Association between Oxidative Balance Score and Migraine among American Adults: National Health and Nutrition Examination Survey

doi:10.21203/rs.3.rs-3863815/v1

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Association between Oxidative Balance Score and Migraine among American Adults: National Health and Nutrition Examination Survey

https://doi.org/10.21203/rs.3.rs-3863815/v1

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Background

Oxidative stress has been observed to be linked with migraines. The oxidative balance score (OBS) serves as a metric for evaluating the overall systemic oxidative stress status, where elevated OBS scores suggest increased exposure to antioxidants. However, the precise connection between OBS and migraines has not been reported to date. This study seeks to investigate the potential association between OBS and migraine occurrences.

Methods

A cohort of 7,238 participants from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2004 was selected for this study. Migraine diagnoses were ascertained using the Patient Health Questionnaire, specifically asking participants if they had experienced a severe headache or migraine in the past three months.The Oxidative Balance Score (OBS) was determined based on the evaluation of 20 dietary and lifestyle factors. Logistic regression and restricted cubic splines (RCS) were employed to examine the association between OBS and migraines. Additionally, adjusted models were scrutinized in the analysis.

Results

The prevalence of migraine was 19.43%. There was a significant negative linear relationship between OBS, dietary OBS and migraine (p for nonlinear > 0.05). Compared to the lowest tertile of OBS, the adjusted ORs for the highest tertile of OBS and dietary OBS and migraine were 0.72(95% CI: 0.59 ~ 0.88), 0.70 (95% CI: 0.56 ~ 0.86) respectively, and all P for trend < 0.05. Compared to the lowest tertile of OBS, the adjusted ORs for the highest tertile of lifestyle OBS and migraine was 0.97 (95% CI:0.82 ~ 1.14), and all P for trend > 0.05.

Limitations:

This research was cross-sectional design, and it was not possible to deduce causality.

Conclusions

Diet and lifestyle might influence migraine by modulating oxidative balance. Antioxidant diets and lifestyles were important in reducing migraine and our study also provided new ideas for improving migraine.

Oxidative balance score

NHANES

Migraine

Diet

Lifestyle

Migraine is a widespread neurological condition that affects more than 1 billion people worldwide and accounts for 45.1 million years of life lived with disability [1].According to the 2016 Global Burden of Disease, Injury, and Risk Factors Studies, migraine is the second most significant cause of disability[2], especially in those under 50 years old[3].

The pathogenesis of migraines is quite complex. According to reports, the etiology of migraines involves various factors, including genetics, diet, oxidants, environmental factors, major and trace elements, and metabolic disorders.Multiple studies indicate that oxidative stress is closely associated with the pathogenesis of migraines[4, 5].Many dietary components have significant antioxidant properties, which play a crucial role in preventing the occurrence of migraines[6].Research indicated that the intake of vitamin C (an antioxidant) can modulate the impact of neuroinflammation and ROS activity on migraines[5].Riboflavin (an antioxidant) has a preventive effect on the occurrence of migraines[7].Magnesium deficiency leading to cortical inhibition or abnormal glutamatergic neurotransmission is a potential mechanism underlying the relationship between magnesium and migraine[8, 9].The impact of lifestyle on migraines should not be overlooked[10, 11].Heavy exposure to secondhand smoke (serum cotinine levels of 1 to 10 ng/mL) is significantly positively correlated with severe headaches or migraines in non-smoking adults[12].Dietary/lifestyle factors with antioxidant activity are particularly crucial in preventing the occurrence of migraines, prompting further investigation into their relationship[5].

The OBS is a comprehensive metric comprising 20 different dietary and lifestyle components[13]. It assesses an individual's antioxidant status by scoring the ranking of antioxidant and pro-oxidant components in diet and lifestyle factors. Generally, a higher OBS indicates a prevalence of antioxidants over pro-oxidants[13, 14].

Previous studies have highlighted a noteworthy negative correlation between the OBS and depression[15], with a particular emphasis on this association among females[16]. Additionally, in older adults, the OBS demonstrates a positive correlation with cognitive function[17]. Conversely, the OBS is inversely correlated with sleep disorders while exhibiting a positive correlation with sleep duration[18].Further, an inverse relationship is noted between the OBS and periodontal disease among American adults[19]. Moreover, a higher OBS is associated with a lower incidence of non-alcoholic fatty liver disease[20]. Despite these identified connections in various health domains, the specific relationship between the OBS and migraines remains unclear.

