Epilepsia

Beta-carotene, a provitamin A carotenoid, is consistently found at lower levels in women with cervical dysplasia and cancer. Observational studies associate higher carotenoid intake with lower CIN risk. However, multiple RCTs have not demonstrated significant regression of established CIN with beta-carotene supplementation, and in one trial, regression rates were slightly (non-significantly) lower in the beta-carotene group for HPV-positive women.

I3C from cauliflower has been directly tested in a placebo-controlled clinical trial for cervical intraepithelial neoplasia (CIN), showing complete regression in 50% of women at 200–400 mg/day. Mechanisms include modulation of estrogen metabolism and induction of apoptosis in HPV-infected cervical cells.

Curcumin, the main active polyphenol in turmeric, suppresses HPV16/18 oncoproteins E6/E7 and restores p53/pRb function in cervical cancer cells in vitro. Multiple RCTs are underway: a Baylor Research Institute trial tests 500 mg twice daily orally for CIN3, and a prospective RCT tests intravaginal curcumin (2000 mg weekly) for LSIL/HSIL. No completed human clinical trial data for cervical dysplasia regression have been published, but preclinical evidence is robust.

Diindolylmethane (DIM), the active stomach-acid condensation product of indole-3-carbinol, has been evaluated in multiple clinical trials for CIN. A pilot RCT found 47% of CIN 2/3 subjects improved by 1–2 grades at 2 mg/kg/day. A larger double-blind RCT (n=551) showed a non-significant trend toward reduced CIN2+ progression. A phase IIa multicenter RCT using vaginal DIM suppositories also demonstrated benefit for CIN I–II.

EGCG, the principal polyphenol in green tea, has been tested in clinical trials for HPV-related cervical lesions. A pilot study of 51 women found a 69–74% response rate with topical polyphenon E (EGCG-rich) ointment versus 10% in untreated controls. A phase II RCT (n=98) showed oral EGCG was safe but did not significantly outperform placebo for CIN1 with HR-HPV.

Low folate is consistently associated with elevated cervical dysplasia risk and HPV infection prevalence. An early RCT in OC users found significant improvement in CIN biopsy and cytology scores with 10 mg/day folic acid vs. placebo. However, two larger definitive RCTs (235–331 women, 5–10 mg/day) found no significant regression of established CIN, leading to the conclusion that folate is a cofactor in CIN initiation rather than a therapeutic agent for established disease.

Green tea extracts (polyphenols including EGCG) have been studied in women with HPV-infected cervical lesions. A pilot clinical trial of 51 women found a 69% overall response rate for green tea extract treatment versus 10% in untreated controls, with topical application most effective. A subsequent phase II RCT (n=98) of oral green tea extract was safe but did not significantly outperform placebo for CIN1 with HR-HPV.

Indole-3-carbinol (I3C), derived from cruciferous vegetables, has been studied in a placebo-controlled trial at 200–400 mg/day, showing improved regression of cervical intraepithelial neoplasia (CIN). It modulates estrogen metabolism toward less oncogenic metabolites and exerts anti-estrogenic activity in cervical cells. Evidence is promising but limited by small trial size.

L. crispatus-dominant vaginal communities are associated with antiviral mucosal stability and lower HPV persistence. Observational data show that L. crispatus depletion at CIN2 diagnosis predicts significantly lower regression rates at 12 and 24 months. A 160-patient clinical study of oral L. crispatus M247 in HPV-infected women investigated eubiosis restoration and viral clearance. Mechanistically, L. crispatus suppresses HPV oncogene-related pathways and inhibits precancerous cervical cell proliferation in vitro.

L. jensenii is one of the Lactobacillus species enriched in cervicovaginal samples that are cytologically normal and BV-negative, and depleted in women with high-risk HPV infection, cervical intraepithelial neoplasia, and cervical cancer. A large retrospective study of over 15,000 specimens demonstrated that L. jensenii abundance inversely correlates with hrHPV positivity and abnormal cytology. Lactobacillus dominance, including L. jensenii, appears to modulate local mucosal immunity and HPV persistence.

Resveratrol, a stilbene polyphenol from grapes, reduces proliferation, induces apoptosis, and decreases HPV E6/E7 oncoprotein expression while increasing p53 in multiple cervical cancer cell lines. In vivo animal studies show reduced tumor volume. No completed human RCT data for cervical dysplasia specifically exist; resveratrol is a component of the TriCurin combination being developed for HPV+ cervical dysplasia trials.

Selenium deficiency is inversely correlated with cervical dysplasia severity in multiple observational studies. A 2015 randomized double-blind placebo-controlled trial (n=58, biopsy-proven CIN1) found 200 mcg/day selenium yeast for 6 months produced significantly higher CIN1 regression (88% vs. 56% placebo; p=0.01). An expression of concern was later published for this trial; the 2023 MDPI micronutrients review identified selenium as having among the stronger evidence for a protective role in CIN.

Vitamin A and related retinoids regulate cervical epithelial cell differentiation and proliferation. Lower dietary vitamin A is associated with increased cervical cancer risk in case-control studies. However, clinical trials of vitamin A and provitamin A supplementation have not shown significant regression of established CIN, and a systematic review concluded no proven beneficial role of vitamin A supplementation for established cervical carcinoma has been confirmed.

Low serum vitamin B12 is significantly associated with both low-grade (4-fold) and high-grade (3.5-fold) increased cervical dysplasia risk vs. high B12 levels. A Hawaii case-control study found B12 supplement intake inversely dose-responsive with high-grade SIL. A 2025 meta-analysis found B12 consistently protective against HPV persistence and cervical dysplasia risk across four studies.

Vitamin B9 (folate) deficiency is a recognized risk-modifying cofactor for cervical dysplasia and HPV persistence. A 2025 meta-analysis (Frontiers in Nutrition) found higher folate levels consistently associated with reduced HPV persistence and lower cervical dysplasia risk across four studies (pooled SMD 0.80; p<0.00001). A Hawaii case-control study found total folate intake inversely dose-responsive with both low- and high-grade SIL. Supplementation trials have not confirmed regression of established CIN.

Serum vitamin C is consistently lower in women with CIN versus controls. A 2025 meta-analysis found vitamin C protective against HPV-associated cervical disease. A Korean case-control study found statistically lower dietary vitamin C in cervical cancer cases. However, a double-blind RCT (n=141, 500 mg/day) found no significant effect of vitamin C supplementation on CIN regression or progression, and available RCT evidence does not confirm therapeutic reversal of established CIN.

Vitamin E (tocopherol) is lower in women with cervical abnormalities and cancer in multiple observational studies. A meta-analysis of 15 case-control studies (3,741 cases, 6,328 controls) found vitamin E intake inversely associated with cervical neoplasia risk. One RCT demonstrated that vitamin E supplementation promoted reversal of cervical dysplasia. A review of 22 studies on >10,000 women confirmed higher vitamin E intake significantly protective against cervical neoplasia.

Zinc's immunomodulatory and antioxidant properties are relevant to HPV clearance and cervical dysplasia prevention. The 2023 MDPI micronutrients review identified zinc as having a potential protective role in the natural history of HPV infection and CIN. A 2025 meta-analysis attributed zinc supplementation to better HPV clearance and lesion regression. Evidence is primarily observational and mechanistic; dedicated RCTs for zinc alone in CIN are limited.