Here’s the backdrop. A post by Peter at Hyperlipid. And then, A Second Post. Many comments on both threads, including Dr. Mike Eades participating in the second one. TL;DR: from what I gather of Peter’s posts: Inuit not in ketosis. It’s just a high fat diet.
Let’s look into this. First, Duck and I put together a series calling into question the very common practice of referring to the traditional Inuit population as clear, population-level justification for the long-term propriety of a ketogenic diet. Here’s all 17 posts and about 1,500 total comments: Leaving The Inuit Behind: Hormesis For The Rest Of Us.
The series has been generally dismissed by everyone I’m aware of that advocates for a ketogenic diet—both imagined ones (too high of protein intake) and real ones (very high fat, low—”chocolate cake”-like—protein, near nil carbohydrate). If that series had been dismissed on the basis of what we actually wrote—and the 75+ years of studies cited—then it would be upon us to look into the objections (we’d be delighted, as we have been with those raising legitimate questions all along the way in comments). But when the vast number of dismissals I’ve seen are mere scoffing at the idea of “a carb-munching Inuit;” or, their “high-carb diet” (neither of which remotely represents what we wrote), then it’s clear we’re dealing with disingenuous and dishonest posturing (from some who may, or may not, have actually read any of what we published—but same dishonesty and disingenuousness, either way). A commenter on Peter’s second post signals that the message got through to at least some.
All the FTA guys know the Inuit/glucose [via glycogen] consumption is a side issue anyway. The glucose discussion is to show how misinformed it appears we have been over the Inuits’ diet in general . But the FTA guys know that the elephant in the room is what appears to be their high level of protein consumption. This has to be addressed.
…Here, we’re talking about a specific gene mutation, CPT-1A, to be exact (P479L variant). Peter’s first post was the first I learned of it. Thanks to Google, one can get a “degree” in a matter of hours. In a nutshell, this gene provides instructions to make a liver enzyme (carnitine palmitoyltransferase 1A) that attaches to certain fatty-acid chains, allowing them to enter the inner “combustion chamber” of mitochondria, where they’re oxidized to produce energy.
From what I learned, Peter called it exactly right, on the surface.
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. […]
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.
On the other hand, the mutation may be no big deal. Initially, Peter’s [1st] post was greeted by the LC peanut gallery with fireworks and confetti, thinking that the extremely high prevalence of the CPT-1A gene somehow proved that the Eskimo could not eat any carbs and ate the equivalent of a high fat ketogenic diet. Unfortunately for the gullible LCs, modern Inuit eat large quantities of sugar without immediate fatalities.
Few LCs seemed to realize that what Peter actually showed is that the Inuit could not easily produce ketones—something the literature has been showing for over 75 years. In fact, CPT-1A presents as a kind of ketogenesis disorder where the individual cannot rely on ketones for energy—it becomes dangerous for them to fast for significant periods. This may explain why Eskimos were known to snack constantly on their native diet.
The key point being that the Inuit could not have been in ketosis because they have difficulty making ketones!
Some VLCers have now latched onto the idea that free fatty acids are more important for energy than ketones, and seem oblivious to the fact that Westerners naturally produce ketones on a high fat diet while the Inuit cannot.
…I have a quibble with Peter, though. To me, this is a Bell Curve-esque situation, at an extreme. In that context, it’s difficult for me to say that it’s “highly positively selected for,” rather than, in the context of Planet Earth (a rotating-on-axis—on a tilt—orbiting spheroid with a single source of energy), a deleterious mutation that doesn’t get SELECTED OUT, owing to a very unique environment, As The World Turns. Simply, for me: a unique and very obscure environment with a weird-ass diet that allows an otherwise nefarious gene to propagate where it would have otherwise been selected out, because: As The [Rest of] World Turns.
Let me give you an aside.
Ever heard of PKU: Phenylketonuria? Well, when I was a kid, the only thing I knew about it was that Protein Kills U. See, I had a cousin not far from my age with that PAH gene mutation. His mom was so very diligent about his diet, 50 years ago. It was, essentially, a vegan diet that saved his life and brain (oh, NO!). Here’s what I recall growing up: Matt could never eat what we were all eating at any common family affair. I recall salads with tomato and cucumber, green beans, and fruits, mostly. When he was a teenager, he was over the hump and was able to eat normally. He’s still alive, 50-something by now. Has kids and grandkids.
Fucking YEA science!
So let me ask you: is that condition in any way relevant to the question of whether a vegan diet is likely optimally healthful long term for most people? Is that gene “highly positively selected for” in vegan populations (hypothetically: if there were such a thing)? If you think, if it were the case, of course not, then in what way does that Inuit “paradox” let ketosis qua lifestyle off the hook—much less suggest it’s the cat’s meow?
Are epileptics evidence that ketosis at 85% fat and minimal protein something you ought must look into?
