MONTREAL – Epilepsy treatment with the ketogenic diet for more than 6 months slowed the long-term skeletal development of 29 children who participated in a prospective, longitudinal study.
Children who went on the diet fell behind by a mean of 0.1756 lumbar Z-units every year, compared with children who had normal bone growth, Dr. Mark Mackay said at the 30th International Epilepsy Congress.
"Put simply, they accrue bone mass at a slower rate than their age-matched peers," Dr. Mackay of the Royal Children’s Hospital Melbourne, Parkville, Australia, said in an interview.
Children in Dr. Mackay’s study were treated with the ketogenic diet for more than 6 months during 2002-2009. They were a mean of 6 years old when they started the diet, and they followed it for a mean of 6 years.
Dr. Mark Mackay
In addition to the high-fat dietary treatment, they received supplements of calcium and vitamin D to reach the minimum daily requirements. They had dual-energy x-ray absorptiometry (DXA) scans at baseline and every 6 months while on the diet. Normative bone data were used for comparison.
The children also had regular assessment of bone health biomarkers, including serum calcium, potassium, 25-hydroxyvitamin D, parathyroid hormone, bone alkaline phosphatase, osteocalcin, and urinary calcium/creatinine ratio.
Children were grouped at baseline according to mobility status on a 5-point scale, ranging from walking without limitations (1) to being transported in a manual wheelchair (5). At baseline, 11 children had a score of 1 or 2, while 18 scored greater than 2.
Before treatment, their mean bone mineral density lumbar Z-score was 0.99. Children who had no mobility problems had higher baseline scores than did those with mobility problems (mean, –0.125 vs. –1.18). This was not a surprise, said Dr. Mackay, a pediatric neurologist at Royal Children’s Hospital Melbourne. "Many of the children we treat have comorbid physical disability, which also places them at risk of poor bone health, due to factors including decreased weight bearing, physical activity, and sunlight exposure, which is important for vitamin D production."
Subjects on the ketogenic diet demonstrated a mean bone mineral density lumbar Z-score decrease of 0.1756 units/year. Bone loss was greater in children who had higher baseline Z-scores (–0.28 vs. –0.04 units/year).
Their mean serum alkaline phosphatase levels remained in the normal range throughout the study period. However, the investigators measured elevations in mean osteocalcin (26.5 nmol/L) and mean urinary calcium/creatinine ratio (0.77).
The findings highlight the risks of a ketogenic diet, which relies on fat metabolism to induce ketoacidosis. A neutral pH is necessary to mobilize calcium from bone, Dr. Mackay said.
Children who are on the diet are also at risk for deficiencies in micronutrients important for health, including vitamin D and calcium. The timing of diet initiation also plays an important role, he said.
"Childhood and adolescence are critical periods for the normal accrual of bone mass. The bone that is laid down needs to last that person for the rest of their life. Therefore any intervention that affects accrual of bone can have long-lasting health consequences for the child."
While the ketogenic diet is a very effective treatment for some seizure disorders, it’s not risk free, he added. "Some parents see the ketogenic diet as a ‘natural’ alternative to medications, which it is not. Therefore it is important to be improving our knowledge about potential serious long-term side effects so parents can make an informed decision about treatment."
The findings should prompt more study of the diet’s potential long-term impact on skeletal health, Dr. Mackay said. "These will inform development of guidelines for bone surveillance in this high-risk group of predominantly children to minimize potential negative health consequences of the ketogenic diet. ... However, I don’t think we can make any comments at this stage about the role of antiresorptive treatments."
The study was partially funded by Pfizer Australia. Dr. Mackay did not have any financial disclosures.