As mentioned in the introductory
article, the ketogenic diet is
a high fat, adequate protein, low carbohydrate diet that for years
has been used primarily to treat
difficult-to-control (refractory) epilepsy in children.
In a high
carbohydrate diet, which is the ‘normal’ diet for most people, the carbohydrates
contained in food are converted into glucose, which is then transported
around the body and is particularly important in fueling brain function.
However, if there is very little carbohydrate in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace
glucose as an energy source. An elevated level of ketone bodies in the blood, a
state known as ketosis, leads to a reduction in the frequency of epileptic seizures.[1]
Physicians in ancient Greece
treated diseases, including epilepsy, by altering their patients' diet.
The original therapeutic diet
for paediatric epilepsy provides just enough
protein for body growth and repair, and sufficient calories to maintain the correct weight for age and height. 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]
The classic therapeutic ketogenic
diet was developed for treatment of
paediatric epilepsy in 1924 by
Dr. Russell Wilder at the Mayo Clinic and
was widely used into the next decade, but its popularity decreased with the
introduction of effective anticonvulsant drugs.
Prior to the classic therapeutic ketogenic diet development
in 1924, Dr. Hugh Conklin used a more extreme method to treat epilepsy, the
"water diet" treatment.
There were even more harsh treatment modalities, for example, the royal
physician Erasistratus declared, "One inclining to epilepsy should be
made to fast without mercy and be put on short rations. In an early treatise in
the Hippocratic
Corpus, On
the Sacred Disease, which dates
from c. 400 BC.; the author argued against the prevailing view that
epilepsy was supernatural in origin and cure, and proposed that dietary therapy had a rational and physical basis.
Dr. Hugh Conklin's fasting
therapy was adopted by neurologists in mainstream practice. In 1916, Dr. McMurray wrote
to the New York Medical Journal claiming to have successfully
treated epilepsy patients with a fast, followed by a starch- and sugar-free
diet, since 1912.
In 1921, Rollin Woodyatt reviewed
the research on diet and diabetes. He reported that three water-soluble
compounds, β-hydroxybutyrate, acetoacetate and acetone (known collectively as ketone bodies), were produced by the liver in otherwise healthy people
when they were starved or if they consumed a very low-carbohydrate, high-fat
diet.
Russel Wilder, at the Mayo Clinic, built on this research and
coined the term ketogenic diet to
describe a diet that produced a high level of ketone bodies in the blood (ketonemia)
through an excess of fat and lack of carbohydrate. Wilder hoped to obtain the
benefits of fasting in a dietary therapy that could be maintained indefinitely.
His trial on a few epilepsy patients in 1921 was the first use of the ketogenic
diet as a treatment for epilepsy.[6]
Russel Wilder's colleague, Paediatrician Mynie Peterman, later
formulated the classic diet, with a
ratio of one gram of protein per kilogram of body weight in children,
10–15 g of carbohydrate per day, and the remainder of calories from fat. Peterman's
work in the 1920s established the techniques for induction and maintenance of
the diet. Peterman documented positive effects (improved alertness, behaviour
and sleep) but also adverse effects (nausea and vomiting due to excess
ketosis).
The diet proved to be very
successful in children. Peterman
reported in 1925 that 95% of 37 young patients had improved seizure control on
the diet and 60% became seizure-free. By 1930, the diet had also been
studied in 100 teenagers and adults. Clifford
Barborka, also from the Mayo Clinic, reported
that 56% of those older patients improved on the diet and 12% became
seizure-free. Although the adult results are similar to modern studies of
children, they did not compare as well to contemporary studies. Barborka
concluded that adults were least likely to benefit from the diet, and the use
of the ketogenic diet in adults was not studied again until 1999.[6][7] Research into the Ketogenic diet largely
declined with the introduction of drugs.
Almost half of children and young
people with epilepsy who have tried some form of the ketogenic diet saw the
number of seizures drop by at least half, and the effects persist even after
discontinuing the diet.[2]
There is evidence that adults
with epilepsy may benefit from the diet, and that a less strict regimen, such
as a modified Atkins diet, is
similarly effective.[1] Clinical trials and studies in animal models (including C.
elegans[3]) suggest that ketogenic diets provide neuroprotective
and disease-modifying benefits for a number of adult neurodegenerative
disorders.[4][5]
Hollywood producer Jim
Abrahams, two year old son, Charlie Abraham had uncontrolled epilepsy, suffered from daily seizures despite trying
all available anti-seizure medications, alternative therapies and enduring a
futile brain surgery. Abrahams discovered a reference
to the ketogenic diet in an epilepsy guide for parents and brought Charlie
to John Freeman at Johns
Hopkins Hospital, which had
continued to offer the therapy.
