Genetic adaptation to a chronic high fat diet – The Inuit situation

I was recently advised that 80% of the Inuit population was incapable of producing ketones. This intrigued me as the traditional Inuit diet has always been touted as being ketogenic. I started scouring research papers trying to find any link to this “fact”. What I found was nothing stating that Inuits cannot go into ketosis but that they have a gene mutation that inhibits quick transition to ketosis in a fasted state:

CPT1A mutation in Arctic population

This was a sweep of the Arctic population to to determine how much of the population have this gene mutation that seems to inhibit ketogenesis. The reason they where doing the sweep is because there were a large number of infants deaths as a result of hypoketotic hypoglycemia. This is when blood glucose drops and there is inadequate ketone production to sustain brain activity. The result is a coma and death. The hypothesis for the reason for this variant was evolutionary adaptation to chronic levels of high ketones due to their very high fat intake. Wether it was higher in fat or higher in protein or even 50/50 they would have eaten at least 300g of fat a day and no matter how much protein you eat, in the absence of any carb intake, that is going to make ketones. We will get to how shortly. First we need to add some common sense to the issue of macro composition of the Inuit diet.

When researching what the macronutrient composition of the traditional inuit diet was, I found numbers ranging anywhere from 40% fat to 90% fat and from 10% protein to 60% protein. Going by the rule that the truth lies somewhere in the middle it was likely it was in the range of 65-75% fat and would vary from day to day from the lower end to the higher end. If we think about this in a common sense way it would make logical sense that it would be higher in fat. Why? The one thing all studies/articles agree on is that the Inuit would eat between 4-6lbs of meat a day. Even at the lower end of the scale, 40% fat, 4 pounds of meat would be 2500 cals and 400g of protein. Can you imagine eating 400g of protein a day? It would be physically impossible from my experience. Not to mention this doesn’t take into account another bit of info every study agrees with, that the Inuit gorged on and prized the fat of seal, whale and walrus

This is an excerpt from one study describing the eating practices of the Inuit:

The seal is cut in a specific way directly after a hunt. Borré explains the cutting of the seal is this way “one of the hunters slits the abdomen laterally, exposing the internal organs. Hunters first eat pieces of liver or they use a tea cup to gather some blood to drink.” At this time, hunters also chop up pieces of fat and the brain to mix together and eat with meat.

Women and children are accustomed to eating different parts of the seal because they wait until the hunters are done eating. Intestines are the first thing to be chosen and then any leftover pieces of the liver are consumed. Finally, ribs and backbone are eaten and any remaining meat is distributed among the camp.

If you look at the order in which they ate the animal, liver, blood, chopped up fat and brain mixed with the meat, intestines, ribs and backbone (marrow), you can see that the fat content is high in just this one meal. This does not take into account a favoured staple of the Inuit, whale blubber cured with salt. It is very evident that this diet could not have been less than 60% fat. I still lean towards 70% but even at 60%, it is totally possible to maintain ketogenesis at 60% fat. That would still be a ketogenic ratio of roughly 1:1 which is considered enough to maintain ketosis. Now at 4lbs of meat at a 60% fat ratio that is 4900 calories, 450g of protein and 345g of fat. Still sounds unlikely to me that anyone could eat 450g of protein but this is the most conservative estimate I can use while still using any common sense.

So now that we have the macros worked out, lets talk about how ketones are made in relation to what the Inuit were eating. Recent studies done by Benjamin Bikman show that in a low carb environment, protein ingestion causes a very low insulin to glucagon ratio and therefore does not produce any significant insulin spike.  Since this diet is ultra low carb, their insulin levels would be low enough that fat would not likely be stored. During times of aerobic activity, anything besides fast running essentially, uses some fat and some glucose to run the Krebs cycle which produces ATP. ATP is the energy for the body. Since the Inuit ate no glucose, the only way they could get the inputs for the Krebs cycle is by converting protein and fat. Protein breaks down into amino acids. Some amino acids are glucogenic (can be converted to glucose) and some amino acids are ketogenic (can be converted to ketones) and some are both. Automatically the breakdown of ketogenic amino acids will contribute some ketones. When fat is broken down it converts to a chemical called Acetyl-CoA. This fuels the Krebs cycle as well as the glucose from the converted amino acids. When you eat alot of fat like they were it produces alot of Acetyl-CoA. Here is where automatic ketones come in to the Inuit diet. The Krebs cycle can only take so much input. When the limit is exceeded all the left over Acetyl-CoA goes to the liver and gets converted to ketones. With the amount of fat and the amount of excess protein they ate, there would be way too much Acetyl-CoA to get used.  Here is where the gene mutation from the beginning of this comes in and why it is important.

Don’t worry, we are getting to the point. 😉

If these people are eating this much fat and this much protein there is a chance that there will be an opportunity for high ketones and high glucose all at the same time. The actual protein need in a man is about 40g a day so the majority of the extra will be converted to either ketones or glucose. Only so much glucose can be used to fuel the Krebs cycle so that will leave a surplus of glucose and some ketones. All of the fat eaten will get converted to Acetyl-CoA, and since only so much can be used, the surplus that will get converted to ketones. When I was eating 5,000 cals a day my ketones where reaching in excess of 8.0 mmol/L. How much higher I don’t know as that is as high as the meter goes. If ketones are high and glucose is also high there is a chance of ketoacidosis. Even if the glucose was not high enough to cause ketoacidosis, who knows the possible risks of having chronically elevated ketone levels long term? So the evolutionary response to avoid this seems to be this gene mutation that prevents ketone levels from reaching high levels. The flip side is that the mutation does not allow the quick flip into ketosis that infants without the mutation experience. Without the protection of ketogenesis, a period of hypoglycaemia would be fatal for an infant.

This does not mean they didn’t eat a ketogenic diet or that they couldn’t make ketones, it is just an evolutionary adaptation that is no longer working due to dietary changes in long lived populations. I am sure there are other yet to be discovered evolutionary gene mutations that allow some cultures to thrive eating much higher carb content in the diet without experiencing the same issues as those who get sick eating a similar amount.

Keto ON!

Coach Jack

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