Echinacea angustifolia and Echinacea purpurea Supplementation Combined with Vaginal Hyaluronic Acid to Boost the Remission of Cervical Low-Grade Squamous Intraepithelial Lesions (L-SILs): A Randomized Controlled Trial

Abstract

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality of evaluated evidence, emphasizing the need for additional studies to validate these findings.

Preventing Persistence of HPV Infection with Natural Molecules

“…Only combining the oral supplementation of Echinacea with the administration of the HA soft gel caps seemed to boost viral clearance and reduce the persistence of LSIL/CIN1 lesions during the 12-month follow-up. This evidence confirms that HA not only may act as a preventive approach to inhibit virus infection, but it also represents a pivotal adjuvant approach to boost the efficacy of other compounds and decrease the number of lesions [ 93 ].…”

“…For the first time, a recent randomized controlled trial provided evidence for using HA in association with other compounds to boost their efficacy. Indeed, the association of vaginal HA-based soft gel capsules with orally taken Echinacea extracts reduced the number of remaining CIN1 samples and improved histological, cytologic, and colposcopic outcomes with respect to vaginal HA or Echinacea purpurea (EP) plus Echinacea angustifolia (EA) alone [ 93 ]. Only combining the oral supplementation of Echinacea with the administration of the HA soft gel caps seemed to boost viral clearance and reduce the persistence of LSIL/CIN1 lesions during the 12-month follow-up.…”

Evaluating the Efficacy of Pervistop®, a New Combination Based on EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on Patients with Human Papilloma Virus (HPV) Persistent Infections and Cervical Lesions: A Pilot Study

“…Indeed, we found out that an oral treatment with tablets containing 200 mg of EGCG, 400 mcg of FA, 1 mg of vitamin B12, and 50 mg of HA for 12 weeks reduces the rate of viral persistence. Despite our clinical trial providing the first evidence on such combination, the effects of EGCG alone, folic acid alone, hyaluronic acid alone, and vitamin B12 alone are already described in the literature [ 32 , 33 , 34 , 35 , 36 , 37 ].…”

“…In the case of HPV-positive patients, due to its effects in maintaining the integrity of mucosa, HA is effective in preventing the entry of viral particles into the cells, blocking the infection process. Riemma et al [ 37 ] also provided the first evidence on the clinical effects of HA in HPV-infected women with LSIL. Indeed, they tested a combination of natural products in presence or absence of HA topical treatment.…”

Case Report: Combination of Electrocautery and Echinacea Therapy in Condylomata Acuminata

“…18,19 Study from Mehedintu et al 2017, using echinacea as an immunomodulator for the treatment of patients with cervical HPV positive for 6 months [15]. Study from Riemma et al 2022, echinacea extracts supplementation in women with L-SIL ( low-grade squamous intraepithelial lesions)/CIN-1 (cervical intraepithelial neoplasia) significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months [16].…”