Ketogenesis and Fat Metabolism

Did you know that adding MCT oil to your pasta is more ketogenic than restricting your carbohydrates to ten percent of calories? Many people think of carbohydrate and insulin as central to ketogenesis, but the direct biochemical event that initiate ketone formation is actually the oversupply of acetyl groups to the TCA cycle during conditions of oxaloacetate depletion. While largely a biochemistry lesson, in this episode I also teach you the practical implications of this. There is more than one route to ketogenesis, and while they all produce ketones, they are fundamentally different in important ways. Adding coconut, MCT oil, or exogenous ketones allows you to reap benefits of ketones without necessarily restricting carbohydrates and insulin, and that may be useful if you are also trying to reap some of the benefits of carbohydrate and insulin. On the other hand, certain conditions that respond to ketogenic diets, for example refractory childhood epilepsy, need stronger degrees of ketogenesis than you can achieve simply by adding MCT oil to pasta. Understanding the difference allows you to better make practical decisions about your diet that are most consistent with your priorities. In this episode, you will find all of the following, and more: An overview of the TCA cycle and burning carbohydrate for energy; the critical importance of oxaloacetate (OAA) to allow acetyl groups to enter the TCA cycle; how we burn fat on a mixed diet; the meaning of the phrase, "fat burns in the flame of carbohydrate" or “fat burns in a carbohydrate flame"; loss of lean muscle mass can occur if dietary carbohydrate and protein are too low to maintain OAA levels, and fat cannot spare this loss; under carbohydrate restriction, OAA is not repleted by carbohydrate and is used for gluconeogenesis, while more fatty acids reach the liver to make acteyl CoA;  the oversupply of acetyl groups in excess of OAA initiates ketogenesis; insulin shifts fat to adipose tissue, but this doesn't cause obesity; MCTs go straight to the liver via the portal vein rather than going to the blood via the lymph in chylomicrons, and they thereby avoid that effect of insulin; insulin suppresses the carnitine shuttle; MCTs do not require the carnitine shuttle and are therefore immune to this effect of insulin; MCTs at breakfast suppress food intake at lunch; MCTs added to pasta increase beta-hydroxybutyrate; two ways of getting ketones: selective deprivation vs. abundance; if you are trying to get ketones but having negative effects of carbohydrate restriction (e.g. declining exercise performance in sports requiring anaerobic glycolysis, declining thyroid hormone and sex hormones, elevated cortisol and LDL-C) you can add MCTs to get the ketones; comparison of beta-hydroxybutyrate concentrations from MCT vs. 10% carb vs. classical ketogenic diet.

Access the show notes, transcript, and comments here:

https://chrismasterjohnphd.substack.com/p/022-ketogenesis-isnt-all-about-carbs