{"paper_id":"14356423-2656-4408-beee-82a20e480192","body_text":"Naeini et al. BMC Women’s Health          (2025) 25:232  \nhttps://doi.org/10.1186/s12905-025-03798-w\nRESEARCH Open Access\n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 \nInternational License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long \nas you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if \nyou modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or \nparts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated \notherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not \npermitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To \nview a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.\nBMC Women’s Health\nMCT-modified ketogenic diet as an adjunct \nto standard treatment regimen could alleviate \nclinical symptoms in women with endometriosis\nFatemeh Naeini1, Fatemeh Davari Tanha2, Maryam Mahmoudi3, Hastimansooreh Ansar3 and \nMohammad Javad Hosseinzadeh-Attar1* \nAbstract \nBackground Endometriosis as a chronic gynecological condition impairs the quality of life of affected women \nbecause it usually accompanied by painful clinical symptoms such as persistent severe acyclic pelvic pain, dys-\npareunia, and dyschezia. The aim of the present study was to examine the effects of MCT-modified ketogenic diet \nas an adjunct to standard treatment regimen in women with endometriosis.\nMethods This is a 12-weeks randomized controlled clinical trial that was conducted on 50 patients with endometrio-\nsis who referred to Yas hospital complex infertility clinic, Tehran, Iran. Participants were randomly allocated to inter-\nvention group receiving MCT-modified ketogenic diet plus standard treatment regimen (n = 25) and control group \nreceiving standard treatment regimen (n = 25). Clinical symptoms, anthropometric parameters, lipid profile, and serum \naminotransferases were measured at the beginning and end of the study. Statistical analysis was done by SPSS version \n27 software and P-value < 0.05 was regarded significant.\nResults Finally, 44 patients including 19 subjects in the intervention group and 25 subjects in the control group \ncompleted the study. Dyspareunia and dyschezia significantly reduced in the MCT-modified ketogenic diet group \ncompared to the control group at the end of the study (P = 0.02 and P = 0.001, respectively). Also, there was a margin-\nally significant reduction in the final values of pelvic pain (P = 0.07). However, no significant differences in the final \nvalue of anthropometric indices including weight, BMI, and WC, serum levels of TG, TC, HDL-C, LDL-C, and aminotrans-\nferases including ALT and AST was detected.\nConclusions MCT-modified ketogenic diet as an adjunct to standard treatment regimen could alleviate clinical \nsymptoms including pelvic pain, dyspareunia, and dyschezia in women with endometriosis.\nTrial registration Iranian Registry of Clinical Trials IRCT20131125015536N15. Registered on 24 July 2024. https:// \nwww. irct. ir/ trial/ 78113.\nKeywords MCT-modified ketogenic diet, Pelvic pain, Dyspareunia, Dyschezia, Endometriosis\n*Correspondence:\nMohammad Javad Hosseinzadeh-Attar\nhosseinzadeh.md.phd@gmail.com; mhosseinzadeh@tums.ac.ir\nFull list of author information is available at the end of the article\n\nPage 2 of 9Naeini et al. BMC Women’s Health          (2025) 25:232 \nBackground\nEndometriosis, an estrogen-dependent chronic condi -\ntion, characterized by the ectopic implantation of func -\ntional tissue lining the uterus outside of the uterine cavity \n[1]. Endometriosis as the most perplexing gynecological \ncondition affecting women of reproductive age mani -\nfests in infertility, chronic pelvic pain, severely painful \nmenstrual periods, dyspareunia, dyschezia, abdominal \nbloating, and constipation [2–4]. The prevalence of endo-\nmetriosis was high in developing countries. The inci -\ndence of endometriosis in women of reproductive age \nranges from 5 to 15% [5]. Endometriosis increases health-\ncare resource utilization and costs because of its high \nburden of comorbidities [6].