Walnuts and brain aging: metabolites associated with better-preserved cortical thickness

An analysis of 104 participants followed for two years

The WAHA trial compared daily walnut consumption for two years with a control diet. This substudy includes 104 participants from the Barcelona center who underwent structural MRI at the beginning and end of follow-up.

The researchers measured urinary concentrations of urolithins, metabolites produced by the gut microbiota from ellagitannins found in walnuts. They then looked for associations between changes in these concentrations and changes in cortical thickness, using adjusted statistical models.

The analyses also accounted for participants’ metabotype, a classification related to individual differences in urolithin production.

A signal observed mainly in certain brain regions

Among the 55 participants in the walnut group, greater increases in urolithin A, urolithin C and a glucuronide conjugate of the latter were associated with better preservation of cortical thickness. The associations mainly involved regions of the right hemisphere and were stronger in people with metabotype B.

Cortical thickness is a biomarker used to study age-related neurodegeneration. Its preservation alone, however, does not establish a noticeable benefit for cognitive abilities. The abstract provided reports no findings on memory or dementia risk.

The trial is randomized, but the association does not prove causation

The distinction matters: dietary assignment was randomized, but increases in urolithins were not. Linking changes in these metabolites to changes in the cortex therefore remains an association analysis, even within a clinical trial.

These findings support a line of research into how responses to the same food differ depending on the gut microbiota. They demonstrate neither that urolithins cause the observed preservation nor that a urolithin supplement would reproduce this association. The abstract also provides no direct comparison that would allow a conclusion here that walnuts have a protective effect compared with the control diet.

What we can take away

This study links certain walnut metabolites to a better-preserved brain marker. It does not demonstrate that eating walnuts or taking urolithins prevents cognitive decline.