Endometriosis and diet – can anti-inflammatory foods alleviate symptoms?

endometriosis, anti-inflammatory diet, pain, endometriosis treatment Endometrioza to przewlekła, estrogenozależna choroba zapalna charakteryzująca się implantacją tkanki endometrium poza jamą macicy. Do czynników patogenetycznych zalicza się dysfunkcję układu odpornościowego, zaburzenia angiogenezy i równowagi hormonalnej oraz predyspozycje genetyczne. Główną rolę odgrywają tu m.in. aktywowane makrofagi i cytokiny prozapalne (IL-1, IL-6, TNF-α), a także zaburzona równowaga limfocytów Th1/Th2 i obniżona aktywność komórek NK. Endometrioza znacząco obniża jakość życia, wpływając na zdrowie fizyczne, psychiczne i społeczne pacjentek. Zgodnie z zaleceniami European Society of Human Reproduction and Embryology leczenie endometriozy powinno być wielotorowe i obejmować terapię hormonalną oraz metody niefarmakologiczne, takie jak zmiana nawyków żywieniowych. Coraz więcej badań potwierdza korzystny wpływ diety przeciwzapalnej na zmniejszenie stanu zapalnego i łagodzenie objawów endometriozy. Dieta ta bazuje na spożywaniu produktów bogatych w wielonienasycone kwasy tłuszczowe omega-3, polifenole i terpeny, które wykazują właściwości przeciwzapalne i antyoksydacyjne. Mechanizmy jej działania obejmują m.in. modulację mikrobioty jelitowej, zmniejszenie stężenia markerów zapalnych (białka C-reaktywnego, IL-6, TNF-α) i regulację stresu

Streszczenie Małgorzata Maria Radowicka, Damian Warzecha 42 DOI: 10.15557/PiMR.2025.0004 PEDIATR MED RODZ Vol. 21 No. 1, p. 41–45 oksydacyjnego. Badania wskazują, że u kobiet stosujących dietę przeciwzapalną przez co najmniej 3 miesiące obserwuje się zmniejszenie stężenia markerów zapalnych i złagodzenie dolegliwości bólowych. Główne składniki diety, takie jak kwas eikozapentaenowy i dokozaheksaenowy, działają poprzez hamowanie metabolizmu kwasu arachidonowego i syntezę mediatorów proresolucyjnych, co przyczynia się do zmniejszenia produkcji cytokin prozapalnych. Z kolei polifenole i terpeny wpływają na szlaki sygnalizacyjne komórek i zmniejszają ekspresję genów prozapalnych. Podsumowując, dieta przeciwzapalna stanowi obiecujące uzupełnienie terapii endometriozy, wspierając redukcję stanu zapalnego i poprawiając jakość życia pacjentek. Wymaga jednak dalszych badań, aby ustalić optymalne składniki i dawki. Słowa kluczowe: endometrioza, dieta przeciwzapalna, ból, leczenie endometriozy E ndometriosis is an oestrogen-dependent, progres - sive chronic disease with an inflammatory basis, in which endometrial cells implant outside the uterine cavity. According to World Health Organization data, en - dometriosis affects approximately 190 million women of reproductive age. However, due to still imperfect diagnos - tic methods, it is estimated that the actual prevalence may be significantly higher(1). The disease was first described in 1690 by Daniel Shroen, while Karl von Rokitansky authored the first reports on the pathogenesis of endometriosis in 1860(2). Despite over 150 years of knowledge about the dis - ease, its aetiology remains unclear. Furthermore, it is still not understood why some women experience the classic symptoms of endometriosis, while others, despite signifi - cant pelvic changes, experience neither pain nor issues with conceiving. Moreover, the time from the onset of symptoms to diagnosis remains lengthy, averaging 5–12 years (3). Endometriosis significantly affects women’s physical health. The National Health Service lists it among the 20 most painful diseases globally (4). It often leads to prolonged ab - sences from work or school, creating an economic burden. The disease profoundly impacts women’s mental and emo- tional well-being, social activity, and sexual relationships. Research has shown that endometriosis can reduce the quality of life to a degree similar to cancer (5). One of the pathomechanisms of endometriosis is a chron - ic inflammatory process linked to immune system dys - function, which varies in severity depending on the disease stage(6). Macrophages play a crucial role in identifying for - eign cells and presenting them to T lymphocytes. Women with endometriosis exhibit an increased number of acti - vated macrophages in the peritoneal cavity, which have re- duced phagocytic capabilities. Proinflammatory cytokines, such as interleukin (IL) 1, IL-6, IL-8, and tumour necrosis factor-alpha (TNF-α), are also produced in higher concen- trations. Additionally, macrophages in the peritoneal cavity of women with endometriosis show increased expression of cyclooxygenase-2 (COX-2), leading to elevated prostaglan- din secretion. Increased cytokine release and decreased an- ti-inflammatory factor production contribute to both the de novo development and progression of endometriosis(6,7). Another critical mechanism in the pathogenesis of endome- triosis is the disrupted balance between helper T lympho - cytes type 1 (Th1) and type 2 (Th2). Th1 lymphocytes are responsible for cytokine production and promoting cellular immune responses, while Th2 lymphocytes regulate cyto - kine secretion to support B cell differentiation and humor - al responses. Studies indicate that Th2 lymphocyte activity predominates in women