Study Links 14 Blood Metabolites to Midlife Cognition as Antacids Cut Ergothioneine by 31.5%
Updated
Updated · Nature.com · Jun 24
Study Links 14 Blood Metabolites to Midlife Cognition as Antacids Cut Ergothioneine by 31.5%
3 articles · Updated · Nature.com · Jun 24
Summary
In 1,082 dementia-free middle-aged adults, researchers linked 14 blood metabolites to cognition and 22 to MRI brain measures, with ergothioneine showing the strongest positive association with cognitive performance.
Replication in older cohorts supported the signal: all 14 cognition-linked metabolites held up in at least one external test, and the overall metabolite pattern tracked future Alzheimer’s risk in 1,229 participants.
Lifestyle, clinical factors and medication explained more of these metabolite levels than genetics or gut microbes, accounting for up to 28.6% of variance; smoking, BMI, alcohol use, diabetes and antidiabetic therapy were key drivers.
Antacid use stood out because it was tied to lower ergothioneine and worse cognition, with mediation analysis suggesting reduced ergothioneine explained 31.5% of the drug’s negative cognitive association.
The authors say the findings point to potentially modifiable metabolic pathways for Alzheimer’s prevention, but stress the largely cross-sectional data cannot prove causation or justify changing prescribing practice yet.
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Landmark 2024-2025 Study: Antacid Use Reduces Ergothioneine, Mediating 31.5% of Cognitive Decline in Midlife Adults
Overview
A major study published in 2026 by Ahmad and colleagues has advanced our understanding of midlife cognitive health by exploring how blood metabolites relate to brain function. The research found that ergothioneine, a diet-derived antioxidant, is strongly linked to better cognitive performance in midlife, and this finding was confirmed in multiple study groups. The study also showed that common factors like genetics, gut microbiome, lifestyle, and especially medication use—such as antacids—can influence these important metabolites. These insights highlight new ways to detect early signs of cognitive decline and suggest possible strategies for prevention and intervention.