Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet

Am J Clin Nutr. 2008 Dec;88(6):1678-84. doi: 10.3945/ajcn.2008.26099.


Background: The ketogenic diet (KD) is a high-fat, low-carbohydrate, and protein diet that effectively treats intractable epilepsy (IE).

Objective: The purpose of this study was to measure the change in bone mineral content (BMC) in children with IE treated with the KD for 15 mo.

Design: Prepubertal children >or=5 y of age with IE were eligible. A 4:1 ketogenic diet was maintained for 15 mo, and whole-body and spine BMCs were measured with dual-energy X-ray absorptiometry. Z scores were generated by comparing the children with IE with a cohort of 847 healthy children. Other measurements included demographics, anthropometry, serum 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone, electrolytes, and dietary intake. All measurements were performed at baseline and at 3, 6, 12, and 15 mo. Longitudinal mixed effects models were used to analyze change in BMC over time.

Results: Twenty-five children (9 girls, 16 boys) with IE [age (x +/- SD): 7.3 +/- 1.9 y] participated. Growth and bone health status were suboptimal as were serum 25-OHD concentrations and dietary intake of calcium and vitamin D. Whole-body and spine BMC-for-age both declined by 0.6 z score/y and whole-body and spine BMC-for-height declined 0.7 z score/y and 0.4 z score/y, respectively. Height declined 0.5 z score/y. Body mass index (BMI; in kg/m(2)) z score, age, and ambulation were positive predictors of BMC, which declined sharply over 15 mo of KD treatment.

Conclusion: Bone health in children with IE was poor, particularly for younger nonambulatory children with low BMI status. The KD resulted in progressive loss of BMC. The mechanism is unclear. Further studies are needed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D 2 / blood
  • Absorptiometry, Photon / methods
  • Body Mass Index
  • Bone Density* / drug effects
  • Bone Density* / physiology
  • Bone and Bones / metabolism*
  • Calcium / blood
  • Calcium, Dietary / administration & dosage
  • Calcium, Dietary / metabolism
  • Child
  • Diet, Ketogenic / adverse effects*
  • Epilepsy / complications
  • Epilepsy / diet therapy*
  • Female
  • Humans
  • Ketosis / metabolism*
  • Longitudinal Studies
  • Male
  • Nutritional Status
  • Osteoporosis / epidemiology
  • Osteoporosis / etiology
  • Vitamin D / administration & dosage
  • Vitamin D / blood


  • Calcium, Dietary
  • Vitamin D
  • 25-Hydroxyvitamin D 2
  • Calcium