\nA great variety of treatments for endometriosis-asso -\nciated symptoms have been implemented [7]. The com -\nbined oral contraceptive pill and progestogens as the \nfirst-line treatments and surgical approaches as the sec -\nond- and third-line treatments are recommended [8]. \nHowever, the recurrence rate of symptoms after five \nyears is 50% [9]. Thus, developing novel therapeutic strat-\negies focus on inflammatory and angiogenesis pathways \nas the most important mechanisms responsible for endo -\nmetriosis is of paramount importance [10]. Activation \nof estrogen signaling, systemic inflammation, oxidative \nstress, angiogenesis, cell division, and inhibition of apop -\ntosis are the main factors involved in the pathogenesis of \nendometriosis [11]. Also, based on the available evidence, \nWnt/B-catenin signaling pathway is the most well-known \npathway responsible for initiation and progression of the \nendometriosis lesions [12].\nKetogenic diet, a high-fat and very low-carbohydrate \ndiet, could consider as promising therapeutic option for \nthe management of various disorders including epilepsy, \ndiabetes, dyslipidemia, cardiovascular disease, malig -\nnancies and diseases of the female reproductive system \n[13]. By suppressing inflammation and oxidative stress, \nattenuating angiogenesis and cell division, promoting \napoptosis, and inhibiting Wnt/B-catenin signaling path -\nway, ketogenic diets may alleviate endometriosis and \nits related symptoms [14–17]. Among different kinds of \nketogenic diets, MCT-modified ketogenic diet acceler -\nates the process of ketogenesis [18]. Also, risk of some \ncomplications such as drowsiness, nausea, vomiting, \npossible low blood sugar, increased blood cholesterol, \nincreased liver enzymes, and gastrointestinal complica -\ntions is very low in modern ketogenic diets, such as the \nMCT oil-based ketogenic diet [19]. For example, a study \nconducted on breast cancer patients undergoing radio -\ntherapy showed that the administration of an MCT-based \nketogenic diet formula, compared to a standard diet, not \nonly did not cause the deleterious complications associ -\nated with the classic ketogenic diet, but also significantly \nimproved liver and kidney function indicators such as \ncreatinine and liver enzymes, as well as improved serum \ntriglyceride levels [20].\nAn animal study by Wang et al. [21] demonstrated that \nketogenic diet could attenuate cell division and promote \napoptosis in mouse with induced colorectal cancer. Also, \nthe authors reported that Wnt/B-catenin signaling path -\nway was suppressed and the expression of B-catenin as \na main mediating protein in this pathway was decreased \n[21]. In addition, a systematic review concluded that \nketogenic diets could be helpful for inflammation-associ -\nated pain, such as pelvic pain of endometriosis, by atten -\nuating inflammatory cascade [22].\nSince no clinical trial has investigated the effects of \nketogenic diets in the management of endometriosis, \nthis study aims to assess the effects of MCT modified-\nketogenic diet as an adjunct to standard treatment regi -\nmen in women with endometriosis.\nMethods\nStudy design\nThis current research is a randomized controlled clinical \ntrial that is registered at the Iranian Registry of Clinical \nTrials (ID: IRCT20131125015536 N15. https:// www. irct. \nir/ trial/ 78113. Registered on 24 July 2024.) and received \napproval from Medical Ethics Committee of Tehran \nUniversity of Medical Sciences, Tehran, Iran (IR.TUMS.\nMEDICNE.REC.1403.167). The present investigation \nconducted at the Yas Hospital Complex, Tehran, Iran in \naccordance with the Declaration of Helsinki. Also, this \nstudy adheres to CONSORT guidelines. Researchers \nobtained written informed consent from study subjects \nbefore participation in the clinical trial. Study subjects \nselected from women with endometriosis who were \ndiagnosed by a skilled specialist based on laparoscopic \nand pathological findings. Women with endometriosis \nenrolled from the clients of Yas hospital complex infer -\ntility clinic. An expert gynecologist diagnosed women \nwith endometriosis according to the laparoscopic and \npathological findings. Patients that satisfy the following \ninclusion criteria were eligible to participate in the pre -\nsent clinical trial. We included individuals aged between \n25 to 35 years, subjects whose BMI ranged between 21 \nto 25 kg/m 2, patients with diagnosis of endometriosis