In our study, we investigated the relationship between migraines and the OBS. The existence of this correlation suggests that, in specific populations, improving or preventing migraines may be achieved by adjusting the OBS through dietary/lifestyle modifications. Therefore, the findings of this study could have significant implications for migraine prevention and enhancing the quality of life for the American population.

2.1 Study population

The National Health and Nutrition Examination Survey (NHANES) is a comprehensive research initiative designed to evaluate the health and nutritional status of both adults and children across the United States. Combining questionnaire surveys and physical examinations, the study strategically focuses on diverse demographic groups and various health issues. The results of this survey will be utilized to determine the prevalence of major diseases and risk factors for diseases. This information will be used to assess nutritional status and its relationship with promoting health and preventing diseases.Our study recruited participants during three NHANES survey cycles spanning from 1999 to 2000, 2001 to 2002, and 2003 to 2004.In total, 31,126 participants completed the interview, of whom 15,794 participants were less than 20 years old. We excluded pregnant women (n = 836), those missing data on migraine (n = 11), those missing data on participants with missing data for OBS components (n = 6331), or those with covariates (n = 916). Ultimately, this cross-sectional study included 7238 participants from the NHANES between 1999 and 2004 in the analysis. The detailed inclusion and exclusion process is shown in Fig. 1.

The Ethics Review Board of the National Center for Health Statistics approved the implementation of the National Health and Nutrition Examination Survey study, with participants providing written informed consent.

2.2. migraine assessment (outcome)

We determined whether a participant experienced migraine based on their replies to the question in the portion of the miscellaneous pain questionnaire: “Have you had a severe headache or migraine in the past three months”? In the NHANES dietary survey, respondents were questioned about the types and quantities of foods and beverages they consumed within 24 h. Dietary intake data were gathered from 1999 to 2001 using the NHANES Computer-Assisted Dietary Interview System (CADI), a multiple pass recall method that gives interviewers instructions for collecting food information. The United States Department of Agriculture collected dietary consumption data using the Automated Multiple Pass Method (AMPM) between 2002 and 2004. This fully computerized recall system comprehensively composes food-specific standard questions and possible responses. Using CADI and AMPM, accurate nutritional values were calculated for each individual depending on their consumption of food and beverages[21]. The NHANES Dietary Interviewers Procedure Manuals contains a complete overview of the dietary survey methodology[22]. The subjects were placed into three groups based on their OBS.

2.3 Oxidative balance score (exposure)

The calculation of OBS was based on an earlier study[23].The OBS is categorized into two types: 16 dietary OBS and 4 lifestyle OBS, encompassing 5 pro-oxidants and 15 antioxidants. The overall OBS is calculated by summing the scores of these variables, where a higher OBS indicates greater exposure to antioxidants. Dietary intake of 16 nutrients, including dietary fiber,carotene, riboflavin, niacin, vitamin B6, total folate, vitamin B12,vitamin C, vitamin E, calcium, magnesium, zinc, copper, selenium, totalfat, and iron, was obtained from the first dietary review interview. Thefour lifestyle factors are physical activity, body mass index (BMI),alcohol consumption, and smoking, with the degree of smoking expressed in terms of cotinine.

2.4. Covariate assessment

A variety of potential covariates were assessed according to the literature [24–28], including age; sex; marital status; race/ethnicity; education level; family income; smoking status; hypertension; diabetes; stroke; coronary heart disease; calorie consumption; protein consumption; carbohydrate consumption; dietary supplements taken; and C-reactive protein. Race/ethnicity was categorized as non-Hispanic white, non-Hispanic black, Mexican American, or other races. Marital status was classified as married, living with a partner, or living alone. Educational attainment was categorized as High school or less, Some College and College graduate. According to a US government report[29], family income was categorized into three groups by the poverty income ratio (PIR): low (PIR ≤ 1.3), medium (PIR > 1.3 to 3.5), and high (PIR > 3.5). According to preceding literature definitions, smoking status was categorized as never smokers (smoked less than 100 cigarettes in life), current smokers(smoked moth than 100 cigarettes in life and smoke some days or every day), and former smokers (smoked more than 100 cigarettes in life and smoke not at all now)[30]. The determination of previous disease (hypertension, diabetes, stroke, and coronary heart disease) was based on the inquiry in the questionnaire of whether the doctor had been informed of the condition in the past. A dietary recall interview preceded an interview at MEC to obtain participants’ 24-h nutritional information, including total dietary calories, protein, and carbohydrates. Dietary supplements were determined by the question regarding nutritional supplements and medications consumed during the past month. C-reactive protein was quantified by latex-enhanced nephelometry.

