6 ms·

Ketogenic diets inhibit mitochondrial genesis, induce cardiac fibrosis in rats

53 points by auslegung 6y ago

JMTQp8lwXL 6y ago
Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis in rats
- something98 6y ago
  I get so annoyed by authors that bury this point. Rodents are NOT tiny humans. Although there are some findings that carry over, there is much that does not.
- dang 6y ago
  Ok, we've squeezed rats in the title above.
- bhk 6y ago
  Still, all those people who were recommending keto diets for rats have some explaining to do.
- aent 6y ago
  https://twitter.com/justsaysinmice https://twitter.com/justsaysinmice
todipa 6y ago
This paper was surprisingly easy to read and understand.
gnicholas 6y ago
Is cardiac fibrosis good or bad? I skimmed through the article but couldn’t immediately tell.
- denkmoon 6y ago
  Fibrosis = Scarring. Not good for the heart.
  - gnicholas 6y ago
    Thanks! Would love a TLDR from you or another knowledgeable HNer. I couldn’t tell how big a problem this would be for people who are on the keto or IF spectrums.
    - denkmoon 6y ago
      My guess, noting that I am not a doctor or medically trained, merely have a BSc Biology. The study has only been done on rats, which are a good model species but not perfect. The next logical step would be investigating pigs perhaps. The mechanism of heart damage here is probably that the process for maintaining cardiac tissue requires material that is not available on a ketogenic diet, thus unmaintained cardiac tissue is replaced with scar tissue (mostly collagen) The problem with scar tissue in the heart is that it doesn't contribute to fibrilation/pumping blood. Article mentions nothing about intermittent fasting. Again, just guessing.
ggm 6y ago
This is concerning, because whilst not strictly ketogenic, my (and my partners) diet has shifted to significantly less carbs, as part of managed weightloss and if the consequence is cardiac fibrosis, thats a significant concern for her: she has pre-existing conditions including lack of strong heart function.
- novia 6y ago
  I think the vilification of all carbs is misguided. Complex carbohydrates and resistant starch should be kept in the diet. Straight sugar is the real killer.
  - ggm 6y ago
    We reduced. we didn't cut out entirely. We still have a high fibre (carb sourced) breakfast every day. Pasta moved to a special treat, potato likewise. Bread is mostly avoided.
ineedasername 6y ago
It's important to remember that the whole point of the keto diet is to introduce a near-fundamental change in your body's metabolism, including brain function. It should be regarded the same way you would regard a very potent medication-- one that does not have FDA approval. It's probably the sort of thing you should approach with extreme caution and the advice of a doctor & dietician.
samatman 6y ago
The title of this paper is so deliberately misleading that I flagged the submission. There is no reason whatsoever to think that the human response to ketosis would be at all similar to that of rats. And rats are what they studied. As long as rags like Nature keep publishing this garbage, hacks will keep producing it. Sad state of affairs all around.
- dvsfish 6y ago
  While I agree they should be more clear that the main focus of the study is about rats, reading the study suggests they did link it to human patients with atrial fibrosis. AF patients had higher β-OHB concentrations than healthy people, which is one of the by products of a ketogenic diet. Not a direct link to KD, but certain a point of interest. I think this study is a decent case for follow up studies at the very least.
daemonk 6y ago
There are a lot of good work digging into the mechanism of how it causes cardiac fibrosis in rats. I don't think we should completely dismiss it just because it is in a non-human model. If anything, this study allows us to try to use the same assays on humans to see if we can observe similar results.
40four 6y ago
It annoying to me the extraordinary divisiveness conversations on ketogenic diets generate at this point. But I get we are still in the middle of the learning curve scientifically, and there is a lot of confusion. If you follow the threads though, it’s becoming more and more clear though that practicing keto on a more or less ‘permanent’ basis, might not be the best choice for everyone. It goes both ways though, the ‘food pyramid’ they taught us growing up where the whole thing is based on bread & pasta is almost certainly bad too. The real benefits come from having a flexible metabolism that can ‘switch gears’ and go back and forth between carb burning and fat burning. This switch triggers a cascade of beneficial mechanisms is our bodies, so riding the line and being flexible is the best place to be I think. In the short term however, there are clear benefits to strict keto. An anecdotal example in my own case after practicing strict keto for about 6 months, I inadvertently cured my lifelong battle with acid reflux. I had no idea that would happen. I was honestly doing it in a general attempt to be more healthy and cut sugar out of my life. But I had a problem with heartburn literally since I was 13 years old. I used to have to eat rolaids like candy. I had on and off bouts with prescription strength stuff like Prilosec & others. After 6 months of keto my gut was permanently healed, even after stopping keto. I no longer need any medicine. Short term keto is a real treatment for acid reflux, this is something I think gets overlooked. I no longer practice keto, but a lot of the concepts I learned still stick with me. I practice intermittent fasting many days but not always. If I feel like eating breakfast I do. If I want some bread or pasta I eat it. But I don’t base my diet on it.
- orwin 6y ago
  I behave exactly the same way (fasting then keto for 6 month, not practicing keto long term but still lowering my sugar/alcohol intake). I still have occasional acid reflux, though less than before. I thing that when you start something like IF or keto, you already care enough for most of diet-related issues to tone done, like a placebo effect somehow.
- sleepysysadmin 6y ago
  >It annoying to me the extraordinary divisiveness conversations on ketogenic diets generate at this point. But I get we are still in the middle of the learning curve scientifically, and there is a lot of confusion. One of the big name diet plans blamed Keto for when they lost a huge portion of their revenue. At exactly the same time advertisements everywhere were about 'keto crotch' which is no longer a thing. Clearly were paid for articles to discourage women from going keto. There's a ton of $ to prevent people from going keto. Why? Imagine what a grocery store looks like if there were no carbs. A meat department, some drinks? The entire business model collapses. How about fast food? Some fast food joints have been catering to keto folks. The fast food joints that dont and traditionally push nothing but sugar are struggling. >I no longer practice keto, but a lot of the concepts I learned still stick with me. I practice intermittent fasting many days but not always. If I feel like eating breakfast I do. If I want some bread or pasta I eat it. But I don’t base my diet on it. How come you quit keto? Were there effects you didnt like or was it just the inconvenience that you basically cant eat anywhere?
kcplate 6y ago
Perhaps keto can kill me at 75, I kind of feel like that is slightly better than stroking out from T2 diabetes at 55.
chjahi92 6y ago
I wonder what David Sinclair thinks about this, and it’s effects on longevity in humans.
amanaplanacanal 6y ago
It seems obvious that various animals have different natural diets, that is, different diets that they are evolutionarily adapted to. A horse eats grass, a cat eats meat. I expect that of you performed the same dietary experiments using horses as the experimental animal, you would get very different results than if you used cats as the experimental animal. Cats are obligate carnivores, and are on a ketogenic diet, always. Is the rat natural diet the same as the human? If so, this might have some relevance to the human diet. This appears to be another example of the garbage that passes for nutrition science.