by \nan adept gynecologist according to the laparoscopic and \npathological findings (patients affected by endometriosis \nstage I or II based on diagnostic laparoscopy, or patients \nwith a higher stage who underwent diagnostic-therapeu -\ntic laparoscopy and the stage of their disease was reduced \nto I or II, three months after laparoscopy), and who fill \nout a written informed consent. Also, having a visual \nanalog scale (VAS) score of 3 out of 10 or greater than \n3 out of 10 for pelvic pain, dyspareunia, and dyschezia \n\nPage 3 of 9\nNaeini et al. BMC Women’s Health          (2025) 25:232 \n \nwas considered as another inclusion criterion. Women \nwho were pregnant or breastfeeding or menopause, \nwho were afflicted by liver and kidney disorders, kidney \nstones, cancer, intestinal malabsorption, diabetes, cardio-\nvascular diseases, and endocrine abnormalities, and who \nwere smokers or addicted to alcohol were excluded. Also, \npatients with uterine myoma or polyp and subjects who \ntake medications including anti-depressant drugs, clo -\nmifene, letrozole, and gonadotropins were excluded.\nRandomization\nRandom allocation was done by the Permuted Block \nRandomization method at the termination of the Run-\nin period. In this method, eligible people who met the \neligibility criteria were selected and then randomly \nassigned using 4 blocks based on the severity of endome -\ntriosis (stage I or stage II) in a random allocation method. \nThey were assigned to either MCT-modified ketogenic \ngroup or control group. In random allocation, based \non the list of random numbers, the letters A and B are \nassigned equally to the random numbers. In this way, \nthe letters A and B spread between the patient codes. \nNumbers assigned to patients according to the order of \nparticipants’entry, and patients received standard treat -\nment regimen (oral contraceptive pill (OCP)) plus MCT-\nmodified ketogenic diet or standard treatment regimen \nlonely based on specific letters (A or B). The intervention \ngroup received MCT-modified ketogenic diet plus stand -\nard treatment regimen and only standard treatment regi -\nmen was assigned to control group.\nStudy interventions\nWomen with diagnosed endometriosis who met the \ninclusion criteria and volunteer to participate in the \nstudy entered a two-week run-in period to obtain suf -\nficient data about their food habits and dietary intakes. \nAlso, compliance to the diet measured in this period of \ntime. Fifty eligible patients with endometriosis were \nrandomly allocated to intervention (n = 25) and control \ngroup (n = 25). The intervention group received MCT-\nmodified ketogenic diet plus standard treatment regi -\nmen (OCP) for 12 weeks and the control group received \nonly standard treatment regimen (OCP) for 12 weeks. It \nshould be noted that there was no dietary intervention in \nthe control group and they were recommended to follow \ntheir regular diet. MCT-modified ketogenic diet contains \n70–80% fat, 15–20% protein and 5–10% carbohydrates. \nThe calories of the diets were calculated based on the \nMefflin formula and based on the current body weight. \nThe ratio of grams of fat and protein to carbohydrates was \n3:1. A limited amount of pistachios, almonds, or olives \nwas recommended for snacks. Consumption of water, tea \nand spices was not limited. It was recommended not to \nuse rice, bread, sugar, sweets, potatoes, pasta and dairy \nproducts during the intervention period. The amount \nof protein was limited and comes from eggs, cheese, \nfish, chicken, quail and meat. The amount of fruit in the \ndiet was very limited and vegetables could be used in \nthe amount allowed in the diet. Ketogenic diet started \nand stopped gradually. Patients advised to consume two \nmeals of regular diet and one meal of ketogenic diet on \nthe first two days. Two meals of ketogenic diet and one \nmeal of regular diet consumed on the third and fourth \nday and finally on the 5 th day, the consumed completely. \nAlong with the diet, 500 cc of MCT oil was given to the \npatients every three weeks to accelerate the process of \nketosis. Since MCT oil was tasteless, patients advised to \ntake 8 cc of it (based on the amount prescribed in the \ndiet) with a salad or on its own after a main meal. Con -\nsumption of MCT oil was gradually started with a dose \nof 5 ml and within 3 days, it reached the final dose calcu -\nlated in the diet. About 40 food menus were planned for \npatients to use any menu they like based on their individ-\nual preferences. Multivitamin supplements and calcium-\nvitamin D supplements were also prescribed for patients \nin both study groups.