Ketogenic diet

The ketogenic diet is a high fat, adequate protein, low carbohydrate diet, primarily used in the treatment of difficult-to-control epilepsy in children. Developed in the 1920s, its popularity waned with the introduction of effective anticonvulsant drugs. In the mid 1990s the Hollywood producer Jim Abrahams, whose son's severe epilepsy was effectively controlled by the diet, created the Charlie Foundation to promote it. Publicity included an appearance on NBC's Dateline program and a TV movie starring Meryl Streep. The foundation funded a multi-centre study that was published in 1996, which marked the beginning of renewed scientific interest in the diet.^[1]

The diet mimics starvation by forcing the body to use fat rather than carbohydrate as an energy source. The "classic" ketogenic diet contains a 4:1 ratio of fat to combined protein and carbohydrate. To achieve this, a number of foods are effectively eliminated (for example, starchy fruits and vegetables, bread, pasta, grains and sugar). A variant known as the MCT diet uses a form of coconut oil that is very high in medium chain triglycerides (MCT; most dietry fat contains long chain triglycerides). This oil has a strong ketogenic effect, which allows some relaxation of the regime.^[1]

A number of studies demonstrate the effectiveness of this diet in treating refractory epilepsy in children. For this patient group, the diet is more likely to successful than attempting another anticonvulsant drug. However, the diet has not been tested in a large, prospective, randomised, double-blinded controlled trial. A blinded control group is regarded as practically impossible, at least for children fed orally. There is some evidence that adults may benefit too, and that a less strict diet (such as a modified Atkin's) might also be effective.^[1]

Additional recommended knowledge

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Indications

The ketogenic diet is indicated as an adjunctive treatment in children with drug-resistant epilepsy.^[2][3] Children with intractable epilepsy may be referred to a tertiary care hospital with expertise in the ketogenic diet.^[4]

Contraindications

In the UK, the National Institute for Health and Clinical Excellence state that the diet should not be recommended for adults with epilepsy.^[2]

Adverse effects

Possible long-term side effects of the diet include:^{[citation needed]}

• kidney stones
• abnormal liver function
• high cholesterol
• weight loss
• dehydration
• bone thinning

Mechanism

The diet prescribes foods high in fat, and heavily restricts carbohydrate intake. As fats become the body's primary source of metabolic energy, ketones accumulate in the brain, which can alleviate epileptic symptoms. The diet is often perceived as more effective in children than adults, particularly when anticonvulsant drug therapy is ineffective (20%-30% of patients) or contraindicated, however, data from the 1920s and 1930s, as well as recently, shows similar results.^{[citation needed]}

Foods used in the diet include high-triglyceride dairy products (e.g., butter, cream), mayonnaise and peanut butter. Carbohydrates, found in breads and starches, are eliminated in the diet, and liquid and calorie intake are often restricted as well in order to aid ketone accumulation. The diet is typically supplemented with calcium, vitamin D, iron, and folic acid.

Status

The ketogenic diet is endorsed by national guidelines in Scotland,^[4] England and Wales^[2] and by US insurance companies.^[5][6][7]

Scientific studies

A study undertaken at Johns Hopkins Hospital in 1998 reported that 50% of those patients starting the ketogenic diet reported a decrease in seizures of 50% or more, with 29% of patients reporting a 90% reduction in symptoms; these patients had previously tried an average of six anticonvulsant drugs.^[8] The success rate on patients who responded to anticonvulsants was not measured in that study (and appears to be lacking in other recent studies as well - there appears to be reluctance to try the diet on subjects except as a last resort). The success rate of the diet on those who are successfully treated with anti-convulsants may be higher, lower, or the same as those who do not respond. It may be that the diet and anti-convulsants are effective on different segments of the population. This has continued to be the statistics today, with approximately half of patients having at least half of their seizures improve.

The ketogenic diet has been reported to work in cases where multiple epilepsy drugs have failed.^{[citation needed]} There may also be cases where the ketogenic diet has failed and epilepsy drugs succeeded. When one epilepsy drug fails, there is a high likelihood that other drugs will also fail. When the diet works, the response is often rapid and dramatic.

Double blind studies

Lack of double blind studies is an issue preventing wider acceptance by the medical profession. Reliance on proper studies rather than anecdotal evidence or flawed studies is important. Double blind studies help eliminate:

• Placebo effect
• Spontaneous remission
• Researchers' expectations prejudicing their observations
• Researchers inadvertently prejudicing patients through body language, tone of voice, etc.

