4 ms·

Polymoprphisms in the CPT1A gene control the amount of fatty acids that enter the cell to be broken down into ketones. Since the Inuit eat so much fat, after ge

Polymoprphisms in the CPT1A gene control the amount of fatty acids that enter the cell to be broken down into ketones. Since the Inuit eat so much fat, after generations this gene has selected to be slower so they are not in a constant state of ketosis and therefore save glucose. The Inuit have a very low glucose diet so this makes sense that they need to try to hoard glucose. You will notice in kids with full CPT1A deficiency that they have an almost total inability to make ketones and suffer hypoglycemia when fasting. The problem is that you are thinking like a Caucasian when it comes to ketosis and you all think ketosis is always good. It is not always good, it should be balanced. https://pubmed.ncbi.nlm.nih.gov/32088118/ https://pubmed.ncbi.nlm.nih.gov/32088118/ The role that Omega 3 plays in all of this, for people like me who need it, is so underestimated it is depressing. I had to lower my Omega 6 fats so drastically before I saw any change sin my lipids. It was amazing honestly. You see, only the Inuit and people with these genetics should be eating a very low carbohydrate diet. All you "Farmers", stick to your oily grains, nuts and seeds.

depressedpanda 5y ago
> Since the Inuit eat so much fat, after generations this gene has selected to be slower so they are not in a constant state of ketosis and therefore save glucose. I'm not following - ketosis happens after glucose levels are low. How would making the switch to a ketogenic metabolic state a slower process save any glucose? Ketosis doesn't consume sugar, as far as I know. Also, what are the detrimental effects of ketosis?
- FollowingTheDao 5y ago
  I worded that poorly, sorry. "and therefore save glucose" would have better read, "the body does not need glucose for energy". This question is doing more for me than you know. I hope I can explain everything right now since it is all a just a picture in my head. So if this does not make sense I can go on. I want to take a step waaaay back. Most people think it is ketones, glucose, protein, or fats that the body wants for energy. Well, they are all wrong. The body wants Actyl-CoA for energy. Acetyl-CoA drives the TCA cycle and that is what keeps us alive. All of those things are sources of Acetyl-CoA. https://www.researchgate.net/figure/Origin-and-fate-of-acetyl-coenzyme-A-Acetyl-coenzyme-A-is-a-critical-intermediate-for_fig3_312005662 https://www.researchgate.net/figure/Origin-and-fate-of-acety... Next, the body does not prefer ketones as a source of Acetyl-CoA, in MOST PEOPLES (depending on genetics) it prefers glucose above all else. https://www.ncbi.nlm.nih.gov/books/NBK493179/ https://www.ncbi.nlm.nih.gov/books/NBK493179/ "Most organs and tissues can use ketone bodies as an alternative source of energy. The brain uses them as a major source of energy during periods where glucose is not readily available. This is because, unlike other organs in the body, the brain has an absolute minimum glucose requirement." So being in ketosis is a rescue situation when there is not enough Acetyl CoA being made from glucose. You want proof of this? Fasting increases ketones levels more than any diet. https://www.medicalnewstoday.com/articles/324599#_noHeaderPrefixedContent https://www.medicalnewstoday.com/articles/324599#_noHeaderPr... If a person genetically prefers glucose over fats for making Acetyl CoA, my guess is that they will go into ketosis much more slowly. So once the body runs out