\nTo assess adherence to the diet during the intervention, \na three-day food recall questionnaire was collected from \nthe participants by phone calls at the beginning of the \nstudy and every two weeks. If the study patients did not \nanswer phone calls more than twice or consumed 3 inap -\npropriate meals per week for more than 2 consecutive \nweeks, they considered non-compliant. Also, the patients \nwere asked to measure their urinary ketones daily, while \nfasting and using a urine ketone strip, during the first two \nweeks and once a week after that. Persistent ketonuria \nwas determined by urinary ketones above 0.5 mmol/L. If \nthere was not even one day of stable ketonuria after the \ncomplete start of the diet (the fifth day), patients were \nconsidered non-compliant and excluded from the study. \nAbout follow-up schedule, all parameters except body \nweight and dietary intakes were assessed at the initiation \nof the study and after the intervention period, 12 weeks.\nMeasurements and assessments\nAssessment of anthropometric parameters\nBody weight was estimated fasting, without shoes, with \nminimal clothing and using a digital scale (Seca, Ham -\nburg, Germany) with an accuracy of 100 g at the begin -\nning and end of the study. Also, once every 2 weeks, \nbody weight of participants was asked by phone call. The \nheight of people standing without shoes was measured \nwith a tape measure installed on the wall with an accu -\nracy of 0.5 cm. BMI was calculated using the formula of \ndividing weight in kilograms by the square of height in \nmeters. We measured waist circumference (WC) using \n\nPage 4 of 9Naeini et al. BMC Women’s Health          (2025) 25:232 \nthe middle of the lowest gear, the high point of the iliac \ncrest and on the biggest environmental gluteal muscle, \nrespectively.\nLaboratory assessments\nBlood samples (10 mL) were drawn following an 8 to \n12-h overnight fasting before and after the intervention. \nIt was used to separate the serum by centrifuging at a \nspeed of 3500 rpm for 10 min. The serum was transferred \ninto sterile microtubes and kept in a −80 ℃ freezer until \nthe test. Commercial kits (Pars Azmoon Inc. kit, Tehran, \nIran) used to measure the concentrations of total cho -\nlesterol (TC), triglyceride (TG), low-density lipoprotein \ncholesterol (LDL-C), high-density lipoprotein cholesterol \n(HDL-C), and liver transaminases including aspartate \naminotransferase (AST) and alanine aminotransferase \n(ALT).\nClinical assessments\nClinical symptoms including pelvic pain, dyspareunia, \nand dyschezia were estimated at the beginning and ter -\nmination of the study using a visual analog scale (VAS) \nquestionnaire that its validity and reliability have been \nconfirmed. Blood pressure was checked out using a mer -\ncury sphygmomanometer after at least five-minutes rest -\ning. The measurement was carried out on two occasions.\nSample size calculation\nBy considering type I error of 5% (α = 0.05) and power \nof 90%, the sample size was calculated to be 19 for each \ngroup according to the two sided t test. We upraised the \nfinal sample size to 25 women in each group to compen -\nsate for drop-out rate of 25% during the research period.\nStatistical analysis\nDescriptive and analytical statistics was applied for data \nanalysis and all analyzes were run using SPSS version 27 \nsoftware. The normal distribution of the variables was \nchecked through scatter diagram, histogram and Shap -\niro–Wilk test. Median (interquartile range) applied for \nvariables with non-normal distribution. Mean (standard \ndeviation) and number (percentage) were respectively \nused for quantitative and qualitative variables. Between-\ngroup differences were assessed using a general linear \nmixed model (GLM) for continuous variables and chi-\nsquare test for categorical variables. P-value < 0.05 was \naccounted statistically significant.