The therapeutic potential of a calorie-restricted ketogenic diet for the management of Leber hereditary optic neuropathy

Nutr Neurosci. 2019 Mar;22(3):156-164. doi: 10.1080/1028415X.2017.1368170. Epub 2017 Oct 10.


Leber hereditary optic neuropathy (LHON) is a maternally inherited, bilateral, sequential optic neuropathy that usually affects young males. LHON arises from a defect in complex I of the oxidative phosphorylation chain that generates increased reactive oxygen species and causes a decline in cellular ATP production. There exists no cure at present for LHON. Asymptomatic LHON mutation carriers show signs of increased mitochondrial biogenesis that may compensate for the compromise in complex I activity. Partial recovery in LHON is associated with a wider optic disc diameter and a younger age at disease onset, which may allow for greater mitochondrial bioenergetic capacity. Rescuing a mitochondrial bioenergetic deficit soon after disease onset may improve the chances of recovery and reduce visual loss in the second eye. We here propose that a calorie-restricted ketogenic diet has the potential to enhance mitochondrial bioenergetic capacity and should be explored as a potential therapeutic option for treating LHON.

Keywords: Complex I; Ketogenic diet; Leber hereditary optic neuropathy; Mitochondrial disorders; Neurodegeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Catalase / metabolism
  • Diet, Ketogenic*
  • Glutathione / metabolism
  • Humans
  • Mitochondria / metabolism
  • Optic Atrophy, Hereditary, Leber / diet therapy*
  • Optic Atrophy, Hereditary, Leber / metabolism*
  • Reactive Oxygen Species / metabolism


  • Reactive Oxygen Species
  • Catalase
  • Glutathione