with endometriosis(8). Women with endometriosis also exhibit reduced activity of natural killer (NK) cells, which are crucial for natural cyto- toxicity. NK cell dysfunction limits their ability to eliminate endometrial elements from the peritoneal cavity, which en- ter through retrograde menstrual flow, allowing endometri- al cell implantation outside the uterus(9). Angiogenesis plays a vital role in the development of ecto - pic endometrium, especially in the microenvironment of the peritoneal cavity. This process is accompanied by the formation of nerve fibres, which contribute to pain in pa - tients. Vascular endothelial growth factor (VEGF) is re - sponsible for the formation and growth of new blood vessels. Elevated VEGF levels have been found in the peri - toneal fluid of women with endometriosis, with levels cor- relating positively with disease severity(10). Treatment for endometriosis depends on the symptoms and a woman’s reproductive plans. Hormonal therapy is the cornerstone of treatment, aiming to alleviate pain and slow disease progression. According to the European Society of Human Reproduction and Embryology (ESHRE) guide - lines, endometriosis treatment should be multi-faceted, encompassing hormonal therapy alongside non-pharma - cological methods. These methods include dietary adjust - ments, regular physical activity, physiotherapy, and psy - chotherapy. Surgical intervention, once considered the gold standard for diagnosing endometriosis, is no longer viewed as a first-line approach. Surgery should be undertak- en only after a careful assessment of the benefits and risks, and when conservative treatment is ineffective(11). Emerging evidence highlights the positive role of dietary changes in managing endometriosis. An anti-inflamma - tory diet helps reduce systemic chronic inflammation. Studies show that 76% of women adopt non-pharmacolog- ical methods to manage symptoms after being diagnosed with endometriosis, with almost half (44%) modifying their dietary habits(12). Another study found that 55.5% of wom- en experienced reduced pain due to conscious food choices. Dietary factors can influence the development and pro - gression of endometriosis by regulating steroid hormone Endometriosis and diet – can anti-inflammatory foods alleviate symptoms? 43 DOI: 10.15557/PiMR.2025.0004 PEDIATR MED RODZ Vol. 21 No. 1, p. 41–45 metabolism, the menstrual cycle, inflammation, oxidative stress, and muscle contractions(13). This article aims to dis - cuss the principles of an anti-inflammatory diet and review research findings on its impact on the disease. Dietary interventions in chronic pain patients have been shown to reduce intestinal barrier permeability by lowering the production of pro-inflammatory mediators, prevent - ing harmful metabolites from entering the bloodstream. Moreover, consuming anti-inflammatory foods appears to improve the quality of life (14). Dietary habits depend, among other factors, on geograph - ical location. The typical Western diet is characterised by high consumption of saturated fats, refined carbohy - drates, red meat, salt, and sugary beverages. This diet pro - motes excessive production of pro-inflammatory mediators while reducing anti-inflammatory mediators, including an- tioxidants. The Western diet has been shown to negative - ly impact chronic diseases, such as cardiovascular diseases, diabetes, gastrointestinal disorders, immune system dys - function, and endometriosis (14,15) . Geographical and so - ciodemographic factors also influence the prevalence of endometriosis (16). The principles of the anti-inflammatory diet were first in - troduced in 1995 by Barry Sears in “The Zone Diet” , with a revised version appearing in 2015. The diet’s concept is based on macronutrient proportions and their effect on in- sulin and cortisol levels. Various types of anti-inflammato- ry diets exist, such as the Nordic diet, the Okinawa diet, and the Mediterranean diet(17). Two studies analysed the relationship between green vege- table and fruit consumption, measured in servings per week or day, and the risk of endometriosis(18,19). An inverse rela- tionship was observed between the consumption of green vegetables and fruits and the risk of endometriosis. Data were analysed based on the number of servings per week. Significant risk reduction was noted with high consumption of green vegetables (odds ratio, OR 0.3; 95% confidence in- terval, 95% CI 0.2–0.5; p = 0.0001) and fresh fruits (OR 0.6; 95% CI 0.4–0.8; p = 0.002). These relationships remained consistent even after adjusting for confounding factors(18). In a case-control study by Trabert et al., the role of a diet rich in green vegetables and fruits was analysed similarly to the Italian study, considering daily servings. Increased daily fruit servings were associated with a higher disease risk (two or more servings per day compared to one or few- er: OR 1.5; 95% CI 1.2–2.3; p = 0.04), while no association with vegetable consumption was found(19). Interestingly, vegetables (particularly green ones) contain folic acid, methionine, and vitamin B6, which are associat- ed with “nutritional genomics” . A group of nutrients known as