Sarah Rice BSc. (Hons), MCOptom (UK), MHP, NNP
Neuroinflammation is a common underlying feature of many neurological disorders, which may include neurodegenerative, psychiatric and trauma-related conditions. While there are many factors that contribute to these conditions, studies are emerging that show common themes in the pathophysiology, which include brain hypometabolism, immune responses, and inflammatory processes.
Recent work demonstrates emerging interest in ketogenic diet applications in a range of neurological disorders where neuroinflammation is a key feature.
Monda et al. discuss the role of inflammation in triggering immune responses, which can be influenced by various factors such as environmental (diet, exposure to infections, gut dysbiosis, etc.) and genetic vulnerability (eg, apoe4 mutations).
Astrocytes, microglia and resident macrophages are the main drivers of neuroinflammation through their function as immune cells. Proliferation and activation of these cells contributes to the release of inflammatory mediators. When immune processes fail to resolve inflammation, a chronic inflammatory state ensues, leading to neuronal toxicity and, in the case of neurodegeneration, possibly promoting protein aggregation. In this chronic setting, proinflammatory cytokines (eg, interleukin-6 and TNFalpha) can contribute to impaired mitochondrial function and reduced brain energy metabolism.
A ketogenic state allows the production of ketone bodies, which are able to modulate immune responses by various cells, including astrocytes, T-cells, and dendritic cells, by reducing activation and polarization. Dietary ketosis promotes an anti-inflammatory macrophage phenotype and modulates microglial activity to resolve inflammation and promote tissue repair.
The anti-inflammatory and antioxidant properties of β-hydroxybutyrate have been shown to reduce oxidative stress and reduce neuroinflammation in the setting of cerebral hemorrhage. In a study by Zhang et al., markers of oxidative stress and C-reactive protein (CRP, a marker of inflammation) were measured in a group of patients receiving a ketogenic diet as a therapeutic intervention after cerebral hemorrhage. Patients in the intervention group showed significantly lower levels of CRP and oxidative stress compared to the control group, indicating lower inflammation—an important component of a successful recovery. The ketogenic diet group also showed improved cognitive function, lower depression scores and increased physical activity, which were not seen in the control group.
Ketone bodies provide an efficient fuel source for the brain, increasing mitochondrial function, reducing inflammation and oxidative stress, and increasing BDNF levels, which is important for neuronal health and neuroplasticity. These mechanisms support the repair of brain damage.
Another recent study by Perlman et al. found that a ketogenic intervention improved sleep quality in people with multiple sclerosis by reducing daytime sleepiness. Poor sleep is associated with an increased pro-inflammatory state through cytokine release and activation of astrocytes and microglia, key features of MS pathophysiology. The ketogenic diet has been found to improve sleep quality, unexplained by weight loss or sleep duration, suggesting alternative mechanisms of action by which the sleep cycle is improved.
Finally, two papers in the last month talk about the role of neuroinflammation in psychiatric diseases. Laurent et al. Explore the role of the ketogenic diet in clinical psychology, as well as the ability of a ketogenic metabolic state to reduce inflammation, modulate neurotransmitters, improve mitochondrial function, reduce oxidative stress, and moderate cerebral glucose hypometabolism. These are key features of neurological and psychiatric conditions. Frank et al. Also consider the contribution of neuroinflammation to anxiety and comment on research that found elevated markers of inflammation in patients with anorexia nervosa (AN). Potential neurobiological mechanisms through which the ketogenic diet may alleviate AD symptoms are discussed.
Taken together, these emerging streams of evidence strongly suggest that a ketogenic diet can improve conditions where neuroinflammation is a key feature.
The Neurology section and the Metabolic Psychiatry section of the Nutrition Network reference resource have an extensive list where you can read more about the application of therapeutic carbohydrate restriction (TCR) for neurological disorders.
The Nutrition Network offers educational modules where you can learn more about TCR for these applications.
- Monda, A. et al. (2024) ‘Exploring the Potential of the Ketogenic Diet in Reducing Neuroinflammation and Modulating Immune Responses’, Frontiers in Immunology, 15. Available at: https://doi.org/10.3389/fimmu.2024.1425816.
- Perlman, J. et al. (2024) ‘Effect of a ketogenic diet on sleep quality in people with relapsing multiple sclerosis’, Sleep Medicine, 122, pp. 213–220. Available in: https://doi.org/10.1016/j.sleep.2024.08.2020.
- Zhang, X. and Liu, Q. (2024) ‘Ketogenic Diet as a Therapeutic Intervention in Cerebral Hemorrhage Recovery’, Current Topics in Nutraceutical Research, 22(3), pp. 993–999. Available in: https://doi.org/10.37290/ctnr2641-452X.22:993-999.
- Laurent, N. et al. (2024) ‘Ketogenic diets in clinical psychology: a review of the evidence and implications for practice’. Frontiers in Psychology15. Available at: https://doi.org/10.3389/fpsyg.2024.1468894.
- Frank, GKW and Scolnick, B. (2024) ‘Therapeutic ketogenic diet as a treatment for anorexia nervosa’, Frontiers in Nutrition11. Available at: https://doi.org/10.3389/fnut.2024.1392135.
