The Role of Dietary Supplements in the Treatment of Endometriosis: A Critical Review

The meta-analysis of nine studies including 976 women with endometriosis and 676 controls showed that the studies assessing the deficiency of vitamin D in women with endometriosis are inconclusive. Three of them showed no differences in vitamin D levels between women with and without endometriosis, while six showed significantly lower levels of this vitamin in women with endometriosis [ 12 ]. Vitamin D influences cell differentiation and proliferation by an immunomodulating effect [ 13 ]. Its receptors and metabolizing enzymes are found in various immune cells as well as in ovaries and the endometrium [ 14 ]. It has also been shown that vitamin D increases anti-inflammatory and decreases pro-inflammatory cytokine release [ 15 ]. These effects indicate a potential benefit of vitamin D supplementation in the treatment of endometriosis. We analyzed the results of four available studies that assessed vitamin D supplementation in women with endometriosis. This analysis is presented in Table 2 . Only one of the four studies showed the effectiveness of vitamin D supplementation in treating endometriosis-related pain. Furthermore, the administration of a single high dose of vitamin D did not affect the rate of clinical pregnancy in women with endometriosis subjected to an in vitro procedure. Thus, although some studies have shown lower serum vitamin D concentrations in women with endometriosis [ 16 ] and an association between low vitamin D consumption in the diet and the higher risk of the development of endometriosis [ 17 ], its supplementation does not affect the course of this disease. Vitamin C is one of the most important anti-oxidants in the human body [ 21 ]. It also has anti-inflammatory and anti-angiogenic effects [ 22 ]. Some studies suggested that higher dietary intake of vitamin C decreased the rate of endometriosis diagnosis [ 23 , 24 ]. However, only one randomized placebo-controlled trial, including 245 women with endometriosis aged 28–35 years, assessed the effect of supplementation of 1000 mg vitamin C for 2 months on the outcome of in vitro fertilization. This study showed no significant change in retrieved oocyte, implantation and clinical pregnancy rate between the study and control groups [ 25 ]. The main effects of vitamin E include the inhibition of lipid peroxidation and oxidative stress [ 26 ]. Lower serum vitamin E levels in women with moderate-to-severe endometriosis were observed than in women with minimal to mild endometriosis [ 27 ]. In the prospective cohort Nurses’ Health Study II performed between 1991 and 2005 a total of 1383 incident cases of laparoscopically confirmed endometriosis were observed among 70,617 women during 735,286-person years of follow-up. Dietary intake of thiamine, folate, vitamin C and vitamin E was inversely associated with the risk of the development of endometriosis, while taking these vitamins in supplement form had no such effect [ 23 ]. There is a lack of randomized controlled clinical trials assessing vitamin E supplementation in the treatment of endometriosis. We analyzed four studies that assessed the supplementation of high doses of both vitamin C and E ( Table 3 ). Three of these studies showed a reduction in the severity of chronic pain, three in pain associated with menstrual cycle, and two in dyspareunia. However, it should be noted that the time of observation in all analyzed studies was short (8 weeks). Therefore, considering the variability of pain intensity in the natural course of endometriosis based on an observation time equal to two menstrual cycles, it is difficult to draw conclusions that this supplementation is effective in the treatment of pain associated with it.