Charlie started the ketogenic diet and remained on it for 5
years and the seizures stopped, the epilepsy was
rapidly controlled and his developmental progress resumed. In 1994, Jim
Abrahams and his family started The Charlie Foundation after his son’s complete
recovery. The Charlie Foundation promotes
the Ketogenic diet and actively funds research into the diet.
A multicenter prospective study
began in 1994; the results were presented to the American Epilepsy Society in
1996 and were published [8] in
1998. There followed an explosion of scientific interest in the diet. In 1997,
Abrahams produced a movie First
Do No Harm in which a young boy's intractable epilepsy is
successfully treated by the ketogenic diet.
By 2007, the ketogenic diet was
available from around 75 centres in 45 countries, and less restrictive
variants, such as the modified Atkins diet, were in use, particularly among older children and
adults. The ketogenic diet was also under investigation for the treatment of a
wide variety of disorders other than epilepsy.[1]
According to available research, the ketogenic diet reduces seizure frequency by more than 50% in half of
the patients who try it and by more than 90% in a third of patients.[9] Three-quarters of children who respond do so within two weeks, though
experts recommend a trial of at least three months before assuming it has been
ineffective.[10] Children with refractory epilepsy are more likely to benefit from the
ketogenic diet than from trying another anticonvulsant drug.[1] There is some evidence that adolescents and adults may also benefit
from the diet.[10]
A meta-analysis conducted in
2006, looked at 19 studies on a total of 1,084 patients.[11] It concluded that half the patients achieved a 50% reduction in
seizures and a third achieved a 90% reduction.[9]
References
1.
Freeman JM,
Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007
Mar;119(3):535–43. doi:10.1542/peds.2006-2447. PMID 17332207
2.
Levy RG, Cooper
PN, Giri P. Ketogenic diet and other dietary treatments
for epilepsy. Cochrane
Database Syst Rev. 2012 Mar
3.
Mobbs C. Treatment of diabetes and
diabetic complications with a ketogenic diet. Journal of Child Neurology. 2013
May;28(8):1009–14. doi:10.1177/0883073813487596.PMID 23680948
4.
Gasior M, Rogawski MA, Hartman
AL. Neuroprotective and disease-modifying
effects of the ketogenic diet. Behav Pharmacol.
2006;17(5–6):431–9. PMID 16940764
5.
Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie
restriction, the ketogenic diet, and ketone bodies. Brain Res
Rev. 2009 Mar;59(2):293–
6.
Wheless JW. History and origin of the ketogenic
diet (PDF). In: Stafstrom CE, Rho JM,
editors. Epilepsy and the ketogenic diet. Totowa: Humana Press; 2004. ISBN 1-58829-295-9 .
7.
Kossoff EH. Do ketogenic diets work for adults
with epilepsy? Yes! epilepsy.com. 2007, March.
Cited 24 October 2009.
8.
Vining EP, Freeman JM, Ballaban-Gil
K, Camfield CS, Camfield PR, Holmes GL, et al. A multicenter study of the efficacy of the
ketogenic diet. Arch Neurol. 1998
Nov;55(11):1433–7. PMID 9823827
9.
Kossoff EH, Zupec-Kania BA, Rho JM.
Ketogenic diets: an update for child neurologists. J Child Neurol. 2009
Aug;24(8):979–88.doi:10.1177/0883073809337162. PMID 19535814
10. Kossoff EH,
Zupec-Kania BA, Amark PE, Ballaban-Gil KR, Bergqvist AG, Blackford R, et
al. Optimal clinical management of
children receiving the ketogenic diet: recommendations of the International
Ketogenic Diet Study Group.Epilepsia. 2009
Feb;50(2):304–17. doi:10.1111/j.1528-1167.2008.01765.x. PMID 18823325
11. Henderson CB,
Filloux FM, Alder SC, Lyon JL, Caplin DA. Efficacy of the ketogenic diet as a
treatment option for epilepsy: meta-analysis. J Child Neurol. 2006 Mar;21(3):193–8.doi:10.2310/7010.2006.00044. PMID 16901419
No comments:
Post a Comment