The association between vitamin intake and endometriosis: a cross-sectional study of the NHANES 1999-2006

According to the exclusion criteria, a total of 3351 participants from NHANES 1999–2006 were included in our study (Fig.  1 ). Table 1  illustrates the demographic characteristics of participants. Participants with endometriosis were older, had a higher percentage of non-Hispanic Whites, higher levels of education, were more likely to smoke, had an age at menarche less than 13, used oral contraceptives, and were less likely to have had multiple pregnancies (P < 0.05). More importantly, individuals with endometriosis had lower intakes of Vitamin B1, Vitamin B6, Vitamin C, and folate (Table  1 ). Table 1 Baseline characteristics of the participants with and without endometriosis Non-endometriosis Endometriosis P-value Age (years) 39.390 (38.949, 39.831) 41.515 (40.656, 42.374)  < 0.001 BMI (kg/m 2 ) 28.398 (28.013, 28.784) 28.137 (27.214, 29.060) 0.589 Race (%)  < 0.001  Mexican American 8.601 (7.095, 10.390) 2.528 (1.522, 4.171)  Other Hispanic 6.104 (4.346, 8.511) 2.263 (0.873, 5.740)  Non-Hispanic White 66.768 (62.903, 70.421) 84.132 (79.397, 87.944)  Non-Hispanic Black 14.194 (11.870, 16.886) 7.205 (5.457, 9.457)  Others 4.333 (3.501, 5.351) 3.871 (1.901, 7.722) Education (%)  < 0.001  Less than high school 18.661 (16.849, 20.620) 10.472 (7.577, 14.303)  High school or equivalent 25.089 (22.814, 27.510) 34.499 (28.888, 40.579)  College or above 56.250 (53.095, 59.355) 55.028 (48.525, 61.365) PIR (%) 0.243  < 1 15.286 (13.549, 17.201) 11.802 (8.012, 17.052)  ≥ 1,  < 3 33.746 (31.531, 36.034) 31.260 (24.287, 39.199)  ≥ 3 50.968 (47.880, 54.050) 56.938 (49.699, 63.892) Smoking (%) 0.032  Yes 45.121 (42.466, 47.805) 52.752 (46.477, 58.941)  No 54.879 (52.195, 57.534) 47.248 (41.059, 53.523) Drinking (%) 0.438  Yes 66.749 (63.950, 69.436) 69.756 (61.959, 76.559)  No 33.251 (30.564, 36.050) 30.244 (23.441, 38.041) Hypertension (%) 0.429  Yes 20.334 (18.593, 22.193) 22.708 (16.946, 29.729)  No 79.666 (77.807, 81.407) 77.292 (70.271, 83.054) Diabetes (%) 0.219  Yes 4.440 (3.725, 5.284) 2.847 (1.368, 5.832)  No 95.560 (94.716, 96.275) 97.153 (94.168, 98.632) Marital status (%) 0.158  Married 64.144 (61.560, 66.648) 65.663 (57.387, 73.086)  Never married 25.908 (23.942, 27.977) 28.725 (21.619, 37.063)  Others 9.948 (8.424, 11.713) 5.611 (3.428, 9.056) Age at menarche 0.047   3 29.507 (27.542, 31.551) 23.417 (18.509, 29.160) Oral contraceptive use (%) 0.007  Yes 84.236 (82.663, 85.691) 90.256 (86.040, 93.298)  No 15.764 (14.309, 17.337) 9.744 (6.702, 13.960)  Vitamin A 495.825 (472.247, 519.403) 456.518 (395.491, 517.545) 0.844  Vitamin B1 1.393 (1.353, 1.433) 1.290 (1.195, 1.384) 0.010  Vitamin B12 4.254 (4.067, 4.440) 3.810 (3.321, 4.300) 0.416  Vitamin B2 1.859 (1.816, 1.902) 1.804 (1.651, 1.958) 0.467  Vitamin B6 1.595 (1.549, 1.640) 1.443 (1.329, 1.556) 0.006  Vitamin C 80.746 (75.779, 85.713) 67.275 (57.528, 77.022) 0.005  Vitamin E 6.864 (6.658, 7.071) 6.797 (5.835, 7.758) 0.168  Folate 347.879 (337.106, 358.652) 311.096 (287.475, 334.717) 0.009 Data was presented as median (95%CI). BMI body mass index, PIR poverty income ratio Baseline characteristics of the participants with and without endometriosis Data was presented as median (95%CI). BMI body mass index, PIR poverty income ratio Table 2 demonstrates the results of the multivariate regression models between different vitamin intakes and endometriosis. After adjusting for all confounding factors, it