Zinc has anti-inflammatory properties. It also plays an important role in reductions in oxidative stress [ 32 , 33 ]. Some studies have shown lower serum zinc levels in women with endometriosis [ 34 , 35 ]. Moreover, lower zinc levels were observed in the ovarian follicular fluid of infertile women with endometriosis than women with tubal infertility [ 36 ]. There is a lack of studies assessing zinc supplementation solely in the treatment of endometriosis. So far only one multicenter open-label non-comparative clinical trial, including 346 women with endometriosis aged 27–42 years, assessed zinc supplementation as a part of the oral administration of N -acetyl cysteine 600 mg, alpha-lipoic acid 200 mg, bromelain 25 mg and zinc 10 mg daily for 6 months in the treatment of chronic pain associated with endometriosis. This study showed a statistically significant decrease in the pain severity assessed on the basis of the visual analog scale (VAS) after 3- and 6-month therapy periods [ 37 ]. No conclusions can be drawn from this study about the benefits of zinc supplementation in the treatment of chronic pain associated with endometriosis. Magnesium participates in protein and deoxyribonucleic acid (DNA) synthesis, enzyme activity, and neuromuscular excitability [ 38 ]. It has been found that magnesium relaxes smooth muscles and may decrease the retrograde menstruation considered to be one of the causes of endometriosis [ 39 ]. Moreover, in the results of a prospective cohort study including 70,556 premenopausal US women that assessed consumption of macro and micronutrients based on a 130-item food-frequency questionnaire (FFQ) at baseline and every four years during follow-up, a 14-year period showed an inverse association between magnesium consumption and the occurrence of endometriosis [ 17 ]. There is a lack of studies assessing magnesium supplementation solely in the treatment of endometriosis. Currently, only one prospective, randomized, double-blind, placebo-controlled trial assessed the effect of the magnesium sulfate (50 mg in 100 mL saline administered intra venous) (MAG) addition to tincture of opium (TOP) and buprenorphine (BUP) on pain and quality of life in women with dysmenorrhea (106 with diagnosed and 57 with suspected endometriosis). In this study patients were randomized into six subgroups (1:1:1:1:1:1) treated with TOP + MAG, BUP + MAG, TOP + placebo, BUP + placebo, placebo + MAG, and placebo + placebo for the duration of six monthly menstrual periods. There were no significant differences in pain severity and quality of life between subgroups treated with placebo + MAG and placebo + placebo [ 40 ]. Selenium is an anti-oxidant necessary for intracellular redox reactions by regulation of the enzyme glutathione peroxidase. So far only one triple-blind randomized controlled trial including 64 Iranian women with endometriosis aged 15–49 years assessed the effect of 3 months of 200 μg/day selenium or placebo supplementation on the intensity of dysmenorrhea, dyspareunia, dysuria, dyschezia and noncyclic pain using the VAS and changes in endometrioma size. The study showed a statistically significant decrease in the severity of dysmenorrhea, dyspareunia, dysuria, dyschezia and noncyclic pain and a reduction in endometrioma size in the group using selenium compared to the placebo [ 41 ]. However, the small study group size and short time of supplementation do not allow confirmation of this treatment effectiveness.

Alpha-lipoic acid (α-LA) has anti-inflammatory and anti-oxidant properties. There is a lack of studies assessing the administration of α-LA alone. We analyzed three studies in which α-LA was one of the components of the used dietary supplements ( Table 4 ). All analyzed studies showed a significant decrease in the severity of chronic pelvic pain, dysmenorrhea and dyspareunia. However, it should be noted that none of these studies were randomized, double-blind, placebo-controlled clinical trials. Polyunsaturated fatty acids omega-3 have antiproliferative, anti-angiogenic, anti-inflammatory, and anti-apoptotic effects [ 44 ]. However, the data from two case–control studies conducted in Northern Italy between 1984 and 1999 including 504 women aged <65 years with a laparoscopically confirmed diagnosis of endometriosis and 504 controls showed no association between fish consumption and endometriosis [ 45 ]. We analyzed the results of three available randomized controlled trials ( Table 5 ). Just one of these studies showed the effectiveness of omega-3 fatty acids in treating symptoms caused by endometriosis.

Probiotics modulating intestinal microbiota improved immunity. Moreover, the Lactobacillus plantarum , Lactobacillus reuteri , Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum contained in probiotics produce vitamin B [ 48 ]. These properties may potentially influence the course of endometriosis. We analyzed two available randomized placebo-controlled trials ( Table 6 ). Their results do not allow us to conclude that probiotics are effective in treating pain associated with endometriosis.

