One of the earliest scientific articles about ketones appeared in the German literature in 1865 by J. Gerhardt. This article discusses the discovery of ketones in the urine of people with diabetes. Thirty years later, another German article discussed the presence of an abundance of ketones in the urine of people who were in diabetic coma (Hirschfield, 1895). For many years thereafter, ketones were simply thought to be abnormal byproducts of disease, such as diabetes. Even today, many doctors think of diabetic ketoacidosis when they first hear about the discussion of ketones and Alzheimer’s disease. They worry that their patients might become acidotic if they consume medium-chain fatty acids. This is simply not true (see section on Diabetic Ketoacidosis in Chapter 16).
The story of the effect of ketones in treating disease actually begins much earlier. There are historical references to fasting as a successful treatment for epilepsy and seizures in the Bible and again in the literature of the Middle Ages. In 1921, a pediatrician, Rawle Geyelin, M.D., reported at an American Medical Association convention successful treatment of three patients with epilepsy by an osteopath, Hugh Conklin, D.O. One of these patients was a ten-year-old boy with severe epilepsy who endured two very long periods of fasting, after which he had no seizures for the next year. Dr. Geyelin also reported that eighteen of twenty-six patients he treated showed marked improvement, and two were seizure-free for more than a year. He found that a twenty-day fast appeared to have the best results. Drs. Geyelin and Conklin did not know at that point that starvation produces high levels of ketones, and that these high levels of ketones were almost certainly responsible for the reduction of seizures in their patients.
Also in 1921, R. M. Wilder, M.D., reported in a brief article in the Mayo Clinic Bulletin, “The Effects of Ketonemia on the Course of Epilepsy,” that the ketone bodies acetone, acetoacetate, and beta-hydroxybutyric acid appear not only in the urine of people in diabetic ketoacidosis, but also in the urine of normal people who are starving. Not only that, but ketones appear in the urine of people who consume “a diet that contains too low a proportion of carbohydrate and too high a proportion of fat.” Thus, the classic “ketogenic diet” as a treatment for disease was born about ninety years ago.
In the classic ketogenic diet, about 80 percent of calories come from fat and the other 20 percent from protein and carbohydrate combined. Protein is limited because it can be converted in the liver to carbohydrate—when carbohydrate stores have been used up—by a process mentioned earlier called gluconeogenesis. At the same time, it is necessary to provide enough protein to prevent the breakdown of muscle and other tissues in the body, the so-called lean body mass. For children on a ketogenic diet to reduce epileptic seizures, protein is strictly calculated to allow for preservation of muscle and adequate growth. A ketogenic diet is not an easy one for most people to follow for the long haul, due to the small amount of carbohydrate allowed and the requirement to measure accurately every morsel of food eaten. But adhering to the classic ketogenic diet has a distinct advantage: it produces levels of ketone bodies considerably higher, in some cases ten times or more, than levels produced by ingesting oils with medium-chain fatty acids.
A review of the literature shows that, from the 1920s to 1960s, considerable research investigated the ketogenic diet and epilepsy. Other researchers studied the production of ketones during starvation in various groups of people and for various lengths of time. Better methods were developed for measuring ketones, and many of the details were worked out regarding how ketones are made and how they are broken down in the body. Lab animals were used in many cases to discover these details, and then these studies were duplicated in humans to confirm their findings. Some of the men who worked out these details in the 1960s are still actively involved in the study of ketones today: Drs. George Cahill, Sami Hashim, Oliver Owens, Theodore VanItallie, and Richard Veech. (There will be more about these physicians and their work in Chapter 19.)
The ketogenic diet as a treatment was largely put on the back burner for many years in the middle of the twentieth century, as various anti-seizure medications came into widespread use. The ketogenic diet was a topic of discussion during my own medical school and pediatric training and was used on occasion at that time for children with the most relentless forms of epilepsy. Little did I know at that time the role ketones would play in our own lives several decades later.
In the early 1990s, Jim Abrahams, a Hollywood director, came upon the ketogenic diet in the course of his own research as a potential treatment for his twenty-month-old son, who had severe epilepsy. Little Charlie endured as many as 100 seizures a day, in spite of treatment with strong anticonvulsants that resulted in heavy sedation. He did not even improve with brain surgery. The family decided to undertake the diet in spite of resistance from five pediatric neurologists Charlie had seen. Within days, the seizures stopped completely. Abrahams was angry that doctors had not made his family aware of the ketogenic diet. He soon learned that Charlie was just one of hundreds of thousands of children treated for epilepsy every year who did not have access to the ketogenic diet as a treatment due to lack of awareness of this option. He made it his mission to inform parents of other children with the disease and to educate doctors, hospitals, dieticians, and nurses, as well as promote research into the ketogenic diet.
In 1994, Abrahams founded The Charlie Foundation for this purpose (www.charliefoundation.org) and has had considerable success in achieving these goals. In 1992, he made a movie starring Meryl Streep, First Do No Harm, about a family dealing with severe epilepsy and their discovery of the ketogenic diet as a treatment for their son. In 2004, Dateline NBC aired two segments, and in 2008 a follow-up story about Charlie and the ketogenic diet greatly increased awareness and stimulated research. The first major international symposium covering the ketogenic diet took place in April 2008, and the related articles were published in a special edition of the medical journal Epilepsia in October 2008. The next symposium took place in October 2010 in Edinburgh, Scotland.
It is important to note that children with epilepsy who are on a strict ketogenic diet can greatly reduce the frequency of seizures and even become seizure-free over time, but it requires extremely rigid adherence to the diet. Very recently, the diet has been tried by older people, and some adults with epilepsy benefit significantly from the ketogenic diet as well. However, not everyone with epilepsy responds dramatically to the diet, but many have a considerable reduction in seizures, by half or more.
People with Alzheimer’s disease, Parkinson’s, and other neurodegenerative diseases who do not see improvement by consuming oils with medium-chain fatty acids should consider going all the way with the ketogenic diet. Conversely, modification of the ketogenic diet to include medium-chain fatty acids may allow for a slightly less-restrictive diet and assurance that some ketone production will go on, even if there is a slip-up in how much carbohydrate is consumed. Some research has shown that this type of modification might allow for more carbohydrate in the overall diet, which may be easier for some families (Huttenlocher, 1971).
The Atkins diet is one popular version of the ketogenic diet used for several decades. With Atkins, the primary focus is on reducing carbohydrates, but protein and fat can be eaten in unlimited quantity. There is a two-week induction period in which carbohydrates are limited to 20 grams per day; thereafter, carbohydrates are increased by 5 grams per week until weight loss stalls, then it is stepped back to the previous level. Considerable water is lost from muscle initially, which is very encouraging on the scale, but it does not represent true loss of fat, which is the desired goal. With restriction of carbohydrates, ketones are produced, since the body is forced to break down fat for fuel. With unlimited protein, however, it is conceivable that, for people who consume large quantities of it, not much ketosis may be going on, since the body can also convert protein to carbohydrate.
The South Beach diet is very similar to Atkins except there is more emphasis on eating “good” carbohydrates—foods with a low-glycemic index that do not cause the sudden spike in glucose followed by a spike in insulin levels that are characteristic of “bad” carbohydrates.