\nResults\nAs demonstrated in Fig.  1, among the 119 women exam -\nined for the eligibility criteria, 50 met the inclusion crite -\nria and recruited in the study. As six of the patients were \nFig. 1 Study flowchart. OCPs, oral contraceptive pills\n\nPage 5 of 9\nNaeini et al. BMC Women’s Health          (2025) 25:232 \n \nlost to follow up, finally, 44 (19 in the intervention group \nand 25 in the control group) completed the trial.\nTable  1 indicated baseline characteristics of study \npatients. The mean age of the patients was 27 ± 4 years \nand 29 ± 4 years in the intervention and control group, \nrespectively. Fifty-three percent of the women in the \nintervention group and forty-eight percent of them in \nthe control group were affected with endometriosis \ngrade II. There were no statistically significant differences \nbetween the two groups in terms of age, weight, height, \nmarital status, educational level, occupational posi -\ntion, socio-economic status, and grade of endometriosis \n(Pvalue > 0.05).\nThe anthropometric parameters of the participants \nare shown in Table  2. There were no significant within- \nor between-group differences in terms of weight, \nBMI, and WC in the study groups post-intervention \n(Pvalue > 0.05). Also, comparing change-from-baseline \nvalues for all the mentioned parameters indicated no \nstatistical significant difference between study groups \n(Pvalue > 0.05). As indicated in Table  3, after adjusting \nfor baseline values and weight changes, no significant \ndifferences in the final value of serum levels of TG, \nTC, HDL-C, LDL-C, and aminotransferases includ -\ning ALT and AST were observed in the intervention \ngroup compared to the control group post-intervention \n(Pvalue > 0.05). Also, comparing change-from-baseline \nvalues for all the mentioned parameters except TC indi -\ncated no statistical significant difference between study \ngroups (P value > 0.05). There was a significant increase \nin change-from-baseline value for TC in the interven -\ntion group compared to the control group (P value=0.04). \nHowever, regarding within-group differences, serum \nlevels of AST was significantly reduced in both of \nthe MCT-modified ketogenic diet group and control \ngroup at the end of the trial (P value=0.02 and Pvalue=0.03, \nrespectively).\nTable  4 reported clinical symptoms of the partici -\npants during the study. After adjustment for potential \nconfounders including baseline values, weight changes, \nand endometriosis grade, dyspareunia (MD = 0.82; 95% \nCI = 0.12, 1.52; p = 0.02) and dyschezia (MD = 1.06; \n95% CI = 0.46, 1.6; p = 0.001) significantly reduced in \nthe MCT-modified ketogenic diet group compared to \nthe control group at the end of the study. Comparing \nchange-from-baseline values for dyspareunia (p  = 0.05) \nand dyschezia (p  = 0.001) showed a significant decrease \nin the intervention group. Also, there was a marginally \nsignificant reduction in the final values of pelvic pain \n(MD = 0.42; 95% CI = − 0.04, 0.88; p = 0.07) in the inter -\nvention group compared to the control group at the \ntermination of the trial. However, comparing change-\nfrom-baseline values for pelvic pain demonstrated \nno statistical significant difference between the study \ngroups (P value > 0.05). Regarding within-group differ -\nences, a significant decrease in the scores of pelvic pain, \ndyspareunia, and dyschezia was detected in both of the \nstudy groups (P value < 0.005).\nTable 1 Baseline characteristics of the study subjects\nData are presented as mean ± SD for quantitative and frequency (%) for qualitative variables\nKD ketogenic diet\n* based on aindependent sample t test, bchi-square, and cmann-whithney test\nvariables Groups P-Value*\nMCT-modified KD (n = 25) control (n = 25)\nAge (years) 27 ± 4 29 ± 4 0.1a\nweight (kg) 60.3 ± 8.4 61.4 ± 6.3 0.65a\nHeight (cm) 163 ± 7 163 ± 6 0.87a\nMarital status married 22 (88%) 21 (84%) 0.68b\ndivorced 3 (12%) 4 (16%)\nEducation Diploma and lower 5 (20%) 6 (24%) 0.73c\nBachler and higher 20 (80%) 19 (76%)\noccupation Housewife 8 (32%) 4 (16%) 0.4b\nEmployee 11 (44%) 13 (52%)\nSelf-employed 6 (24%) 8 (32%)\nSocio-economic status High 13 (52%) 10 (40%) 0.39c\nmoderate 12 (48%) 15 (60%)\nEndometriosis grade grade 1 9 (47%) 13 (52%) 