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Adjunctive vitamin D3 therapy enhances clinical response to tadalafil in men with erectile dysfunction: a randomized, placebo-controlled study

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Erectile dysfunction (ED) is increasingly recognized as a sentinel marker of systemic vascular disease, characterized by impaired nitric oxide (NO) bioavailability and endothelial dysfunction. Emerging evidence suggests that vitamin D deficiency—a global health pandemic—compounds this pathology by exacerbating oxidative stress and downregulating endothelial nitric oxide synthase (eNOS). While observational data link low vitamin D to ED, interventional evidence regarding its role as a therapeutic adjunct remains limited. To determine whether pharmacological correction of vitamin D deficiency synergistically enhances the efficacy of daily tadalafil in men with symptomatic ED. This triple-blind randomized clinical trial was conducted at two urology clinics in Mashhad, Iran. Forty men with ED (IIEF score < 25) and laboratory-confirmed vitamin D deficiency (10–30 ng/mL) were randomized (1:1) to receive either 5 mg daily tadalafil plus 50,000 IU of weekly vitamin D3 (Group A), or tadalafil plus a matched placebo (Group B) for 10 weeks. The primary outcome was the change in the IIEF scores. Multiple linear regression was employed to adjust for confounding factors. Baseline demographic characteristics and IIEF scores were comparable between the study arms. Following the 10-week intervention, Group A demonstrated significant superior improvements in the erectile function subdomain of IIEF score (21.7 ± 3.9 vs. 18.4 ± 2.4; p = 0.005) and total IIEF scores (52.8 ± 8.8 vs. 48.3 ± 4.5; p = 0.030) compared to Group B. Furthermore, 25% of the intervention group achieved complete resolution of ED symptoms, a threshold not reached by any member of the control group. After adjusting for baseline variables, vitamin D supplementation remained a significant independent predictor of clinical improvement ( p = 0.001). Weekly high-dose vitamin D3 supplementation significantly potentiates the therapeutic efficacy of daily tadalafil. These findings advocate for the routine integration of vitamin D screening and correction into the diagnostic workup and management of organic ED to optimize both sexual and vascular health outcomes.

Source: Scientific Reports

DOI: 10.1038/s41598-026-67266-7

Authors: Alireza Akhavan Rezayat, Amir Abbas Asadpour, Seyyed Parham Ahmadi, Fatemeh Sadabadi, Naeimeh Farhangnezhad

Institutions: Mashhad University of Medical Sciences, Ghaem Hospital

Language: English

Topic: Sexual function and dysfunction studies

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690