A double blind study of the Ketogenic Diet has been completed and is being analyzed.^[9]

Research

The diet usually referred to in the context of epilepsy treatment is the classic 4:1 fat to protein plus carbohydrate ratio Johns Hopkins Hospital protocol,^[10][11] but there is more than one type of ketogenic diet. There's also the Sanggye Paik Hospital protocol (also 4:1) developed by Drs. Kim and Park, the medium chain triglyceride diet,^[12] the Atkins diet,^[13] and supplementation with polyunsaturated fats.^[14]

Kim Dong Wook and colleagues at the Inje University Sanggye Paik Hospital Epilepsy Center found that patients treated with the nonfasting, introduce high-fat foods to existing diet gradually protocol (August 1999-February 2001) achieved urinary ketosis just as fast, with just as much improvement in seizures, as patients using the initial fasting Johns Hopkins protocol (July 1995-July 1999), with 1/6 the dehydration and a shorter average hospital stay.^[15] A team led by Dr. Inna I. Vaisleib reported that same year that the 4:1 diet could also be done outpatient and with no caloric restrictions.^[16] According to Freeman et al, the ketogenic diet reduces atonic and myoclonic seizures by over 50% immediately.^[17]

Proposed mechanisms of action for the ketogenic diet include acetone elevation,^[18] changes in brain amino acid metabolism,^[19]

Like any other therapeutic intervention, the ketogenic diet is not without adverse effects. In 2004, Drs. Hoon Chul Kang, Da Eun Chung, Dong Wook Kim, and Heung Dong Kim reported that out of 129 patients who were on the diet at the Epilepsy Center at Inje University Sanggye Paik Hospital between July 1995 and October 2001, 46.5% experienced—in the 4-week trial period—dehydration, 38.8% experienced gastrointestinal symptoms (diarrhea (32.6%), nausea/vomiting (27.9%), and constipation (2.3%)), hypertriglyceridemia in 27.1%, hyperuricemia in 26.4%, hypercholesterolemia (14.7%), infections (pneumonia, cystitis, etc) in 9.3%, symptomatic hypoglycemia (7.0%), hypoproteinemia (5.4%), hypomagnesemia (4.7%), repetitive hyponatremia (4.7%), HDL hypocholesterolemia (3.9%), lipoid pneumonia due to aspiration (2.3%), hepatitis (2.3%), acute pancreatitis and persistent metabolic acidosis.^[20] After those first four weeks, the side effects, in descending order of prevalence, were gastrointestinal discomfort (27.9%), infectious disease (20.9%), hypertriglyceridemia (20.2%), hypercholesterolemia (19.4%), osteopenia (14.7%), hypomagnesemia (10.9%), hyperuricemia (7.8%), hepatitis (5.4%), lipoid pneumonia due to aspiration (4.7%), hypoproteinemia (3.9%), kidney stone(s) (3.1%), iron-deficiency anemia (1.6%), secondary hypocarnitinemia (1.6%), HDL hypocholesterolemia (0.8%), symptomatic hypoglycemia (0.8%), hydronephrosis (0.8%), and cardiomyopathy (0.8%).^[20] The person who had cardiomyopathy died, along with three other people, one with lipoid pneumonia and the other two with sepsis.^[20]

The majority of side effects of the diet are transient and can be addressed without diet discontinuation. Kidney stones can be treated with extra hydration and oral citrates. Hypercholesterolemia is improved with lowering the diet ratio and substituting higher amounts of polyunsaturated fats. Weight loss can be corrected with extra calories.

Recent work on the mechanism of action for ketogenic diet as a treatment for epilepsy have investigated the role of glycolysis in the disease.^[21] The glycolytic inhibitor 2-Deoxy-D-glucose has been proposed as a mimic for the ketogenic diet, and shows great promise as a new anti-epileptic drug.

Other conditions

The ketogenic diet has been proposed as a potential treatment for the neurodegenerative disease amyotrophic lateral sclerosis (ALS). A study of the G93A SOD1 transgenic mouse model of ALS showed that the diet altered the progression of the disease.^[22] A small pilot study of children with autism who managed to tolerate the ketogenic diet, showed some behavioural benefits.^[23]

See also

• Medical research related to low-carbohydrate diets

References