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.
^ Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC, Kelly LM. The efficacy of the ketogenic diet—1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998 Dec;102(6):1358–63. doi:10.1542/peds.102.6.1358. PMID 9832569. https://web.archive.org/web/20040629224858/http://www.hopkinsmedicine.org/press/1998/DECEMBER/981207.HTM Lay summary]—JHMI Office of Communications and Public Affairs. Updated 7 December 1998. Cited 6 March 2008.
Because people with type 2 diabetes are at an increased risk for cardiovascular disease, there’s a specific concern that the saturated fat in the diet may drive up LDL, or “bad,” cholesterol levels, and further increase the odds of heart problems. If you have type 2 diabetes, talk to your doctor before attempting a ketogenic diet. They may recommend a different weight-loss diet for you, like a reduced-calorie diet, to manage diabetes. Those with epilepsy should also consult their doctor before using this as part of their treatment plan.
For patients who benefit, half achieve a seizure reduction within five days (if the diet starts with an initial fast of one to two days), three-quarters achieve a reduction within two weeks, and 90% achieve a reduction within 23 days. If the diet does not begin with a fast, the time for half of the patients to achieve an improvement is longer (two weeks), but the long-term seizure reduction rates are unaffected. Parents are encouraged to persist with the diet for at least three months before any final consideration is made regarding efficacy.
A Cochrane systematic review in 2018 found and analysed eleven randomized controlled trials of ketogenic diet in people with epilepsy for whom drugs failed to control their seizures. Six of the trials compared a group assigned to a ketogenic diet with a group not assigned to one. The other trials compared types of diets or ways of introducing them to make them more tolerable. In the largest trial of the ketogenic diet with a non-diet control, nearly 38% of the children and young people had half or fewer seizures with the diet compared 6% with the group not assigned to the diet. Two large trials of the Modified Atkins Diet compared to a non-diet control had similar results, with over 50% of children having half or fewer seizures with the diet compared to around 10% in the control group.
This might be because the body increases insulin secretion in anticipation that sugar will appear in the blood. When this doesn’t happen, blood sugar drops and hunger increases. Whether this chain of events regularly takes place is unclear. Something odd happened when I tested Pepsi Max though, and there are well-designed studies showing increased insulin response when using artificial sweeteners.
There’s also some evidence that it might help with type 2 diabetes. “An emerging body of research is finding that a keto plan may have some real benefits thanks to its ability to improve the body’s ability to use insulin and also help control appetite, which can result in easier weight loss,” says Karen Ansel, R.D.N., co-author of Healthy in a Hurry.
The brain is composed of a network of neurons that transmit signals by propagating nerve impulses. The propagation of this impulse from one neuron to another is typically controlled by neurotransmitters, though there are also electrical pathways between some neurons. Neurotransmitters can inhibit impulse firing (primarily done by γ-aminobutyric acid, or GABA) or they can excite the neuron into firing (primarily done by glutamate). A neuron that releases inhibitory neurotransmitters from its terminals is called an inhibitory neuron, while one that releases excitatory neurotransmitters is an excitatory neuron. When the normal balance between inhibition and excitation is significantly disrupted in all or part of the brain, a seizure can occur. The GABA system is an important target for anticonvulsant drugs, since seizures may be discouraged by increasing GABA synthesis, decreasing its breakdown, or enhancing its effect on neurons.
First reported in 2003, the idea of using a form of the Atkins diet to treat epilepsy came about after parents and patients discovered that the induction phase of the Atkins diet controlled seizures. The ketogenic diet team at Johns Hopkins Hospital modified the Atkins diet by removing the aim of achieving weight loss, extending the induction phase indefinitely, and specifically encouraging fat consumption. Compared with the ketogenic diet, the modified Atkins diet (MAD) places no limit on calories or protein, and the lower overall ketogenic ratio (about 1:1) does not need to be consistently maintained by all meals of the day. The MAD does not begin with a fast or with a stay in hospital and requires less dietitian support than the ketogenic diet. Carbohydrates are initially limited to 10 g per day in children or 20 g per day in adults, and are increased to 20–30 g per day after a month or so, depending on the effect on seizure control or tolerance of the restrictions. Like the ketogenic diet, the MAD requires vitamin and mineral supplements and children are carefully and periodically monitored at outpatient clinics.
I was very curious about this, so I asked the opinion of metabolic expert Dr. Deborah Wexler, Director of the Massachusetts General Hospital Diabetes Center and associate professor at Harvard Medical School. Here is what she told me. “There is evidence to suggest that the circadian rhythm fasting approach, where meals are restricted to an eight to 10-hour period of the daytime, is effective,” she confirmed, though generally she recommends that people “use an eating approach that works for them and is sustainable to them.”
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). 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.
Keto breath, on the other hand, is less of a side-effect and more of a harmless inconvenience (your breath literally smells like nail polish remover). Basically, when your body breaks down all that extra fat on the keto diet, it produces ketones—one of which is the chemical acetone, Keatley previously told WomensHealthMag.com. (Yes, the same stuff that's in nail polish remover.)
Initial human studies that compared fasting every other day to eating less every day showed that both worked about equally for weight loss, though people struggled with the fasting days. So I had written off IF as no better or worse than simply eating less, only far more uncomfortable. My advice was to just stick with the sensible, plant-based, Mediterranean-style diet.
It is important to understand that weight is entirely a function of input and output. The input is the food you eat and the calories contained therein. The output is your energy output. To lose weight the output needs to be greater than the input. It is that simple. Do not believe any of the diet fads. If you are currently not gaining or losing weight then just burning 300 extra calories per week or eating/drinking 300 calories less per week (2 sodas for example or a small burger) WILL make you lose weight - in this case around 5 pounds of fat per year.
In addition, the healthy habits and kinds of foods recommended on the Mayo Clinic Diet — including lots of vegetables, fruits, whole grains, nuts, beans, fish and healthy fats — can further reduce your risk of certain health conditions. The Mayo Clinic Diet is meant to be positive, practical, sustainable and enjoyable, so you can enjoy a happier, healthier life over the long term.