Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity
Open accessAbstract
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.
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A ketogenic diet mediates its neuroprotective function through the attenuation of oxidative stress and induction of protein expression of antioxidants.
“Moreover, a ketogenic diet mediates its neuroprotective function through the attenuation of oxidative stress and induction of protein expression of antioxidants (Greco et al., 2016), as well as the modulation of neurotransmitter levels such as GABA, monoamines and glutamate (Hartman et al., 2007;Yudkoff et al., 2008).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Greco et al., 2016
The Discussion reports reduced oxidative stress after traumatic brain injury, and the antioxidant-protein results report increased NQO1 and SOD expression with the ketogenic diet. The Summary limits these improvements to juvenile (PND35) animals and says they were not observed in adult (PND70) animals, so the unqualified claim is broader than the findings. (LLM, conf=0.88)
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- Authors
- Greco, T., Glenn, T. C., Hovda, D. A., & Prins, M. L.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Greco, Tiffany
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2016-07-22
- Volume
- 36
- Issue
- 9
- Pages
- 1603-1613
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC5012517
- OpenAlex
- W2285042112
- Cited by
- 210
- References
- 43
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 27 · 2023: 18 · 2022: 24 · 2021: 28 · 2020: 22 · 2019: 15 · 2018: 13 · 2017: 6 · 2016: 7
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NFL Charities
- Brain Injury Research Center
- Topics
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- ketogenic diet, traumatic brain injury, oxidative stress, mitochondrial dysfunction, respiratory chain complexes, ketone body metabolism, neuroprotection, antioxidant enzymes, NQO1, superoxide dismutase, controlled cortical impact, brain metabolism
- MeSH terms
- Animals, Antioxidants, Brain Injuries, Free Radicals, Ketones, Male, Mitochondria, Time Factors, Electron Transport Complex III, Oxidative Stress, Electron Transport Complex II, Rats, Diet, Ketogenic
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