The ketogenic diet is not a benign, holistic, or natural treatment for epilepsy; as with any serious medical therapy, complications may result.[28] These are generally less severe and less frequent than with anticonvulsant medication or surgery.[28] Common but easily treatable short-term side effects include constipation, low-grade acidosis, and hypoglycaemia if an initial fast is undertaken. Raised levels of lipids in the blood affect up to 60% of children[38] and cholesterol levels may increase by around 30%.[28] This can be treated by changes to the fat content of the diet, such as from saturated fats towards polyunsaturated fats, and if persistent, by lowering the ketogenic ratio.[38] Supplements are necessary to counter the dietary deficiency of many micronutrients.[18]


First, that study, which was reported upon widely, was on mice. Mice are not like humans in the way they fatten or contract metabolic diseases. Journalists/media should stop reporting on mice stories as if they were applicable to humans, especially when there is such a large body of clinical trial data on humans. Let’s be clear: rigorous clinical trial data on humans trumps any data on mice. Every time. And what does the rigorous data on humans say?
Even hibernating bears do not go into ketosis[2]. And predatory animals who undergo extended periods of food deprivation, such as elephant seals[3], are metabolically resistant to ketosis; instead, they have upregulated gluconeogenesis pathways through which they can steadily produce glucose. This makes perfect sense, since predators’ survival depends on their ability to catch their prey, which usually requires intense bursts of activity. And sprinting capacity is dependent on glucose, as humans who adopt a ketogenic diet quickly discover.

Recently, many of my patients have been asking about a ketogenic diet. Is a ketogenic diet safe? Would you recommend it? Despite the recent hype, a ketogenic diet is not something new. In medicine, we have been using it for almost 100 years to treat drug-resistant epilepsy, especially in children. In the 1970s, Dr. Atkins popularized his very-low-carbohydrate diet for weight loss that began with a very strict two-week ketogenic phase. Over the years, other fad diets incorporated a similar approach for weight loss.


“If someone with diabetes is [taking insulin or oral type 2 meds in the sulfonylurea or meglitinide class and is] following this diet, they need to know that their blood sugar can drop really quickly, so it’s critical that they check it more frequently,” says Toby Smithson, MS, RDN, CDE, author of Diabetes Meal Planning & Nutrition for Dummies. “Don’t wait for it to happen. Meet with your doctor or diabetes educator in advance so that you can troubleshoot exactly what to do if your blood sugar drops.” If it’s an infrequent occurrence, you may be advised to treat with fast-acting glucose. But frequent lows may require medication adjustments or the addition of more carbs to your eating plan.
^ Ketogenic "eggnog" is used during induction and is a drink with the required ketogenic ratio. For example, a 4:1 ratio eggnog would contain 60 g of 36% heavy whipping cream, 25 g pasteurised raw egg, saccharin and vanilla flavour. This contains 245 kcal (1,025 kJ), 4 g protein, 2 g carbohydrate and 24 g fat (24:6 = 4:1).[17] The eggnog may also be cooked to make a custard, or frozen to make ice cream.[37]

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]
When you eat tons of carbs, your blood sugar is consistently elevated, and then so is insulin. Insulin is a hormone that keeps your blood sugar in check by shuttling the glucose into cells, but when there’s a consistently high amount of insulin, your cells become resistant. This insulin resistance makes it easier to store fat, and chronically high levels of insulin also cause excessive inflammation in the body, which contributes to heart disease, high blood pressure, and potentially type 2 diabetes.
The ketogenic diet has been studied in at least 14 rodent animal models of seizures. It is protective in many of these models and has a different protection profile than any known anticonvulsant. Conversely, fenofibrate, not used clinically as an antiepileptic, exhibits experimental anticonvulsant properties in adult rats comparable to the ketogenic diet.[58] This, together with studies showing its efficacy in patients who have failed to achieve seizure control on half a dozen drugs, suggests a unique mechanism of action.[56]

Infants and patients fed via a gastrostomy tube can also be given a ketogenic diet. Parents make up a prescribed powdered formula, such as KetoCal, into a liquid feed.[19] Gastrostomy feeding avoids any issues with palatability, and bottle-fed infants readily accept the ketogenic formula.[31] Some studies have found this liquid feed to be more efficacious and associated with lower total cholesterol than a solid ketogenic diet.[18] KetoCal is a nutritionally complete food containing milk protein and is supplemented with amino acids, fat, carbohydrate, vitamins, minerals and trace elements. It is used to administer the 4:1 ratio classic ketogenic diet in children over one year. The formula is available in both 3:1 and 4:1 ratios, either unflavoured or in an artificially sweetened vanilla flavour and is suitable for tube or oral feeding.[51] Other formula products include KetoVolve[52] and Ketonia.[53] Alternatively, a liquid ketogenic diet may be produced by combining Ross Carbohydrate Free soy formula with Microlipid and Polycose.[53]