was observed that the intaking of vitamin A, B1, B2, B6, C and folate was negatively associated with the occurrence of endometriosis. The odds ratios (OR) associated with a per- standard deviation (SD) increase were 0.836 (95%CI: 0.702, 0.997), 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), respectively. In addition, when the vitamin intakes were divided into quartiles, the ORs for endometriosis with the intakes of vitamin A, B2, B6, C, E, and folate in the Q4 group were 0.689 (95%CI: 0.474, 1.000), 0.641 (95%CI: 0.440, 0.936), 0.629 (95%CI: 0.435, 0.910), 0.523 (95%CI: 0.347, 0.787), 0.630 (95%CI: 0.435, 0.912) and 0.834 (95%CI: 0.741, 0.938), respectively, compared to those in Q1 group. The P-value for trend was statistically significant. Table 2 Association between vitamins intake and the risks of endometriosis in logistic regression analysis Vitamins (As continuous, per SD) Model A OR (95% CI) P-value Model B OR (95% CI) P-value Model C OR (95% CI) P-value Vitamin A 0.942 (0.815, 1.088) 0.415 0.845 (0.713, 1.001) 0.051 0.836 (0.702, 0.997) 0.046  Q1 (− 0.937–0.570) Reference Reference Reference  Q2 (− 0.570–0.228) 0.833 (0.581, 1.195) 0.321 0.785 (0.544, 1.133) 0.196 0.743 (0.511, 1.080) 0.120  Q3 (− 0.228–0.299) 1.125 (0.802, 1.577) 0.496 0.960 (0.679, 1.357) 0.817 0.910 (0.637, 1.299) 0.603  Q4 (0.300–18.735) 0.938 (0.660, 1.332) 0.721 0.713 (0.497, 1.023) 0.066 0.689 (0.474, 1.000) 0.049 P for trend 1.011 (0.905, 1.129) 0.849 0.922 (0.823, 1.032) 0.159 0.913 (0.811, 1.027) 0.130 Vitamin B1 0.833 (0.721, 0.962) 0.013 0.815 (0.703, 0.945) 0.007 0.817 (0.702, 0.951) 0.009  Q1 (− 1.903–0.644) Reference Reference Reference  Q2 (− 0.644–0.147) 1.090 (0.784, 1.516) 0.609 1.043 (0.745, 1.459) 0.806 1.018 (0.723, 1.432) 0.919  Q3 (− 0.147–0.470) 0.815 (0.574, 1.158) 0.253 0.815 (0.570, 1.164) 0.261 0.803 (0.559, 1.155) 0.237  Q4 (0.471–19.889) 0.713 (0.496, 1.024) 0.067 0.675 (0.467, 0.975) 0.036 0.690 (0.474, 1.005) 0.053 P for trend 0.025 0.017 0.025 Vitamin B2 0.961 (0.846, 1.091) 0.536 0.863 (0.752, 0.990) 0.036 0.860 (0.746, 0.991) 0.037  Q1 (− 1.975–0.670) Reference Reference Reference  Q2 (− 0.669–0.165) 1.081 (0.767, 1.523) 0.657 1.014 (0.714, 1.439) 0.939 0.978 (0.686, 1.395) 0.903  Q3 (− 0.165–0.497) 1.003 (0.708, 1.420) 0.988 0.858 (0.600, 1.227) 0.402 0.828 (0.576, 1.192) 0.311  Q4 (0.497–10.741) 0.873 (0.610, 1.249) 0.457 0.645 (0.445, 0.936) 0.020 0.641 (0.440, 0.936) 0.021 P for trend 0.954 (0.854, 1.066) 0.407 0.864 (0.771, 0.969) 0.012 0.862 (0.766, 0.969) 0.013 Vitamin B6 0.791 (0.680, 0.921) 0.003 0.788 (0.675, 0.920) 0.003 0.784 (0.669, 0.919) 0.003  Q1 (− 1.735–0.636) Reference Reference Reference  Q2 (− 0.636–0.179) 0.804 (0.575, 1.126) 0.204 0.793 (0.563, 1.116) 0.183 0.760 (0.536, 1.076) 0.122  Q3 (− 0.179–0.416) 0.792 (0.565, 1.109) 0.174 0.762 (0.540, 1.075) 0.121 0.753 (0.531, 1.069) 0.113  Q4 (0.417–16.354) 0.638 (0.447, 0.910) 0.013 0.633 (0.441, 0.909) 0.013 0.629 (0.435, 0.910) 0.014 P for trend 0.016 0.014 0.017 Vitamin B12 0.887 (0.739, 1.066) 0.201 0.866 (0.714, 1.049) 0.141 0.869 (0.713, 1.058) 0.161  Q1 (− 0.833–0.445) Reference Reference Reference  Q2 (− 0.445–0.187) 1.244 (0.881, 1.758) 0.215 1.252 (0.881, 1.779) 0.210 1.269 (0.889, 1.812) 0.190  Q3 (− 0.187–0.195) 1.137 (0.800, 1.615) 0.474 1.080 (0.755, 1.544) 0.674 1.071 (0.746, 1.538) 0.711  Q4 (0.196–24.270) 0.915 (0.633, 1.321) 0.634 0.868 (0.597, 1.261) 0.458 0.883 (0.605, 1.290) 0.521 P for trend 0.966 (0.865, 1.080) 0.546 0.946 (0.845, 1.059) 