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Tuesday, November 20, 2007

History of the diet and its side effects

Perhaps one of the least discussed but most important of the changes in ketogenic diet research in the past decade has been the identification of its side effect profile. During the 1920s and 1930s, when the ketogenic diet was one of the most popular anticonvulsant therapies, side effects such as acidosis (low bicarbonate levels in the blood), constipation, and abnormal menstrual periods (in adult women) were discussed and were just starting to be investigated.

However, over the following 60 years, research into the ketogenic diet focused nearly exclusively on demonstrating that it worked in order to answer its critics, rather than researching side effects. All this has changed in the past decade, and now that the ketogenic diet is no longer perceived as an alternative treatment, as James Wheless, MD, titled his editorial in 2001, the ketogenic diet is a “medical therapy with side effects”, and researchers have agreed.(1) Although most of the side effects I will discuss are important to be observant for, and can be bothersome, it is rare to have to stop the diet because of them.

What are the side effects?

The most common, almost “expected”, side effects of the diet are constipation, acidosis (especially with illness), and decreased weight gain (not often weight loss). These are often addressed immediately when the diet is started, especially using Miralax™ for constipation. The less common side effects, generally occurring in 1 in 20 children, include high cholesterol, kidney stones, growth slowing, and gastrointestinal upset.

In 2001, Peter Kwiterovich, MD, reported in JAMA our experience at Johns Hopkins Hospital in regards to cholesterol of children on the diet.(2) In general, most children have a 30% increase in total cholesterol, LDL cholesterol, and triglycerides. Fortunately, this increase happens within 3 months but usually doesn’t continue to increase (and in studies of children on the diet for over 6 years, may return to normal). Although we often recommend adding MCT oil (link to Keto News article), increasing the percentage of polyunsaturated fatty acids, and lowering the ketogenic diet ratio, these interventions have been looked at in only small numbers of patients. Many families are worried about the long-term effects of high cholesterol, but we suspect that the short periods of time that most children are on the diet do not impact later atherosclerosis.

Around the same time, in 2000, Susan Furth, MD, showed both that there is a 5% chance of kidney stones in children on the diet and that it was more likely to occur in those who had high amounts of calcium in their urine.(3) She suggested that using Polycitra K™ to make the urine less acidic and bind up calcium would help prevent stones. Just this year, Amitha Sampath, MD, from our group proved she was right: by using Polycitra K™ there was 3 times less risk of stones.(4) Since January 2006 at Hopkins, all children started on the diet are also started on Polycitra K™.

Growth is also slowed somewhat by being on the diet. Children tend to follow the growth curves, but mostly stay around the 5th percentile.(5) Children under age 2 years are at the most risk for growth disturbance, and therefore we tend to use lower ketogenic diet ratios (e.g. 3:1) in this age group to allow for more protein. In children on the diet for over 6 years, nearly all were at the 5th percentile. It is hard to argue that this is probably a minor problem for a child having hundreds of daily seizures, but it is worth monitoring to keep children as healthy and normal as possible.

Very recent information also suggests that bone density can be a problem while on the diet, similar to being on medications. Children appear to have lower bone mineral density, which can lead to an increased risk of bone fractures, especially in children on the diet for over 6 years.(6) Christina Bergqvist, MD, found that Vitamin D levels initially increase due to supplementation on the diet, and after several months they decline, and this may partially explain the problems with bone density.(7) Studies are underway using DEXA scans to monitor children on the diet.

The rare side effects

Over the past decade, several case reports have described unusual, but serious side effects possibly attributable to the ketogenic diet. They include inflammation of the pancreas, prolonged QT intervals in heart rhythms, enlargement and problems with the heart muscle, selenium deficiency, severe carnitine deficiency, and basal ganglia changes (a deep part of the brain). We do not know at this time the true incidence of these problems, but they appear to be very rare.

The Charlie Foundation and many ketogenic diet experts are interested in creating a web-based side effect registry for the diet, as already exists for anticonvulsant drugs by the Food and Drug Administration. Physicians would enter anonymous information about a side effect they think may be due to the diet, and then could find out if any other doctors have seen it, too (and then contact them for how they treated the side effect.)

We are clearly in an exciting time for the ketogenic diet, but as its use grows, the occurrence of side effects will also grow. The future is bright because physicians are trying not only to identify side effects, but prevent them from happening.

References

  1. Wheless JW. (2001). The ketogenic diet: an effective medical therapy with side effects. J Child Neurol 16, 633-635.
  2. Kwiterovich PO, Jr., Vining E P, Pyzik P, Skolasky R, Jr., Freeman JM. (2003). Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA 290, 912-920.
  3. Furth SL, Casey JC, Pyzik PL, Neu AM, Docimo SG, Vining EP, Freeman JM, Fivush B A. (2000). Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol 15, 125-128.
  4. Sampath A, Kossoff EH, Furth SL, Pyzik PL, Vining EPG (2007). Kidney stones and the ketogenic diet: risk factors and prevention. J Child Neurol 22, 375-8.
  5. Vining EP, Pyzik P, McGrogan J, Hladky H, Anand A, Kriegler S, Freeman JM. (2002). Growth of children on the ketogenic diet. Dev Med Child Neurol 44, 796-802.
  6. Groesbeck DK, Bluml RM, Kossoff EH. (2006) Long-term use of the ketogenic diet. Dev Med Child Neurol 48, 978-81.
  7. Bergqvist AG, Schall JI, Stallings VA (2007). Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia. 48, 66-71.
Authored by: Eric Kossoff, MD on 11/2007
Reviewed by: Steven C. Schachter, MD on 11/2007
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