0.76c\ngrade 2 10 (53%) 12 (48%)\n\nPage 6 of 9Naeini et al. BMC Women’s Health          (2025) 25:232 \nDiscussion\nCurrently, no curative treatment for endometriosis exists \nsince pathogenesis of this disorder is not fully recognized \n[23]. Even after treatment of these patients using hormo -\nnal suppression, surgery, or a combination of both, the \nseverity of endometriosis remained unchanged in most of \nthe cases [24]. Therefore, investigating an adjuvant ther -\napy such as an appropriate diet could be beneficial for \nthe management of endometriosis [25, 26]. To the best \nof our knowledge, this is the first randomized controlled \ntrial investigating the effects of MCT-modified ketogenic \ndiet as an adjuvant therapy in patients with endometrio -\nsis. Based on our main findings, dyspareunia and dysche -\nzia significantly reduced in the MCT-modified ketogenic \ndiet group compared to the control group at the end of \nthe study. Also, there was a marginally significant reduc -\ntion in the final values of pelvic pain. However, no sig -\nnificant differences in the final value of anthropometric \nindices including weight, BMI, and WC, serum levels of \nTG, TC, HDL-C, LDL-C, and aminotransferases includ -\ning ALT and AST was detected.\nIn line with our findings, a systematic review by \nMasino et al. [22] concluded that ketogenic diets could be \nhelpful for inflammation-associated pain like pelvic pain \nin endometriosis by attenuating inflammatory cascade. \nAlso, a recent prospective study conducted by Cirilo et al. \n[27] disclosed that there was a clear tendency toward a \nrelationship between pain relief in endometriosis and \nMediterranean diet. After 3 months of intervention, \ndyspareunia, non-menstrual pelvic pain, dysuria, and \ndyschezia were significantly reduced. Moreover, after six \nmonths of intervention, there was a significant decrease \nin terms of dyspareunia and dyschezia [27].\nAnother clinical study by Haaps et  al. [28] found that \npatients who were on both a low-FODMAP diet and an \nendometriosis-specific diet for 6 months experienced less \npelvic pain and had better quality of life scores compared \nto the control group. Overall, the study concluded that \nnutritional interventions including both a low-FODMAP \ndiet and an endometriosis-specific diet improved pain \nand quality of life in patients with endometriosis [28].\nMarziali et al. [29] indicated that prescription a gluten-\nfree diet for 12 months can significantly reduce painful \nsymptoms associated with endometriosis. Another study \nby Moore et al. [30] revealed that prescribing a low-FOD-\nMAP diet for 4 weeks in patients with endometriosis who \nhad IBS significantly improved pain in the abdomen and \npelvis. The hypothesis for the effectiveness of these diets \nin patients with endometriosis is that they often have \nintestinal disorders such as IBD, IBS, and celiac disease, \nand the presence of these disorders and their associated \nabdominal pain doubles the amount of pelvic pain asso -\nciated with endometriosis. Therefore, following a gluten-\nfree diet or low-FODMAP diet, due to the improvement \nin abdominal pain of the aforementioned intestinal dis -\norders, generally reduces abdominal and pelvic pain [29, \n30].\nActivation of estrogen signaling, systemic inflamma -\ntion, oxidative stress, angiogenesis, cell division, and \ninhibition of apoptosis are the main factors involved in \nTable 2 Anthropometric parameters of the study subjects at baseline and after the 12-weeks of intervention\nData are presented as mean ± standard deviation\nBMI Body mass index, WC waist circumference, KD ketogenic diet\n* based on aindependent sample t test, and bgeneral linear model adjusted for baseline values\n** based on paired sample T test\nparameter Time Groups Mean difference 95% CI P*\nMCT-Modified KD \n(n = 19)\nControl (n = 25) Lower Upper\nweight Before 60.3 ± 8.4 61.4 ± 6.3 1.05 −3.65 5.76 0.65a\nAfter 60.2 ± 8.4 61.4 ± 6.1 0.21 −0.45 0.87 0.52b\nChange −0.11 ± 0.78 0.08 ± 1.2 0.18 −0.43 0.81 0.55a\nP-within** 0.54 0.76\nBMI Before 22.6 ± 1.8 22.9 ± 1.2 0.34 −0.64 1.34 0.48a\nAfter 22.6 ± 1.9 22.9 ± 1.3 −0.005 −0.28 0.27 0.97b\nChange 0.02 ± 0.4 0.02 ± 0.49 0 −0.26 0.27 0.97a\nP-within** 0.86 0.84\nWC Before 79.2 ± 3.6 81.2 ± 5.02 