0.333 0.948 (0.846, 1.063) 0.363 Vitamin C 0.796 (0.679, 0.932) 0.005 0.842 (0.716, 0.989) 0.036 0.845 (0.718, 0.994) 0.043  Q1 (− 0.949–0.660) Reference Reference Reference  Q2 (− 0.660–0.305) 0.903 (0.647, 1.259) 0.548 0.866 (0.618, 1.216) 0.406 0.847 (0.600, 1.196) 0.346  Q3 (− 0.305–0.323) 1.000 (0.722, 1.385) 1.000 1.009 (0.723, 1.407) 0.960 1.037 (0.736, 1.461) 0.835  Q4 (0.324–14.575) 0.474 (0.320, 0.701) < 0.001 0.522 (0.350, 0.779) 0.001 0.523 (0.347, 0.787) 0.002 P for trend 0.001 0.010 0.016 Vitamin E 0.981 (0.864, 1.114) 0.765 0.938 (0.822, 1.069) 0.335 0.935 (0.818, 1.068) 0.321  Q1 (− 1.395–0.612) Reference Reference Reference  Q2 (− 0.610–0.216) 0.768 (0.542, 1.086) 0.135 0.747 (0.524, 1.064) 0.106 0.743 (0.519, 1.064) 0.105  Q3 (− 0.215–0.294) 0.953 (0.685, 1.327) 0.776 0.866 (0.618, 1.214) 0.404 0.848 (0.600, 1.198) 0.351  Q4 (0.296–10.709) 0.685 (0.480, 0.979) 0.038 0.633 (0.441, 0.910) 0.014 0.630 (0.435, 0.912) 0.015 P for trend 0.914 (0.818, 1.022) 0.114 0.886 (0.791, 0.993) 0.037 0.883 (0.786, 0.992) 0.036 Folate 0.805 (0.695, 0.932) 0.004 0.774 (0.665, 0.900) < 0.001 0.772 (0.660, 0.903) 0.001  Q1 (− 1.786–0.652) Reference Reference Reference  Q2 (− 0.651–0.179) 1.130 (0.813, 1.572) 0.467 1.115 (0.796, 1.560) 0.527 1.112 (0.789, 1.566) 0.545  Q3 (− 0.179–0.399) 0.948 (0.675, 1.333) 0.760 0.916 (0.647, 1.296) 0.619 0.905 (0.634, 1.291) 0.582  Q4 (0.401–13.294) 0.600 (0.410, 0.878) 0.009 0.547 (0.371, 0.807) 0.002 0.554 (0.372, 0.825) 0.004 P for trend 0.857 (0.767, 0.958) 0.007 0.833 (0.743, 0.934) 0.002 0.834 (0.741, 0.938) 0.002 Model A adjust for: None Model B adjust for: Age; BMI; Race Model C adjust for: Age; BMI; Race; Education; Poverty-to-income ratio; Hypertension; Diabetes; Smoking; Number of pregnancies; Marital status; Age at Menarche; Oral contraceptive use 95% CI 95% confidence interval, OR odds ratio Association between vitamins intake and the risks of endometriosis in logistic regression analysis Model A adjust for: None Model B adjust for: Age; BMI; Race Model C adjust for: Age; BMI; Race; Education; Poverty-to-income ratio; Hypertension; Diabetes; Smoking; Number of pregnancies; Marital status; Age at Menarche; Oral contraceptive use 95% CI 95% confidence interval, OR odds ratio The effect sizes of the ORs at quartile intervals suggest a potential linear dose–response relationship between vitamin intake and endometriosis. After adjusting for all covariates, analysis using a smooth curve model revealed that the intake of vitamins A, B1, B6, B12, C, and folate was negatively associated with the risk of endometriosis (P < 0.05, Fig.  2 A-F). In contrast, vitamin E showed a saturating effect on the risk of endometriosis (Fig.  2 G), with an optimal cutoff point at 13.18. Below this cutoff, the intake of vitamin E was negatively correlated with the risk of endometriosis (OR = 0.947, 95% CI: 0.906, 0.989), whereas above the cutoff, there was no significant correlation between vitamin E intake and the risk of endometriosis (OR = 1.001, 95% CI: 0.997, 1.005). Additionally, only the intake of vitamin B12 showed no significant association with endometriosis (P > 0.05, Fig.  2 H). Fig. 2 Smoothed curve fitting (penalized spline) analysis between the intake of Vitamin A ( A ), Vitamin B1 ( B ), Vitamin B2 ( C ), Vitamin B6 ( D ), Vitamin C ( E ), Folate ( F ), Vitamin E ( G ), and Vitamin B12 ( H ) and endometriosis. Adjusted for age, BMI, race, education, poverty-to-income ratio, hypertension, diabetes, smoking, number of