A Modified Mediterranean Ketogenic Diet mitigates modifiable risk factors of Alzheimer's Disease: a serum and CSF-based metabolic analysis.

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 10021, USA., Batra R; Department of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY 10021, USA., Neth BJ; Department of Neurology, Mayo Clinic, Rochester, MN., Martino C; Department of Pediatrics, University of California San Diego, La Jolla, CA., 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, 7008 Tasmania, 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., 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., Knight R; Departments of Pediatrics, Computer Science and Engineering, Bioengineering, University of California San Diego, La Jolla, CA., 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 10021, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Nov 27. Date of Electronic Publication: 2023 Nov 27.
DOI:	10.1101/2023.11.27.23298990
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: Conflicts of interest Dr. Krumsiek holds equity in Chymia LLC and iollo, owns intellectual property in PsyProtix, and serves as an advisor for celeste. Annalise Schweickart is a co-founder of celeste. Dr. Kaddurah-Daouk in an inventor on a series of patents on use of metabolomics for the diagnosis and treatment of CNS diseases and holds equity in Metabolon Inc., Chymia LLC and PsyProtix.
Databáze:	MEDLINE
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