Sunday, November 16, 2014

Coconuts and Cornstarch in the Arctic?

EDIT There is a follow on post to this one including some clinical data on the hypoglycaemia episodes. I'll put a link in here now it's up. END EDIT

Remi and Ken both pointed me toward this paper:

A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations

The paper itself is largely an account of the detective work involved in pinning down a specific mutation which has been positively selected for in a Siberian population living in the Arctic. The same mutation is also present in non related groups inhabiting the Arctic areas of northern America. The mutated gene is very common and frequently homozygous. It puts a leucine in the place of a proline in CPT-1a, the core enzyme for getting long chain fatty acids in to mitochondria. Putting a leucine where there should be a proline means the protein is basically f*cked. The mutation is linked, not surprisingly, to failure to generate ketones in infancy and can be associated with profound hypoglycaemia, potentially causing sudden death.

From the evolutionary point of view we have here a mutation which is significantly lethal at well below reproductive age, so it should have been weeded out because affected individuals are less likely to live long enough to pass on the gene. But it has been highly positively selected for in several populations, the common factors being cold climate and minimal access to dietary carbohydrate. It's a paradox.

Following a link in the paper gives us this abstract, with this snippet:

"Investigation of seven patients from three families suspected of a fatty acid oxidation defect showed mean CPT-I enzyme activity of 5.9 ± 4.9 percent of normal controls"

A value 6% with an SD of 5% suggests to me that some of these people may well have a CPT-1a function very close to zero. How common is the mutation?

"We screened 422 consecutive newborns from the region of one of the Inuit families for this variant; 294 were homozygous, 103 heterozygous, and only 25 homozygous normal; thus the frequency of this variant allele is 0.81"

I think "very common" is a reasonable description.

How dangerous is it?

"Three of the seven patients and two cousins had hypoketotic hypoglycemia attributable to CPT-Ia deficiency"

Quite dangerous.

The next thing we can do is google CPT-1a deficiency and have a look what needs to be done to stay alive if you carry this gene.


Clearly, if you can't transport LCFAs in to your mitochondria, you should run your metabolism on glucose/pyruvate and avoid the dysfunctional fatty acid transporter. This means raw corn starch, as we have seen used (probably wrongly) for glycogen storage diseases. Properly cooked starches are too short acting to reliably keep a child alive all through the night. They aren't safe enough.

Of course MCT oils have a role too. A CPT-1a defect has no effect on MCT metabolism so these can be used either directly by tissues or indirectly via liver/glial produced ketones.

LCFAs, unable to be metabolised, accumulate in the tissues as a storage disease. The advice is to avoid them as far as possible.

So the archetypical CPT-1a defect tolerant environment would seem to be a person sitting on a South Seas Island beach by a pile of coconuts chewing on a raw yam, with copious flatus night and day.

But it's not.

The CPT-1a defect evolved in multiple non related populations where both starch and MCT were very notable by their near-complete absence. It's an Arctic selected gene. No starches. No coconuts.



Let's take a speculative look at what is going on.

Living on a very low carbohydrate diet is associated with chronically elevated free fatty acids, chronically low levels of insulin and an ignorance of glucose. i.e. the body ignores glucose. Synthesise what glucose is needed but, beyond that, who cares?

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.

Of course, the minute you lower free fatty acids, perhaps to the level of a post prandial starchivore, beta oxidation is going to grind to a halt without the concentration gradient effect. This is pathological. The temporary fix of substrate level ATP synthesis and related pyruvate supply to the mitochondria is fine for a while, but any reactive hypoglycaemia is going to be potentially fatal, especially if you are asleep or food deprived at the time. We know that insulin suppresses lipolysis at levels which don't budge GLUT4s. When insulin has suppressed lipolysis and blood glucose is low, FFAs might be fatally limited.

If you have the mutation but you never do the starchivore thing your FFAs are high 24/7, whether you have just chewed on a lump of seal blubber or not. No paper in the reference list appears to have looked at the FFA levels of children with this mutation on a mixed diet, let alone on the ancestral fat based diet of the polar regions. Given sustained very high levels of FFAs, you might even make some ketones.

If free fatty acids are high and there is no insulin to divert them in to storage, all of the nasty storage diseases associated with CPT-1a dysfunction might well disappear. This is the situation where the mutation allows carriers to thrive.

I think elevated free fatty acids, without elevated insulin, is a recipe for the tolerance of this mutation.




But the mutation is not just tolerated. This is no neutral mutation, it is positively advantageous. The prevalence of the mutated gene is far from random. Why is it beneficial?

This is not quite so simple.

Uncoupling is one component. Uncoupling respiration generates heat. There might just be a positive advantage to running your metabolism fairly uncoupled in a very low temperature environment. Elevated FFAs are completely essential to uncoupling and heat generation. Limiting fatty acid removal from the cytoplasm to the mitochondria might be a facilitator of uncoupling. It's FFAs on the cytosolic side of UCPs which facilitate proton translocation. Having a higher level of cytoplasmic FFAs at a given level of plasma FFAs might give an advantage over the normal level of uncoupling seen under near ketogenic diet conditions.

The second possibility is that, once you have established high enough levels of FFAs to push through the CPT-1a bottle neck, you simply run at this level flat out, all the time. One of the features of the CPT-1a from the modified gene is that it fails to be inhibited by malonyl-CoA.  Even with limited CPT-1a activity there must be times at which ATP synthesis exceeds metabolic requirements and fatty acid transport ought to slow. There is no longer any brake to be applied to FFA transport if excess acetyl-CoA, exported to form malonyl-CoA in the cytoplasm, fails to inhibit CPT-1a . Oversupply of ATP within the matrix is likely to provide optimal uncoupling conditions, in excess of those from a ketogenic diet with regulated fatty acid uptake. That would be my guess. If it's cold enough, this might make the difference between survival or not. It keeps you warm, especially when you are asleep and the TCA should be quiescent.

Flicking through other references in the paper it does appear that indigenous Siberian people do have an elevated resting metabolic rate. In fat free mass it is 17% above calculated values i.e. they are uncoupled.

Finally, adults are not affected by the hypoglycaemia syndrome. My presumption is that, after puberty, they are sufficiently insulin resistant to have adequate FFAs present to maintain relatively normal mitochondrial function. It's the children who need their ancestral diet.



People with glycogen storage diseases die of hypoglycaemia (amongst other problems). We know that a deeply ketogenic diet both protects from hypoglycaemia and sets the body up to run perfectly well without any dietary glucose, which might be lost to glycogen stored permanently in the liver/muscles. There is every justification for giving the finger to cornstarch here and the folks suggesting a modification of ketogenic eating appear to be on fairly safe biochemical ground.

For the P497L mutation everything from the evolutionary perspective suggest that a very high FFA inducing diet may be equally efficacious. But the risks associated with failure, from the occasional safe starch meal or unsafe birthday cake at a party, carries the potential for catastrophe once insulin puts free fatty acids in to free fall.

Peter

BTW: You just have to wonder if any other CPT-1 mutations might behave in a similar manner to the P497L change in the Arctic... Could it be bye-bye time for cornstarch?

127 comments:

Tucker Goodrich said...

Some of the papers that Nikoley has been mindlessly pushing of late comment on the unique ability of Eskimos to burn fatty acids. Guess we know why now. They may well have evolved a mechanism to promote FA metabolism over ketones.

I've come to the conclusion that cardiomyopathy is the result of chronic glucose over-consumption.

That paper seem to seal the deal...


Tim Steele said...
This comment has been removed by the author.
Puddleg said...

This is very interesting. I've been looking into contraindications for keto diet and fatty acid transport disorders came up.
MCTs do seem to require carnitine,
http://www.ncbi.nlm.nih.gov/pubmed/8036622
and are not well metabolised in carnitine-acylcarnitine translocase deficiency
http://www.ncbi.nlm.nih.gov/pubmed/10472533

If you inherited the ability to use ketones in hepatocytes this would suppress ketosis.

Tim Steele said...

As an avid reader of FTA, I do have to chuckle at this from the main paper talked about:

"It is also possible that the selection signal is somehow associated with the high fat
diet of Northeastern Siberian populations who have to cope with
ketosis [56,57]."

Cites 56 and 57:

56. Phinney SD (2004) Ketogenic diets and physical performance. Nutr Metab(Lond) 1: 2.

57. Reynolds JE, Wetzel DL, Hara TM (2009) Human Health Implications of Omega-3 and Omega-6 Fatty Acids in Blubber of the Bowhead Whale (Balaena
mysticetus).

If we are to believe Nikoley's misfits, and the Inuit did not live in ketosis even part of the time, this makes it look like a high meat diet would result in ample glycogen production, similar to living on SuperStarch corn starch.

Possibly these isolated Inuit groups perpetuated this genetic mutation because they never needed to be in ketosis as they were continually fueled with glycogen from all the meat they ate.

One of the most interesting things I learned about the Inuit recently was that fat was a very scarce resource, used for lamp oil when available, and as a dip and preservative for some of the foods they ate. But never a main macronutrient.



Puddleg said...

Sinclair thought Eskimos had "the highest intake of fat in the world", and he was a trained chemist who ate the diet for 100 days and analysed it for years.

Fat that you could use in a lamp would require heat to make and containers to keep, unlike blubber or other high-fat foods.

http://garfield.library.upenn.edu/classics1985/A1985AQU5900001.pdf

donny said...

Those old ketosis studies Duck Dodgers brought up at free the animal...

What time of year did they test the subjects? Summer? I doubt they picked deepest darkest winter. The one paper that showed resistance to fasted ketosis gave 1/3 to 1/2 as the fat portion of the diet in winter... sounds pretty ketogenic to me. Of course, even then, the calories might have been high enough to prevent ketosis.

In that study, they mentioned that obese subjects, serially fasted, showed a resistance to fasting ketosis similar to the Inuit in the study. But they said these Inuit had no previous history of fasting, so that couldn't be it.

Big butt, though--would a sufficiently ketogenic diet, at least periodically, count towards that "previous history of fasting?"

I also find the bits on that post about glycogen in whale blubber a little funny. Dodgers gives as an example of how high glycogen in blubber can get, that it's 25 percent glycogen calories in the posterior dorsal--I read that as tail, the smallest part of the animal's blubber. He just happened to choose the most glycogen-rich part of the animal. It's like using the liver as an example of how high in glucose organ meat can be. Maybe a tasty, valued treat--but how substantial in relation to the total calorie value of the animal?

donny said...

But yeah, if metabolic rate were extremely high, maybe that could preclude ketosis. I've seen claims of Inuit men eating five or six thousand calories a day. At six thousand calories, seventy five percent fat, even if that didn't mean enough protein to keep them out of ketosis--the ten percent glycerol alone is 450 calories, theoretically about enough to produce glucose for the brain.

Galina L. said...

About the relevance of Inuits being in ketosis all the time or not. Are we all really taking principles of paleo-movement dead seriously? Well, modern diet can be really instrumental in the preventing people from living past retirement age what mass-smoking was achieving till recently. Not to mention the growing economical input from the new niche of goods for morbidly obese people and wide variety of pharm products to treat symptoms of a metabolic syndrome.
It is one thing when masses of young guys out of blue decided the live in a ketosis to play Inuits while drinking bulletproof coffee inside their cubicles(there is nothing wrong with the desire of caged humans to escape in any shape or form). I remember how some day they became profoundly happy when Richard allowed them to eat raw carrots, then potatoes, later beans and rice. It is another thing when we feel better eating a LC diet because it address the particular health needs created by life in a modern environment. It may be not only publicly accepted management of epilepsy and migraines, but also stable energy or mood during the day, or absence of a hunger after a weight-loss. Even if ketosis was not the most wide-spread physiological state on a pre-historic Earth, just imagine medications which may be used as appetite suppressants, blood-sugar stabilizers, mood-stabilizers, stimulants, not to mention anty-seizures drugs. So far no one agreed yet on how to prevent and treat Alzheimer , but ketosis looks like something what could at least make a difference. Basically, ketosis is used mostly by nutritional hobbyists for the management of a metabolic syndrome manifestations which are wide spread in a modern population.

ItsTheWooo said...

I was all over this blog entry last night on twitter, great work Peter!

Hyperlipid: absolutely destroys the work of duck dodgers/nikoley/gabkab et al in a few minutes.

I visually imagine a bunch of midgets zerg rushing a giant, pretty much THE SAME THING with regard to insight/creative thinking.

