Nutrition and Endometriosis: Current Evidence on Dietary Risk Factors and Clinical Impact - A Narrative Review

Endometriosis (EM) is a severe, chronic inflammatory disease affecting 10% of women of reproductive age. 1 EM is characterized by a wide range of serious symptoms including cyclic or chronic (pelvic) pain, dysmenorrhea, infertility, dysuria or dyspareunia. 2–5 Beyond the gynecological symptoms, EM is associated with non-specific gastrointestinal symptoms including diarrhea, abdominal pain, cramps, nausea, constipation, and the cyclical painful bloating of the abdomen (‘Endo belly`) as well as psychological comorbidities such as fatigue, depression or anxiety. 1 , 5–7 Thus, quality of life is substantially affected in multiple domains including social and socioeconomic functioning, 8 , 9 productivity loss and work absence with estimated annual costs of up to $20,000 per women. 10 Despite this substantial burden, the etiology of EM is barely understood, reflected by poor and delayed diagnosis and limited treatment options. 11 Standard treatment for EM encompasses a combination of hormone therapy, pain management and/or surgical remediation of lesions. 11 , 12 However, while some of the patients benefit from these treatments, the substantial part gains only limited or short-term benefits with residual symptoms and high recurrence rates. 13–15 Therefore, there is an urgent need for new, multimodal well-orchestrated treatment options beyond surgery or medication. 11 , 16 Evidence shows that diet and nutrition-related factors modulate inflammatory processes, immune function, and gut physiology that have been implicated in EM risk, disease course, pain, gastrointestinal symptoms and symptom progression in EM. 17–22 Given that a substantial proportion of women with EM suffer from gastrointestinal symptoms, nutrition represents a particularly compelling therapeutic target, as dietary modifications affect gut, microbiome, inflammation and may alleviate both gastrointestinal and systemic disease burden. Hence, individualized nutritional interventions are of utmost importance as a significant treatment approach sustainably improving health in women with EM in the long term. EM is characterized by the growth of endometrium-like tissue outside the uterine cavity – the so-called ectopic lesions. These lesions typically localize around reproductive organs, on the outside of the uterus, or the tissues surrounding the uterus and ovaries. Yet, they can also infiltrate pelvic organs like the bowels, ureter, stomach, bladder or rectovaginal septum. 23 Several theories postulate the dissemination of (stem) cells as principal cause for ectopic lesions eg, by retrograde menstruation or the lymphatic system - each failing to fully explain disease development or progression. 24–26 Beyond those hypotheses there are several other factors that impact the development of EM. Additional contributing factors include genetic predisposition, which may affect steroid hormone signaling, immune response and estrogen/progesterone receptor activity, 27–29 as well as inflammation, oxidative stress and immunological factors which promote lesion establishment and disease progression. 30 Changes in the estrobolome and gut microbiome might further contribute to immunometabolic alterations and hormonal imbalances associated with EM. 31 , 32 EM is therefore best explained as a multifactorial disease with a complex systemic nature. Ectopic endometrial lesions actively shape pro-inflammatory and immunologically altered microenvironments that support their survival, drive pain, and promote disease progression. 33 , 34 These lesions provoke a dysregulated immune response marked by simultaneous increase in pro-inflammatory and anti-inflammatory factors, contributing to persistent inflammation, impaired immune clearance of ectopic tissue up to neurogenic inflammation. 35–37 While inflammation in EM is most pronounced at the lesion site and even might differ between EM types, 33 , 38 systemic inflammation seems to drive disease progression and symptom severity 37 , 39–41 and might also contribute to an increased prevalence of cardiovascular disease, rheumatoid arthritis and systemic lupus erythematosus in EM. 42 , 43 In total, this points towards profound immunological alterations in EM, but their complexity and meaning, however, are not yet fully understood. Tightly linked to inflammation is the role of oxidative stress, defined as an imbalance between reactive oxygen species (ROS) production and the capacity of antioxidant defense systems to neutralize them. ROS are normally generated during cellular metabolism. However, under conditions of persistent inflammation as found in EM, excessive ROS production can overwhelm antioxidant defenses, leading to oxidative damage of cells or even DNA. 44 In EM, one source of ROS is the iron metabolism in the pelvic cavity. Through the menstrual influx via retrograde menstruation or bleeding lesions, the number of erythrocytes undergoing lysis increases, possibly causing iron overload which acts as a catalyst in ROS-generating reactions, causing oxidative stress which might play a role in increased symptom severity. 45 To counteract ROS, antioxidant defense mechanisms are activated, involving enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, as well as non-enzymatic antioxidants like vitamins C and E. The activity and expression of these antioxidants are diminished in women with EM, resulting in sustained oxidative damage. 46–48 In summary, hormonal and immunological dysregulation in EM foster a systemic pro-inflammatory milieu in which excessive ROS production contributes to inflammation and oxidative damage and may exacerbate symptom severity. Therefore, dietary interventions targeting anti-inflammatory and antioxidant effects might be a beneficial aspect in the treatment of EM. After systemic circulation, estrogens are conjugated in the liver, primarily through sulfonation and glucuronidation, and excreted into the intestine via bile. 49–51 In the gut, members of the estrobolome deconjugate these metabolites via enzymes such as β-glucuronidases and arylsulfatases, enabling reabsorption of biologically active estrogens through enterohepatic circulation. 52 , 53 Consequently, alterations in estrobolome composition or activity may influence systemic estrogen levels, 54 which are implicated in the pathophysiology of EM. 55 Gut microbial dysbiosis has been associated with EM in both humans and animal models. Reported alterations include an increased Bacillota/Bacteroidota ratio and higher abundances of Bifidobacterium relative to healthy controls. 36 , 56 , 57 Several studies have also identified enrichment of taxa with elevated β-glucuronidase activity, potentially increasing estrogen reactivation and systemic exposure. 58 Although causality remains unresolved, these microbial changes may contribute to disease progression. Supporting this hypothesis, broad-spectrum antibiotic treatment reduced lesion size and inflammation in a mouse model of EM, whereas fecal microbiota transplantation from diseased animals restored these phenotypes. 59 Metabolomic analyses further identified quinic acid as a microbiota-derived metabolite enriched in EM mice; quinic acid promoted endometriotic epithelial cell proliferation in vitro and exacerbated lesion growth in vivo. 60 To date, most studies have focused on taxonomic alterations associated with EM. However, taxonomic shifts do not necessarily reflect functional changes because of the substantial metabolic redundancy within the gut microbiome. 61 Functional characterization of microbiome–host metabolic interactions, particularly those involving the estrobolome, may therefore provide deeper mechanistic insight into EM pathogenesis and progression. Given that estrobolome composition is shaped by environmental factors, particularly diet, 62 targeted dietary interventions may represent a promising strategy to modulate estrogen metabolism and alleviate disease burden in patients with EM. Inflammation in EM leads to a pro-inflammatory and pro-oxidative microenvironment, which contributes to the persistence and growth of ectopic lesions, nociceptor sensitization, tissue remodeling, and systemic immune alterations. These inflammatory processes are closely linked to symptom manifestation, including chronic pelvic pain, dysmenorrhea, gastrointestinal disturbances, fatigue, and reduced quality of life. At the same time, alterations in the gut microbiome and estrobolome may exacerbate these effects by disrupting estrogen metabolism, promoting systemic low-grade inflammation, and influencing immune responses, thereby potentially amplifying both gynecological and gastrointestinal symptoms. Given the interplay between inflammation, oxidative stress, hormone dysregulation, and microbiome imbalance, dietary interventions emerge as a promising strategy to modulate these pathways. By targeting inflammatory processes, oxidative stress, and gut microbiota composition, nutrition could help alleviate symptom severity, support hormonal balance, and improve overall health outcomes in women with EM. The major fermentative products of the microbiome in the large intestine are the short-chain fatty acids (SCFAs), mostly butyrate, propionate and acetate. 63 SCFAs are produced during the fermentation of unabsorbed carbohydrates, such as dietary fiber, complex carbohydrates, or resistant starch. In the balanced microbiome–host interaction, SCFAs have manifold health-promoting effects, like supporting barrier integrity 64 and anti-inflammatory activity of cells from the innate immune system. 65 SCFAs reduce gut permeability and thus prevent the translocation of pro-inflammatory and oxidative stress-inducing molecules like lipopolysaccharide. 65 Both the reduced inflammation status and an improved redox balance can be beneficial for EM, since this is characterized by an elevated level of inflammatory cytokines 66 and oxidative damage in endometriotic lesions. 67 Chadchan et al reported an imbalance in composition of the gut microbiome, resulting in reduced production of n-butyrate in endometriotic mice 68 In their pre-clinical mouse model, n-butyrate, but not acetate or propionate, inhibits endometriotic lesion growth. The authors describe the three underlying mechanisms: activating GPR43 and GPR109A, inhibiting histone deacetylase activity, and activating expression of RAP1GAP, which inactivates the pro-growth RAP1 signaling pathway. The data from a mouse model of EM suggest a therapeutic potential for butyrate in the treatment of EM in humans, underscoring the importance of considering the gut microbiota and SCFA production in innovative therapeutic strategies. 69 Besides SCFAs, bile acids can also exert immunomodulatory effects and thus can contribute indirectly to the etiology of EM. 70 Bile acids are produced as conjugated primary bile acids in the liver and transported via the bile duct into the small intestine. There, they are essential for taking up lipids. 71 Together with them, they are partially reabsorbed and transported with the enterohepatic circulation to the liver. 72 Changes in the bile acid profile and abundance have been linked to EM by the findings of Cano-Sancho et al, who found that patients with EM showed lower levels of bile acids. The underlying mechanism might be a reduced biosynthesis of bile acids in the EM. 73 More specifically, chenodeoxycholic acid (CDCA) was found to be elevated in an EM mouse model. 74 However, neither CDCA nor ursodeoxycholic acid (UDCA) showed therapeutic effects. In summary, many microbiome-derived metabolites can influence the redox balance in the body of the host and especially the immune cells, by binding to a variety of specific receptors acting as transcription factors. Within the bacteria of the microbiome, the capacities for producing or modifying these metabolites are highly redundant. Consequently, it is hard to predict which changes in the composition result in an overall alteration in the metabolite-dependent microbiome-host interaction. This review aims to introduce nutrition as a promising treatment approach that could influence the course of EM on multiple pathomechanistic levels, including inflammation, oxidative stress, hormonal imbalance and gut microbiome composition. Based on the current state of research, we discuss the role of various nutrients and further food ingredients, food groups as well as dietary pattern, to evaluate their potential to support EM therapy by alleviating pain and further associated symptoms. Finally, first dietary recommendations for EM are derived based on the current state of research. This narrative review aimed to summarize and critically discuss the current evidence regarding the effects of the daily diet on EM risk and symptoms. Due to the broad range of nutrition-associated influences on the clinical manifestation of EM and the heterogeneity of study designs, populations, and outcome measures, a narrative synthesis approach was considered most appropriate. We conducted a literature search using the electronic databases PubMed, Web of Science, and Google Scholar. Studies published until December 2025 that dealt with the influence of nutrients, food groups, defined metabolites and contaminants covering the risk factors and treatment options for EM were included. We incorporated original research, including randomized and randomized and non-randomized clinical trials, prospective observational studies, retrospective cohort studies, case–control studies as well as mouse model data for selected topics (eg, area 7,8,9). Articles with available full text in English or German were included. Studies were considered eligible if they: Included adult human participants with EM, Reported EM outcomes related to nutrient intake/status, And were published in peer-reviewed journals in English or German. Included adult human participants with EM, Reported EM outcomes related to nutrient intake/status, And were published in peer-reviewed journals in English or German. An exceptional cases, animal studies were also taken into account where no human data were available. Case reports, conference abstracts, editorials, and studies lacking relevant outcome data were excluded. Titles and abstracts identified through the database search were screened for relevance. Potentially eligible articles were subsequently assessed in full text. Studies were selected based on their relevance to the review objective and their methodological quality. Preference was given to systematic reviews, meta-analyses, randomized controlled trials, and large prospective cohort studies. Relevant information from the included studies was extracted narratively, including study design, population characteristics, dietary assessment methods, main outcomes, and key findings. The research aspects were divided into thirteen areas: (1) dietary fat and fatty acids, (2) dietary protein and essential amino acids, (3) water-soluble vitamins, (4) fat-soluble vitamins, (5) minerals, (6) trace elements, (7) secondary plant compounds, (8) probiotics, (9) food additives, (10) MedD, and elimination diets such as (11) sugar-free and low in histamine, (12) impact of gluten, allergens, and food intolerances, as well as (13) fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs). The search was conducted using the following keywords and Medical Subject Headings (MeSH) terms “endometriosis”, “endometriosis risk” in combination with the discussed nutrients, food groups, metabolites, and contaminants (area 1–15). Results were summarized qualitatively and then critically analyzed in terms of effect size, physiological significance, and the consistency of the findings/evidence. Limitations: As a narrative review, this work does not follow a fully systematic review methodology and may therefore be subject to selection bias. Furthermore, heterogeneity in dietary assessment methods, and outcome measures limited direct comparability between studies. Dietary fat is an essential component of the human diet, exerting a significant influence on a wide range of physiological and pathophysiological inflammatory processes within the body. 75 The presence of selected saturated fatty acids (SFA) and industrial trans fatty acids (TFA) in plasma has also been shown to be associated with increased inflammation markers. 