Variations on the Johns Hopkins protocol are common. The initiation can be performed using outpatient clinics rather than requiring a stay in hospital. Often, no initial fast is used (fasting increases the risk of acidosis, hypoglycaemia, and weight loss). Rather than increasing meal sizes over the three-day initiation, some institutions maintain meal size, but alter the ketogenic ratio from 2:1 to 4:1.[9]
One downside to a ketogenic diet for weight loss is the difficulty maintaining it. “Studies show that weight loss results from being on a low-carb diet for more than 12 months tend to be the same as being on a normal, healthy diet,” says Mattinson. While you may be eating more satiating fats (like peanut butter, regular butter, or avocado), you’re also way more limited in what’s allowed on the diet, which can make everyday situations, like eating dinner with family or going out with friends, far more difficult. Because people often find it tough to sustain, it’s easy to rely on it as a short-term diet rather than a long-term lifestyle.
Cancer, a very common and sometimes fatal cause of unexplained (idiopathic) weight loss. About one-third of unintentional weight loss cases are secondary to malignancy. Cancers to suspect in patients with unexplained weight loss include gastrointestinal, prostate, hepatobiliary (hepatocellular carcinoma, pancreatic cancer), ovarian, hematologic or lung malignancies.
^ 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 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]

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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 low glycaemic index treatment (LGIT)[49] is an attempt to achieve the stable blood glucose levels seen in children on the classic ketogenic diet while using a much less restrictive regimen. The hypothesis is that stable blood glucose may be one of the mechanisms of action involved in the ketogenic diet,[9] which occurs because the absorption of the limited carbohydrates is slowed by the high fat content.[5] Although it is also a high-fat diet (with approximately 60% calories from fat),[5] the LGIT allows more carbohydrate than either the classic ketogenic diet or the modified Atkins diet, approximately 40–60 g per day.[18] However, the types of carbohydrates consumed are restricted to those that have a glycaemic index lower than 50. Like the modified Atkins diet, the LGIT is initiated and maintained at outpatient clinics and does not require precise weighing of food or intensive dietitian support. Both are offered at most centres that run ketogenic diet programmes, and in some centres they are often the primary dietary therapy for adolescents.[9]
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A study with an intent-to-treat prospective design was published in 1998 by a team from the Johns Hopkins Hospital[20] and followed-up by a report published in 2001.[21] As with most studies of the ketogenic diet, no control group (patients who did not receive the treatment) was used. The study enrolled 150 children. After three months, 83% of them were still on the diet, 26% had experienced a good reduction in seizures, 31% had had an excellent reduction, and 3% were seizure-free.[Note 7] At 12 months, 55% were still on the diet, 23% had a good response, 20% had an excellent response, and 7% were seizure-free. Those who had discontinued the diet by this stage did so because it was ineffective, too restrictive, or due to illness, and most of those who remained were benefiting from it. The percentage of those still on the diet at two, three, and four years was 39%, 20%, and 12%, respectively. During this period, the most common reason for discontinuing the diet was because the children had become seizure-free or significantly better. At four years, 16% of the original 150 children had a good reduction in seizure frequency, 14% had an excellent reduction, and 13% were seizure-free, though these figures include many who were no longer on the diet. Those remaining on the diet after this duration were typically not seizure-free, but had had an excellent response.[21][22]
Those studies above, in working with small sample sizes, and different types of fasting than recommended here, would lead me to believe that fasting affects men and women differently, and that many of the weight loss benefits associated with intermittent fasting (that affect insulin and glucose responses) work positively for men and negatively for women.
The Mayo Clinic Diet is generally safe for most adults. It does encourage unlimited amounts of vegetables and fruits. For most people, eating lots of fruits and vegetables is a good thing — these foods provide your body with important nutrients and fiber. However, if you aren't used to having fiber in your diet, you may experience minor, temporary changes in digestion, such as intestinal gas, as your body adjusts to this new way of eating.
Unintentional weight loss can occur because of an inadequately nutritious diet relative to a person's energy needs (generally called malnutrition). Disease processes, changes in metabolism, hormonal changes, medications or other treatments, disease- or treatment-related dietary changes, or reduced appetite associated with a disease or treatment can also cause unintentional weight loss.[25][26][27][31][32][33] Poor nutrient utilization can lead to weight loss, and can be caused by fistulae in the gastrointestinal tract, diarrhea, drug-nutrient interaction, enzyme depletion and muscle atrophy.[27]

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]


Continuing weight loss may deteriorate into wasting, a vaguely defined condition called cachexia.[30] Cachexia differs from starvation in part because it involves a systemic inflammatory response.[30] It is associated with poorer outcomes.[25][30][31] In the advanced stages of progressive disease, metabolism can change so that they lose weight even when they are getting what is normally regarded as adequate nutrition and the body cannot compensate. This leads to a condition called anorexia cachexia syndrome (ACS) and additional nutrition or supplementation is unlikely to help.[27] Symptoms of weight loss from ACS include severe weight loss from muscle rather than body fat, loss of appetite and feeling full after eating small amounts, nausea, anemia, weakness and fatigue.[27]
Unintentional weight loss may result from loss of body fats, loss of body fluids, muscle atrophy, or a combination of these.[25][26] It is generally regarded as a medical problem when at least 10% of a person's body weight has been lost in six months[25][27] or 5% in the last month.[28] Another criterion used for assessing weight that is too low is the body mass index (BMI).[29] However, even lesser amounts of weight loss can be a cause for serious concern in a frail elderly person.[30]
Anticonvulsants suppress epileptic seizures, but they neither cure nor prevent the development of seizure susceptibility. The development of epilepsy (epileptogenesis) is a process that is poorly understood. A few anticonvulsants (valproate, levetiracetam and benzodiazepines) have shown antiepileptogenic properties in animal models of epileptogenesis. However, no anticonvulsant has ever achieved this in a clinical trial in humans. The ketogenic diet has been found to have antiepileptogenic properties in rats.[56]

Those issues can be part of what's known as the “keto flu,” Warren says. Other side effects of the keto diet, all of which are tied to carb withdrawal, can include lightheadedness, nausea, mental fog, cramps, and headaches, in addition to tiredness. Luckily, the keto flu doesn't usually last more than a week—which is coincidentally about when people start to see the number on the scale go down, says Warren.


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.
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