lipotropic, including methionine, choline, folic acid, and vitamin B6, plays a key role in this context. These nutrients can influence the human genome by altering gene expres - sion or their products and affecting DNA methylation(20). The primary components of an anti-inflammatory diet are polyunsaturated fatty acids, phenolic compounds, and terpenes/terpenoids. Omega-3 PUFAs exhibit immuno - modulatory and anti-inflammatory effects. Their mech - anism of action is complex. Prostaglandins and leukotri - enes, produced from arachidonic acid (AA), a member of the omega-6 fatty acids, have pro-inflammatory effects. Omega-3 fatty acids – eicosapentaenoic acid (EPA) and doc- osahexaenoic acid (DHA) – demonstrate a range of anti-in- flammatory actions. Increasing EPA and DHA levels in the membranes of cells involved in the inflammatory process impacts the physical properties of these membranes and the formation of signalling platforms called lipid rafts. EPA and DHA disrupt arachidonic acid metabolism. EPA gen - erates weaker (less pro-inflammatory) analogues, and both EPA and DHA are substrates for the synthesis of resolvins, protectins, neuroprotectins, and maresins, which are spe - cialised pro-resolving mediators. By affecting early mem - brane signals and the profile of lipid mediators produced, EPA and DHA alter intra- and intercellular signalling. This leads to modified patterns of gene expression and protein production within cells, resulting in reduced production of inflammatory cytokines, chemokines, adhesion molecules, proteases, and enzymes. The anti-inflammatory effects of EPA and DHA are significant for both the prevention and treatment of inflammatory conditions. It has been shown that increasing EPA and DHA intake inhibits arachidon - ic acid metabolism and reduces the expression of COX-2 genes and proteins(21). Studies have observed decreased pro- duction of series-2 prostaglandins (e.g. PGE2) and series-4 leukotrienes by inflammatory cells following EPA and DHA supplementation for several weeks to months. In these stud- ies, a dose-dependent effect on PGE 2 production was ob - served, with an EPA intake of 1.35 g/day for three months being insufficient to inhibit PGE 2, while 2.7 g/day signif - icantly reduced PGE 2 production. This suggests that the threshold for EPA ’s anti-inflammatory effect lies between 1.35 and 2.7 g/day (22). Phenolic compounds are a large, heterogeneous group of molecules widely distributed in nature. Polyphenols are found in many plants, fruits (particularly berries), tea, and cocoa, and possess anti-inflammatory and antioxi - dant properties. They have been shown to influence cellu - lar signalling pathways, such as NF-κB, thereby reducing the expression of pro-inflammatory cytokines. Additionally, some polyphenols, such as resveratrol and quercetin, act as AMPK activators, promoting anti-inflammatory respons - es and improving metabolism. Research indicates that con- suming polyphenol-rich foods is associated with a reduced risk of cardiovascular diseases, type 2 diabetes, and overall inflammation. However, due to limited clear scientific evi - dence, establishing reference intake norms for polyphenols is challenging. Some studies suggest that total flavonoid intake above 500 mg/day offers health benefits(23). Terpenes and terpenoids, a large group of compounds pri - marily derived from the secondary metabolism of plants, have demonstrated anti-inflammatory properties both in vi- tro and in vivo by regulating pro-inflammatory mediators Małgorzata Maria Radowicka, Damian Warzecha 44 DOI: 10.15557/PiMR.2025.0004 PEDIATR MED RODZ Vol. 21 No. 1, p. 41–45 and transcription factors, disrupting signalling pathways, and reducing oxidative stress(24). Current literature suggests that following an anti-inflamma- tory diet for at least three months can significantly reduce inflammatory marker levels, thereby alleviating pain symp- toms in women with endometriosis(14). This phenomenon is complex and involves several mechanisms. One such mechanism is the modulation of gut microbio - ta by an anti-inflammatory diet. The human gut contains trillions of microorganisms that play crucial roles in diges- tion, immune function, and neurotransmitter production. Dietary components, especially polyphenols and fibre, can significantly influence the composition and function of gut microbiota. A plant-rich diet promotes microbiota diversity, which is highly beneficial for health. Through the produc - tion of short-chain fatty acids, gut microbiota positively af- fects nervous system function by reducing symptoms such as fatigue, low mood, stress sensitivity, and cognitive dys - function. Enriching the diet with prebiotics (e.g. ferment - able fibre) and probiotics can further help reduce inflam - mation and improve intestinal barrier integrity. Dysbiosis, or microbial imbalance, is associated with chronic inflam - matory diseases(25). Another mechanism of action for an anti-inflammatory diet involves the modulation of inflammatory pathways. Dietary components can either exacerbate or reduce inflamma - tion by lowering levels of inflammatory markers, including C-reactive protein (CRP), IL-6, and TNF-α(26). A