karppaus.info

MINI REVIEW article
Front. Nutr., 21 February 2024
Volume 11 - 2024 | https://doi.org/10.3389/fnut.2024.1266690

Ketogenic therapy towards precision medicine for brain diseases



Precision nutrition and nutrigenomics are emerging in the development of therapies for multiple diseases. The ketogenic diet (KD) is the most widely used clinical diet, providing high fat, low carbohydrate, and adequate protein. KD produces ketones and alters the metabolism of patients. Growing evidence suggests that KD has therapeutic effects in a wide range of neuronal diseases including epilepsy, neurodegeneration, cancer, and metabolic disorders. Although KD is considered to be a low-side-effect diet treatment, its therapeutic mechanism has not yet been fully elucidated. Also, its induced keto-response among different populations has not been elucidated. Understanding the ketone metabolism in health and disease is critical for the development of KD-associated therapeutics and synergistic therapy under any physiological background. Here, we review the current advances and known heterogeneity of the KD response and discuss the prospects for KD therapy from a precision nutrition perspective.

6 Conclusion
As an endogenous fuel that bridges metabolism to epigenetic regulation, the recent understanding of the function of ketones in both areas is encouraging for the development of new drugs for these previously identified “incurable diseases.” The benefits of ketogenic intervention in clinical practice are thusly highlighting its therapeutic potential for multiple brain diseases. Ketogenic intervention can be simply achieved through an associated diet that is relatively affordable and accessible. Growing evidence suggests that KD has a therapeutic effect on a wide range of human diseases, such potential makes KD an encouraging therapeutic strategy for many brain diseases. Being a low-side-effect treatment, elucidation of its therapeutic mechanism is a promising topic in the development of novel biotechnological drugs and synergistic therapy. However, the mechanism of KD benefits is still not fully understood, despite some evidence indicating its multiple targets and ability to regulate histone deacetylase, glycolysis, neurotransmitter levels, the function of NLRP3 inflammasome, and oxidative stress.

Moreover, KD is not suitable for all diseases and even the ratio difference in the KD formula may lead to unexpected therapeutic outcomes, thus increasing the need for precision nutrition and nutrigenomics research. A recent study revealed a distinct cell type–specific KD response in the brain: metabolic plasticity is found in astrocytes and neurons, but not in oligodendrocytes (129), which highlights the importance of narrowing the variation in KD responses. Available standards for clinical KD therapies are still very limited, and a certain level of precision nutrition is required as KD moves into clinical translation. Further studies to identify the clear mechanisms of KD and drug interactions, different KD responses in heterogeneous patient backgrounds, and clear mechanisms of KD intervention in the fight against numerous specific central nervous system diseases are crucial. In addition, in clinical applications, precision nutrition should also be considered as slight changes in dietary composition could impact/ameliorate the potential side effects of KD in certain populations.