2.5. Statistical analysis

To facilitate our current research, we acquired relevant NHANES data from the years 1999 to 2000, 2001 to 2002, and 2003 to 2004. As part of our data processing and analysis, we examined the continuous variables for normal distribution. The outcomes revealed that all continuous variables were non-normally distributed.This is a secondary examination of publicly accessible datasets. Categorical variables were represented by proportions (%) while continuous variables were described by the mean (standard deviation, SD) or median (interquartile range, IQR), as appropriate.

To compare the differences across groups, one-way analyses of variance (normal distribution), Kruskal–Wallis tests (skewed distribution), and chi-square tests (categorical variables) were undertaken. Logistic regression models were used to determine the odds ratios (OR) and 95 percent confidence intervals (95% CIs) for the relationship between Oxidative Balance Score and migraine.Model 1 was unadjusted.Model 2 was adjusted for age and sex.Model 3 was adjusted for marital status, race/ethnicity, education level, and family income,building upon the adjustments made in Model 2.Model 4 was adjusted for energy consumption, protein consumption, carbohydrate consumption, dietary supplements taken, and C-reactive protein,building upon the adjustments made in Model 3.Model 5 was adjusted for smoking status, hypertension, diabetes, stroke, and coronary heart disease, building upon the adjustments made in Model 4.

Finally, considering the potential close association of dietary OBS and lifestyle OBS with migraines, we separately examined the correlation of dietary OBS and lifestyle OBS with migraine occurrence. Furthermore, ensuring the robustness of our model was imperative for drawing reliable conclusions; hence, adjustments were made accordingly. All statistical analyses were conducted with a two-sided approach, and the significance threshold (alpha) was set at 0.05. All analyses were performed using the statistical software packages R 3.3.2 (http://www.R-project.org, The R Foundation, Shanghai, China) (accessed on 10 March 2022) and Free Statistics software version 1.9.1.

3.1. Baseline Characteristics

7238 individuals recruited in our current study, consisting of 3889 male and 3349 female.There were 1406(19.43%) individuals with migraine.The average age of the study participants was 48.5(± 17.8)years.Most subjects were non-Hispanic white (57.0%).Table 1 depicted a summary of the baseline characteristics of the participants by tertile.Compared to the lowest OBS tertile, participants in the highest OBS tertile were younger, had higher wealth, higher education, higher total energy intake, higher Protein intake, higher CRP, higher Dietary supplements intake, lower migraine. were non-Hispanic White, and were married/ living with a partner. The differences in sex between OBS groups were not statistically significant. The prevalence of migraine with its co-morbidities, including Coronary heart disease,stroke,hypertension,diabetes, gradually decreased as OBS increased(Table 1).

3.2. Relationship between OBS and Migraine

The univariate analysis demonstrated that age,sex,race,family income,education level,smoking status,coronary heart disease,hypertension,protein consumption,carbohydrate consumption,dietary supplements, Dietary OBS, Lifestyle OBS and OBS were associated with migraines (Table 2).

The relationship between OBS and migraine was shown in Table 3, the correlation between OBS and migraine was assessed based on a logistic regression.

When the OBS is a continuous variable,In model 1, OBS was inversely associated with migraine(OR 0.99, 95%CI 0.98 ~ 0.99, P < 0.001; Table 3). In model 5, with adjustments for all covariates, the significant negative correlation between the OBS and migraines persists(OR 0.97, 95%CI 0.96 ~ 0.99, P < 0.001; Table 3).

When the OBS is a categorical variable,In model 1, the higher the OBS, the lower the incidence of migraine(OR 0.81, 95%CI 0.70 ~ 0.93, P = 0.003; Table 3). In model 5, when the first OBS category was used as a reference point, the third OBS group's OR (95% CI) was 0.72 (0.59 to 0.88), and the P for trend was 0.002, indicated when the value of OBS was > 22.0, the probability of migraine decreased by 28% for each unit increased in OBS(Table 3).

3.3. Association between the dietary OBS/lifestyle OBS and migraine

We also divided OBS into dietary OBS and lifestyle OBS and further evaluated their association with migraine independently (Table 4).

