Englander Institute for Precision Medicine

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

TitleConsuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.
Publication TypeJournal Article
Year of Publication2025
AuthorsNeth BJ, Huynh K, Giles C, Wang T, Mellett NA, Duong T, Blach C, Schimmel L, Register TC, Blennow K, Zetterberg H, Batra R, Schweickart A, Dilmore AHazel, Martino C, Arnold M, Krumsiek J, Han X, Dorrestein PC, Knight R, Meikle PJ, Craft S, Kaddurah-Daouk R
JournalCommun Med (Lond)
Volume5
Issue1
Pagination11
Date Published2025 Jan 09
ISSN2730-664X
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.

DOI10.1038/s43856-024-00682-w
Alternate JournalCommun Med (Lond)
PubMed ID39779882
PubMed Central IDPMC11711287
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
R01AG046171, RF1AG051550, RF1AG057452, R01AG059093, RF1AG058942, U01AG061359, U19AG063744 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
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
P30 AG049638 / AG / NIA NIH HHS / United States
#DAOU16AMPA / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
RF1 AG058942 / AG / NIA NIH HHS / United States
RF1 AG051550 / AG / NIA NIH HHS / United States

Weill Cornell Medicine Englander Institute for Precision Medicine 413 E 69th Street
Belfer Research Building
New York, NY 10021