Science Update

Review Explores Role of Micronutrients, Antioxidative Status, and Endometrial Health

Endometriosis is characterized by the presence of endometrial tissue outside of the uterus, mainly in ovaries or other parts of the abdomen, often resulting in severe pelvic pain and significant impacts on quality of life. It affects approximately 10% of reproductive-aged women; however, diagnosis is commonly delayed between 4 and 11 years after symptom onset and there is currently no known cure. While the pathophysiology of endometriosis is not fully understood, the pain associated with endometriosis has been linked to the inflammatory response; the overproduction of prostaglandins and pro-inflammatory cytokines can incite central nervous system sensitization and stimulate a pain response. 

Some preliminary research suggests that antioxidative status in the body may be associated with certain aspects of endometrial health. One study linked a higher intake of citrus fruits with a lower risk of endometriosis. Recent clinical evidence suggests that certain vitamins and micronutrients may help support endometrial health and the body’s response to endometriosis-associated pain. 

A systematic review and meta-analysis by Zheng and colleagues investigated the role of vitamins known to support antioxidative status and the inflammatory response in endometrial health. The study included data from 13 randomized controlled trials, involving a total of 589 participants and supplementation with either vitamin C, D, or E. When compared with a placebo, decreases in pain scores were observed in studies using vitamin C and vitamin E. Overall, significant reductions in chronic pelvic pain associated with endometriosis were reported in this meta-analysis.  

In addition, the meta-analysis found significant decreases in certain inflammatory markers in peritoneal fluid upon supplementation with vitamins C and E compared with placebo. These inflammatory markers include interleukin(IL)-6 and monocyte chemoattractant protein-1 (MCP-1/CCL2). MCP-1/CCL2 helps regulate the migration and infiltration of monocytes and macrophages from the bloodstream across the vascular endothelium as part of the inflammatory response. Improvements in antioxidative status, including malondialdehyde levels, were also reported in the presence of vitamin C and E when compared with placebo. Improvements in pain associated with dyspareunia were observed when a combination of vitamin C and E was administered for 8 weeks. However, due to the size and lack of heterogeneity among the studies, clinical conclusions cannot be made from this meta-analysis. Further research is required, particularly studies with fewer variables, more unified primary outcomes, clearly stated forms of vitamin E used, and larger patient populations. 

Genistein, a flavonoid derived from soybeans and other legumes, may help support the inflammatory response, antioxidative status, and endometrial health. In an animal study, genistein was shown to help decrease the expression of cyclooxygenase-2 (COX-2) in endometriosis mouse models. Genistein may also reduce pro-inflammatory cytokines including IL-6, IL-1ꞵ, and tumor necrosis factor-α. It also may influence nitric oxide production and intracellular levels of reactive oxygen species (ROS).

While more research is needed, certain vitamins and phytonutrients may help promote endometrial health. They may also help promote a healthy inflammatory response, antioxidative status, and a normal pain response.

By Dr. C. Ambrose, ND, MAT