Inuit Genetics Show Us Why Evolution Does Not Want Us In Constant Ketosis

science
(chris girten) #31

this seems to be where I am at.

(You've tried everything else; why not try bacon?) #32

The body needs only 4-5 g of circulating glucose, total, which is not much. It is not particularly stressful for the liver to manufacture such a small amount. In fact, both ketogenesis and gluconeogenesis occur together in the liver, being (a) stimulated by glucagon, which rises in the absence of dietary glucose (also known as carbohydrate); and (b) inhibited by insulin, which rises when dietary glucose rises past a certain, rather low, level.

So any diet low enough in carbohydrate to permit ketogenesis is also going to be accompanied by gluconeogenesis. Conversely, any diet high enough in glucose to inhibit gluconeogenesis is also going to inhibit ketogenesis, thus depriving us of the benefits of circulating ketone bodies. The three ketone bodies not only make an excellent fuel for the brain, heart, and other organs, but they also have powerful, beneficial epigenetic effects. So to my mind, it is better to have them in circulation and not worry about how much “work” the liver has to do to make glucose—even if it does prevent me from eating the quantity of glazed doughnuts I’d really prefer to be eating, lol!

#33

Perhaps this gene meant that the best hunters were selectively passing on their genes more than those who were capable of ketosis? If they are incapable of being in ketosis it would mean that they would require successful hunting all the time to avoid starvation.

Anyone in ketosis would have an advantage as they wouldn’t need to be as successful at hunting as they can use body fat stores. Their hunts can be less frequent, but would gorge themselves. However this handicap likely would mean their population would be very low.

Population is directly correlated with food availability. The family groups that couldn’t do ketosis would need to outhunt those that could and their population would increase relative to the ketosis groups - resulting in their genes being more common until it becomes the standard. So rather than evolution not favouring ketosis, it could just be one group being better at hunting game which is in small numbers out of necessity. Just a hypothesis though.

#34

This is huffing and puffing about semantics not nutrition. What carbohydrates exactly were Inuit - pre-European contact - supposedly eating from October to May each year to avoid ketosis? My educated guess: none. There were none to eat. They ate fat and meat. Stefansson’s accounts confirm this. End of diet story.

Since the CPT1A variant supposedly prevents ketone synthesis, then GNC by necessity was required to generate sufficient glucose for the brain to avoid ‘brain death’ in addition to whatever other cells lack mitochondria. The brain will utilize ketones - when present - but otherwise glucose. As will all other cells that lack mitochondria.

‘Ketosis’ technically means ‘in a state of generating and utilizing ketones’ rather than in a state of ‘running exclusively or mostly on glucose’. So if the Inuit have a genetic variant that prevents the generation of ketones, then that simply indicates they have a genetic variant that prevents ketogensis. Eating exclusively fat and meat, they were not ‘running on glucose’; they were running on fatty acids and needed glucose only to run the cells that lack mitochondria provided by GNC. Period. End of story. They did this for at least 10s of thousands of years if not more. The conclusion that this in some way indicates that long-term ketosis is undesirable is nonsense.

In my humble opinion.

(You've tried everything else; why not try bacon?) #35

Ketones are not “synthesised,” they are a breakdown product, produced in the course of fatty-acid metabolism—just as charcoal is produced during the burning of wood. Technically, ketones are “intermediate metabolites;” just as charcoal is an intermediate combustion product. In both cases, the process can either be stopped and the intermediate product saved for later use, or else allowed to run to completion.

Just to make it even clearer, an example of synthesis would be the way proteins are built up from their constituent amino acids, or the way Vitamin D is made from cholesterol.

To say that someone cannot produce ketones is to say that he or she cannot metabolise fatty acids, which is just like saying that a stove cannot burn wood. In either case, something is gravely wrong, and the end will not be good.

#36

Thank you for the clarification. I don’t think there’s any doubt that Inuit metabolize fatty acids. The question is whether or not the CPT1A variant prevents ketone production as part of that metabolism. Maybe it prevents only the ‘ketone specific’ product of it by increasing oxygen. I don’t know. Still, if the two nutritional state options are ‘glycolysis’ or ‘ketosis’, the Inuit eating the traditional diet were not in glycolysis by any stretch. Maybe we should be looking at this as a way to refine the process of lipolysis more definitively. Whatever, I still don’t think it in any way suggests that long-term ‘ketosis’ - as defined now - is undesirable.

