Tuesday 25 July 2017

Medical Team Required to Effectively Implement the Ketogenic Diet

As indicated in the previous article on side effects, the Ketogenic diet must be initiated in a hospital environment to monitor and effectively manage any adverse effects.

The Ketogenic Diet is Medical Nutrition Therapy and requires a well-trained team to effectively implement. A Registered Paediatric Dietitian who coordinates the diet programme, a Paediatric Neurologist who is experienced in administering the ketogenic diet, a Registered Nurse, a Pharmacist who can advise on the carbohydrate content of medicines to inform the Dietitian when planning the diet ratio and a Medical Social Worker who works with the family and does follow-up on implementation. The patient and other caregivers must be educated in many aspects of the diet for it to be safely implemented.  

The Dietitian should ideally work with the family to create a meal plan for home implementation that takes into consideration all factors that may hinder full implementation, including the socioeconomic status, religious and cultural.   



Indications, Contraindications and Side effects of the Ketogenic Diet

Indications
The Ketogenic diet is highly recommended for children with uncontrolled or drug-resistant epilepsy and other neurological conditions.  More research into the diet has indicated that it could also be used to effectively manage other conditions, as indicated in the follow-up articles. The diet should be introduced in a controlled setting, preferably the hospital. 
  
The Ketogenic Diet is approved by national clinical guidelines in Scotland,[1] England and Wales[2] and reimbursed by nearly all US insurance companies.[3] Kenya is however quite behind in Clinical Nutrition, more so research and Medical Nutrition Therapy, therefore the diet is not widely used in our country.     
A liquid form of the ketogenic diet is well tolerated by, infants on formula and children who are tube-fed.[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%.[6][7][8] The diet can be considered earlier for some epilepsy and genetic syndromes where it has shown particular usefulness. These include Dravet syndromeinfantile spasmsmyoclonic-astatic epilepsy and tuberous sclerosis complex.[6][9]

The ketogenic diet alters the body's metabolism, therefore it is a first-line therapy in children with certain congenital metabolic diseases such as pyruvate dehydrogenase (E1) deficiency and glucose transporter 1 deficiency syndrome, which prevent the body from using carbohydrates as fuel, leading to a dependency on ketone bodies. The ketogenic diet is beneficial in treating the seizures and some other symptoms in these diseases.[13]

Contraindications
On the other hand, it is absolutely contraindicated in the treatment of other diseases such as pyruvate carboxylase deficiencyporphyria and other rare genetic disorders of fat metabolism.[6]A person with a disorder of fatty acid oxidation is unable to metabolize fatty acids, which replace carbohydrates as the major energy source on the diet. On the ketogenic diet, their body would consume its own protein stores for fuel, leading to ketoacidosis, and eventually coma and death.

Side Effects
As we mentioned in the introductory article, the Ketogenic diet/Keto-diet uses fats as the main energy source. Any drastic change from using carbohydrates for energy to fat results in various side effects as the body moves into a state of ketosis.    
The side effects however occur during the initial stages as the body adapts to the diet. The side effects are generally less severe and less frequent than with anticonvulsant medication or surgery. 

Common side effects include;  
        i.            Lethargy or lack of energy in the initial stages as the body gets into a state of Ketosis.
      ii.            Increased hunger, especially when the diet is drastically introduced. To counter this, the Nutritionist should gradually introduce the diet. 
    iii.            Decreased mental function
   iv.            Nausea 
     v.            Stomach discomfort
   vi.            Keto-breath
 vii.            Sleep issues
viii.            A fruity urine smell. This is usually due to excretion byproducts of the ketosis process
    ix.            Some people experience digestion issues such as constipation or diarrhea in the first 1 or 2 weeks. However this side effect subsides once the body adjusts to the diet. If the problems persist, the Nutritionist may look into increasing the fibre content in the diet and prescribe Probiotics to improve the gastrointestinal system health. 
      x.            Depending on the type of fats included in the diet, the blood lipids and cholesterol levels may be elevated. This can be averted by choosing unsaturated fats. If it persists, the Ketogenic ratio can be changed, to decrease the fat content.
    xi.            Low Micronutrient intake. This can be solved by the Nutritionist/Dietitian prescribing a Nutritional Supplement that covers the deficit in Micronutrients.
  xii.            Long-term use of the ketogenic diet in children increases the risk of slowed or stunted growth, bone fractures and kidney stones.
xiii.            The ketogenic diet reduces levels of insulin-like growth factor 1 (IGF-1), which is important for childhood growth. 
xiv.            The ketogenic diet like many anticonvulsant drugs has an adverse effect on bone health. Many factors may be involved such as acidosis and suppressed growth hormone.
 xv.            About 1 in 20 children on the ketogenic diet will develop kidney stones (compared with one in several thousand for the general population).  Kidney stones are treatable and do not justify discontinuation of the diet. Johns Hopkins Hospital gives oral potassium citrate supplements to all ketogenic diet patients, resulting in a sevenfold decrease in the incidence of kidney stones.[16]