third key mechanism is the regulation of oxidative stress, defined as an imbalance between free radicals and anti - oxidants. Antioxidants are compounds that help neutral - ise harmful free radicals in the body, preventing cellular damage. They are categorised into two main types: exog - enous and endogenous antioxidants. Exogenous antioxi - dants, such as vitamins, minerals, and polyphenols, cannot be synthesised by the body in sufficient quantities and must be supplied through diet. Endogenous antioxidants, such as superoxide dismutase (SOD), glutathione, and ubiqui - nol, are produced within the body. Many components of an anti-inflammatory diet, including vitamins C and E, carot - enoids, and polyphenols, act as antioxidants, directly neu - tralising harmful free radicals(27). The effectiveness of an anti-inflammatory diet can be as - sessed by monitoring three key markers: 1. lipid stress – a TG/HDL ratio (in mg/dL) <1 indicates good insulin sensitivity; 2. inflammatory stress – an AA/EPA ratio in the range of 1.5–3 maintains inflammatory balance; 3. glycaemic stress – HbA1c levels between 4.9–5.1% reflect proper carbohydrate metabolism regulation(28). Not all dietary patterns are strictly pro- or anti-inflamma - tory. Classifying a specific dietary pattern can be facilitat - ed using the empirical Dietary Inflammatory Index (DII). The DII was created to analyse the overall dietary pattern in relation to plasma markers of inflammation and to de - termine the inflammatory potential of diets. Developed based on global literature from 1950 to 2010, the DII incor- porates 1,943 articles and 45 selected dietary components. The authors of the DII assessed the relationship between dietary products/components and inflammatory markers (IL-1β, IL-4, IL-6, IL-10, TNF-α, and CRP). They deter - mined whether the 45 individual dietary components in - creased (+1), decreased (−1), or had no effect (0) on these inflammatory markers. The DII can be used for initial as - sessment of the inflammatory contribution of a patient’s current diet and to monitor dietary changes over time(29).

Various biological mechanisms have been proposed to ex - plain the influence of dietary factors on the risk of develop- ing endometriosis. However, available epidemiological data and observational studies do not always consistently sup - port these hypotheses. Due to the limited number of scien- tific studies, this report provides a detailed overview of the

from several available studies to highlight even mi - nor effects that could serve as a foundation for further re - search, emphasising the need for additional analyses. Hormonal therapy remains the cornerstone of endometri- osis treatment. Implementing non-pharmacological treat - ment methods, including an anti-inflammatory diet, signifi- cantly improves the effectiveness of therapy. However, there is a group of patients for whom hormonal therapy cannot be applied – for example, women trying to conceive, those with contraindications to hormonal treatment, or those who refuse hormonal therapy. For these women, the cor - nerstone of care will be the implementation of non-phar - macological methods of pain reduction, with the anti-in - flammatory diet playing a key role. It is important to note that endometriosis is a multi-stage condition, beginning with the initial development of the disease, followed by proliferation, vascularisation, and peritoneal invasion of endometrial lesions, all accompa - nied by an inflammatory response. Various dietary compo- nents may have varying effects at specific stages of disease progression. Future research should aim to separately anal- yse the impact of diet on both the development of endome- triosis and its clinical consequences.

In summary, endometriosis is an oestrogen-dependent, chronic, and progressive disease. Its pathomechanism in - volves chronic inflammation and immune system dysfunc- tion. Treatment is primarily based on hormonal therapy, but non-pharmacological methods, including an anti-in - flammatory diet, are playing an increasingly important role. The key components of an anti-inflammatory diet include PUFAs, phenolic compounds, and terpenes/terpenoids. A diet rich in these substances helps regulate oxidative stress and inflammation, positively affecting gut microbi - ota and immune system function as early as three months Endometriosis and diet – can anti-inflammatory foods alleviate symptoms? 45 DOI: 10.15557/PiMR.2025.0004 PEDIATR MED RODZ Vol. 21 No. 1, p. 41–45 after implementation. Further research is needed to explore the effects of diet on the different stages of endometriosis development and the need for personalised therapy. Conflict of interest The authors do not report any financial or personal connections with other persons or organisations which might negatively affect the content of this publication and/or claim authorship rights to this publication. Author contribution Original concept of study; collection, recording and/or compilation of data; analysis and interpretation of data: MMR. Writing of manuscript; critical review of manuscript; final approval of manuscript: MMR, DW .

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