4.5. Relevance of Presystemic Conversion of Spermidine
Although it has been speculated that intestinal polyamine uptake might be similar in rodents and humans, our data indicate that—different from rodent data—dietary spermidine is not quantitatively recovered in the systemic circulation but is subject to extensive presystemic metabolism. These findings are supported by previous studies. For instance, Soda et al. demonstrated millimolar concentrations of dietary polyamines in the duodenum and jejunum in humans after high-dose oral intake yielded maximal plasma concentrations of only 10–20 μM [Both the enterocytic and hepatic conversion of spermidine to spermine might explain the increased spermine concentration in blood plasma after oral spermidine intake, while spermidine concentrations remained unchanged. Alternative explanations could be a complete intraluminal degradation, a lack of intestinal absorption, or a rapid distribution to tissues and organs with peripheral uptake rates being similar to intestinal absorption, which would leave blood concentrations at a constant level. Since none of these mechanisms can explain the observed increase in spermine levels over time, our data strongly suggest that in humans, dietary spermidine is at least partly presystemically converted into spermine, which then occurs in the systemic circulation. Since no spermine pharmacokinetics were evaluable, these processes are probably concealed by other metabolic or distributing processes, as discussed above.