Spermidine Human Trial Results Fail to Impress

The results of a human clinical trial for spermidine against cognitive decline have recently been published, but the results are not positive.

What is spermidine?

Spermidine is a polyamine, meaning it has two or more primary amino groups. It is naturally occurring and is widely encountered in ribosomes and living tissues. It plays a critical role in cell function and survival.

The spermidine clinical trial

Researchers set out to test if supplementation with spermidine has a beneficial effect on memory and potential effects against age-related cognitive decline.

In this randomized trial, 100 adults aged 60 to 90 years were given either spermidine or a microcrystalline cellulose placebo. The test and placebo groups were of equal size. The main criteria for trial participation was subjective cognitive decline (SCD).

SCD describes a feeling of persistent cognitive decline in cognitively healthy older persons. In a nutshell, it is the self-reported perception of worsening of memory or, more frequently, confusion. It is a form of cognitive impairment and thought to be an early sign of Alzheimer’s disease and similar dementias.

The primary endpoint was a change in memory performance when compared to pre-trial baseline levels. The researchers also looked at additional neuropsychological, behavioral, and physiological parameters as a secondary way to determine positive changes.

Unfortunately, the researchers concluded that supplementation with spermidine did not modify memory performance or biomarkers compared with the placebo group. They noted that “Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage”.

What could have gone wrong?

The researchers do propose potential reasons that these results failed to impress.

The daily dose of 0.9 milligrams may have been too low to elicit significant effects on memory or the secondary biomarkers examined.

The test subjects had SCD, but at that point, cognitive function is essentially normal. It is possible that spermidine does not act as a memory booster but instead protects against memory decline. If this turns out to be the case, then that would explain the lack of results in SCD participants.

The other consideration is that biomarkers for Alzheimer’s disease, such as amyloid, tau, and phosphorylated tau, were not examined or required for trial participation. The researchers suggest that many of the participants did not have amyloid or tau pathology. That could mean that their cognitive decline may be due to other reasons and may not be amenable to dietary interventions.

Abstract

Importance: Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline.

Objective: To determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group.

Outcome: In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.

Conclusion

While the results of this particular study and its design were not positive, further studies are still needed to address the issues that it raised.