Case is settled. This mutation has automatically invalidated any concept the inuit are anything but a super high FFA culture, with chronic cold exposure to deplete glucose/raise FFA even further for good measure. The CPT-1a mutation is reproductively defunct death in infancy, otherwise.

I was also thinking what this means for inuit populations. If 25% are homozygous and "eatingbread and using oil lamps" for at least the past few decades as described on FFA, this suggests 25% of this population is subjected to CHRONIC nocturnal cerebral energy starvation in childhood. While some die of this, the survivors likely have profound brain damage and learning disabilities.

This is a major health issue for the inuit. They should receive genetic counseling and be placed on 0 carb diets with perhaps therapeutic cold exposure or insulin suppressive drugs to live. If they have cpt-1a, insulin suppression will not cause diabetes (they can't induct FFA insulin resistance thus hypeglycemia from an insulin reduction) and the insulin suppression would only save their brains from hypoglycemia.


Perhaps if similar genes altering fat metabolism are distributed in other native american groups this can explain the wide spread risk of alcoholism. Alcohol is an energy substrate for the brain, and chronic metabolic starvation may provoke the use of it.

There are so many wide reaching implications of this.
"Inuit savoring their carbs" is definitely not one of them, sorry nikoley/duck dodgers... back on the short bus guys!

raphi said...

@Tim Steele

We pesky humans do not possess lion livers. We cannot fuel ourselves on protein like cats. Protein is first and foremost a structural component although we can partly/occasionally convert some of it into glucose when need be.

You either fuel with dietary intake of CHO or fat AFAIK. Have your investigations revealed a 4th macronutrient?

What you quoted goes shows how being fuelled by fat is highly advantageous because it can be adapted to many environments/situations. Fuel on CHO but are now starving? Ketosis. You're an Inuit who requires UCP-derived heat &/or an appropriate insulin response to your local diet? FFA to the rescue. You get unlucky and cannot find enough fat/carbs? Protein can temporarily step in.

How you construe those quotes to mean that ketosis is fundamentally undesirable is beyond me. Hey, maybe I'm CHO deficient & should fill up on sugary Arctic animals bathed in RS.

Ash Simmonds said...

Alcohol is the body's "preferred fuel".

Tucker Goodrich said...

Sorry to bring that up!

Duck's exercise in cherry picking isn't even reading papers. The best way to debunk his premise is to read in full the stuff he quotes selectively.

But back to the original point, I don't know that the heat argument is the final answer.

It is certainly a pretty interesting question, but research on this started recently enough and the Eskimos are far enough from their ancestral diet that we may never get an answer...

Tim Steele said...

Alright, well, here's the deal. I don't know as much about how great ketosis is 24/7 like you guys, but I do know a lot about Eskimos.

You realize it is dark 24/7 for several months of the winter and extremely cold. They lived in huts dug into the ground, covered in whale bones and tundra sod. It was dark as hell. They had to see. And cook.

They used these for lamps, not a Coleman lantern as woooo supposes: http://www.ku-prism.org/quicktimeVR/Websites/Blubberlamps.html

I live just 400 mi from the Arctic Ocean, and travel/hunt there frequently. It is a fat-poor land. Sure they caught lots of seals and a whale or two, but they never got good at whaling until white-man came along with big whaling ships.

The Inuit subsisted mainly on caribou and fish, both relatively lean, but they also had piles of seaweed, berries, and way more vegetation than given credit for.

So, if you think outside the box for a minute, and suppose that maybe the papers Duck Dodger cherry-picked have some truth, and the Inuit were not in ketosis unless starving, maybe there is a better lesson to learn from the CPT1A P479L variant.

I would characterize the Inuit diet as high protein, medium fat, with highly prebiotic low carbs.

A far cry from steak, eggs, and cream.

raphi said...

@Tim Steele

How much of your total calories do you expect one gets from the high-fiber portion of a VLC diet? Very little I suspect.

If you disagree with the genetic &/or metabolic arguments made about CPT-1a then please say why, addressing them head on. The biological picture fits so well with anthropological one that if you want to turn it all upside down then your arguments should do more than nit-pick on the exact quantities of seasonal berries or the 10-20g of glycogen here and there.

The basic biology is yours for the taking - don't shy away form it. It's less fun that otherwise.

@Ash
Alcohol? Hell, if it's a drug, you'll always find me rooting for the curious and informed.

Tim Steele said...

CPT1A deficiency is a disorder of gluconeogenesis (including glycogen storage disease type I).

Reading from here, now: http://www.ncbi.nlm.nih.gov/books/NBK1527/

"Carnitine palmitoyltransferase I (CPT I) is a mitochondrial membrane protein that converts long-chain fatty acyl-CoA molecules to their corresponding acylcarnitine molecules."

Maybe I'm seeing it all wrong, but being CPT-1 deficient means you cannot go 'into ketosis' well. When you should normally be in ketosis you can die. But there are all kinds of gylcogen storage diseases (http://en.wikipedia.org/wiki/Glycogen_storage_disease),maybe we should find out which ones the Inuit present with when they express the Pro479Leu mutation before we get too far.

The main paper says this allele is associated with "hypoketotic hypoglycemia." (low ketones and low blood sugar). It doesn't seem to imply they have a problem with gluconeogenesis.

Many people don't even realize they have CPT-1a deficiency until they are adults, and then they find out when they get sick or pregnant.

There is this one case on file:

"In a single individual of Inuit origin who was homozygous for the p.Pro479Leu mutation, the presenting feature was a history of exercise-induced sudden-onset muscle cramping with no indication of hypoglycemia or hepatic failure."

So, moving on to glycogen storage disease. The normal treatment is multiple feedings of a special corn starch, SuperStarch, which is very high resistant starch. Regular corn starch has been used, but much less effectively.

Regular, raw corn starch requires several nighttime feedings, SuperStarch allows one to sleep all night. I will let you make up your mind why a high RS feeding would normalize the metabolism at night.

So, to tie this all together, if the Inuits were a society that relied on being in ketosis much of the time, how would a gene which kills people who need to go into ketosis, stay in the gene pool? It seems it would be deleted extremely fast.

A more likely scenario to me is that Inuit babies are fed a nice, sugary diet of HMO rich breast milk, then weaned on high RS foods like Eskimo Potatoes and other nuts, seeds, and roots pre-chewed by momma, and slowly introduced to glycogen-rich aquatic meats and fat.

Truth be told, the Inuit did not live up on the coast all that long, and their diet was probably not conducive to a long, healthy life. But they managed, just as humans do, on what they had available.

Peter mentions this study on a ketogenic diet for Glycogen Storage Disease: http://www.ncbi.nlm.nih.gov/pubmed/21857385

But it isn't really a normal ketogenic diet:

"These findings show that synthetic ketone bodies as well as low-carbohydrate, high-lipid, and high-protein diet may be a more beneficial therapeutic choice therapeutic choice for GSD III patients with cardiomyopathy."

So, I guess we have two issues:

1. Were the Inuit a model ketogenic society?

2. Why is the CPT-1A,Pro479Leu mutation more prevalent in the Inuit communities?

If the answer to #1 is 'no,' then that would indicate that the gene has stayed because they did not have to enter ketosis, and when they did, like the single adult Inuit who exercised too hard, they had problems.

Tim Steele said...

I think this whole blog post points to the fact that the Inuit did not know ketosis.

But I don't know if that was the intent of this blog post.

"For the P497L mutation everything from the evolutionary perspective suggest that a very high FFA inducing diet may be equally efficacious..."

To me it looks as if Peter is saying that he thinks the mutation stayed because the Inuit had continually high levels of FFA in their blood, so the mutation was just ignored. It never killed anyone, so it remained in the small, close-knit communities.

This actually agrees with the first comment above and also the 'cherry-picked' studies at FTA:

Many of the FTA 'Inuit-weren't-in-ketosis' papers cited observed high FFAs.

Bang & Dyerberg mentioned some high LCFAs, which Peter also suggested:

Bang & Dyerberg said: "One of the most remarkable differences is the high amount of certain long-chained fatty acids in the Greenland Eskimos, not occurring to that extent in other groups. This is valid especially for timnodonic acid (20:5), which represented in the Eskimo maritime food and in their plasma lipids."

Ho 1972 said: "Each Eskimo's serum was tested for the presence of ketone bodies....and all serums were negative.... The fact that the Eskimos had high serum FFA and low glucose levels...indicated that free fatty acids played a major role in body energy production.

Duck Dodgers said...

Good work, Peter! What you discovered here falls right in line with the studies that I quoted on FTA.

- Rabinowitch and Corcoran, in 1936, concluded no ketosis but high FFAs.

- Ho, in 1972, concluded no ketosis and high FFAs.

- Bang & Dyerbergy, in 1975 showed high FFAs, particularly LCFAs.

Very interesting, indeed!

@itsthewoo. Sorry, not destroyed. Try reading the studies for a change. What Peter found explains the high FFAs observed in the studies I quoted. I never said the Inuit were high carb. They were LC, high FFAs, but not in ketosis (too much protein).

LeenaS said...

@Tim Steele:

So this is what you think that arctic winter is like? Sitting in huts for several months?

Inside hut is inside hut, not depending on the season, but, actually, outside it is very seldom truly dark in Norhern Lappland (which is far Norther than where you live, methinks), thanks to the snow in winter and the never setting sun in summer. The darkest time ever is in the fall, before the snow comes... but the further up you go, the sooner that happens :)

Us westeners may require reading lights throughout the day. Eskimoes (or Lapps) most probably did not.

Tim Steele said...

Leena - I live very far north! Latitude 65 to be exact. The Arctic Circle is at 66 deg north. The Arctic Ocean and land of the Eskimo are just a bit north of that.

I know what you are saying about the dark of the Arctic Winter not really being DARK. Snow makes everything seem lighter. Fall darkness is much darker with no snow.

But, the Eskimo and Inuit certainly spent lots of time inside dark, smoky huts filled with people. They needed to cook and see. They were great artists, carving ivory and bone. They had lots of time on their hands in the winter, as I do, lol.

I'm sure they got out when they could and didn't sit indoors 24/7, and there were outdoor chores to tend to. But there was no firewood, heating and lighting was all done with blubber/oil.

Some nice Inuit anthropology sites:

http://www.inuvialuitsodhouse.ca/

http://firstpeoplesofcanada.com/fp_groups/fp_inuit2.html

JS said...

"It is a fat-poor land. Sure they caught lots of seals and a whale or two, but they never got good at whaling until white-man came along with big whaling ships."

Tim, I fear you are constructing an alternate reality. Bowhead whale hunting in skin boats has occurred since the Thule Inuit arrived from Alaska perhaps 800-1000 years ago, long before the arrival of Europeans. Many references can be found here:

http://www.uark.edu/misc/jcdixon/Historic_Whaling/Trad_Whaling/trad_whaling.htm
The layman's introduction to First People of Canada (navigation at the bottom):
http://www.historymuseum.ca/cmc/exhibitions/aborig/fp/fpz3a01e.shtml

This sort of trivially incorrect blanket statement casts doubt on all your work -- doubt I feel, based on my very limited investigations, to be justified.

Also, I've spoken at length, in person, with someone who has physically participated in a traditional, village-sustaining bowhead whale hunt, with pictures on their phone and over an hour of gory details to prove it. No forklifts were harmed in the process. (They're not involved in any way with the paleo community.) Based on the composition and sheer quantity of food distributed, even in modern days where everyone has access to imported food and doesn't depend on the hunt, "fat-poor" is not an accurate description.

JS

JS said...
This comment has been removed by the author.
JS said...

It's also necessary to note that caribou hunting, contrary to assumptions, would have provided a substantial amount of calories from fat.

In fact, I've already gone through those figures in great detail - all the way back in 2010! Of particular interest is the section "Hunters Didn't Choose Random Animals" in this article debunking some of Cordain's old assumptions. (The caribou actually selected and taken by hunters under real-world conditions would average over 55% of calories from fat.)

Again, "fat-poor land" is not an accurate description.

JS

Unknown said...

Peter, I'm sure you're right about uncoupling being important here. Brown fat does not have CPT-1a, it has CPT-1b, so fatty acids will get into brown fat mitochondria with no problem. I am wondering whether the mutation is beneficial in a very cold climate because it stops the liver from using fatty acids needed by brown fat?

Perhaps these people's liver mitochondria can get just enough fatty acids to fuel gluconeogenesis, and the rest can be used to keep them warm.

Anonymous said...

"Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6–23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment."

In other words, the diet eaten by the Inuit (low carb, high protein, high fat, replete with FFAs and no ketones, according to the studies cited by Duck Dodgers) allows for massive proliferation of an extremely pathogenic genetic mutation that would otherwise be weeded out of a population eating any sensible diet. If the likely result of observing normal human customs like feeding your kids occasionally some cornstarch and birthday cake is death in infancy and thus failure to reproduce, this would tend to put a break on such a SNP spreading. This study would seem to me to be new evidence that the Inuit diet actually results in reduced fitness of a population forced to eat this way since it puts them in a weird situation of being in mortal danger from eating all three macronutrients which most human populations seem to consume when presented with the choice of eating a wider variety of foods than what is available to the Inuit. To my mind, this is further evidence that the Inuit are simply making the best out of a bad situation, i.e. trying to subsist in extreme Arctic conditions, hardly a template for the ideal human diet.

GK said...

So, an otherwise deleterious mutation confers survival benefits in an extreme environment. This reminds me of sickle-cell in a mosquito-filled habitat, where it's better to be anemic than to be dead.

I f*** love natural selection.

Tim Steele said...

JS - It would be fun to take a time-machine back to see how the Inuit lived in their first thousand or so years on the Arctic coast. It's amazing to me they stayed. I think the evidence shows the most Northern coastal communities were transient and never very prosperous. There was extensive trade with inland tribes, too, trading seal/whale oil for furs or foods they could not source. I believe it was all way more complex than we can imagine.

Concerning the whaling, all prehistoric whaling was done from the shore, and mainly for smaller bowhead whales. Some archeology digs found they may have only targeted calves, which would have been easier to handle. They seemed to have only hunted whales in spring and fall when migration routes brought the whales close to land and open ice leads. Skin-covered boats were used to retrieve or kill the whales, but not the way modern boats are used to hunt down and chase whales way out into open water.

If the ice shifted or the migration route changed, there would be no whales for that village for the year. Same with caribou. The Inuit had to rely heavily on migratory patterns of these animals, but I'm sure it caused many hungry, lean years, and lots of death due to starvation if an alternate food source was not available.

Modern whaling is done with power boats, explosive harpoon tips, and GPS. And they can go after whales far from land.

But, this is not a history lesson or an argument about the exact diet of the Inuit.

I still stand by my assertion that the Arctic is a 'lean' land. Windfalls of fat could be had, but they were not reliable and had many more uses than food.

The Inuit certainly ate fat, but also lots of meat and other foods. Their diet was in no way comparable to a modern day ketogenic diet.

tomR said...

Gary Katch said... @"So, an otherwise deleterious mutation confers survival benefits in an extreme environment."

We - homo sapiens sapiens - tend to deal with extreme environments by using technology. It's the Neanderthals that utilized physiological adaptations as a way to live in a difficult environment - and where are they now?

Duck Dodgers said...

JS said: "It's also necessary to note that caribou hunting, contrary to assumptions, would have provided a substantial amount of calories from fat."

Fat and blubber were also saved, and traded as a heat and light source during the long, dark winter (it's dark 24/7 during the Winter there). So, it was a commodity for them. Caribou was their favorite fat to eat, while marine fats tended to taste more like fuel to them.

Secondly, Per Wikholm recently published an article in Sweden's LCHF Magasinet, which shows that the Inuit could not have been in ketosis based on the data in the scientific literature as well as Stefansson's own observations.

Per gives us a short overview, from his article, where he shows how Stefansson admits that Arctic caribou is too lean:

http://freetheanimal.com/2014/10/damned-inuit-diet.html#comment-662864

And if that weren't enough, here’s a study on the dietary preferences of Inuit. It’s a survey on what they “preferred” and what was eaten “often” in each household.

Use of and Preference for Traditional Foods among the Belcher Island Inuit, [Free Download] by Eleanor E. Wein, Milton M. R. Freeman and Jeanette C. Makus (1996)

You can see that muktuk (sweet-tasting, glycogen-rich skin) and meat were eaten and preferred most often. Blubber and fat scored much lower in preference and frequency of consumption. Incidentally, of the non-traditional foods modern Inuit consume, they seem to like Mac and Cheese. :)

Galina L. said...

@TomR,
Different human species didn't get started at the same time, in the same environment. Neanderthals extincted, but they emerged from Africa much earlier than Homo Sapience and spent on Earth more than 200 000 years. There is no warranty we will fire much better, our average brain size is already smaller than CroMagnons had, and it is easy to observe that humans get weaker and sicker as our civilization advances which is natural when health and intelligence don't give modern people a particular survival advantage.

Duck Dodgers said...

JS said: "Also, I've spoken at length, in person, with someone who has physically participated in a traditional, village-sustaining bowhead whale hunt, with pictures on their phone and over an hour of gory details to prove it."

Very cool! Though, it's worth noting that blubber is not pure fat. For instance, when day-old sperm whale blubber is analyzed for carbohydrates by direct measurements (as opposed to the standard subtraction method) it was typically found to be between 8 to 30% carbohydrates.

Body composition of the sperm whale, Physeter catodon, with special reference to the possible functions of fat depots, by Christina Lockyer (1991), p. 9

"Carbohydrate which has been directly assessed (not deduced by subtraction of other compotents from total weight of sample) is significant in amount, reaching levels in the range 8-30%, except in the anterior dorsal and ventral regions (head) where levels are 6% and <1% respectively."

Interestingly, their favorite part of the whale was the skin and attached blubber (mattak), where the carbohydrates and ascorbic acid were concentrated—as Alfred Bertelsen discovered in 1911 (and reported by Krogh & Krogh). It was said to taste sweet, like hazelnuts. And it was "arguably...the most favored delicacy in the Inuit cuisine."

I would also point out that Arctic explorer, John Murdoch, wrote that seal and whale blubber was mostly burned for fuel.

On Some Popular Errors in Regard to the Eskimos, by John Murdoch (1887)

"We found, indeed, at Point Barrow, that comparatively little actual blubber either of the seal or whale was eaten, though the fat of birds and the reindeer was freely partaken of. Seal or whale blubber was too valuable,—for burning in the lamps, oiling leather, and many other purposes, especially for trade."

Sam Knox said...

Is this really the best use of our time?

Tim Steele said...

Sam - I think this is a long, long, long overdue discussion! Not so much each person's personal belief on how Inuits lived, ate, and passed the time in Winter, but the emulation of the Inuit diet as a healthy eating style.

Many people point to the Inuit as an H-G society that prospered while living in a total ketogenic state, obtaining nearly all calories from fat. Now we are finding that maybe that view was wrong.

And even if it wasn't wrong, seeing now that the Inuit have carried a gene for thousands of years that should spell doom for a high-fat society, they lived with the gene and it seemed to cause no harm, or even protected them.

Again, this all points to the fact we should not look to the Inuit for diet advice.

Richard Nikoley said...

Hi Peter:

It might surprise a lot of your commenters/readers (but not Duck or Tim) that I love this post. It's another huge piece of the puzzle for me, and I'm drafting a post now in thanks, and trying to do some dot-connecting.

I do have some quibbles with how you frame the evolutionary selection, but it's "small potatoes," so I'll save it for the post.

I think that the import of your discovery may have gone over the heads of some of your readers who JUST KNOW Duck's and my 17-post series is now trashed...TRASHED, I tell you!

In fact, for those who actually read the series, the dozens of studies going back 100 years, minimally understood the point, this constitutes another fabulous piece of the puzzle. I'll address that too.

...In the meantime, what interests me most is that, according to my very quick "Google Degree" on the CPT1A mutation (arctic version), one ought expect FFA to be deleterious, so paradox. Still chewing on your speculation.

I wonder if you could add this to your speculation, as I'm not quite sure how it fits in (about to give your speculative section a 3rd read).

The Inuit were shown to perfectly handle a Glucose TT while fed (back in 1928, 140g bolus glucose, if I recall), but it went to poopoo when fasted 80 hours.

http://freetheanimal.com/2014/03/reiterate-elevated-ketone.html

But, when Stefansson and Anderson dis that year at Bellevue on an "Inuit Diet" they failed a GTT while fed, at the conclusion of the experiment.

http://freetheanimal.com/2014/07/stefansson-experiement-compromised.html

Thanks again, Peter.

Duck Dodgers said...

To clarify Richard's comment, above. The year long Bellevue Experiment (McClellan & DuBois, 1930) done on Stefansson and Anderson was a high fat, ketogenic diet.

However, McClellan & DuBois admitted that the Bellevue Experiment did not follow a true Eskimo diet, which had been observed by researchers to be a non-ketogenic high protein diet. The researchers had attempted to emulate the Inuit diet at the beginning of the experiment, but Stefansson quickly became ill from protein poisoning and demanded more fat to make him ketogenic. Draper (1977) found that the Inuits appeared to have evolved abnormally enlarged livers which enabled to process higher protein intake than white men (Inuit Paradox, Discover Magazine, Oct 2004).

Tolstoi (1929) tested Stefansson and Anderson after the conclusion of the Bellevue Experiment and found the white explorers on the ketogenic diet failed their glucose tolerance tests. While Heinbecker (1928) showed that Eskimos on their native diet passed their glucose tolerance tests when in their fed state, but failed their tests when fasted for almost two days.

Heinbecker performed three studies between 1928-1932 and they all showed that while the Inuit were not in chronic ketosis from their diets, they were adapted to starvation ketosis however.

Our review of the literature can be found here for those who are curious. And it's worth paying attention to Per Wikholm's comment below the article.

Again, Peter, this is a very cool discovery. Well done.

Tucker Goodrich said...

"Given sustained very high levels of FFAs, you might even make some ketones."

"Although the enzyme has reduced maximum activity as 20% of normal enzyme, it also has unregulated capacity for FAO. Theoretically, this would allow an individual to slowly and continuously generate energy via ketone body production from fatty acids even when not fasted. Once could conceive this as being advantageous during long winter months when food is scarce and provided that there are ample fat stores generated during the summer season (Greenberg et al. 2009). Fasting in the absence of adequate fat stores may possibly be harmful in this scenario, particularly in infants, and this may account for the high infant mortality rate."

"Pathophysiology of fatty acid oxidation disorders"

http://link.springer.com/article/10.1007/s10545-010-9170-y

Puddleg said...

The inhabitants of the Faroe islands also carry a carnitine mutation - Systemic primary carnitine deficiency (SPCD)
This is also more common in Japan and than in the US.

This cannot be a co-incidence - these are colder places with high seafood intake.

http://www.ncbi.nlm.nih.gov/books/NBK84551/

Puddleg said...

" though the fat of birds and the reindeer was freely partaken of."

Sea birds are very fatty - have you ever eaten a muttonbird? Penguins used to be hunted for their oil; the Inuit would have had the Great Auk (a kind of Arctic penguin) in vast amounts until this was wiped out by Europeans a few hundred years ago.
R. M. Ballantyne in Ungava, one the Arctic books he based on his life in Hudson bay describes fat "an inch think" on a reindeer haunch.

tomR said...

@Galina L - a normal occurence for Northern people is to move South or invade South if already occupied. If Inuit have problem with this because their genes make it difficult to tolerate Southern food, then it means these genes are faulty, they make them stuck at at the dead-end, unattractive location.

The Neanderthals are a good analogy because by what we know about the way they evolved: they adapted morphologically and physiologically to difficult climate. Modern humans didn't; they just invented tailoring, and then went up North. Inuits with their weird genes are going the way of Neanderthals.

Richard Nikoley said...

Don't be so quick to judge, tomR.

By many accounts I'm reading, the work Duck and I did to show why the Inuit are not a great analog has been interpreted as a slam dunk to show why a mutant gene is what EVERYONE WANTS, kinda like Brando.

Only, that's for the plants. It's what they crave.

Richard Nikoley said...

Don't be so quick to judge, tomR.

By many accounts I'm reading, the work Duck and I did to show why the Inuit are not a great analog has been interpreted as a slam dunk to show why a mutant gene is what EVERYONE WANTS, kinda like Brando.

Only, that's for the plants. It's what they crave.

tomR said...

Notice there's another group that is worse at fat burning - South Asians:

http://www.nhs.uk/news/2010/12December/Pages/greater-diabetes-risk-in-south-asians.aspx

"The findings suggest that South Asian men have a lower rate of fat metabolism during exercise than European men. During resting states, fat metabolism was the same. The South Asian men also had a reduced sensitivity to insulin compared with the European group."

