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

Abstract

<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> <jats:p>This trial was registered at clinicaltrials.gov as NCT02387931.</jats:p> </jats:sec>

Endometriosis: Etiology, pathobiology, and therapeutic prospects

“…Results from trials in women with painful endometriosis have been less clear cut; in a pilot trial comparing women taking 1,000 mg O-PUFA with 1,000 mg olive oil for 8 weeks, there were no adverse effects but the study was underpowered for efficacy (Abokhrais et al, 2020). In a study focused on 147 young women (12-25 years of age) who were assigned to groups taking vitamin D, 1,000 mg O-PUFA, or placebo for 6 months, the change in pain scores was not statistically significant and there was improvement in the placebo group (Nodler et al, 2020). Further properly powered RCTs are required, and the impact of placebo on pain perception needs to be considered before we can be sure O-PUFA offers real clinical benefit.…”

Endometriosis, an Ongoing Pain—Step-by-Step Treatment

“…Thus, an anti-inflammatory diet could be useful. A prospective study has shown, for example, that the intake of fish oil (omega-3 unsaturated fatty acids) reduced the risk of EM recurrences [32]. The ratio of unsaturated fatty acids to saturated fatty acids was important in this context [32].…”

“…A prospective study has shown, for example, that the intake of fish oil (omega-3 unsaturated fatty acids) reduced the risk of EM recurrences [32]. The ratio of unsaturated fatty acids to saturated fatty acids was important in this context [32]. Vitamin C, E and A, selenium and zinc also have an antioxidant effect.…”

Targeting Oxidative Stress Involved in Endometriosis and Its Pain

“…Researchers have also compared the efficacy of vitamin D and omega-3 fatty acids in reducing oxidative stress, pain, and the sizes of endometriotic lesions. In a randomized, double-blind, placebo-controlled study, female patients suffering from dysmenorrhea experienced a significant reduction in pain using the VAS score after taking vitamin D [ 129 , 130 ]. The participants in this study were randomly assigned to take either a placebo, 1000 mg fish oil, or 2000 IU vitamin D 3 [ 129 ].…”