Here’s What Happens Inside Your Body When You Start Keto!

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Special Thanks to my team and Nicholas Norwitz – Oxford Ketone PhD Researcher and Harvard Med Student – for working diligently on research as well!

Here’s What Happens Inside Your Body When You Start Keto – Thomas DeLauer

How Does Ketosis Start in the Body?

Fundamental Principles:

1) The brain can use glucose or ketones as fuel, but not fat
2) The liver stores 600 calories of glycogen (glucose) to defend blood sugar, whereas the body contains almost an unlimited reserve of calories in the form of fat
3) Glucose can be made from lean (muscle) tissue through gluconeogenesis
4) Insulin inhibits fat mobilization and ketogenesis

Despite weighing only 3 lbs, your brain consumes 500 kcal per day. For most people, this energetic demand is met entirely by glucose that comes either directly from the diet or from the stored form of glucose (glycogen) in the liver. Your brain can’t eat fat.

Since your brain burns 500 kcal per day, and your liver stores only 600 kcal of glycogen (and muscle glycogen cannot be used to defend blood glucose), after about one day of fasting – or a slightly longer period of carbohydrate deprivation – your liver runs low on glycogen.

At this point, your body should be forced to make a sacrifice: Lean (muscle) tissue can be converted into glucose through gluconeogenesis. Therefore, your body should be forced to break down muscle tissue to feed your brain’s requirement for glucose.

But there’s a twist. Evolution wouldn’t tolerate this sacrifice. If our ancestors had to break down lots of muscle tissue every time they were deprived of food, we would have gone extinct. Evolution found a work around: ketones, which are an alternative fuel for the brain.

Initiation of ketosis can be conceptually summarized as follows: Insulin is released in response to carbohydrates. Insulin (1) promotes fat storage/inhibits fat mobilization and (2) inhibits ketogenesis.

Therefore, when you restrict carbohydrates (and excess gluconeogenic protein) and your insulin goes down, your body begins to burn fat and takes the breaks off of ketogenesis. Your body then presses down on the accelerator for ketogenesis once your liver glycogen stores are depleted and your brain demands more fuel.

At the cellular level: Free fatty acids (FFAs) are transported into liver cells through the CD36 transporter. Long chain fatty acid-CoA synthetase (LCFACS) adds a CoA group onto FFAs to make fatty acyl CoA (FA-CoA).

This FA-CoA is transported into mitochondria by the carnitine shuttle system, which requires carnitine, the transporter carnitine acylcarnitine translocase (CACT), and the enzymes carnitine palmitoyltransferase 1 and 2 (CPT1 and 2).

The long FA-CoA carbon chain is then broken down into two-carbon acetyl-CoA (Ac-CoA) chunks by β-oxidation. These Ac-CoA chunks are converted, via two enzymes – HMG-CoA synthase (HMGCS) and HMG-CoA lyase (HMGCL) – into the ketone body acetoacetate (AcAc).

AcAc is then converted into the storage form of ketones, β-hydroxybutyrate (βHB), by βHD dehydrogenase (BDH). βHB is then exported from the mitochondria and from the liver cell by monocarboxylate transporters (MCTs) into the bloodstream, from where it can traffic to peripheral tissues or the brain.

Once at its destination, βHB goes into the cell via MCTs and is converted back into the ketone body AcAc by BDH. AcAc is then acted upon by the rate limiting enzyme of ketolysis, succinyl-CoA:3-oxoacid CoA transferase (SCOT), and then acted upon by acetyl-CoA acetyltransferase (ACAT) to generate Ac-CoA.

Ac-CoA is the convergence point of glucose, fat, and ketone body breakdown and enters the Krebs Cycle to be completely oxidized/broken down into carbon dioxide.

Special Thanks to Nicholas Norwitz – Oxford Ketone PhD Researcher and Harvard Med Student:

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