Basically you need to check your genes before deciding on a diet, especially when it comes to fat percentage in a diet.

tomR said...

About South Asians again - yes their feautres are partially due to the CPT1A gene...

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014197

"Skeletal muscle expression of oxidative and lipid metabolism genes

Expression of oxidative and lipid metabolism genes in skeletal muscle is shown in Table 4. Expression of carnitine palmitoyltransferase 1A (CPT1A) was 1.79-fold greater (p = 0.023) and expression of fatty acid synthase (FASN) was 1.96-fold greater (p = 0.036) in South Asians than Europeans."

Galina L. said...

TomR, I think many people who are too enthusiastic about being in ketosis belong to a self-selected group with some weird genetic as well, we are less adapted to live on different plant foods .
I guess I have some Asian genetic in me - my tolerance to alcohol is very poor, and it take forever to metabolize.
May be Inuits love their land. I guess they could be less happy in a climate where they would have to tolerate warm temperatures.

Unknown said...

@tomR

"you need to check your genes before deciding on a diet"

Actually checking your gut bacteria might make a lot more sense. Did you know that most of the milk drinking Masai have lactose intolerance?

'... Data are presented in this paper that show that 1) the Masai regularly drink considerable quantities of milk without apparent symptoms, 2) milk is an important constituent of the Masai diet, and 3) 62% of 21 Masai examined were malabsorbers of lactose as measured by the lactose tolerance test. This finding of lactose malabsorption in a nomadic cattle raising and milk drinking people is interesting and is contrary to the views often expressed by anthropologists and others. ...'
http://www.ncbi.nlm.nih.gov/pubmed/581925

v/vmary said...

i don't think my gut bacteria could help me deal with a 80 carb g container of ice cream. i go to 155 at one hour from a lack of insulin (not insulin resistance). this is due to a risk T allele in my TCF7L2 gene. i don't think bacteria will help me produce more insulin.

Unknown said...

Hi v/vmary

Well the effects of the T allele on progression to diabetes can be reduced to non significant by 'lifestyle intervention' or metformin, according to this study.

'TCF7L2 Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program'
http://www.nejm.org/doi/full/10.1056/NEJMoa062418#t=abstract

It isn't completely clear from the paper what the dietary advice was, but it's probably safe to say it included 'eat more fruit/veg/whole grains', which means food for gut bacteria.

We know that fermentable fibre improves magnesium absorption
http://www.ncbi.nlm.nih.gov/pubmed/12514257

... and magnesium improves beta cell function.
http://www.ncbi.nlm.nih.gov/pubmed/21241290

John said...

Jane,

How does the milk itself affect symptoms? I don't have lactose intolerance, but I will get digestive distress if I drink 1/2 gallon of milk sometimes. Certain brands will lead to much distress, while others I will notice nothing.

Tim Steele said...

I'm curious where we are on the original blog post.

From what I can tell, it is a fact that 80% of Eskimo children born today in Alaska are homozygous with the P479L Inuit variation of CPT1A disorder.

http://www.ohsu.edu/xd/education/schools/school-of-medicine/academic-programs/graduate-programs-human-nutrition/programs/combined-di-masters/upload/Sarah-Lowe-manuscript.pdf

So what we see is a gene that was prevalent in the old days when Eskimos were eating their traditional diet, and still around today while they are eating a modern, high sugar/carb diet.

It seems this genetic mutation was not harmful then and it's not harmful now.

What it does seem to indicate, is that the Inuit do not have the capability to produce enough ketones to fuel a ketogenic diet.

All that this implies to me is that the work of Phinney and Volek was done on faulty pretense as they often cite the Inuit as a ketogenic success story. It appears now that the modern day ketogenic diet is the first of its kind and has no ancestral counterpart.

Lots of confusion from the blog, I guess. The Inuit/Eskimo do not have Glygogen Storage Disorders that sometimes arise from CPT1A mutations, instead they simply have a faulty ketone production system. 80% have it, yet none worry about it and it doesn;t effect anyone unless they don't eat for 15-20 hours and need ketones, then they go hypoglycemic and hypoketotic. A handful of Sugar Pops clears it up.

Looks like their ancestral diet kept their glycogen stores full and their brain and body running fully on glycogen. Yay sugar burners!

Duck Dodgers said...

Excellent points, Tim! Hopefully everyone can put their thinking caps on and dig into the science on this one. No need for anyone to defend dogmas at this point considering that the Inuit are clearly nothing like us Westerners (i.e. we can't emulate their metabolisms even if we wanted to).

Here's a study that confirms what Tim is saying. It shows that the modern Inuit mainly survive on a high sugar/high fat diet:

Changing dietary patterns in the Canadian Arctic: Frequency of consumption of foods and beverages by Inuit in three Nunavut communities, by Sheehy, et al. (2014)

"Results. The 30 most frequently consumed foods were identified. Non-nutrient-dense foods (i.e., high-fat and high-sugar foods) were the most frequently consumed food group (median intake, 3.4 times/day), followed by grains (2.0 times/day) and traditional meats (1.7 times/ day). The frequency of consumption of fruits (0.7 times/ day) and vegetables (0.4 times/day) was low. The median values for the three most frequently consumed food items were sugar or honey (once/day), butter (0.71 times/day), and Coffee-mate (0.71 times/day). Apart from water, coffee, and tea, the most frequently consumed beverages were sweetened juices (0.71 times/day) and regular pop (soft drinks) (0.36 times/day). This study showed that non-nutrient-dense foods are consumed most frequently in these Inuit communities."

So, the evidence clearly shows us that the modern-day Inuit consume lots of sugar and grains, multiple times per day. Their modern day, junk-food, diet is fairly well known. So, I'm not entirely sure why this even needs to be pointed out.

Even Krogh & Krogh (1914) fed the Inuit mostly bread and sugar for 2 of the 4 days in the Krogh's respiration chamber, before switching them to their native diet. And Heinbecker (1928) gave them glucose tolerance tests—and they all passed, except when fasted!

So, it really should be obvious that the Inuit don't have problems metabolizing sugar.

Tim Steele said...

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.

Is anyone still thinking the Inuit were living in a state of ketosis? They can't. Well, 80% can't today. Maybe before Steffansen made his blonde-inuit baby it was closer to 100%.

Duck Dodgers said...

...And Tim. Don't forget the Inuit were known to have abnormally large livers. Harold Draper, who studied the Inuit in the late 1970s, was referenced in the October 2004 issue of Discover Magazine, as saying:

"On a truly traditional diet, says Draper, recalling his studies in the 1970s, Arctic people had plenty of protein but little carbohydrate, so they often relied on gluconeogenesis. Not only did they have bigger livers to handle the additional work but their urine volumes were also typically larger to get rid of the extra urea."

Draper also mentions the high protein and increased urea in his 1977 paper.

Perhaps their enlarged livers assisted them in prolonged fasts, when they couldn't rely on ketones.

Michael Frederik said...

So let me get this straight: The Inuit are doing fine on their high sugar/carb diet, and if they do happen to run into a hypo, why, no worries, some sugar pops to the rescue.
Never mind the media reports of ever increasing rates of diabetes and the obvious obesity of Inuit eating a western diet I've seen in documentaries. No, no harm done.
It takes some doing to beat the imbecility of the likes of Stone and Peat, but there you go.

Duck Dodgers said...

Michael Frederik said: "So let me get this straight: The Inuit are doing fine on their high sugar/carb diet"

Um, no. The point is that a dose of sugar is not fatal to them. They are obviously better off on their ancestral diet (which is High Protein, High Fat, according to the literature).

I find it rather odd that nobody here is interested in digging into the science that Tim uncovered. The common theme seems to be ridiculing anybody who tries to read into the literature a bit more. WTF?

Unknown said...

Hi John, good to see you. I'm sorry to say I have absolutely no idea.

Peter said...

I have more information. Another post to follow.

Peter

v/vmary said...

jane said: "... and magnesium improves beta cell function.
http://www.ncbi.nlm.nih.gov/pubmed/21241290."

i had red blood cell magnesium tested and i am right in the middle of the reference range. I am not magnesium deficient. it does does improve my blood sugar disposal. would taking in more magnesium reduce the insulin needs of a type 1? that would convince me.

Michael Frederik said...

Um, yes. That's exactly what Tim wrote above.

Btw, I've now seen the Inuit diet typified as high fat, medium fat, and fat-poor on just this one thread of comments. Apparently the Inuit diet can be just about anything, a bit like the Mediterranean diet.

Now I've just seen this statement by Tim on his latest blog post:
"Ketoacidosis is a condition that diabetics find themselves in if they eat too much fat and protein and not enough carbs."
There are others there, equally insane. Really, how is one to believe anything by these idiots?

tomR said...

"Apparently the Inuit diet can be just about anything, a bit like the Mediterranean diet."

I disagree with that. There are many aspect of Mediterranean diet that are clearly defined. Like oil choices - preference for olive oil over others. Or fruits like oranges as compared to apples of the North.

Some confusion may come from dietary experts who in one sentence tell you that you should eat the Mediterranean diet, then in another sentence tell you that you should eat a giant breakfast, the most important meal of the day, while in Mediterranean countries people eat tiny breakfast, with larger dishes in the evening...

Duck Dodgers said...

"Um, yes. That's exactly what Tim wrote above"

Well, when someone with this condition is admitted to the hospital, they apparently administer them an IV with dextrose in it. So, I suppose Tim is technically correct. :)

John said...

Duck,

Digging further into what? You two just keep repeating that they didn't seem to be in ketosis. Tim also said that their modern diet isn't harmful...?

When one pushes an idea like a salesman, some people are going to lose interest. In Nikoley's case: low carb, potatoes, kefir, resistant starch, Indian gooseberry, tortillas--everything is a miracle. He is on the same path as Matt Stone but two years behind.

tomR said...

@john - so how many measurments of Inuits fed their traditional diet (not fasting) have shown:
1) That they were in ketosis
2) They were not in ketosis

tomR said...

@Tim - couldn't the very large liver itself be a storage organ for proteins? I've read a hypothesis that people actually have some storage for proteins - in the form of internal organs being above sizes needed to sustain them.

Tim Steele said...

I will be the first to admit I am no expert in the ketogenic arts. The comment I made on my blog about ketoacidosis was to a person who was asking the difference between 'ketosis' and 'ketoacidosis.' I went straight to Wikipedia, and found this:

"Ketoacidosis is most common in untreated type 1 diabetes mellitus, when the liver breaks down fat and proteins in response to a perceived need for respiratory substrate."

Is Wiki wrong? Did I get it wrong? No matter!

The issue at hand here is, "Is the Inuit diet a good template for the modern day ketogenic diet?"

The answer is , "No."

The reason I may sound like a salesman here is because I am trying to correct 40 years of such salesmanship. Ever since the Atkins diet came out in 1974, everyone has been spouting that a ketogenic diet is wonderful, as evidenced by the ketogenic Inuit.

It doesn't take very many mouse clicks to find jewels like:

"Stefansson dropped 10 pounds on his meat-and-fat regimen and remarked on its “slenderizing” aspect, so perhaps it’s no surprise he’s been co-opted as a posthumous poster boy for Atkins-type diets. No discussion about diet these days can avoid Atkins. Even some researchers interviewed for this article couldn’t resist referring to the Inuit way of eating as the “original Atkins.”" -Discovery Magazine, 2004

or

"The question one needs to ask is did staying in ketosis most of their lives lead the Inuit to live longer lives than they would have in the conditions under which they lived?" Dr. Eades, 2006

or

"Finally, and I may be wrong, only in uncontrolled diabetes would ketone production be high, and certainly not in Type 2 diabetes. Then there’s all the evidence that isolated populations eating their traditional diets got relatively little to no cancer. I discuss this in GCBC. This includes populations that ate no carbohydrates (the Inuit, the Masai, etc.). So that would argue for glucose and insulin related drivers, not ketones." Gary Taubes

As far as I'm concerned, once the Inuit myth falls, the Keto Diet will soon follow. There is no ancestral counterpart.

This may not be why Peter wrote this blog, but it's a perfect jumping off point for the falsification of the 'ketogenic Inuit' myth.

Duck Dodgers said...
This comment has been removed by the author.
Duck Dodgers said...

tomR said: "@john - so how many measurments of Inuits fed their traditional diet (not fasting) have shown:
1) That they were in ketosis
2) They were not in ketosis"

The answer to #1 is ZERO.