In vitro and vivo studies showed that polyphenol curcumin has anti-inflammatory, anti-oxidant, anti-mutagenic, anti-metastatic, anti-tumor, and hormonal regulation properties [ 51 ]. It has also been found that curcumin inhibits estrogen production and in this way the development of endometriosis [ 52 ]. We analyzed two available randomized placebo-controlled trials and one open-label study ( Table 7 ). Their results do not allow us to conclude that curcumin is effective in treating pain associated with endometriosis. Resveratrol has anti-inflammatory, anti-oxidant, anti-atherogenic, and anti-angiogenic properties [ 56 ]. The experimental studies assessing the effect of resveratrol use in endometriosis showed that resveratrol may inhibit the development of endometriosis [ 57 , 58 , 59 , 60 , 61 ]. One randomized controlled trial and one observational study assessed the addition of resveratrol to contraceptive pills ( Table 8 ).

The flavonoids contained in propolis have anti-inflammatory, anti-oxidant, anti-bacterial, and anti-viral properties [ 64 ]. An experimental study showed that chrysin, one of the flavonoids found in propolis, suppresses the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, decreasing the proliferation of endometriotic cells and increasing its apoptosis [ 65 ]. Only one study assessed the effect of propolis use in women with endometriosis. This prospective, randomized, placebo-controlled, blind trial including 40 women with laparoscopically diagnosed minimal or mild endometriosis aged 28–36 years treated with 500 mg of bee propolis or placebo daily for 9 months showed that bee propolis was superior to the placebo for pregnancy rate [ 66 ]. However, this study is not sufficient to recommend the use of propolis in the treatment of endometriosis. Quercetin is a flavonoid with a potential effect on apoptosis and anti-estrogenic and progestogenic properties [ 67 , 68 ]. There were no clinical trials assessing the effectiveness of quercetin monotherapy in the treatment of endometriosis. Two studies that assessed quercetin use as a component of fixed combination were described above [ 46 , 54 ], one of them being a randomized placebo-controlled clinical trial confirming the effectiveness of the combined preparation containing quercetin in the treatment of endometriosis. However, it should be noted that quercetin was one of the components of a combined preparation including quercetin, curcumin, parthenium, nicotinamide, 5-methyltetrahydrofolate, and omega-3/6 [ 46 ]. Experimental studies found that NAC, the acylated form of cysteine, decreases cell proliferation and its locomotor behavior as well as downregulates inflammatory cytokine activity [ 69 ]. There is a lack of randomized placebo-controlled trials assessing the effectiveness of NAC in the treatment of endometriosis. We analyzed data from three available studies including two observational cohort studies and one randomized clinical trial ( Table 9 ). Although two observational studies showed the effectiveness of NAC in treating pain associated with endometriosis, these data are insufficient to recommend its use. EGCG is bioactive polyphenol especially found in green tea with anti-oxidant and anti-inflammatory properties. Experimental studies showed that EGCG suppresses the estrogen-related activation and proliferation of endometrial cells [ 73 , 74 , 75 ]. There is a lack of available clinical trials assessing the effectiveness of EGCG in the treatment of endometriosis. We found one registered clinical trial in the database of registered clinical trials: ‘Randomised Double-blinded Placebo Controlled Trial of Green Tea Extract for Endometriosis’. This study was planned to be performed from 2016 to 2022. According to data from 2023, all of the planned 185 women were included in the study with ultrasound-confirmed endometriosis [ 76 ]. However, the results of the study have not yet been published. Thus, there is currently no data to recommend EGCG in the treatment of endometriosis. DIM arises with indole-3-carbinol as a result of the digestion of cruciferous vegetables by stomach acid. It has been suggested that DIM may stimulate the production of a less potent, more beneficial form of estrogen known as 2-hydroxyestrone [ 77 ]. Only one single-center clinical observational study included an assessment of DIM effectiveness as a supplement to dienogest in endometriosis therapy. This study showed a significantly higher decrease in the severity of chronic pelvic pain associated with endometriosis. However, the cited study included only eight women with endometriosis which is insufficient to determine the effectiveness of DIM [ 78 ]. A structural analog of anandamide N -Palmitoylethanolamine (PEA) has anti-inflammatory, immunosuppressive, analgesic, neuroprotective, and anti-oxidant properties [ 79 ]. While polydatin (PLD) is a natural glucoside of resveratrol, inhibiting the synthesis and release of pro-inflammatory cytokines and mast cells degranulation as well as modifying eicosanoid synthesis [ 80 ]. We analyzed data from three available studies assessing the effects of PEA and PLD supplementation on pain associated with endometriosis including one randomized, double-blind, parallel-group, placebo-controlled clinical trial ( Table 10 ). The cited trial showed that the combination of PEA and PLD is superior to placebo but not to Celecoxib regarding the treatment of pain in endometriosis [ 81 ]. The effectiveness of this combination in treating endometriosis-related pain is also suggested by observational studies [ 82 , 83 ]. However, these data are insufficient to recommend the combination of PEA and PLD in the treatment of endometriosis-related pain.

