Spermidine, also known chemically as N-(3-aminopropyl) butane-1,4-diamine, is one of the naturally occurring polyamines. It occurs as a natural substance in amino acid metabolism of all living organisms and in all cells, and therefore also in a variety of plant and animal foods. Particularly rich food sources are wheat germ, but hard cheese, dried soybeans and some other foods also provide good amounts of spermidine. Recently, it was shown in mice that spermidine from food actually reaches the brain, thus crossing the blood-brain barrier (1).
It has been known for a while that spermidine is an effective autophagy inducer. This means that it is able to mimic cellular processes of fasting. One important cellular process activated during fasting is known as autophagy (translated from the Greek as “eating oneself”). Autophagy is considered an important component in the context of health maintenance, as these processes dispose of cellular ‘garbage’, such as misfolded proteins or damaged cellular components, which can lead to neurodegeneration in old age, for example.
Based on these well-documented age-protective and autophagy-promoting properties of spermidine, a possible neuroprotection (protection of the nervous system) has therefore become the focus of spermidine research in recent years. After preclinical studies have clearly shown that spermidine has strong brain-protective properties, more and more human studies are currently taking place to confirm this evidence in humans.
In a recent intervention study, a group of researchers from Austria speculated that, based on a direct link between spermidine and the incidence of dementia, the level of this biogenic amine should decrease with age and that, consequently, oral supplementation of spermidine could have a positive effect on memory performance (2,3).
To investigate these hypotheses, 92 nursing home residents aged 60 to 96 years with mild cognitive impairment were recruited in a multicenter double-blind study and randomly divided into 2 groups. Both groups received a roll with wheat germ for breakfast 6 days per week. In the first group, the spermidine content per cookie was 3.3 mg spermidine after baking. In the second group B, the subjects received a pastry containing 1.9 mg spermidine.
To test cognitive performance, a so-called ‘CERAD Plus’ test was conducted with all participants at baseline and after 3 months. This cognition test comprises 7 individual tests to assess memory, orientation, language and motor skills.
The results first proved the hypothesis that spermidine levels decrease with age (2). It was also shown that there is a clear relationship between detected spermidine concentrations and memory performance. Comparison of CERAD Plus total scores showed a significant increase in both intervention groups: on average, the first group improved by 6.25 points and the second by 4.00 points. Thus, a dose-response relationship was also evident.
Since the end of the study, all residents of the nursing home where the study took place are receiving a spermidine-rich diet. An initial evaluation already showed that the ‘Mini Mental Score’ (another cognition test) improved in 42% of those tested as a result, a more detailed evaluation is still pending.
The results from Austria also coincided with the findings of the so-called ‘PreSmartAge’ study, which was conducted shortly before at the Charité in Berlin. In this randomized double-blind study, a group of researchers investigated whether spermidine could exert a positive influence on memory performance in patients with mild cognitive impairment (4). For this purpose, 30 participants between 60 and 80 years of age who suffered from self-reported (but not yet clinically manifested) memory decline were recruited. The subjects performed better than the placebo group in 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 (4).
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, investigates the brain-protective properties in 100 patients with incipient cognitive decline (5,6). However, the results of this study have not yet been published – we will keep you updated!
All these data impressively confirm the assumption that spermidine already leads to an improvement in memory performance within a short period of time and thus plays an important protective role in dementia. More than that, one could also deduce the potential suitability of spermidine plasma levels also as a possible biomarker candidate for predicting Alzheimer’s disease, even before the functional deficits appear.
If you would like to have additional and more detailed information on spermidine and its properties, visit us here at “Knowledge stops Dementia”. You can also find the video “Alzheimer: Essen gegen das Vergessen ORF Treffpunkt Medizin” in the media library at “Knowledge stops Dementia” (in German language).
Based on this clear scientific data, the naturally occurring polyamine spermidine is now considered a promising substance with the potential to reduce the risk of developing dementia. A logical consequence of these studies is to take spermidine orally if laboratory detection has shown an insufficient concentration in the blood. This is already being successfully implemented in nursing homes in Austria.
It can also be possible in the future to use spermidine blood levels to predict Alzheimer’s disease before the functional deficits occur.
And you can already use this knowledge for yourself: Put spermidine-rich foods on your menu every day, such as wheat germ: one tablespoon already contains 1-2 mg of the protective polyamine! In this way, you too can benefit directly from the brain-protecting properties of spermidine and remain mentally wide awake for a long time!
- Schroeder S, Hofer SJ, Zimmermann A , Pechlaner R, et al. (2021) Dietary spermidine improves cognitive function. Cell Reports. 35(2):108985. doi: 10.1016/j.celrep.2021.108985;
- Pekar T, Wendzel A, Flak W, Kremer A, Pauschenwein-Frantsich S, Gschaider A, Wantke F, Jarisch R. (2020) Spermidine in dementia: Relation to age and memory performance, Wien. Klin. Wochenschr., vol. 132, no. 1–2, pp. 42–46, Jan. 2020, doi: 10.1007/s00508-019-01588-7.
- Pekar T, Bruckner K, Pauschenwein-Frantsich S, Gschaider A, Oppliger A, et al. (2020) The positive effect of spermidine in older adults suffering from dementia: First results of a 3-month trial, Wien. Klin. Wochenschr., 2020, doi: 10.1007/s00508-020-01758-y.
- Wirth M, Benson G, Schwarz C, Köbe T, Grittner U, Schmitz D, et al. (2018). The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial. Cortex. 109: 181–188. doi: 10.1016/j.cor-tex.2018.09.014
- Wirth M, Schwarz C, Benson G, et al. (2019) Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial. Alzheimer’s Res. Ther., 11 (2019), p. 36ff.
- Klinische Studie SmartAge: https://clinicaltrials.gov/ct2/show/NCT03094546