Therapeutic Effects of Vitamins in Endometriosis Patients: A Systematic Review of Randomized Controlled Trials.

The short version

This systematic review pulled together seven randomized controlled trials to ask whether vitamin D, vitamin C, and vitamin E supplements affect endometriosis, a long-term inflammatory condition in which tissue like the uterine lining grows outside the uterus and affects roughly 1 in 10 women of reproductive age. Common symptoms include painful periods (dysmenorrhea), chronic pelvic pain, pain during intercourse (dyspareunia), and difficulty conceiving. The vitamins were chosen because vitamin D helps regulate immune signaling, while vitamins C and E act as antioxidants that neutralize reactive oxygen species (unstable molecules that damage cells and add to inflammation). Both processes are central to how endometriosis develops and causes pain. The authors registered their protocol in PROSPERO and searched PubMed, Scopus, and ScienceDirect, screening 5,639 records down to seven eligible trials. Two reviewers screened independently, and trial quality was graded with the Jadad scale and the Cochrane RoB 2 tool. The trials varied widely: vitamin D doses ranged from 2000 IU daily to 50,000 IU weekly, vitamin C and E doses from 343 mg and 84 mg to 1000 mg and 800 IU daily, and treatment lasted from about 8 weeks to 6 months. Because of this variation, results were described narratively rather than pooled. High-dose vitamin D (50,000 IU every two weeks) cut pelvic pain scores by 1.12 points (95% CI -2.1 to -0.09; p = 0.03) and lowered hs-CRP, an inflammation marker, by 0.64 mg/L. A weekly 50,000 IU regimen lowered active β-catenin (a signaling protein linked to lesion invasion) in endometrial tissue. Lower daily doses did not clearly beat placebo, since both groups improved by similar amounts. Vitamin C plus E for eight weeks reduced oxidative stress markers, and one trial reported pain drops of 43% for daily pelvic pain, 37% for painful periods, and 24% for painful intercourse. Pregnancy rates did not rise in the trial that measured them. Side effects were generally minor, mostly occasional digestive upset. Three trials were rated low risk of bias and four had some concerns. The authors describe vitamins as a possible well-tolerated adjunct for pain and oxidative stress, though not for fertility. The evidence base is small, with only seven trials, English-language inclusion only, very different dosing across studies, and no trial using a publicly available preregistered protocol. Few trials checked participants' baseline vitamin levels, so it remains unclear whether any benefit depends on deficiency. The authors call for larger multicenter trials with standardized doses, longer follow-up, and fertility and lesion outcomes.

Key findings

• A systematic review of seven randomized controlled trials (RCTs) examined whether vitamins D, C, and E help women with endometriosis, a chronic inflammatory condition in which uterine-lining-like tissue grows outside the uterus.
• High-dose vitamin D (50,000 IU every two weeks for 12 weeks) reduced pelvic pain by 1.12 points compared with placebo (95% CI -2.1 to -0.09; p = 0.03) and lowered hs-CRP (a blood marker of inflammation) by 0.64 mg/L.
• Combined vitamin C and E (1000 mg and 800 IU daily for eight weeks) lowered oxidative stress markers (signs of cell damage from unstable molecules) and was linked to improved dysmenorrhea (painful periods), dyspareunia (painful intercourse), and chronic pelvic pain, with one trial reporting reductions of 43%, 37%, and 24% in pain measures.
• Lower-dose vitamin D (2000 IU daily) and post-surgery vitamin D did not clearly beat placebo, and the trial that measured pregnancy found no rise in pregnancy rates with vitamin C and E.
• The evidence is limited by only seven mostly small trials, very different doses, English-only inclusion, and no pooled analysis, and the authors call for larger multicenter trials with longer follow-up.

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