ArticleMedComm2026
Oral Spermidine Supplementation Preserves Submandibular Gland Function After Radiotherapy: Mechanistic Insights and Use in a Phase II Randomized Clinical Trial.
Article in MedComm, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
Radiotherapy for head and neck cancer commonly induces salivary gland dysfunction, resulting in xerostomia that substantially impairs quality of life after treatment. To identify protective strategies, we established the irradiation-induced submandibular glands (SMG) injury mice model and performed integrated proteomic and metabolomic profiling of gland tissue and saliva. Spermidine levels were significantly altered in irradiated SMG during the postradiotherapy recovery phase. Oral spermidine supplementation restored salivary flow, preserved acinar aquaporin-5 expression, and attenuated vacuolization, apoptosis, and fibrosis in vivo; these effects were validated in SMG organoids. Single-cell RNA transcriptomic analysis further showed that spermidine increased the proportion of acinar cells, enhanced Golgi-mediated secretory gene expression, and suppressed inflammatory cytokine signaling. In the randomized, double-blind, proof-of-concept clinical trial, oral spermidine supplementation during peri-radiotherapy significantly reduced the incidence of xerostomia at 3 months compared with placebo (48.28 vs. 79.31%,
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