1.9 −0.63 4.61 0.13a\nAfter 79.1 ± 3.4 81.2 ± 4.6 0.23 −0.29 0.76 0.38b\nChange −0.05 ± 0.5 0.01 ± 1.1 0.06 −0.46 0.58 0.81a\nP-within** 0.69 0.97\n\nPage 7 of 9\nNaeini et al. BMC Women’s Health          (2025) 25:232 \n \nthe pathogenesis of endometriosis [11]. ketogenic diets \nmight alleviate endometriosis and its-related complica -\ntions by targeting main factors involved in its pathogen -\nesis. They suppress inflammation and oxidative stress, \nattenuates angiogenesis and cell division, and promotes \napoptosis. Also, as a theoretical explanation, ketogenic \ndiets could inhibit Wnt/B-catenin signaling pathway as \nthe most well-known pathway responsible for initiation \nand progression of the endometriosis lesions [12, 14–17, \n21]. They suppress Wnt/B-catenin signaling pathway by \ndecreasing the expression of B-catenin, main mediating \nprotein in this pathway [21].\nStrengths and weaknesses of the trial\nThe strengths of our trial included long duration of the \nintervention, a personalized and prescription-based \ndietary intervention, and robust statistical analysis that \nadjusted findings for probable confounders to minimize \nbiases. Also, investigating the effects of MCT-modified \nketogenic diet as an adjunct to standard treatment regi -\nmen in women with endometriosis, for the first time, \nwould be considered as another strong points. Our trial \nalso has some notable limitations. First, our results \ncould not be generalized to patients with moderate to \nsevere disease (endometriosis grade III and IV) because \nwe exclusively included patients with endometriosis \ngrade I and II. Also, narrow inclusion criteria for age \n(25–35 years) and BMI (21–25 kg/m 2) may limit the \nexternal validity of the study. It should be noted that the \nfindings may not apply to populations with overweight/\nobesity or older reproductive-age women. Second, due \nto the remarkable drop-out rate, the sample size seems \nto be not sufficient. Third, some other unknown con -\nfounders could affect the obtained results despite of \nconsidering probable confounding variables in statisti -\ncal analysis. And finally, given the anti-inflammatory \nTable 3 Biochemical parameters of the study subjects at baseline and after the 12-weeks of intervention\nData are presented as mean ± standard deviation or Median (IQR)\nALT alanine aminotransferase, AST aspartate aminotransferase, TG triglyceride, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, \nTC total cholesterol, KD ketogenic diet\n* based on aindependent sample t test, cmann-whithney, and bgeneral linear model adjusted for baseline values and weight changes\n** based on dpaired sample T test or eWilcoxon\nparameter Time Groups Mean difference 95% CI P*\nMCT-modified KD \n(n = 19)\nControl (n = 25) Lower Upper\nAST Before 18 (17, 24) 19 (16, 24) 1.6 −1.9 5.2 0.82c\nAfter 18 (16, 21) 19 (17, 22) 0.8 −0.13 1.73 0.09b\nChange −1 (−3, 0) 0 (−3, 0) 0.31 −1.1 1.8 0.53c\nP-within** 0.02e 0.03e\nALT Before 19.7 ± 6.7 17.8 ± 7.1 −1.8 −6.1 2.3 0.37a\nAfter 18.9 ± 6 17.6 ± 6.1 0.14 −1.02 1.32 0.8b\nChange −0.84 ± 2.5 −0.28 ± 2.03 0.56 −0.87 1.9 0.43a\nP-within** 0.16d 0.49d\nTG Before 111 ± 36 100 ± 42 −11.5 −35.07 12.03 0.32a\nAfter 109 ± 36 102 ± 35 2.9 −2.2 8.2 0.25b\nChange −2.2 ± 8.3 2.36 ± 10.4 4.57 −1.16 10.3 0.11a\nP-within** 0.26d 0.27d\nTC Before 143 ± 30 171 ± 26 27.8 10.58 45.11 0.02a\nAfter 147 ± 28 164 ± 21 −3 −12.05 6.04 0.5b\nChange 3.7 ± 17.7 −6.3 ± 11.7 −10.1 −19.7 −0.48 0.04a\nP-within** 0.36d 0.01d\nHDL Before 52 ± 14 53 ± 12 1.05 −7.1 9.2 0.79a\nAfter 52 ± 12 54 ± 12 0.66 −1.5 2.8 0.55b\nChange 0.05 ± 5.2 0.6 ± 2.8 0.54 −2.17 3.23 0.68a\nP-within** 0.96d 0.3d\nLDL Before 101 ± 22 95 ± 23 −6.8 −20.69 7.06 0.32a\nAfter 107 ± 27 96 ± 17 −4.9 −11.05 1.08 0.1b\nChange 5.58 ± 12.5 1.32 ± 7.93 −4.2 −10.81 2.29 0.19a\nP-within** 0.06d 0.41d\n\nPage 8 of 9Naeini et al. BMC Women’s Health          (2025) 25:232 \nhypothesis of the ketogenic diet, it is a missed oppor -\ntunity not to measure biomarkers such as CRP , IL-6, or \nTNF-α.