Targeted Natural Interventions
Omega-3 Fatty Acids
The pain and infertility associated with endometriosis are likely due to increased levels of inflammation (Sekhon 2013; Bulun 2009). Omega-3 fatty acids have generated interest because of their anti-inflammatory abilities (Zhang 2012). These anti-inflammatory capabilities are likely one mechanism by which omega-3 fatty acids help prevent the development of endometriosis (Missmer 2010). Animal studies have helped validate the importance of omega-3 fatty acids for treating endometriosis. One study using an animal model of endometriosis found that supplementation with eicosapentaenoic acid (EPA), an important omega-3 fatty acid found in fish, reduced inflammation of the endometrium and also reduced levels of other molecules associated with endometriosis (eg, prostaglandin E synthase, an enzyme related to the chronic inflammation in endometriosis) (Netsu 2008). Another study examined the effects of fish oil supplementation on an animal model of endometriosis and found that fish oil was able to reduce the incidence of endometriosis-associated adhesions (Herington 2013). A large study found that women who ate greater amounts of long-chain omega-3 fatty acids were also less likely to develop endometriosis (Hansen 2013).
Vitamins E and C
Many lines of evidence suggest that oxidative stress, which is caused by reactive oxygen species, contributes to several aspects of endometriosis (Carvalho 2012; Augoulea 2012; Augoulea 2009; Gupta 2006; Sekhon 2013). Therefore, it is not surprising that vitamins E and C, both of which possess considerable antioxidant properties, have been studied in the context of endometriosis. In a study of 91 infertile women, those with endometriosis were shown to have lower levels of vitamin C in their follicular fluid (ie, fluid surrounding the eggs in the ovaries) compared to women who did not have endometriosis; women with endometriosis also had lower levels of the endogenous antioxidant superoxide dismutase in their plasma (Prieto 2012). In another study of 78 women aged 18–40, a modest association was observed between endometriosis and increased levels of a marker of oxidative stress called thiobarbituric acid-reactive substances (Jackson 2005).
Other evidence suggests that lower intake of antioxidants, including vitamins E and C, selenium, and zinc, in women with endometriosis correlate with more severe disease (Hernandez Guerrero 2006). These findings suggest that increasing consumption of antioxidants may benefit women with endometriosis. Accordingly, in a randomized, placebo-controlled trial, 59 women between 19 and 41 years of age were allocated to receive a combination of 1200 IU of vitamin E along with 1000 mg of vitamin C or a placebo each day for 8 weeks. Following the 8-week treatment period, 43% of women who received the vitamin E and C combination experienced reduction in chronic pain, 37% experienced reduction in pain associated with menstruation, and 24% experienced reduction in pain during intercourse compared to the placebo group. Moreover, several markers of inflammation and oxidative stress were reduced in the peritoneal fluid of women who took the antioxidants (Santanam 2013).
N-acetyl cysteine (NAC) is a modified form of the natural amino acid cysteine (Muranaka 2013). It exerts several direct antioxidative actions and helps bolster the body’s intrinsic ability to combat oxidative stress by aiding the production of the endogenous antioxidant glutathione (Samuni 2013; Sadouska 2007). Several animal and human studies have shown that NAC may be an effective treatment option for endometriosis. In one animal model of endometriosis, 40 rats were randomized to receive one of 4 regimens: amifostine (a DNA protectant with antioxidant properties sometimes used to combat the side effects of cancer treatments), NAC, leuprolide acetate, or no treatment. Animals that received amifostine, lueprolide, and NAC exhibited a decrease in endometriotic lesion size and reduction in levels of the inflammatory marker TNF-α. When the groups were compared, the greatest reductions were noted in the animals allocated to NAC (Onalan 2013). Another study that examined the effects of NAC treatment both in human cell culture and in mice found that it reduced the oxidative stress burden and cellular proliferation in endometriosis. These findings led the researchers to conclude “Our […] model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis” (Ngo 2009). Additional positive results were noted in a study in which 92 women with endometriosis were allocated to receive NAC or no treatment for 3 months. Those who received NAC were administered 600 mg 3 times daily on 3 consecutive days per week. After the 3-month study period, endometriotic cysts were slightly reduced in size among women who took NAC, while a significant increase in cyst size was observed in the women who received no treatment. The researchers noted their findings for the efficacy of NAC were better than those reported after hormonal treatment of endometriosis. Significantly, 24 women who took NAC cancelled scheduled laparoscopy, whereas only a single non-treated subject did so. The scientists who conducted this study remarked “We can conclude that NAC actually represents a simple effective treatment for endometriosis, without side effects, and a suitable approach for women desiring a pregnancy” (Porpora 2013).
Additional Experimental Therapies
Green tea. Green tea is rich in compounds called polyphenols, which have a number of beneficial effects. In particular, green tea contains large amounts of a sub-class of polyphenols, called catechins, of which the most extensively studied is epigallocatechin gallate (EGCG). EGCG is the most abundant catechin in green tea, comprising 50–80% of the total catechins. EGCG and the other catechins have a variety of effects that may benefit women with endometriosis. They can inhibit the development of endometriotic lesions, inhibit inflammation, and exert anti-angiogenic effects (Man 2012).
The anti-angiogenic effects of green tea and EGCG have been researched in the context of endometriosis. In preclinical research of endometriosis, EGCG was able to decrease the growth of endometrial implants and reduce the formation of new blood vessels to ectopic endometrial tissue (Xu 2009; Ricci 2013).
Resveratrol. Resveratrol is a polyphenolic compound found in certain foods, including grapes, peanuts, some berries, and red wine (Higdon 2005). In preclinical research of endometriosis, resveratrol treatment reduced endometrial implants by 60% and total volume of lesions by 80%. Resveratrol inhibited angiogenesis in endometriotic lesions, a potential mechanism for resveratrol’s growth suppressing effects on this tissue (Bruner-Tran 2011; Rudzitis-Auth 2013; Ricci 2013).
Curcumin. Curcumin is a polyphenol derived from the Curcuma family of plants (Sharma 2005). Curcumin has anti-inflammatory, antioxidant, and anti-proliferative properties (Swarnakar 2009). Preclinical studies have suggested curcumin treatment would be helpful in endometriosis. Curcumin has shown anti-endometriotic effects by acting on cellular signaling pathways (eg, inhibiting NF-kB translocation and MMP-3 expression) and inducing apoptosis in endometriomas (Jana, Paul 2012; Jana, Rudra 2012; Swarnakar 2009).