In order to minimize negative effects and ease your body into the Ketogenic diet, the Nutritionist/Dietitian can start with a low Glycemic Index diet, or the Atkins diet, which is a high protein, moderate fat, low carbohydrate diet. The Nutritionist will then gradually increase the fat content and decrease carbohydrates.

All three diets; the Ketogenic, Atkins and Low Glycemic Diet MUST be prescribed by a qualified Dietitian/Nutritionist and both the patient and diet reviewed frequently. 
It is important to note that the Keto diet usually causes weight loss. For weight lifters, muscle builders and athletes, it is important to work closely with your Nutritionist/Dietitian to monitor protein intake, in order to prevent muscle loss.

The ketogenic diet, more so the standard Keto diet is low in Micro-Nutrients, therefore it is necessary to supplement. Your Nutritionist should advice on whether and how you can include vegetables low in carbohydrates/Glycemic Load in your meal plan to increase micronutrient intake.
Please note that the Ketogenic diet requires medical supervision, to avert and effectively manage any side effects. Therefore the diet needs to be initiated in a hospital setting.  

References
1.       Scottish Intercollegiate Guidelines Network. Guideline 81, Diagnosis and management of epilepsies in children and young people. A national clinical guideline(PDF). Edinburgh: Royal College of Physicians; 2005. ISBN 1-899893-24-5.     
2.       Stokes T, Shaw EJ, Juarez-Garcia A, Camosso-Stefinovic J, Baker R. The diagnosis and management of the epilepsies in adults and children in primary and secondary care.(PDF). London: Royal College of General Practitioners; 2004. ISBN 1-84257-808-1.
3.       Turner Z, Kossoff EH. The ketogenic and Atkins diets: recipes for seizure control (PDF). Pract Gastroenterol. 2006 Jun;29(6):53, 56, 58, 61–2, 64.
4.       Zupec-Kania BA, Spellman E. An overview of the ketogenic diet for pediatric epilepsy. Nutr Clin Pract. 2008 Dec–2009 Jan;23(6):589–96.doi:10.1177/0884533608326138PMID 19033218
5.       Kossoff EH, McGrogan JR, Freeman JM. Benefits of an all-liquid ketogenic diet. Epilepsia. 2004 Sep;45(9):1163. doi:10.1111/j.0013-9580.2004.18504.xPMID 15329084.
6.       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.xPMID 18823325
7.       Kossoff EH, Freeman JM. The ketogenic diet—the physician's perspective. In: Stafstrom CE, Rho JM, editors. Epilepsy and the ketogenic diet. Totowa: Humana Press; 2004. p. 53–61. ISBN 1-58829-295-9.
8.       Spendiff S. The diet that can treat epilepsy. Guardian. 2008 Aug 15;Sect. Health & wellbeing.
9.       Wang S, Fallah A. Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options. Neuropsychiatr Dis Treat. 2014 Oct 23;10:2021-30. doi:10.2147/NDT.S51789PMID 25364257
10.    Mastriani KS, Williams VC, Hulsey TC, Wheless JW, Maria BL. Evidence-based versus reported epilepsy management practices. J Child Neurol. 2008 Feb 15;23(5):507–14.doi:10.1177/0883073807309785PMID 18281618
12.    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
13.    Huffman J, Kossoff EH. State of the ketogenic diet(s) in epilepsy (PDF). Curr Neurol Neurosci Rep. 2006 Jul;6(4):332–40. PMID 16822355
14.    Zupec-Kania B, Werner RR, Zupanc ML. Clinical Use of the Ketogenic Diet—The Dietitian's Role. In: Stafstrom CE, Rho JM, editors. Epilepsy and the ketogenic diet. Totowa: Humana Press; 2004. p. 63–81. ISBN 1-58829-295-9.
15.    Kossoff EH, Zupec-Kania BA, Rho JM. Ketogenic diets: an update for child neurologists. J Child Neurol. 2009 Aug;24(8):979–88.doi:10.1177/0883073809337162PMID 19535814

16.    McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics. 2009 Aug;124(2):e300–4. doi:10.1542/peds.2009-0217PMID 19596731

Monday 24 July 2017

Ketogenic Diet’s Health Benefits (Keto Diet)

The Ketogenic diet is actually one of the most researched diets, and numerous studies now indicate that this is not another fad diet. For the Ketogenic diet to work effectively, all food high in carbohydrate must be avoided and the total carbs intake calculated, including from medicine and supplements sources.

