A randomized controlled trial investigating the effect of spermidine-enriched dietary supplementation on fertility-related outcomes and sleep quality in men with spermatogenic failure

Background: Male infertility accounts for nearly half of all infertility cases and profoundly affects psychological well-being and quality of life. Spermidine, a naturally occurring polyamine with autophagy-promoting and antiaging effects, has been associated with improved sleep and emotional health. However, its effect on fertility-related quality of life in men with spermatogenic failure (SPGF) remains unknown. This study aimed to investigate the effects of spermidine-enriched dietary supplementation on fertility-related quality of life and sleep quality in men with SPGF and to assess its safety. Materials and methods: In this randomized, double-blind, placebo-controlled trial (registration No.: ChiCTR2300077972), 60 men with SPGF were assigned (1:1) to receive spermidine (4 mg/d) or placebo for 3 months alongside standard therapy. Primary outcomes were changes in Fertility Quality of Life and Pittsburgh Sleep Quality Index. Secondary and exploratory outcomes included semen parameters, hepatic and renal safety markers, and sex hormone levels. Results: Among 60 randomized participants, spermidine supplementation significantly improved Fertility Quality of Life (adjusted p < 0.01) and reduced the risk of poor sleep quality (odds ratio for worse sleep, 0.08 [95% confidence interval, 0.02–0.29]; p < 0.001) compared with placebo. Although a higher proportion of the spermidine group achieved increased sperm concentration (18.5% vs. 4.0%), this difference was not statistically significant ( p = 0.19). No serious adverse events were observed during the 3-month study period. Conclusions: Spermidine supplementation improved fertility-related quality of life and sleep quality in men with SPGF and was well tolerated. These findings support its potential as a noninvasive adjunct to enhance well-being in male infertility.