Does a low-carb diet increase the risk of ketones?

Post by Elizabeth Hodgkins DVM on a public message board, October 2000.

It is helpful to understand the whys and whens of ketones (or ketone bodies as they are sometimes called) in order to understand the answer to this (these) questions. In the animals with which we are most familiar (including people and cats), the brain's preferred fuel source is glucose. Skeletal muscle and other tissues are pretty happy using fat (triglycerides) for energy, but the brain is characteristically picky about this (and it's generally wise to give the brain what it wants!). One of insulin's chief jobs is to make sure that circulating glucose gets into the brain on demand; insulin is the molecule that "drives" glucose across the cell membrane.

When insulin is in short supply or absent, the body (and the brain) perceive that there is a shortage of glucose (even if there really isn't, as when the animal is hyperglycemic), and the brain's second and final fuel source begins to be produced, ketones. Ketones are produced by the liver from the oxidation of the body's fat stores. In conditions of true starvation (when body fat is legitimately broken down for necessary calories), or perceived starvation (hyperglycemic, uncontrolled diabetes), the liver believes it needs to produce ketones from body fat for the brain. This is the reason you see ketones in the urine of unregulated feline diabetics. You see ketosis in humans on some of the more strict high protein, low carb diets, because there is little dietary carbo to supply glucose from the g.i. tract, and the human body is not as efficient at gluconeogenesis (liver production of glucose from protein) as the cat (we have discussed this very major difference between cats and most other mammals on the board in the past). Because gluconeogenesis in people cannot keep up with the brain's needs under these circumstances, the liver makes up the shortfall with ketone body production. Except in extreme prolonged ketosis, this is not harmful to the normal human. After all, it is a normal survival mechanism. Naturally, it is not good to have severe metabolic acidosis (ketones cause the body to become relatively acid) for too prolonged a period (many weeks) because it can deplete body stores of buffers (mineral, generally). In starvation, however, it certainly beats the alternative (rapid brain death).

This brings us to the question of whether a low carb, high protein diet is bad for a diabetic cat, and does it cause ketosis? If you've been following this discussion so far, you are probably ready to guess that no, such diets do not cause ketosis in cats, diabetic or normal. In diabetic cats on high carbo diets (especially dry, extruded commercial cat foods where the dietary glucose is rapidly absorbed into the bloodstream from the gastrointestinal tract), the cat's brain nonetheless perceives "starvation" and ketones from the liver catabolism of fat begin circulating (and spilling into the urine, right along with the excess dietary glucose). This chronic circulating glucose has a suppressive effect on the cat's pancreas (mechanism unknown at this point), not to mention all of the other undesirable effects of chronic, poorly regulated diabetes. Most, if not all, commercial preparations of exogenous insulin work poorly in the cat (I don't have to tell all of you that!), so the hyperglycemia is essentially constant in most diabetic cats on high carbo diets.

When the cat eats a low carbo, high protein diet, however, little preformed glucose enters the blood stream. The liver produces what glucose the brain needs in a much more moderate, "time-released" fashion through gluconeogenic transformation of dietary protein, the pancreas-suppressive effects of hyperglycemia is significantly lessened (and in many cats, endogenous production of insulin resumes) and the body of the cat perceives a much more normal process of glucose production and uptake that satisfies the brain's needs.

We have not seen ketosis in cats on low carbo, high protein diets. This is the normal diet of the cat and its metabolic machinery is especially adapted to such a diet as the normal order of things, in times of feast as well as famine.