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Effects of Spermidine supplementation on cognition

Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer’s disease. Therefore, it is our primary goal to determine whether Spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of Spermidine intake on other neuropsychological, behavioral, and physiological parameters.
Spermidine and its implication in healthy aging
Given these observational findings, it has been hypothesized that external supply of polyamines may protect against age-related memory loss. Indeed, a first study in aging fruit flies showed that Spermidine-rich diet restored endogenous Spermidine levels and thereby rescued memory performance [30]. This beneficial effect of Spermidine intake appears to be mediated by several protective pathways [31]. For example, Spermidine may act through autophagy to regulate synaptic transmission/plasticity [32] and clear cellular “waste” including pathogenic protein aggregates [30]. Nutritional Spermidine is also associated with a number of cardio-protective [33] and anti-inflammatory [34] actions, which may help to preserve higher-order brain functions. Overall, these findings in aging model organisms have suggested a promising role of Spermidine in the promotion of brain and cognitive health.
Spermidine supplementation in older adults with SCD: initial evidence
Spermidine supplementation is thus proposed to open a new avenue in the protection and restoration of memory abilities in higher age. This expected benefit is of particular need in older individuals at risk for the development of dementia. It is, however, unknown whether the memory-promoting effect of Spermidine is detectable in humans and to what extent this effect may be attributed to the influence of Spermidine on biomarkers of healthy aging. An initial study showed that polyamine-enriched diet over 2 months increased blood Spermidine levels in healthy middle-aged men [35]. Our group has conducted a first 3-month phase IIa trial with nutritional Spermidine in 30 older adults with SCD (ClinicalTrials.gov identifier NCT02755246). Trial outcomes demonstrated high compliance, tolerance, and safety profiles as well as preliminary efficacy of the administered Spermidine-rich plant extract [36, 37]. Specifically, we found a moderate enhancement of memory performance, measured using the mnemonic similarity task (MST) [38], in the Spermidine-treated group compared with placebo intervention.

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