76 , 77 Among polyunsaturated fatty acids (PUFA), arachidonic acid (ARA, n -6) serves as a direct precursor of prostaglandin (PG) E 2 and PGF 2 -α, which are involved in triggering uterine cramps and are thus associated with dysmenorrhoea. 78 In addition, ARA serves as a predictor for leukotriene B 4 (LTB 4 ), which strongly mediates inflammatory symptoms. 79 In contrast, LTBs and PGs derived from long-chain n-3 PUFA exert anti-inflammatory effects and resolvins derived from EPA and DHA act pro-resolving. 79 , 80 As inflammation might play a role in the progression of the disease, they may contribute to alleviating endometriosis-associated symptoms. 81 Consequently, regulating both the type and amount of dietary fatty acids could be a potential strategy for disease management. Several observational studies have investigated the relationship between fatty acid quality and risk of EM, yielding contradictory results. In the Nurses’ Health Study II, the fatty acid intake of 1199 women with EM was analyzed. No associations were found between total fat intake, SFA and monounsaturated fatty acid (MUFA) and the risk of EM. In contrast, higher TFA intake was associated with an increased risk (0.9 En% vs 2.3 En%, multivariable RR 1.48, 95% CI: 1.17, 1.88, p < 0.001), while the intake of n-3 PUFA was linked to a reduced risk (0.8 En% vs 0.4 En%, multivariable RR 0.78, 95% CI: 0.62, 0.99, p = 0.03). Moreover, each isocaloric 1% En from n-3 PUFA as opposed to TFA was correlated with almost a 50% lower risk of EM (RR 0.52, 95% CI: 0.32, 0.85). 21 Similarly, Savaris et al found a lower intake of n-3 and n -6 PUFA in 25 EM patients compared to controls (n-3: 0.7 g ± 0.5 vs 1.5 g ± 1.6, p = 0.045; n-6: 9.6 g ± 7.7 vs 16.0 g ± 9.7, p = 0.006). 82 In contrast, Trabert et al demonstrated that a higher total fat intake (49.4 g and 67.7 g vs 31.8 g, p < 0.05) was associated with a reduced risk of EM in 284 patients (second quartile OR 0.6, 95% CI: 0.4, 1.0; third quartile OR 0.6, 95% CI: 0.3, 1.0, p < 0.05), although the result was no longer significant at the fourth quartile of intake (100.2 g). A similar, but not consistent, inverse association across different quartiles of SFA, MUFA and TFA intake and EM risk was observed. However, no such association was observed for the intake of n-6 or n-3 PUFA as well as consumption of fish in general. 83 In addition, three studies that have examined fatty acid composition in serum and erythrocytes as biomarkers of fatty acid intake, have yielded inconsistent findings. Khanaki et al identified a significant correlation between the EPA/ARA ratio and the severity of EM, ranging from stage I to stage IV (r = 0.34, p = 0.006). 84 In addition, stearic acid was lower in patients with EM compared to controls (12.5% vs 13.4%, p = 0.030). Kim et al compared women with EM to women with ovarian cysts and found no differences in fatty acid composition of their EM tissue, however EM patients exhibited elevated levels of EPA (17% vs 1.1%, p = 0.03) and DHA (9.4% vs 7.9% p < 0.01) in erythrocytes. 85 In contrast, Hopeman et al found lower levels of serum EPA in women diagnosed with EM (0016 vs 0.02, p = 0.005) and women with the highest serum levels were 82% less likely to be diagnosed with EM (OR 0.18, 0.04, 0.78, p < 0.05). 86 An examination of intervention studies reveals the challenge of ensuring comparable durations of study and supplementation doses. In a randomized controlled trial, Abokhrais et al found no significant improvement in various questionnaires on quality of life in 33 EM patients over a period of 8 weeks when administered with n-3-acid ethyl ester PUFA filled capsules, one capsule (1000mg, twice a day) vs placebo (olive oil). 87 Similarly, Nodler et al examined the improvement in pain scores (Visual Analogue Scale, VAS) in EM patients comparing a 6-month administration of either 720 mg EPA+DHA (n = 20), 2000 IE vitamin D (n = 27) or lactose powder as a placebo (n = 20). As demonstrated by the intervention, serum levels of EPA and DHA increased significantly (both p < 0.0001). Nonetheless, the observed improvement in VAS scores was not significant and did not differ from the reduction observed in the placebo group. 88 Even though additional n-3 intake has not consistently shown benefits for EM, several studies in women with primary dysmenorrhoea have reported beneficial effects from fish oil supplementation. The dosage of total n-3 (EPA+DHA) ranged from 300 mg to 755 mg over a period of 2–3 months, with various endpoints ( Cox Menstrual Symptom Scale , VAS,  Pain Severity Score ) and frequency of pain medication intake. 89–92 However, no definitive dose–response relationship can be drawn from the available data. Pain relief is a major goal in EM therapy and the doses of n-3 fatty acids used so far in the context of EM may still be too low to support the therapy, as therapeutic doses between 1.4 and 2.7 g may be necessary to alter prostaglandin and leukotriene concentrations which induce cardinal inflammation symptoms. 93 Overall, the number of intervention studies investigating the effects of LC n-3 PUFA on the symptoms of EM is limited as of now. To date, there have been no studies directly investigating the effects of optimizing the quality of dietary fats as a treatment strategy for EM. Overall, the available studies do not provide explicit recommendations for women with EM regarding the optimal intake of total SFA, MUFA, PUFA as well as ARA, EPA and DHA. Moreover, there is a lack of research evaluating the effectiveness of optimizing the intake of precursors, such as linoleic acid (n-6) and α-linolenic acid (n-3), in this population. For optimal health it is generally advisable to reduce the intake of SFA in favor of MUFA and PUFA. 94–96 Improving the quality of dietary fats—specifically by reducing SFA and industrially produced TFA in favor of n-3 LC-PUFA, as well as maintaining a balanced n-6/n-3 ratio in the diet—could exert anti-inflammatory effects that might enhance the treatment of EM. Nevertheless, further studies are required to verify their therapeutic efficacy in EM. Proteins and amino acids are essential for cellular function, muscle maintenance, enzyme and hormone activity, and immune support as well as growth, repair, and metabolic processes, therefore it is crucial to ensure women with EM meet the adequate requirement. A case–control study 97 of Iranian women with and without EM investigated the association of food consumption and nutrient intake with EM risk. The dietary intake was assessed by a food frequency questionnaire (FFQ) and women with unusual total energy intake levels (more than 4,300 kcal or less than 670 kcal) were excluded. The consumption of total protein differed between women with and without EM, but not significantly. In women with higher protein intake (fourth quartile OR 0.36, 95% CI: 0.14, 0.91, p = 0.06), especially animal protein (OR 0.37, 95% CI: 0.29, 0.95, p = 0.02) the incidence of EM was lower. Consequently, higher intake of animal-based protein sources such as eggs, fish, and meat, which provide the full spectrum of essential amino acids (EAAs), may be associated with a reduced risk of EM. 97 In line with this, Trabert et al reported that the consumption of dairy products was associated with a reduced risk of EM (>1–2 servings/day: OR 0.6, 95% CI: 0.4, 0.9, >2 servings/day: OR 0.7, 95% CI: 0.4, 1.2, p = 0.13). 83 As part of the prospective cohort study, Nurses’ Health Study II, Nodler et al observed a 32% lower risk of laparoscopically confirmed EM in women who consumed >4 servings/day of dairy foods (milk, yogurt, cheese, instant breakfast, ice cream, milkshake, sherbet, butter) compared to women consuming ≤1 servings/day (HR 0.68, 95% CI: 0.47, 0.96, p = 0.04). The association was similar for low-fat (low fat or skim milk, yogurt, cottage cheese, sherbet) and high-fat (whole milk, ice cream, milkshake, cream cheese, other cheese, butter) dairy foods. Specifically, the yogurt consumption was associated with a lower EM risk as women who consumed ≥2 servings of yogurt per week had a 29% lower risk of EM diagnosis compared to those consuming <1 serving/week (HR 0.71, 95% CI: 0.52, 0.97, p = 0.02). 98 The case–control study by Ashrafi et al observed similar results in Iranian women with and without EM. The consumption of dairy products, especially a higher intake of milk (OR 0.65, 95% CI: 0.47, 0.92, p = 0.014) and cheese (OR 0.53, 95% CI: 0.37, 0.76, p < 0.001) was significantly associated with a lower risk for EM. 99 However, red meat consumption, as a major protein source, yielded inconsistent results. Ashrafi et al showed associations with lower EM risk and red meat intake (OR 0.61, 95% CI 0.41, 0.91, p = 0.015). 99 Yamamoto et al found that women, who took part in the Nurses’ Health Study II, consuming >2 servings/day of red meat had a 56% higher risk of EM (RR 1.56, 95% CI: 1.22, 1.99, p < 0.0001) compared to those consuming ≤1 serving/week. The strongest association was shown for non-processed red meat (RR 1.57, 95% CI: 1.35, 1.83 for ≥2 servings/day versus ≤1 servings/week, p < 0.0001). On the other hand, the intake of poultry, fish, shellfish, and eggs was not related to EM risk. 100 The case–control study by Parazzini et al observed similar results. An increased risk was associated with high intake (≥7 portions/week) of beef and other red meat (OR 2.0, 95% CI: 1.4, 2.8, p = 0.0004) and a high intake (≥3 portions/week) of ham (OR 1.8, 95% CI: 1.3, 2.5, p = 0.001) compared to women in the lowest tertile of intake. 101 Murgia et al examined metabolic alteration in a cohort of patients with and without EM to identify disease-associated biomarkers. They discovered that tryptophan as EAA was significantly reduced in EM patients (AUC = 0.75, 95% CI: 0.54, 0.95). 102 Tryptophan-rich foods include dairy products, meat, and fish. This suggests that reduced tryptophan levels may play a role in the pathophysiology of EM and could serve as a potential nutritional or diagnostic target and needs further research. Inflammatory cytokines such as IFN-γ activate the enzyme indoleamine 2,3-dioxygenase, which increases the breakdown of tryptophan via the kynurenine pathway. Lower tryptophan levels in combination with increased kynurenine metabolites exert immunosuppressive effects via the aryl hydrocarbon receptor (AhR) (eg, by promoting regulatory T cells). The kynurenine/tryptophan ratio serves as a marker for inflammation-related indoleamine 2,3-dioxygenase activity. 103 In addition, Anastasi et al investigated the effects of oral supplementation with N-acetylcysteine (NAC), the acetylated derivative of the amino acid cysteine, in EM. All EM patients received 600 mg NAC supplements for 3 consecutive days of the week over 3 months. Pain parameters were measured via VAS scale and transvaginal ultrasound was used to detect the size of the endometrioma. After 3 months, the intensity of dysmenorrhea (p < 0.0001) and dyspareunia (p < 0.001) was significantly improved and the size of the endometriomas decreased (p < 0.001). 104 Taken together, current evidence suggests that higher intake of certain animal proteins and selected amino acids, including tryptophan and NAC may be associated with a reduction in EM symptoms, in contrast high consumption of red or processed meat might be associated with adverse effect. Water-soluble vitamins include vitamin C and a variety of B vitamins. Prior studies found associations of EM and elevated levels of ROS, oxidation products and detoxification enzymes. High levels of oxidative stress may play a crucial role in the pathogenesis of EM by contributing to inflammatory processes, degradation of extracellular matrix (ECM), angiogenesis and proliferation. 105 Antioxidants such as vitamin C could potentially counteract those mechanisms thus making it a promising target for research. 106 Beyond their antioxidant capacities, B vitamins play vital roles in several metabolic processes including cell division and growth as well as DNA synthesis and repair. 107 A significantly positive association between dietary intake of vitamin B6 and EM risk was observed by Yin et al using a multiple linear regression model (OR Q2: 1.22, 95% CI: 0.88, 1.69, p= 0.24, Q3: 1.22, 95% CI: 0.86, 1.73, p = 0.279, Q4: 1.51, 95% CI: 1.01, 2. 24, p = 0.04). 108 Whereas Sheng et al found lower intake of niacin (p = 0.026), vitamin B6 (p = 0.04) and folic acid (p = 0.044) in patients with EM compared to healthy controls. Logistic regression analysis showed an inverse association of niacin (model I: OR 0.98, 95% CI 0.96, 1.00, p = 0.019; model II: OR 0.98, 95% CI: 0.96, 1.00, p = 0.023; model III: OR 0.98, 95% CI: 0.96, 1.0, p = 0.021) and B6 intake (model I: OR 0.79, 95% CI: 0.62, 0.99, p = 0.033; model II: OR 0.80, 95% CI: 0.63, 1.01, p = 0.044; model III (OR 0.79, 95% CI: 0.63, 0.99, p = 0.033) with EM risk. However, the effect was age-related, as separating patients by age eliminated the effect in those aged 25 to 35 years. 109 Zhang et al found no significant associations for vitamins B2 and B6 but lower vitamin B1 intake in participants with EM (138 ± 0.59 mg/day) compared to controls (1.52 ± 0.72 mg/day, p = 0.003). Restricted cubic spline (RCS) regression showed a steady decrease in EM risk for vitamin B1 intake >1.84 mg/day, the effect plateaued beyond this point. Thus, indicating that identifying the optimal intake levels may enhance effectiveness. 110 A negative correlation between EM risk and intake of vitamins B1, B2, B6 and C (OR 0.817, 95% CI: 0.702, 0.951), 0.860 (95% CI: 0.746, 0.991), 0.784 (95% CI: 0.669, 0.919), 0.845 (95% CI: 0.718, 0.994), and 0.772 (95% CI: 0.660, 0.903) was observed by Xu et al, 111 In two retrospective case–control studies, the nutrient intake of EM patients was assessed using FFQs. Schink et al found significantly lower intake of vitamin C and vitamin B12 in the EM group (vitamin C: 137.9 mg/d ± 103.9; vitamin B12: 4.6 mg/d ± 2.2) compared to controls (vitamin C: 152.9 mg/d ± 77.8, p = 0.031; B12: 5.4 mg/d ± 2.1, p = 0.008). For both groups, the daily intake of pantothenic acid (EM: 4.5 ± 1.7 mg/d; control: 4.8 ± 1.4 mg/d) was −25 ± 28% and folic acid (EM: 101.5 ± 42.0 mg/d; control: 107.2 ± 30.9 mg/d) −20 ± 23% below the recommended intake of the German Nutrition Society (DGE). 