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Is the Ketogenic Diet Natural for Humans?

Is the Ketogenic Diet Natural for Humans?

As discussed in the first article of this series, ketosis is a metabolic state in which the brain switches to using ketone bodies – derived from the breakdown of fat – as its primary energy source, instead of glucose. This way body protein, which would otherwise be broken down and converted into glucose through the process of gluconeogenesis, are spared.

Ketosis is an adaptive state that allowed our ancestors to survive temporary food shortages. When food was not available at all, or the only food available was extremely low in energy (such as leaves and grasses), their bodies could start to break down their body fat reserves after a couple of days. Ketone bodies were generated as a result allowing them to sustain their brains and preserve their muscle and other vital proteins.

Our human ancestors did not consume high-fat, low-carbohydrate diets and therefore would not have been in diet-induced ketosis.

Note the emphasis on ketosis as a temporary adaptive state. Our ancestors could not be in fasting-induced ketosis permanently because they would eventually exhaust their fat reserves (which were presumably far more limited than ours, owing to the simple fact that they ate less and moved more than we do). They would then progress from fasting to starving, and subsequently die.

Yet ketogenic diet proponents advocate that we should aim to keep ourselves in a permanent state of ketosis, something that is completely foreign to human experience – and to the experience of all other animals, for that matter.

Ketosis in Non-Human Animals

No animal on earth lives permanently in ketosis. Omnivorous animals such as bears and dogs, and obligate carnivores such as cats – the ultimate low-carbers – use gluconeogenesis to transform amino acids from protein into glucose[1]. This allows them to maintain optimal blood glucose levels to fulfill their bodies’ needs for this vital nutrient. Only in prolonged starvation or a diabetic state will these animals enter ketosis.

Even hibernating bears do not go into ketosis[2]. And predatory animals who undergo extended periods of food deprivation, such as elephant seals[3], are metabolically resistant to ketosis; instead, they have upregulated gluconeogenesis pathways through which they can steadily produce glucose. This makes perfect sense, since predators’ survival depends on their ability to catch their prey, which usually requires intense bursts of activity. And sprinting capacity is dependent on glucose, as humans who adopt a ketogenic diet quickly discover.

Even when exercising at a submaximal level (for example, biking at a moderate speed), heart rate and adrenaline levels rise more when people are eating a high-fat, low-carbohydrate diet[4] vs. a high-carbohydrate, low-fat diet. This results in those on the high fat diet perceiving that they are working harder to achieve the same pace as the high-carbers, and they have much more difficulty speeding up their pace in sprints or climbs.

Even in endurance sports that don’t require sprinting, ketogenic-style diets are disadvantageous according to a ketogenic diet and exercise article published in Sports Medicine[5]: “a high-fat, low-carbohydrate ketogenic diet may impair exercise performance via reducing the capacity to utilize carbohydrates, which forms a key fuel source for skeletal muscle during intense endurance-type exercise.” The article concluded, “At present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes’ performance under conditions where evidence-based nutritional strategies are applied appropriately.”

Ketosis in Early Humans

Our human ancestors did not consume high-fat, low-carbohydrate diets and therefore would not have been in diet-induced ketosis. Even the most successful early hunters could not possibly have consumed enough fat to enter ketosis since african wildlife such as wildebeests, warthogs and impalas all have low body fat – well under 10%, and as low as 0.3%[6] in the dry season.

Furthermore, humans develop a condition dubbed ‘rabbit starvation’[7] when they eat a diet that is low in fat and carbohydrates, and high in protein (> 35% of total daily energy intake). This is due to the inability of the human liver to sufficiently upregulate urea synthesis to meet excessive loads of protein. Consequently, hyperaminoacidemia, hyperammonemia, hyperinsulinemia, nausea, diarrhea, and even death can ensue within 2 to 3 weeks. These effects were recognized historically through the excess consumption of lean wild meat by early American explorers.[8]

“But What About the Inuit?”

The Inuit (Eskimo) peoples inhabiting the Arctic regions of Greenland, Canada and Alaska are frequently cited by ketogenic diet advocates as an example of a human population adapted to eating a high fat, low carbohydrate and relatively low protein diet. Here’s a typical example:

What is the Ketogenic Diet?

The Eskimos and Maasai group are cultures we often look at to learn how their scant consumption of carbohydrates sustained their bodies through harsh weather conditions. It turns out their low carb diet switched their metabolism to burn fat instead of sugar or glucose.

