- Liittynyt
- 17.8.2006
- Viestejä
- 16 384
Genetic and Epigenetic Modifiers of Ketogenic Diet Responses: Roles of Sex and Age
Abstract
The ketogenic diet (KD) is a metabolic intervention characterized by high fat and very low carbohydrate intake, showing significant metabolic, neuroprotective, and therapeutic ef fects. However, its efficacy varies widely due to individual genetic and epigenetic factors. This review synthesizes current knowledge of genes most strongly associated with KD response, including polymorphisms in FTO, APOA2, PPAR, SCN1A, KCNQ2, STXBP1, CDKL5, the MODY gene group, and SLC2A1, which shape outcomes across lipid metab olism, energy expenditure, inflammation, and neurotransmission. Epigenomic modifica tions induced by a KD, such as changes in DNA methylation and histone acetylation in volving BDNF, SLC12A5, KLF14, and others, modulate functional metabolic and neuro logical effects. Sex and age further modulate KD effects through distinct patterns of gene activation and hormonal interactions. These variables together impact metabolic and neu rological outcomes and are critical for developing personalized nutrition and disease management strategies. Based on the reviewed evidence, genetic and epigenetic profiling can help identify patients who are likely to benefit from a KD (e.g., GLUT1DS, PDH defi ciency) and those in whom a KD may be ineffective or harmful (e.g., SCOT or SLC2A1 independent defects). The review concludes that genetic and epigenetic profiling is rec ommended for personalized dietary interventions
Conclusions
The ketogenic diet offers a broad range of benefits for metabolic and neurological health, but its effectiveness strongly depends on an individual’s genetic and epigenetic context, as well as sex and age. A personalized nutritional approach considering these factors is essential to optimize therapeutic outcomes of a KD. It should be explicitly cau tioned that broad epigenetic profiling is not yet ready for routine clinical decision-making and should currently be applied within research or highly specialized centers, ideally in conjunction with standardized KD phenotyping and long-term follow-up. Further re search is needed to clarify molecular mechanisms and establish guidelines for safe and effective KD application in diverse populations with different genetic profiles. This ap proach could enable targeted use of the KD for prevention and treatment of metabolic and neurodegenerative diseases in the future.
www.mdpi.com/2673-4168/5/4/92
Abstract
The ketogenic diet (KD) is a metabolic intervention characterized by high fat and very low carbohydrate intake, showing significant metabolic, neuroprotective, and therapeutic ef fects. However, its efficacy varies widely due to individual genetic and epigenetic factors. This review synthesizes current knowledge of genes most strongly associated with KD response, including polymorphisms in FTO, APOA2, PPAR, SCN1A, KCNQ2, STXBP1, CDKL5, the MODY gene group, and SLC2A1, which shape outcomes across lipid metab olism, energy expenditure, inflammation, and neurotransmission. Epigenomic modifica tions induced by a KD, such as changes in DNA methylation and histone acetylation in volving BDNF, SLC12A5, KLF14, and others, modulate functional metabolic and neuro logical effects. Sex and age further modulate KD effects through distinct patterns of gene activation and hormonal interactions. These variables together impact metabolic and neu rological outcomes and are critical for developing personalized nutrition and disease management strategies. Based on the reviewed evidence, genetic and epigenetic profiling can help identify patients who are likely to benefit from a KD (e.g., GLUT1DS, PDH defi ciency) and those in whom a KD may be ineffective or harmful (e.g., SCOT or SLC2A1 independent defects). The review concludes that genetic and epigenetic profiling is rec ommended for personalized dietary interventions
Conclusions
The ketogenic diet offers a broad range of benefits for metabolic and neurological health, but its effectiveness strongly depends on an individual’s genetic and epigenetic context, as well as sex and age. A personalized nutritional approach considering these factors is essential to optimize therapeutic outcomes of a KD. It should be explicitly cau tioned that broad epigenetic profiling is not yet ready for routine clinical decision-making and should currently be applied within research or highly specialized centers, ideally in conjunction with standardized KD phenotyping and long-term follow-up. Further re search is needed to clarify molecular mechanisms and establish guidelines for safe and effective KD application in diverse populations with different genetic profiles. This ap proach could enable targeted use of the KD for prevention and treatment of metabolic and neurodegenerative diseases in the future.
www.mdpi.com/2673-4168/5/4/92