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Nutrition Past and Future

The Drivers of the Herd, Part 15               

The NuSI Guys, Part 5, The Ketogenic Advantage


Slide 3         

You know those Holiday Inn Express commercials, right? The premise is always the same: someone is an instant expert in a difficult field just because he had a good night’s sleep at one of their hotels. Here a professor is shocked that a legendary math problem has been solved by a dad visiting campus. It’s funny because no one gets to be an expert in anything without first paying their dues in school.


Slide 4                   p.178. Taubes, Gary. Why We Get Fat and What to Do About It. New York: Alfred A. Knopf, 2011. Print.

Ketogenic diets must have a Holiday-Inn-Express-like effect that convinces dilettantes that they have special insights into evolution. Here is Gary Taubes telling us that ketosis is the normal human metabolism because there were no carbs in human history or something – I defy you to apprehend a cogent thought from those two sentences. If he’s saying hominids didn’t depend on carbs until the Neolithic and someone out there is believing that then there isn’t much I can say.


Slide 5                   p.227. Taubes, Gary. Why We Get Fat and What to Do About It. New York: Alfred A. Knopf, 2011. Print.

I’ll just remind you that all these people read what you just saw and those lines still made it into this book. Remember this the next time someone says we shouldn’t teach evolution in public schools.


Slide 6                   p.178. Taubes, Gary. Why We Get Fat and What to Do About It. New York: Alfred A. Knopf, 2011. Print.

If you have this book then go check this page out. He immediately goes on to say that evidence in support of these statements you’re looking at is that some kids with intractable epilepsy have fewer seizures when they’re on a ketogenic diet. That’s a little like saying that we can infer that America never fought a revolution against the British because Downton Abbey’s a popular TV show. Not only is it a non sequitur, it’s a non sequitur that’s supposed to make us forget well-known history.



Slide 7         

Peter Attia is more intelligible if not more logical. He wants us to understand the evolution of our species. He says ketosis is a “cool trick” “we” evolved. He says, “No ability to produce ketone bodies = no human species.”

It looks like that’s pretty much all he wants us to understand about human evolution.


Slide 8                   I made some videos on this very topic. Are we the animals who evolved ketosis? Or do we see it in other animals?


Slide 9                   McCue, Marshall D. "Starvation physiology: reviewing the different strategies animals use to survive a common challenge." Comparative Biochemistry and Physiology-Part A: Molecular & Integrative Physiology 156.1 (2010): 1-18.

Since I made those videos the best answer I’ve found is that ketosis is common to all warm-blooded animals. No, Dr. Attia, we did’t come up with this cool trick. Lots of other animals pull it off when they’re in this nifty state called “starvation”.


Slide 10                 MacIntosh, Andrew JJ, et al. "Urological screening of a wild group of Japanese macaques (Macaca fuscata yakui): investigating trends in nutrition and health."International Journal of Primatology 33.2 (2012): 460-478.

To give you a sense of where we are on the spectrum of tendencies toward ketosis, when Japanese macaques go into energy deficit they start cranking up the ketone bodies. No ketone bodies = no Japanese macaque species. So are they low-carbers?


Slide 11                 Hanya, Goro. "Diet of a Japanese macaque troop in the coniferous forest of Yakushima." International Journal of Primatology 25.1 (2004): 55-71.

No. Those macaques eat mostly plant foods and have a strong preference for fruits and seeds.


Slide 12                 Eisert, Regina. "Hypercarnivory and the brain: protein requirements of cats reconsidered." Journal of Comparative Physiology B 181.1 (2011): 1-17.

On the other hand, obligate carnivores are highly resistant to ketosis. Their livers turn up the dial on the conversion of protein into glucose when their diets are inadequate. They make relatively fewer ketone bodies.


Slide 13                 Slingerland, L. I., et al. "Insulin sensitivity and β-cell function in healthy cats: assessment with the use of the hyperglycemic glucose clamp." Hormone and metabolic research 39.05 (2007): 341-346.

When they are starving they need to preserve glucose for those tissues that need it. To manage this, they have a high degree of insulin resistance. For them, insulin resistance can be advantageous. There’s a lesson from evolution. Animals that eat lots of meat are more insulin resistant. This is the “carnivore connection” idea of Miller and Colagiuri.


