This equation represents the relative tendency for a given macronutrient to either promote
or prevent a ketogenic state (1). Recalling from the previous chapter that insulin and glucagon
are the ultimate determinants of the shift to a ketotic state, this equation essentially represents
the tendency for a given nutrient to raise insulin (anti-ketogenic) or glucagon (pro-ketogenic).
For the treatment of epilepsy, the ratio of K to AK must be at least 1.5 for a meal to be
considered ketogenic (1). Typically, this results in a diet containing 4 grams of fat for each gram
of protein and carbohydrate, called a 4:1 diet. More details on the development of ketogenic diets
for epilepsy can be found in the references, as they are beyond the scope of this book.
Although this ratio is critically important for the implementation of the ketogenic diet in
clinical settings, we see in chapter 9 that it is not as important for the general dieting public.
Each macronutrient is now briefly discussed within the context of the equation in figure 1.
Carbohydrate
Carbohydrate is 100% anti-ketogenic. As carbohydrates are digested, they enter the
bloodstream as glucose, raising insulin and lowering glucagon, which inhibits ketone body
formation. In fact, any dietary change that raises blood glucose is anti-ketogenic.
As mentioned in the previous chapter, the brain is the only tissue which requires glucose in
amounts of roughly 100 grams per day. If sufficient carbohydrate is consumed to provide this
much glucose, the brain will have no need to begin using ketones. Therefore any diet which
contains more than 100 grams of carbohydrate per day will not be ketogenic (2). After
approximately three weeks, when the brain’s glucose requirements have dropped to only 40
grams of glucose per day, carbohydrates must be restricted even further.
Additionally, from the standpoint of rapidly depleting liver glycogen, the more that
carbohydrates are restricted during the first days of a ketogenic diet, the faster ketosis will occur
and the deeper the degree of ketonemia. When examining the diet studies, any diet with more
than 100 grams of carbohydrates is considered to be non-ketogenic (often called a ‘balanced’ diet)
while any diet with less than 100 grams of carbohydrates is ketogenic (2).
Protein
Protein has both ketogenic effects (46%) and anti-ketogenic effects (58%). This reflects
the fact that 58% of dietary protein will appear in the bloodstream as glucose (3), raising insulin
and inhibiting ketogenesis. Note that the insulin response from consuming dietary protein is
much smaller than that from consuming dietary carbohydrates. Consequently protein must be
restricted to some degree on a ketogenic diet as excessive protein intake will generate too much
glucose, impairing or preventing ketosis. Protein also stimulates glucagon release and has some
pro-ketogenic effects.
The most critical aspect of protein intake has to do with preventing the breakdown of body
protein. By providing dietary protein during starvation, the breakdown of body protein can be
decreased or avoided entirely (4). The interactions between protein and glucose intake and protein
sparing are the topic of the next section.