In 1938, the discovery of diphenylhydantoin lessened the interest in the KD. In the late 1980s, after learning about the KD, a family of a 20-month-old boy with refractory epilepsy desperately approached the Johns Hopkins Hospital, requesting the treatment; the KD was effective for him. There was subsequently a Dateline episode on the effectiveness of the KD for this boy, Charlie. The family also established the Charlie Foundation, a nonprofit organization that began providing information to parents and instructional videos to practitioners and dietitians. Further publicizing and supporting the KD was the production of “Do No Harm,” directed by Charlie’s father and narrated by and starring Meryl Streep in 1997. Reflective of the subsequent increase in interest is the increase in medical literature; there were 2–8 publications per year between 1970 and 2000 on the KD and >40 per year since [1]. There are 102 KD programs listed on the Charlie Foundation Web site (www.​charliefoundatio​n.​org); the majority are in North America, but centers are also located in Europe, South America, Asia, and Australia.

In 1971, Peter Huttenlocher at the University of Chicago introduced the MCT Diet. Whereas the classic KD uses standard foods as source of fat, this utilizes MCT oil as a source of medium-chain fatty acids, which is more easily absorbed and delivered directly to the liver; thereby, more efficiently generating ketones and allowing greater consumption of protein and carbohydrates. The MCT diet provides 60–70% calories from fat. The downside of the MCT diet is gastrointestinal side effects including diarrhea, vomiting, and abdominal pain [4]. However, a randomized controlled trial comparing the tolerability and efficacy of the MCT diet versus classical KD showed no significant differences in either [5].

The MAD was developed at Johns Hopkins Hospital, first reported in 2003, and aimed at children with behavioral difficulties, adolescents, and adults [6]. The standard Atkins diet has a goal of weight loss and includes an induction phase in which there is limitation of carbohydrates to induce ketosis. In the MAD, this initial phase of carbohydrate restriction is continued, and weight loss is not encouraged unless nutritionally indicated.

The fat to protein plus carbohydrate ratio of the MAD is 0.9:1, providing approximately 60–65% of calories from fat, 30% from protein (higher than the KD and “normal” diet), and 10% from carbohydrates (higher than the KD). Based upon the protocol at Johns Hopkins, in children, initial carbohydrate restriction is to 10 grams per day for a month, with liberalization to 15 g, then 20–30 g per day. Adults are started at 15 g of carbohydrates per day and then increased to 20–30 g per day after a month. This initial stricter period is based upon data from a randomized, prospective cross-over design study which showed higher incidence of >50% seizure reduction at 3 months in patients who initially consumed 10 grams per day (60%) versus 20 g per day (10%). The glycemic index of carbohydrates is not controlled. Fiber is subtracted from the total carbohydrate count.

Initiation of the MAD is done as an outpatient process and no weighing of foods is required, although counting carbohydrates is required. Low-carbohydrate multivitamin and calcium supplementation is prescribed. Medications may be changed to lowest carbohydrate formulations. Urine ketones are checked twice per week and may be elevated to the “large” level, but sometimes are lower than those generated by the KD. Monitoring includes phone follow-up in a month and clinic follow-up at 3 and 6 months, with complete blood count (CBC), complete metabolic panel (CMP), fasting lipid profile at baseline, 3 and 6 months [7].