Slide 14                 I’ve explained all this in past videos.


Slide 15                 Cherel, Yves, et al. "In vivo glucose utilization in rat tissues during the three phases of starvation." Metabolism 37.11 (1988): 1033-1039.

Dr. Attia would have been better off leaving out his claim that our production of ketone bodies makes us unique and instead pointed out that we in fact do seem to be unique in our ability to fuel our brain to a significant extent with ketone bodies. As you see here, rodents can’t do that.


Slide 16                 p.35. Cunnane, Stephen C, and Kathlyn M. Stewart. Human Brain Evolution: The Influence of Freshwater and Marine Food Resources. Hoboken, N.J: Wiley-Blackwell, 2010. Google Books.

Why we are unique this way is anyone’s guess. This observation doesn’t tell us that our ancestors were extreme low carbers. Here is a researcher who thinks this peculiarity was the result of the fetal development of a species with such a large brain.


Slide 17                 Heinbecker, Peter. "Studies on the metabolism of Eskimos." Journal of Biological Chemistry 80.2 (1928): 461-475.

Considering where we see ketosis in the animal kingdom, all examples I’ve seen are suggestive of a trend where increasing carnivory is associated with an increasing resistance to ketosis. If we’re going to try to build an argument for a ketogenic diet based on evidence from evolution we’re going to have a hard time coming up with examples where it’s ever been common, much less the normal condition of humanity. Not even the Eskimos in this 1928 study were in ketosis while eating their traditional diet. These Eskimos lived in Baffin Island near Greenland.


Slide 18       

When Peter Attia was asked about that study he responded that those Eskimos “very likely” adopted a European cultural value of preferring protein over fat. What? That makes no sense. He is saying they were so Europeanized that their tastes changed from what they were for countless generations, but they weren’t so Europeanized that they were eating European foods. He’s just caught up in the usual Paleo practice of making up just-so stories to rationalize his fringe beliefs. This guy’s sitting in sunny San Diego declaring that these Eskimos in the Arctic Circle in 1928 weren’t authentic. Give me a break.


Slide 19                 He’s apparently missing a key point of this study. Not only were they not in ketosis, they were more resistant to ketosis than people from lower latitudes. The lesson from evolution about ketosis is that it’s a state we humans are evolved to avoid. Lacking enough carbohydrate the natives of the Arctic seem to have developed an enhanced capacity to turn protein into glucose.


Slide 20                 Heinbecker, P. “Studies on the metabolism of Eskimos.” J. Biol. Chem. 1928, 80:461-475.

The doctor studying them said they had “a relative non-susceptibility to ketosis.” Dr. Attia, you are not an Eskimo. Real Eskimos resisted ketosis. They adapted to their low-carb environment over thousands of years. I have seen no evidence of free-living Eskimos maintaining ketosis without fasting. If you want to disagree with me you should you should try to come up with an example that contradicts me. Good luck with that.


Slide 21                 Actually, those Eskimos handled carbohydrate especially well. When they were given a glucose tolerance test they had no sugar in their urine.


Slide 22                 Tolstoi, Edward. The effect of an exclusive meat diet lasting one year on the carbohydrate tolerance of two normal men. Waverly Press, Incorporated, 1929.

That couldn’t be said of one of the Eskimo wannabes who did that year-long all-meat diet study. Karsten Andersson had sugar in his urine after a glucose tolerance test. Karsten Andersson tried eating like a real Eskimo. He was not a real Eskimo.



Slide 23                 That’s why he had such poor glucose tolerance after a year of low-carb.


Slide 24                 Numao, S., et al. "Short-term low carbohydrate/high-fat diet intake increases postprandial plasma glucose and glucagon-like peptide-1 levels during an oral glucose tolerance test in healthy men." European journal of clinical nutrition66.8 (2012): 926-931.

This is what a typical low carber Eskimo-wannabe will experience today as well. Here a short-term ketogenic diet made healthy young men glucose intolerant. Their reduction in first-phase insulin secretion was suggestive of early diabetes. Some low carbers have a euphemism for this: “physiologic insulin resistance.” More on that in the last video.


