Is it safe to take spermidine supplements and what is the recommended dosage?

Spermidine Supplementation: Safety and Dosage

Spermidine supplementation at doses up to 40 mg/day appears to be safe and well-tolerated in healthy adults, with no significant adverse effects reported in clinical trials. 1

Safety Profile

• High-purity spermidine trihydrochloride (spermidine-3HCl) has been tested in toxicological studies and shown to be non-genotoxic with no adverse effects reported in 90-day oral toxicity studies in rats at doses up to 728 mg/kg/day for males and 829 mg/kg/day for females 2
• Clinical trials in healthy older men (50-70 years) demonstrated that 40 mg/day of spermidine for up to 28 days did not result in any significant changes in clinical, lipid, chemistry, or hematological parameters compared to placebo 1
• No study product-related adverse events were reported in human trials, suggesting good tolerability 1

Dosage Considerations

• Current evidence suggests that doses of spermidine below 15 mg/day are unlikely to exert significant short-term effects, as they don't appreciably increase blood plasma or saliva spermidine levels in healthy adults 3
• The most recent clinical trial used 40 mg/day for up to 28 days with good safety outcomes 1
• Interestingly, dietary spermidine appears to be presystemically converted into spermine, which then enters systemic circulation, suggesting that the clinical effects of spermidine may be partly attributable to its metabolite, spermine 3

Potential Health Benefits

• Spermidine is a polyamine that plays crucial roles in cellular functions and has been implicated in protecting against several age-related diseases 4
• In animal models, spermidine has shown promise in protecting against diet-induced obesity 5
• Spermidine enhances autophagy, which becomes dysfunctional with aging and contributes to immunosenescence 6
• Tissue levels of spermidine decline with age in model organisms and humans, although they are unusually high in healthy nonagenarians/centenarians 6

Important Considerations

• Spermidine supplementation does not significantly alter serum and urine polyamine concentrations, suggesting effective homeostatic control even at doses of 40 mg/day 1
• There is no evidence of adaptation of spermidine metabolism at the 40 mg/day dosage level 1
• While spermidine shows promise in preclinical models for prolonging lifespan and healthspan, more long-term human studies are needed 4

Contraindications and Drug Interactions

• No specific contraindications for spermidine supplements have been identified in the available literature
• Unlike some other supplements, spermidine has not been shown to interact with medications such as PDE5 inhibitors that are commonly used for erectile dysfunction 6
• Unlike spermicides, which have specific contraindications related to HIV risk 6, spermidine supplements have not shown similar concerns

Conclusion

Based on the most recent and highest quality evidence, spermidine supplementation appears safe at doses up to 40 mg/day in healthy adults. While lower doses (<15 mg/day) may not significantly increase circulating spermidine levels, a dosage of 40 mg/day has been clinically tested with good safety outcomes. More research is needed to fully establish the long-term effects and optimal dosing for specific health benefits.