#37

PS: It occurred to me that all this may be just a process of efficiency. I think it’s safe to say that many of us in long-term ‘ketosis’ experience a decline in ketone levels over time. Why, exactly? We don’t know. Maybe we just oxidize fatty acids more efficiently the longer we do it and produce less ‘partially oxidized residue’ (aka ‘ketones’). Maybe the CPT1A variant is just ‘hard wired’ efficient fatty acid oxidation resulting in zero ‘partially oxidized residue’.

Maybe the CPT1A variant maximized survival at the margin of glacial ice during the Pleistocene - for those who chose the edge of the ice as their habitat and followed it north and south as it advanced and retreated during glacial maxima and minima. The rest of us could get away with less efficient fat metabolism - and get ketones as a result.

I’ve read multiple studies showing the beneficial and healthful effects of keeping your innards awash in ketones, especially β-hydroxybutyrate. I’ve read none that show negative effects. The brain specifically benefits from the presence of ketones, and the more of them the better. Glucose not so much.

Maybe ‘the rest of us’ who don’t have the CPT1A variant get by with less efficiency because we gain the benefits of having at least some ketones massaging our innards.

(You've tried everything else; why not try bacon?) #38

Please use your terms correctly. Lipolysis is to fatty acids as glycogenolysis is to glucose, and fatty-acid metabolism is to fatty acids as glycolysis is to glucose (notice, please, that the terminology is not parallel). We used to have another member who made this exact same mistake, and the error in terminology causes a great deal of confusion.

So the process of lipolysis, which is the breakdown of triglycerides into glycerol and three fatty acids, has been pretty well elucidated. It is mediated by hormone-sensitive lipase, which is inhibited by insulin above a certain level. Since triglycerides are too large to pass through the walls of adipocytes, they must be lipolysed in order to get in or out. Elevated insulin encourages fats to get into adipocytes, but once they are inside, its effect of inhibiting lipolysis traps them there. Lowering serum insulin is required in order to allow lipolysis, let the fatty acids out of the cell, and get them to cells that need energy, so that they can be broken down by the further process of fatty-acid metabolism.

Now the process of fatty-acid metabolism, which is the equivalent process to glycolysis, is also pretty well understood. If you can come up with a description of that process that does not involve the production of acetoacetate or β-hydroxybutyrate, that would be remarkable. I could believe that a genetic variant might interfere with the process of halting fatty-acid metabolism at the point where ketone bodies are produced, but not that the process doesn’t produce them.

If the paper you are reading doesn’t describe normal fatty-acid metabolism and elucidate specifically how that process avoids producing ketone bodies in Inuit with this genetic variation, then the authors are misinterpreting their data. I seriously doubt that gluconeogenesis is a robust enough process to feed the brain, even if the liver were to switch from using protein to using fatty acids as a substrate. And we know that the Inuit were not eating enough carbohydrate on their traditional diet for dietary glucose to be adequate to the purpose, either. Though I suppose it is possible (though not likely) that the blood-brain barrier in the Inuit is capable of passing molecules as large as triglycerides so that the brain could use full-on fatty-acid metabolism, but no one seems to be arguing that.

#39

My apologies and thank you. I certain don’t want to add confusion. I was grasping for a glucose-derived term that is the equivalent of ‘ketosis’, but I guess there are none.

Our results suggest that the association between traditional diet and blood cell fatty acid composition… support the hypothesis that omega-3 fatty acids may have been important for adaptation to the Arctic diet… Furthermore, it is highly associated with circulating fatty acid composition in Inuit, suggesting that the selection pressure on the variant occurred as an adaptation to the Arctic diet.

… We can speculate on explanations for the directions of the observed interaction effects. Omega-6 PUFAs are rare in traditional foods and having a genetic variant that favors higher levels of these would be beneficial when depending on this diet, as they are essential to ingest for humans…

… Based on our study, we suggest that the high intake of marine foods of the ancestral Inuit and the consequently high level of circulating long-chain omega-3 PUFAs is currently the best candidate for explaining why L479 in CPT1A underwent positive selection.