of it's preferred source of energy, glucose, it resorts to its second best source; fat. Now how are fats used for energy? https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/asset/e172a8cd-1964-4188-a840-f1dec7b58b0e/gr1.jpg https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/asset/e1... They are turned into Acetyl CoA BEFORE it enters the cell and needs CPT1A to enter the cell. Both glucose and protein enter the cell and THEN are turned into Acetyl CoA. But all this is NOT TRUE of the Inuit. Their preferred source is from fat, not glucose. Why? Because of the genetic changes resulting from a diet high in fat. So for the Inuit, a high glucose diet causes problems like a high fat diet does for most European caucasians. Let's look at the problem for people with CPT1A deficiency. They enter a state of "hypoketotic hypoglycaemia". Low glucose AND low ketones. So we know that we need CPT1A to function to make ketones to power the TCA cycle. I am still trying to reason why CPT1A transport slows down so much for the Inuit. But I know it is because of generational dependance on a high fat diet. It seems that Omega 3 might change the expression of CPT1A making it more effective. Omega 9 fats increase CPT1A activity. https://www.nature.com/articles/s41431-020-0674-0 https://www.nature.com/articles/s41431-020-0674-0 This is probably the best Paper on this confusing topic. https://escholarship.org/content/qt8wz5h9kp/qt8wz5h9kp.pdf?t=q3sb1q https://escholarship.org/content/qt8wz5h9kp/qt8wz5h9kp.pdf?t... "Given that the PUFA content of traditional Arctic diets may compensate for the genetic reduction of CPT1A activity, and that the absence of urinary ketones found in early studies in North America may reflect fat adaptation and limitations in testing technology, current speculation about the lack of a ketogenic state in traditionally living Arctic peoples cannot be considered settled." I mean, if you think about it, having high ketones means your body is not USING the ketones for energy. Wow, that just blew my mind! Time to look at my ketone genetics! Thank you!
  - depressedpanda 5y ago
    And thank you for giving me more information about a topic you've obviously studied intensely :-) I know that the 'standard' western diet has been catastrophic for the Inuit, but to me it's just been kind of obvious that it's because it diverges so much from what they've traditionally eaten for so long. Good to see that there's actually some research to back it up. > I mean, if you think about it, having high ketones means your body is not USING the ketones for energy. That said, I was curious about your comments about ketosis on a personal level. I have no Inuit blood that I'm aware of, but I never get 'keto flu', and any overabundance of free ketones (which also cause 'acetone breath', I think) disappear within a few days of strict low carb carb eating. Fasting also seems much easier for me than it is for my peers. Would you still say it's harmful for a person like me to eat very few carbs and no sugar?
    - FollowingTheDao 5y ago
      > I have no Inuit blood that I'm aware of" That you re aware of is the key point. You can get your full genome and find out if you carry these CPT1A polymorphisms. You do not need to be Inuit. As pointed out, my genetics come from the Sami people, but any cold adapted population should have these changes in these genes. I do not recommend any diet until you know your genetics. It may be that there are two keto diets. One that needs high omega 3 and another that needs high omega 6. Omega 3 changes the function of the CPT1A enzyme.

