Effect of a Dietary Supplement Containing EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid in Supporting Male Genital Balance in Subjects Exposed to HPV Risk

This pilot, randomized interventional study aims to assess the effect of a dietary supplement containing epigallocatechin gallate (EGCG), vitamin B12, hyaluronic acid, and folic acid on the maintenance of physiological balance and natural defenses of the male genital tract in men with HPV infection attending natural procreation centers. The study also seeks to evaluate whether supplementation may support sperm quality, improve reproductive well-being of participating couples, and reduce risk factors associated with HPV transmission to the female partner.

A total of 48 couples (96 participants) will be enrolled at the Istituto Scientifico Internazionale "Paolo VI" of the Policlinico A. Gemelli. Eligible couples, characterized by an HPV-positive male partner and an HPV-negative female partner, will be randomized into two groups: a supplement group, in which both partners will receive oral supplementation with EGCG (200 mg), vitamin B12 (1 mg), hyaluronic acid (50 mg), and folic acid (400 μg) once daily for 6 months, and a control group receiving no supplementation. Randomization will be performed using a computer-generated list.

The primary endpoint is the proportion of male participants achieving a negative HPV DNA test at the end of the 6-month intervention period. Secondary endpoints include changes in sperm quality parameters assessed by semen analysis according to WHO 2021 guidelines, measures of reproductive outcomes such as fertility potential and achievement of pregnancy, and maintenance of genital mucosal health, including absence of infections or recurrences and reduced risk of HPV transmission. HPV genotyping will be assessed by PCR on urethral swab samples. The overall study duration is expected to be 18 months following ethics committee approval.

Inclusion criteria

• Signed informed consent
• Couple seeking pregnancy
• Male partner aged 25-65 years
• HPV DNA test indicating active HPV infection in the male partner
• HPV DNA test indicating negativity for HPV infection in the female partner

Exclusion criteria

• Concomitant diseases causing immunosuppression
• Treatment with immunomodulatory therapies
• Use of EGCG or other green tea extracts