pregnancies, marital status, age at Menarche, oral contraceptive use Smoothed curve fitting (penalized spline) analysis between the intake of Vitamin A ( A ), Vitamin B1 ( B ), Vitamin B2 ( C ), Vitamin B6 ( D ), Vitamin C ( E ), Folate ( F ), Vitamin E ( G ), and Vitamin B12 ( H ) and endometriosis. Adjusted for age, BMI, race, education, poverty-to-income ratio, hypertension, diabetes, smoking, number of pregnancies, marital status, age at Menarche, oral contraceptive use After establishing the relationship between eight vitamins and endometriosis, we further investigated how this association might differ in various subgroups. Figure  3 presents the results of stratified subgroup analyses based on factors such as age, BMI, race, education level, PIR, hypertension, diabetes, smoking status, number of pregnancies, marital status, age at menarche, and oral contraceptive use. The results indicate that, with the exception of the diabetes subgroup, where a significant interaction between vitamin B12 intake and endometriosis risk was observed (P for interaction  0.05, Fig.  3 ). Fig. 3 Forest plots of subgroup analysis between the intake of Vitamin A ( A ), Vitamin B1 ( B ), Vitamin B2 ( C ), Vitamin B6 ( D ), Vitamin C ( E ), Folate ( F ), Vitamin E ( G ) and Vitamin B12 ( H ), and endometriosis Forest plots of subgroup analysis between the intake of Vitamin A ( A ), Vitamin B1 ( B ), Vitamin B2 ( C ), Vitamin B6 ( D ), Vitamin C ( E ), Folate ( F ), Vitamin E ( G ) and Vitamin B12 ( H ), and endometriosis

The NHANES is a program of studies designed to assess the health and nutritional status of adults and children in the United States. Conducted by the National Center for Health Statistics (NCHS), which is part of the Centers for Disease Control and Prevention (CDC), NHANES combines interviews and physical examinations to provide a comprehensive view of the nation's health [ 15 ]. For this study, we utilized data from four consecutive two-year cycles of NHANES (1999–2006). The data collection methods employed in NHANES are designed to ensure a representative sample of the U.S. population, and all procedures are approved by the NCHS Research Ethics Review Board. Informed consent is obtained from all participants, ensuring ethical compliance with research standards [ 16 ]. We excluded the following individuals: (1) males; (2) those lacking vitamin intake data; (3) those lacking endometriosis data; (4) pregnant women; and (5) women lacking important covariates, including age, body mass index (BMI), race, education, poverty-income ratio (PIR), smoking, drinking, hypertension, diabetes, marital status, age at menarche, number of pregnancies and oral contraceptive. Finally, 3351 participants were enrolled in the study and the flow chart is shown in Fig.  1 . Fig. 1 Flowchart of participants selection in the National Health and Nutrition Examination Survey Flowchart of participants selection in the National Health and Nutrition Examination Survey Vitamin intakes were obtained from the total nutrient intakes recorded in the dietary data of NHANES 1999–2006. The study included vitamin A, B1, B2, B6, B12, C, E and folic acid. Notably, the dietary interview questionnaire was administered twice during the two cycles of NHANES 2003–2006. For participants who completed both dietary interviews, we utilized the average of the two vitamin intakes. In the NHANES study, data on endometriosis were collected from health questionnaires completed by participants. Participants