Friday, November 21, 2014

Of Eskimos and Atkins

Not sure if any of ya'all have caught wind of the Hyperlipid blog post, Coconuts and Cornstarch in the Arctic?  It's a very hard-to-read story of a common genetic mutaion found in 80% of Inuits.

I think it was written to support a high-fat, low carb diet.  But I'm not sure.

What the article did show is that 80% of the Inuit/Eskimo population has a genetic mutation that does not allow them to generate ketones, so the entire theory that keto dieters have been using, the one that says the "Inuit Diet" is proof that a ketogenic diet is safe and effective, is completely blown apart!

My friend "Duck Dodgers" has been tearing into the Inuit Diet for about a year on Free the Animal, and they have about 20 posts on the subject.  Mostly, Duck's research has shown that the Inuit diet was not ketogenic because it contained too much protein and animal-type starches.  All very fascinating, but now we see that not only was the diet not conducive to ketosis, but a ketogenic diet would have quickly wiped out the Inuit population, or at least those carrying the mutated gene some 2000 years ago when they settled the Arctic coastline.

I'm sure Richard and all the bloggers will soon be writing about this in a much more spectacular fashion than I am here, but I wanted to post this for your reading pleasure and a place to look at some of the science and studies before it is blown into a million pieces in the blogosphere.

This is a quick note I just wrote to Ned Rozell, director of the Geophysical Institute at the University of Fairbanks, Alaska.  I'd like to get these guys on the case and make a real splash in the science and medical world.  Wouldn't this make a great thesis for a grad student?

Hi, Ned -  I've recently stumbled across some information that could set the science world abuzz.  I'd love for you to take a look and help me spread the word.

I'm sure you are familiar with the concepts of "low carb" and "ketogenic" dieting.  The world looks to the Inuit and Eskimo as the poster-children of a high fat, high protein diet.  Eating a diet like this should force a person to generate ketones, and many diet programs, i.e., "Atkins," have been developed around ketogenic diets to induce weightloss.

Nearly any medical or scientific paper that discusses a ketogenic diet also discusses the Inuit as a group of people who remained healthy while in constant ketosis. 

For instance:  Ketogenic diets and physical performance by Stephen D Phinney:

"Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow"

And from:  Arguments in Favor of Ketogenic Diets:

"This is demonstrated by Inuit peoples, who can live on a diet based almost exclusively on fat; they do not suffer acidosis as a result of ketones, and therefore do not suffer from Ketoacidosis."

This recent journal study has come to my attention: A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations.  This 2014 paper discusses a genetic mutation carried by 81% of those of Inuit and Eskimo descent.  This mutation effects the CPT1A gene which is used in metabolic processes involving mitochondrial long-chain fatty-acid oxidation (ie. glycogen storage and ketosis).  Specifically the mutation in the Arctic is called the "Inuit varient, Pro479Leu" mutation due to its location on the gene involved.

Approximately 80% of Eskimo children born in Alaska have this mutation, as explored in this 2011 Paper: Impaired fasting tolerance among Alaska native children with a common carnitine palmitoyltransferase 1A sequence variant.

In this study, 5 Eskimo children with this gene mutation aged 3 and 4 were fasted for 20 hours, all of the kids displayed problems switching from stored glycogen to burning ketones when the glycogen stores were depleted.

The point of the study was whether or not to screen Eskimo newborns for this deleterious gene mutation.  The conclusion was that screening was warranted, but that 80% would be found to have the variance.  So counseling should be in order for all new Eskimo parents. 

In an earlier paper on this CPT1A mutation in Inuits, Metabolic Disease Newsletter, 2006, from the Sheffield Children's Trust (UK), (pg 21), the disease was described in the same manner, and made extensive notes on the "traditional ketogenic diet" of the Inuit, using available references from the medical literature.

I thought you would find this interesting, and could even possibly get some interest at UAF to study this phenomenon and get the medical journals and history books corrected.  The Eskimo and Inuit did not survive on a ketogenic diet, in fact, they could not!  80% of the now living Eskimos and Inuits cannot physically produce ketones.  Surely the instance of this mutation was closer to 100% before western explorers began interbreeding with the indigenous peoples of the Arctic.

Also, warnings should be given to overweight Eskimos that an Atkins type ketogenic diet could be extremely harmful to their health.

I have lots more papers and references if you are interested in exploring this further. 


  1. I'm confused about the positive aspects of a ketogenic diet for non-Inuits and the state of ketoacidosis which can be fatal, especially in diabetics. Could you explain the difference in your erudite comprehensible language style? Thanks so much.