\nConclusion\nAltogether, MCT-modified ketogenic diet as an adjunct \nto standard treatment regimen could significantly allevi -\nate clinical symptoms including dyspareunia and dys -\nchezia in women with endometriosis. Also, there was a \nmarginally significant reduction in pelvic pain. Future \nwell-designed randomized controlled trials with greater \nsample size enrolling patients with all stages of endome -\ntriosis are recommended to establish the benefits of the \nMCT-modified ketogenic diet as an adjuvant therapy in \nthe management of endometriosis. Also, it is important \nto incorporating validated quality of life assessment tools \nsuch as the SF-36 or EHP-30 questionnaires to evaluate \nthe broader impact of the MCT-modified ketogenic diet \non patients’ well-being in future studies.\nAbbreviations\nBMI  Body mass index\nALT  Alanine aminotransferase\nAST  Aspartate aminotransferase\nPBMCs  Peripheral blood mononuclear cells\nWC  Waist circumference\nVAS  Visual analog scale\nTG  Triglyceride\nTC  Total cholesterol\nLDL-C  Low-density lipoprotein cholesterol\nHDL-C  High-density lipoprotein cholesterol\nAcknowledgements\nWe sincerely thanked Tehran university of medical sciences (TUMS) for its \nfinancial support.\nAuthors’ contributions\nFN and FD contributed to the conception of research and searched databases, \ndata collection was done independently by 2 reviewers (FN and FD), MM and \nHA performed the statistical analysis, FN wrote the manuscript, and MJHA \ncritically revised the manuscript.\nFunding\nThe trial funding was supported by Tehran University of Medical Science \n(Grant number: 73845). The funder is not involved in the study design, collec-\ntion, management, analysis and interpretation, writing of the manuscript, and \nthe decision to submit the report for publication, including whether they will \nhave ultimate authority over any of these activities.\nData availability\nThe datasets generated and/or analysed during the current study are not \npublicly available, but are available from the corresponding author on reason-\nable request.\nDeclarations\nEthics approval and consent to participate\nWritten informed consent was obtained from participants before participation \nin the research project. The current trial received approval from Medical Ethics \nCommittee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.\nMEDICNE.REC.1403.167). This study was conducted in accordance with the \nDeclaration of Helsinki.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nTable 4 Clinical symptoms of the study subjects at baseline and after the 12-weeks of intervention\nData are presented as or Median (IQR)\nKD ketogenic diet\n* based on cmann-whithney and bgeneral linear model adjusted for baseline values, weight changes, and endometriosis garde\n** based on Wilcoxon test\nparameter Time Groups Mean difference 95% CI P*\nMCT-modified KD \n(n = 19)\nControl (n = 25) Lower Upper\nPelvic pain Before 5 (4, 8) 5 (4, 7) −0.29 −1.63 1.04 0.63c\nAfter 4 (3, 5) 4 (3, 6) 0.42 −0.04 0.88 0.07b\nChange −1 (−2, 0) −1 (−1, 0) 0.5 −0.11 1.12 0.13c\nP-within** 0.001  < 0.001\nDyspareunia Before 6 (3, 8) 6 (3, 7) −0.34 −1.87 1.17 0.61c\nAfter 4 (3, 6) 4 (3, 7) 0.82 0.12 1.52 0.02b\nChange −2 (−2, 0) −1 (−1, 0) 0.89 0.05 1.73 0.05c\nP-within** 0.001 0.001\nDyschezia Before 4 (3, 6) 3 (3, 5) −0.48 −1.5 0.54 0.33c\nAfter 3 (2, 4) 3 (2, 4) 1.06 0.46 1.6 0.001b\nChange −2 (−3, 1) 0 (−1, 0) 1.09 0.47 1.71 0.001c\nP-within**  < 0.001 0.002\n\nPage 9 of 9\nNaeini et al. BMC Women’s Health          (2025) 25:232 \n \nAuthor details\n1 Department of Clinical Nutrition, School of Nutritional Sciences and Dietet-\nics, Tehran University of Medical Science, No#44, Hojjatdoust St., Naderi \nSt., Keshavarz Blvd, Tehran 141556117, Iran. 2 Department of Obstetrics \nand Gynecology, Yas Hospital, Tehran University of Medical Science, Tehran, \nIran. 3 Department of Cellular and Molecular Nutrition, School of Nutritional \nSciences and Dietetics, Tehran University of Medical Science, Tehran, Iran. \nReceived: 1 April 2025   Accepted: 9 May 2025\nReferences\n 1. Kalaitzopoulos DR, Samartzis N, Kolovos GN, Mareti E, Samartzis EP , Eber-\nhard M, et al. Treatment of endometriosis: a review with comparison of 8 \nguidelines. BMC Womens Health. 2021;21(1):397.\n 2. Chauhan S, More A, Chauhan V, Kathane A. Endometriosis: A \nReview of Clinical Diagnosis, Treatment, and Pathogenesis. Cureus. \n2022;14(9):e28864.\n 3. Lamceva J, Uljanovs R, Strumfa I. 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