112 Roshanzadeh et al observed a lower consumption of folate (p = 0.04), vitamin B12 (p = 0.02), B6 (p = 0.04), B2 (p = 0.01) and C (p = 0.02) in a group of 78 women with EM compared to 78 women without endometriosis. Dietary intake of vitamin B12 (OR 0.71, 95% CI: 0.53, 0.95, p = 0.02), B6 (OR 0.73, 95% CI: 0.55, 0.98, p = 0.04), B2 (OR 0.73, 95% CI: 0.55, 0.98, p = 0.01) and C (OR 0.70; 95% CI: 0.52, 0.94, p = 0.02) was inversely correlated with risk for EM. In addition, average vitamin B12 intake was 3.32 (2.65–4.44) µg in the EM group which is below the referenced value of DGE. 113 Several studies investigated the effect of combined supplementation of vitamin C (1000 mg/d) and E (400–1200 mg/d) over 8 weeks, findings include improvements in the perception of pain 114–116 and reduction of inflammation markers such as malondialdehyde (p = 0.002), ROS (p < 0.001), IL6 (p ≤ 0.05), and monocyte chemotactic protein 1 (p ≤ 0.01). 114 , 116 Signorile et al observed an alleviation of pain and reduction of serum dosage of PGE2 from 3404 ± 346 ng/L to 1377 ± 326 ng/L and serum dosage of Cancer Antigen 125 from 614 U/mL to 38 U/mL in EM patients after 3 months supplementation with a combination of linoleic acid (n-6), alpha linolenic acid (n-3), quercetin, nicotinamide, 5-methyltetrahydrofolate calcium salt, titrated turmeric, titrated parthenium, whilst a supplementation of linseed oil and 5-methyltetrahydrofolate, alone showed only a minor reduction for PGE2 and no significant improvement for pain. 117 In addition, as shown by Darling et al, dietary nutrient intake may be more effective than supplementation, as consuming a variety of nutrients through whole foods ensures diverse nutrient combination. 118 In summary, a needs-based provision of water-soluble vitamins may support therapy by alleviating EM symptoms, and in this context, a combination of varied nutrients that exerts antioxidant and anti-inflammatory effects appears to be effective. Beneficial effects of fat-soluble vitamins such as vitamin A (retinol), D (calciferol), E (tocopherol) and K (phylloquinone and menaquinone) in treating EM were shown in a variety of studies. A prospective cohort study 119 using data from 70.835 premenopausal women from 1991 to 2013 as a part of the Nurses’ Health Study II investigated the association between the intake of fruits and vegetables and the risk of laparoscopically confirmed EM. Higher intake of beta-cryptoxanthin, a provitamin A, was associated with a lower risk of EM (RR fifth quintile 0.88, 95% CI: 0.78, 1.00, p = 0.02). 119 Consistently, Mier-Cabrera et al showed that women with EM have lower vitamin A intake than women without EM (p < 0.05). After following a diet high in antioxidants (1,050 μg retinol equivalents, 500 mg vitamin C, and 20 mg vitamin E daily) for four months, antioxidant enzyme activity increased (superoxide dismutase: 4.0 ± 1.1 U/mL to 9.2 ± 3.2 U/mL and glutathione peroxidase: 1033.6 ± 108.6 nmol/min/mL to 1564.3 ± 137.3 nmol/min/mL) and oxidative stress markers decreased (malondialdehyde: 31.1 ± 4.7 μM/l to 23.0 ± 2.3 μM/l and lipid hydroperoxides: 12.1 ± 3.3 μM/l to 8.2 ± 1.9 μM/l) compared to a normal diet (p < 0.05). 120 The effects of vitamin D on EM have been investigated in several studies. A study showed that a vitamin D deficiency is associated with an increased risk of EM in Iranian women at the age of 18–49 years. Compared to the control group women with stage 1/2 or stage 3/4 of EM had significantly lower levels of 25(OH)D (p = 0.003 and p = 0.03). In addition, women with serum levels lower than 20 ng/mL exhibited a 2.7 higher risk of EM compared to those with higher levels (OR = 2.7, 95% CI: 1.24, 5.80, p = 0.01). 121 A number of intervention studies have been conducted in order to examine the impact of vitamin D supplementation on the symptoms of EM. Nodler et al administered 2000 IU of vitamin D3 per day over a period of six months and demonstrated a significant reduction in pelvic pain among young women diagnosed with EM (OR 7.0, 95% CI: 6.2, 7.8 to 5.5, 95% CI: 4.2, 6.8, p = 0.02). 88 A supplementation of 50.000 IU/2 weeks of vitamin D over 12 weeks reduced symptoms of dysmenorrhea (−1.12, 95% CI: −2.1, −0.09, p = 0.03), total-/high-density lipoprotein (HDL)-cholesterol ratio (−0.29, 95% CI: −0.57, −0.008, p = 0.04), high-sensitivity C-reactive protein (hs-CRP) (−0.64, 95% CI: −0.97, −0.30, p < 0.001) and increased the total antioxidative capacity (TAC) (47.54, 95% CI: 19.98, 75.11, p = 0.001) in women with EM compared to a placebo group. 122 Despite the positive effects of supplementation, high doses should be viewed critically. The upper limit for vitamin D intake from all sources is 4.000 IU per day. 95 Exceeding this amount may lead to adverse health effects such as hypercalcemia, cardiac arrhythmias, kidney function disorders, and reduction of bone density. 123 Roshanzadeh et al analyzed the relationship between intake of dietary micronutrients including vitamin K and EM of 156 women. There were no significant differences in the dietary intake between women with (case) and without (control) EM (p = 0.70) and the OD between vitamin K and EM (p = 0.07). Although the total OD of 0.78 (0.58–1.04; p = 0.07) suggest a possible inverse trend of risk reduction by vitamin K. 113 A cohort study with 3,351 participants from the National Health and Nutrition Examination Survey (NHANES) observed that increasing vitamin E intake was associated with a significantly lower risk of developing EM up to a threshold of 13.2 mg/day (OR 0.947, 95% CI: 0.906, 0.989). Beyond this intake level, no further protective association was evident, in fact, a slight trend toward a positive correlation was noted (OR 1.001, 95% CI: 0.997, 1.005). 111 This intake corresponds with the recommended intake of 12 mg/day, 124 which can be easily covered with a balanced diet, rich in food such as almonds, hazelnuts, sunflower oil or avocado. The available evidence suggests that intake of fat-soluble vitamins is associated with a risk reduction of EM. In addition, data showed that a controlled supplementation of vitamin D is suitable for symptoms reduction. In this context, the optimal dietary intake levels of fat-soluble vitamins and the specific threshold values required to support therapy must be further investigated in intervention studies. Minerals are essential inorganic nutrients which exert numerous physiological functions such as the formation of bones, teeth and cell structures, and the regulation of nerve and muscle functions. They also contribute to maintaining water and electrolyte balance in the human body. As a component of hemoglobin, iron plays a vital role in oxygen transport. 125 Therefore, insufficient intake of iron can lead to several symptoms such as impaired immune function. 126 Heavy menstrual bleeding, which can occur in EM or adenomyosis, promotes iron deficiency. 127 Two studies investigated the relation between the occurrence of EM and the development of iron deficiency. Gete et al found that prevalence of iron deficiency was higher in women with EM (22%) compared to women without EM (17%). The OR for risk of iron deficiency was higher for women with EM than without EM after adjusting for sociodemographic, lifestyle, reproductive, and nutrition factors (OR = 1.54, 95% CI: 1.35, 1.74). 128 A cross-sectional study analyzed blood count, ferritin, and transferrin saturation of 251 women with endometriosis. Results showed 53.4% (134/251) of the patients were deficient in iron and prevalence of iron deficiency anemia was 13.5% (34/251). 129 On the contrary, in a case–control study including 107 women with EM and 210 healthy controls, a significant association between consumption of heme iron and the incidence of EM was observed (OR = 5.48, 95% CI: 1.72, 7.81, p < 0.001). 130 Polak et al measured hemoglobin and iron as markers for iron metabolism, and total oxidative status (TOS) and antioxidant status as parameters of oxidative stress in the peritoneal fluid of women with EM or benign ovarian cysts to investigate whether a disrupted iron metabolism leads to elevated oxidative stress levels. For patients with endometriosis, hemoglobin, iron levels and TOS were significantly higher, whilst antioxidant status was lower compared to patients without EM (p < 0.01). 131 The role of calcium intake for EM incidence was investigated in several studies. Harris et al calcium intake via dairy products and found a reduced EM risk with higher intake (RR 0.82, 95% CI 0.71, 0.95, p = 0.03). Analysis of specific dairy products showed the strongest association between skim/low-fat milk and EM risk. 132 In this context, it should be noted that dairy products are also rich in EAAs, B vitamins as well as trace elements such as iodine. 133 An inverse association between EM and total magnesium and phosphorus intake as well as consumption of potassium (OR 0.74, 95% CI: 0.56, 0.99, p = 0.01) and calcium (OR 0.70, 95% CI: 0.52, 0.94, p = 0.003) was observed. 113 , 132 Magnesium can relieve chronic pelvic pain by reducing excessive muscle contractions, especially in the pelvic muscles as it acts as physiological calcium antagonist by inhibiting the influx of Ca 2 ⁺ into muscle cells, thereby reducing excessive muscle contractions and neuromuscular hyperexcitability. 134 , 135 Calcium is particularly relevant in EM due to disrupted calcium signaling pathways, which can increase cell growth, inflammation, muscle contractility, and pain. 136 Phosphorus may act indirectly via vitamin D metabolism, which influences inflammatory processes. 137 Overall data suggests that iron deficiency as well as iron overload may have a negative impact on the risk for EM. In addition, an unbalanced intake of further minerals such as calcium, magnesium, potassium and phosphorus seem to be associated with EM risk. Therefore, ensuring an adequate intake of these minerals is recommended to help reduce the risk and support the treatment of patients with EM. The trace elements such as selenium, iodine, zinc, and copper have attracted attention due to their roles in oxidative stress regulation, immune function, and angiogenesis, processes that are highly relevant to the pathophysiology, the onset and progression of EM. Selenium is an essential trace element known for its incorporation into selenoproteins such as glutathione peroxidases and selenoprotein P, which can modulate redox balance. Observational data from large cohorts suggest that higher dietary selenium intake is associated with a reduced prevalence of EM (OR = 0.66, 95% CI: 0.45, 0.97). 138 Mechanistically, selenium may attenuate the oxidative stress observed in peritoneal lesions, thereby reducing cellular damage and inflammatory signaling. However, smaller serum-based studies have provided inconsistent results, likely due to methodological heterogeneity and limited sample sizes. 139 Although selenium supplementation represents a biologically plausible therapeutic approach, further prospective clinical trials are still required to confirm its efficacy. In contrast, iodine remains underexplored in the context of endometriosis. Endometrial tissues express iodide transporters, suggesting a potential physiological role. 140 Given that iodine is indispensable for thyroid hormone biosynthesis, its influence on estrogen metabolism and reproductive function could represent an indirect link to EM. However, clinical data are scarce, and no large-scale investigations have yet clarified whether iodine status contributes to disease risk or progression. Thus, iodine currently remains a hypothesis-generating element warranting further study. Zinc, another essential trace element, participates in numerous enzymatic processes, immune responses, and cellular signaling pathways. It has also been recognized for its anti-oxidative and anti-inflammatory properties. Findings related to zinc and EM are contradictory: while early case–control studies reported reduced serum zinc levels (adjusted OR = 0.39, 95% CI: 0.18, 0.88) in affected women, 141 more recent analyses from the US NHANES cohort described a positive association between dietary zinc intake and EM prevalence (the adjusted OR for dietary zinc intake and EM in the 8–14 mg/day and >14 mg/day groups were 1.19 (95% CI: 0.92, 1.54, p = 0.189) and 1.60 (95% CI: 1.12, 2.27, p = 0.009), respectively. 142 This discrepancy highlights the complexity of distinguishing between dietary intake, systemic zinc concentrations, and tissue bioavailability. Nevertheless, given its key role in oxidative stress regulation, zinc remains a biologically plausible factor in EM pathophysiology. Copper, in contrast, has been more consistently associated with EM. Elevated copper concentrations have been observed in follicular fluid of affected women (first tertile vs second tertile group: aOR = 0.39, 95% CI: 0.19, 0.81; third tertile vs second tertile group: aOR = 2.73, 95% CI: 1.61, 4.66). 143 Biologically, copper contributes to both oxidative stress and angiogenesis, thereby supporting the establishment and maintenance of endometriotic lesions. Experimental studies demonstrated that copper chelation with ammonium tetrathiomolybdate significantly inhibited lesion progression in murine models. 144 These findings point to copper not only as a biomarker of disease activity but also as a potential therapeutic target in innovative treatment strategies. In summary, current evidence suggests that trace elements exert important but distinct influences on the pathophysiology of EM. Selenium may provide protective effects through its antioxidant role, while copper appears to contribute to angiogenesis and lesion progression. Zinc shows inconsistent associations, reflecting the complexity of its biological role, while iodine remains largely unexplored in this context. Despite promising associations, the majority of available studies are cross-sectional, often with small sample sizes, and thus limited in their ability to establish causality. Prospective, mechanistic, and interventional studies are urgently warranted to clarify the role of trace elements in EM and to evaluate their potential as therapeutic targets or preventive strategies. Polyphenols are naturally produced in plants and constitute a large group of secondary plant compounds, mainly including flavonoids, lignans, stilbenes and phenolic acids. Polyphenols act as antioxidants, influence signaling pathways and enzyme activities, and are associated with positive effects on cardiometabolic health, inflammation inhibition and cancer prevention. 