The main symptoms of endometriosis are various types of pain, such as chronic pelvic pain, dysmenorrhea, and dyspareunia. Pain significantly impacts the daily functioning, mental state, and social interactions of women with endometriosis. Effective treatment is difficult in clinical practice because the pain experience and response to treatment are individual. The results of numerous experimental studies demonstrating the effectiveness of various dietary supplements in the treatment of endometriosis, as well as the results of studies demonstrating the relationship between vitamin and other dietary intake and the occurrence of endometriosis, may raise hopes not only among women with endometriosis but also among physicians that supplementation will bring beneficial results. These hopes may be supported by research demonstrating the effectiveness of various dietary supplements. This critical review of such studies clearly indicates that there is a lack of evidence supporting the effectiveness of the dietary supplements analyzed in the treatment of endometriosis. In Table 11 , we once again summarize the results of randomized placebo-controlled clinical trials assessing the effect of the analyzed dietary supplements on the severity of pain associated with endometriosis. It should be noted that all these studies were single-center and included a small number of participants. It should be noted that there is a lack of RCT studies assessing the effectiveness of vitamin E, zinc, α-LA, EGCG, and DIM. The supplementation of vitamin C, magnesium, selenium, resveratrol, propolis, NAC and PEA and PLD were assessed in single RCTs. Four RCTs evaluating vitamin D supplementation varied in dose and duration, the number of patients included, and patients’ age and endometriosis severity, as well as endpoints (3: severity of pain; 1: pregnancy rate). Among the four RCTs assessed, supplementation with vitamins C and E was assessed in three studies; the doses, durations, and endpoints were the same across all four, but the number of patients, age, and endometriosis severity varied between studies. Of the two RCTs evaluating omega-3 supplementation, only one assessed its use alone. In two RCTs analyzing probiotics, the effectiveness of supplementation with different strains was assessed. Two RCTs assessed curcumin supplementation, varying in dose and duration; they included different numbers of patients, different ages, and different endometriosis severities, as well as endpoints (1: severity of pain; 1: severity of pain and endometrioma size). Despite being classified as RCTs, the strength of evidence is low due to small group sizes, short observation periods, and the lack of multicenter studies. The characteristics of the analyzed RCTs are presented in Table 12 . In summary, the endpoints in most RCTs were subjective assessments of endometriosis-related pain intensity; some assessed only chronic pain intensity, and some also included dysmenorrhea and dyspareunia. It is also important to note the different doses used for these supplements, which were studied more extensively; the variable duration of intervention; the lack of analysis of endometriosis stages and duration; missing laparoscopic confirmation in some studies; and the lack of analysis of other clinical conditions that may influence pain intensity, such as depression or functional gastrointestinal disorders, could have significantly impacted the results of the analyzed studies. Despite the hopes raised by the results of experimental and some observational studies as well, their comparison with RCTs, even those conducted in small groups, does not allow us to conclude that any of the supplements analyzed should be included in the standard treatment of women with endometriosis. However, at this stage, the low quality of the RCTs does not allow us to fully deny their effectiveness. Therefore, large, multicenter studies are necessary, especially for supplements that have demonstrated potential efficacy in all types of studies conducted to date. A summary of the effectiveness of the individual supplements analyzed in various types of studies is presented in Table 13 . It should be noted that for a significant part of the dietary supplements discussed in this study, observational studies or RCTs assessing their effectiveness primarily in the treatment of pain caused by endometriosis, in vitro studies have not been conducted; these include zinc, magnesium, selenium, α-LA, probiotics and the combination of PEA and PLD. Some of them, including zinc, selenium, α-LA, and probiotics, have also not been studied in animal models. The rationale for their use was sought based on potential mechanisms of action known from other studies. On the other hand, for supplements such as vitamin D, vitamin C, magnesium, omega-3, curcumin, resveratrol, NAC, and the combination of PEA and PLD, despite encouraging results from in vitro and/or experimental animal studies, RCTs have yielded either negative or inconsistent findings. This may be due to biological diversity, insufficiently low doses, or too-short duration of application, and the use of endpoints that primarily focus on subjective pain assessment. Considering the limitations of the existing research and the discrepancies between experimental, observational, and RCT studies, well-designed RCTs are essential to confirm or refute the role of dietary supplements in the treatment of endometriosis. These studies should be multicenter and include an appropriate statistically supported study group size, stage of endometriosis, surgical treatment, disease duration, location, standardized doses, potential combinations of supplements with different mechanisms of action, and well-established endpoints (in the case of subjective scales analyzing pain intensity, the use of more than one tool should be considered). Study duration is also important; following the example of many clinical trials, we suggest a minimum of 54 weeks of intervention, with at least 12 weeks of follow-up after treatment, and finally, an assessment of willingness to maintain the intervention after trial completion.

