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Research Paper|Volume 10, Issue 1|pp 19—33

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

Claudia Schwarz1,2, Slaven Stekovic3, Miranka Wirth1,2,4, Gloria Benson1,2, Philipp Royer3, Stephan J Sigrist2,5, Thomas Pieber6,7,8, Christopher Dammbrueck3, Christoph Magnes8, Tobias Eisenberg3,6, Tobias Pendl3, Jens Bohlken9, Theresa Köbe1,2, Frank Madeo3,6, Agnes Flöel10
  • 1Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Hochschulambulanz für Neurologie, Berlin, Germany
  • 2Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Cluster of Excellence, Berlin, Germany
  • 3Institute of Molecular Biosciences, University of Graz, NAWI Graz, Graz, Austria
  • 4Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Stroke Research Berlin, Berlin, Germany
  • 5Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany
  • 6BioTechMed, Graz, Austria
  • 7Department of Internal Medicine, Medical University of Graz, Graz, Austria
  • 8Joanneum Research Forschungsgesellschaft m.b.H., HEALTH, Institute for Biomedicine and Health Sciences, Graz, Austria
  • 9Medical Practice Bohlken for Neurology and Psychiatry, Berlin, Germany
  • 10Department of Neurology, University Medicine Greifswald, Greifswald, Germany

* * Equal contribution

Received: November 27, 2017Accepted: December 23, 2017Published: January 8, 2018

Copyright: © 2018 Schwarz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.