This created a metabolic state known as ketosis, a process in which the body burns ketones to make energy, instead of relying on sugar or carbohydrate.

Yet as far back as 1928, researchers conducted experiments on Inuit people who were still eating their traditional diet[10] comprised on average of 280 g of protein, 135 g of fat, and 54 g of carbohydrate per day ( the latter derived primarily from muscle glycogen found in raw meat) which established two important facts:

  1. Inuit people were not in ketosis on their regular diet; instead, their high protein intake resulted in gluconeogenesis – just like carnivores and omnivores.
  2. Even in the fasting state, Inuit people showed resistance to entering ketosis. The researchers observed that “On fasting he develops a ketosis, but only of mild degree compared to that observed with other human subjects.”

Ketosis in Pregnancy and Infancy

Modern-day ketogenic diet promoters such as Pete Evans advocate low-carbohydrate diets for babies and children. However, the Inuit practiced exclusive breastfeeding until their children reached 2 years of age,[11] at which time meat was introduced in their diets. In other words, at the time of most rapid brain growth, the low-carb eating Inuit provided their children with the only carbohydrate-rich food available to them – human milk.

Speaking of babies, keto enthusiasts cite the fact that human infants’ brains utilize more ketone bodies than adult brains[12] to argue that our brains prefer ketones and run best on them. However, the reality is distinctly different[13]:

As in adults, glucose is the predominant cerebral fuel for the fetus and newborn. Studies in experimental animals and humans indicate that cerebral glucose utilization initially is low and increases with maturation with increasing regional heterogeneity. The increases in cerebral glucose utilization with advancing age occur as a consequence of increasing functional activity and cerebral energy demands… glucose plays a critical role in the developing brain, not only as the primary substrate for energy production but also to allow for normal biosynthetic processes to proceed.

In other words, our brains primarily use glucose from infancy, utilizing ketones only as a back-up fuel source when glucose is scarce, and as we develop and become capable of more complex tasks our brains demand more and more glucose.

And with good reason: glucose yields more energy (expressed as molecules of adenosine triphosphate [ATP]) than ketones, at 36 ATPs per glucose molecule vs 24 ATPs per acetoacetate (ketone body), and as previously mentioned, the human brain requires a disproportionate amount of energy given its size.

Here’s the real kicker: the reason why the Inuit don’t go into ketosis as readily as other ethnic groups is the high prevalence of a deleterious mutation in the CPT1A gene.[14] This mutation permitted adaptation to a high fat, low carbohydrate diet in the sense that those carrying the gene could survive to reproductive age while eating a diet entirely at odds with our evolutionary history. However this gene is associated with high infant mortality rates due to hypoketotic hypoglycemia: when Inuit babies’ blood glucose levels drop, they are unable to utilize ketone bodies to sustain their brains. The very mutation that permits adult survival in extreme circumstances compromises infant health – a powerful example of the trade-offs inherent to evolution. Humans can indeed adapt to an extreme environment and an extreme diet, but that adaptation comes at a high cost.

The idea that ketosis is human beings’ natural state is also contradicted by the heavy dependence of human embryonic and fetal development on glucose. All women become insulin resistant during normal pregnancy[15] as glucose is directed toward the developing baby. Pregnant women deprived of carbohydrates are at high risk of developing ketoacidosis in later pregnancy.[16] This dangerous condition can occur as the nutrient needs of the developing fetus reach their peak and drive up maternal ketone production.

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Mouse experiments show abnormal organ development and growth patterns in the fetuses of mothers fed a ketogenic diet. Similarly, women who consumed a low-carb diet[17] during pregnancy were found to be 30% more likely to give birth to a baby with a neural tube defect such as spina bifida.[18]

As a paper on the role of carbohydrates in human evolutionary development[19] pointed out:

Glucose is the main source of energy for fetal growth, and low glucose availability can compromise fetal survival. Pregnant females have a minimal requirement for 70–130 g/day of preformed glucose or glucose equivalents to maintain optimum cognitive function in the mother and to nourish the fetus.

Given these facts, it is evidently reckless to recommend that women consume a low-carbohydrate diet during pregnancy, yet that is exactly what many bloggers[20] and diet websites[21] tout.

Is a Ketogenic Diet a Natural Diet for Humans?

