Association of the dietary anti-oxidant index with inflammatory marker such as interleukin-6 in women with and without polycystic ovarian syndrome: a comparative case‒control study.

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Abstract

BackgroundAlthough the main cause of polycystic ovarian syndrome (PCOS) is still unknown, diet plays a significant role in the pathophysiology of PCOS, possibly through effects on the inflammatory response and oxidative stress pathways in the body.MethodThe present study was conducted as a case‒control study on 45 women with PCOS and 40 healthy women in the control group between May 2021 and February 2022 in Robat Karim, Iran. A food frequency questionnaire (FFQ) was completed for all participants, and the antioxidant indices of the diet were calculated via two different methods: ferric reducing ability of plasma (FRAP) and oxygen radical absorption capacity (ORAC) using the data obtained from the FFQ.ResultsThe antioxidant indices of the diet determined via the FRAP index were significantly lower in the women with PCOS than in the control group (4.94 ± 1.97 vs. 3.48 ± 1.77, P˂ 0.05), but no significant difference was observed between the two groups in terms of the antioxidant index of the diet based on the ORAC index (P˃ 0.05). Additionally, the antioxidant indices of the diet based on both the ORAC (R = 0.94, P˃ 0.05) and FRAP (R = 0.82, P˃ 0.05) indices were not significantly correlated with the inflammatory marker interleukin-6 (IL-6).ConclusionThe present study supports the hypothesis of the importance of diet, especially food antioxidants, in the occurrence and exacerbation of PCOS, but the use of a suitable tool to determine the general antioxidant index of the diet in epidemiological studies related to diet and PCOS seems necessary.
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Result

