other deceases, but not for cancer and heart ones.