Serum and CSF metabolomics analysis shows Mediterranean Ketogenic Diet mitigates risk factors of Alzheimer's disease.

Autor: Schweickart A; Tri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY USA., Batra R; Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY USA., Neth BJ; Department of Neurology, Mayo Clinic, Rochester, MN USA., Martino C; Department of Pediatrics, University of California San Diego, La Jolla, CA USA., Shenhav L; Department of Microbiology, New York University Grossman School of Medicine, New York, NY USA., Zhang AR; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC USA., Shi P; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC USA., Karu N; Tasmanian Independent Metabolomics and Analytical Chemistry Solutions (TIMACS), Hobart, TAS Australia., Huynh K; Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC Australia.; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Bundoora, VIC Australia., Meikle PJ; Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC Australia.; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Bundoora, VIC Australia., Schimmel L; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC USA., Dilmore AH; Department of Pediatrics, University of California San Diego, La Jolla, CA USA., Blennow K; Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden., Zetterberg H; Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden., Blach C; Duke Molecular Physiology Institute, Duke University, Durham, NC USA., Dorrestein PC; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA USA., Knight R; Departments of Pediatrics, Computer Science and Engineering, Bioengineering, University of California San Diego, La Jolla, CA USA., Craft S; Department of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston Salem, NC USA., Kaddurah-Daouk R; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC USA.; Duke Institute of Brain Sciences, Duke University, Durham, NC USA.; Department of Medicine, Duke University, Durham, NC USA., Krumsiek J; Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY USA.
Jazyk: angličtina
Zdroj: NPJ metabolic health and disease [NPJ Metab Health Dis] 2024; Vol. 2 (1), pp. 15. Date of Electronic Publication: 2024 Jul 01.
DOI: 10.1038/s44324-024-00016-3
Abstrakt: Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean Ketogenic Diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.
Competing Interests: Competing interestsP.C.D. consulted for DSM animal health in 2023, is an advisor and holds equity in Cybele, bileOmix and Sirenas, and a Scientific co-founder, advisor and holds equity in Ometa, Enveda, and Arome with prior approval by UC San Diego. K.B. has served as a consultant and on advisory boards for Abbvie, AC Immune, ALZPath, AriBio, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; has served on data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper.
(© The Author(s) 2024.)
Databáze: MEDLINE
Externí odkaz: