No improvement in memory, biomarkers with spermidine supplement compared with placebo

Long-term supplementation with spermidine improved neither memory function nor biomarkers compared with placebo in older adults with subjective cognitive decline, according to results of a clinical trial published in JAMA Network Open.

“Maintenance of cognitive function and brain health are of utmost importance in an aging society with an increase in age-related diseases, such as Alzheimer’s disease,” Claudia Schwarz, PhD, of the department of neurology at Charité University Medicine Berlin, and colleagues wrote.

Schwarz and fellow researchers sought to determine the effect of long-term spermidine on memory performance and biomarkers in older adults with subjective cognitive decline and those at risk for developing AD.

They conducted a 12-month randomized, double-masked, placebo-controlled phase 2b trial at the NeuroCure Clinical Research Center between January 2017 and May 2020 and enrolled 100 participants, aged 60 to 90 years, who were randomized on a 1:1 basis to dietary supplementation with either a wheat germ-based supplement (0.9 mg per day of spermidine) or microcrystalline cellulose placebo. The primary outcome was change in memory performance from baseline to 12-month postintervention assessment, operationalized by mnemonic discrimination performance via the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral and physiological parameters.

Of the initial cohort of 100 participants, 89% completed the trial intervention. Over 12 months, researchers observed no significant changes in mnemonic discrimination performance (between-group difference = 0.03; 95% CI, 0.11 to 0.05) and secondary outcomes. Exploratory analyses revealed possible beneficial effects of the supplement on inflammation and verbal memory, which should be validated in future studies at higher doses.

“Supplementation with spermidine that increased daily supply by about 10% did not result in a beneficial effect on memory function or other neuropsychological, behavioral or physiological parameters,” Schwarz and colleagues wrote.