PS: The publication date of this article is subsequent to the date this topic was started, so I presume it includes additional data/understanding not included originally by the studies cited by Masterjohn. I think it clear that Masterjohn’s interpretation that any of this data suggests long-term ketosis is undesirable is mistaken. Really! - if long-term ketosis was undesirable/non-beneficial it would have been selected out long ago or the human race extincted by it.

(Joey) #40

A variation on such musings might yield a clearer explanation…

Those who survived long enough to reproduce and protect those offspring until they reached puberty were the ones who managed to successfully pass on their genes.

This is what drives genetic evolution.

Everything else we try to understand about inheritance of traits (and epigenetics) should be understood as a means toward this end. :face_with_monocle:

(You've tried everything else; why not try bacon?) #41

Another clue would be the fact that human beings get into ketosis very easily, whereas all other mammals become ketotic only in the late stages of starvation (or when fed completely unnatural diets by researchers).

Moreover, the fact that once we become keto-adapted, our skeletal muscles actively pass up glucose and ketones in favour of fatty acids would seem to be another indication of how well the human body does on a high-fat, low-carbohydrate diet…

(Bob M) #42

I see some people arguing we shouldn’t be in ketosis all the time. Just listened to this:

The guest had been given a diagnosis of terminal cancer, and used a PKD (Paleo keto diet), along with other protocols, to overcome this. Even he no longer stayed in ketosis, and was eating carbs 2 days week. The host said he believes we as humans weren’t always ketotic, likely coming out each summer when there were berries and the like to eat.

I think it depended on where you lived and whether you followed the animals or stayed in one place.

(Joey) #43

@ctviggen Is it the case that cancer is, to a great extent, a more modern day disease? No doubt there were cancerous growths back in the Middle Ages, but infections (and war) likely killed far more people. As such, folks didn’t often age long enough to get to the point where they succumbed to a cancerous growth.

If this is so, then evolutionary diet trends and implications for forestalling cancer are not likely linked much at all.

Again, lasting long enough to reproduce is what would favor one particular diet over another in the evolutionary sense. Whether you lived a few years or a few decades beyond that (unless of course you were continuing to reproduce) would not likely have been a trait affecting species selection.

As such, diets that forestalled cancerous growths would not likely have played much of a role in our evolution.

Just guessing here. :man_shrugging:

#44

Those who think humans didn’t evolve almost if not exclusively in ketosis resulting from eating a diet of animal fat and meat have the onus of showing what they think our ancestors were eating that kept them out of it.

PS: I had the education of actually living for several years in an environment where ‘fattening up’ on carbohydrates during summer was not on the table. Even in an area favourable to wild berries it was not worth the time and effort to gather them.

(You've tried everything else; why not try bacon?) #45

The respected cancer researcher, Dr. Thomas Seyfried, is convinced, he says, that all cancers are the result of metabolic damage to cells. You’d have to consult medical statistics to be sure, but I certainly have the impression that there are a lot more cancers today than there were when I was a kid, back before the promulgation of the dietary guidelines.

The argument that there is more cancer because people are living longer these days is spurious. The average age at death is certainly greater these days, but that is the result of the availability of antibotics. Infant mortality is a small fraction of what it used to be, even as recently as a century ago. But people who survived childhood, and who weren’t felled by infectious disease in adulthood, usually lived to quite an advanced age, and I’d be willing to bet that cancer was still rare among those old people.

This may not be wrong, but it is certainly debatable. There is a hypothesis among evolutionary biologists called the “grandmother effect.” Basically it’s an argument that there is evolutionary utility for people to live well past reproductive age. I’m not qualified to have any kind of opinion on this hypothesis, but the fact that serious people are seriously proposing it does say something, I believe.

(You've tried everything else; why not try bacon?) #47

Again, it’s worth repeating that life expectancy is a tricky concept. Before they adopted the white man’s diet, the Plains Indians of the U.S. were noted for the number of centenarians among them, but because of childhood diseases, the average life expectancy was quite a bit lower than 100.

(Joey) #48

Indeed. As I was growing up, we would only whisper the word cancer.

We’re in agreement: Cancer was not likely a major cause of death in prehistoric times.

