Englander Institute for Precision Medicine

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

TitleSerum and CSF metabolomics analysis shows Mediterranean Ketogenic Diet mitigates risk factors of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2024
AuthorsSchweickart A, Batra R, Neth BJ, Martino C, Shenhav L, Zhang AR, Shi P, Karu N, Huynh K, Meikle PJ, Schimmel L, Dilmore AHazel, Blennow K, Zetterberg H, Blach C, Dorrestein PC, Knight R, Craft S, Kaddurah-Daouk R, Krumsiek J
Corporate AuthorsAlzheimer’s Gut Microbiome Project Consortium
JournalNPJ Metab Health Dis
Volume2
Issue1
Pagination15
Date Published2024
ISSN2948-2828
Abstract

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.

DOI10.1038/s44324-024-00016-3
Alternate JournalNPJ Metab Health Dis
PubMed ID38962750
PubMed Central IDPMC11216994
Grant ListR01 AG046171 / AG / NIA NIH HHS / United States
R01 AG069901 / AG / NIA NIH HHS / United States
U19 AG063744 / AG / NIA NIH HHS / United States
P30 AG049638 / AG / NIA NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
RF1 AG059093 / AG / NIA NIH HHS / United States
U01 AG061359 / AG / NIA NIH HHS / United States
RF1 AG057452 / AG / NIA NIH HHS / United States
RF1 AG058942 / AG / NIA NIH HHS / United States
RF1 AG051550 / AG / NIA NIH HHS / United States

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