Studies have shown that the Principles used in the Keto diet can be used in the management of the following medical conditions;
       I.            Cardiovascular/Heart diseases: The keto diet can improve risk factors like body fat, HDL levels, blood pressure and blood sugar (32, 33).
     II.            Cancer: The diet is currently being used to treat several types of cancer and slow tumor growth (4, 34, 35, 36).
  III.            Alzheimer’s disease: The diet may reduce symptoms of Alzheimer’s and slow down the disease’s progression (5, 37, 38).
  IV.            Epilepsy: Research has shown that the ketogenic diet can cause massive reductions in seizures in epileptic children (3).  
    V.            Parkinson’s disease: One study found that the diet helped improve symptoms of Parkinson’s disease (39).
  VI.            Polycystic ovary syndrome: The ketogenic diet can help reduce insulin levels, which may play a key role in polycystic ovary syndrome (40).
VII.            Brain injuries: One animal study found that the diet can reduce concussions and aid recovery after brain injury (41).
VIII.            Acne: Lower insulin levels and eating less sugar and processed foods may help improve acne (42). 


I must emphasize that as much as the Keto diet is a high fat diet, the dietary fat sources must be the healthy sources and most importantly, unsaturated, which explains why you need to be guided by a qualified Nutritionist before implementing this diet. 
     
The ketogenic diet’s health benefits with metabolic, neurological and insulin-related diseases have significant scientific backing. There are many diseases whose management we are struggling with including Cancer and Autoimmune conditions. We pump hefty funding in drug-related researches, while there lay many unexplored answers in Nutrition. Truth be told, sometimes the answers are simply hashed down and considering how much money the Pharma industry makes from Non-Communicable and Autoimmune diseases, the answers as to why these diets are hardly implemented are in black and white. 

NCDs and autoimmune diseases are very expensive to manage for patients, their families and governments worldwide and it is time we became cognizant of the fact that we need to go back to basics. The human body is 100% Nutrition. We however ironically ignore this and go to chemicals for answers. Now, I’m not saying that people should stop taking medicine, because unfortunately there are many instances where medicines need to be used to eliminate pathogens in the body, more so because the majority of people don’t have optimal immune function.

In addition to sugary foods and foods high in unhealthy fats, the Keto diet also limits fruits, legumes, pulses, grains, roots and tubers which are high in carbohydrates. This goes against Conventional Nutrition, and for that reason, the Ketogenic diet gets a lot of resistance from many quarters, in spite of all the evidence that shows tremendous health benefits.  


The most important thing to keep in mind even on the Ketogenic diet and any other prescribed meal plan is that Micro-Nutrient Supplementation must be done in order to support immune function and all body functions. A qualified Nutritionist/Dietitian must closely monitor and review the individual and the diet. More to this, all the medication the patient is using must be regularly evaluated to identify any negative reactions with the prescribed diet.  

Sunday 23 July 2017

The Ketogenic Diet (Keto-Diet) in Diabetes Management

The Ketogenic diet uses similar principles in Diabetes and weight management. As mentioned in the previous article on weight management, the Keto diet is a low carbohydrate, moderate protein, high fat diet.

Regulating blood sugars is very important in Diabetics to prevent complications, such as Kidney/renal failure, amputations, heart disease, impotence, retinopathy among other serious complications. In all types of Diabetes; Type 1, 2 and gestational diabetes, the challenge of blood sugar control and reduced insulin sensitivity is highly influenced by carbohydrate intake, more so the amounts and type of carbohydrate.

The Keto diet can be implemented in diabetics and has actually been seen to help persons with poor blood sugar control. To prevent hypoglycemia, I would advise you to have a Nutritionist/Dietitian create an individualized meal plan. Using the glycemic index and glycemic load of foods to determine the overall carbohydrate intake gives better results in blood sugar control.

