Ketogenic diets: Part 2 - Is ketosis 'natural'?

Is ketosis the "natural state" of humans, or any other animal species?

As discussed in Part 1 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, sparing body proteins which would otherwise be broken down and converted into glucose (gluconeogenesis).

Is ketosis our ‘natural’ state?

Ketosis is an adaptive state that allowed our ancestors to survive temporary periods of food shortage. 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, after a couple of days, start to break down their body fat reserves in order to generate ketone bodies to sustain their brains and conserve their muscle and other vital proteins.

Note the emphasis on ketosis as a temporary adaptive state. Our ancestors could not be in fasting-induced ketosis on a permanent basis since their fat reserves (which were presumably far more limited than most modern-day people’s, owing to the simple fact that they ate less and moved more than we do) would eventually become exhausted, and they would 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, in order to maintain an optimal blood glucose level to supply 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. And predatory animals who undergo extended periods of food deprivation, such as elephant seals, are metabolically resistant to going into ketosis; instead, they have upregulated gluconeogenesis pathways which allow them to maintain steady production of glucose.

This makes perfect sense, since predators’ survival depends on their capacity to catch prey animals, which usually requires intense bursts of activity. 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 level rise when people are eating a high fat, low carbohydrate diet 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, making it much more difficult to speed up their exercise pace.

Even in endurance sports that don’t require sprinting, ketogenic-style diets are disadvantageous:

“A high fat, low carbohydrate ketogenic diet may impair exercise performance via reducing the capacity to utilize carbohydrate, which forms a key fuel source for skeletal muscle during intense endurance-type exercise.”

Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?

Ketosis in early humans

Our human ancestors were not eating high fat, low carbohydrate diets and therefore could not have been in diet-induced ketosis. African wildlife such as wildebeest, warthog and impala all have low body fat – well under 10%, and as low as 0.3% in the dry season – so even the most successful early hunters could not possibly have consumed enough fat to enter diet-induced ketosis.

And in fact, humans develop a condition dubbed “rabbit starvation” when they eat a diet that is low in fat and carbohydrate, and high in protein – so our early ancestors would have to have been eating ample carbohydrate-rich plant foods to prevent protein toxicity induced by eating such low-fat meat.

“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:

Yet as far back as 1928, researchers conducted experiments on Inuit people who were still eating their traditional diet (comprising on average 280 g of protein, 135 g of fat, and 54 g of carbohydrate per day, the latter derived primarily from muscle glycogen from 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: “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, yet the Inuit practised exclusive breastfeeding until their children reached 2 years of age, at which time meat was introduced to 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 utilise more ketone bodies than adult brains to argue that our brains prefer ketones and run best on them. However, the reality is distinctly different:

“As in adults, glucose is the predominant cerebral energy 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 occurs 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.”

Glucose metabolism in the developing brain

In other words, our brains primarily use glucose from the get-go, utilising ketones only as a back-up fuel source when glucose is scarce, and as we develop and become capable of more complex tasks than eating, sleeping, pooping, crying and sucking our thumbs, our brains demand more and more glucose.

And no wonder – 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 brain requires a disproportionate amount of energy given its size.

Here’s the real kicker: the reason why Inuit don’t go into ketosis as readily as other ethnic groups is the high prevalence of a deleterious mutation in the CPT1A gene. 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 in the Inuit, due to hypoketotic hypoglycaemia. When Inuit babies’ blood glucose levels drop, they are unable to utilise 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 in the process of evolution. Sure, humans can adapt to an extreme environment and an extreme diet, but that adaptation comes at a high cost.

The idea that ketosis is the natural state of human beings is also contradicted by the heavy dependence of human embryonic and foetal development on glucose. All women become insulin resistant during normal pregnancy as glucose is directed toward the developing baby. Pregnant women who are deprived of carbohydrate are at high risk of developing the dangerous condition known as ketoacidosis in later pregnancy as the nutrient needs of the developing foetus reach their peak, driving up maternal ketone production.

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

As a paper on the role of carbohydrates in human evolutionary development 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.”

The Importance of Dietary Carbohydrate in Human Evolution

Given these facts, only an ignorant fool would recommend that women consume a low-carbohydrate diet during pregnancy, yet that is exactly what many low-carb bloggers and diet websites tout.

So is a ketogenic diet a natural diet for humans?

No human population has ever lived in a permanent state of ketosis, a ketogenic diet is dangerous for pregnant women and developing foetuses, and the only human population that has ever subsisted on the type of diet advocated by keto diet proponents could only do so because of a genetic mutation that prevents them from going into ketosis, and as an unintended but unavoidable consequence, reduces 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 post in this series, we’ll take a good look at the scientific evidence for ketogenic diets for weight loss.

For information on my private practice, please visit Empower Total Health. I am a Certified Lifestyle Medicine Practitioner, with an ND, GDCouns, BHSc(Hons) and Fellowship of the Australasian Society of Lifestyle Medicine.