145 Resveratrol is among the most studied bioactive compounds related to EM. 146 Its therapeutic potential is partly attributed to anti-angiogenic properties that may inhibit the growth of endometriotic lesions: 147 in a double-blind RCT in stage III–IV EM patients (n = 34), daily supplementation with 2 × 400 mg trans-resveratrol (99% pure; n = 17) over 12–14 weeks significantly reduced VEGF (mRNA fold change: treatment baseline ~1.3 vs post-interventive ~0.8, p < 0.05; control post-interventive ~1.3, vs treatment p = 0.017; protein expression: vs baseline = 0.017, vs, control p = 0.012) and TNF-α levels (mRNA fold change: treatment baseline = p < 0.05, vs control p = 0.018; protein expression: vs baseline = 0.011, vs control p = 0.019) in eutopic endometrial tissue compared to placebo (n = 17). Still, these findings are not reflected in symptom relief. 147 Mendes da Silva et al could not confirm clinical effectiveness by resveratrol as an adjunct to monophasic combined oral contraceptives on pain perception in women with laparoscopically confirmed EM (n = 22). Although the resveratrol group showed a reduction in pain scores on the VAS from 5.7 (4.8–6.6) at baseline to 3.2 (2.1–4.3) after 42 days, the difference compared to the placebo group was not statistically significant. Since the resveratrol supplement formulation used was not further specified, potential differences in bioavailability cannot be assessed. 148 Even though resveratrol may exhibit therapeutic potential due to its molecular effects on inflammation and lesion growth in EM, further studies are needed to determine dose–response relationships and assess whether such effects can translate into symptom relief in clinical settings. Notably, the supplemental doses used in clinical trials cannot be matched by dietary intake. The highest resveratrol concentrations per 100 g are found in lingonberries (3.0 mg), European cranberries (1.9 mg), redcurrants (1.6 mg), bilberries (0.7 mg), and strawberries (0.4 mg). 149 Another polyphenol of scientific interest is epigallocatechin-3-gallate (EGCG), the predominantly found catechine in black tea (7.2 mg/100 g) and especially green tea (19.7 mg/100 g). 149 Green tea ( Camellia sinensis ) has received considerable scientific attention for its potential role in cancer prevention and therapy. Nonetheless, a comprehensive Cochrane review found no consistent evidence to support the pharmacological relevance of green tea extract in cancer therapy or green tea consumption in cancer prevention, as well as reports of adverse effects such as gastrointestinal disturbances or elevated liver enzymes. 150 Mechanistic evidence from preclinical models suggests that EGCG may suppress the development of endometriotic lesions, with enhanced efficacy in inhibiting angiogenesis by prodrugs forms such as ProEGCG. 151 Ricci et al demonstrated in a combined model approach (BALB/c mouse model and endometrial epithelial cells) that both EGCG and resveratrol significantly inhibited proliferation and angiogenesis while increasing apoptosis (p < 0.05). 152 Clinical trials such as the registered intervention study by Wang et al (2 × 400 mg EGCG/day vs placebo) are expected to provide further insights into its safety, physiological effects, and symptom-related outcomes (Wang et al, https://clinicaltrialsgov/study/NCT02832271 ). Curcumin, the major active compound of turmeric ( Curcuma longa ), is widely studied for its anti-inflammatory, antioxidant, and hormone-modulating properties. Potential molecular effects have been demonstrated in various in vitro models using tissue from EM patients. 153–156 Curcumin reduced inflammatory signaling pathways (eg, KKα/β, NF-κB, STAT3, and JNK), leading to lower expression of pro-inflammatory cytokines and chemokines, 154 and downregulated VEGF signaling, potentially impairing cellular survival of endometriotic lesions. 153 Additionally, curcuminoids and their metabolites were found to inhibit 17β-HSD1, a key enzyme in estradiol synthesis, which may counteract the estrogen dominance associated with EM. 156 Curcumin also increased the expression of fertility-related growth factors, as shown in peritoneal fluid-derived cell cultures from infertile women with EM. 155 This may be significantly relevant given the association between EM and infertility. 157 Potential influences of improved oxidative and inflammatory parameters on fertility were reflected in positive correlations of total antioxidant capacity (TAC) and catalase (CAT) with the MII oocyte rate (TAC: r s = 0.688, p = 0.012; CAT: r s = 0.652; p = 0.021), oocyte fertilization rate (TAC: r s = 0.644, P = 0.024) and embryo quality (TAC: r s = 0.411, p = 0.039; CAT: r s = 0.546, p = 0.034), as well as for TAC with the number of retrieved oocytes (r s = 0.644, p = 0.024). Conversely, MDA, IL-18, and TNF-α each correlated negatively with oocyte fertilization rate (MDA: r s = −0.431, p = 0.032; IL-18: r s = −0.179, p = 0.041; TNF-α: r s = −0.273, p = 0.036) and embryo quality (MDA: r s = −0.449, p = 0.025; IL-18: r s = −0.176, p = 0.039; TNF-α: r s = −0.319, p = 0.046), while IL-18 and TNF-α correlated negatively with the number of oocytes (IL-18: r s = −0.173, p = 0.038; TNF-α: r s = −0.284, p = 0.024). In addition, TNF-α was negatively associated with the MII oocyte rate (r s = −0.222, p = 0.024). Despite higher fertilization rates (81.64 ± 13,67%) and cleavage rates (79 ± 1.67%) in the curcumin group compared to placebo group (p = 0.033; p = 0.049), no significant differences were observed in either chemical or clinical pregnancy rates following transfer of a comparable number of embryos in the ICSI cycle. 158 Sargazi-Taghazi et al executed an 8-week RCT to assess the pain-relieving potential of nancurcumin (80 mg daily) as an adjunct to hormonal therapy (2 mg dienogest daily) compared to placebo in 86 patients (1:1) with moderate-to-severe endometriosis-related pain (VAS ≥ 4) and stage II–III pelvic endometriosis. Adjunctive nanocurcumin treatment led to greater improvements in pain outcomes, with reductions in dysmenorrhea (−69%), dyspareunia (−69%), and dyschezia (−70%), and significantly improved VAS scores compared to the control group (dysmenorrhea: aMD: −1.55 (95% CI: −2.04 to −1.06; p < 0.001); dyspareunia: aMD: −0.93 (95% CI: −1.37 to −0.49; p < 0.001); dyschezia: aMD: −0.30 (95% CI: −0.58 to −0.03; p = 0.030). These results support the use of nanocurcumin as a complementary treatment to hormonal therapy for managing endometriosis-related pain. 159 In contrast, another recent RCT found no significant pain-relieving effects of curcumin (500 mg capsules twice daily) in women (n = 68; 1:1) with laparoscopically confirmed EM compared to placebo. No significant differences were observed in pain perception scores based on the ENDOPAIN-4D questionnaire (usual and worst pain) or the VAS scale. Quality of Life (QoL) parameters assessed via the EHP-30 questionnaire also remained unchanged. 160 Inconsistencies in clinical outcomes may partly be attributed to differences in the pharmacokinetic properties of phytochemical formulations. With particular interest in curcumin, its free form is poorly bioavailable due to low water solubility, pH sensitivity, rapid metabolism, and fast elimination. Reported curcumin plasma concentrations range from 1 to 3200 ng/L. 161 Curcumins therapeutic efficacy depends heavily on formulation strategies that enhance bioavailability and stability, which can be improved by nanoformulations and carrier encapsulation. 162 Since most studies evaluate the bioavailability of curcumin in supra-dietary doses with enhanced pharmacokinetic, there is a lack of evidence for the therapeutic relevance of turmeric intake by diet. A standardized test meal representing the typical daily turmeric intake in India (~3 g) resulted in measurable plasma concentrations of free parent (unconjugated) curcumin in only one out of four participants. However, systemic availability was reflected in higher measurable levels of conjugated metabolites, particularly curcumin glucuronide (C max  ≈ 47.6 ± 28.5 nM). 163 Bioavailability of curcumin is influenced by dietary context: lipid- or lecithin-rich meals (eg, with eggs or plant oils) enhance absorption, while protein- and fiber-rich meals can reduce it. Co-administration with piperine inhibits curcumin’s glucuronidation and thus modestly enhances systemic levels. 163 Based on current evidence, nanoformulated curcumin supplements appear more relevant for therapeutic use in EM patients. Further analyses need to clarify the clinical relevance and mediating activity of curcumin metabolites to assess the therapeutic potential of turmeric as a dietary component. 163 Another polyphenolic compound of potential therapeutic interest is quercetin. Even though human data on clinical outcomes with EM patients are scarce, there are promising molecular connections. Quercetin might specifically improve decidualization, a progesterone dependent differentiation process of endometrial stromal cells which is potentially impaired in EM and crucial for embryo implantation and fertility. 164 An ex vivo study by Delenko et al demonstrated that quercetin restored decidualization in menstrual effluent derived endometrial stromal cells from histologically confirmed EM patients, evidenced by enhanced expression of decidual markers (IGFBP1, PRL). These effects were accompanied by modulation of AKT- and ERK- signaling pathways, higher p53 levels and a less senescence-like cellular phenotype. 164 Fadin et al investigated the effects of a combined daily supplement containing quercetin (200 mg), N-acetyl-cysteine (NAC, 150 mg) and curcuma extract (210 mg) in 33 women with clinical diagnosis of EM over two months, reporting significant pain reduction (p < 0.05). Quercetin modulates inflammation by suppressing mast cell degranulation and inhibiting histamine release and IL-6 production. These findings suggest a potential therapeutic role for quercetin and related compounds in the inflammatory processes associated with EM. 165 Still, isolated supplemental studies with quercetin are necessary to elicit its therapeutically potential and necessary dosages. This might further contribute to evaluate the consumption of quercetin-rich food sources like black elderberry (42 mg/100 g), dark chocolate (25 mg/100 g), capers (32.82 mg/100 g), dried mexican oregano (42.00 mg/100 g), shallots (2.00 mg/100 g) or red onions (1.31 mg/100 g) within an optimized diet for EM patients. 149 Overall, a higher intake of polyphenolic compounds may contribute to the modulation of inflammatory processes in EM. Current preliminary evidence from human intervention studies is largely based on trials using isolated supplements such as resveratrol, EGCG, curcumin and quercetin, which have demonstrated anti-inflammatory effects and symptom improvement in women with EM. Nevertheless, it is plausible that the combined intake of diverse phytonutrients through an increased consumption of plant-based foods, particularly a wide range of fruits and vegetables, may elicit synergistic effects within a holistic dietary pattern. Future research should explore the potential advantages of polyphenols acting additively or synergistically in whole foods, as opposed to when they are consumed as isolated supplements. Phytoestrogens are phenolic compounds that can bind to estrogen receptors (ER) due to their structural similarity to estrogen. 166 The potential of these compounds to elicit both estrogenic and anti-estrogenic effects complicates the interpretation of their physiological role, particularly in the context of the estrogen-dependent pathogenesis of endometriosis. This two-way effect is contingent on various factors, including the activated receptor subtype (eg, ERα vs ERβ), the tissue context, and the availability of co-regulators. 167 The main classes of phytoestrogens include isoflavonoids, lignans, and coumestans. Soy products are considered a key dietary source due to their high isoflavone content, the predominant subtype of isoflavonoids. 166 Foods with especially high isoflavone levels (≥100 mg/100 g) include soy flour, raw and roasted soybeans and soybean flakes. Fermented or concentrated products such as natto, miso, soy protein concentrates and soy-based drinks may also provide substantial amounts of isoflavones (30–100 mg/100 g). 168 The isoflavone content varies depending on the degree of ripeness, germination and processing of products. Accordingly, processed products such as soy milk, cooked soybeans or tofu typically contain lower amounts (2.6 to 35 mg/100 g). 168 Soy product consumption is often assessed via urinary levels of the primary isoflavones daidzein and genistein, which serve as biomarkers of phytoestrogen intake. In the prospective ENDO cohort study (n = 526), no significant association was observed between EM and regular soy consumption (>1 portion/week). Furthermore, urinary concentrations of isoflavone and lignan metabolites did not vary according to the laparoscopically confirmed EM status. Nevertheless, urinary phytoestrogen concentrations were positively associated with reported soy intake, supporting their use as intake biomarkers. 169 Subsequent studies have reported inverse associations between phytoestrogen intake 170 or urinary levels 171 and EM risk. In a Japanese case-control study by Tsuchiya et al, a higher isoflavone concentration in urine was associated with a lower risk of advanced EM (stage III–IV), particularly for genistein (p = 0.01). A 79% risk reduction was observed in the highest quartile of urinary genistein concentration compared to the lowest (OR 0.21, 95% CI: 0.06, 0.76). 171 In a case–control study by Youseflu et al, phytoestrogen intake was estimated using food frequency questionnaires from 78 laparoscopically confirmed EM patients. Higher total phytoestrogen intake was significantly associated with a lower risk of EM (p = 0.01), including intake of isoflavones (p = 0.002), lignans (p = 0.01), and coumestrol (OR in the third quartile 0.38, 95% CI: 0.15, 0.96, p = 0.10). 170 This contrasts with individual case reports suggesting an association between high soy or isoflavone intake and gynecological complaints in EM patients. 172 , 173 In two reports by Chandrareddy et al, the regular high consumption of soy products (eg, soy milk, tofu, soy granules, soy protein concentrate) was associated with severe dysmenorrhea, abnormal uterine bleeding, and benign uterine tumors such as leiomyomas. In both cases, pharmacological treatment (norethindrone acetate) and surgical interventions had been unsuccessful. Symptom relief was achieved only after discontinuing soy intake, and one patient subsequently conceived despite previous fertility issues. However, details on soy consumption levels, overall dietary habits, and supplement use were not reported, limiting the generalizability of the findings. Nonetheless, the observed symptom improvement raises questions about the potential adverse effects of excessive soy intake in individual cases. 172 Noel et al reported the case of a 75-year-old woman diagnosed with malignant Müllerian carcinosarcoma of the ureter, who had undergone hysterectomy with bilateral salpingo-oophorectomy 30 years earlier due to extensive endometriosis. The patient had taken a daily isoflavone supplement (72 mg/day; daidzein, genistein, glycitein) for five years. The authors discussed the possible role of phytoestrogen supplementation in the malignant transformation of endometriotic tissue, a phenomenon previously associated primarily with chronic estrogen therapy. 