So the evolutionary benefit one might enjoy in terms of cancer-related survival through a paleo/keto diet would be weak at best.

Put differently: Since cancer was rare, there was little selection difference between those who never would have had cancerous growths (had they lived long enough) and those who would have experienced such growths (had they lived long enough).

Either way, few lived long enough to enjoy any paleo/keto dietary benefits as they pertain to surviving cancer. Ergo, not likely an evolutionary variable of note.

Yeah, I’ve heard about this but remain somewhat doubtful - especially given the short prehistoric lifespans throughout most (all?) of our evolution. Then again, with earlier puberty onset, perhaps that mitigates some of my skepticism.

I do firmly believe that today - i.e., in modern times - the “grandmother effect” (sexist of me?) is very real and strongly influences family outcomes. Having an older experienced woman in the household can make a world of positive difference on so many levels for all members of the family.

But I still find it hard to believe it was much of a factor in prehistoric evolutionary terms. Whatever the role of the grandmother may have been back when homo sapiens went about their daily business, I’ll assume she wasn’t nursing babies nor doing much strenuous cavework. Nor was she likely freeing up mom enough to make a difference in the tribe’s survival against the perilous odds of death. Perhaps the role that prehistoric grandmothers played was most evident in cave-dwellers’ divorce rates. :roll_eyes:

OTOH, perhaps a “grandfather effect” afforded the benefit of a few scraggly old extra experienced warriors with spears joining the hunt? Or at least they barked orders at the rest - complaining that mammoths just ain’t what they used to be back in the day? :wink:

(Bob M) #49

I’m not arguing for or against how cancer comes about or whether we should or should not be in ketosis for long periods. I had just listened to that particular episode, and also other episodes where Brian Sanders was basically saying that the people adding fruit and honey to carnivore were doing good things.

Part of that is because he went to Africa and stayed with the Hazda, Masai, and more. The Hazda, he saw them eat honey and tubers. Even the Masai ate some tubers I think.

And I’ve heard other discussions with people looking at aboriginal-type tribes, and many ate higher caloric foods, as long as they learned how to detoxify them, or ate things with low toxins, like fruit if they were around.

Let’s all agree that plants for salads, things like broccoli or asparagus or cauliflower wouldn’t be eaten (let’s ignore that those are recent plants anyway). I’ve tried to grow leaf lettuce, and it’s a freaking ton of work to keep off the animals and insects, for almost no benefit. So, most things people eat are tubers or other high calorie foods like nuts or corn (assuming they are detoxified).

Dr. Danenberg has some ideas about cancer:

https://drdanenberg.com/unconventional-cancer-protocols/

I see here he increases carbs one day per week, not two. But he also fasts 72 hours multiple times per year. Seems to conflict somewhat.

Unfortunately, cancer is a brutal disease. If you look at later updates, his cancer has come back.

#50

actually science does know this :slight_smile:
studies clearly show how ketones ‘change’ as are ‘used’ in the bodies of long term ketogenic functions. I have to go search for my most perfect darn science info to support this cause it tells all and wish I could find it on demand right now, but this is not some mystical function/process at all for long term ketogenic bodies. Ketones are used diff. from a newbie to a long term on how our bodies truly use them and what process we are in at our time in a ketogenic lifestyle so…but darn let me go try to find it :slight_smile:

OK THIS IS not in response to above…this is just more good info.

#51

Maybe I’m misreading and/or misinterpreting both the Ruled Me article and the above response from @PaulL here:

[quote=“PaulL, post:35, topic:76511, full:true”]

Ketones are not “synthesised,” they are a breakdown product, produced in the course of fatty-acid metabolism—just as charcoal is produced during the burning of wood. Technically, ketones are “intermediate metabolites;” just as charcoal is an intermediate combustion product. In both cases, the process can either be stopped and the intermediate product saved for later use, or else allowed to run to completion.

… To say that someone cannot produce ketones is to say that he or she cannot metabolise fatty acids, which is just like saying that a stove cannot burn wood. In either case, something is gravely wrong, and the end will not be good.

In the situation where fat fuel exceeds the capacity of the liver to oxidize it fully due to insufficient oxygen there are two options: (1) excrete the excess; or, (2) use whatever oxygen is available to oxidize only partially. Option #2 results in ketones.