The average ages of the participants in the case and control groups were 27.93 ± 6.64 and 33.02 ± 7.19 years, respectively. Table  1 provides an overview of some demographic characteristics of the participants in the two groups of women. Except for the age variable, the two groups had no significant differences in terms of other demographic variables, which was taken into account in the subsequent statistical analysis in order to match the cases and controls. Table 1 Demographic characteristics of the tested group Variable Case group ( N  = 45) Mean (SD) Control group ( N  = 40) Mean (SD) P value Age (years)* 27.93(6.64) 33.02(7.19) 0.001 BMI (kg/m 2 )* 25.42(3.93) 25.85(5.07) 0.53 Education (years)** ≥ 12 35(77.8) 28(70) 0.27 > 12 10(22.2) 12(30) Occupation** Housewife 29(64.4) 18(45) 0.12 Employed 16(35.6) 22(55) Marital status** Single 18(40) 10(25) 0.26 Married 27(60) 30(75) Income (million)** 2.5˃ 15(33.3) 6(15) 0.10 2.5–5.5 19(42.2) 18(45) > 5 11(24.4) 16(40) Housing** Privet 32(71.1) 27(67.5) 0.71 Rental 13(28.9) 13(32.5) Smoking** Yes 4(8.9) 4(10) 0.86 No 41(91.1) 36(90) Alcohol consumption ** Yes 3(6.66) 3(7.5) 0.54 No 42(93.33) 37(92.5) Exercise** 1 ˃ 32(71.2) 31(77.5) 0.76 1–3 11(24.4) 8(20) 3˂ 2(4.4) 1(2.5) BMI Body mass index *Values are given as the mean ± SD via the independent t test **Values are given as numbers and percentages via the chi-square test Demographic characteristics of the tested group BMI Body mass index *Values are given as the mean ± SD via the independent t test **Values are given as numbers and percentages via the chi-square test The data in Table  2 show that there was no significant difference between the case and control groups in terms of the antioxidant index of the diet based on the ORAC index (P˃0.05), but the difference between the two groups in terms of the antioxidant index of the diet based on the FRAP index was significant, and in the control group, it was greater than that in the case group (P˂0.05). Table 2 Examination of dietary antioxidant indices and the serum levels of IL-6 in the case and control groups Variable Case group ( N  = 45) Mean (SD) Control group ( N  = 40) Mean (SD) P value* FRAP 2720.59(5631.48) 9282.23(1910.33) 0.001 ORAC 62109.01(2134.49) 64753.90(23356.05) 0.307 IL-6 * 4.94(1.97) 3.48(1.77) 0.001 FRAP Ferric reducing ability of plasma, ORAC Oxygen radical absorption capacity, IL-6 Interleukin-6 *Values are given as the means ± SDs from the analysis of covariance test Examination of dietary antioxidant indices and the serum levels of IL-6 in the case and control groups FRAP Ferric reducing ability of plasma, ORAC Oxygen radical absorption capacity, IL-6 Interleukin-6 *Values are given as the means ± SDs from the analysis of covariance test As mentioned in the results of previous works [ 21 ], there was a significant difference between the two groups in terms of the inflammatory marker IL-6, and the subjects in the case group had a higher serum concentration of IL-6 (Table 2 ). Given that the difference in mean age between the two groups was significant, the age variable was entered into the model and a multivariate analysis of covariance was performed. The results of this analysis showed that the ORAC level in the control group was 5283 units higher than the case group, but it was not statistically significant ( p  = 0.307). Also, the FRAP level in the control group was 7468 units higher and IL6 in the control group was 1.42 units lower, and it was statistically significant ( p  = 0.001) (Table  3 ). Table 3 Age-adjusted estimates and 95% confidence interval of dietary antioxidant indices and the serum levels of IL-6 in the case and control groups Dependent Variable Parameter Age-adjusted estimates Std. Error t p-value. 95% Confidence Interval Lower Bound Upper Bound ORAC Intercept 7658 1.037E4 7.384 0.000 55947.220 97212.207 Age −518.044 351.964 −1.472 0.145 −1218.214 182.125 Control 5283 5137.997 1.028 0.307 −4938.506 15503.719 Case Reference group . . . . . FRAP Intercept 7692 4262.979 1.804 0.075 −788.435 16172.410 Age −177.973 144.665 −1.230 0.222 −465.759 109.812 Control 7468 2111.833 3.536 0.001 3266.707 11668.925 Case Reference group . . . . . IL6 Intercept 5.172 0.886 5.835 0.000 3.409 6.935 Age − 0.008 0.030 − 0.268 0.789 − 0.068 0.052 Control −1.42 0.439 −3.230 0.001 −2.292 − 0.545 Case Reference group . . . . . FRAP Ferric reducing ability of plasma, ORAC Oxygen radical absorption capacity, IL-6 Interleukin-6 Age-adjusted estimates and 95% confidence interval of dietary antioxidant indices and the serum levels of IL-6 in the case and control groups FRAP Ferric reducing ability of plasma, ORAC Oxygen radical absorption capacity, IL-6 Interleukin-6 The results of the present study also showed that the antioxidant indices of the diet based on both the ORAC ( R  = 0.94, P˃ 0.05) and FRAP ( R  = 0.82, P˃ 0.05) indices were not significantly correlated with the inflammatory marker interleukin-6 (IL-6) (Table  4 ). Table 4 Investigating the correlation between IL-6 and FRAP and ORAC Variable IL6 Pearson correlation* P value* Case group FRAP 0.31 0.35 ORAC 0.28 0.05 Control group FRAP 0.011 0.94 ORAC 0.26 0.09 FRAP Ferric reducing ability of plasma, ORAC Oxygen radical absorption capacity *Values are given by Pearson’s correlation test Investigating the correlation between IL-6 and FRAP and ORAC FRAP Ferric reducing ability of plasma, ORAC Oxygen radical absorption capacity *Values are given by Pearson’s correlation test