173 The safety and mechanistic understanding of increased phytoestrogen intake from foods and supplements warrant further investigation to clarify their potential role in the development and management of endometriosis. Genetic polymorphisms in estrogen receptors (eg, ESR2) and the influence of the intestinal microbiota on phytoestrogen metabolism and bioavailability have been proposed as potential modulators 167 , 171 However, substantial human research on the bioefficacy of phytoestrogens is scarce, particularly within the scope of holistic dietary approaches. The “Endometriosis Diet” is characterized by the exclusion of soy products such as soy milk, tofu, soy sprouts, miso, tempeh, soy sauce and natto, as well as the avoidance of gluten and dairy products. 174 , 175 A dietary intervention study based on this concept reported improvements in bloating (p < 0.001) and fatigue (p = 0.002) among participants with laparoscopically confirmed endometriosis, although no significant effects were found for pain-related symptoms such as dysmenorrhea or chronic pelvic pain. 175 In a cross-sectional survey of self-initiated dietary changes, the exclusion of soy was described as one of the most effective individual strategies for pain reduction. 174 In an intervention study by Ott et al, the consumption of soy products (bean sprouts, soybeans, soy flour, tofu) was explicitly encouraged as part of a MedD in 68 participants with endometriosis. After five months, intention-to-treat analysis using the Numeric Rating Scale showed significant reductions in general pain perception (from 4.2 ± 2.5 to 2.5 ± 2.4; p < 0.01), dysmenorrhea (4.6 ± 2.8 to 2.9 ± 2.5; p < 0.001), dyspareunia (1.8 ± 2.2 to 0.9 ± 1.3; p = 0.011), and dyschezia (2.9 ± 3.1 to 2.0 ± 2.5; p = 0.032). However, the intervention was delivered exclusively via telephone contact, and detailed information on actual dietary intake is lacking. 176 Although some dietary approaches for EM suggest avoiding soy, current evidence is insufficient to justify such exclusion. Existing observations do not indicate an increased risk associated with soy consumption, with exception of individual case-reports of symptom aggravation in cases of regular, notably high soy intake. At present, no conclusions can be drawn regarding safe or effective intake levels of phytoestrogens based on dose–response relationships, particularly within holistic dietary approaches. However, the consumption of very high amounts of soy or isoflavones, especially in concentrated forms, should be considered with caution. Alongside dietary records, the primary isoflavones daidzein and genistein serve as effective biomarkers for assessing soy consumption as relevant phytoestrogens. β-carotene has nutritional importance as a provitamin A carotenoid, protecting cells from oxidative stress and free radicals and plays an important role for vision, the immune system and cell growth. High amounts are found in orange, red and dark green fruits and vegetables, particularly in sweet potatoes, pumpkin, carrots, green leafy vegetables, mango, and apricots. A very high carotenoid concentration is classified as >2 mg/100 g. 177 For example, 100 g of sweet potato already provides 9.23 mg β-carotene (orange-flash variety Beauregard, fresh weight). 178 Observational studies provide conflicting results on carotenoid intake and EM risk. 83 , 119 A case–control study by Trabert et al including 284 women with laparoscopically confirmed EM and 660 controls reported an inverse association with β-carotene intake. Dietary analyses via FFQ showed a significantly increased OR from the 3rd quartile onward, although the p-trend was not significant (vs Q1, Q3: OR 1.7, 95% CI 1.1–2.6; Q4: OR 1.6, 95% CI 1.0–2.5; p = 0.16). Median β-carotene intake was similar between groups (EM cases: 1941.2 μg; controls: 1878.5 μg). Surprisingly, higher fruit intake was also associated with an increased risk of EM (>2 servings/day vs <1 serving/day: OR = 1.5; 95% CI = 1.0–2.3; p = 0.04), whereas no associations were observed for vegetable intake. 83 In contrast, Harris et al reported a significantly lower risk of EM for higher intakes of the carotenoid β-cryptoxanthin (Q1 vs Q5, RR = 0.88; 95% CI = 0.78–1.00; p = 0.02). Other carotenoids analyzed (β-carotene, α-carotene, lycopene, lutein, and zeaxanthin) showed no significant risk associations. 119 Huang et al show a correlation between serum levels of lutein and zeaxanthin combined and a significantly reduced risk of EM (Q3 vs Q1: OR = 0.62, 95% CI: 0.42–0.90; Q4 vs Q1: OR = 0.54, 95% CI: 0.36–0.81, p trend = 0.001), whereas other carotenoids (α-carotene, β-carotene, β-cryptoxanthin, trans-lycopene) were not significantly related. 179 Which carotenoid-rich foods ultimately influence EM risk remains unclear. Similarly, Luo et al found no significant associations for β-carotene intake alone in a NHANES cross-sectional analysis, though it was inversely associated with EM risk as part of the composite Dietary Antioxidant Index (CDAI), along with vitamin A, C and E, zinc and selenium, across all adjusted models (Model 1–3: OR range = 0.907–0.950; all p < 0.05). 180 Chen et al also reported inverse correlations between the CDAI and EM risk (OR = 0.92, 95% CI 0.86–0.98, p = 0.011). In addition, they identified carotene as a key antioxidant component of the CDAI using LASSO and RF machine learning analyses, as well as showing independent risk associations (OR = 1.000, 95% CI 1.000–1.000, p = 0.034). 181 Although oxidative stress is recognized as a hallmark of EM, 182 causal relationships remain unclear. For example, a Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) revealed no genetic associations between circulating antioxidants (including β-carotene and lycopene) and EM risk. 183 Despite the controversial observations regarding the role of carotenoids in EM, their antioxidant potential appears to be of relevance. Associations with increased oxidative stress and inflammation in affected women support the rationale of enhancing antioxidant potential through diet. Mier-Cabrera et al provide preliminary evidence in this regard, demonstrating that women with EM had a lower dietary intake of antioxidants such as vitamin A (110 ± 23 vs 163 ± 45% recommended daily intake (RDI)), C (308 ± 162 vs 446 ± 142% RDI), E (66 ± 27 vs 112 ± 26% RDI), zinc (122 ± 40 vs 178 ± 62% RDI), and copper (299 ± 57 vs 418 ± 97% RDI) in comparison to women without EM (p < 0.05). Following the administration of a high antioxidant diet, peripheral concentration of vitamins A, C and E as well as peripheral enzymatic superoxide dismutase and glutathione peroxidase activity increased after 3 months of intervention in comparison to the control diet group. In addition, peripheral concentration of malondialdehyde and lipid hydroperoxides decreased after three months of intervention in comparison to the control diet group. These results indicate a potential therapeutic benefit of a diet rich in antioxidants. 120 Observational evidence on the association between carotenoid intake and EM risk is inconsistent. However, considering the antioxidant properties of carotenoids, regular consumption of orange- or red-colored fruits and vegetables, as well as leafy green vegetables appears to be a reasonable component of a holistic dietary approach. In addition, the investigation of carotenoids should always be done jointly with zinc levels as the conversion of carotenoids to vitamin A depends on sufficient zinc levels. This might be able to explain some of the inconsistent findings. There are ambivalent findings regarding the consumption of cruciferous vegetable ( Brassicaceae ) like broccoli, brussels sprouts, cauliflower, cabbage, kohlrabi or turnip, ranging from risk-increasing associations 119 , 184 to protective effects 185 attributed to its main bioactive compounds, glucosinolates. Prospective cohort data indicate a potentially increased risk of EM with higher cruciferous consumption. In the Nurses’ Health Study II (1991–2013), including 70,835 premenopausal women with 2,609 laparoscopically confirmed cases, women consuming ≥1 portion of cruciferous vegetables per day had a 13% higher risk compared with those consuming <1 portion per week (HR = 1.13; 95% CI = 0.95–1.34; p = 0.03). 119 Cruciferous intake was assessed by FFQ and included broccoli, cabbage, cauliflower, and brussels sprouts. When individual foods were analyzed, significant p-values remained for raw cabbage/coleslaw (p = 0.02), cauliflower (p = 0.03), and Brussels sprouts (p = 0.02), with the most pronounced risk in women consuming 1–3 servings/week compared with <1/month (cabbage: HR 1.26, 95% CI 1.05–1.51; cauliflower: HR 1.16, 95% CI 1.02–1.33; Brussels sprouts: HR 1.30, 95% CI 1.04–1.63). 119 This association was further supported by another Nurses’ Health Study II analysis including 81,961 premenopausal women with 3,810 laparoscopically confirmed cases, which showed that higher fiber intake specifically from cruciferous vegetables was associated with increased EM risk (RR Q1: 0–0.39 (0.25) g/d vs Q5: 1.31–23.9 (1.7) g/d: 1.17; 95% CI 1.06–1.29; p = 0.02). 184 Even though direct effects of cruciferous intake on EM symptoms are lacking evidence, there are potential system-biological interactions, warranting further investigation. Consumption of cruciferous might contribute to gastrointestinal symptoms like the “Endo-Belly”. The glucosinolates contained in cruciferous vegetables are broken down into sulfur-containing compounds (eg, isothiocyanates and thiocyanates) which are mainly digested via microbial gut fermentation and possibly exacerbating gastrointestinal symptoms. 186 Given that some individuals are more histamine-sensitive and that histamine degradation may be limited (due to reduced DAO activity) in EM, pain-related symptoms and inflammation may be amplified. 187 Another potential indirect effect of cruciferous vegetables is related to goitrogenic effects of glucosinolates, which inhibit thyroid iodine uptake. 188 Reduced goitrogen intake might be of therapeutically importance as hypothyroidism is widely prevalent in women with EM (9.6% versus 1.5% in general USA female population, p < 0.0001). 189 Cooking processes substantially reduce the conversion of glucosinolates in goitrogenic metabolites (eg, progoitrin to goitrin) by inactivating the enzyme myrosinase. 190 Nevertheless, glucosinolates also facilitate protective phytochemical potential, especially in modulating inflammatory pathways. A key compound is indole-3-carbinol (I3C), abundant in broccoli and cabbage. 191 Morales-Prieto et al demonstrated potential adjunctive effects of 3,3′-diindolylmethane (DIM), a condensation product of I3C. The combination of DIM and dienogest reduced cell viability in endometriotic tissue from EM patients, showing stronger anti-proliferative and estradiol-lowering effects compared to dienogest alone. They further explored clinical effects in a small supplementation study in EM patients (n = 5 per group), comparing DIM (3 × 100 mg/d) and dienogest (2 mg/d) to dienogest monotherapy. The combination of DIM and dienogest was associated with shorter bleeding pattern (DNG-DIM: 5.5 ± 1.2 days vs DNG: 17.3 ± 4.9 days, p < 0.05) compared to dienogest alone, resulting in significantly more bleeding-free days within 84 days (DNG-DIM: 64.5 ± 8.0 days vs DNG: 47.0 ± 2.5, p < 0.05.). 185 Nevertheless, these findings remain preliminary and warrant further investigation, particularly in light of conflicting associations that range from increased risk to potential adverse effects, as well as broader nutritional significance of cruciferous vegetables with respect to their micronutrient, fiber and phytochemical content. Cruciferous vegetables are rich in bioactive compounds that have been shown to have anti-inflammatory and hormone-modulating properties. Since excessive consumption of raw and unprocessed cruciferous vegetables can be associated with potential side effects such as histamine intolerance or hypothyroidism, consumption should be limited if these side effects occur. Trillions of microorganisms colonize the digestive system of the human body. Probiotics foster a healthy gut microbiota composition and are mainly composed of Lactobacteria and Bifidobacteria, which can enhance intestinal epithelial integrity and protect the intestinal barrier. Thus, they promote balance between commensals and pathogenic microbes of the gut microbiota, potentially contributing to improved immune function. 192 Therefore, they might aid in managing EM. In an Iranian pilot study, 37 women with EM (stage III–IV) supplemented one capsule of LactoFem® (containing four Lactobacillus strains such as L. acidophilus, L. plantarum, L. fermentum and L. gasseri ) daily for eight weeks. Significant pain relief was observed in dysmenorrhea compared to the placebo group (−3.5 ± 3.0 vs −2.2 ± 1.1, p = 0.018). The total pain score decreased by −7.3 ± 7.0 in the LactoFem® group and by −4.1 ± 1.7 in the control group after 8 weeks (p = 0.017). However, after discontinuation of treatment, pain levels increased again, indicating a temporary effect. 193 An Ukrainian study investigated the effect of the probiotic Femina Probiz (tablet containing 10 × 10^9 colony-forming units (CFU) Lactobacillus organisms) twice daily for one month in 20 women with EM-related infertility who underwent assisted reproduction. After intake of Femina Probiz for one month, the expression of the pro-inflammatory NLRP3 inflammasome in patients with EM decreased significantly from 24.4 to 0.7 (p < 0.05). This anti-inflammatory effect was not observed in the control group. 194 In a randomized placebo-controlled trial 72 patients (36 patients in each arm) received either oral sachets containing 5 billion CFU each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 or placebo twice daily for three months. QoL scores did not differ between both groups, but both groups showed significant improvement in pain (VAS) and severity (verbal rating scale) scores. The regularly intake of probiotics resulted in a lower use of nonsteroidal anti-inflammatory drug (OD: 0.69, 95% CI: 0.26–1.83) and an improvement of mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) in comparison with the placebo group. The use of non-steroidal anti-inflammatory drugs also had an influence on QoL scores and cytokines. The latter did not differ between both groups. 195 Animal models provide further evidence of the potential benefits of probiotics in EM. 196 Chouzenoux et al used a mouse model of EM. The animals were orally treated with one (P1: Saccharomyces boulardii ) or two probiotics (P2: Saccharomyces boulardii + Lactobacillus acidophilus ) during 4 or 12 weeks (W4-W12). They monitored growth of lesions by ultrasonography, the pain suffered by the mice with behavioural and qRT-PCR tests and their immune status by FACS and ELISA techniques. Clinically, heat sensitivity was significantly lower in P1-treated mice from W4, while tactile sensitivity was decreased by P2 treatment. The expression of the nerve growth factor (NGF), a potent regulator of growth, maintenance, proliferation, and survival of certain target neurons, was significantly increased by P1 treatment at W12 (p < 0.05). The oral administration of P2 for 4 to 12 weeks led to a reduction in volume and size of the lesions and improved pain sensitivity (p < 0.05). In addition, both treatments resulted in a reduction of advanced oxidation protein products in the sera, levels of zonulin, a marker of the intestinal barrier permeability, and in the inflammatory markers IL-6 and TNF-α (p < 0.05). 