were categorized as having endometriosis based on their response to the question, "Has a doctor or health professional ever told you that you have endometriosis?" with an affirmative response leading to classification as affected. Although relying on questionnaire answers to determine the primary study outcome may introduce a degree of uncertainty, the absence of direct diagnostic evidence such as laparoscopy or ultrasound examinations in the NHANES dataset poses challenges in accurately identifying cases of endometriosis. Nonetheless, previous studies have validated the feasibility and acceptability of using survey data to ascertain the status of endometriosis among NHANES participants [ 17 , 18 ]. With reference to recent relevant studies [ 19 , 20 ], covariates in our study included the following variables: age, BMI, race, education, Poverty-income ratio (PIR), smoking, drinking, hypertension, diabetes, marital status, age at menarche, number of pregnancies and oral contraceptive. Race was self-reported and categorized as Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black and Others. Education levels were classified as less than high school, high school or equivalent, and college or above. The PIR was divided into three categories: low (< 1), middle (≥ 1 to < 3) and high (≥ 3). Marital status was categorized as married, never married and Other. Age at menarche, defined as the age at which participants first began menstruating, was divided into two groups: less than 13 and 13 or older. The number of pregnancies was categorized as up to 3 and more than 3. Oral contraceptives use was categorized as “Yes” or “No” based on participant responses. Data from NHANES 1999–2006 were extracted, combined, processed and analyzed using R software (vision 4.3.0, http://www.R-project.org ) and Empower software (vision 4.1, http://www.empowerstats.net/analysis/ ). The weighted t-test or Kruskal–Wallis test was employed to analyze the relationship between continuous variables, and the weighted chi-square test was used for categorical variables. Considering potential collinearity among covariates, variance inflation factors for all covariates were calculated, with a value > 5 indicating multicollinearity [ 21 ]. Moreover, the presence of heteroscedasticity was assessed using the Breusch-Pagan statistical test, a robust method for evaluating non-constant variance in regression models [ 22 ]. Detailed collinearity screening and heteroscedasticity analysis information are presented in Supplementary Tables 1 and 2. To analyze the association between vitamin intake and endometriosis, vitamin intake was divided into quartiles from the lowest (Q1) to the highest (Q4) group. Multivariate logistic regression analysis was used to construct three regression models: Model A was unadjusted for any covariates, Model B was adjusted for age, BMI, and race, and Model C was adjusted for all covariates, including age, BMI, race, education, PIR, hypertension, diabetes, smoking, drinking, marital status, number of pregnancies, age at menarche, and use of oral contraceptives. Based on the fully adjusted model, we further fitted the relationship between different vitamin intakes and the risk of endometriosis by smoothed curve (penalized spline) analysis. Finally, subgroup analysis and interaction tests were performed to determine the role of covariates between different levels of vitamin intake and endometriosis. The P-value < 0.05 was considered statistically significant difference.

