The Effect of Combined Vitamin C and Vitamin E Supplementation on Oxidative Stress Markers in Women with Endometriosis: A Randomized, Triple-Blind Placebo-Controlled Clinical Trial

Abstract

Background. Endometriosis is a chronic and estrogen-dependent pelvic inflammatory disease, which may have various causes, such as oxidative stress. Dysmenorrhea, dyspareunia, and pelvic pain are well-known symptoms of endometriosis. The present clinical trial assessed the role of supplementation with antioxidant vitamins on the indices of oxidative stress as well as the severity of pain in women with endometriosis. Materials and Methods. We enrolled 60 reproductive-aged (15–45 years) women with pelvic pain in this triple-blind clinical trial. They had 1–3 stages of laparoscopic-proven endometriosis. The participants were randomized to group A (n = 30), given vitamin C (1000 mg/day, 2 tablets of 500 mg each) and vitamin E (800 IU/day, 2 tablets of 400 IU each) combination, or group B (n = 30), given placebo pills daily for 8 weeks. Results. Following treatment with vitamin C and vitamin E, we found a significant reduction in MDA and ROS compared with the placebo group. There was no significant decline in total antioxidant capacity after treatment. However, the severity of pelvic pain ( p value <0.001), dysmenorrhea ( p value <0.001), and dyspareunia ( p value <0.001) significantly decreased in the treatment group after 8 weeks of supplementation. Conclusions. The present findings support the potential role of antioxidants in the management of endometriosis. The intake of vitamin C and vitamin E supplements effectively reduced dysmenorrhea severity and improved dyspareunia and severity of pelvic pain.

Towards Personalized Antioxidant Use in Female Infertility: Need for More Molecular and Clinical Studies

“…As to endometriosis, RCTs showed that in vivo treatment of patients with vitamins C and E reduced pelvic pain and decreased the concentration of peritoneal fluid inflammatory markers as compared with untreated patients ( Table 1 ). The study failed to detect any positive effect of in vivo treatment of patients with endometriosis with vitamin C on in vitro fertilization (IVF) outcomes [ 21 ], while resveratrol supplementation during IVF cycles even appeared to be detrimental to pregnancy outcomes ( Table 1 ) [ 22 ]. Further studies are needed to find out whether other combinations of antioxidant medicines could also improve IVF outcomes, in addition to reduce pain and inflammation, in patients with endometriosis.…”

Targeting Oxidative Stress Involved in Endometriosis and Its Pain

“…Due to ascorbic acid’s potential as a powerful antioxidant and anti-inflammatory agent, other studies have suggested its potential benefit in treating endometriosis [ 46 , 114 , 115 , 117 ]. Another mechanism for reducing oxidative stress due to iron overload or iron deficiency is by utilizing ascorbic acid’s regulatory function on iron metabolism [ 118 ]. Thus, vitamin C and other similar antioxidants may be efficacious treatment options for disorders with underlying iron overload which leads to ferroptosis [ 118 ].…”

“…Another mechanism for reducing oxidative stress due to iron overload or iron deficiency is by utilizing ascorbic acid’s regulatory function on iron metabolism [ 118 ]. Thus, vitamin C and other similar antioxidants may be efficacious treatment options for disorders with underlying iron overload which leads to ferroptosis [ 118 ]. Vitamin E, α-tocopherol ( Figure 3 ), is a fat-soluble vitamin that has been utilized in other studies to treat cancer and atherosclerosis, yet the results have been conflicting [ 117 , 119 ].…”

“…Another study conducted by Amini et al, gave women with pelvic pain placebo tablets (control group) or a combination supplement of vitamin C (1000 mg) and E (800 IU) daily for eight weeks [ 118 ] and found a significant decrease in the severity of pelvic pain, dyspareunia, and dysmenorrhea in the treatment group after 8 weeks of combined vitamin C and E therapy [ 118 ]. These supplemented women had a significant decline in the pro-oxidant marker malondialdehyde (MDA) and ROS levels in comparison to the placebo group [ 118 ].…”

“…Another study conducted by Amini et al, gave women with pelvic pain placebo tablets (control group) or a combination supplement of vitamin C (1000 mg) and E (800 IU) daily for eight weeks [ 118 ] and found a significant decrease in the severity of pelvic pain, dyspareunia, and dysmenorrhea in the treatment group after 8 weeks of combined vitamin C and E therapy [ 118 ]. These supplemented women had a significant decline in the pro-oxidant marker malondialdehyde (MDA) and ROS levels in comparison to the placebo group [ 118 ]. Though some studies have not been able to demonstrate a correlation between vitamin C and E therapy and reduced ROS levels, other studies have demonstrated the efficacy of these supplements as a viable means to reduce oxidative stress markers and pain in endometriosis [ 45 , 121 ].…”