Materials

This case‒control study was conducted in Robat Karim city in Tehran Province from May 2021 to February 2022. The subjects were selected via a consecutive sampling method. Participants were chosen for study based on their ease of access and availability, rather than through random selection. This method is a common technique in research, particularly when quick and cost-effective data collection is needed. case-control studies provide a valuable tool for investigating disease etiology particularly when dealing with limited resources, or when little is known about the disease process and allows us to quantitatively assess the relationship between exposure and outcome. All of the participants were aged between 18 and 45 years at the beginning of the study and signed informed consent before the onset of the study. The calculation of an adequate sample size was done based on the results of the unpublished pilot study and using the following formula: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$n\geq2\frac{\left(z_{\alpha/2}+z_\beta\right)^2\sigma^2}{\left(\mu_1-\mu_2\right)^2}$$\end{document} Where, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\alpha=0.05\Rightarrow z_{\alpha/2}=1.96\\$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\beta=0.10\Rightarrow z_\beta=1.28\\$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1-\beta=0.90$$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$n=2\left(1.96+1.28\right)^2\left(\frac1{0.73}\right)^2=40$$\end{document} Where, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${}^\alpha\;^\alpha$$\end{document}  is the probability of type 1 error, and is the probability of type 2 error, which is 0.1 with 90% power. The observed effect size based on the level of IL-6 in a pilot sample of 40 women (20 women in each group) was equal to 0.73, (µ1-µ2 = 0.73.(Considering the obtained 95% confidence interval, 90% power and 0.73 effect size in the pilot sample and substituting these numbers in the above formula, the minimum sample size in each group was determined to be 40 women. Fig.  1 shows the flow chart of the study. Fig. 1 Flow chart of study.  * Individuals who did not meet any of the inclusion criteria previously mentioned in the Materials and Methods section were excluded from the study. **People who were excluded from the study due to reasons such as the length of the questionnaire and unwillingness to complete the questionnaire process Flow chart of study.  * Individuals who did not meet any of the inclusion criteria previously mentioned in the Materials and Methods section were excluded from the study. **People who were excluded from the study due to reasons such as the length of the questionnaire and unwillingness to complete the questionnaire process Adherence to the International Conference on Harmonization (ICH) guidelines for Good Clinical Practice (GCP), particularly in aspects such as ethical considerations, data management, study design and documentation, was observed in the current study. Prior to undertaking the investigation, ethical clearance was obtained from the Ethics Committee of Tarbiat Modares University of Medical Sciences (IR.MODARES.REC.1399.177). The initial sample consisted of 95 women who were recruited from gynecologic clinics in Robat Karim city. The following 10 were excluded from the study for reasons such as not having the inclusion criteria (unwilling to continue participating in the study and participating in laboratory investigations, finding out about pregnancy between completing the questionnaire and performing laboratory tests) and failure to complete the questionnaire. Finally, 45 women with PCOS in the case group and 40 women in the control group were selected (Fig. 1 ). The criteria for selecting the subject in the current study included the following: diagnosis of PCOS according to the Rotterdam criteria in the case group; not breastfeeding or pregnant; no history of chronic diseases, including diabetes; liver, thyroid, cardiovascular and kidney diseases; not suffering from inflammatory diseases, such as endometriosis and myoma; not using antihypertensive drugs; and not using insulin and metformin. Participants whose caloric intake was less than 800 or more than 4200 calories after completing the questionnaire, who followed a special diet and who did not want to participate in the study were excluded from the study. The diagnosis of PCOS was performed on the basis of the Rotterdom criteria and with two or more of the following criteria [ 16 ]: oligovulation/amenorrhea or anovulation (menstrual cycles >35 days or amenorrhea >3 months), biochemical hyperandrogenism (total testosterone level ≥ 2.6 nmol or clinical (Ferriman–Galwey score ≥ 12), and polycystic ovary morphology (POM) using ultrasound (≥ 12 follicles measuring 2–9 mm in diameter, mean of both ovaries). A demographic information questionnaire was completed for all participants, which included questions about age, height, weight, Smoking and alcohol consumption, physical activity levels health status, medication use, educational status, employment status, income, and fertility information. For the purpose of calculating the dietary antioxidant index of diet, all participants were asked about their usual dietary intake via a validated 168-item food frequency questionnaire (FFQ) whose validity and reliability were previously evaluated [ 17 , 18 ]. The FFQ presents a list of food items and a standard serving size for each one. Participants reported food consumption in specific amounts during the past year, and then the information obtained from the questionnaire was entered into the IV Nutritionist software to obtain the exact intake of energy and micronutrients. The questionnaires were