53 points by auslegung 6y ago

JMTQp8lwXL 6y ago

Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis in rats

something98 6y ago
I get so annoyed by authors that bury this point. Rodents are NOT tiny humans. Although there are some findings that carry over, there is much that does not.
dang 6y ago
Ok, we've squeezed rats in the title above.
bhk 6y ago
Still, all those people who were recommending keto diets for rats have some explaining to do.
aent 6y ago
https://twitter.com/justsaysinmice https://twitter.com/justsaysinmice

todipa 6y ago

This paper was surprisingly easy to read and understand.

gnicholas 6y ago

Is cardiac fibrosis good or bad? I skimmed through the article but couldn’t immediately tell.

denkmoon 6y ago
Fibrosis = Scarring. Not good for the heart.
- gnicholas 6y ago
  Thanks! Would love a TLDR from you or another knowledgeable HNer. I couldn’t tell how big a problem this would be for people who are on the keto or IF spectrums.
  - denkmoon 6y ago
    My guess, noting that I am not a doctor or medically trained, merely have a BSc Biology. The study has only been done on rats, which are a good model species but not perfect. The next logical step would be investigating pigs perhaps. The mechanism of heart damage here is probably that the process for maintaining cardiac tissue requires material that is not available on a ketogenic diet, thus unmaintained cardiac tissue is replaced with scar tissue (mostly collagen) The problem with scar tissue in the heart is that it doesn't contribute to fibrilation/pumping blood. Article mentions nothing about intermittent fasting. Again, just guessing.

ggm 6y ago

This is concerning, because whilst not strictly ketogenic, my (and my partners) diet has shifted to significantly less carbs, as part of managed weightloss and if the consequence is cardiac fibrosis, thats a significant concern for her: she has pre-existing conditions including lack of strong heart function.

novia 6y ago
I think the vilification of all carbs is misguided. Complex carbohydrates and resistant starch should be kept in the diet. Straight sugar is the real killer.
- ggm 6y ago
  We reduced. we didn't cut out entirely. We still have a high fibre (carb sourced) breakfast every day. Pasta moved to a special treat, potato likewise. Bread is mostly avoided.