Upon starting the diet, some patients report symptoms like fatigue, headaches, and muscle aches. However, these short-lived symptoms are, in fact, a sign that the diet is working, and the body is switching over from burning glucose as fuel to burning fat. This transition involves upregulating certain enzymes and down-regulating others; it is a profound shift for the human body that can have uncomfortable symptoms. However, these side effect usually last only 3-4 weeks. They can be ameliorated in most cases, by drinking several cups of bouillion broth during the day until the transition is completed.15
To minimize the risk of hypoglycemia, Yancy and his team decrease medication as soon as a patient starts the diet. While drugs like metformin and liraglutide (Victoza) are less of a concern, there are others that pose a substantial hypoglycemia threat. In addition to insulin, the sulfonylurea drugs glipizide and glyburide require a watchful eye, as they work by stimulating the pancreas to make more insulin, increasing the risk of dangerous lows in the face of insufficient carbohydrate intake. “People on this diet need to be prepared to check their blood glucose any time they feel like it could be getting too low,” says Urbanski. “I would say a minimum of twice a day, but ideally three to four times a day, at least in the beginning in order to see the effect of the diet on their blood glucose readings.”
Advocates for the diet recommend that it be seriously considered after two medications have failed, as the chance of other drugs succeeding is only 10%.[9][31][32] The diet can be considered earlier for some epilepsy and genetic syndromes where it has shown particular usefulness. These include Dravet syndrome, infantile spasms, myoclonic-astatic epilepsy, and tuberous sclerosis complex.[9][33]
Because it lacks carbohydrates, a ketogenic diet is rich in proteins and fats. It typically includes plenty of meats, eggs, processed meats, sausages, cheeses, fish, nuts, butter, oils, seeds, and fibrous vegetables. Because it is so restrictive, it is really hard to follow over the long run. Carbohydrates normally account for at least 50% of the typical American diet. One of the main criticisms of this diet is that many people tend to eat too much protein and poor-quality fats from processed foods, with very few fruits and vegetables. Patients with kidney disease need to be cautious because this diet could worsen their condition. Additionally, some patients may feel a little tired in the beginning, while some may have bad breath, nausea, vomiting, constipation, and sleep problems.
The only issue with keto, is really that I’m afraid that it might be hard to up my calories to a maintenance weight now that I’ve gotten a taste preference for the rich assortment of foods with no carbs in them. I’m satisfied with less calories than I will need after my excess fat is burned off… but , maybe I bet my body will send more hunger signs once there isn’t anymore body fat in the cupboard to use instead of what goes down my throat.
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.[44] Parents are encouraged to persist with the diet for at least three months before any final consideration is made regarding efficacy.[9]

Because some cancer cells are inefficient in processing ketone bodies for energy, the ketogenic diet has also been suggested as a treatment for cancer.[59][60] A 2018 review looked at the evidence from preclinical and clinical studies of ketogenic diets in cancer therapy. The clinical studies in humans are typically very small, with some providing weak evidence for anti-tumour effect, particularly for glioblastoma, but in other cancers and studies, no anti-tumour effect was seen. Taken together, results from preclinical studies, albeit sometimes contradictory, tend to support an anti-tumor effect rather than a pro-tumor effect of the KD for most solid cancers.[61]
The idea that ketosis is human beings’ natural state is also contradicted by the heavy dependence of human embryonic and fetal development on glucose. All women become insulin resistant during normal pregnancy[15] as glucose is directed toward the developing baby. Pregnant women deprived of carbohydrates are at high risk of developing ketoacidosis in later pregnancy.[16] This dangerous condition can occur as the nutrient needs of the developing fetus reach their peak and drive up maternal ketone production.
The original therapeutic diet for paediatric epilepsy provides just enough protein for body growth and repair, and sufficient calories[Note 1] to maintain the correct weight for age and height. The classic therapeutic ketogenic diet was developed for treatment of paediatric epilepsy in the 1920s and was widely used into the next decade, but its popularity waned with the introduction of effective anticonvulsant medications. This classic ketogenic diet contains a 4:1 ratio by weight of fat to combined protein and carbohydrate. This is achieved by excluding high-carbohydrate foods such as starchy fruits and vegetables, bread, pasta, grains, and sugar, while increasing the consumption of foods high in fat such as nuts, cream, and butter.[1] Most dietary fat is made of molecules called long-chain triglycerides (LCTs). However, medium-chain triglycerides (MCTs)—made from fatty acids with shorter carbon chains than LCTs—are more ketogenic. A variant of the classic diet known as the MCT ketogenic diet uses a form of coconut oil, which is rich in MCTs, to provide around half the calories. As less overall fat is needed in this variant of the diet, a greater proportion of carbohydrate and protein can be consumed, allowing a greater variety of food choices.[4][5]
Advocates for the diet recommend that it be seriously considered after two medications have failed, as the chance of other drugs succeeding is only 10%.[9][31][32] The diet can be considered earlier for some epilepsy and genetic syndromes where it has shown particular usefulness. These include Dravet syndrome, infantile spasms, myoclonic-astatic epilepsy, and tuberous sclerosis complex.[9][33]
As discussed in the first article of this series, ketosis is a metabolic state in which the brain switches to using ketone bodies – derived from the breakdown of fat – as its primary energy source, instead of glucose. This way body protein, which would otherwise be broken down and converted into glucose through the process of gluconeogenesis, are spared.
People claiming huge benefits of these supplements – despite the lack of solid scientific support – may sometimes have a financial reason to believe in the supplements. Some of these products are sold under a multi-level marketing arrangement, where sales people are paid based on commission. For example, the company Prüvit sells drinkable ketones, called KETO//OS with a multi-level marketing structure.
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