Sound ridiculous? It’s intended to sound ridiculous. When I saw Peter’s post, it was the first thing that came to my mind and no, I didn’t jump up and say: SEE, the ‘highly positively selected for’ gene mutation responsible for PKU suggests that VEGAN DIETS MIGHT BE RIGHT FOR EVERYONE AND ANYONE WHO’S SAID DIFFERENTLY HAS NOW BEEN SCHOOLED!
The point of Duck’s and my series was this, and this time, it’s in order of emphasis:
- There is no shred of evidence leading to a rational conclusion that an Inuit-like diet is any justification for what our diet ought be (our = everyone). In fact, both of Peter’s posts lend weight to our primary thesis. Now, another piece: owing to a very unique environment, dietary necessity allowed the propagation of a genetic mutation that might otherwise have killed itself off.
- They were not in ketosis in any way ever measured, yet had reasonable glucose regulation in a fed state (although critiqued by Rabinowitch & Smith, 1936). Peter’s post gives insights but still, I’ve not yet seen an accounting for their high protein consumption (av. 270-300g per day: HUGE). In fact, I’ve rather seen every effort to avoid that exhaustively documented fact, in preference for an adventuresome Stefanssson.
- They prized every shred of carbohydrate they could get their hands on, and apart from whatever the earth wrought in appropriate months, they got some glycogen from fresh or frozen kills, unlike the way we eat animals.
- Nonetheless, they were a low carb society. But, by necessity, not preference. Home is where the heart is. Perhaps they thought they lived plenty long enough in that doG forsaken land, I suppose.
I could expound upon each of those points and they are not exhaustive. Feel free in comments.
Moving onto Peter’s second post; now, with a very substantial comment thread including moi-memme, Dr. Mike Eades, Tim Steele and Duck Dodgers. Significant snark at first, but eventually some pretty good and healthy dialog between Eades and Dodgers, eventually. As always, you are your own judge.
I don’t want to rehash what’s been hashed in comments, but for two things; one, in terms of Peter, and the other, in terms of Eades.
- He speculates that dietary PUFA from seafood may be the key here for the propagation of this mutation. Makes some sense in an evolutionary context.
- He says accurately: “People clearly have very differing ideas of what the Inuit did or did not eat as an ancestral diet.” I would say: People clearly have very differing tolerances for accepting 75 years of research that uniformly put the Inuit at a most notably high protein, not high fat ancestral diet. Fat was high (40-50%, according to research) by western standards, but protein is way more notable—unless you think the Tokoleans are more notable (highest recorded dietary fat and saturated fat consumption qua population).
- “While it is perfectly possible to invoke a high protein diet to explain a lack of ketosis in the fed state this goes nowhere towards explaining the limited ketosis of fasting. P479L fits perfectly well as an explanation.” Of course, but it’s a point or explanation without a contravening argument. Shorter: P479L is a rare, weird mutation. Means nothing really, beyond a few more dots connected. People without it are not in ketosis in a fully fed or over-fed state, and they are in ketosis even on a sugar diet, if not fully fed. Ketosis is primarily a starvation/significant energy deficit adaptation.
- “I have some level of discomfort with using the Inuit as poster people for a ketogenic diet. That’s fine. They may well have eaten what would be a ketogenic diet for many of us, but they certainly did not develop high levels of ketones when they carried the P479L gene.” It looks like Peter and Mike Eades are at odds on this point.
- “…while systemic ketones are a useful adjunct, a ketogenic diet is essentially a fatty acid based diet with minimal glucose excursions and maximal beta oxidation. Exactly how important the ketones themselves are is not quite so clear cut.” Shorter version: it’s just a high fat diet. All the purple pee and magical numbers on a meter are probably hype.
- “Confirming that the Inuit are not poster boys for ketosis is a ‘so what?’ moment for me.” I’d hesitate to say concession noted, but only because it’s Peter and I know quite well that he has never touted the virtue of perpetual ketosis and likes to stay just out of it. The problem is, so very many others point to these extreme environments as an excuse to be fat gluttons. I’m anti-glutton (with good reason), and I resent the suggestive marketing in that regard…unless you’re living on an ice sheet and it’s dark and below ZERO for several months of every year. If you are, please glutton away at every opportunity. Your life may depend on it. If you have a supermarket nearby, you’re foolishly fooling yourself. You know why you’re fat, or can’t lose weight. You eat too much, too often. Whether that’s a satiation root problem is another issue. It’s certainly not a macronutrient issue, per se.
- “Using their P479L mutation to argue against ketogenic diets is more of a problem. It’s a massive dis-service to any one of the many, many people out there who are eating their way in to metabolic syndrome to suggest that a ketogenic diet is a Bad Thing because no one has lived in ketosis before.” Uh, this was brought up (by You, Peter) long after my blog series with Duck demonstrating over and over, backed by 100% of the actual research, that the Inuit were not in perpetual ketosis because of insane protein consumption. In other words, even without the mutation, people in fed states consuming 270-300g daily of protein would have to walk 15 miles, without eating, to pee pink. You brought it up, man, and I have a hard time thinking it wasn’t to distract from the real issue: a high protein diet, well documented.