depressedpanda 5y ago

> Since the Inuit eat so much fat, after generations this gene has selected to be slower so they are not in a constant state of ketosis and therefore save glucose. I'm not following - ketosis happens after glucose levels are low. How would making the switch to a ketogenic metabolic state a slower process save any glucose? Ketosis doesn't consume sugar, as far as I know. Also, what are the detrimental effects of ketosis?

FollowingTheDao 5y ago
I worded that poorly, sorry. "and therefore save glucose" would have better read, "the body does not need glucose for energy". This question is doing more for me than you know. I hope I can explain everything right now since it is all a just a picture in my head. So if this does not make sense I can go on. I want to take a step waaaay back. Most people think it is ketones, glucose, protein, or fats that the body wants for energy. Well, they are all wrong. The body wants Actyl-CoA for energy. Acetyl-CoA drives the TCA cycle and that is what keeps us alive. All of those things are sources of Acetyl-CoA. https://www.researchgate.net/figure/Origin-and-fate-of-acetyl-coenzyme-A-Acetyl-coenzyme-A-is-a-critical-intermediate-for_fig3_312005662 https://www.researchgate.net/figure/Origin-and-fate-of-acety... Next, the body does not prefer ketones as a source of Acetyl-CoA, in MOST PEOPLES (depending on genetics) it prefers glucose above all else. https://www.ncbi.nlm.nih.gov/books/NBK493179/ https://www.ncbi.nlm.nih.gov/books/NBK493179/ "Most organs and tissues can use ketone bodies as an alternative source of energy. The brain uses them as a major source of energy during periods where glucose is not readily available. This is because, unlike other organs in the body, the brain has an absolute minimum glucose requirement." So being in ketosis is a rescue situation when there is not enough Acetyl CoA being made from glucose. You want proof of this? Fasting increases ketones levels more than any diet. https://www.medicalnewstoday.com/articles/324599#_noHeaderPrefixedContent https://www.medicalnewstoday.com/articles/324599#_noHeaderPr... If a person genetically prefers glucose over fats for making Acetyl CoA, my guess is that they will go into ketosis much more slowly. So once the body runs out of it's preferred source of energy, glucose, it resorts to its second best source; fat. Now how are fats used for energy? https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/asset/e172a8cd-1964-4188-a840-f1dec7b58b0e/gr1.jpg https://els-jbs-prod-cdn.jbs.elsevierhealth.com/cms/asset/e1... They are turned into Acetyl CoA BEFORE it enters the cell and needs CPT1A to enter the cell. Both glucose and protein enter the cell and THEN are turned into Acetyl CoA. But all this is NOT TRUE of the Inuit. Their preferred source is from fat, not glucose. Why? Because of the genetic changes resulting from a diet high in fat. So for the Inuit, a high glucose diet causes problems like a high fat diet does for most European caucasians. Let's look at the problem for people with CPT1A deficiency. They enter a state of "hypoketotic hypoglycaemia". Low glucose AND low ketones. So we know that we need CPT1A to function to make ketones to power the TCA cycle. I am still trying to reason why CPT1A transport slows down so much for the Inuit. But I know it is because of generational dependance on a high fat diet. It seems that Omega 3 might change the expression of CPT1A making it more effective. Omega 9 fats increase CPT1A activity. https://www.nature.com/articles/s41431-020-0674-0 https://www.nature.com/articles/s41431-020-0674-0 This is probably the best Paper on this confusing topic. https://escholarship.org/content/qt8wz5h9kp/qt8wz5h9kp.pdf?t=q3sb1q https://escholarship.org/content/qt8wz5h9kp/qt8wz5h9kp.pdf?t... "Given that the PUFA content of traditional Arctic diets may compensate for the genetic reduction of CPT1A activity, and that the absence of urinary ketones found in early studies in North America may reflect fat adaptation and limitations in testing technology, current speculation about the lack of a ketogenic state in traditionally living Arctic peoples cannot be considered settled." I mean, if you think about it, having high ketones means your body is not USING the ketones for energy. Wow, that just blew my mind! Time to look at my ketone genetics! Thank you!
- depressedpanda 5y ago
  And thank you for giving me more information about a topic you've obviously studied intensely :-) I know that the 'standard' western diet has been catastrophic for the Inuit, but to me it's just been kind of obvious that it's because it diverges so much from what they've traditionally eaten for so long. Good to see that there's actually some research to back it up. > I mean, if you think about it, having high ketones means your body is not USING the ketones for energy. That said, I was curious about your comments about ketosis on a personal level. I have no Inuit blood that I'm aware of, but I never get 'keto flu', and any overabundance of free ketones (which also cause 'acetone breath', I think) disappear within a few days of strict low carb carb eating. Fasting also seems much easier for me than it is for my peers. Would you still say it's harmful for a person like me to eat very few carbs and no sugar?
  - FollowingTheDao 5y ago
    > I have no Inuit blood that I'm aware of" That you re aware of is the key point. You can get your full genome and find out if you carry these CPT1A polymorphisms. You do not need to be Inuit. As pointed out, my genetics come from the Sami people, but any cold adapted population should have these changes in these genes. I do not recommend any diet until you know your genetics. It may be that there are two keto diets. One that needs high omega 3 and another that needs high omega 6. Omega 3 changes the function of the CPT1A enzyme.