Endometriosis, a condition with an unknown etiology, presents a medically intractable problem. Despite this, clinical treatments including medications and surgery, can manage its symptoms [ 1 , 23 ]. The aim of our cross-sectional study was to investigate the association between vitamin and endometriosis, as both vitamins and endometriosis have significant impacts on human fertility. In a large general population study in the United States, we found that the intake of vitamins A, B1, B2, B6, C, and folate were negatively correlated with the risk of endometriosis, while vitamin E showed a saturating effect, with its intake also negatively correlated with the risk of endometriosis before reaching a saturation point. In addition, subgroup analyses revealed no significant interactions between the intake of these seven vitamins and the risk of endometriosis across different subgroups (P for interaction > 0.05). These findings may aid in the development of targeted treatment strategies or personalized dietary interventions that could potentially provide preventive or therapeutic benefits for patients with endometriosis. We conducted a multifactorial logistic regression analysis and curve fitting to examine the association between the intake of eight different vitamins and the risk of endometriosis. Our findings indicated that, of these vitamins, only vitamin B12 was not significantly associated with the risk of endometriosis. In contrast, the intake of the other seven vitamins showed a negative correlation with the risk of endometriosis, suggesting that a higher intake of these vitamins may be associated with a reduced risk of developing the condition. This finding challenges the previous conclusion from another study that reported no significant relationship between vitamins and endometriosis [ 14 ]. The conflicting results may be attributed to differences in study populations, interventions, outcome definitions, and analytical methods. Roshanzadeh et al. found that intake of appropriate amounts of vitamin B6 and vitamin C can reduce the risk of endometriosis, and they noted that folic acid intake was significantly lower in the endometriosis group [ 24 ]. In a prospective cohort study, dietary sources of vitamin B1, folic acid, and vitamin C were found to be negatively associated with the risk of endometriosis [ 25 ]. These results are consistent with our study. Decreased levels of vitamin A may affect the proliferation of endometrial cells and the balance of immune responses, leading to the occurrence of endometriosis [ 26 ]. The metabolite of vitamin A, retinoic acid, can significantly prevent the proliferation of endometrial tissue cysts and reduce the production of local estradiol [ 27 ]. Impaired biosynthesis of retinoic acid in endometriosis lesions may disrupt the regulation of local inflammatory and cell signaling processes [ 27 ]. This also suggests that the reduction of vitamin A and its metabolites may be an important factor in the pathophysiology of endometriosis. Research into the relationship between B vitamins (B1, B2, B6, B12 and folic acid) and endometriosis has focused on vitamin B6 and folic acid. Vitamin B1 is recognized for its antioxidant properties, including the scavenging of reactive oxygen species (ROS), which are implicated in the pathogenic mechanisms of endometriosis [ 28 ]. However, there is a paucity of research on the relationship between vitamin B2 and endometriosis, and this study provides new insights into their association. Vitamin B6 facilitates the metabolism of estrogen into its inactive form and converts linoleic acid to gamma-linoleic acid, a crucial component in the synthesis of anti-inflammatory prostaglandins [ 29 ]. These prostaglandins have been shown to inhibit the proliferation of endometrial tissue. In addition, vitamin B6, as a lipophilic nutrient, has the capacity to modify gene expression and potentially DNA methylation in humans, thus potentially decreasing the risk of endometriosis [ 30 ]. Folic acid has been the subject of previous studies that have suggested it may reduce the risk associated with endometriosis [ 25 ]. Interestingly, in a recent case–control study, Gersekowski et al. found that higher folic acid intake was correlated with an increased risk of ovarian cancer in patients with endometriosis, but the correlation was not observed in women without the condition [ 31 ]. Further research into the benefits of folic acid in endometriosis is necessary. With regard to vitamin B12, existing research has suggested that it may improve dysmenorrhea symptoms in individuals with endometriosis. However, combined with the findings of this study, it appears that vitamin B12 intake does not reduce the risk of endometriosis. Vitamin C, an essential water-soluble vitamin, is known for its ability to reduce oxidative stress [ 32 ]. It has been suggested that intravenous vitamin C helps to prevent the induction of endometriotic implants and reduce the size of endometriotic implants, potentially due to its anti-inflammatory and antiangiogenic effects [ 33 ]. Studies have shown that endometriotic implants treated with vitamin C were significantly smaller compared to those in the control group [ 7 , 33 ]. These findings indicate that vitamin C has potential as a complementary treatment for endometriosis. Vitamin E, a lipid-soluble antioxidant, plays a crucial role in neutralizing oxidative stress in endometriosis by scavenging free radicals and reactive oxygen species [ 34 ]. In conjunction