Neuroprotective effects of spermidine – Evidence in humans
In addition to the now very solid preclinical evidence in various animal models for spermidine as a neuroprotective molecule, more and more human studies are being conducted.
In 2018, a group of researchers at the Charite Hospital in Berlin, Germany, investigated in a pilot study in humans, the so-called PreSmartAge study, whether spermidine could exert a positive influence on memory performance in patients with mild cognitive impairment . For this purpose, 30 participants between 60 and 80 years of age who suffered from self-assessed but not yet clinically manifested loss of memory function were recruited for a randomized double-blind study. Subjects performed better than the placebo group on a cognitive performance test after taking 750 mg of a spermidine-rich plant extract containing 1.2 mg of spermidine for 3 months. Thus, dietary spermidine intake had a positive effect on memory performance in older adults with incipient cognitive decline. This positive effect, the researchers concluded, could be mediated by stimulation of neuromodulatory actions in the memory system .
Due to the promising results, a larger and longer study by the same research group is currently taking place: this so-called SmartAge study, a randomized 12-month clinical trial in which 100 patients with incipient cognitive decline were recruited, is intended to help validate the therapeutic potential of spermidine supplementation and to describe possible neurophysiological mechanisms of action . However, the results of this study have not yet been published – we will keep you updated!
In parallel with the SmartAge study, a cross-sectional study was recently conducted to investigate the relationship between spermidine intake and structural brain measures. For this purpose, 108 patients with subjectively perceived cognitive impairment and 51 healthy subjects were prescribed a Mediterranean diet, and spermidine intake in this diet was calculated and documented. The result was that spermidine intake correlated positively with greater cerebral cortex thickness (cortical thickness) in brain regions at risk for Alzheimer’s disease. Also, spermidine intake was related to a greater volume of the hippocampus, the part of the brain functionally involved primarily in the formation and maintenance of memory content and in learning processes. The authors concluded that in the Mediterranean diet, spermidine may be a critical component for brain health .
The dementia-protective potential of spermidine was also recently confirmed in a three-month multicenter intervention study in Austria. The researchers were able to show that spermidine levels not only decrease with age, but are also significantly lower in Alzheimer’s and MCI patients  . As a logical consequence, a low level in the blood would then be followed by oral supplementation with spermidine. This was done in the Austrian study, showing that increasing spermidine plasma levels in patients with mild cognitive impairment led to an improvement in memory performance as early as within 3 months.
Based on current knowledge, researchers believe that the physiological polyamine system (see Figure 1) plays an important protective role in the body. Moreover, it is hoped that the measurement of spermidine as a possible biomarker candidate could also be used in the future to predict Alzheimer’s disease even before the functional deficits occur.
Look at the video “Alzheimer’s: Eating against forgetting ORF treffpunkt Medizin” in our media library (video in German).