Low-grade chronic metabolic acidosis is a contributory mechanism in the development of chronic epilepsy

Epilepsy Behav. 2006 Mar;8(2):347-9. doi: 10.1016/j.yebeh.2005.11.012. Epub 2006 Feb 3.


In most people with epilepsy, the condition is readily controlled, but 20-30% develop chronic epilepsy. An estimated 80,000 patients with epilepsy require ongoing specialist care in the United Kingdom. Nutrition may be a factor in the development of chronic epilepsy. Modern Western diets are thought to produce a low-grade chronic metabolic acidosis. The hydrogen ion, H+, is a potent modulator of NMDA-activated currents, and in cultured neurons, increased external [H+] strongly suppresses these currents. The effect of chronic metabolic acidosis in vivo has not been fully studied. It is possible that low-grade chronic metabolic acidosis chronically inhibits the NMDA-activated currents, and this may lead to upregulation of the NMDA receptor. This would result in a greater hyperexcitable state and may contribute to the development of chronic epilepsy.

MeSH terms

  • Acidosis / complications*
  • Acidosis / metabolism
  • Anticonvulsants / therapeutic use*
  • Brain / metabolism
  • Carbonic Anhydrase Inhibitors / therapeutic use*
  • Chronic Disease
  • Diet / adverse effects
  • Epilepsy / diet therapy
  • Epilepsy / drug therapy
  • Epilepsy / etiology*
  • Humans
  • Ketosis / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Anticonvulsants
  • Carbonic Anhydrase Inhibitors
  • Receptors, N-Methyl-D-Aspartate