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
Main article: Endometriosis and getting pregnant
In women with endometriosis, oxidative stress is believed to be one of the causes of increased inflammation. Oxidative stress on its own occurs when there is an imbalance between reactive oxygen species (ROS) and antioxidant levels in the body.
Previous studies found that women with endometriosis have higher levels of ROS and decreased total antioxidant capacity (TAC) compared to healthy women. This led to the idea that improving antioxidant levels in these women may correct some of the endometriosis related changes in the body.
Two of the most prominent antioxidants, vitamin C and E are generally combined, to help with vitamin E recycling, which together can neutralise free radicals and ROS.
However studies to date on vitamin C and E supplementation in women with endometriosis have been contradictory with experts concluding that more randomized controlled trials of sufficient size are needed to confirm any real benefit.
To evaluate the effect of vitamin C and vitamin E coadministration on oxidative stress markers and the severity of pain in women with endometriosis.
To answer this question a triple-blinded, randomized, placebo-controlled trial was carried out with the assistance of 60 women diagnosed with endometriosis (Stage 1-3) and pelvic pain.
To minimise potential bias all participants had no history of pelvic inflammatory disease, chronic autoimmune disease or metabolic/endocrine diseases, did not use supplements (past 6 months), smoke or drink alcohol and where not vegetarian.
Participants were then randomized into 2 even groups (Group A=30, Group B=30) by an independent person not involved in the study. This ensured that participants, researchers and the statistician were completely blinded to the group allocations.
Group A was given a combination of vitamin C (1000mg/day) and vitamin E (800IU/day), while Group B was given a similar combination of placebo pills, to take daily for a total of 8 weeks.
Blood samples were collected before and after to measure malondialdehyde (MDA), ROS and TAC levels, while a visual analogue scaling (VAS) system was used to estimate the (pelvic) pain intensity of women before, and every 2 weeks, following the trial.
Baseline (pre-trial) characteristics of the 2 groups showed no statistically significant differences in their mean age, BMI, fertility, menstruation and prevalence of dysmenorrhea. On the other hand baseline levels of MDA and ROS were significantly lower in Group B (Placebo) however this had no impact on final results.
After 8 weeks, the combined administration of vitamin C and E significantly reduced the levels of MDA and ROS compared to pre-trial levels in both groups (p≤0.002) while TAC levels showed no real change.
|Before (µM)||After (µM)|
Analysis of secondary outcomes showed a significant reduction in the VAS scores for dysmenorrhea, dyspareunia and chronic pelvic pain in Group A while the Group B (Placebo) only reported significant improvement in dysmenorrhea and dyspareunia.
Advanced statistical analysis showed the reduction in dysmenorrhea and dyspareunia VAS scores was significantly greater in Group A compared to Group B (Placebo), P≤0.006, suggesting the combined supplementation of vitamin C and vitamin E in women with endometriosis can significantly improve endometriosis related symptoms.
These results add further evidence to previous study findings that combined supplementation of vitamin C and E decreases peripheral MDA and ROS levels, moderating inflammation and other pathways linked to endometriosis associated pain.
SUMMARY: VITAMINS FOR ENDOMETRIOSIS
In this study, combined supplementation of vitamin C and vitamin E in women with endometriosis for 8 weeks significantly reduced levels of oxidative stress (MDA) and reactive oxygen species (ROS), leading to a significant decrease in dysmenorrhea, dyspareunia and chronic pelvic pain intensity scores.
- Small scale study
- Short study period (8 weeks)
This study was funded by the Iran University of Medical Sciences and Sarem Fertility and Infertility Research Center.
Pain during menstruation.
Pain during intercourse.
Naturally occurring compound in the body commonly used as a biomarker for oxidative stress.
Darling A M, et al. (2013). A Prospective Cohort Study of Vitamins B, C, E, and Multivitamin Intake and Endometriosis. https://doi.org/10.5301/JE.5000151
Santanam N, et al. (2013). Antioxidant supplementation reduces endometriosis-related pelvic pain in humans. https://doi.org/10.1016/j.trsl.2012.05.001
Mier-Cabrera J, et al. (2009). Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet. https://doi.org/10.1186/1477-7827-7-54
Mier-Cabrera J, et al. (2008). Effect of vitamins C and E supplementation on peripheral oxidative stress markers and pregnancy rate in women with endometriosis. https://doi.org/10.1016/j.ijgo.2007.08.018
Jackson L W, et al. (2005). Oxidative stress and endometriosis. https://doi.org/10.1093/humrep/dei001
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