The answer to #2 is FIVE.

Researchers who either demonstrated or concurred that the Inuit diet was high protein and not ketogenic:

Krogh & Krogh 1914 (Nobel Prize winner)
Lusk 1914
Joslin 1921 (first doctor to ever specialize in diabetes in the US)
Schaffer 1921
Heinbecker, 1928, 1931, 1932
Tolstoi 1929
McClellan & DuBois 1930 (Stefansson's own doctors)
Rabinowitch 1936
Rabinowitch & Corcoran 1936
Rabinowitch and Smith 1936
Kaare Rodahl 1952
Sinclair 1953 (A detailed review of the literature)
Ho 1972
Hui 1975
Draper 1977
VanItallie & Nufert 2003

The only person who claimed that the Inuit were ketogenic was Stefansson—and he didn't provide any detailed measurements.

In a paper on ketosis, Phinney references Stefansson's experience in the Bellevue Experiment as a proxy for the Eskimo diet, saying:

"It is interesting to note from the careful observations published from the Bellevue study that Stafansson ate relatively modestly of protein, deriving between 80–85% of his dietary energy from fat and only 15–20% from protein. This was, and still remains, at odds with the popular conception that the Inuit ate a high protein diet, whereas in reality it appears to have been a high fat diet with a moderate intake of protein."

So, Phinney doesn't even rely on actual measurements on living Eskimos to make his case. He literally just used Stefansson's Bellevue Experiment as his measuring stick—despite the fact that the authors of that study admitted that it didn't represent the Eskimo diet that had been measured in other studies. What a joke.

The CPT1A papers that call for a ketogenic diet use Phinney's flawed references as their guide. It's a huge mess.

tomR said...

@Peter - "I have more information. Another post to follow."

When writing a new article about CPT1a gene please don't forget about South Asians. There are like over billion of them! Compared to like 100k of Inuits. If you were to compute an average human - the South Asians would be a big input into this. Concentrating on Inuits rather than on a billion may look like cherrypicking...

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014197

"Skeletal muscle expression of oxidative and lipid metabolism genes

Expression of oxidative and lipid metabolism genes in skeletal muscle is shown in Table 4. Expression of carnitine palmitoyltransferase 1A (CPT1A) was 1.79-fold greater (p = 0.023) and expression of fatty acid synthase (FASN) was 1.96-fold greater (p = 0.036) in South Asians than Europeans."

tomR said...

What carbsane wrote about it:

"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."

About peroxisomes:

http://www.biocarta.com/pathfiles/boxnpPathway.asp

"In addition to the beta-oxidation of fatty acids in mitochondria, animal cells carry out beta-oxidation in another organelle, the peroxisome. Although the mitochondrial and peroxisomal beta-oxidation pathways are similar, the details differ somewhat."
"The first difference between the pathways is that the initial substrate in peroxisomes is very long chain fatty acids, longer than those that mitochondria can efficiently oxidize." "The lack of ATP generation in peroxisomes at this step makes peroxisomal beta-oxidation a less efficient energy source than the mitochondrial pathway."

http://en.wikipedia.org/wiki/Beta_oxidation

"One significant difference is that oxidation in peroxisomes is not coupled to ATP synthesis. Instead, the high-potential electrons are transferred to O2, which yields H2O2. It does generate heat however."

So it looks like a solution - Inuits need a lot of heat, so they burn long fats in peroxisomes for heat, rather than mitochondria for mechanical energy (ATP).

It looks like it has been known for a long time, that there's a split between ATP-production preference vs. heat generation preference in human genes based on the climate the humans live. Example:

http://johnhawks.net/weblog/reviews/neandertals/neandertal_dna/ruiz-pesini_selection_mtdna_2004.html

"So in other words, populations in northern latitudes today are enriched for a number of mtDNA haplogroups that are likely adaptive to cold. Today, these haplogroups (as a class) are largely protective against degenerative diseases of aging, possibly because they reduce oxygen free radical production. But they are also more susceptible to disorders of energy metabolism, because they reduce ATP production."

tomR said...

@Tim - Wikipedia says that ketoacidosis is just a higher level of ketones in the blood than ketosis.

http://en.wikipedia.org/wiki/Ketosis


Ash Simmonds said...

http://highsteaks.com/forum/health-nutrition-and-science/nutritional-ketosis-vs-ketoacidosis-369.0.html

Anonymous said...

Quoting the University of Wikipedia is so lame and lazy.

Peter Attia alluded to this in the first of two in-depth articles on ketosis:

"Before we begin, a disclaimer in order: If you want to actually understand this topic, you must invest the time and mental energy to do so. You really have to get into the details..."

http://eatingacademy.com/nutrition/ketosis-advantaged-or-misunderstood-state-part-i

And from the second article:

"Parting shot - Ok, if you’re still reading this, give yourself a pat on the back. This was a bit of chemistry tour de force. Why did I do it? Well, frankly, I’m tired of reading so much nonsense on this topic. Everybody with a WordPress account (and countless people without) feels entitled to spew their opinions about ketosis without even the slightest clue of what they are talking about."

Biochemistry and metabolism are NOT simple. Understanding often requires significant effort beyond Wikipedia, "reference spamming", and "cherry picked" quotes. Ketosis is no different.

John said...

Duck,

My point was just that there is no fierce debate as to whether Inuit are in ketosis--at least here. But you and Tim keep providing it as the answer to any question: "How does the CPT1a mutation affect Inuits?" "They weren't in ketosis!" ..."How does a low carb diet affect health?" "Duh, don't you know the Inuit weren't in ketosis?"

Instead of directly addressing a specific point, you attack some mainstream low carb idea and then use it against someone here, usually Peter. Carbsane used to do that all the time: find any flaw in something Taubes said/wrote and then conclude that all low carb eaters/researchers were wrong.

Obviously you two are more reasonable and polite, but I don't see the logical connection between Inuit ketosis and the benefits/troubles of a low carb diet (with WAPF foods for example). How does showing the Inuit weren't in ketosis show that low carb diets are unhealthy?

tomR said...

@hithaeglir - There's nothing about perixosomes in the Peter Attia articles you linked to. Or in tags on this site. And they seem to be important for fat utilization by the body. Does that mean that both sources are not in depth enough, especially compared to Wikipedia, that does have this info?

tomR said...

@john - the discussion about ketosis was started with the first blog post of Peter, notice that he used the word "here" - meaning he was talking about either Inuit or in general people with this CPT1a gene variant:

"We know that a deeply ketogenic diet both protects from hypoglycaemia and sets the body up to run perfectly well without any dietary glucose, which might be lost to glycogen stored permanently in the liver/muscles. There is every justification for giving the finger to cornstarch here and the folks suggesting a modification of ketogenic eating appear to be on fairly safe biochemical ground."

This passage required at least a clarification that Iniuts are not in ketosis, at least the nutritional one (when fed).

Unknown said...

@John
The point here is that the authors of both papers on the CPT-1a mutation say the Inuit ate a ketogenic diet. They should have read the literature, as Duck has done, but they didn't.

Duck Dodgers said...

Krogh & Krogh arrived in Greenland in 1908 and conducted detailed experiments in their respiration chamber. In order to get the Eskimos to agree to sit in the chamber for 4 days straight, and have their urine and feces analyzed, the Eskimos demanded to be fed carbs for two days (bread, coffee with sugar), and in exchange they agreed to eat their native diet for the other two days, as long as they were provided a little bread and coffee with sugar. Those were their demands. The Kroghs then analyzed Rink's statistical nutritional survey data from 1855 and wrote:

"...The normal diet of Eskimos contains an excessive amount of animal protein (280 gr.) and much fat (135 gr.) while the quantity of carbohydrate is extremely small (54 gr. of which more than 1/2 is derived as glycogen from the meat eaten)."

For those who are interested, you can pour over all the data here. Auguste Krogh was very well respected as he won a Nobel Prize a few years later for his groundbreaking work in cardiovascular and muscle physiology.

If you do the math, their estimation comes to a diet of 47% Fat, 44% Protein, and 8.3% Carbohydrates. In those experiments, the Kroghs only fed the Inuit about 2 pounds of lean seal meat from what I can gather. It was warm at the time, so perhaps the subjects didn't need the extra calories. But, it had been reported that the Eskimos could easily consume 8 to 10 pounds of meat per day (Sinclair 1953 discusses this exceptionally high protein intake and believes the total calories would have been much higher in the extreme cold). The Kroghs didn't attempt to reproduce such large amounts of protein, so their caloric estimation was apparently based on more Western amounts.

By 1928, Heinbecker showed that the Inuit had trouble producing ketones. He recognized the Krogh's estimations and wasn't surprised that they weren't in ketosis. Heinbecker performed two other studies showing that the Inuit had trouble producing ketones. Now we know why, thanks to CPT1A. But, Heinbecker also showed that the Eskimos could tolerate carbs well too.

In 1930, McClellan & Dubois performed the famed "Bellevue Experiment". From the very beginning Stefansson's doctors attempted to feed him the equivalent Eskimo diet that had been observed by Krogh and Krogh. They wrote:

"August and Marie Krogh, in 1908, studied the dietary of the Greenland Eskimo...they estimated that the daily diet contained approximately 280 gm of protein, 135 gm of fat, and 54 gm of carbohydrate...During the first 2 days [Stefansson's] diet approximated that of the Eskimos, as reported by Krogh and Krogh, except that he took only one-third as much carbohydrate. The protein accounted for 45 per cent of his food calories. The intestinal disturbance began on the 3rd day of this diet. During the next, 2 days he took much less protein and more fat so that he received about 20 percent of his calories from protein and 80 per cent from fat. In these two days his intestinal condition became normal without medication. Thereafter the protein calories did not exceed 25 percent of the total for more than 1 day at a time. The high percentage of calories from protein may have been a factor in the production of the diarrhea."

What we can see from the Bellevue Experiment is that McClellan & DuBois tried to get Stefansson to eat like the Greenland Eskimos but Stefansson got protein poisoning. In Harper's Monthly Magazine, Stefansson basically pleads for more fat.

[continued...]

Duck Dodgers said...

...At the conclusion of the Bellevue Experiment, Tolstoi tested Stefansson and Anderson for carb tolerance and found that they had lost their tolerance to carbs. Whereas Heinbecker's Eskimos maintained carb tolerance on their native diet.

In 1936, Rabinowitch travels deep into Norther Canada to do his own measurements. Rabinowitch confirms that the Eskimos there are very high protein, writing:

"When consideration is given to these facts and to the additional fact that about 58 percent of protein is convertible into sugar, it is obvious that the ratio of fatty-acid to glucose is well below the generally accepted level of ketogenesis. I estimate that when food is abundant, the average daily diet of the adult Eskimo consists approximately of 30 to 40 grams of carbohydrate (which includes glycogen), 250 to 300 grams of protein, and about 150 grams of fat (FA/G=1.2). These amounts of meat are apparently not heroic, for it has been alleged that the Yakuts, on the Low Steppe, east of the Lena, eat as much as 25 and 30 pounds of meat a day."

Rabinowitch also noted elevated FFAs in the blood of his Eskimos.

In 1972, Ho found no ketosis and he found elevated FFAs. Ho wrote:

"Each Eskimo's serum was tested for the presence of ketone bodies....and all serums were negative.... The fact that the Eskimos had high serum FFA and low glucose levels...indicated that free fatty acids played a major role in body energy production."

In 1977, Harold Draper wrote a paper explaining that the Inuit processed considerable quantities of protein. In 2004, a Discover Magazine article referenced Draper, as they wrote:

"On a truly traditional diet, says Draper, recalling his studies in the 1970s, Arctic people had plenty of protein but little carbohydrate, so they often relied on gluconeogenesis. Not only did they have bigger livers to handle the additional work but their urine volumes were also typically larger to get rid of the extra urea."

We now know that CPT1a tends to cause enlarged livers. Perhaps this was advantageous to them, maybe even during prolonged fasts when they couldn't rely on ketones.

Despite the hard evidence for high protein consumption and enlarged livers, Phinney discards it all, using the Bellevue Experiment on two white men as a proxy for the Inuit diet. Phinney writes:

"It is interesting to note from the careful observations pub- lished from the Bellevue study that Stafansson ate relatively modestly of protein, deriving between 80-85% of his dietary energy from fat and only 15-20% from protein. This was, and still remains, at odds with the popular conception that the Inuit ate a high protein diet, whereas in reality it appears to have been a high fat diet with a moderate intake of protein."

