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]

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.[7]

The day before admission to hospital, the proportion of carbohydrate in the diet may be decreased and the patient begins fasting after his or her evening meal.[19] On admission, only calorie- and caffeine-free fluids[37] are allowed until dinner, which consists of "eggnog"[Note 8] restricted to one-third of the typical calories for a meal. The following breakfast and lunch are similar, and on the second day, the "eggnog" dinner is increased to two-thirds of a typical meal's caloric content. By the third day, dinner contains the full calorie quota and is a standard ketogenic meal (not "eggnog"). After a ketogenic breakfast on the fourth day, the patient is discharged. Where possible, the patient's current medicines are changed to carbohydrate-free formulations.[19]
The Johns Hopkins Hospital protocol for initiating the ketogenic diet has been widely adopted.[43] It involves a consultation with the patient and their caregivers and, later, a short hospital admission.[19] Because of the risk of complications during ketogenic diet initiation, most centres begin the diet under close medical supervision in the hospital.[9]

Dehydration. With fewer water-binding carbohydrates in the diet, the body is less able to hold onto fluids, which can lead to dehydration. Eating more salt can help offset this, but it can also raise blood pressure, creating a whole new set of issues. If you plan to follow a keto diet, hydration is key. To know how many ounces of fluid you need each day, Yancy recommends dividing your body weight in half. Then think of the resulting number as your daily fluid goal in ounces. So if you weigh 200 pounds, strive for 100 ounces of water a day.
Short-term results for the LGIT indicate that at one month approximately half of the patients experience a greater than 50% reduction in seizure frequency, with overall figures approaching that of the ketogenic diet. The data (coming from one centre's experience with 76 children up to the year 2009) also indicate fewer side effects than the ketogenic diet and that it is better tolerated, with more palatable meals.[18][50]
There are three instances where there’s research to back up a ketogenic diet, including to help control type 2 diabetes, as part of epilepsy treatment, or for weight loss, says Mattinson. “In terms of diabetes, there is some promising research showing that the ketogenic diet may improve glycemic control. It may cause a reduction in A1C — a key test for diabetes that measures a person’s average blood sugar control over two to three months — something that may help you reduce medication use,” she says.
Even in endurance sports that don’t require sprinting, ketogenic-style diets are disadvantageous according to a ketogenic diet and exercise article published in Sports Medicine[5]: “a high-fat, low-carbohydrate ketogenic diet may impair exercise performance via reducing the capacity to utilize carbohydrates, which forms a key fuel source for skeletal muscle during intense endurance-type exercise.” The article concluded, “At present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes’ performance under conditions where evidence-based nutritional strategies are applied appropriately.”
The classic ketogenic diet is not a balanced diet and only contains tiny portions of fresh fruit and vegetables, fortified cereals, and calcium-rich foods. In particular, the B vitamins, calcium, and vitamin D must be artificially supplemented. This is achieved by taking two sugar-free supplements designed for the patient's age: a multivitamin with minerals and calcium with vitamin D.[18] A typical day of food for a child on a 4:1 ratio, 1,500 kcal (6,300 kJ) ketogenic diet comprises three small meals and three small snacks:[28]
In the 1960s, medium-chain triglycerides (MCTs) were found to produce more ketone bodies per unit of energy than normal dietary fats (which are mostly long-chain triglycerides).[15] MCTs are more efficiently absorbed and are rapidly transported to the liver via the hepatic portal system rather than the lymphatic system.[16] The severe carbohydrate restrictions of the classic ketogenic diet made it difficult for parents to produce palatable meals that their children would tolerate. In 1971, Peter Huttenlocher devised a ketogenic diet where about 60% of the calories came from the MCT oil, and this allowed more protein and up to three times as much carbohydrate as the classic ketogenic diet. The oil was mixed with at least twice its volume of skimmed milk, chilled, and sipped during the meal or incorporated into food. He tested it on 12 children and adolescents with intractable seizures. Most children improved in both seizure control and alertness, results that were similar to the classic ketogenic diet. Gastrointestinal upset was a problem, which led one patient to abandon the diet, but meals were easier to prepare and better accepted by the children.[15] The MCT diet replaced the classic ketogenic diet in many hospitals, though some devised diets that were a combination of the two.[10]

No human population has ever lived in a permanent state of ketosis. Ketogenic diets are dangerous for pregnant women and developing fetuses, and the only human population that has ever subsisted on this dietary pattern advocated by keto diet proponents could only do so because of a genetic mutation that prevents them from going into ketosis. Unfortunately, it has the unintended but unavoidable consequence of reducing the survival prospects of their infants.
So rather than giving one-size-fits-all dietary advice or weaponizing the word “balanced” it might be better if the medical community suggested that there are Individual differences that need to be considered. This might also help those lay folk who have had success with one dietary lifestyle or another also realize that what’s valid for them may not be good advice for others.
Around this time, Bernarr Macfadden, an American exponent of physical culture, popularised the use of fasting to restore health. His disciple, the osteopathic physician Dr. Hugh William Conklin of Battle Creek, Michigan, began to treat his epilepsy patients by recommending fasting. Conklin conjectured that epileptic seizures were caused when a toxin, secreted from the Peyer's patches in the intestines, was discharged into the bloodstream. He recommended a fast lasting 18 to 25 days to allow this toxin to dissipate. Conklin probably treated hundreds of epilepsy patients with his "water diet" and boasted of a 90% cure rate in children, falling to 50% in adults. Later analysis of Conklin's case records showed 20% of his patients achieved freedom from seizures and 50% had some improvement.[10]
Achieving ketosis is a pretty straightforward, but it can seem complicated and confusing with all of the information out there.4If you want to learn more about ketosis and the scientific process around it, you can visit a very in-depth discussion about on Dr. Peter Attia’s website. Here’s the bottom line on what you need to do, ordered in levels of importance:
For many people, one of the more surprising side effects of starting a ketogenic diet is a bout with the “keto flu.” How so? “When you go on this diet, your kidneys don’t retain as much salt or water, which can lead to flu-like symptoms, such as fatigue and headache, or constipation,” says Laura Saslow, PhD, an assistant professor at the University of Michigan School of Nursing. “But these are typically short-lived symptoms that can be prevented or treated by increasing your salt and water intake.” However, if you have high blood pressure, speak with your doctor before adding more sodium to your diet. And know that the keto flu only lasts a week or two; symptoms typically subside once the body adjusts to the diet.
One of the most-cited worries about the keto diet is the long-term impact it may have on heart health—especially because people with diabetes are at greater risk for heart disease. In the small Diabetic Medicine study that found people with type 1 improved their A1Cs on a keto diet, participants had higher triglycerides and LDL (“bad”) cholesterol. This raises concerns about the diet’s longer-term heart health implications, as do the results of research published last year in The Lancet. That study followed more than 15,000 adults for 25 years and found that people who consumed less than 40 percent of their calories from carbohydrates were significantly more likely to die from heart disease than those whose diets contained 50 to 55 percent of calories from carbs—especially if the foods that replaced those carbs were rich in animal fats and proteins.
When you’re eating the foods that get you there (more on that in a minute), your body can enter a state of ketosis in one to three days, she adds. During the diet, the majority of calories you consume come from fat, with a little protein and very little carbohydrates. Ketosis also happens if you eat a very low-calorie diet — think doctor-supervised, only when medically recommended diets of 600 to 800 total calories.
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