completed by a trained researcher by a nutritionist on the research team and through a face‒to-face interview. Adaptation of the FFQ for the Iranian Population were done by ensuring cultural relevance (FFQ should involves local foods and dishes that are commonly consumed, as well as accounting for traditional cooking methods and portion sizes.), minimizing bias, and employing rigorous validation methods. To address potential interviewer bias, we used a structured format of FFQ where interviewers ask the same questions in the same manner for all participants. The total antioxidant capacity of the diet was calculated via two methods: ORAC (oxygen radical absorption capacity) and FRAP (ferric reducing ability of plasma). The ORAC database expresses the total antioxidant capacity of the diet for 207 food items with units of µmol trolex per 100 g of each food item [ 19 ]. Another method that was used to calculate the antioxidant index of the diet was the use of the FRAP database, which is based on the table of dietary antioxidants published by the Food Research Institute of OLSO University and includes measurements of the antioxidant power of more than 3100 foods, beverages, spices and food supplements. The advantage of using FRAP rather than ORAC is the inclusion of micronutrients in this database [ 20 ]. In this study, the data obtained from the FFQ questionnaire were used to estimate and calculate the antioxidant indices of the diet via these two methods. To calculate the ORAC and FRAP score of each participant’s diet, the antioxidant index of each food item was calculated via the data of two databases for the daily intake of each food item, and the points related to different food items were added together to calculate the overall ORAC and FRAP index for each individual. ORAC is particularly useful for assessing the ability of antioxidants to neutralize peroxyl radicals, which are relevant in biological systems, and it’s a widely used, straightforward method. FRAP is advantageous for its simplicity, speed, and cost-effectiveness, and it measures the antioxidant’s ability to reduce ferric ions to ferrous ions. In the present study, both methods were used to calculate the dietary antioxidant index. Combining both methods provides a more comprehensive understanding of a diet’s antioxidant potential However, we encountered some limitations in using these two methods to calculate the dietary antioxidant index. One of the primary limitations is the scarcity of comprehensive nutritional databases for Iranian foods. Many existing databases focus on Western diets and may not include traditional Iranian foods or accurately represent their nutrient profiles, particularly for antioxidants measured by FRAP. The diversity of regional diets within Iran means that even if some food items are included in databases, they may not reflect the variations in preparation methods, portion sizes, or ingredient substitutions commonly used in different regions. To investigate the associations between the dietary antioxidant index and inflammatory markers, venous blood samples were taken from all participants between 8 and 9 in the morning and after 12 h of fasting. The serum of the blood samples was separated via centrifugation at 5,000 rpm for 5 min, and the blood samples were stored at −80 °C for 6 months. Finally, the concentrations of the inflammatory marker IL-6 were measured with suitable kits (the human interleukin-6 ELISA kit produced by the Zell Bio Company (Germany)) via a specific method. The Sensitivity for human interleukin-6 ELISA kit were detected as low as 0.1 mg/L. Also this kit recognizes Human IL-6 in samples. No significant cross-reactivity or interference between Human IL-6 and analogues was observed and it had an acceptable specificity. The intra/inter-assay coefficients of variation (CV) for IL-6 was below 10%. In order to check the accuracy of the samples after storage at −80 °C, the values ​​of interleukin 6 were measured on several samples before and after storage, and no difference was observed in the values ​​obtained. Also, in order to prevent freeze-thaw cycles, all serum samples were simultaneously tested in the laboratory after collection from all participants. In the present study, the exposure is the dietary anti-oxidant index, the outcomes are the variables of interest that are being measured to assess the impact of the exposure. In this case control study, the outcomes are PCOS diagnosis and the inflammatory marker (IL-6). The variables that are associated with both the exposure (diet) and the outcome (PCOS or inflammatory marker), and can distort the observed relationship are confounders. Variables that could be considered as confounding factors in the current study include age, BMI, physical activity, socioeconomic status, other diseases such as diabetes, thyroid disorders, smoking and alcohol consumption, and adherence to specific diets. Our strategy to control for confounding factors in the current study includes matching cases and controls, adjusting inclusion and exclusion criteria based on confounding factors (chronic diseases such as diabetes, thyroid disorders, inflammatory and autoimmune diseases, and adherence to specific diets), and using appropriate statistical tests such as analysis of covariance. The variables such as age, obesity, and chronic diseases such as diabetes, in addition to their confounding effects, can also act as effect modifiers. Data management and analysis were performed via SPSS (ver20). Statistical significance was analyzed via analysis of variance, independent t tests and chi-square tests, as appropriate. The data were normalized via the Kolmogorov‒Smirnov test, and significance levels were set at the 5% level.

