Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humans
Abstract Background Alzheimer’s disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying m...
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Nature Portfolio
2025-01-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00682-w |
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| author | Bryan J. Neth Kevin Huynh Corey Giles Tingting Wang Natalie A. Mellett Thy Duong Colette Blach Leyla Schimmel Thomas C. Register Kaj Blennow Henrik Zetterberg Richa Batra Annalise Schweickart Amanda Hazel Dilmore Cameron Martino Matthias Arnold Jan Krumsiek Xianlin Han Pieter C. Dorrestein Rob Knight Peter J. Meikle Suzanne Craft Rima Kaddurah-Daouk |
| author_facet | Bryan J. Neth Kevin Huynh Corey Giles Tingting Wang Natalie A. Mellett Thy Duong Colette Blach Leyla Schimmel Thomas C. Register Kaj Blennow Henrik Zetterberg Richa Batra Annalise Schweickart Amanda Hazel Dilmore Cameron Martino Matthias Arnold Jan Krumsiek Xianlin Han Pieter C. Dorrestein Rob Knight Peter J. Meikle Suzanne Craft Rima Kaddurah-Daouk |
| author_sort | Bryan J. Neth |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear. Method In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform. Results Here we identified substantial changes in response to MMKD intervention, aside from metabolic changes associated with a ketogenic diet, we identified a a global elevation across all plasmanyl and plasmenyl ether lipid species, with many changes linked to clinical and biochemical markers of AD. We further validated our findings by leveraging our prior clinical studies into lipid related changeswith AD (n = 1912), and found that the lipidomic signature with MMKD was inversely associated with the lipidomic signature of prevalent and incident AD. Conclusions Intervention with a MMKD was able to alter the plasma lipidome in ways that contrast with AD-associated patterns. Given its low risk and cost, MMKD could be a promising approach for prevention or early symptomatic treatment of AD. |
| format | Article |
| id | doaj-art-1d683ff91c3b4ab8869f7b492b29745e |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-1d683ff91c3b4ab8869f7b492b29745e2025-01-12T12:37:15ZengNature PortfolioCommunications Medicine2730-664X2025-01-015111510.1038/s43856-024-00682-wConsuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humansBryan J. Neth0Kevin Huynh1Corey Giles2Tingting Wang3Natalie A. Mellett4Thy Duong5Colette Blach6Leyla Schimmel7Thomas C. Register8Kaj Blennow9Henrik Zetterberg10Richa Batra11Annalise Schweickart12Amanda Hazel Dilmore13Cameron Martino14Matthias Arnold15Jan Krumsiek16Xianlin Han17Pieter C. Dorrestein18Rob Knight19Peter J. Meikle20Suzanne Craft21Rima Kaddurah-Daouk22Department of Neurology, Mayo ClinicBaker Heart and Diabetes Institute, 75 Commercial RoadBaker Heart and Diabetes Institute, 75 Commercial RoadBaker Heart and Diabetes Institute, 75 Commercial RoadBaker Heart and Diabetes Institute, 75 Commercial RoadBaker Heart and Diabetes Institute, 75 Commercial RoadDuke Molecular Physiology Institute, Duke UniversityDepartment of Psychiatry and Behavioral Sciences, Duke UniversityDepartment of Pathology – Comparative Medicine, Wake Forest University School of MedicineDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of GothenburgDepartment of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell MedicineDepartment of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell MedicineDepartment of Pediatrics, University of California San DiegoDepartment of Pediatrics, University of California San DiegoDepartment of Psychiatry and Behavioral Sciences, Duke UniversityDepartment of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell MedicineBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San AntonioSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San DiegoDepartments of Pediatrics, Computer Science and Engineering, Bioengineering, University of California San DiegoBaker Heart and Diabetes Institute, 75 Commercial RoadDepartment of Gerontology and Geriatric Medicine, Wake Forest University School of MedicineDepartment of Psychiatry and Behavioral Sciences, Duke UniversityAbstract Background Alzheimer’s disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear. Method In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform. Results Here we identified substantial changes in response to MMKD intervention, aside from metabolic changes associated with a ketogenic diet, we identified a a global elevation across all plasmanyl and plasmenyl ether lipid species, with many changes linked to clinical and biochemical markers of AD. We further validated our findings by leveraging our prior clinical studies into lipid related changeswith AD (n = 1912), and found that the lipidomic signature with MMKD was inversely associated with the lipidomic signature of prevalent and incident AD. Conclusions Intervention with a MMKD was able to alter the plasma lipidome in ways that contrast with AD-associated patterns. Given its low risk and cost, MMKD could be a promising approach for prevention or early symptomatic treatment of AD.https://doi.org/10.1038/s43856-024-00682-w |
| spellingShingle | Bryan J. Neth Kevin Huynh Corey Giles Tingting Wang Natalie A. Mellett Thy Duong Colette Blach Leyla Schimmel Thomas C. Register Kaj Blennow Henrik Zetterberg Richa Batra Annalise Schweickart Amanda Hazel Dilmore Cameron Martino Matthias Arnold Jan Krumsiek Xianlin Han Pieter C. Dorrestein Rob Knight Peter J. Meikle Suzanne Craft Rima Kaddurah-Daouk Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humans Communications Medicine |
| title | Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humans |
| title_full | Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humans |
| title_fullStr | Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humans |
| title_full_unstemmed | Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humans |
| title_short | Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer’s disease in humans |
| title_sort | consuming a modified mediterranean ketogenic diet reverses the peripheral lipid signature of alzheimer s disease in humans |
| url | https://doi.org/10.1038/s43856-024-00682-w |
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