Slide 25                 Heinbecker, P. “Studies on the metabolism of Eskimos.” J. Biol. Chem. 1928, 80:461-475.

It’s only during fasting that those real Eskimos have lower carbohydrate tolerance. Ketosis is for fasting, even for the Eskimos. It’s not normal.


Slide 26       

When Dr. Attia conjectures that those authentic  Eskimos were “Europeanized,” he is in the great low-carber tradition of dismissing evidence from the real world in order to preserve the low-carb fantasy . He’s decided that part of his definition of an Aboriginal Eskimo is someone who is in ketosis, even if we don’t know if anyone like this ever existed. This is a great example of the “no true Scotsman” fallacy.


Slide 27       

What’s so nutty here is that Attia is finding fault with a study of hunter gatherers living in the Arctic 80 years ago even though he has no study of his own to show that real Eskimos were in ketosis. All this is just something he got in his head somehow. Here he imagines that a whole population could be on a ketogenic diet. But no such population has ever existed as far as we can verify. That fact alone should tell you that this not the normal human metabolism.


Slide 28                 Rabinowitch, I. M., et al. "Metabolic studies of Eskimos in the Canadian eastern Arctic." The Journal of Nutrition 12.4 (1936): 337-356.

For what it’s worth, I found another reference for these Eastern Eskimos from another investigator and he, too, declared them free of ketosis.


Slide 29                 Attia says that the real Inuit of his imagination ate vastly more fat than protein. He tells us the original super low-carber Vilhjalmur Stefansson ate a diet that was greater than 80% fat. That’s the level of commitment it takes to be authentic.


Slide 30                 p.31. Stefansson, Vilhjalmur . "Not by bread alone." AJN The American Journal of Nursing 47.5 (1947): 357.

But you can see here that Stefansson said real Eskimos were at about 80% fat, not more than that.


Slide 31                 Getting back to his lesson for us about human evolution, are we to take it that he’s arguing that our ancestors were getting more than 80% of their calories as fat? I hope not. Unless he is prepared to argue that we are all descended from the most fat-loving of Eskimos – and I would advise him not to take up that argument – then he is going to have trouble using the evolution angle to convince us we should all be on extreme high-fat diets. The Inuit had access to blubbery sea mammals. But humans first came from Africa where the wild animals are lean. Where would our imaginary ketogenic African ancestors have possibly found all that fat?


Slide 32                 Eaton, S. Boyd. "The ancestral human diet: what was it and should it be a paradigm for contemporary nutrition?." Proceedings of the Nutrition Society65.01 (2006): 1-6.

The founding fathers of Paleo said our ancestors would have had moderate-fat diets – nothing at all resembling an Inuit diet and definitely nothing that could be called ketogenic.


Slide 33                 p.128. Stefansson, Vilhjalmur, P. D. White, and Fredrick John Stare. The fat of the land. Macmillan, 1956.

Low-carb pioneer Vilhjalmur Stefansson pointed out the paucity of fat that could be found as one approaches the Equator. Where would one find blubber on the savannas or in the rainforests of Africa?


Slide 34                 And this, my friends, is how we find ourselves enjoying Truthiness Paleo-Style. Musings and speculations like these are half the fun of Paleo. Now we have something to argue about on blogs and in message boards and in comment sections and we can all feel like Holiday Inn Express experts in nutrition and evolution!


Slide 35       

Attia’s speculations about ketosis don’t end there. He wants us to believe that ketosis is an advantaged state. He thinks it’s likely that being in ketosis will give us enhanced muscular endurance. He has a reference to back this up.


Slide 36                 Kashiwaya, M. D., et al. "Substrate signaling by insulin: a ketone bodies ratio mimics insulin action in heart." The American journal of cardiology 80.3 (1997): 50A-64A.

Here it is. Someone did some experiments on an isolated rat heart. You know, I’ll confess. I was doubtful about the claimed benefits of a ketogenic diet. But that all changed when I learned from Dr. Peter Attia about experiments on isolated perfused working rat hearts! Those rat hearts were so efficient when doused with ketone bodies! I can only imagine how supercharged I’ll feel eating lots of pig fat and butter! Just thinking of myself as an isolated rat heart makes me feel better! Thank you, doctor!


