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Wednesday, July 15, 2009

Most parents and neurologists consider the ketogenic diet as only including heavy whipping cream, mayonnaise, butter, and oils. For most children receiving this therapy, they are correct. In order to create a solid food diet in which 90% of the calories are fat, these foods make up a large portion of the child’s usual intake. However, the ketogenic diet can alternatively be easily provided as a liquid-only formulation to both infants as well as children with gastrostomy tubes. To some parents this is a surprise, but many ketogenic diet experts have been utilizing these formulas for years with good results.

What are these formulas?

There are several ways to provide the ketogenic diet as a formula. Perhaps the most simple is to use Nutricia KetoCal™, which is available in a powdered mix and either a 3:1 or 4:1 ratio. Water is added and calories are calculated by a dietitian. The 4:1 KetoCal has a slight vanilla flavor; the 3:1 KetoCal is unflavored. These formulas are milk-based, include corn syrup solids, and are nutritionally complete.

Ketogenic Formula

For children in whom separate components (e.g. fat, carbohydrate, and protein) are desired, or who have a lactose intolerance, “modular” ketogenic diets can be created using Ross Carbohydrate Free™ (Abbott Nutrition), Microlipid™ (Nestle Nutrition), and Polycose™ (Abbott Nutrition). A product in South Korea is also in clinical use called Ketonia™ has also been studied and is in active use, specifically for infantile spasms. A revised formulation called Ketonia II™ is now available without MCT (medium chain triglyceride) oil included. Lastly, Accera Pharmaceuticals, Inc. has developed a powdered MCT (medium chain triglyceride) oil-based powder (40 grams) that is designed to provide oral ketones to adults with Alzheimer’s disease. It is clinically available, includes both milk and soy protein, and is called Axona™.

Axona Packets

How well do they work?

Interestingly, not only do the ketogenic diet formulas help in children with epilepsy on the ketogenic diet, but two limited studies suggest they work better than a solid food ketogenic diet. The first study, by our team at Johns Hopkins, was published in Epilepsia in 2004 and described 61 children who were on all-liquid ketogenic diets (27% of all children started on the ketogenic diet at Johns Hopkins over a 6-year period). Surprisingly, 59% of these children had a >90% reduction in seizures, which is nearly twice the average response for children receiving the ketogenic diet overall. One year later, Dr. Hosain and his colleagues at Cornell University Medical Center in New York published similar results in Pediatric Neurology. Six (50%) of 12 children had >90% reduction in seizures after 12 months of receiving a formula-only ketogenic diet.

Why do children receiving an all-liquid ketogenic diet do so well? The answer is not clear. Part of the success may be due to the perfect compliance, with ketosis assured and cheating nearly impossible. However, the reason for the doubling of seizure control is likely clearly more complicated than that, and may have to do with fatty acid composition of these formulas or other factors.

Are there other advantages?

Other than benefits for seizure control and compliance, there are some other potential advantages to liquid ketogenic diets. KetoCal™ is nutritionally complete, so there is no need for additional multivitamin and calcium supplementation. It also includes selenium, carnitine, and zinc, often supplemented additionally on solid food ketogenic diets. We have also heard anecdotally of less constipation with the liquid formulas. Lastly, children receiving all-liquid ketogenic diets appear to be significantly less likely to have elevated total cholesterol. In one study, there was one-third the risk of total cholesterol above 200 mg/dL if the child was receiving only ketogenic diet formula. Only 17% of children taking only ketogenic formulas had elevated total cholesterol during their time on the ketogenic diet. Why would this be the case? When you compare the cholesterol values of formula and a typical solid-food ketogenic diet, it becomes very clear:

Average cholesterol and fat content in one day using three different ketogenic diets (4:1 ratio and 1000 calories). Reproduced from Nizamuddin, et al. 2008.

  Solid food diet* Modular formula** Nutricia KetoCal™
Cholesterol (milligrams) 454 0*** 0***
Total Fat (grams) 104 100 100
Saturated Fat (grams) 63 20 23
Saturated Fat as Percent of Total Daily fat 60% 20% 23%

*This represents using three distinct meals to create a 1000 calorie diet, including chicken, salmon, eggs, oil, heavy whipping cream, and vegetables.
** Microlipid™(Nestle Nutrition), Ross Carbohydrate Free™ (Abbott Nutrition), and Polycose™ (Abbott Nutrition) in combination to create a 4:1 ratio.
***0.01 mg of cholesterol for both products.

The future of ketogenic formulas

Although predominantly used in 2009 for infants and children with gastrostomy tubes with intractable epilepsy receiving the ketogenic diet, these formulas may have other uses in the future. There is an ongoing study at our institution to see if the modified Atkins diet with supplemental KetoCal™ shakes (10 ounces daily) for the first month is more likely to result in seizure control than the modified Atkins diet alone. In this study, the ketogenic formula is used in addition to solid foods, rather than as the entire diet. Ketogenic shakes (e.g. Axona™ and KetoCal™) are being used clinically and in research for non-epilepsy indications such as Alzheimer’s disease and ALS (Lou Gehrig’s Disease) respectively. Information about non-epilepsy indications for the ketogenic diet was discussed in the August 2008 edition of KetoNews.

Girl Drinking Formula

One of our modified Atkins diet study patients and her daily KetoCal™ shakes.

Nutricia is also investigating new ways in which to make KetoCal™ more accessible for children receiving it. One option may be ready-made liquids that children can bring to school such as in cardboard juice-pack styles. These will be available for sale in November 2009 according to the company. Another method to provide the benefits of KetoCal™ might be to use the powder as a flour substitute in recipes. Some of these already exist and are in clinical use, such as at www.myketocal.com.

References

  1. Hosain SA, La Vega-Talbott M, Solomon GE. Ketogenic diet in pediatric epilepsy patients with gastrostomy feeding. Pediatr Neurol. 2005;32(2):81-3.
  2. Kossoff EH, McGrogan JR, Freeman JM. Benefits of an all-liquid ketogenic diet. Epilepsia. 2004;45(9):1163.
  3. Nizamuddin J, Turner Z, Rubenstein JE, Pyzik PL, Kossoff EH. Management and risk factors for dyslipidemia with the ketogenic diet. J Child Neurol. 2008;23(7):758-61.
Authored by: Eric Kossoff, MD on 7/2009
Reviewed by: Robert Fisher MD PhD on 6/2009
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