  2. Me too please.
    I appreciate the segments of essays you have been posting, but personally I need something a little easier to understand and more in your natural chatty writing style. I find essays written in more academic/university language increasingly hard to understand -- my brain is too foggy for it! and I just don't 'get' the essence of what you are trying to argue/say.

  3. Haha - Did you guys read the original Hyperlipid blog post? Now THAT is some confusing stuff! Here's a sample:

    "Living in a sea of free fatty acids, which are taken up in to cells in a largely concentration dependent manner, allows an increased gradient to push FFA-CoA at any residual function in CPT-1a. It would appear, from the evolutionary perspective of Arctic inhabitants, that near ketogenic levels of FFAs are adequate even if you have the proline to leucine substitution at amino acid 479 in CPT-1a. You can do enough beta oxidation to cope."

    I believe what Peter was trying to say, is that even though the Inuit had a genetic problem that prevented them from producing ketones, their high-fat diet protected them from problems that would be encountered by people eating a normal diet.

    The MASSIVE problem that Peter ignores, is that today the Inuits eat like we do, or worse. They no longer eat a traditional high fat diet. They drink Coke and eat macaroni and cheese. And yet, the Inuit don't have any issues as long as they don't starve.

    What Peter says is irrelevant, though. My point is that for 50+ years, diet gurus who advocate a ketogenic diet look to the Inuit and say, "See, it's safe to be on a ketogenic diet your entire life!" But the problem now (for them) is that it was impossible for the Inuit to be in ketosis, because they genetically could not do it.

    This probably didn;t help clarify, sorry. I'm working on another reply with some more info on what ketosis is and what ketones are. Stand by!

    1. I must say that the entire "ketogenic diet for optimal health" movement has me baffled.

      Ketoacidosis is a condition that diabetics find themselves in if they eat too much fat and protein and not enough carbs. The liver produces ketones, and in the diabetic, can do so in an uncontrolled fashion, leading to too many ketones in the blood, a condition which can be fatal.

      In non-diabetics, ketosis is a natural and normal state. As a non-diabetic person eats a 'normal' diet, The carbs and protein are converted to glucose and they store excess glucose as glycogen (a form of sugar) in their liver. Glucose travels all through the body and fuels metabolic processes, including fueling your brain. When you stop eating, the glucose in your body rapidly depletes. When it is almost all gone, your liver releases glycogen to fuel these processes. This can be seen with a blood glucose meter. The body is well-tuned to keep the blood glucose in a tight range, unless you are diabetic.

      If you don't eat enough carbs or protein, your body has a back-up plan. Your liver can also produce ketones. This is a survival mechanism to protect us during prolonged starvation. The brain can efficiently run on these ketones just as it can glucose.

      In a ketogenic diet, like Atkins, the person eats a ton of fat and little protein or carbs. This will force the liver to produce ketones. As the brain converts over to the new fuel source, brain fog develops. After a few days, they say, the brain fog lifts and you are once again able to think clearly.

      The proponents of a ketogenic diet say that 'proof' of the safety of a long-term ketogenic diet can be found by looking at the Inuit. But the problem has been that old studies showed the Inuit ate too much protein to be in ketosis and also blood tests showed they were not in ketosis.

      Now we have a genetic mutation discovered in the Inuit that shows that they could not be in ketosis even if they wanted to...the mutation prevents them from making ketones.

      If you or I stopped making ketones, we'd never know it unless we fasted for a day or so, then we would get very ill as our blood glucose disappeared and no back-up fuel took its place. But if we kept ourselves well-fed, we'd never know it.

      So, the positive aspects of a ketogenic diet for the normal person is that you can lose weight without hunger (supposedly) as your body runs on ketones with a deficit of carbs and fat.

      In reality, a ketogenic diet is a survival mechanism that fuels our basic metabolism as we deplete fat stores. I don't think anyone should willingly go on a ketogenic diet to lose weight. Keto diets have been shown therapeutic for epilepsy, but beyond that, they should not be used. And now the people who like to support ketogenic diets cannot look to the Inuit and say they were in ketosis

    2. And maybe this helps, too:

      If the Inuits that carried this gene were to starve for several days, they should have died. I think it's safe to say that the Inuit knew hunger 'back in the day' yet they are still here and the deleterious gene survives.

      A biology lesson from Wikipedia:

      "The human starvation response is unique among animals in that human brains do not require the ingestion of glucose to function. During starvation, less than half the energy used by the brain comes from metabolized glucose. Because the human brain can use ketone bodies as major fuel sources, the body is not forced to break down skeletal muscles at a high rate, thereby maintaining both cognitive function and mobility for up to several weeks. This response is extremely important in human evolution and allowed for humans to continue to find food effectively even in the face of prolonged starvation.[8]"

      So, read that, and tell me how the Inuit survived periods of starvation when they had faulty ketone production.

