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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 &lt; 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.

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