Supplementation with vitamin D or ω-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomized, placebo-controlled trial

Am J Clin Nutr. 2020 Jul 1;112(1):229-236. doi: 10.1093/ajcn/nqaa096.


Background: Adolescents with endometriosis are a particularly underserved population who struggle with chronic pain. Despite widespread use, there are no published trials examining the individual effects of vitamin D and omega-3 (n-3) fatty acid supplementation on endometriosis-associated pain in adolescents.

Objectives: We aimed to determine whether supplementation with vitamin D or ω-3 fatty acids remediates pain, changes frequency of pain medication usage, or affects quality of life in young women with endometriosis.

Methods: Women (aged 12-25 y) with surgically confirmed endometriosis and pelvic pain enrolled in a double-blind, randomized, placebo-controlled trial. The primary outcome was pain measured by the visual analog scale (VAS). Secondary outcomes were quality of life, pain catastrophizing, and pain medication usage. Participants were randomly assigned to receive 2000 IU vitamin D3, 1000 mg fish oil, or placebo daily for 6 mo.

Results: A total of 147 women were screened and 69 were randomly assigned as follows: 27 to vitamin D3; 20 to fish oil; and 22 to placebo. Participants in the vitamin D arm experienced significant improvement in VAS pain [mean (95% CI) worst pain in the past month, from baseline to 6 mo: 7.0 (6.2, 7.8) to 5.5 (4.2, 6.8), P = 0.02]; however, an improvement of nearly identical magnitude was observed in the placebo arm [6.0 (5.1, 6.9) to 4.4 (3.0, 5.8), P = 0.07]. A more modest improvement was observed in the fish oil arm [5.9 (4.8, 7.0) to 5.2 (3.7, 6.8), P = 0.39]. Neither of the intervention arms were statistically different from placebo.

Conclusions: In young women with endometriosis, supplementation with vitamin D led to significant changes in pelvic pain; however, these were similar in magnitude to placebo. Supplementation with fish oil resulted in about half of the VAS pain reduction of the other 2 arms. Studies are needed to better define the physiology underlying the observed reduction in pain score in the placebo arm that persisted across 6 mo.This trial was registered at as NCT02387931.

Keywords: adolescents; endometriosis; omega-3 fatty acids; pelvic pain; randomized controlled trial; vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cholecalciferol / administration & dosage*
  • Dietary Supplements
  • Double-Blind Method
  • Endometriosis / drug therapy*
  • Endometriosis / psychology
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Humans
  • Pelvic Pain / drug therapy
  • Placebo Effect
  • Quality of Life
  • Young Adult


  • Fatty Acids, Omega-3
  • Cholecalciferol

Associated data