It is possible to combine the results of several small studies to produce evidence that is stronger than that available from each study alone—a statistical method known as meta-analysis. One of four such analyses, conducted in 2006, looked at 19 studies on a total of 1,084 patients.[23] It concluded that a third achieved an excellent reduction in seizure frequency and half the patients achieved a good reduction.[18]
During the 1920s and 1930s, when the only anticonvulsant drugs were the sedative bromides (discovered 1857) and phenobarbital (1912), the ketogenic diet was widely used and studied. This changed in 1938 when H. Houston Merritt, Jr. and Tracy Putnam discovered phenytoin (Dilantin), and the focus of research shifted to discovering new drugs. With the introduction of sodium valproate in the 1970s, drugs were available to neurologists that were effective across a broad range of epileptic syndromes and seizure types. The use of the ketogenic diet, by this time restricted to difficult cases such as Lennox–Gastaut syndrome, declined further.[10]
Unfortunately, there’s no long-term data on ketogenic diets versus other diets. In a 2015 Italian study, those on a ketosis diet lost 26 pounds in three months. About half of the participants stayed on the diet for a year but lost little additional weight in the next nine months. People in a 2014 Spanish study who followed a very-low-calorie ketogenic diet lost an average of 44 pounds in a year—but a third of them dropped out, possibly because it was too hard to maintain.
Gary D. Foster, Ph.D., Holly R. Wyatt, M.D., James O. Hill, Ph.D., Brian G. McGuckin, Ed.M., Carrie Brill, B.S., B. Selma Mohammed, M.D., Ph.D., Philippe O. Szapary, M.D., Daniel J. Rader, M.D., Joel S. Edman, D.Sc., and Samuel Klein, M.D., “A Randomized Trial of a Low-Carbohydrate Diet for Obesity — NEJM,” N Engl J Med 2003; 348:2082- 2090. http://www.nejm.org/doi/full/10.1056/NEJMoa022207.
On a ketogenic diet, your entire body switches its fuel supply to run mostly on fat, burning fat 24-7. When insulin levels become very low, fat burning can increase dramatically. It becomes easier to access your fat stores to burn them off. This is great if you’re trying to lose weight, but there can also be other, less obvious benefits, such as less hunger and a steady supply of energy (without the sugar peaks and valleys we can get from high carb meals). This may help keep you alert and focused.
Gary D. Foster, Ph.D., Holly R. Wyatt, M.D., James O. Hill, Ph.D., Brian G. McGuckin, Ed.M., Carrie Brill, B.S., B. Selma Mohammed, M.D., Ph.D., Philippe O. Szapary, M.D., Daniel J. Rader, M.D., Joel S. Edman, D.Sc., and Samuel Klein, M.D., “A Randomized Trial of a Low-Carbohydrate Diet for Obesity — NEJM,” N Engl J Med 2003; 348:2082- 2090. http://www.nejm.org/doi/full/10.1056/NEJMoa022207.
Although many hypotheses have been put forward to explain how the ketogenic diet works, it remains a mystery. Disproven hypotheses include systemic acidosis (high levels of acid in the blood), electrolyte changes and hypoglycaemia (low blood glucose).[19] Although many biochemical changes are known to occur in the brain of a patient on the ketogenic diet, it is not known which of these has an anticonvulsant effect. The lack of understanding in this area is similar to the situation with many anticonvulsant drugs.[56]

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Electrolytes: To reiterate, maintaining electrolyte balances is critical on a ketogenic diet, in order to prevent side effects and the “keto-flu.” While this can be done exclusively through whole foods, some individuals may require additional sources. Sodium, magnesium, potassium, and in some cases, calcium, can all be replenished via supplementation.
The easiest macro to calculate in the ketogenic diet is fat. Once you've got your carbs and protein set, simply fill the rest of your daily calorie needs with fat sources. If you find yourself wanting to gain a bit of weight, add approximately 500 calories, or 55 grams. If you want to lose weight, cut down on your fat intake by 200-500 calories, or 22-55 grams.
Physicians of ancient Greece treated diseases, including epilepsy, by altering their patients' diet. An early treatise in the Hippocratic Corpus, On the Sacred Disease, covers the disease; it dates from c. 400 BC. Its author argued against the prevailing view that epilepsy was supernatural in origin and cure, and proposed that dietary therapy had a rational and physical basis.[Note 3] In the same collection, the author of Epidemics describes the case of a man whose epilepsy is cured as quickly as it had appeared, through complete abstinence of food and drink.[Note 4] The royal physician Erasistratus declared, "One inclining to epilepsy should be made to fast without mercy and be put on short rations."[Note 5] Galen believed an "attenuating diet"[Note 6] might afford a cure in mild cases and be helpful in others.[11]
This article was reviewed by Jes Harvey, RD, on November 7, 2019. Harvey is a registered dietitian specializing in the ketogenic diet for children and adults. She is a certified specialist in Pediatric Nutrition and educates children with epilepsy on the ketogenic diet as an anti-seizure medication. Harvey also manages a private nutrition practice consulting adults on the ketogenic way of eating.
As for branched-chain amino acids, you'll find smart people who swear that they're keto-friendly, and others who don't. One of the BCAAs, valine, can be glucogenic, meaning that it can lead to glucose production and potentially contribute to leaving ketosis behind.[1] But does that mean it will happen? Not necessarily, particularly if you're just an occasional supplement user.
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