As mentioned in the introductory article, the Ketogenic diet uses fat as the main energy source, instead of carbohydrates. Fat and protein take much longer to digest compared to carbohydrates. This means that it takes longer for sugars to be released in the blood stream, which automatically solves the problem of blood sugar spikes in diabetics.  
    
Weight management is a challenge in most diabetics, and it is majorly due to impaired insulin sensitivity. Various studies have found that the ketogenic diet improved insulin sensitivity in diabetics. Diabetics on the Keto diet have been reported to have better weight control, which prevents them from developing obesity, which is a risk factor for other Non-Communicable Diseases. 
   
Many diabetics also have various co-morbidities; therefore it is important for the Nutritionist/Dietitian to work closely with the Endocrinologist to ensure that the Keto diet does not cause any negative side effects.

The use of the Ketogenic diet in Diabetes management and its success in the same is not as vastly researched as its use in Neurological disorders such as Epilepsy, however the existing research indicates positive results. 

Saturday 22 July 2017

The Ketogenic Diet (Keto-Diet) and Weight Management

Can the Ketogenic Diet help you lose weight? As we discussed in a previous article, the Keto Diet is a very low carbohydrate, high fat, moderate protein diet. Research has shown that the Ketogenic diet is far more effective in weight loss compared to the more common low-fat diet.  

An analysis of the staple Kenyan diet which is mostly made up of Ugali, rice, chapatti, githeri, bananas and potatoes, indicates that most Kenyans feed on medium to high Glycemic Index foods on a daily basis. These foods are digested much faster than low glycemic index foods, therefore the person feels hungry much sooner, snacks several times in the day and ends up taking way more calories than their body actually needs. The standard Kenyan plate is high in Carbohydrate, medium to low protein depending on the socio-economic status, low fat to medium fat, and low in vegetables. 
     
In the Keto diet the body uses fat as the main energy source, not carbohydrate. Fats release more energy compared to carbohydrates. The Keto diet is more filling; therefore you stay full for a longer period and won’t need to snack in between meals, which is a major contributing factor in weight gain. 
  
The limited carbohydrate, increased ketones, lowered blood sugar levels and improved insulin sensitivity all play a key role in weight management. Carbohydrates, more so, those with a medium to high glycemic index are digested and released into the blood stream as glucose much faster in comparison to fats and proteins. The increased glucose in the blood leads to release of a hormone to help regulate the increased blood sugars, Insulin. 

Insulin is a storage hormone. Its work is to basically remove all excess glucose in the blood, and have it stored in the body as glycogen. Improving insulin control and sensitivity has a significant influence in weight management.   
There are many factors that come to play in weight management which include hormonal balance; however it is important to note that even on a Ketogenic diet, physical fitness must be a part of the daily routine. 
    
The Ketogenic Diet is more filling due to the high protein and fat content and research indicates that it has more success in weight loss compared to a low-fat diet. Sustainability is however something I always emphasize on, before a person decides to choose any diet plan or like I prefer to call it, meal plan.  

Constant hunger, feeling lethargic among other side effects, is some of the reasons why people don’t stay on different diet plans for the long-run. The protein and fat content in the keto-diet ensure that there’s no constant hunger, which would result in unhealthy snacking and increased simple carbohydrate intake.

Considering the fact that the Ketogenic Diet has been proven by research to have many health benefits for general health improvement and disease management, I would recommend easing your way into the diet. You can implement the standard Ketogenic Diet which is a high fat, moderate protein and low carbohydrate diet, but go carbohydrates that are low in the glycemic index. Also, please choose healthy sources of fats like nuts, fish, avocado, seeds, olive oil, Omega 3 and unsaturated fats.

The Nutritionist/Dietitian needs to create an individualized meal plan for you in order to incorporate low carbohydrate vegetables and most importantly, assess the total daily Micro-Nutrient content in your diet to prevent low intake and deficiencies that will compromise your immunity, organ function and overall optimal health. Micro-Nutrient Supplementation is usually necessary for persons implementing the Ketogenic diet.


Lastly, always consult your Nutritionist/ Dietitian before implementing any diet that introduces drastic shifts to your usual meal plan. For persons with any Fat-Metabolism Disorders, this is one Meal Plan both your Doctor and Nutritionist Must evaluate and give a green light for safety, before you can implement it. 

The Evolution of the Ketogenic Diet

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 CorpusOn 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, Î²-hydroxybutyrateacetoacetate 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.2006-2447PMID 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:10.1177/0883073809337162PMID 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.xPMID 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:10.2310/7010.2006.00044PMID 16901419