Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity

J Cereb Blood Flow Metab. 2016 Sep;36(9):1603-13. doi: 10.1177/0271678X15610584. Epub 2015 Oct 13.


Cerebral metabolism of ketones after traumatic brain injury (TBI) improves neuropathology and behavior in an age-dependent manner. Neuroprotection is attributed to improved cellular energetics, although other properties contribute to the beneficial effects. Oxidative stress is responsible for mitochondrial dysfunction after TBI. Ketones decrease oxidative stress, increase antioxidants and scavenge free radicals. It is hypothesized that ketogenic diet (KD) will decrease post-TBI oxidative stress and improve mitochondria. Postnatal day 35 (PND35) male rats were given sham or controlled cortical impact (CCI) injury and placed on standard (STD) or KD. Ipsilateral cortex homogenates and mitochondria were assayed for markers of oxidative stress, antioxidant expression and mitochondrial function. Oxidative stress was significantly increased at 6 and 24 h post-injury and attenuated by KD while inducing protein expression of antioxidants, NAD(P)H dehydrogenase quinone 1 (NQO1) and superoxide dismutase (SOD1/2). Complex I activity was inhibited in STD and KD groups at 6 h and normalized by 24 h. KD significantly improved Complex II-III activity that was reduced in STD at 6 h. Activity remained reduced at 24 h in STD and unchanged in KD animals. These results strongly suggest that ketones improve post-TBI cerebral metabolism by providing alternative substrates and through antioxidant properties, preventing oxidative stress-mediated mitochondrial dysfunction.

Keywords: Traumatic brain injury; juvenile; ketogenic diet; mitochondria; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / analysis
  • Brain Injuries / diet therapy*
  • Brain Injuries / metabolism
  • Diet, Ketogenic*
  • Electron Transport Complex II / metabolism*
  • Electron Transport Complex III / metabolism*
  • Free Radicals / analysis
  • Ketones / metabolism
  • Male
  • Mitochondria / metabolism
  • Oxidative Stress*
  • Rats
  • Time Factors


  • Antioxidants
  • Free Radicals
  • Ketones
  • Electron Transport Complex II
  • Electron Transport Complex III