No human population has ever lived in a permanent state of ketosis. Ketogenic diets are dangerous for pregnant women and developing fetuses, and the only human population that has ever subsisted on this dietary pattern advocated by keto diet proponents could only do so because of a genetic mutation that prevents them from going into ketosis. Unfortunately, it has the unintended but unavoidable consequence of reducing the survival prospects of their infants.

Clearly, a high fat, low carbohydrate diet is not natural to humans, and long-term or permanent ketosis is not a natural state for us either.

In the next instalment in this series, we’ll take a good look at the scientific evidence for ketogenic diets for weight loss. Learn more about the ketogenic diet from the previous article in this series: What Is the Ketogenic Diet?

References

  1. Eisert, R (2011), Hypercarnivory and the brain: protein requirements of cats reconsidered. J Comp Physiol B. 181(1):1-17. doi: 10.1007/s00360-010-0528-0. https://www.ncbi.nlm.nih.gov/pubmed/21088842 1.
  2. Nelson, R.A. (1980), Protein and fat metabolism in hibernating bears. Fed Proc. 39(12):2955-8. https://www.ncbi.nlm.nih.gov/pubmed/6998737
  3. Tavoni, S.K., Champagne, C.D., Houser, D.S. & Crocker, D.E. (2013), Lactate flux and gluconeogenesis in fasting, weaned northern elephant seals (Mirounga angustirostris). J Comp Physiol B. 183(4):537-46. doi: 10.1007/s00360-012-0720-5. https://www.ncbi.nlm.nih.gov/pubmed/23180193
  4. Helge, W.J., Richter, E.A. & Kiens, B. (1996), Interaction of training and diet on metabolism and endurance during exercise in man. J Physiol 492(1):293-306. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1158881/pdf/jphysiol00293-0292.pdf
  5. Pinckaers, P.J., Churchward-Venne, T.A., Bailey, D. & van Loon, L.J. (2017), Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Sports Med. 47(3):383-391. doi: 10.1007/s40279-016-0577-y. https://www.ncbi.nlm.nih.gov/pubmed/27430501
  6. http://carnivoraforum.com/topic/10414110/1/
  7. https://www.raising-rabbits.com/rabbit-starvation.html
  8. Shane Bilsborough and Neil Mann. A Review of Issues of Dietary Protein Intake in Humans. International Journal of Sport Nutrition and Exercise Metabolism, 2006, 16, 129-152.
  9. https://thetruthaboutcancer.com/ketogenic-diet-weakens-cancer-cells/
  10. Heinbecker, J. (1928), Studies on the metabolism of Eskimos. J Biol Chem 80:461-475.
  11. ibid
  12. Settergren, G., Lindblad B.S. & Persson, B (1976), Cerebral blood flow and exchange of oxygen, glucose, ketone bodies, lactate, pyruvate and amino acids in infants. Acta Paediatr Scand.65(3):343-53. https://www.ncbi.nlm.nih.gov/pubmed/5840/
  13. Vannucci, R.C. & Vannucci, S.J. (2000), Glucose metabolism in the developing brain. Semin Perinatol. 24(2):107-15. https://www.ncbi.nlm.nih.gov/pubmed/10805166
  14. Clemente, F.J. et al. (2014), A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations. Am J Human Genetics 95(5): 584-589. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225582/
  15. Sonagra, A.D., Biradar, S.M., Dattatreya, K. & Murthy, D.S.J. (2014), Normal pregnancy- a state of insulin resistance. J Clin Diagn Res. I(11):CC01-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290225/
  16. Sussman, D., van Eede, M., Wong, M.D., Adamson, S.L. & Henkelman, M. (2013), Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse. BMC Pregnancy Childbirth 13:109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685567/
  17. ibid
  18. Desrosiers, T.A., Siega-Riz, A.M., Mosley, B.S. & Meyer, R.E. (2018), Low carbohydrate diets may increase risk of neural tube defects. Birth Defects Res. 110(11):901-909. https://www.ncbi.nlm.nih.gov/pubmed/29368448
  19. Hardy, K., Brand-Miller, J., Brown, K., Thomas, M., Copeland, L., & Handling Editor Dykhuizen, D.E. (2015). The Importance of Dietary Carbohydrate in Human Evolution. The Quarterly Review of Biology, 90(3), 251-268. https://www.jstor.org/stable/10.1086/682587
  20. E.g. https://lowcarbislekker.wordpress.com/2014/09/10/my-low-carb-twin-pregnancy-journey/
  21. E.g. https://www.dietdoctor.com/low-carb/pregnancy

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