So, Phinney uses the experience of two white guys and discards all of the actual measurements on the Eskimos to make his case.

The CPT1A papers that are now recommending a ketogenic diet for Eskimos are only referencing the flawed Phinney paper as proof that the ancestral diet was a moderate level of 15-20% protein.

So, there's a large body of evidence that the Inuit ate a very high protein diet that is being ignored by proponents of ketosis in the literature. And I think it's probably more than a little irresponsible for researchers to acknowledge the Inuit had a rare metabolism and then make recommendations that are solely based on the experience of two white guys.

Tim Steele said...

"Obviously you two are more reasonable and polite, but I don't see the logical connection between Inuit ketosis and the benefits/troubles of a low carb diet (with WAPF foods for example). How does showing the Inuit weren't in ketosis show that low carb diets are unhealthy?"

I have never once said that a low carb diet is bad or unhealthy. You could probably say I eat a low carb diet. My interest in LC is what keeps me reading Peter's great blog.

This whole thing about the Inuit being in ketosis or not is simply about correcting a form of circular reasoning that has been kept going for decades.

The Inuit are cited as a model community to study and emulate based on their thousands of years as hunter-gatherers in 24/7 ketosis.

The problem here is, the Inuit were never in ketosis. The diet was not nearly as ketogenic as people have made it out to be and now we find that the Inuit couldn't be in ketosis even if they followed the Atkins Diet book and peed on Ketostix 10 times a day...

The 'circular' part is easy to see. Researchers cite Phinney who cites Vilhjalmur Stefansson who just seemed to make stuff up. Now there are all these studies and papers out there that started with a false basis, but no one has questioned the faulty beginnings until Duck Dodgers noted all of the inconsistencies in earlier Inuit studies that said they were NOT in ketosis.

That is the only point I am interested in driving home.

I personally think that a ketogenic diet is short-sighted and starves out our gut flora, but has potential therapeutic value.

If people want to try a ketogenic diet, I won't try to stop them but I do want to take away their false sense of security that it must be safe 'because the Inuit did it.'

Another blog I keep up with is Fathead. His thoughts of LC and ketosis mirror mine almost exactly. Read his ideas about the difference in LC and ketogenic diets, but read with the viewpoint that all of the researchers he mentions use the circular reasoning that ketosis is harmless based on the Inuit experience.

http://www.fathead-movie.com/index.php/2012/07/09/low-carb-ketosis-not-necessarily/

and another:

http://www.fathead-movie.com/index.php/2014/09/08/review-keto-clarity/

raphi said...

McTimmins & Dr.Duckster

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1561651/pdf/canmedaj00512-0065.pdf] dated 1936.

"Parenthetically, it may be observed that, from the metabolic point of view, it would appear that many of the Eskimos are now in greater danger of alkalosis than acidosis, because of their practices with flour. The 'bannock', which some eat in large quantities when finances permit, is essentially a mixture of flour and baking soda, and the Eskimo, according to the amounts which I saw used, had no sense whatsoever of the necessary relative proportions of flour and baking soda for the preparation of food."

"Since life is incompatible without salt, it would appear that, in order to keep the concentrations of this salt in the blood constant, the renal threshold is raised. Also of interest in the metabolic data is the inability to tolerate large doses of glucose, judging from the blood sugar time curves."

I admit, I never tire of saying this, but...as a wise Dr.Lagakos once mused over at http://caloriesproper.com/dietary-protein-does-not-negatively-impact-blood-glucose-control/ ""Dietary protein-derived amino acids have a purpose, and that purpose is not carbs"".

These population were seriously fat adapted. What whether that's primarily via ketogenesis, FFA oxidation or pink unicorns (or a mishmash of all 3) this only goes to show the versatility/flexibility of our general metabolism and particularly that of our fat-based one.

The Greenberg et al. & Clemente et al. papers Peter brought up argued for some pretty cool stuff and raise even better questions.

So far only the allelic liver variant of CPT1 is recognized [CPT1-a/b/c = liver, muscle & brain, respectively] and that deserves a look into possible co-segregation patterns amongst all 3 - what could those tell us about how different organs meet their energy needs in populations with frozen balls?

We could use...? Segregation analyses? Greenberg for that question. Funny you should ask, they are a statistical tool for determining the inheritance of any character & gives evidence for or against any particular locus, partly defining its properties (producing good hints for linkage analyses). Similarly to LOD score (Logarithm Of Odds), its posed question weighs the likelihood of 1 hypothesis over another. All it can do is maximize the likelihood across given parameters & in so doing pushing the issue further back to the quality of inputted factors.

An e.g....
Medical students were asked “Which relatives of medical students attended medical school?". The segregation analysis identified a recessive gene for medical school attendance!

You guys are falling into a similar trap.

So segregation analyses provide a top-down birds eye view but misses the high genetic heterogeneity of complex diseases.

You guys are missing the metabolic heterogeneity of fat-based metabolism in humans.

Tim Steele said...

Raphmeister - You lost me, dude.

Duck Dodgers said...

My apologies... It seems that I confused Rabinowitch's findings on FFAs with others. Rabinowitch only used Soya Bean oil when testing lipids and may have introduced some errors, according to Sinclair.

Hugh Sinclair's detailed review covers the literature that was available at the time. The key quote on FAs is found here:

"The high ingestion of protein alters blood and urinary composition : non-protein nitrogen and amino-acids are raised in plasma, and urinary nitrogen is increased (Rabinowitch & Smith, 1936), even during fasting (Heinbecker, 1931); plasma protein has been found to be normal by all observers. The fairly high ingestion of fat appears to raise somewhat the lipid constituents of the blood (Sinclair, Brown & Cronk, 1949), although the results are not consistent : Corcoran & Rabinowitch (1937) made claims that do not appear to be supported by a statistical analysis of the figures they give (which is not assisted by errors in their table of means if the individual figures they give are correct) ; Wilber & Levine (1950) claimed higher values than normal but did not state the age of their subjects ; Brown (1951) found normal values...

...Corcoran & Rabinowitch (1937) concluded that meat-eating Eskimos had a very active and unusual mechanism for utilization of fats ; part of their evidence was that the ratio of phospholipids to total cholesterol rose in two subjects after ingestion of zoo ml. of soya-bean oil, but this is not in accord with the figures they give. To the unusual mechanism they attributed the absence of ketosis in the Eskimo. Tolstoi’s (1929) two men [Stefansson and Anderson] had ketonuria over the entire period of the experiment, despite the C02- combining power of plasma remaining within normal limits ; these men of course were not Eskimos. The serum lipids increased in four Eskimos in Southampton Island who subsisted for 6 days exclusively on pemmican (75% of calories from fat), and increased further when they fasted ; ketonuria developed during the fast only (Sinclair, Brown & Cronk, 1949). The ketonuria of U.S. soldiers in the Arctic on normal rations has been attributed to the general adaptation syndrome (Kark, Johnson, Bly & Consolazio, 1949 ; Sargent & Consolazio, 1951)"

Thanks to CPT1A, even when fed 75% fat pemmican (Stefansson had said the recipe for pemmican from Arctic Caribou was at best 65% fat) they couldn't produce ketones.

Anyhow, Bang & Dyerberg 1975 and Ho 1972 observed the high FFAs after Sinclair's comments.

Duck Dodgers said...

"That is the only point I am interested in driving home."

And I'm with Tim on that one.

We are simply trying to stop the circular reasoning which is now unfortunately being used to create new dietary recommendations for a highly unique culture.

Recommendations and analyses on what the Inuit ate should be based on actual measurements—on actual Eskimos—not the measurements on two white explorers in New York, who got sick when they tried to eat like full-blooded Eskimos.

That's all we're saying. It's hardly a controversial position.

Duck Dodgers said...

Raphi, the "enormous" quantities of protein that were observed by Rabinowitch (his words) were much, much higher than what Bill Lagakos was referring to in the studies he cited.

Bill wrote:

"Negative energy balance promotes ketosis even with relatively high protein intake...It was, however, a rather severe caloric restriction...The point is that high protein won't 'knock you out of ketosis' if you're losing weight."

In the comments of that post, Bill clarifies:

"You can easily maintain ketosis with 30% protein if it's divided into a few meals, and especially if there is a mild energy deficit. That's how most of the studies in this post were designed (except Phinney 1983 which had no energy deficit). The participants in Phinney 1980 were able to get 50% protein and still maintain ketosis because of a larger energy deficit."

Phinney's 1983 subjects were eating 45% less protein than the Inuit and twice the levels of fat, according to detailed measurements from Krogh & Krogh (1914) and Rabinowitch (1936).

So, unless you can show that the Inuit were chronically starving themselves every day, or at the very least obtaining most of their calories from fat, Bill's post doesn't show us anything that relates to the observed Eskimo diet.

But, hey, if you can eat 44% protein and be ketogenic, then go for it!

raphi said...

@Tim

Consider me flabbergasted.

@Duck

We're not lions. Ask Peter, he's a vet.

Duck Dodgers said...

The Kaare Rodahl's study, which I referenced above, tells us more on their enormously high protein intake:

Basal Metabolism of the Eskimo, by Kaare Rodahl (1952)

"It is hardly fair to compare the metabolism of Eskimos on high protein diets with White people on comparatively low protein diets, and perhaps one would be justified in speaking of an "Eskimo basal condition."...

...It is well known that considerably higher amounts of protein are regularly consumed by the Eskimos (DuBois, '28), who generally speaking, prefer a diet where approximately 50% of the calories come from protein and the greater part of the remaining 50% are derived from fat. August and Marie Krogh ('13) report that the normal diet of the West Greenland Eskimos contained an excessive amount of animal protein — 280 gm daily — and they noted that there seemed to be a considerable delay in the metabolism of protein and excretion of nitrogen, only 60% of the nitrogen being excreted during the first 24 hours after eating large meals rich in protein. In East Greenland the Eskimos consume an average of 300 gm of protein daily (Hoygaard, '41). In Alaska a daily protein consumption of more than 300 gm has been observed among the most primitive Eskimos.

In order to study the significance of the specific dynamic action of the protein in the high meat diet, with reference to the high basal metabolic rates in Eskimos, a special series of studies was carried out on representative subjects from each of the 4 groups..."

Rodahl was not the only researcher to investigate Inuit metabolisms during that time period. There were others. The results are all very interesting.

But it should be obvious from the literature that they ate enormous quantities of protein and their metabolisms are nothing like ours.

Duck Dodgers said...
This comment has been removed by the author.
Duck Dodgers said...

Raphi said: "We're not lions. Ask Peter, he's a vet."

Raphi, I think you have to put the high protein diet into context. They would have died out long ago if they hadn't adapted to such high protein intakes, for the simple reason that they would have gone through periods or seasons when fat was hard to come by.

Heck, even Stefansson described such a three-week period where the caribou were so thin he could barely find any fat in the marrow or behind their eyes. He would have died were if not for the generosity of some passing traveler offering him and his buddies a cup of seal oil.

I suspect their enlarged livers—which sounds like is a product of CPT1A—gave the Inuit an huge advantage in that situation and on prolonged fasts.

Maybe instead of trying to dig for shreds of evidence of high fat consumption in an ecosystem of lean meats—while conserving blubber as fuel for their lamps over the long dark winters—we should wonder how they may have adapted to prolonged periods without fat without going extinct. After all, I think they would have to be extremely metabolically flexible to survive in such a harsh environment.

Ash Simmonds said...

I had bacon and eggs with onion for brekky - EXTREME CRAZY DIET I HAVE I KNOW RIGHT?

I gonna die of the ketoes. OH IF ONLY I HAD A POTATO OR TIGER NUT.

--> http://i.imgur.com/KlvTCFN.png

RIP me. :(

Tim Steele said...

Raphi - You are flabbergasted that I am reg'larly flummoxed by your palaver?

Ash - I skipped breakfast and had a slice of prime rib and some cheese for lunch...ha!

I would like to apologize for hijacking these comments to further my narrow-scope of simply wanting to assert that the Inuit diet was not a ketogenic diet.

I think we will find there are many, many reasons why most people cannot imitate the Inuit diet, CPT1 genes notwithstanding. I'd like to see how the contributions of brown fat, gut microbes, and other metabolic processes play in all this.

As the science of genetics grows, targeted diet strategies may be next.

Fut2 nonsecretors for instance. Do they overlap with CPT1A mutations?

