Is Spermidine safe?
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Safety of Spermidine Supplementation: A Comprehensive Review
Introduction to Spermidine Safety
Spermidine, a naturally occurring polyamine, has garnered attention for its potential health benefits, including anti-aging, neuroprotection, and cardioprotection. However, the safety and tolerability of spermidine supplementation are critical factors that need thorough evaluation.
Preclinical Safety in Animal Models
Murine Studies on Spermidine Safety
Several studies have investigated the safety of spermidine in animal models. In a preclinical toxicity study, BALBc/Rj mice were administered spermidine orally for 28 days. The results showed no significant morbidities, behavioral changes, or increases in tumorigenic and fibrotic events upon post-mortem examination . These findings suggest that spermidine is well-tolerated in mice, even with repeated dosing.
Human Clinical Trials
Safety in Older Adults with Cognitive Decline
A randomized, placebo-controlled, double-blind Phase II trial assessed the safety and tolerability of spermidine in older adults with subjective cognitive decline. Over a 3-month period, participants received a spermidine-rich wheat germ extract. The study found no significant differences between the spermidine and placebo groups in terms of vital signs, weight, clinical chemistry, hematological parameters, or self-reported health status. Compliance rates were above 85%, indicating excellent tolerability .
Pharmacokinetics and Metabolism
Conversion and Systemic Effects
A pharmacokinetic study revealed that oral administration of spermidine (15 mg/day) in healthy adults did not significantly increase spermidine levels in blood plasma or saliva. Instead, it increased levels of spermine, a metabolite of spermidine, suggesting presystemic conversion. This indicates that the beneficial effects of spermidine may be partly due to its conversion to spermine.
Health Benefits and Safety Correlation
Cardioprotection and Lifespan Extension
Spermidine has been shown to extend lifespan and provide cardioprotective effects in animal models. It reduces cardiac hypertrophy, preserves diastolic function, and enhances mitochondrial function. These benefits are linked to its ability to induce autophagy, a cellular cleanup process. Importantly, these studies also highlight the low toxicity of spermidine, supporting its safety for long-term use.
Neuroprotection and Cognitive Function
In models of neurodegeneration, spermidine supplementation has demonstrated protective effects against memory impairment and neuroinflammation. It improves cognitive function by enhancing mitochondrial respiratory capacity and autophagy, crucial for maintaining neuronal health. These neuroprotective effects further underscore the safety and potential therapeutic benefits of spermidine.
Conclusion
The current body of research indicates that spermidine supplementation is safe and well-tolerated in both animal models and human clinical trials. Its conversion to spermine and the associated health benefits, such as cardioprotection and neuroprotection, further support its safety profile. However, longer-term studies are necessary to fully understand the impact of spermidine on human health and to confirm its safety over extended periods.
Sources and full results
Most relevant research papers on this topic
P57. Safety and tolerability of spermidine supplementation: A translational study in mice and older adults with subjective cognitive decline
Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline
A comprehensive review of spermidine: Safety, health effects, absorption and metabolism, food materials evaluation, physical and chemical processing, and bioprocessing.
High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study
Spermidine in health and disease
Spermidine ameliorates 3-nitropropionic acid (3-NP)-induced striatal toxicity: Possible role of oxidative stress, neuroinflammation, and neurotransmitters
Spermidine Prolongs Lifespan and Prevents Liver Fibrosis and Hepatocellular Carcinoma by Activating MAP1S-Mediated Autophagy.
Spermidine as a target for cancer therapy.
Cardioprotection and lifespan extension by the natural polyamine spermidine
Dietary spermidine improves cognitive function.
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