5. Conclusions
oropharyngeal SARS-CoV-2
The results presented here for the first time provide a pharmacokinetic basis for future translational research on spermidine. Oral spermidine intake of 15 mg/d for 5 days significantly increased spermine levels in the plasma but did not affect spermidine or putrescine levels. Our data strongly suggest that dietary spermidine is presystemically converted into spermine, which then occurs in the systemic circulation. Consequently, we postulate that the in vitro and clinical effects of spermidine are (at least in part) not attributable to spermidine itself but rather to its metabolite, spermine. It is rather unlikely that spermidine supplements with doses <15 mg/d exert any effect. Moreover, even spermidine doses of 15 mg/d do not affect salivary polyamine concentrations; in particular, pharmacological spermidine concentrations in the saliva that, due to preclinical data, might be effective at inhibiting oropharyngeal SARS-CoV-2 replication are not remotely achieved.Finally, epidemiological studies that have correlated dietary spermidine intake with biological effects are challenged by our results, as such studies have not considered the variability of presystemic spermidine metabolism and dietary spermine intake.