Effects of folate supplementation on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2/3 in overweight and obese women: a randomized double-blind placebo-controlled trial

Randomized, double-blind, placebo-controlled trial in overweight or obese folate-deficient women with pathologically confirmed CIN2/3 in Kashan, Iran. The active folate arm included 30 participants; baseline mean age was 41.0 ± 3.7 years and baseline BMI was 26.8 ± 3.3 kg/m2.

Folate supplementation was given as folic acid 5 mg/day orally once daily for 12 weeks, compared with placebo. The active regimen contained folic acid with standard tablet excipients; the placebo contained starch.

Folate supplementation did not significantly reduce CIN2/3 recurrence over 12 weeks, but it improved several metabolic and inflammatory markers. Recurrence was 3.3% in the folate group versus 16.7% with placebo (P = 0.08). Folate lowered insulin, HOMA-IR, and hs-CRP and increased QUICKI and total antioxidant capacity; for example, insulin changed from 13.7 ± 3.4 to 10.8 ± 4.6 µIU/mL, HOMA-IR from 2.9 ± 0.8 to 2.2 ± 1.0, QUICKI from 0.32 ± 0.01 to 0.33 ± 0.01, and TAC from 869.8 ± 141.9 to 981.9 ± 190.9 mmol/L. Homocysteine also fell significantly, while most lipid and glucose measures did not change meaningfully.

The trial was small and short, limiting power to detect a difference in CIN2/3 recurrence. The primary clinical endpoint was not statistically significant, and benefits were mainly seen in intermediate biomarkers. Findings are specific to overweight/obese folate-deficient women with CIN2/3 in one Iranian center, and diet and physical activity were instructed to remain stable rather than tightly controlled.