- “Ultimately, point scoring on the internet about what the Inuit did or didn’t eat shouldn’t destroy people’s chances of health. Destroying a circular argument about Inuit diets may may the destructor feel good. Destroying the feet, eyes and kidneys of a person with type 2 diabetes, who need a ketogenic diet, as a spin off from that victory must be difficult to live with. I don’t know how anyone can do this.” Appeal to emotion. But more notably, the idea that lying to people is cool, if for a “good cause.” I submit that in the final analysis, lies kill and maim more people than anything else. Moreover, whatever the root cause or what got them there, we have the technology. We have brains, meters, insulin, and needles. Some may find an LC/VLC approach the method they like best to manage their diabetes. Others, millions of them, find that those technological tools can come pretty close to doing what a pancreas does.
That last point makes me laf, and cry. How very often is it that a falsehood becomes so very valuable, so commonplace, so widely believed and practiced that telling the PLAIN FUCKING TRUTH is tantamount to “destruction?” And not just plain destruction. We’re talking dismembering humans, here.
- He still will not take on the question of high protein, instead preferring to argue the finer points of glycogen degradation, all while plain old readers got the point we were trying to make (see above). I even asked in Peter’s comments: why “Protein Power” and not “Fat Power?” Have your views changed over the years, or are you just going with the flow?
- He explains away the failure of researchers being unable to detect measurable ketones 100% of the time over about 75 years to “keto adaptation.” I asked if he still held to that, in light of the mutation. He said: “The short answer is probably.”
He explained it in a blog post too:
“What he fails to understand is that the Inuit are keto-adapted. Their lifelong diet of high-fat meat has gotten their ketone-producing-and-consuming systems working in precisely controlled fashion. Like, dare I say it, a well-oiled machine.
The Inuit burn ketones as they make them, so it stands to reason that they might not have measurable ketones under normal circumstances.”
If anyone has a more precise definition of “keto-adapted,” or any literature, please drop in comments, by all means. Because, I’m having a serous logical problem here. In essence: if demand equals supply in a dynamic flow system, then supply cannot be detected.
Or, as one commenter elegantly put it, paraphrasing: if there’s traffic, but no traffic jam, you can’t see the cars.
Or, how about this? Human respiration. It’s so elegant, both a positive feedback loop, and the negative one that dominates nature and keeps everything from going hog wild, fission chain-reaction at all times. When asleep, your breathing is very light. It’s just what you only need to provide oxidation in that rested state (sleep is the ultimate anti-oxidant?). When you wake, you breathe more deeply…and if into that morning run or treading the mill like a hamster—only for a smoothie, not nuts—you’re going to huff and puff.
The thing is, it’s a very tightly controlled positive-negative feedback mechanism. When sleeping, they’re probably so close as to be not worth mentioning. When running, it’s going to be a way wider distinction between which is predominately in play. But, as you initially gasp for air, uptake gets on line, and eventually, negative feedback comes into play and you eventually find a groove. Charted, it’s going to look like a wave with initially high amplitude over (positive) and under (negative) the x-axis, with the amplitude diminishing over time to a narrow band of positive-negative feedback handoffs.
Here’s the kicker: at every point along the whole process, you can precisely measure blood oxygen.
Dr. Eades: you have some serious explaining to do about keto-adaptation meaning they’re producing lots of ketones, using them at roughly the same rate, and hence, they are not detectable. It’s an extraordinary claim. One way to do that would be to acknowledge that calories really do count, importantly. You also mentioned that in your practice, you noticed that over time, less and less ketones were detected by your patients. I have no doubt. You explain this by “keto adapted,” but calories count makes more sense.
I explained it here: Synthesis: Low-Carb and Food Reward/Palatability, and Why Calories Count. TL;DR: LC, VLC, and/or “ketogenic” diets are renowned for initial satiation factors (in spite of the fact that boiled potatoes are the most satiating—why the “potato hack” is so effective). So, for example, on a moderate to high protein and fat diet with minimal carbohydrate, it’s easier for a person to run a 700+ kcal deficit than on a low-fat diet of any color (veg*n, Weight Watcher’s, etc.).
It’s that deficit that’s primarily producing ketones because of significant fat oxidation, just like our “potato hack subjects” in comments were measuring significant ketones (significant caloric deficit due satiation, fat mobilization, ketones).
But what happens when that 700 kcal deficit becomes homeostatic; i.e., as is so typical for so many, when energy requirements via weight loss reduce to about the same level as the person is eating—10-30 pounds from target weight and they “stalled?” They didn’t “stall.” They’re burning calories at the rate they’re expending them. Let’s call it “caloric adaptation,” only in this adaptation, you can measure the various associated parameters, as should be expected.
They aren’t invisible.
…Only magical, flying, rainbow-farting ketones are invisible.
Thanks to Duck, Tim, Gemma, and Philip for checking up on my work and providing valuable input in the final draft.