Although the intracellular de novo synthesis of the polyamines decreases with age, there is no similar trend in blood polyamine levels, but rather there is wide individual variability. We hypothesized that dietary polyamines attenuate a decrease in blood polyamine levels with age and augment the previously observed individual variability. The effect of a polyamine rich diet, in both mice and humans, on blood polyamine concentrations was examined in this study. Jc1:ICR male mice were fed test diets containing 3 different polyamine concentrations. Healthy human male volunteers added 50 to 100 g of the polyamine-rich fermented soybean product, natto, to their daily intake. After 26 wk, the mean blood spermine concentration in mice receiving the test diet with high polyamine concentrations was 10.1+/-2.4 micromol/L, while the mean concentrations found in mice fed with a diet with normal or low polyamine concentrations were 5.2+/-0.9 and 4.7+/-0.5 micromol/L, respectively (p<0.05). A mean daily intake of 66.4+/-3.7 g (range=46.4-89.3 g) of natto for 2 mo by human volunteers increased the mean blood spermine concentration by a factor of 1.39 (n=10) (p<0.01), while in control volunteers (n=7), asked to exclude polyamine-rich foods from their diet, blood spermine concentration remained unchanged. The individual variability of blood polyamine levels was enhanced after polyamine intake in mice and, to a lesser extent, in humans. The long-term oral intake of enhanced polyamine diets increases blood polyamine levels in both mice and humans.