Research Paper Volume 10, Issue 1 pp 19—33
Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline
- 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
Received: November 27, 2017 Accepted: December 23, 2017 Published: January 8, 2018
https://doi.org/10.18632/aging.101354How to Cite
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.