Until then, we can only eat in a way that we find intuitive based on our best judgment. I like to think there is no genetic basis for eating a SAD diet, but all the tweaks involving macro- and micro-nutrients surely have their place based on ones genes.





Unknown said...

George finds the needle in the haystack of this morass, when he said, "This cannot be a co-incidence - these are colder places with high seafood intake."

Well done George.

Unknown said...

The first paragraph says it all. http://jackkruse.com/organization-structural-failure-8-ketosis-appears-fail/

Danny Albers said...

A truly excellent article.

To JS - Spot on

Richard Nikoley said...

Danny:

I think so too.

In fact, I'm making dinner now. It's mainly electrons. I'm sure you know how important they are.

I've got a small side of protons, and in terms of a nucleus, haven't decided yet, but I'm thinking DHA.

...I truly wish I could get a handle on the circadian rhythms that I'm always hearing about in those "Metaphysical" shops you go in that smell of incense and have AMAZING books written by people with dreds and smelly tie dies.

But sometimes, I can't sleep for shit when it's 2 am and dark, but can take a deep sleep nap at high noon.

I guess I'm just weird and the other 7 billion less one are perfectly normal.

They know electrons when they [don't] see them.

Tim Steele said...

I see Jack even got the story wrong:

"Not even the Inuit have lived in the Arctic as long as the Sherpa’s have in the Himalayas. The Inuit also ate an animal diet high in marine mammals. Both diets were mostly ketogenic."

Jack's Holy Trinity

It's OK. Everyone was fooled.

JohnN said...

@raphi: "So far only the allelic liver variant of CPT1 is recognized [CPT1-a/b/c = liver, muscle & brain, respectively] and that deserves a look into possible co-segregation patterns amongst all 3 - what could those tell us about how different organs meet their energy needs in populations with frozen balls?"

Excellent point. I'm sure we'll read more about on the next post.

In the cold, sterile land of the frozen balls gut bacteria is over rated.

raphi said...

A Ketogenic Diet is one consisting of a macronutrient ratio that is conducive to ketogenesis.

- Say I eat a traditional Inuit diet; my plasma BhB will likely float above 1mmol/L.

- Say an Inuit with the CPT1-a mutation eats his/her diet traditional diet; my guess is that their levels of ketosis will be below mine (don't know exactly how much of course).

- Say an Inuit without the mutation eats his/her traditional diet; I'd venture you'd see ketosis (don't know how much).

In all 3 cases, a Ketogenic Diet is served. What the body/environment does with that diet is another story.

@JohnN
Thanks.
Although, I'd never discount the role of bacteria. They've ruled the planet for ever and will long after us. Understanding their role in ball freezing regions is part of the general puzzle that is human health.

LeenaS said...

Not a comment on inuits, but as northener (I live few degrees from the Arctic Circle and my ancestors are exlusively from hereabouts) I'm thriving on the nearly 80 E% fat diet without ketosis. Actually, no seafood either, due to innate allergies; and no fish oil, as it makes me bleed badly. My plasma BhB this morning was well below 0.5 mmol/l.

Cheers

Cheers

Duck Dodgers said...

raphi said: "A Ketogenic Diet is one consisting of a macronutrient ratio that is conducive to ketogenesis."

I believe you. But, is ~45% protein diet conducive to ketogensis? Seems like that's what you need to figure out.

Incidentally, we may not be lions, but according to Bill Lagakos, hypercarnivores such as lions also resist ketosis. Let's find out why that is...

Ketosis in an evolutionary context, by Bill Lagakos

"Hypercarnivores (eg, cats) don’t develop ketosis on very low carb diets, like humans would, which seems to be due to their inability to down regulate protein catabolism (urea cycle takes care of the nitrogen; gluconeogenesis the carbon)... but they will do so readily during starvation because of relatively big brains (Blanchard et al., 2002):"

Well, guess what? The Eskimos were well known to have disposed of an unusually large metabolic load of urea, which is of course formed during the conversion of amino acids to glucose. Animals fed high-protein diets exhibit excessive urination and an increase in water consumption, and the exact same thing was observed with the Eskimos. The very high water consumption observed in the Eskimos is a feedback mechanism of high protein consumption to dilute and excrete excess urea. And their enlarged livers no doubt assisted them in this process of high protein consumption.

So, again, the observations are matching up with enormous levels of protein consumption.

We all agree they ate a lot of fat, but the evidence shows they were processing a lot of protein.

Jane said...

Duck, you said "I suspect their enlarged livers—which sounds like is a product of CPT1A—gave the Inuit an huge advantage in that situation and on prolonged fasts."

This would be very interesting, wouldn't it. The CPT-1a variant is what gives them the enormous capacity for gluconeogenesis and urea synthesis. But it has occurred to me that the enlarged liver seen in other cases of CPT-1a malfunction might be due to fat deposition rather than healthy growth. Do you have evidence on this? I haven't been able to find any.

raphi said...
This comment has been removed by the author.
raphi said...

Why wouldn't you expect their livers to adapt to their particular diet & environment?

Didn't you read what J. Stanton said in the comments above?::: Again, "fat-poor land" is not an accurate description.

So much so in fact, that the "paradox" papers (& many others) explains what happens when fat is inadequate:
"[..] given the conditions above some Inuit suffer from 'rabbit malaise', a condition well known to these traditional peoples, seemingly the result of consuming too much protein and abruptly switching off ketogenesis. Given enough protein it is still possible to switch off ketogenesis as the variant does not appear to completely abolish malonyl-CoA sensitivity. It therefore seems likely that the P479L variant enzyme is an adaptation to a state of perpetual ketosis where a high sensitivity to malonyl-CoA would be undesirable.
Equally it may be that the lower flux of the mutant enzyme is also an important part of the adaptation. Aboriginal peoples consumed a traditional high fat diet. Such a diet is known to be very rich in n-3 polyenoic fatty acids particularly eicosapentaenoic acid and docohexaenoic acid. Both of these fatty acids are known, at least in animals and most probably in humans, to lead to increased hepatic fatty acid B-oxidation, primarily by significantly increasing the activity of hepatic CPT-Ia and other enzymes of fatty acid oxidation."

Please dig into (for e.g.) Human Molecular Genetics (4th Ed.) or a number of other college-level textbooks about genetics if you disagree with the fundamentals being argued in those papers, by Peter or myself.

It's when you have no clue about what you don't know that f*cking yourself over becomes easy peasy. [I'd know!]

This thread is way past hijacked...

Gemma said...

@raphi

You said:

"- Say an Inuit with the CPT1-a mutation eats his/her diet traditional diet; my guess is that their levels of ketosis will be below mine (don't know exactly how much of course)."

What is your idea of a traditional Inuit diet? I do not ask about specific food items, as the list would be long or imprecise, but macronutrient composition.

Richard Nikoley said...

"This thread is way past hijacked..."

Yes, it's certainly inconvenient when research on the Inuit that I and others had never seen, going back 75+ years (20-something papers), is raised for consideration over the writings of an "adventurous" arctic explorer who abandoned his half Eskimo son at the age of nine (never to be heard from again, never mentioned in his writings) in order to promote his Arctic Fairy Tales.

Fortunately, there are historians who've studied Stefansson in depth, including all of his journals, etc. They even did a documentary that's a damn decent production.

Arctic Dreamer - The lonely quest of Vilhjalmur Stefansson:

http://www.isuma.tv/DID/community/CambridgeBay/arctic-dreamer

Nor am I really seeing the relevance of JS's comment. After all, it's not news that "excessive" protein shuts down ketogenesis. Guess when I first learned that? Here, Peter, way back in like 2008. As I gathered, Peter keeps protein pretty low, fat very high, but "supplements" with enough carbohydrate to stay just out of perpetual ketosis. It was even on his sidebar way back then.

The points that Duck, I (and now Tim) have tried to raise is that a population with a specific genetic mutation, that eats an astoundingly high protein diet combined with high fat (nearly 50/50, per the research), where a huge portion of that fat/protein is from high n-3 marine mammals, that has normal glucose tolerance on that diet (but not when fasted) is simply no sane justification for this "nutritional ketosis" deal of super high fat, low protein and nearly nil carbohydrate.

In other words, if that diet is just right for virtually everyone, it needs to be shown on its own merits with no reference to the Inuit. Moreover, it's disingenuous, even manipulative to justify it on those merits, even so "innocently" as to say "it worked for the Inuit," which it didn't because that was never their diet ever.

raphi said...

@Gemma

I'm not sure what the precise macronutrient composition is. I keep a significant margin of error 'in my mind' (I'd guess, 10-20%?). Why? Ultimately, it doesn't change the fact that they're predominantly fuelled on fat, fat adapted beasts. Also, it leaves open the possibility that I may not know the extents to which their metabolism(s) can adapt or how their genetics play into it. You live, you learn!

What we do know is that glucose is available in quantities that cannot be used for fuelling & that food sources of fat & protein were plentiful. Sometimes, fat would lack & they could temporarily rely more protein for survival, not for thriving. They did not transform into lions. A veterinarian wrote this post and that should count for something (given his strong arguments).

This makes them obligate fat burners, however you slice it. Arguing otherwise is not a position I'd be comfortable with (to put it gently).

As we can see from observing couch potatoes all the way to high level athletes nowadays, a state of ketosis (say, >0.5mmol/L) can be achieved with 0 up to ~150g CHO (by some accounts: see Ben Greenfileds lab biopsies with Volek). Insulin sensitivity, protein intake, circadian timing, glycogen depletion, stress, individual SNPs & a b*tt load of other stuff can shift you in or out of ketosis.

I think people call that "life". There were no coconuts or cornstarch in the Arctic.

What's your idea?

raphi said...

@RN

Your confusing ad hominem attacks on a dead man with scientific argumentation.

The fact that Peter eats more or less protein isn't proof of anything, either way.

Tim Steele said...

Raphi - Surely you see the real paradox in this statement:

""[..] given the conditions above some Inuit suffer from 'rabbit malaise', a condition well known to these traditional peoples, seemingly the result of consuming too much protein and abruptly switching off ketogenesis. Given enough protein it is still possible to switch off ketogenesis as the variant does not appear to completely abolish malonyl-CoA sensitivity. It therefore seems likely that the P479L variant enzyme is an adaptation to a state of perpetual ketosis where a high sensitivity to malonyl-CoA would be undesirable."

THERE WAS NO KETOGENESIS TO SHUT OFF. There was no perpetual ketosis.

Unless this is describing the first couple Inuit that wandered to the Arctic Ocean, the ones that died out because they DID make ketones normally, then that entire statement is based on the fairytale that the Inuit lived in 24/7 ketosis as so many would love to believe.


Richard Nikoley said...

"Ultimately, it doesn't change the fact that they're predominantly fuelled on fat"

Shorter rafi: I'm just going to ignore 75+ years of research by actual arctic researchers and make an assertion backed by a popular, convenient arctic explorer.

"The fact that Peter eats more or less protein isn't proof of anything, either way."

And in the exact previous post:

"They did not transform into lions. A veterinarian wrote this post and that should count for something (given his strong arguments)."

Shorter rafi:

When it seems like Peter agrees with me, an argument from authority is fine. When not, not.

Shorter Nikoley: I'm dealing with a dishonest person.

Tim Steele said...

And Raphi...really?

"A Ketogenic Diet is one consisting of a macronutrient ratio that is conducive to ketogenesis."

Then why do they need Ketostix and KetoNix?

Now who's re-writing Wikipedia?

Gemma said...

@raphi

You said: (I'd guess, 10-20%?).

Can you clarify the macronutrient composition?

You mentioned a good point about the CPT1-a/b/c, I think they play a role, as well as other factors that can influence their expression (it seems there are many). I hope more research can help to prevent such a high rate of sudden infant deaths.

Next I am glad the paper finally explained the paradox of metabolically healthy but OBESE Inuits. Of course, they only remain healthy if they keep to their traditional diet.

Ash Simmonds said...

This be so dumbs...

Can't be buggered reading the last ~10 posts but I saw mention of lions and hypercarnivory?

*siiiiiiiiiigh*

There is a TON of GOOD data about cats, because we can observe AND control what they eat and do - unlike humans (mostly) - go and read the damn things.

I've read the stuff on cats, and the only bit that is completely unreferenced in the literature is that cats can't do (much) GNG via glycerol (ie fat burnin), which AFAIK is unsupported in biology (or my misunderstanding thereof).