Slide 37                 Of course, I’m just being silly. He doesn’t actually say this should convince us of his claim that it is likely that a ketogenic diet will enhance your muscular endurance. For that, he says he’s seen data, data you can’t see. But when the day comes that you’ll see it you’ll be damn impressed. See, these researchers fed ketone esters to mice. That’s not the same thing as a ketogenic diet, but if you don’t think about it that’s close enough. Now you can finally stop asking low-carbers why our Olympic athletes aren’t all in ketosis to enhance their muscular endurance. The real proof is in these mice we’ll all be talking about one day.

I think you know how the saying goes. “If you can’t impress them with brilliance,” right?


Slide 38                 Vitola, Bernadette E., et al. "Weight loss reduces liver fat and improves hepatic and skeletal muscle insulin sensitivity in obese adolescents." Obesity 17.9 (2009): 1744-1748.

If you feel like you need evidence about ketogenic diets that’s a little more germane than isolated perfused rat hearts then we’re going to have to resort to studies of humans and animals who were actually on ketogenic diets. I’ve done many videos showing you the weaknesses of low-carb trials, including some that put their subjects in ketosis. One of the points I make repeatedly is that for any intervention on overweight people that causes them to restrict calories and lose weight, we should see some marked improvements in key biomarkers. Here you see that caloric restriction brings about improvements that might be sold as evidence for one diet or another, but the diet used here was nothing unusual. Just because some diet was used to bring about improvements during a weight loss trial, that doesn’t mean that diet was so great. Ketogenic diets do tend to make people want to eat less – not exactly surprising – so they do often achieve voluntary caloric restriction.


Slide 39                 Ribeiro, Letícia C., et al. "Ketogenic diet‐fed rats have increased fat mass and phosphoenolpyruvate carboxykinase activity." Molecular nutrition & food research 52.11 (2008): 1365-1371.

Let’s look at animal studies first. This study in rats showed us that a ketogenic diet caused the ratio between fat mass and lean mass to increase. The researchers said this suggested a risk of visceral fat accumulation from ketogenic diets.


Slide 40                 Bielohuby, Maximilian, et al. "Lack of dietary carbohydrates induces hepatic growth hormone (GH) resistance in rats." Endocrinology 152.5 (2011): 1948-1960.

In this one, rats put on a ketogenic diet developed a resistance to growth hormone.


Slide 41                 Those researchers felt that this finding explained why rats on these diets show greater visceral fat accumulation and stunted bone growth. They were sure the poor growth was not a result of calorie restriction.


Slide 42                 Krebs, Nancy F., et al. "Efficacy and safety of a high protein, low carbohydrate diet for weight loss in severely obese adolescents." The Journal of pediatrics157.2 (2010): 252-258.

That undesirable effect from ketogenic diets on the proportion between fat mass and lean mass has also been observed in humans. This low-carb trial in young people showed that the ketogenic dieters “lost significantly more lean body mass” than did those in a comparison low-fat group.


Slide 43                 Volek, Jeff S., et al. "Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet." Lipids 44.4 (2009): 297-309.

The same thing happened in this trial run by the low-carb all stars. Of course, their low-fat diet wasn’t a model low-fat diet, but it still preserved more lean body mass than the ketogenic diet.



Slide 44                 p.197. Taubes, Gary. Why We Get Fat and What to Do About It. New York: Alfred A. Knopf, 2011. Print.

But of course, that is not where we should be looking to see the serious risks posed by ketogenic diets. Here is Gary Taubes telling us that high blood sugar is so bad because it leads to the formation of advanced glycation end products. He says AGEs promote all sorts of undesirable processes, from the stiffening of arteries to accelerated aging of the skin. If he really is concerned about those things then he should rethink his ideas about ketogenic diets.


Slide 45                 Beisswenger, Benjamin GK, et al. "Ketosis leads to increased methylglyoxal production on the Atkins diet." Annals of the New York Academy of Sciences1043.1 (2005): 201-210.

In this study a ketogenic Atkins diet caused a dramatic increase in methylglyoxal levels.


