High fat and ketogenic diets are all the craze now, but it is important to remember that High Fat and High Carbohydrate diets in a hypercaloric situation are both going to induce metabolic inflexibility and…

“It is likely that the pyruvate dehydrogenase flux is key to mitochondrial metabolic flexibility.”
-Jorgensen et al. 2017.

Pyruvate dehydrogenase converts pyruvate to acetyl CoA and is essentially the link between glycolysis (the breakdown of sugar) and the citric acid cycle.

“Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal that ultimately decreases insulin sensitivity.”
-Fisher-Wellman and Neufer 2011

So too many calories, from fat or carbohydrate are going to increase H2O2 and turn down the ability of the cell to use glucose as fuel for cellular respiration.

Remember insulin resistance in a compensatory strategy by the cells to protect against damage from overnutrition (usually combined with physical inactivity).

and YOU CAN INDUCE INSULIN RESISTANCE on a 100% Fat diet. That’s right – ZERO carbohydrates.

“Surprisingly, switching rats from a standard high-carbohydrate chow diet to 100% fat (lard) for 3 days or a 60% high-fat diet for 3 weeks induced a remarkable 3- to 4-fold increase in the maximal rate of mitochondrial H2O2 emission.”
-Anderson 2009

This is why hypocaloric diets regardless of macronutrient breakdown result in improvements in diabetic markers.

This is why improving food quality, reducing food quantity, and increasing physical activity and movement are the show.

“Finally, linking mitochondrial bioenergetics to insulin sensitivity provides a mechanistic basis for the clinical strategies that have proven most effective in treating obesity-induced insulin resistance and type 2 diabetes; i.e., simply reestablishing cellular metabolic balance by limiting caloric intake and/or increasing metabolic demand through increased physical activity.”
-Anderson 2009

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