Spermidine safety studies
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Spermidine Safety Studies: Toxicological Assessment and Human Trials
Preclinical Toxicology and Animal Safety Data
Multiple studies have evaluated the safety of spermidine in animal models. A 90-day oral toxicity study in rats using high-purity spermidine trihydrochloride (spermidine-3HCl) found no adverse effects at doses up to 728 mg/kg body weight per day for males and 829 mg/kg for females, establishing a high no observed adverse effect level (NOAEL) and confirming the compound was non-genotoxic in standard in vitro assays . Similarly, a 28-day repeated-dose study in mice using a spermidine-rich wheat germ extract showed no morbidities, behavioral changes, or increased tumorigenic or fibrotic events, supporting the safety of spermidine supplementation in animal models .
Human Safety and Tolerability Studies
Several clinical trials have investigated the safety of spermidine supplementation in humans. In a randomized, double-blind, placebo-controlled trial, healthy older men (aged 50–70) received 40 mg/day of high-purity spermidine for up to 28 days. The study found no significant changes in clinical, lipid, chemistry, or hematological parameters compared to placebo, and no product-related adverse events were reported, indicating that this dosage is safe and well-tolerated . Another trial in older adults with subjective cognitive decline used a spermidine-rich plant extract (1.2 mg/day) for three months and found no differences in safety parameters or self-reported health status between the spermidine and placebo groups, with high compliance rates .
Pharmacokinetics and Metabolic Considerations
A pharmacokinetic study in healthy adults showed that oral supplementation with 15 mg/day of spermidine did not increase spermidine levels in blood plasma or saliva, but did increase plasma spermine, suggesting that dietary spermidine is rapidly converted to spermine before entering systemic circulation. No adverse effects were reported, and the study concluded that short-term supplementation at this dose is unlikely to cause harm . Another human trial also found that 40 mg/day of spermidine did not substantially alter serum or urine polyamine concentrations, supporting the idea of effective homeostatic control and metabolic adaptation to supplementation .
Comprehensive Reviews and Broader Safety Perspectives
A recent comprehensive review of spermidine highlighted its long history of safe dietary use, its presence in many foods, and its potential health benefits. The review emphasized that current research supports the safety of spermidine-rich foods and supplements, but also noted the need for further studies to address long-term safety and efficacy in diverse populations .
Conclusion
Current evidence from animal studies, human clinical trials, and comprehensive reviews consistently indicates that spermidine supplementation—whether as a purified compound or in plant extracts—is safe and well-tolerated at doses tested in both preclinical and clinical settings 12357. No significant adverse effects or safety concerns have been identified in short- to medium-term studies, supporting the continued investigation of spermidine for potential health benefits. However, further research is needed to confirm long-term safety and to explore effects in broader populations.
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