      My theory is that the Inuit dipped into another pathway and started to metabolize bodily protein (muscles) to fuel their glycogen needs instead of ketones.

    3. Tim said "This probably didn;t help clarify, sorry. I'm working on another reply with some more info on what ketosis is and what ketones are. Stand by!"

      If you are writing about fat metabolism don't forget to embrace the the tiny but mysterious peroxisomes. Everybody writes about ketosis, mitochondria and these are largely uncovered and unknown. A hypothesis by Carbsane is that they contribute to the elimination of fatty acids in Inuit tissues:

      "They seem to survive despite that mutation probably because they do burn a lot of fatty acids. Very long chain fats are burned in peroxisomes for heat."

    4. Tim wrote: "My theory is that the Inuit dipped into another pathway and started to metabolize bodily protein (muscles)" - one low-carb bodybuilder - John Kiefer has a hypothesis that one of the role of our internal organs is to provide proteins in the times of needs. Thus the enlargement of the livers of Inuits would have 3 functions at once:
      1) More gluconeogenesis
      2) More glycogen storeage
      3) More protein storage

    5. That idea is backed up by at least one rat study! (hattip Gemma)

      Rat Liver Catabolism

      "The present data are consistent with the view that in starved animals the loss of liver protein is mostly accounted for by increased breakdown, due, in part at least, to enhanced autophagocytosis. "

    6. Ahh... brilliant! Thanks heaps Tim, now I get what the article was saying.

    7. So when you explained one of Hyperlipid's text fragments can you please explain another, from his newest post:

      "From the Hyperlipid and Protons perspective I would be looking to maximise input to the electron transport chain as FADH2 at electron-transferring-flavoprotein dehydrogenase and minimise NADH input at complex I. Ketones do not do this. Ketones input at complex II, much as beta oxidation inputs at ETFdh, but ketones also generate large amounts of NADH in the process of turning the TCA from acetyl-CoA to get to complex II, which ETFdh does not. I'm not a great lover of increasing the ratio of NADH to NAD+"

    8. Oh, that's easy!

      Electrons are transferred from NADH to O2 through a chain of three large protein complexes called NADH-Q oxidoreductase, Q-cytochrome c oxido-reductase, and cytochrome c oxidase. Electron flow within these transmembrane complexes leads to the transport of protons across the inner mitochondrial membrane. Electrons are carried from NADH-Q oxidoreductase to Q-cytochrome c oxidoreductase, the second complex of the chain, by the reduced form of coenzyme Q, also known as ubiquinone because it is a ubiquitous quinone in biological systems.

      Get it? What! You don't?

      Just messing with you. I have never really dissected it down to that level.

      He's discussing the Citric Acid Cycle I believe. I think that we just need to eat real food, plenty of fiber, and not worry about all the electrons and manipulating them with a ketogenic diet.

      Maybe someone can provide a better answer, I just wanted to be a smart-ass. Sorry!

    9. Careful Tim, you'll be spouting sub-atomic particles within a year. ;)

    10. TomR - Just wanted to apologize, I can see you are hoping for a good discussion on this. I have read your comments at Hyperlipid and see that you are well-versed in metabolism.

      Ketogenic diets have never really interested me. I gave Atkins a go back in the late 90's and lost a bunch of weight, but it was very short-lived as I never learned anything about nutrition, just keeping ketones high.

      What I see on the forums, people are still doing Atkins the same way...they lose until they stop being so careful, then punish themselves with endless induction.

      To me, a ketogenic diet is the worst form of orthorexia. Anything that knocks you out of ketosis is banned forever. I do not see how eating so much fat can provide proper nutrition and that maintaining a high level of ketones 24/7 can be healthy.

      One of the 'red flags' that has always popped up for me was the fact that our blood glucose is maintained right up until we die if starved. The brain switches to ketones at some point to preserve brain function, but the body refuses to stop creating glucose.

    11. It was a joke on my part, so no needs to apologize. I was even imagining how a debate between two people who communicate this or other complicated way :-) Like Peter vs. Ray Peat, as their views on nutrition are oppoisite, and both like to suddenly dwelve into details.

  4. Wow. I wonder how many "truths" genetic testing will bring into question. At one point the earth was flat. Now it is not. Just when you think you have things figured out, a new set of data appears and turns everything around. Science.

    1. Yes, and even my favorite subject, 'gut health,' has limitations based on genetics.

      80% of the world's population produce a substance called fucose in their gut. This fucose is a natural prebiotic food for beneficial gut microbes.