There was a significant correlation between dietary OBS and migraine.When the dietary OBS is a continuous variable, In model 1, the dietary OBS was inversely associated with migraine(OR 0.99, 95%CI 0.98 ~ 1, P = 0.004; Table 4). In model 5, with adjustments for all covariates, the significant negative correlation between the dietary OBS and migraines persists(OR 0.97, 95%CI 0.96 ~ 0.98, P < 0.001; Table 4).When the dietary OBS is a categorical variable,In model 1, the higher the dietary OBS, the lower the incidence of migraine (OR 0.84, 95%CI 0.72 ~ 0.97, P = 0.018; Table 4).In model 5, when the first dietary OBS category was used as a reference point, the third dietary OBS group's OR (95% CI) was 0.70 (0.56 to 0.86), and the P for trend was 0.001, indicated when the value of dietary OBS was > 18.0, the probability of migraine decreased by 30% for each unit increased in dietary OBS(Table 4).

Nevertheless, The correlation between lifestyle OBS and migraines is not stable.When lifestyle OBS is considered as a continuous variable, there was no significant correlation between lifestyle OBS and migraines(Table 4).When the dietary OBS is a categorical variable,In model 1, the higher lifestyle OBS, the lower the incidence of migraine (OR 0.78, 95%CI 0.68 ~ 0.90, P = 0.001; Table 4).However, after adjusting for covariates, starting from the model 3, there was no longer a significant correlation between the two(Table 4).

3.4. Analysis of restricted cubic spline regression

In the restricted cubic spline regression, after adjusting for various covariates, we observed a linear relationship between OBS, lifestyle OBS, dietary OBS, and migraines.(p for nonlinear > 0.05, Fig. 2).

3.5. Additional analysis

In several subgroups, stratified analysis was performed to assess potential effect modifications on the relationship between OBS,dietary OBS and migraine. No significant interactions were found in any subgroups after stratifying by sex, age(20–40,40–50,and > 50 years),race,marital status, family income, education level,smoking status,coronary heart disease and hypertension(Fig. 3,4).

To illuminate the relationship between OBS and migraine, we conducted a cross-sectional analysis of 7238 individuals in the NHANES cohort. Our study found that total OBS, and dietary OBS were all negatively associated with the prevalence of migraine. Collectively, the higher the different OBS scores, the lower the risk of migraine. Nevertheless, The correlation between lifestyle OBS and migraines is not stable.Our findings emphasize the importance of adhering to an antioxidant diet and lifestyle, especially for the prevention of migraine.

Our findings on OBS and migraine were reliable and similar to most previous studies.The dietary components of OBS encompass numerous ingredients, many of which have been substantiated in prior studies for their antioxidant effects.A research demonstrated that increasing the intake of fiber-rich foods can prevent severe headaches or migraines[31].Riboflavin plays a crucial role in preventing various health conditions, including migraines[32, 33].Riboflavin may exert neuroprotective effects through its clinically beneficial anti-inflammatory and antioxidant stress properties. A German randomized, placebo-controlled, double-blind, multicenter trial has demonstrated that intervention with a patented supplement containing magnesium, riboflavin, and Q10 significantly reduces the frequency of migraine attacks, migraine symptoms, and disease burden in individuals suffering from migraine attacks compared to a placebo[34].Niacin is an essential coenzyme in mitochondrial energy metabolism. The relationship between daily niacin intake and migraines follows an L-shaped curve[35]. The OR of developing migraine was 0.975 (95% CI: 0.956 − 0.994, p = 0.011) in participants with niacin intake < 21.0 mg/day[35]. A cohort of 141 adult females of Caucasian descent with MA was genotyped for the MTHFR C677T variant using restriction enzyme digestion. Dietary folate information was collected from all participants and analyzed using the "FoodWorks" 2009 package[36]. The results from this study indicate that folate intake in the form of FA may influence migraine frequency in female migraine with aura (MA) sufferers[36].Supplementation of folic acid with pyridoxine could decrease the characteristics of migraine attacks including headache severity and attack frequency[37].A case-control study recruited 70 migraine patients and 70 healthy controls, utilizing enzyme-linked immunosorbent assay (ELISA) to measure serum vitamin B12 levels[38].The serum B12 levels in migraine patients were significantly lower than those in the healthy population, and individuals with lower functional activity of vitamin B12 had a higher likelihood of suffering from migraines[38].In terms of mechanisms, vitamin B12 plays a crucial role in restraining elevated homocysteine levels and excessive nitric oxide production,and a deficiency in B12 can result in disruptions to methionine metabolism[39].Vitamin B12 functions in the central nervous system, and a deficiency in this vitamin can give rise to detrimental neurological effects.Thus,Vitamin B12 has been used clinically for the prevention of migraines[40].

