Sarah Rice BSc. (Hons), MCOptom (UK), MHP, NNP

Neuroinflammation is a common underlying feature of many neurological disorders, which can include neurodegenerative, psychiatric, and trauma-related conditions. While there are many factors that contribute to these conditions, studies are emerging that point to common themes in the pathophysiology, which include brain hypometabolism, immune responses, and inflammatory processes.

Recent papers demonstrate the emerging interest in ketogenic diet applications across a range of neurological disorders where neuroinflammation is a key feature.

Monda et al. discuss the role of inflammation in the triggering of immune responses, which may be influenced by a number of factors including environmental (nutrition, infection exposure, gut dysbiosis, etc.) and genetic vulnerability (e.g., apoe4 mutations).

Astrocytes, microglia, and resident macrophages are the primary drivers of neuroinflammation via their function as immune cells. Poliferation and activation of these cells contribute 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 (e.g., interleukin-6 and TNFalpha) can contribute to impaired mitochondrial function and reduced brain energy metabolism.

A ketogenic state enables the production of ketone bodies, which are able to  modulate immune responses from various cells, including astrocytes, T-cells, and dendritic cells, decreasing activation and polarisation. Nutritional ketosis promotes an anti-inflammatory macrophage phenotype and modulates the microglial activity to resolve inflammation and promote tissue repair.

The anti-inflammatory and anti-oxidant properties of beta-hydroxybutyrate have been shown to decrease oxidative stress and reduce neuroinflammation in the setting of cerebral heamorrhage. 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 given a ketogenic diet as a therapeutic intervention following cerebral heamorrhage. Patients in the intervention group demonstrated 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 experienced improved cognitive function, lower depression scores, and increased physical activity, which were not noted in the control group.

Ketone bodies provide an efficient fuel source for the brain, increasing mitochondrial function, reducing inflammation and oxidative stress, and increasing levels of BDNF, which is important for neuronal health and neuroplasticity. These mechanisms support brain injury recovery.

Another recent study by Perlman et al. found a ketogenic intervention improved sleep quality in people with multiple sclerosis, reducing daytime sleepiness. Poor sleep is associated with an increased proinflammatory state via the release of cytokines and activation of astrocytes and microglia, key features of MS pathophysiology. The ketogenic diet has been found to improve sleep quality, not explained by weight loss or sleep duration, indicating alternative mechanisms of action whereby the sleep cycle is improved. 

Finally, two papers in the last month speak to the role of neuroinflammation in psychiatric conditions. Laurent et al. investigate the role of ketogenic diets 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 mitigate cerebral glucose hypometabolism. These are key features of neurological and psychiatric conditions. Frank et al. also examine the contribution of neuroinflammation to anxiety and comment on research finding elevated inflammatory markers in patients with anorexia nervosa (AN). Potential neurobiological mechanisms through which the ketogenic diet may mitigate symptoms of AN are discussed.

Taken together, these emerging streams of evidence strongly suggest that a ketogenic diet can improve conditions where neuroinflammation is a core feature. 

Further resources

The neurology section and metabolic psychiatry section of the Nutrition Network reference resource have an extensive listing where you can read more about the application of therapeutic carbohydrate restriction (TCR) for neurological disorders. 

Nutrition Network offers training modules where you can learn more about TCR for these applications.

References

1. Monda, A. et al. (2024) ‘Exploring the ketogenic diet’s potential in reducing neuroinflammation and modulating immune responses’, Frontiers in Immunology, 15. Available at: https://doi.org/10.3389/fimmu.2024.1425816.
2. Perlman, J. et al. (2024) ‘Impact of a ketogenic diet on sleep quality in people with relapsing multiple sclerosis’, Sleep Medicine, 122, pp. 213–220. Available at: https://doi.org/10.1016/j.sleep.2024.08.020.
3. 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 at: https://doi.org/10.37290/ctnr2641-452X.22:993-999.
4. Laurent, N. et al. (2024) ‘Ketogenic diets in clinical psychology: examining the evidence and implications for practice’, Frontiers in Psychology, 15. Available at: https://doi.org/10.3389/fpsyg.2024.1468894.
5. Frank, G.K.W. and Scolnick, B. (2024) ‘Therapeutic ketogenic diet as treatment for anorexia nervosa’, Frontiers in Nutrition, 11. Available at: https://doi.org/10.3389/fnut.2024.1392135.