ineedasername 6y ago

It's important to remember that the whole point of the keto diet is to introduce a near-fundamental change in your body's metabolism, including brain function. It should be regarded the same way you would regard a very potent medication-- one that does not have FDA approval. It's probably the sort of thing you should approach with extreme caution and the advice of a doctor & dietician.

samatman 6y ago

The title of this paper is so deliberately misleading that I flagged the submission. There is no reason whatsoever to think that the human response to ketosis would be at all similar to that of rats. And rats are what they studied. As long as rags like Nature keep publishing this garbage, hacks will keep producing it. Sad state of affairs all around.

dvsfish 6y ago
While I agree they should be more clear that the main focus of the study is about rats, reading the study suggests they did link it to human patients with atrial fibrosis. AF patients had higher β-OHB concentrations than healthy people, which is one of the by products of a ketogenic diet. Not a direct link to KD, but certain a point of interest. I think this study is a decent case for follow up studies at the very least.

daemonk 6y ago

There are a lot of good work digging into the mechanism of how it causes cardiac fibrosis in rats. I don't think we should completely dismiss it just because it is in a non-human model. If anything, this study allows us to try to use the same assays on humans to see if we can observe similar results.

40four 6y ago

It annoying to me the extraordinary divisiveness conversations on ketogenic diets generate at this point. But I get we are still in the middle of the learning curve scientifically, and there is a lot of confusion. If you follow the threads though, it’s becoming more and more clear though that practicing keto on a more or less ‘permanent’ basis, might not be the best choice for everyone. It goes both ways though, the ‘food pyramid’ they taught us growing up where the whole thing is based on bread & pasta is almost certainly bad too. The real benefits come from having a flexible metabolism that can ‘switch gears’ and go back and forth between carb burning and fat burning. This switch triggers a cascade of beneficial mechanisms is our bodies, so riding the line and being flexible is the best place to be I think. In the short term however, there are clear benefits to strict keto. An anecdotal example in my own case after practicing strict keto for about 6 months, I inadvertently cured my lifelong battle with acid reflux. I had no idea that would happen. I was honestly doing it in a general attempt to be more healthy and cut sugar out of my life. But I had a problem with heartburn literally since I was 13 years old. I used to have to eat rolaids like candy. I had on and off bouts with prescription strength stuff like Prilosec & others. After 6 months of keto my gut was permanently healed, even after stopping keto. I no longer need any medicine. Short term keto is a real treatment for acid reflux, this is something I think gets overlooked. I no longer practice keto, but a lot of the concepts I learned still stick with me. I practice intermittent fasting many days but not always. If I feel like eating breakfast I do. If I want some bread or pasta I eat it. But I don’t base my diet on it.

orwin 6y ago
I behave exactly the same way (fasting then keto for 6 month, not practicing keto long term but still lowering my sugar/alcohol intake). I still have occasional acid reflux, though less than before. I thing that when you start something like IF or keto, you already care enough for most of diet-related issues to tone done, like a placebo effect somehow.
sleepysysadmin 6y ago
>It annoying to me the extraordinary divisiveness conversations on ketogenic diets generate at this point. But I get we are still in the middle of the learning curve scientifically, and there is a lot of confusion. One of the big name diet plans blamed Keto for when they lost a huge portion of their revenue. At exactly the same time advertisements everywhere were about 'keto crotch' which is no longer a thing. Clearly were paid for articles to discourage women from going keto. There's a ton of $ to prevent people from going keto. Why? Imagine what a grocery store looks like if there were no carbs. A meat department, some drinks? The entire business model collapses. How about fast food? Some fast food joints have been catering to keto folks. The fast food joints that dont and traditionally push nothing but sugar are struggling. >I no longer practice keto, but a lot of the concepts I learned still stick with me. I practice intermittent fasting many days but not always. If I feel like eating breakfast I do. If I want some bread or pasta I eat it. But I don’t base my diet on it. How come you quit keto? Were there effects you didnt like or was it just the inconvenience that you basically cant eat anywhere?

kcplate 6y ago

Perhaps keto can kill me at 75, I kind of feel like that is slightly better than stroking out from T2 diabetes at 55.

chjahi92 6y ago

I wonder what David Sinclair thinks about this, and it’s effects on longevity in humans.

amanaplanacanal 6y ago

It seems obvious that various animals have different natural diets, that is, different diets that they are evolutionarily adapted to. A horse eats grass, a cat eats meat. I expect that of you performed the same dietary experiments using horses as the experimental animal, you would get very different results than if you used cats as the experimental animal. Cats are obligate carnivores, and are on a ketogenic diet, always. Is the rat natural diet the same as the human? If so, this might have some relevance to the human diet. This appears to be another example of the garbage that passes for nutrition science.