      20% of the people on Earth do not produce fucose and subsequently should probably be eating a much different diet than those who do secrete fucose.

      The fucose is made by the Fucosyltransferase 2 (FUT2) gene, and those that are missing this working gene are called Fut-2 non-secretors.

      Read more:

    2. Thanks Tim. Good article, especially because it was free. I had a screening for IBD/UC, but it did not include this specific genetic analysis (some others were included). Guess that could come from a 23andMe type analysis? Maybe I need to do one of those sometime.

      And speaking of 'gut health', the shift from culturing towards genetic testing for composition / pathogens is sure to bring about many new findings too. The volume of data could actually overwhelm for scientists for a while. As long as funding is available, their should be great opportunities for researchers.

  5. "20% of the people on Earth do not produce fucose and subsequently should probably be eating a much different diet than those who do secrete fucose."

    Hi Tim,

    Any idea what that diet would look like?

    1. Since fucose can be a big part of our daily prebiotics requirement (food for gut microbes), people that don't make fucose should never attempt a low carb diet and especially should ensure a higher than normal intake of fermentable fibers.

      If the recommended daily intake of fiber for 'Fut2-normal' people is 25-35g/day, Fut-2 non-secretors should probably aim for 35-50g/day.

    2. Thank you for your suggestion for people with FUT2-non-secretor for fibres. Would you a suggestion for the ratio of daily intake for RS2/RS3/several fibres for FUT2 (approximately)? I

  6. That is completely speculative. There are no studies indicating that FUT2 non-secretors needs to follow a special diet as far as I've seen. I'm one of those 20 % that do not secrete FUT2, and low-carb diet has not caused any problems whatsoever. I currently consume plenty of fiber, but I can both fast and eat no plants for long periods without suffering any issues.

    The FUT2 mutation must also have had significant survival benefits as it is so highly present in the caucasian population as well as a secondary mutation occuring in Pacific Islanders. Being a fucose non-secretor renders the host immune to the norovirus which causes 20 million cases of illness in the US alone.

    "We found a strong association (P = 0.003 [Fisher exact test, two-tailed, 95% confidence interval]) between nonsecretors and resistance to symptomatic norovirus GGII.4 infections. Indeed, we could not find any nonsecretor with symptomatic norovirus GGII.4 infection. This observation is similar to a previous study from Sweden (17). Our results thus extend previous reports showing that nonsecretors appear resistant against experimental and authentic infections with genogroup I and II viruses".

    So the benefits of not being infected with gastroenteritis-causing viruses were more important than secreting fucose. What would be interesting to find out is when this mutation occurred. If it occurred in the paleolithic it could be related to the fact that the ice age significantly reduced the availability of consumable plants, thus reducing the need for gut bacterias that aids in plant digestion enough to favor non-secretion. If it occurred in the neolithic period it could be related to the reduced immune function caused by a nutritionally poor, grain-based diet. I think the first alternative is more likely, as the mutation appears to be evenly distributed among caucasian populations, something that could not be the case if the mutation happened during agriculture when populations were so widely spread. Just my thoughts on the subject.

    1. I appear to be wrong in my speculations. FUT2 mutations are found in most populations, not just caucasian. Not all confer norovirus-resistance, so it must have other benefits to be a non-secretor as well.

    2. The fact that non-secretors were maintained worldwide rather suggests that something was making up for the deficiency. The body normally presents fucose during GI illness to fight the pathogens, and the non-secretors are disadvanteged.

      Traditional diets provides a lot of fiber and creates favourable niche for gut microbiota (bacteria, friendly yeasts) that help fighting the pathogens, and perhaps can even create some fucosylated glycans, instead of the host.

      It can also be that non-secretor babies demanded and were provided with long breastfeeding (up to 4-5 y) which helped them to establish the right gut flora.

      The western diet and mainstream medicine is detrimental to FUT2 non-secretors who tend to develop IBD, Crohns etc. E. coli gets very virulent if there is no fucose around.

      Norovirus mutates and has found a way around the non-secretor protection anyway...

    3. I've never seen anything about a special diet for Fut2 nonsecretors, either, but it makes some sense that if you are not secreting something that feeds the gut microbiome, you'd need to ensure that you have an alternate form of food for the gut flora.

      And, yes, this mutation seems to convey protection from Norovirus and even HIV, to some extent, but the mutation was selected for over millions of years, during which time 'low carb diets' were probably not very popular.

      But, to the original question...I think that genes play a very important role in how we eat and why one-size does not fit all.

    4. FUT2/Microbiota

      Interesting paper. Fut2 non-secretors have less Bifido.

