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. 2021 Mar 29;9(2):22.
doi: 10.3390/medsci9020022.

Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study

Kuniyasu Soda  1 , Takeshi Uemura  2 , Hidenori Sanayama  1 , Kazuei Igarashi  2   3 , Taro Fukui  1
Affiliations

Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study

Kuniyasu Soda et al. Med Sci (Basel). .

Abstract

The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of mice. To test the effects of increased polyamine intake by humans, 30 healthy male volunteers were asked to eat polyamine-rich and ready-to-eat traditional Japanese food (natto) for 12 months. Natto with high polyamine content was used. Another 27 male volunteers were asked not to change their dietary pattern as a control group. The volunteers' age of intervention and control groups ranged from 40 to 69 years (median 48.9 ± 7.9). Two subjects in the control group subsequently dropped out of the study. The estimated increases in spermidine and spermine intakes were 96.63 ± 47.70 and 22.00 ± 9.56 µmol per day in the intervention group, while no changes were observed in the control group. The mean blood spermine level in the intervention group gradually rose to 1.12 ± 0.29 times the pre-intervention level after 12 months, and were significantly higher (p = 0.019) than those in the control group. Blood spermidine did not increase in either group. LFA-1 on monocytes decreased gradually in the intervention group, and there was an inverse association between changes in spermine concentrations relative to spermidine and changes in LFA-1 levels. Contingency table analysis revealed that the odds ratio to decrease LFA-1 by increased polyamine intake was 3.927 (95% CI 1.116-13.715) (p = 0.032) when the effect of acute inflammation was excluded. The results in the study were similar to those of our animal experiments. Since methylation changes of the entire genome are associated with aging-associated pathologies and our previous studies showed that spermine-induced LFA-1 suppression was associated with the inhibition of aberrant gene methylation, the results suggest that dietary polyamine contributes to human health and longevity.

Keywords: Natto; aging; high polyamine diet; spermidine; spermine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relationship between two measurements of pre-intervention: (a) Age vs. SPM; (b) Age vs. SPD; (c) Age vs. SPM/SPD; (d) Age vs. mono-CD11aMFI; (e) SPM vs. mono-CD11aMFI; (f) SPD vs. mono-CD11aMFI; (g) SPM/SPD ratio vs. mono-CD11aMFI; (h) Age vs. lymph-CD11aMFI; (i) SPM vs. lymph-CD11aMFI; (j) SPD vs. lymph-CD11aMFI; (k) SPM/SPD ratio vs. lymph-CD11aMFI. Concentrations of polyamines were measured by HPLC and expression of CD11a (LFA-1) was determined using a FACScan flow cytometer (FACSVerseTM) with analysis software (BD FACSuite™). SPM; spermine concentrations, SPD; spermidine concentrations, mono-CD11a; LFA-1 (CD11a) expression on monocytes, lymph-CD11a; LFA-1 (CD11a) expression on lymphocytes, MFI; mean fluorescent intensities.
Figure 2
Figure 2
Relationship between changes in polyamine intake and changes in blood polyamine (LOCF approach).: (a) blood SPM changes vs. changes in polyamine intake; (b) blood SPD changes vs. changes in polyamine intake; (c) blood SPM/SPD changes vs. changes in polyamine intake; (d) blood SPM changes vs. changes in SPD intake; (e) blood SPD changes vs. changes in SPD intake; (f) blood SPM/SPD changes vs. changes in SPD intake; (g) blood SPM changes vs. changes in SPM intake; (h) blood SPD changes vs. changes in SPM intake; (i) blood SPM/SPD changes vs. changes in SPM intake. Concentrations of polyamines were measured by HPLC. SPM; spermine, SPD; spermidine. Open circle; control, Closed circle; natto group
Figure 3
Figure 3
Relationship between changes in blood polyamine concentrations and changes in LFA-1 levels in monocyte area (mono-CD11aMFI).: (a) Changes in blood SPM concentrations at 12 months vs. changes in mono-CD11aMFI at 12 months; (b) Changes in blood SPD concentrations at 8 months vs. changes in mono-CD11aMFIs at months; (c) Changes in the blood SPM/SPD ratios at 12 months vs. changes in mono-CD11aMFIs at 12 months; (d) Changes in the blood SPM/SPD ratios at 8 months vs. changes in mono-CD11aMFIs at 12 months. Mono-CD11aMFI; Mean fluorescent intensities (MFI) of CD11a expressions (LFA-1) on cells in monocyte area, SPM; Spermine, SPD; Spermidine, SPM/SPD: Relative content of SPM to SPD.
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