197 In a further murine EM model, Lactobacillus gasseri OLL2809 was able to inhibit the development of ectopic endometrial cells in the abdominal cavity by activating natural killer cells. This was most likely achieved through the induction of IL-12 production. 198 Uchida and Kobayashi reported also an inhibitory effect of Lactobacillus gasseri OLL2809 on the growth of mouse endometrial tissue in the abdominal cavity. 199 Itoh et al were also able to reproduce the above-described results in a placebo-controlled double-blind clinical study with 66 patients with EM. Supplements containing 100 mg of L. gasseri OLL2809 (n = 29) or placebo supplement (n = 33) were administered once a day for 12 weeks. Daily intake of L. gasseri OLL2809 was associated with a reduction in pain intensity assessed by VAS and dysmenorrhea on the verbal rating scales, recording at −3.3 ± 0.4 and −1.4 ± 0.2, respectively, as compared to the - 2.0 ± 0.3 and −1.0 ± 0.2 in the placebo group (p < 0.05). No adverse effects were documented. 198 Current evidence indicates that probiotics, particularly certain strains of Lactobacillus sp., could support the treatment of EM by combating dysbiosis, alleviating pain, modulating the immune system, and potentially inhibiting disease progression. Probiotics can inhibit the progression of EM and reduce EM-associated pain without apparent side effects. However, further large-scale, randomized trials are needed to confirm the long-term efficacy and safety of these therapeutic approaches. As a result, of industrial agriculture, nutritional intake is inevitably linked with exposure to chemical substances applied during food production. This applies to plant protection products, such as herbicides, pesticides, and fungicides, as well as medications for livestock, 200 , 201 including antibiotics, which encompass a diverse range of chemical structures and activities. Here, we focus on the chemical contaminants with reported endocrine-disrupting capacity. Among the nuclear receptors relevant to nutrition and endometriosis, the sex hormone receptors are of particular interest, as estrogen levels and their downstream effects are significant. 202 The estrogen receptor (ER) exists in two isoforms, ERα and ERβ. 167 It binds to a variety of food-borne contaminants, from which ERβ is particularly overexpressed in endometriotic tissue. 203 An important category of estrogen receptor-binding pesticides comprises organochlorine pesticides such as DDT, endosulfan, and dieldrin, which bind to estrogen receptors and exhibit estrogenic activity in vitro. 204 Although many countries, such as those in the EU, have restrictions on this highly persistent substance, they still linger in the environment due to their resistance. Due to their agonistic activity, they potentially play a role in etiology of EM. Among the non-persistent pesticides, the chemicals fludioxonil and fenhexamid have been reported to activate the ER. 205 Another class of highly persistent, also known as forever chemicals, 206 that bind to the ER are specific molecules from the class of perfluoroalkyl acid sulfonate (PFAS). It was found that perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) exhibit estrogenic activity, while others like perfluorobutanoic acid (PFBA) and perfluoropentanoic acid (PFPeA) show antiestrogenic effects. 206 PFAS have been detected in food, and food packaging material are found to be a significant source of PFAS contamination, especially coated paper and board treated with polyfluorinated alkyl phosphate esters (PAPs), which can metabolize into PFAS. 207 Although a causal link between PFAS and EM has not been established, PFAS have been found in EM tissue and are linked to more severe stages of the disease. 208 Due to its endocrine-disrupting properties, BPA is banned in the EU for its use in baby bottles and food contact materials, with a specific migration limit of 0.05 mg/kg food, 209 as well as in toys and thermal papers used for receipts. BPA has been associated with endometrial functions, exhibiting significant differences in activity on the estrogen alpha receptor for BPF and BPS. 210 Packaging material is also a significant source of Bisphenol A (BPA), which can bind to estrogen receptors and affect steroidogenic pathways by inhibiting CYP17 and CYP21, as well as downregulating steroidogenic gene expression. 211 The most widely used phthalate, di(2-ethylhexyl)phthalate (DEHP), has been shown to activate ER under certain conditions, eg, in ER-positive breast cancer cells. 212 However, the effect of DEHP is relatively low in comparison to natural estrogens like 17ß-estradiol. 213 Taken together, there are clear indications that food-borne contaminants and other factors can affect the endocrine balance, 214 thus affecting the regulation of estrogen levels in humans. It remains unclear how strong the impact is in relation to the natural estrogen levels. Evidence suggests that the Mediterranean diet (MedD) supports reproductive well-being and has potential as an adjunct or alternative strategy in the prevention and management of mental health issues like depression and neurogenerative disorders, as well as cardiometabolic disease, and cancer. 215–217 Currently, research accessing the effects of the MedD on EM remains sparse. MedD predominates in fiber-rich foods such as fruits, vegetables, legumes, and grains. These plant-based foods are complemented by moderate intake of fish, seafood and dairy products as the main protein source, and occasional but limited intake of red meat and wine. 216 , 218 Typical Mediterranean foods such as berries, figs, grapes and oranges, and vegetables such as garlic, cabbage, onions, spinach and lettuce, are rich in soluble and insoluble fiber, vitamins and polyphenols. 216 , 218 The MedD also includes plenty of legumes (such as lentils, beans, and chickpeas) and various grains eaten as whole oatmeal or rice or in processes forms like bread and cracker. Almonds, walnuts, hazelnuts, and pistachios are also part of the MedD. These foods are excellent source of dietary fiber, folic acid, vitamins, potassium, and copper, 219 which have a positive influence on cardiometabolic risk factors such as body weight, total- and LDL-cholesterol. 216 In addition, olive oil is a core component of the MedD as the primary fat source, characterized by a high content of MUFA, especially oleic acid. High-quality extra virgin olive oil (EVOO) contains a variety of polyphenols. Oleocanthol is a key phenolic compound of EVOO, which is known to be structurally similar to ibuprofen and also being able to inhibit cyclooxygenases, which are involved in producing inflammatory mediators like prostaglandins. 220 Still, as anti-inflammatory and anti-oxidative effects of oleocanthal are largely derived from studies on isolated compounds, the physiological relevance regarding regular EVOO consumption remains uncertain. 221 Nevertheless, it is plausible that long-term, habitual intake of EVOO may exert biologically meaningful low-dose effects that contribute additively to the broader phytochemical profile of the MedD. Overall, the high proportion of plant-based foods in the MedD contributes to a higher intake of compounds with anti-inflammatory and antioxidant properties. Current data examine the relationship between the risk of EM and the intake of defined plant-based food groups in large cohorts. The resulting epidemiological findings are inconsistent in some respects. Trabert et al reported a positive association between higher fruit intake and EM risk (>2 servings/day vs <1 serving: OR = 1.5, 95% CI: 1.0, 2.3, p = 0.04). 83 In contrast, Harris et al found a non-linear inverse association, particularly for citrus fruits, where ≥1 portion/day was associated with a 22% lower risk (OR = 0.78, 95% CI: 0.69, 0.89, p = 0.004) compared to <1 portion/week. 119 Ashrafi et al also reported an inverse relation with high fruit consumption (OR = 0.68 (95% CI: 0.50, 0.93, p = 0.015), 99 as did Parazzini et al (OR = 0.6 (0.4–0.8)) 101 and Youseflu et al reported a significantly lower risk of EM in women with the highest fruit intake (OR = 0.29 (0.11–0.74)). 97 Overall, a higher intake of fruits and vegetables is associated with a higher consumption of phytochemicals, micronutrients and dietary fiber, which exerts anti-inflammatory effects. Therefore, the MedD recommends regular consumption of fruits ≥3; vegetables ≥2 (á 200 g) with one portion raw/as a salad. 222 The Alternate Healthy Eating Index (AHEI) also awards the highest score for ≥4 portions of fruit and ≥5 portions of vegetables per day. 223 The German Nutrition Society also recommends consuming at least 300 g of fruit and 245 g of vegetables per day. 224 It should be noted that these are recommendations for healthy individuals. Since certain foods (or food groups) can contribute to a worsening of symptoms in patients with EM (eg, cruciferous vegetables, FODMAPs), this must be tested on an individual basis. As these foods are generally rich in micronutrients, avoiding them can lead to nutritional deficiencies. In addition, MedDiet is characterized by high fish consumption. Fatty fishes such as salmon, mackerel, tuna, and herring are main sources of LC n-3 PUFA (EPA, DPA, DHA), which have anti-inflammatory and pro-resolving effects. 216 , 218 , 225 Furthermore, dairy products are regularly consumed in the MedD. Arab et al showed that consuming dairy products (all low-fat and high-fat dairy foods) was associated with decreased risk of EM (RR: 0.90; 95% CI, 0.85 to 0.95; p < 0.001). 226 Possible mechanisms include anti-inflammatory properties of calcium and a reduction of oxidative stress. 98 , 227 , 228 A well-implemented MedD diet results in lower intake of red and processed meat, free sugars, refined carbohydrates, and trans fats, which are associated with higher risk for EM. Arab et al included five cohorts and three case–control studies with a sample size ranging from 156 to 116,607 in their systematic review and meta-analysis A higher intake of total dairy (all low-fat and high-fat dairy foods) was associated with decreased risk of EM (RR: 0.90; 95% CI: 0.85, 0.95; p < 0.001). These findings were not reflected in individual dairy products, as there was no significant association with intake of low- or high-fat dairy, cheese or milk and EM risk. In contrast, higher risk for EM was associated with higher intake of red meat (RR: 1.17; 95% CI: 1.08, 1.26; p < 0.001), TFA (RR: 1.12; 95% CI: 1.02, 1.23; p = 0.019), and SFA (RR: 1.06; 95% CI: 1.04, 1.09; p < 0.001). No association was found for the risk of EM and intake of fruits (RR: 0.97; 95% CI, 0.92 to 1.02; p = 0.209), total vegetables (RR: 0.97; 95% CI, 0.92 to 1.02; p = 0.256) and legumes (RR: 1.00; 95% CI, 0.93 to 1.08; p = 0.921). 226 Given that the Mediterranean diet involves consistent intake of foods high in vitamins, antioxidants, and anti-inflammatory compounds, its therapeutic potential for managing EM is apparent. The impact of MedDiet on EM-related pain, dysmenorrhea, dyschezia and dyspaneuria was investigated in an experimental single-arm study by Ott et al This study included 68 women with laparoscopically diagnosed with EM, who were encouraged to favor a diet with fresh fruit and vegetables, white meat (chicken, turkey) and fatty fish (three times a week), soy-products, whole meal, seed- and grain products, foods high in magnesium (eg, rice, corn, oatmeal, wheat germs) and cold pressed vegetable oils. In addition, they were taught to avoid sugary drinks, red meat, dairy products (hard cheese), salt, sweets and animal fats. The group of patients who adhered to the MedD (n=43) in the 5-month intervention experienced a decrease in general pain based on the numerical rating scale from 4.2 ± 3.0 to 2.0 ± 2.3 (p < 0.01) and significant improvement in dysmenorrhea, dyspareunia, and dyschezia (p < 0.01). Some study participants (approximately 37%) did not adhere to the diet, yet there was a significant improvement in overall pain symptoms as measured by the NRS. The important limitations were that the intervention instructions were delivered by telephone, participants did not attend in person, all data were based on self-report, and the absence of a control group. 176 Another prospective study by Cirillio et al involving 35 EM women, investigated the impact after a 6-month MedDiet intervention on EM-related symptoms. The dietary intervention led to improvements of dyspareunia (p = 0.04), non-menstrual pelvic pain (p = 0.06), dysuria (p = 0.04), and dyschezia (p < 0.001) after three months of intervention. Dyspareunia (p = 0.002) and dyschezia (p < 0.001) declined further throughout the six months. In addition, they observed a significant positive correlation between lipid peroxidation and VAS non-menstrual pelvic pain (r = 0.369, p = 0.029) and dysuria (r = 0.416, p = 0.013) and a significant negative correlation between oxygen radical absorbance capacity and VAS non-menstrual pain (r = −0.394, p = 0.019) and dyschezia (r = −0.515, p = 0.002) at baseline. Furthermore, they found a negative correlation between adherence to the MedD and markers of oxidative stress after six months of intervention (neutrophil-ROS: r = −0.55, p = 0.03; monocyte-ROS: r = −0.66, p = 0.007; lymphocyte-ROS: r = −0.55, p = 0.03). These data are likely related to an increase in plasma/serum levels of vitamin B12, vitamin E, folate, and zinc due to implementation of the MedD, whereby the significant increase in blood folate after six months (p = 0.006) was negatively correlated with lymphocyte-ROS (r = −0.59, p = 0.002) and monocyte-ROS (r = −0.63, p = 0.01). Taken together, adherence to a MedD resulted in improved pain perception and also improved gastrointestinal symptoms and oxidative stress markers. 217 As the EM-related inflammatory process can cause accelerated atherosclerosis, the observed reduction of ROS and total cholesterol (p = 0.01) and LDL-c (p = 0.003) due to the MedD is also favorable. In addition to compliance with the MedD, an increase in the Rapid Assessment of Physical Activity Tool 1 (RAPA) (p < 0.001) and RAPA 2 (p = 0.009) was observed after 3 months, which may also have contributed to the improvement in symptoms. 217 Current evidence indicates that adopting MedDiet improves cardiovascular risk factors and is associated with improved oxidation profiles and anti-inflammatory effects. Thus, the MedDiet serve as a promising therapeutic strategy to support the management of EM. A high intake of sugar and histamine can have adverse effects on health. Excessive sugar consumption is associated with obesity, insulin resistance, and inflammation, which contributes to metabolic disorders and cardiovascular diseases. 229 , 230 Histamine, a compound involved in immune responses, can cause adverse effects in sensitive individuals, leading to headaches, digestive issues, and symptoms similar to allergies. 