with vitamin C, it can have synergistic effects, enhancing the body's defense against oxidative damage and potentially reducing the cellular harm induced by endometriosis [ 35 ]. The combined use of vitamin E and vitamin C may serve as a therapeutic strategy to mitigate the oxidative stress associated with endometriosis. Few studies have investigated the relationship between vitamins and endometriosis, and the mechanisms underlying the association remain unclear. However, diet is a potentially modifiable risk factor for endometriosis. The beneficial effects of dietary antioxidants on endometriosis have been widely discussed [ 36 , 37 ]. Oxidative stress (OS), characterized by an imbalance between ROS and antioxidants, is a major factor in the pathophysiology of endometriosis, leading to cellular damage [ 38 , 39 ]. In the state of OS, the overproduction of pro-oxidants can lead to systemic damage when the expression of pro-oxidants exceeds the ability of biological systems to rapidly detoxify or repair them [ 40 ]. Excessive formation of ROS in women may disrupt antioxidant defense mechanisms, potentially damaging oocytes and follicles, affecting implantation, altering endocrine function, and contributing to the development of endometriosis [ 41 ]. Antioxidants neutralize reactive free radicals, mitigate the formation of ROS, and facilitate the repair of oxidative cellular damage [ 42 ]. Dietary vitamins, which are natural antioxidants predominantly obtained from food, help stabilize and counteract the harmful effects of ROS by neutralizing free radicals [ 37 ]. Therefore, dietary vitamin supplementation is essential for maintaining women's reproductive health. Notably, although our study did not alter existing prevention or treatment strategies for endometriosis, it highlights the potential of dietary therapies to enhance them. However, we acknowledge several inherent in our research. Firstly, the cross-sectional design of our study precludes the determination of causality, limiting our ability to generalize these findings and establish a causal relationship between vitamin intake and endometriosis. Secondly, the dietary data were obtained from two 24-h dietary recall interviews, which may not accurately reflect an individual's habitual dietary patterns. Nonetheless, some studies suggest that two 24-h recalls may be sufficient to assess daily dietary intake ( 43 ). Furthermore, the reliance on self-reported endometriosis diagnoses through questionnaires may lead to an underestimation of the disease's prevalence. Additionally, since the NHANES data is derived from a U.S. population, the findings may not be readily generalizable to other racial or ethnic groups, reflecting a constraint in the study's external validity.

This research indicates a significant inverse correlation between the intake of vitamins A, B1, B6, B12, C, and folic acid and the reduced risk of endometriosis. Vitamin E intake exhibited a threshold effect on endometriosis risk, with an optimal cut-off point; below this point, there was a negative association, and above it, no significant further reduction in risk was observed. These findings suggest that these micronutrients may exert a protective role in the development of endometriosis, and they also provide guidance for clinical dietary therapies that may be more effective in preventing endometriosis.

Endometriosis is an estrogen-dependent, chronic inflammatory disease characterized by the appearance of endometrial tissue in sites other than the uterus [ 1 ]. It affects approximately 10‰ of the female population in the reproductive age group, with a higher prevalence in patients with infertility or chronic pelvic pain [ 2 ]. The etiology of endometriosis is multifactorial and not fully understood [ 3 ], with inflammatory responses, oxidative stress, angiogenesis, apoptosis resistance, and immune regulation implicated in its pathologic process [ 4 – 6 ]. Diets with anti-inflammatory, antioxidant, antiproliferative, estrogenic effects, immunomodulatory, and smooth muscle contraction properties may significantly influence the risk of endometriosis [ 7 ]. While dietary intake of red meat, soy and alcohol has been strongly associated with the development of endometriosis [ 8 ], the relationship between vitamin intake and endometriosis remains a topic of debate. For patients with endometriosis, a well-balanced diet may alleviate pain through interactions with visceral sensory inputs [ 9 , 10 ]. Thus, an anti-inflammatory diet could potentially improve the inflammatory state of endometriosis. Some studies suggest a protective role for antioxidant vitamins such as vitamins C and E in mitigating oxidative stress and associated inflammation [ 11 – 13 ], while others, like the case–control study by Trabert et al. [ 14 ], found no significant correlation between vitamin intake and endometriosis risk. This discrepancy may highlight gaps in previous research regarding the role of vitamins in the pathogenesis of endometriosis and the need for more robust study designs to determine their relationship. The study aims to examine the association between vitamin intake and endometriosis using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006. Eight vitamins were analyzed, including vitamin A, B1, B2, B6, B12, C, E, and folic acid. This analysis may help in the development of targeted dietary interventions, providing a clinical rationale for the prevention of endometriosis.

Supplementary Material 1. Supplementary Material 1.