Slide 46                 Cantero, Anne-Valerie, et al. "Methylglyoxal induces advanced glycation end product (AGEs) formation and dysfunction of PDGF receptor-β: implications for diabetic atherosclerosis." The FASEB Journal 21.12 (2007): 3096-3106.

Methylglyoxal is a highly reactive metabolic byproduct which promotes the formation of those AGEs.


Slide 47                 Beisswenger, Benjamin GK, et al. "Ketosis leads to increased methylglyoxal production on the Atkins diet." Annals of the New York Academy of Sciences1043.1 (2005): 201-210.

This graph shows you the methylgloxal concentrations among the Atkins dieters who achieved ketosis. That’s not good.


Slide 48                 The authors likened this result to what is seen in poorly controlled diabetes.


Slide 49                 Hartman, Adam L., and Eileen PG Vining. "Clinical aspects of the ketogenic diet." Epilepsia 48.1 (2007): 31-42.

Ketogenic diets have been used for a long time as a therapy for children with severe epilepsy which is uncontrolled by medication. It’s from studies of these kids that we have our best information about what a ketogenic diet can do to our health. Here you see a long list of documented side effects experienced by these kids. It’s hard to imagine a diet that was linked to all these problems receiving enthusiastic support from a doctor, yet some low-carb promoting doctors represent ketosis as some sort of advantaged state of health.


Slide 50                 Kang, Hoon Chul, et al. "Early‐and late‐onset complications of the ketogenic diet for intractable epilepsy." Epilepsia 45.9 (2004): 1116-1123.

Here’s one study that looked at 129 patients at an epilepsy center.


Slide 51                 Look at this list of complications these patients encountered. Now I do need to qualify this. Some of these people had serious medical problems in addition to their seizures. The one death from cardiomyopathy was in the case of a patient who began refusing food. The two other patients who died were otherwise sick. But accounts like this are valuable because they are our best evidence of what happens when people are on these diets for long periods of time while they are weight stable. Take for instance the issue of the lipid profile. Normally trials of ketogenic diets that are sponsored by low-carb friendly interests involve obese subjects losing a lot of weight. Their cholesterol doesn’t increase much if at all because they usually start out with high cholesterol, and because they are dropping weight, and because the trials usually aren’t very long.


Slide 52                 Rauchenzauner, Markus, et al. "The ketogenic diet in children with Glut1 deficiency syndrome and epilepsy." The Journal of pediatrics 153.5 (2008): 716-718.

But look what happens in non-obese kids eating this way long term. I’ll be talking about the effect of diet on apolipoprotein-B in a later video. For now realize that apoB is an excellent indicator of cardiovascular health. The higher it goes, the worse off the heart is. Look at this incredible difference in these kids after only six months.


Slide 53                 Coppola, Giangennaro, et al. "The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: A case-control study." Seizure (2013).

Here was a recent study that looked at young people ages 19 to 31 who were on ketogenic diets for an average of two years. The authors compared them with matched controls. The ketogenic dieters had much stiffer arteries, a sign of vascular damage.


Slide 54                 You can see how much worse off their lipids were. A total cholesterol of 224 for young kids is a sad thing to see. This is not a healthy way to start a life.


Slide 55                 Mann, G. V., et al. "Cardiovascular disease in the Masai." Journal of atherosclerosis research 4.4 (1964): 289-312.

If we are going to look to evolution for clues to what is appropriate for our species, I think we’re better off if our speculations are rooted in some data. Here you see how among even the Masai, one of the most often-cited low-carb cultures, most adult men had cholesterol numbers less than 160. When we see children with cholesterol concentrations far above those of these men, and when we aren’t given any evidence of the long term safety of these diets, and when we notice that the arguments for them don’t even make any sense, we should realize someone is taking us for suckers. There is no painless quick fix for obesity. There is no ketogenic advantage. But there are plenty of opportunists out there who will tell you otherwise.

Peter Attia seems like too smart a guy to be professionally invested in the delusions of Gary Taubes. We’ve seen that his reasoning about ketogenic diets is obviously faulty. It’s not the only subject on which he’s gone astray. The next four videos will show you others. First up, what dietary trends have been associated with increasing obesity? Dr. Attia says Americans got fatter despite following official dietary recommendations. He’s wrong. I’ll show you why next.