The main limitation of the review is the lack of multicenter randomized placebo-controlled trials. The second limitation is that all of the studies were performed in small groups. Third is the short duration of all randomized placebo-controlled trials. Fourth, this review did not include publications in languages other than English.

Endometriosis is a frequent cause of chronic pelvic pain in women and may be accompanied by infertility [ 1 ]. The symptoms of endometriosis depend on its localization: abdominal or extra-abdominal. The red flags of pelvic endometriosis include chronic pelvic pain with or without cyclic flares as well as gastrointestinal and urinary symptoms [ 2 ], while the symptoms related to extra-abdominal endometriosis are pain under the shoulder blade, catamenial pneumothorax, cyclical cough/hemoptysis/chest pain, and cyclical scar swelling/pain [ 3 ]. Although endometriosis occurs in 2–10% of women in reproductive age its pathogenesis is still not fully understood. The known mechanisms include uterine tissue damage or scarring; the uterine microenvironment; stem cells; remnant cells from menstrual blood; hormones; and genes products regulating inflammation, apoptosis, invasion, angiogenesis, autophagy, and oxidative stress [ 4 , 5 , 6 ]. It is believed that the key mechanism of the initiation and adhesion of endometriosis lesions as well as infertility and pain related to endometriosis is inflammation involving macrophages, natural killer cells, T cells, and dendritic cells regulated by cytokines, prostaglandins, and chemokines, and excessive estrogen levels [ 4 , 7 , 8 , 9 ]. There are no clear guidelines for the treatment of endometriosis. The recommendations of various scientific societies differ, albeit slightly. Most widely accepted guidelines include those of six nationals [College National des Gynecologues et Obstetriciens Francais, National German Guideline (S2k), Society of Obstetricians and Gynaecologists of Canada, American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM) and National Institute for Health and Care (NICE)] and two internationals (World Endometriosis Society and European Society of Human Reproduction and Embryology). Most of these guidelines in the treatment of endometriosis-associated pain recommended progestins (dienogest or medroxyprogestetrone acetate) and combined oral contraceptive pills as first line therapy with a great evidence grade. As second line should be considered GNRH-agonists and levonorgestrel intrauterine system. The surgical excision of the endometrial implants and the endometriomas also plays an important role in the treatment of pain related to endometriosis. While in the treatment of infertility associated with endometriosis the recommended first line is excision of endometriomas and endometriosis, the second line therapy is ablation of the ovarian endometriosis. Pharmacotherapy is not recommended, except GNRH-agonist used prior to in vitro fertilization or surgery. None of the above societies recommend the use of dietary supplements in the treatment of pain and infertility associated with endometriosis [ 10 ]. However, there is a growing number of studies suggesting the effectiveness of dietary supplements in preventing and treating endometriosis. It has been suggested that deficiencies in vitamins D and E as well as zinc are associated with the increased risk of endometriosis development. Beneficial effects of magnesium, curcumin, resveratrol and epigallocatechin-3-gallate were found in experimental animal studies. A reduction in pain related to endometriosis was shown in women using omega-3 and alpha-lipoic acid. Meanwhile, decreasing endometriotic lesion size after the supplementation of omega-3, N -acetylcysteine, vitamin C and epigallocatechin-3-gallate was observed in animal and human studies [ 11 ]. The rationale for using dietary supplements in the treatment of endometriosis is their potential impact on the pathomechanisms of this disease, as observed in experimental studies. The impact of individual supplements on the potential pathomechanisms of endometriosis is presented in Table 1 . Given that the suffering of women with endometriosis may prompt both them and less experienced doctors to seek alternative treatments, we decided to critically review the studies suggesting the effectiveness of dietary supplements in the treatment of endometriosis. Thus, the aim of the critical review was to summarize the available data describing the effects of dietary supplements such as vitamin D, vitamin C, vitamin E, zinc, magnesium, selenium, α-LA, omega-3, probiotics, curcumin, resveratrol, propolis, quercetin, NAC, EGCG, DIM and the combination of PEA and PLD used in the treatment of endometriosis.

