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. 2018 Aug 1;108(2):371-380.
doi: 10.1093/ajcn/nqy102.

Higher spermidine intake is linked to lower mortality: a prospective population-based study

Stefan Kiechl  1 , Raimund Pechlaner  1   2 , Peter Willeit  1   2   3 , Marlene Notdurfter  4 , Bernhard Paulweber  5 , Karin Willeit  1 , Philipp Werner  6 , Christoph Ruckenstuhl  7   8 , Bernhard Iglseder  5 , Siegfried Weger  4 , Barbara Mairhofer  4 , Markus Gartner  4 , Ludmilla Kedenko  5 , Monika Chmelikova  9 , Slaven Stekovic  7   8 , Hermann Stuppner  10   11 , Friedrich Oberhollenzer  4 , Guido Kroemer  12   13   14   15   16   17 , Manuel Mayr  2 , Tobias Eisenberg  7   8 , Herbert Tilg  18 , Frank Madeo  7   8 , Johann Willeit  1
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Free article

Higher spermidine intake is linked to lower mortality: a prospective population-based study

Stefan Kiechl et al. Am J Clin Nutr. .
Free article

Abstract

Background: Spermidine administration is linked to increased survival in several animal models.

Objective: The aim of this study was to test the potential association between spermidine content in diet and mortality in humans.

Design: This prospective community-based cohort study included 829 participants aged 45-84 y, 49.9% of whom were male. Diet was assessed by repeated dietitian-administered validated food-frequency questionnaires (2540 assessments) in 1995, 2000, 2005, and 2010. During follow-up between 1995 and 2015, 341 deaths occurred.

Results: All-cause mortality (deaths per 1000 person-years) decreased across thirds of increasing spermidine intake from 40.5 (95% CI: 36.1, 44.7) to 23.7 (95% CI: 20.0, 27.0) and 15.1 (95% CI: 12.6, 17.8), corresponding to an age-, sex- and caloric intake-adjusted 20-y cumulative mortality incidence of 0.48 (95% CI: 0.45, 0.51), 0.41 (95% CI: 0.38, 0.45), and 0.38 (95% CI: 0.34, 0.41), respectively. The age-, sex- and caloric ratio-adjusted HR for all-cause death per 1-SD higher spermidine intake was 0.74 (95% CI: 0.66, 0.83; P < 0.001). Further adjustment for lifestyle factors, established predictors of mortality, and other dietary features yielded an HR of 0.76 (95% CI: 0.67, 0.86; P < 0.001). The association was consistent in subgroups, robust against unmeasured confounding, and independently validated in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) Study (age-, sex-, and caloric ratio-adjusted HR per 1-SD higher spermidine intake: 0.71; 95% CI: 0.53, 0.95; P = 0.019). The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-y (95% CI: 3.6, 8.1 y) younger age.

Conclusion: Our findings lend epidemiologic support to the concept that nutrition rich in spermidine is linked to increased survival in humans. This trial was registered at www.clinicaltrials.gov as NCT03378843.

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Comment in

  • Cardioprotective effect of polyamine spermidine.
    Gostner JM, Fuchs D. Gostner JM, et al. Am J Clin Nutr. 2019 Jan 1;109(1):218. doi: 10.1093/ajcn/nqy221. Am J Clin Nutr. 2019. PMID: 30576404 No abstract available.
  • Reply to Gostner and Fuchs.
    Pechlaner R, Madeo F, Eisenberg T, Kroemer G, Tilg H, Willeit J, Kiechl S. Pechlaner R, et al. Am J Clin Nutr. 2019 Jan 1;109(1):218-219. doi: 10.1093/ajcn/nqy222. Am J Clin Nutr. 2019. PMID: 30576412 No abstract available.

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