Elevation of Serum Spermidine in Obese Patients: Results from a Cross-Sectional and Follow-Up Study

Background: Spermidine, a natural polyamine, appears to be a promising intervention for the treatment of obesity in animal studies, but epidemiological studies on the association between spermidine and obesity are inadequate. Methods: In the cross-sectional study, a total of 4230 eligible Chinese rural participants aged ≥ 35 years at baseline were recruited, of whom 1738 completed the two-year follow-up. Serum spermidines were measured using high-performance liquid chromatography with a fluorescence detector. Obesity and change in BMI were used as outcomes. Multivariable logistic regression analysis was applied to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Results: Participants who were obese had higher serum spermidine concentrations than those who were of normal weight (median (IQR), 27.2 ng/mL (14.8−53.4 ng/mL) vs. 23.8 ng/mL (12.8−46.6 ng/mL), p = 0.002). Compared with participants in the first quartile, those in the third quartile (OR 1.327, 95% CI 1.050 to 1.678) and the fourth quartile (OR 1.417, 95% CI 1.121 to 1.791) had a significantly increased risk of prevalent obesity after adjustment for confounding factors. In the follow-up study, participants in the third quartile (OR 0.712, 95% CI 0.535 to 0.946) and the fourth quartile (OR 0.493, 95% CI 0.370 to 0.657) had significantly lower risks of an increase in BMI after adjustment for confounding factors, with the lowest quartile as the reference. Meanwhile, we found a nonlinear relationship between spermidine and BMI in the follow-up study (p < 0.001). Conclusions: Serum spermidine was positively associated with increased odds of obesity in the cross-sectional study but reduced odds of an increase in BMI in the follow-up study among Chinese adults. Future studies are warranted to determine the exact mechanism underlying the association between spermidine and obesity and the scope for interventions.