The PubMed, Embase, Cochrane, and Web of Science databases were searched for related studies until 15 December 2025. A text search with the following keywords singly or in combination was conducted (in alphabetical order): agnus castus, ALA, alpha-lipoic acid, apple pectins, bilberry powder, bromelain, calcium D-glucorate, calcium L-methylofolate, choline, chromium, chrysin, curcumin, diindolylmethane, endometriosis, endometrioma, epigallocatechin-3-gallate, EGCG, folic acid, iodine, magnesium, milk thistle, N -acetyl cysteine, omega-3, palmitoylethanolamide, piper nigrum, polydatin, prebiotics, probiotics, propolis, quercetin, resveratrol, royal jelly, sea buckthorn, selenium, silibinin, silymarin, sulforaphane, synbiotics, Vaccinium myrtillus, vitamin B5, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, zinc, and endometriosis. The final search results were exported into EndNote, and duplicates were removed. The detailed search strategy is shown in Figure 1 . Accepted studies met the following criteria: (1) analysis of diet supplement use in women with endometriosis, (2) articles published in English, (3) studies involving human participants, and (4) studies including longitudinal studies, and meta-analysis. Papers were excluded if they did not fit into the conceptual framework of the study. Data extraction was conducted with the following information: (1) name of the first author, (2) publication year, (3) country, (4) study design, (5) sample size, (6) endometriosis diagnosis, (7) type of dietary supplement used and (8) comparison with a control group. Due to the fact that such a small number of studies were performed among women with endometriosis, and that our manuscript is a narrative review, the quality of the research was not assessed as a meta-analysis.

A detailed analysis of RCTs assessing the effectiveness of dietary supplements on the symptoms of endometriosis showed the lack of RCTs for vitamin E, zinc, α-LA, EGCG, and DIM. Moreover, single RCTs for vitamin C, magnesium, resveratrol, NAC, PEA, and PLD, despite experimental studies, confirmed their effectiveness. Furthermore, single RCTs on selenium, propolis, and quercetin confirmed their effectiveness in treating pain related to endometriosis. Finally, RCTs for vitamin D, omega-3, curcumin, and probiotics have yielded mixed results; only RCTs assessing the effectiveness of vitamin C and E have confirmed it. Despite encouraging observations from experimental studies, the results of RCTs are less encouraging and do not allow for the formulation of recommendations concerning the use of supplements in the treatment of endometriosis symptoms according to EBM.