231 While this information is generally established, emerging scientific data indicate potential benefits of adopting a sugar-free and low-histamine diet for patients with EM. Numerous studies underscore the crucial role of a healthy, balanced diet for individuals with EM, but there is an alarming lack of focus on the impact of added sugar intake. The Dietary Inflammatory Index (DII ® ) is a tool used to assess the inflammatory potential of an individual´s diet. 232 Diets rich in simple carbohydrates and added sugars tend to have higher DII ® scores, indicating a greater pro-inflammatory effect. A higher DII ® scores goes along with an increased risk of EM: 218 , 233 Demézio da Silva et al found that women with DII > 086 were four times more likely to have EM than those with DII ≤ 0.86 (OR = 4.14; 95% CI = 1.50–11.4). 233 Similarly, Kyozuka et al suggested an anti-inflammatory diet with low-sugar intake for pregnant EM patients to decrease preterm risk. 234 Sugar-sweetened beverages, including soft drinks, fruit juices with added sugars, and energy drinks, have also been identified as a potential dietary risk factor for EM. These beverages contribute to excessive calorie intake and rapid spikes in blood glucose levels. 235 Epidemiological studies suggest that a high intake of sugar-sweetened beverages is associated with a greater incidence of dysmenorrhea and may contribute to the hormonal imbalances observed in EM. 236–239 Sugar’s impact on EM is increasingly recognized as a contributor to systemic inflammation and hormonal dysregulation. Reducing sugar intake, particularly added sugars, at least less than 10% of daily energy intake (which is about 50g or about 12 teaspoons for adults) 240 could be a practical dietary approach for alleviating inflammation and enhancing the quality of life for individuals with EM. Further research is needed to explore the long-term effects of sugar reduction on disease outcomes and symptoms. In addition, regular consumption of large amounts of simple sugars can cause dysbiosis, or microbiome imbalance, which can lead to increased intestinal permeability and chronic inflammation. 184 , 241 A diet high in simple sugars may lead to a reduction in the diversity of the gut microbiome and an increase in the population of pro-inflammatory bacteria. As the human microbiome is a key to regulating the immune system and inflammation, thus affecting the development of EM. Simple sugars can increase oxidative stress, which is associated with cellular and tissue damage and can contribute to chronic inflammation. 242 Histamine, a key mediator released by mast cells, has been implicated in inflammatory processes, yet its specific contribution to EM pathophysiology is uncertain. 243 Mast cells are commonly found near nerve endings in the pelvic and abdominal areas, where their activation triggers the release of histamine, prostaglandins, and other inflammatory substances. This can lead to nociceptor activation, vasodilation, and oedema, which may exacerbate pain and inflammation. 243 , 244 In addition, estrogen, a key driver of EM progression, may enhance histamine-related inflammation by promoting mast cell activation through estrogen receptor alpha (ERα). This interaction could contribute to a cycle of increased histamine release and heightened inflammatory responses in endometriotic lesions. 38 Currently, there are no studies available that specifically address the role of a low-histamine diet in EM management. Instead, existing studies examine low-histamine diets in the broader context of anti-inflammatory dietary approaches. 232 , 233 While the exact role of histamine in EM is unclear, a low-histamine diet may provide potential symptom relief, in particular in women who are sensitive to histamine. More research is necessary to determine its effectiveness and underlying mechanisms. Wheat contains various macro- and micronutrients and provides fermentable substrates for the human microbiome. It also contains gluten which is a collective term for numerous different water-insoluble protein structures that make up 70–80% of the total protein content in wheat. 245 Mainly, gluten refers to the protein’s gliadin and glutenin. Due to the presence of various polymorphisms, gluten is considered a complex compound. Each wheat-genotype produces different types and quantities of these proteins. The structures related to gliadin and glutenin are found in rye (secalin), barley (hordein) and oats (avenin). All of these are collectively referred to as gluten. 245 Gliadin contains, among other things, peptide sequences that are resistant to gastric digestion and proteolytic breakdown. These epitopes are known as proline- and glutamine-rich sequences. It is suspected that many different gluten peptides act immunogenic and can trigger T-cell mediated immune responses. Each wheat-grain contains a range of immunogenic gluten peptides, and it remains unclear which specific peptides trigger immune responses in patients with coeliac disease (CD) and Non-Coeliac Wheat Sensitivity (NCSW). 245 Approximately 5–20 g of gluten is consumed daily in the Western diet. 246 An allergy to gluten is mediated by IgE and can lead to symptoms such as rashes, swelling and anaphylaxis. CD refers to the intolerance of gluten digestion and the associated harmful effects on the intestinal mucosa. If neither disease is present but relevant symptoms still occur, it is considered a NCWS. 247 The global prevalence of CD is 1.4% (95% CI, 1.1–1.7%) and patients with this chronic inflammatory condition, must adopt a gluten-free diet. 248 EM is associated with inflammatory bowel disease (IBS) such as Crohn’s disease, CD and NCWS. The reported gastrointestinal symptoms such as constipation or diarrhea, frequent bloating and cramping are often difficult to distinguish between IBS and EM. 249 Therefore, patients with EM and gastrointestinal complaints tend to follow a gluten-free diet (GFD), even though it is not a proven treatment method. An online survey of 4,078 participants with EM revealed that 66% had changed their eating habits after diagnosis. In addition, 92% stated that their quality of life had deteriorated after diagnosis. Of the participants, 15% opted for a gluten-free diet (GFD), 8% for an anti-inflammatory diet, 7.1% for a Mediterranean diet (MedD) and 4% for a ketogenic diet. 250 EM patients have a 12.8% higher prevalence of comorbidities like IBS than the control group. 247 Food intolerances were also more common in the EM group than in healthy control subjects, including intolerances to several types of food, eg, sorbitol, histamine or gluten. 112 The Nurses’ Health Study II collected data from 81,961 premenopausal participants, including 3,810 participants with a laparoscopically confirmed diagnosis of EM. The prospective cohort study applied a follow-up period of 24 years and assessed diets through FFQs every 4 years. Women in the highest quintile of gluten intake had a lower risk of EM diagnosis than those in the lowest quintile (RR (highest vs lowest quintile) = 0.91, 95% CI: 0.80, 1.02; p = 0.01). The result was not consistently significant across all sensitivity analyses. When adjusted for alternative healthy eating index (AHEI) or whole grain intake the results did not change significantly (RR: 0.97; 95% CI: 0.84, 1.11; p = 0.20). The temporal analysis showed the strongest inverse association for gluten intake 2–4 years prior to diagnosis (RR = 0.82, 95% CI: 0.74; 0.91; p < 0.0001). No association was found for gluten intake measured at baseline and with 4–6 year or 6–8 years before diagnosis and risk of EM. 184 Stephansson et al conducted a large, nationwide, population-based cohort study in Sweden to investigate the risk of EM in patients with biopsy-confirmed CD. The study included 11,097 women with CD and 54,992 age matched controls, using data collected between 1973 and 2008. During the follow-up, women with CD had a significantly higher risk of developing EM compared to the control group (HR = 1.39; 95% CI: 1.14, 1.70). The highest risk was observed in the first year after CD diagnosis. The absolute excess risk was 31 cases per 100,000 person-years. This association remained even after controlling for multiple diagnoses and in women of reproductive age. The authors suggest shared genetic susceptibility (eg, Human Leukocyte Antigen - DQ-Isotyp). Chronic inflammation may be a contributing factor in the association between the two diseases. Although surveillance bias and lack of dietary adherence may have influenced the result, the association remained consistent over extended follow-up periods. 251 A Gluten-Free Diet (GFD) decreases the QoL significantly due to the restrictions that come with eliminating gluten from the diet. Both children and adults reported a reduction in QoL due to avoidance of gluten in their daily lives. 252 On the one hand, the availability of gluten-free alternatives remains limited, and commercial products are often highly processed. On the other hand, food spontaneity and flexibility are restricted, further affecting daily food supply, social settings or traveling. 253 A GFD with foods made from alternative grains like corn, rice or tapioca flour instead of wheat contains fewer nutrients and less dietary fiber. 254 Additionally, processed gluten-free foods contain more saturated fats, trans fats and salt. 253 Adhering to GFD has been linked to poorer self-reported health outcomes, with notably higher rates of blood-related, immune-mediated and gastrointestinal disorders. 255 Skodje et al investigated the effects of gluten and rapidly fermentable fructans, both present in grains, on patients with self-reported Non-Celiac Wheat Sensitivity (NCWS). Participants reacted stronger to fermentable fructans than to gluten. The mean Gastrointestinal Symptom Rating Scale for IBS (GSRS-IBS) was higher for fructans (38.6. ± 12.3) compared to both gluten and the placebo group (33.1 ± 13.3; 34.3 ± 13.9; p = 0.04). Thus, the authors suggest that a low FODMAP diet, instead of a GFD, might help lessen the symptoms linked to NCWS. 256 Gluten tolerance is particularly susceptible to psychological influences such as the nocebo effects (= effect occurs when negative symptoms are experienced due to expectation and not because of actual harmful components) which was demonstrated by De Graaf et al, 257 In their international multi-center study, the combination of expectations and actual gluten intake had the greatest influence on gastrointestinal symptoms, suggesting a nocebo effect. EM is often associated with gastrointestinal complaints and conditions such as IBS, making it difficult to distinguish symptoms from other intestinal disorders. Many patients therefore follow a gluten-free diet, even though the benefits of such a diet have not been conclusively proven. A gluten-free diet can impair quality of life and is sometimes associated with unfavorable nutrient profiles. Studies show an increased risk of EM in coeliac disease, but no consistent protective effect of a low-gluten diet. Some individuals may react more strongly to fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) than to gluten, with psychological factors such as the nocebo effect also playing a role. Food hypersensitivities can be grouped into allergic and non-allergic food hypersensitivities. 258 Allergic food hypersensitivity is mediated by the immune systems reaction to typically harmless allergens, which in turn leads to antibody production. These immune system reactions are either IgE or non-IgE mediated. A non-IgE reaction results in a delayed response and gastrointestinal symptoms, whereas IgE mediated responses establish through swelling and hives. Dairy products, various types of nuts, soy, and wheat are examples of common allergens. Non-allergic food hypersensitivities cover a wide range of symptoms and are not mediated by the immune system. They are often referred to as food intolerances, such as lactose intolerance or reactions to salicylates in food. 259 A retrospective case control study conducted by Schink et al with 208 patients (156 with a confirmed diagnosis of EM) were assessed using FFQ and disease-related questionnaires that addressed the symptoms, duration of disease and comorbidities of the participants diagnosed with EM, 25.6% reported non-allergic food hypersensitivities (p = 0.009), especially self-reported intolerances (sorbitol (p = 0.031), histamine (p = 0.045), gluten (p = 0.025)). The control group reported 7.7% (p < 0.001) non-allergic food hypersensitivities. However, self-reported food intolerances are limited by recall bias and a lack of diagnostic clarity. 112 Sinaii et al analyzed 3,680 EM patients via a survey and reported the prevalence of allergies including food hypersensitivities. They found allergies of all sorts in 61% of EM patients and 18% in the control group (p < 0001). However, the survey is limited because it combines food allergies with environmental and chemical allergies. 189 Moreover, Schink et al also reported food allergies, although the findings did not reach statistical significance. 112 Yoshii et al evaluate the incidence rate ratio (IRR) of EM in women with allergic diseases (asthma, allergic rhinitis, urticaria, atopic dermatitis, allergic conjunctivitis, and type 1 allergies combined) compared with women without these diseases. They identified 30516 cases with EM and 120976 control participants and reported a significant positive association between type 1 allergy and EM (IRR, 1.10; 95% CI: 1.06–1.13) and between rheumatoid arthritis and endometriosis (IRR, 1.31; 95% CI: 1.05–1.64). 260 Patients with EM reported allergic and non-allergic food sensitivities more frequently than healthy control groups, although the significance of this finding is limited by self-reported data and a lack of diagnostic clarity. However, it is important to access individual food sensitivities beforehand so they can be incorporated into individualized nutritional concepts. Depending on individual sensitivity, consumption of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can cause gastrointestinal symptoms such as bloating, flatulence, abdominal pain and constipation as their incomplete absorption leads to hypersensitivity of the intestines and increased osmotic activity in the gastrointestinal tract. 249 , 261 Some EM patients adopt a low-FODMAP diet as self-management strategy to alleviate gastrointestinal symptoms. 174 , 262 It is frequently applied by nutritional professionals when counseling EM patients. 263 The low-FODMAP diet was developed at Monash University and originally consists of three phases ( Supplementary, Table S1–S2 ): (1) elimination of high-FODMAP foods for 2–6 weeks, (2) gradual reintroduction of FODMAP-rich food groups, and (3) establishment of a personalized diet based on individually tolerated foods. 261 , 264 High-FODMAP foods include vegetables such as onion, artichoke, garlic, peas, mushrooms, and most legumes; fruits such as apples, stonefruits or cherries; lactose-rich dairy products; wheat, rye, and barley products; and nuts such as cashews and pistachios. 