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Aging (Albany NY). 2018 Jan 8;10(1):19-33. doi: 10.18632/aging.101354.

Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline.

Author information

1
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany.
2
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany.
3
Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria.
4
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany.
5
Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany.
6
BioTechMed, Graz, Austria.
7
Department of Internal Medicine, Medical University of Graz, Graz, Austria.
8
Joanneum Research Forschungsgesellschaft m.b.H., HEALTH, Institute for Biomedicine and Health Sciences, Graz, Austria.
9
Medical Practice Bohlken for Neurology and Psychiatry, Berlin, Germany.
10
Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
#
Contributed equally

Abstract

Supplementation of spermidine, an autophagy-inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28-days repeated-dose tolerance study. Post mortem examination of the mice organs showed no increase in tumorigenic and fibrotic events. In the human cohort (participants with subjective cognitive decline, n=30, 60 to 80 years of age), a 3-month randomized, placebo-controlled, double-blind Phase II trial was conducted with supplementation of the spermidine-rich plant extract (dosage: 1.2 mg/day). No differences were observed between spermidine and placebo-treated groups in vital signs, weight, clinical chemistry and hematological parameters of safety, as well as in self-reported health status at the end of intervention. Compliance rates above 85% indicated excellent tolerability. The data demonstrate that spermidine supplementation using a spermidine-rich plant extract is safe and well-tolerated in mice and older adults. These findings allow for longer-term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.

KEYWORDS:

aging; dietary supplement; polyamines; safety; spermidine; subjective cognitive decline

PMID:
29315079
PMCID:
PMC5807086
DOI:
10.18632/aging.101354
[Indexed for MEDLINE]
Free PMC Article

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