I tried to have a twitter convo with Bill and Wooo about this a while back, but it was frustratingly dodging of the actual topic and they kept bringing it back to humans/keto for some reason... (*sigh*)

--> https://twitter.com/CaloriesProper/status/500778067090874368

..cont..

--> https://twitter.com/CaloriesProper/status/500778067090874368

Anyhoo point being, no, we're not freakin' cats. Cats observed in nature are close to 50/50 fat/protein, and seem to have an obligate requirement for more protein for GNG, whereas humans are completely capable of supporting (almost?) all GNG requirements via glycerol.

Ash Simmonds said...

1st Amendment: this is the correct link for the continued hypercarnivore twitter convo which resulted in no bueno:

--> https://twitter.com/CaloriesProper/status/500805051951353856

Duck Dodgers said...
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Duck Dodgers said...
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Duck Dodgers said...
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Duck Dodgers said...

Raphi,

I don't know what to tell you. If you aren't willing to consider more than a century of scientific evidence, then there's really no point in discussing your keto-fantasy. I had hoped you were willing to weigh all the evidence.

For those who are actually interested in the science...

A study of the diet and metabolism of Eskimos undertaken in 1908 on an expedition to Greenland, by Krogh & Krogh (1914):

"The normal diet of Eskimos contains an excessive amount of animal protein (280 gr.) and much fat (135 gr.) while the quantity of carbohydrate is extremely small (54 gr. of which more than 1/2 is derived as glycogen from the meat eaten). Their dietary habits are vey like those of the carnivorous animals.

In our feeding experiments made under absolute control within the respiratory chamber we observed a maximum intake on one day of 1804 gr. boiled seal meat, containing 85 gr. nitrogen and 218 gr. fat, but this is far below the quantities recorded for Eskimos in the free state.

The large quantities of meat are well absorbed and utilized by the Eskimos. The loss of nitrogen in the feces amounts to 3—5 gr. per day and the loss of energy to less than 10% of the food.

The maximum quantity of nitrogen found in the urine of one day was 53 gr. When meat was given after a diet poor in nitrogen, only about 60% of the nitrogen were excreted during the first 24 hours (from 5 hours after the first meal of meat to 18 hours after the last), 40% (20—30 gr.) being retained."

--------

Studies on The Metabolism of Eskimos, by Peter Heinbecker (1928)

"...The Eskimo dietary would not be expected to cause ketosis, because the calculated antiketogenic effect of the large protein ingestion was somewhat more than enough to offset the ketogenic effect of fat plus protein."

--------

Metabolic Studies Of Eskimos In The Canadian Eastern Arctic, Rabinowitch & Smith (1936)

"These urinary nitrogen data, therefore, support the view that the high concentrations of non-protein nitrogenous constituents of the bloods were not due to impairment of kidney function, but to the habitual use of high protein diets. In our food analyses, for example, it was found that the seal meat con tained 3.58% of nitrogen. One pound of such meat would, therefore, alone account for about 15 gm. of nitrogen in the urine and, as stated, when food is abundant, a healthy adult will eat much larger quantities."

--------

The Relationship of Carbohydrate Metabolism to Protein Metabolism, by Cuthbertson, MaCutcheon and Munro (1940)

"In view of our observations on the adult human organism it might be asked how the Eskimo metabolizes his protein. The observations of Rabinowitch [1936] and many others go to show that the Eskimo does eat carbohydrate. For 2 months in the year berries, lichens etc., are available and throughout the rest of the year he obtains his supplies from the glycogen present in the liver, muscle and skin of animals. He relishes the stomach contents of the caribou and musk ox and the clams found in the walrus stomach."

[...continued]

Duck Dodgers said...

---------

Basal Metabolism of The Eskimo, by Kaare Rodahl (1952)

"It was observed that the Eskimo groups that had the highest basal metabolic rates also had the highest protein intake when comparing the BMR with the urinary nitrogen elimination, the same positive correlation was observed. The highest BMR's and nitrogen eliminations were observed at Anaktuvuk Pass among the caribou meat eaters where the fasting urinary nitrogen at times was as high as 3 gm per hour.

...It was also observed that the basal metabolism was higher in the winter when the protein intake was increased, than in the summer.

...It is well known that considerably higher amounts of protein are regularly consumed by the Eskimos (DuBois, '28), who generally speaking, prefer a diet where approximately 50% of the calories come from protein and the greater part of the remaining 50% are derived from fat. August and Marie Krogh (13) report that the normal diet of the West Greenland Eskimos contained an excessive amount of animal protein—280gm daily—and they noted that there seemed to be a considerable delay in the metabolism of protein and excretion of nitrogen, only 60% of the nitrogen being excreted during the first 24 hours after eating large meals rich in protein. In East Greenland the Eskimos consume an average of 300 gm of protein daily (Hoygaard, '41). In Alaska a daily protein consumption of more than 300 gm has been observed among the most primitive Eskimos."

--------

The Diet of Canadian Indians and Eskimos, by H. M. Sinclair (1953)

"The skin (mattak) is greatly relished and tastes like hazel-nuts; it is eaten raw and contains considerable amounts of glycogen and ascorbic acid...There is in fact nothing unusual about the total intake of aliments; it is the very high protein, very low carbohydrate and high fat intakes that have excited interest. It is, however, worth noting that according to the customary convention (Woodyatt, 1921; Shaffer, 1921) this [Inuit] diet is not ketogenic since the ratio of ketogenic(FA) to ketolytic (G) aliments is 1.09. Indeed, the content of fat would have to be exactly doubled (324 g daily) to make the diet ketogenic (FA/G>1.5)."

--------

Alaskan Arctic Eskimo: responses to a customary high fat diet, by KJ Ho (1972)

"Approximately 50% of the calories were derived from fat and 30 to 35% from protein. Carbohydrates accounted for only 15 to 20% of their calories, largely in the form of glycogen from the meat they consumed [in addition to bread and sugar]."

--------

The Aboriginal Eskimo Diet in Modern Perspective, by Harold Draper (1977)

"Because of its low carbohydrate content, a high concentration of protein therefore was an essential feature of the Eskimo diet, since extra protein was necessary to furnish the amino acids required for glucose synthesis beyond those required for body protein synthesis...Their high-protein diet imposed on Eskimos a need to dispose of an unusually large metabolic load of urea."

--------

The composition of the Eskimo food in north western Greenland1, by Bang, Dyerberg and Sinclair (1980)

"One of us calculated that the true adult Eskimo diet in 1855, with a little [bread and sugar] obtained from white traders, provided daily about 377 g of protein, 59 g carbohydrate, and 162 g of fat."

Duck Dodgers said...

Jane wrote: "But it has occurred to me that the enlarged liver seen in other cases of CPT-1a malfunction might be due to fat deposition rather than healthy growth. Do you have evidence on this? I haven't been able to find any."

Good point, Jane. I don't know. The reference on enlarged livers comes from mentions of increased liver metabolism in Draper's 1977 paper (Free Download).

Interestingly, despite the whole paper being on very high protein consumption, he hypothesizes 66% Fat, 32% Protein and 2% carbohydrates for Premodern Eskimos. Although it's a wild guess, that's the least amount of protein and highest amount of fat I've seen of any estimate or measurement in any of the scientific literature.

Nevertheless, Draper certainly did not believe the Inuit diet was ketogenic, except when fasting or protein was hard to come by.

And as I wrote, above, Draper was referenced in the October 2004 issue of Discover Magazine:

"On a truly traditional diet, says Draper, recalling his studies in the 1970s, Arctic people had plenty of protein but little carbohydrate, so they often relied on gluconeogenesis. Not only did they have bigger livers to handle the additional work but their urine volumes were also typically larger to get rid of the extra urea."

I assumed there might be a connection between Draper's comments and CPT1A. Needs more investigation though.

Unknown said...

I wonder if this mutation could be reversed by modern genetic or epigenetic engineering.

Not sure if any of you guys are aware of the CRISPR/CAS9 genome "editing" tools that have recently been brought to public attention.

The system was built upon the discovery of RNA interference from a few years ago.

Unknown said...

Nikoley and Tim are very focused on macronutritional compositions as an argument for why the Inuit couldn't be ketogenic.

Peter's argument is that the cellular environment of the Inuit must have been "ketogenic" due to the mentioned mutations.

We clearly need to step away from that paradigm, and instead ask what is a "ketogenic cellular environment", which could even occur in the presence of carbs. Conversely, you could be eating high fat and still not be "ketogenic".

We need a better definition of the word "ketogenic", which should be considering the handling of electrons at the mitochondrial complexes, rather than the dietary macro-nutritional composition. Ketone level wont cut the mustard either. The better metric is FFA utilization at the cytochromes. http://forum.jackkruse.com/index.php?threads%2Fa-little-story-about-infrared-and-ct.9675%2Fpage-2#post-146732 The irony to me here, Is Rich wants us to totally disregard something we all fundamentally know is true. Mitochondrial input is run by electrons. The signaling molecules are free radicals with unpaired electrons and the complexes spit out protons. The funny thing is we don't know what they ate precisely but we do know for sure the food they did eat had to be processed by ECT and monitored by their unique circadian cycles.......so let just continue to let Tim and Rich guess about what we don't really know instead of focusing in on what we precisely know. LOL. Food is not the key. You need to know the circadian inputs to make sense of how food is handled in biology. Both oars need to be in the water or you wind up going in circles like most have on this thread.

Richard Nikoley said...

"We need a better definition of the word "ketogenic", which should be considering the handling of electrons at the mitochondrial complexes"

I think we need to pull out all the stops and go full sub-atomic particle, Jack. :)

Look, it's pretty obvious to everyone that matter in the universe is composed of atoms. We could, if we wanted, frame everything we talk about in terms of the elements.

I choose to frame things in terms of actual food people eat. I'm a constructionist.

You aren't even satisfied with the elements. As a dazzle 'em kinda guy, your schtick is deconstruction and the elements aren't even deconstructed enough. This is a job for electrons.

I told someone the other day in an email: give Jack a year, he'll be talking sub-atomic particles.

Unknown said...

Thanks Duck. I think we can safely say that Inuit eating their traditional diet had large healthy livers. Nowadays on their diet of refined carbs they probably have large unhealthy livers.

I must say I do like the idea that the CPT-1a mutation was beneficial because it made the liver larger and super efficient at converting protein into glucose. But why is it still beneficial? Perhaps we also have to say something about sparing fatty acids for brown fat.

Tim Steele said...

"We need a better definition of the word "ketogenic", which should be considering the handling of electrons at the mitochondrial complexes, rather than the dietary macro-nutritional composition."

Talk about getting wrapped around the axle!

How about this definition:

"The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fuelling brain function. However, if there is very little carbohydrate in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures."

Just sayin'

Unknown said...

Peter's posts of late are driving me towards more biochem info on ketosis and FFAs.

Interesting Bill Lagakos ketosis review here http://caloriesproper.com/ketosis-in-an-evolutionary-context/

Laura said...

Thought you might appreciate this article as a follow up to the Inuit discussions: http://www.cmaj.ca/content/early/2014/12/01/cmaj.140657

Richard Nikoley said...

Greetings, All.

New post, recapping both of Peter's posts on the CPT-1A mutation, and some of the stuff in comments.

http://freetheanimal.com/2014/12/acknowledge-ketogenic-recommend.html

JohnN said...

"...a better definition of the word "ketogenic"...should be considering the handling of electrons at the mitochondrial complexes, rather than the dietary macro-nutritional composition."

I'd rather agree with this hypothesis. Few are willing to dig deep enough to consider what's best to prevent the gradual destruction of Complex I of the ETC and carrying out your own self-experiment accordingly.

My own experience only: it's rather easy, from that basis, to develop one's own answer to the question "glycolysis or beta-oxidation, what do your mitochondria want and need?" I'd take that as my true-north.

Moving beyond macro-nutrients, the traditional Inuit diet has something rather beneficial, copious amount DHA in the brain-preferred form of phospholipids.

The current nutritional discussion (comments in this post and the subsequent post), tinged with evangelical zeal, conveniently omits the consideration that the behavior of a complex system is the result of not only the stimulus but also the initial conditions and its past behaviors.

John

JohnN said...

"This passage required at least a clarification that Iniuts are not in ketosis, at least the nutritional one (when fed)."

This is semantic, pretty much.I'm on a high fat, low carb, some protein diet with 24-hr fast at least once a week and my ketostix never shows purple.

nfkb0 said...

Thank you Peter for this explanation, this makes sense to me now.

I'm really impressed by the fllod of comments !

Remi