Spermidine for the Prevention of Radiation-Induced Xerostomia in Head and Neck Cancer: A Randomized Controlled Trial

58 head and neck cancer patients receiving radiotherapy were randomized to spermidine capsules (twice daily with meals) or placebo in a double-blind trial at West China Hospital, Sichuan University. Supplementation started one week before radiotherapy and continued until one week after completion. During radiotherapy and immediately after, both groups showed similar rates of dry mouth and saliva flow reduction. The difference emerged at the 3-month follow-up: 48% of the spermidine group reported dry mouth compared to 79% of the placebo group. Salivary output was higher in the spermidine arm, quality of life scores (EORTC QLQ-C30 and QLQ-H&N35) were better, and no serious adverse events were recorded. The delayed pattern suggests spermidine did not prevent the initial radiation injury but supported gland recovery afterward. This aligns with preclinical findings showing autophagy is required for salivary gland regeneration after radiation, and that spermidine levels shift in irradiated glands during the recovery phase. The trial is relatively small (N=58) and larger studies are needed.

At three months, 48% of the spermidine group had dry mouth compared to 79% of the placebo group. Salivary output was higher, quality of life scores were better, and there were no serious adverse events.