Discussion

Among several agents that affect the pathogenesis of PCOS, diet has an important contribution [ 22 ]. Women with PCOS usually have improper dietary habits [ 23 ]. Evidence suggests that diet can modulate the pathophysiology and severity of PCOS symptoms through effects on the inflammatory and antioxidant indices of the diet [ 24 ]. To the best of our knowledge, the associations of the dietary antioxidant index with PCOS and inflammatory markers such as IL-6 and CRP were assessed for the first time in Iran in the present study. Research has shown that dietary antioxidants are negatively associated with PCOS, on the other hand; however, various clinical trials have shown the favorable effects of dietary antioxidants in the management of PCOS [ 25 , 26 ]. Despite the numerous studies conducted in the field of diet and its association with PCOS, it is still unclear whether the antioxidant index of the diet has a significant relationship with PCOS. According to the results of the present study, there was no significant difference between the two groups in terms of the antioxidant index of the diet on the basis of the ORAC index, but the two groups had a significant difference in terms of the antioxidant index of the diet on the basis of the FRAP index. FRAP may be more directly applicable in clinical and nutritional studies focused on the health benefits of dietary antioxidants, particularly in conditions characterized by oxidative stress. The FRAP assay is generally less sensitive to the effects of sample preparation compared to ORAC. For example, it may not be as influenced by the extraction process or food matrix, providing more reliable results across different food types [ 27 , 28 ]. In Shahrokhi et al.‘s study, two groups of women with and without PCOS presented significant differences in terms of several of the most important antioxidants, such as Vit C, Vit E, selenium, zinc, and beta-carotene [ 29 ]. The results of Shoaibi Nubarian et al.‘s study also support the results of the present study. In this study, which was a cross-sectional study with the aim of investigating the relationship between the antioxidant capacity of the diet and the risk of PCOS, a significant relationship was observed between a higher antioxidant index in the diet and PCOS. In women with a higher dietary antioxidant index, the occurrence risk of PCOS was greater than that in women with a lower dietary antioxidant index [ 13 ]. In contrast to the findings of the present study, in the study of Panti et al. which was conducted with the aim of investigating and comparing some dietary antioxidants in two groups of women with PCOS and healthy controls, the two groups did not significantly differ in terms of Vit A, Vit E, Vit C and Zinc [ 30 ]. In most of these studies investigating the relationship between PCOS and dietary antioxidant markers, only some food components with antioxidant effects have been investigated, while the evaluation of an antioxidant compound alone cannot reveal the antioxidant power of the diet and its effects and reflect the possible synergistic and interaction effects of dietary antioxidants. Therefore, the term total antioxidant capacity of the diet was invented and is used as a suitable tool to evaluate the effects of dietary antioxidants. In the present study, two different methods, ORAC (oxygen radical absorption capacity) and FRAP (ferric reducing ability of plasma), were used to investigate and estimate the antioxidant index of the food diet. In the present study, we did not have values ​​related to the regenerative antioxidant power of iron for Iranian foods, and we used international databases, which may be different from Iranian foods because of their geographical location and growing conditions. On the other hand, in our study, in addition to new cases of PCOS, some participants were previously identified as PCOS patients on the basis of the Rotterdam criteria. Since changing one’s lifestyle and modifying one’s diet are important treatments for this disorder, some women with PCOS may have recently changed their diet, which may have affected the results of various studies. Additionally, different phenotypes of PCOS have physiological and metabolic differences, and it is important to consider these differences, which can affect the results of studies in the field of the relationship between diet and PCOS. One of the possible reasons for the contradictory results in this field may be the lack of attention given to phenotypic divisions in epidemiological studies related to nutrition and PCOS [ 31 ]. A healthy diet, physical activity and appropriate BMI reduce the risk of infertility related to ovulation disorders in women. In addition to diet, other factors, such as genetics, hormonal and environmental factors, age and culture, affect the development and occurrence of diseases [ 23 , 32 ]. The results of the present study revealed no significant associations between the dietary antioxidant indices based on the FRAP and ORAC indices and the inflammatory marker IL-6. Along with the results of the present study, in a study by Vanacore et al. [ 33 ], no significant relationship was observed between the dietary antioxidant index and the inflammatory marker IL-6. In contrast to the results of the present study, Luu et al. reported a significant negative correlation between the dietary antioxidant index and inflammatory markers such as IL-6 [ 34 ]. In a study in Greece by Koluverue et al. [ 35 ], a significant inverse relationship was also observed between total antioxidant capacity and the inflammatory marker IL-6. In explaining the different results regarding the relationship between the dietary antioxidant index and inflammatory markers, these studies were conducted on different populations, and in most of them, the subjects were healthy women without disorders such as PCOS; thus, their results may not be generalizable to all people and populations. On the other hand, IL-6 is a pro-inflammatory cytokine that plays a complex role in immune responses and inflammation. Its levels can be influenced by various factors, including infections, stress, and chronic diseases, which may not directly correlate with antioxidant capacity. The pathways regulating IL-6 production and antioxidant defenses may not be directly linked. For example, oxidative stress can lead to inflammation, but the relationship may not be linear or direct, depending on the context. the timing of blood sample collection for measuring IL-6 and antioxidant indices could affect the correlation. IL-6 levels can fluctuate rapidly in response to acute inflammatory stimuli, while antioxidant levels may change more slowly or be influenced by dietary intake over time. Both IL-6 and antioxidant capacity can vary based on short-term and long-term changes in diet, lifestyle, and health status, making it challenging to establish a consistent correlation [ 36 – 38 ]. We used the valid and reliable FFQ for the Iranian population, which is a suitable tool for nutritional investigations and determining the diet antioxidant index. Although participants may have problems in recalling and accurately reporting the amount of food intake, compared with other dietary assessment methods, it is a valid method in epidemiological studies. This study has several limitations. The sample size was small, and phenotypic division was not performed in the PCOS group; thus, it is suggested that future studies be conducted with larger sample sizes to create a clear distinction between the different phenotypes of PCOS. Also Completing the FFQ questionnaire and accurately calculating antioxidant indices was a time-consuming process, which was one of our limitations in the present study. Considering factors such as the characteristics of the individuals participating in the study, not focusing on a specific age group or individuals with a specific BMI, using a reliable and valid FFQ tool, not sampling in a specific region or clinic, using an appropriate control group, and paying attention to matching the case and control groups, paying attention to confounding factors and considering them in the design and conduct of the study can increase the generalizability and external validity of the result of the present study.