    5. FUT2 non-secretors also have way less clostridium and other significant differences. No mention of bifido or even lactobacillus in this study (unless I missed it). Whether those differences have any practical implications will probably be more apparent as our knowledge of the microbiome expands.

    6. Looked through the full paper, and there was a reduction in bifido. Akkermansia too. It's probably a disadvantage to have that mutation then, in terms of microbiome composition. I wonder how it affects pathogenic bacterias. There seem to be some autoimmune issues related to non-secretor status. Not worried too much by these findings though, but it will be interesting too explore the implications further.

    7. @HappyViking

      FUT2 non-secretors (20% of the population) need to keep the gut flora as healthy as possible.

      Due to the genes, their gut flora "is altered at both the compositional and functional levels".

      Some reading:
      Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism

      Supporting the “Good” Gut Microbes

    8. Another interesting article on the Scientist site was this one on the effect of the mother's gut microbiome on the permeability of the blood-brain barrier (mouse study only).

    9. Kira - I saw that! I love it when scientists say things like:

      “Many neuroscientists staunchly believe that the blood-brain barrier is an incredibly impermeable membrane to many molecules and . . . would hardly believe that gut bacteria would control such an integral part of our neurobiology.”

      But then I read further, and it makes me realize that we still have a long, long way to go!:

      "And that’s not all. “The development and final closure of the blood-brain barrier isn’t quite finished at birth,” added Collins, explaining that the process continues during the early days of postnatal life. “So, again, anything that interferes with intestinal bacteria . . . after the child has been born”—such as antibiotic use or delivery by cesarean section, which is thought to prevent the offspring receiving a dose of microbes from the mother’s birth canal—“could also prevent the proper closure of that barrier and therefore the proper development of the brain,” he said."

  7. isn't glucose inflamatory and the chief cause of arterial diseases?
    And isn't the brain conducive to plaque and dementia under glucose fuel but not ketones?
    That has been my reasons fro trying to stay ketonic, with potato starch supplementation.

    1. Oh, boy. I don't even know where to start. I think the ketogenic diet is the wrong approach to living a healthy life.

      I think we can dip into a ketogenic pathway when we need to, as in fasting or staving situations, but to intentionally eat in a way that tricks our body into thinking we are starving and then maintaining this metabolic pathway forever...I just can't see that as being healthy no matter what the Keto-Experts claim.

      Tom Naughton has a good take on keto diets in these two recent blogs:

      and another:

    2. Ok, i read your comments but in this case I was looking for data rather than opinion regarding the arterial damage now being attributed to carbs and conteracted by ketone metabolism.
      Thanks for blogs. Enjoy reading them regarding RS

    3. philX2 - Hey, talk to me, man! Show me what you are talking about, I'd love to have a look.

      Did you see Bill L's Calories Proper blog today (linked over to the right in banner)? I think Bill knows his stuff and think that what he says about ketones being signalling molecules, etc... is probably spot on. They are certainly protective of something, the normal person generate ketones fairly often, so why wouldn't they be good for something?

      But lets have a look at the studies or papers you've seen. I'd love to learn.

    4. @phil phil

      Looking for some data that ketogenic diet may cause arterial damage?

      See this paper, from 2014:
      The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: a case-control study.

      "The present study aimed to assess the impact of the ketogenic diet on arterial morphology and endothelial function of the big vessels of the neck and on cardiac diastolic function, in a cohort of epileptic children and young adults treated with the ketogenic diet.

      Subjects treated with the ketogenic diet had higher arterial stiffness parameters, including AIx and β-index and higher serum levels of cholesterol or triglycerides compared to those who had never been on the diet (control group) (p<0.001).

      CONCLUSIONS: Arterial stiffness is increased in children and young adults treated with the ketogenic diet, before the increase of the intima media thickness. This supports that arterial stiffness is an early marker of vascular damage."

    5. I guess my biggest issue with the ketogenic diet is that the only way to know if you are "doing it right" you have to measure ketones. As long you make the Ketostix purple or get a certain reading on a breath analyzer, you have confirmation that you are eating how you are supposed to eat.

      I just feel that using this mechanism to hopefully lose some weight is very short-sighted and could lead to long-term problems as the study above indicates.

  8. Inuits obviously have never "not known hunger", so I would say there has to be something else in play here. I don't have a reference, but I read somewhere that Inuits have very large livers and can make glucose from protein at a much higher rate than most people. This still doesn't help the low carb people, but makes a ketonic state irrelevant.

    1. The irony is just remarkable.

      A friend just remarked:

      "What I find telling is that in one of the only populations where long-term ketosis would actually be possible (with some caveats RE: high protein), the advantage was to not enter ketosis..."