261 , 264 FODMAP content can be reduced by preparation methods such as soaking, rinsing, cooking and bioprocessing to promote enzymatic degradation. 264 , 265 Bread, as an important staple food in many diets, shows a substantially greater breakdown of FODMAPs when produced through prolonged sourdough fermentation (24 h or longer) compared to produces with shorter fermentation times (0.5 to 3 h) like Baker’ yeast-leavened bread. 264 , 265 Likewise, lactose in dairy products can be reduced by enzymatic hydrolysis of lactase or fermentation with lactic acid bacteria. 265 As high-FODMAP foods are often also high in gluten, positive effects of a gluten-free diet could therefore also be attributed to the reduction of FODMAPs. 264 In a retrospective analysis, 72% of women with EM and comorbid IBS who attended an IBS service center in New Zealand, reported symptomatic improvement (>50% improvement in abdominal symptoms after 4 weeks) following a low-FODMAP diet. 249 In a pilot study (n = 22) based on Dutch dietary guidelines, a low-FODMAP intervention improved gastrointestinal as well as other EM-related symptoms. 175 Specifically, dysuria (p = 0.015) and bloating (p < 0.001) were significantly reduced compared with baseline, while deep dyspareunia was less pronounced compared with non-diet controls (MD −1.15; p = 0.032). In addition to general pain relief, improving digestive problems was one of the main reasons motivating EM patients to undergo dietary intervention. However, some parameters remained unaffected, including key pain-related symptoms such as dysmenorrhea and chronic pelvic pain. Moreover, stricter adherence to the low-FODMAP protocol did not yield additional significant benefits. 175 A professionally consulted low-FODMAP diet improved constipation in 21 women with EM, with Groningen-DeFeC questionnaire scores (0–30 scale) decreasing from 7.0 to 5.0 (p = 0.023). In addition, 7 of 11 QoL domains assessed by the EHP-30 showed significant improvement (p < 0.05). Despite a considerable dropout rate (10 of 34 participants who initiated the diet), primarily due to lack of motivation, most participants perceived the diet as feasible (63%) and would recommend it to others (90%). 266 Varney et al investigated the impact of dietary FODMAP intake on gastrointestinal symptoms in 35 women with EM using a RCT crossover design (28 days low-FODMAP, 28 days washout phase, 28 days control diet). The low-FODMAP diet contained <5 g/day, whereas the control diet contained ~20 g FODMAPs/day, with precooked meals according to the Australian Dietary Guidelines. Using the VAS, 60% of participants reported an improvement in their overall gastrointestinal symptoms during the low-FODMAP diet, compared to 26% on the control diet (p = 0.008). This corresponds to a higher likelihood of a positive response to the low-FODMAP diet (RR: 0.26, 95% CI: 0.09, 0.71; p = 0.015). The low-FODMAP diet was also superior in reducing diarrhea, bloating and abdominal pain (p < 0.007). Stool consistency normalized after intervention vs baseline (p < 0.001), likely due to a lower osmotic load. Furthermore, FODMAP intake during the control diet (19.9 (18.3–20.3) g/day) was significantly higher than at baseline (12.0 (10.1–16.9) g/day, p < 0.001), which may have influenced comparisons. Nevertheless, the trial suggests that beyond a standardized background diet, lowering FODMAP intake has potential to alleviate gastrointestinal symptoms. 267 To sum up, gastrointestinal symptoms such as bloating, abdominal pain or irritable bowel-like symptoms which are often described by patients with EM, can be reduced by implementing a low-FODMAP diet as reduction of poorly fermentable carbohydrates can alleviate symptoms in the gut. Some high-FODMAP foods are often also high in gluten, thus positive effects of a gluten-free diet could therefore also be mediated by reduction of FODMAPs. It is important to note that the low-FODMAP diet approach was not developed specifically for EM and should be implemented individually with a nutritionist to avoid nutrient deficiencies. Dietary interventions are often pursued by patients with EM as they enhance self-efficacy and enable symptom relief beyond conventional treatment options. However, EM patients are often left with trial and error self-treatment approaches due to the lack of evidence-based nutritional concepts for EM. Some elimination approaches may help identify individual food triggers and promote individualized nutritional strategies. However, their long-term ability to ensure adequate energy, macro- and micronutrient intake remains uncertain, particularly during prolonged elimination/reintroduction phases (6 weeks to 6 months). Notably, approaches with categorical exclusion of entire food groups (eg, dairy, cereals/gluten-containing products, low-FODMAP) must be viewed critically, especially in the absence of food intolerances. Current data, derived primarily from observational studies, demonstrate the potential of nutrition in the treatment of EM. Currently, there is a lack of intervention studies to provide robust dietary recommendations. To address this gap, there is an urgent need for well-designed clinical intervention studies. Future research is warranted to tailor nutritional guidelines that consider currently known influencing factors in a holistic system-biological approach: (1) harnessing the anti-inflammatory potential of diet; (2) individual exclusion/avoidance of foods associated with a proofed worsening of symptoms (eg, gluten, histamine, FODMAPs); or finding solutions for how these foods can be better tolerated (3) identification of potentially critical nutrients to counteract EM related nutritional deficiencies ( Figure 1 ). Future scientific evidence should be translated into practical dietary guidelines for daily application. Figure 1 Food-based recommendations to support therapy of endometriosis (The colors of the rings indicate overlaps between the three nutrition-related concepts. Question marks indicate that it should be individually assessed whether eliminating these components will alleviate symptoms. These components should not be eliminated across the board.). The diagram illustrates food-based recommendations to support therapy for endometriosis, featuring three overlapping nutrition-related concepts: anti-inflammatory diet, elimination diet and Mediterranean diet. The anti-inflammatory diet includes microalgae or fish oil, herbs and spices, whole grains, fermented foods and colorful vegetables. The elimination diet suggests assessing the impact of gluten, histamine, FODMAPs, sugar and contaminants, indicated by question marks. The Mediterranean diet emphasizes dairy products, colorful vegetables, citrus fruits, plant oils and fatty cold-water fishes. The central image depicts a uterus, symbolizing the focus on endometriosis. The diagram suggests individual assessment for eliminating certain components to alleviate symptoms, rather than a universal approach. Diet tips for endometriosis: anti-inflammatory, elimination, Mediterranean. Food-based recommendations to support therapy of endometriosis (The colors of the rings indicate overlaps between the three nutrition-related concepts. Question marks indicate that it should be individually assessed whether eliminating these components will alleviate symptoms. These components should not be eliminated across the board.). Practical recommendations for implementing an anti-inflammatory diet to support therapy of EM ( Figure 1 ). Omega-3 fatty acids – exerts anti-inflammatory effects and regulate the immune system Suitable foods: salmon, mackerel, herring, sardines, cod, plaice, pollock, hake, chia and flax seeds, walnuts, microalgae oil, linseed oil Healthy fats – anti-inflammatory effects and improvement of cholesterol levels Suitable foods: avocado, nuts, seeds, fish, rapeseed oil, olive oil, linseed oil, algae oil Fiber-rich foods – anti-inflammatory effects via SCFAs and counteract imbalance of microbiome Suitable foods: whole meal products, psyllium husks, oat bran, oat flakes, vegetables, (legumes) – tip – drink plenty of water (approx. 2 liters per day) with a fiber-rich diet Probiotic Foods – promote healthy gut flora Suitable foods: Apple cider vinegar, natural yoghurt, kefir or buttermilk with “live cultures”, other probiotic products containing Bifidobacterium infantis or B. longum (histamine-lowering effect) or Lactobacillus rhamnosus, Bifidobacterium breve or B. bifidum (no histamine production) Plant proteins – support muscle building and have a satiating effect Suitable foods: grains, nuts, seeds, oatmeal, quinoa, (legumes), algae Use herbs and spices – anti-oxidative and anti-inflammatory effects Suitable foods: turmeric (improved effect in combination with pepper), ginger, cinnamon, oregano, rosemary, parsley, coriander, mint Antioxidants – protect cells from oxidative stress and free radicals Suitable foods: berries (blueberries, raspberries, strawberries), green leafy vegetables, carrots, tomatoes, peppers, corn, turmeric, ginger, nuts, seeds, lentils Avoid saturated fats – promote inflammation and increase cholesterol levels Unsuitable foods: sausage, pork, high-fat dairy products, palm oil and coconut oil Avoid sugar and processed foods – promote inflammation Unsuitable foods – avoid if possible: white flour products, biscuits, sweets, soft drinks, ready-made products with artificial additives, fast food and fried foods, margarine, processed sausage and meat products (especially pork) Suitable foods: gluten-free flours (buckwheat, rice, corn, oat, lupin flour) – if gluten is well tolerated, whole meal flours based on wheat, rye or spelt can also be used FODMAPs – Can Exacerbate Gastrointestinal Symptoms Potentially unsuitable foods: cow’s milk, yoghurt, whole soy milk, grains, broccoli, mushrooms, legumes, pome fruit, cashews, pistachios, honey, marinated seafood (as these are nutrient-rich foods, they should only be avoided if they are not well tolerated) as well as sugar substitutes, dried fruit, fruit juices, beer, sparkling wine, liqueur, sweet wine Suitable alternatives: aubergines, carrots, green beans, spinach, romaine lettuce, iceberg lettuce, lamb’s lettuce, potatoes, carrots, parsnips, radishes, cucumbers, aubergines, red and green peppers, kiwis, mandarins, oranges, eggs, firm tofu, tempeh, seafood, oats, rice, corn, quinoa, millet, spelt sourdough bread, lactose-free milk, semi-hard cheese with up to 45% fat in dry matter (brie, camembert, feta, hard cheese), still water, unsweetened tea, plant-based drinks, dry wine Histamine – can exacerbate gastrointestinal symptoms (flatulence, diarrhea, abdominal pain) and/or non-specific complaints such as fatigue, headaches, joint pain or skin problems Potentially unsuitable foods: mature cheese, bacon, prosciutto, salami, ham, sea fish (especially tinned), sauerkraut, tomatoes, bananas, strawberries, raspberries, oranges, lemons, nuts, chocolate, yeast extract, red wine vinegar, alcoholic beverages, especially sparkling wine (as some of these foods are rich in nutrients, they should only be avoided if they are not well tolerated after being carefully tried) Suitable alternatives: apples, pears, fresh peaches, courgettes, carrots, potatoes, cucumbers, pistachios, macadamia nuts, almonds (natural, unsalted), quark, natural yoghurt, butter cheese, buttermilk, young herring (matjes) The histamine content in food varies depending on protein content, ripening process, storage time and processing, such as fermentation. These processes are triggered by microorganisms and bacteria, which promote the conversion of histidine into histamine. Fresh, untreated foods should be used whenever possible, because the fresher a product is, the less histamine it contains. As tolerance varies greatly from person to person, gradually eliminating and reintroducing foods can help to determine your personal histamine threshold. Gluten – can exacerbate gastrointestinal symptoms Unsuitable foods: Cereals, pseudo cereals, battered vegetables, cream dishes, breaded products, seitan, beer, malt beer (as some of these foods are rich in nutrients, they should only be avoided if they are not well tolerated after being carefully tried) Suitable alternatives: amaranth, millet, wild rice, rice, quinoa, corn, oats, buckwheat, flours made from rapeseed, legumes, nuts, plantains, legumes, fresh fruit and vegetables, eggs, natural dairy products, fish/seafood (unbreaded), tofu, tempeh, soy products (natural), vegetable oils, honey, seeds and nuts (unprocessed), fresh herbs and spices, mineral water, coffee, pure black, green, white, fruit and herbal tea (without additives)

The “EM Diet” originated as an experience-based approach, involving the restriction and inclusion of specific food groups ( Supplementary, Table S3–S4 ). The guidelines were initially provided via patient-driven online platforms ( https://www.endometriosedieet.nl and https://www.endometriosetelijf.nl ) and based on these initiatives, recommended by the Dutch EM Association. 268 The “EM Diet” emerged as the most frequently adopted dietary self-management strategy by Dutch women with EM (n = 34 of 157) in an exploratory analysis, while most patients had no specific diet (n = 84). 174 Despite recommendations to exclude food groups such as wheat/gluten-containing cereals, fish and meat as well as dairy products, women following the “EM Diet” achieved the highest adherence score to the national dietary guidelines (116.1 ± 14.5 points out of 160 on the Dutch Healthy Diet Index, DHD-15, based on 15 food groups). 174 Self-reported increased adherence to the “EM Diet” showed progressively improved QoL outcomes (range p < 0.001 to p = 0.043; adherence range p = 0.005 to 0.05), compared with women not adhering to the diet. Reported barriers included lack of awareness, perceived complexity and discontinuation mainly due to lack of benefits. 268 To assess the potential of the “EM Diet” in an interventional setting, van Haaps et al conducted a non-randomized pilot study in 21 women over 6 months. The dietary protocol emphasized reducing red meat, gluten, cow’s milk, added and refined sugars, phytoestrogen-rich foods (soy products, flax and sesame seeds, black beans) and caffeine (≤200 mg/day). Compared to baseline, participants reported significant improvements in bloating (p < 0001) and tiredness (p = 0.002) while only bloating improved significantly compared to a non-diet control group (MD −0.99, p = 0.041). Other gastrointestinal or pain-related symptoms, including chronic pelvic pain and dysmenorrhea, did not improve significantly. Nevertheless, 80.6% of participants indicated willingness to continue the “EM Diet”. Long-term nutritional adequacy, potential side effects and specific influence on EM-related outcomes remain unclear. 175 The “Endo Diet Protocol”, developed by the SLUCare Physician Group (Center for Endometriosis) in London, represents a practical example for an elimination and reintroduction approach (Endo Elimination Diet) combined with anti-inflammatory dietary recommendations. It involves the elimination and stepwise weekly reintroduction of dairy, gluten and added sugars under medical supervision (Yeung and Catanzaro via SLUCare). 269