Conclusions

Based on the results of the present study and low antioxidant index of the diet in women with PCOS, a healthy diet especially dietary antioxidants, play an important role in the prevention, improvement and treatment of PCOS. Although the IL6 inflammatory marker was higher in women with PCOS compared to healthy group, there was no significant association between the IL6 and the antioxidant index of the diet, and it seems that the inflammatory and antioxidant pathways separately affect the pathophysiology of PCOS.To investigate the effect of dietary antioxidants on PCOS, the examination of only a few food items cannot reflect the antioxidant effect of the diet on PCOS, and the use of a proper antioxidant evaluation index of the diet is efficient. For this reason, it is recommended to conduct studies with a larger sample size and phenotypic classification in women with PCOS in future studies.

Introduction

Polycystic ovarian syndrome (PCOS) is the most prevalent reproductive health problem and is characterized by clinical and biochemical disorders such as ovulatory dysfunction (OD), menstrual irregularity, infertility, androgen overexpression and polycystic ovarian morphology (PCOM) [ 1 , 2 ]. PCOS affects women of childbearing age, with an overall prevalence rate of 8–13% [ 3 ]. This disease affects various aspects of women’s lives and causes several complications, such as infertility, obesity, diabetes and psychological complications [ 4 , 5 ]. The available evidence indicates a growing increase in the incidence of PCOS due to changes in lifestyle, diet and psychological stress [ 5 , 6 ]. Oxidative stress (OS) is an imbalance between the oxidation system and the antioxidant system in the body and is closely related to the pathogenesis of various disorders [ 7 ]. Recent evidence suggests that OS is strongly associated with ovarian dysfunction in women with PCOS [ 8 ]. Previous research has shown that PCOS is associated with an increase in the levels of some stress-related oxidative markers [ 9 ]. The interactions among hyperandrogenism, insulin resistance and OS play important roles in PCOS pathogenesis and ovarian function disorders [ 10 ]. Currently, the exact cause of PCOS is still unknown, but a combination of genetic and environmental factors is involved in the pathogenesis of PCOS. Several studies have confirmed the association between PCOS and diet, and it has been introduced as the first treatment for PCOS. Nutrition-related interventions have been associated with improvements in metabolic parameters in these patients [ 11 , 12 ]. Also, based on the results of some studies, increasing the antioxidant index of the diet has been associated with a decrease in the incidence of PCOS, and women with PCOS have been found to have a lower dietary TAC compared to healthy controls [ 13 ]. On the basis of various results from related studies, it is unclear what type of diet may work for women with PCOS; some of these studies have demonstrated that the use of foods with high antioxidant properties is inversely related to PCOS [ 14 , 15 ]. These Studies indicate that PCOS women consume significantly less of certain antioxidant micronutrients like selenium, zinc, and vitamin E. Considering the increasing prevalence of this disorder and the relationship between PCOS and OS and the effects of diet on these factors, the present study was designed with the aim of investigating and comparing the antioxidant indices of diet and their associations with inflammatory markers in two groups of women with and without PCOS. For this purpose, we calculated the antioxidant index of the diet using an appropriate tool, measured the inflammatory marker interleukin 6 (IL-6) in two groups of women with and without PCOS and compared the two groups using an appropriate statistical test. Also we examined the association between antioxidant index and IL-6 in PCOS women and healthy control group.

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