Additionally, various trace nutrients also play a role in the occurrence and development of migraines.A cross-sectional study indicated that a high intake of calcium and magnesium in the diet, whether individually or in combination, is inversely associated with migraines in females[24]. Conversely, for males, there is a negative correlation between high dietary calcium intake and migraines[24].The deficiency of magnesium plays a crucial role in the pathogenesis of migraines[41]. A cross-sectional study suggests that in the United States, insufficient magnesium intake is associated with migraines[26].Magnesium is widely used for the prevention and treatment of migraines[8, 41].The research by Huanxian Liu and others indicates that dietary zinc, as a trace element with anti-inflammatory and antioxidant properties, exhibits an inverse relationship with migraines[42].The double-blind, randomized, placebo-controlled clinical trial conducted by Hedieh Ahmadi and colleagues indicated that supplementation of zinc significantly reduced the severity and frequency of headaches[43].Furthermore, Yiyan Sun et al. conducted a National Cross-sectional Study where smooth-fit curves were employed to confirm the non-linear association between copper intake and migraines. An inflection point (0.98 mg/day) was identified in the relationship.Recently, there have been successive reports on the relationship between selenium and migraines.A study indicated that there was a non-linear relationship between selenium intake and migraines in the general population of the United States, with an inflection point at 93.1 micrograms per day[44].In addition, Afsoon Talaie et al. conducted a case-control study, matching 31 migraine patients with 30 healthy individuals based on age and gender. Using biochemical methods, they measured serum selenium [45]. The study indicated that low serum selenium levels were associated with an increased risk of migraines[45].In the case of dietary iron, studies indicated that the intake of dietary iron was inversely related to severe headaches or migraines in women aged 20–50[25].

There are also some reports on the relationship between the components of Lifestyle OBS and migraines, and these lifestyles were incorporated into our OBS components.In a past prospective cohort study, university participants with migraines, tension-type headaches (TTH), or without headaches were monitored for 7 days using an Omron HJ-112 pedometer and daily headache diaries[46]. The study compared daily free-living physical activity (PA) between groups, and differences in PA as a function of headache day versus non-headache day were compared among those with migraines and TTH[46]. Consistent with other studies, individuals with migraines reported lower levels of PA compared to non-headache controls[46].In a cross-sectional survey at the University of Palermo, we employed the ID-migraine questionnaire, incorporating demographic, anthropometric, and sports variables. The study, using the Italian version of the Migraine Disability Assessment Scale, found a protective effect of sports in females with migraines[47].However, the impact of alcohol on migraines is a subject of controversy.In a systematic review of literature published from 1958 to 2015, encompassing 43 articles and 12,400 participants, 21% of patients (95% confidence interval: 16%, 26%) reported alcohol as a trigger for migraines.But,in a study, adjusting for gender, age, and weekly alcohol intake, the probability of post-alcohol migraine the next day did not increase[48]. The alcohol-migraine association may be more complex due to factors like clinical condition, pre-attack alcohol, and individual susceptibility[48].The relationship between BMI and migraines has also been confirmed.A meta-analysis indicated that, through a non-linear association, individuals with underweight or obesity face an increased risk of developing migraines[49].Another study suggested that both total body obesity and abdominal obesity were associated with the prevalence and frequency of migraines.Therefore, weight control is beneficial for preventing headache disorders.There are also relevant reports on the relationship between smoking and migraines.A study showed a significant positive association between severe headaches or migraines in never-smoking adults and substantial exposure to secondhand smoke (serum cotinine ranging from 1 to 10 ng/mL)[12].

Our research had several advantages. Initially, our focus in the study was on the composite indicator OBS rather than individual components. This approach aimed to provide a comprehensive understanding of the intricate relationships among factors and to conduct a more thorough investigation into the outcomes of interest. Secondly, we utilized NHANES data, employing a sophisticated multi-stage probability sampling design to secure a representative sample of the civilian noninstitutionalized resident population, thereby ensuring the high quality of the data. Thirdly, this study controlled for numerous confounding factors, encompassing sociodemographic characteristics, calorie, protein, and carbohydrate consumption, dietary supplement use, C-reactive protein levels, as well as multiple co-morbidities, ensuring a comprehensive analysis. Fourthly, we independently assessed the distinct impacts of lifestyle OBS and dietary OBS on migraines. Separate subgroup analyses were conducted for each OBS and lifestyle OBS, as it was crucial to consider potential effects of sex, age, race/ethnicity, marital status, family income, education level, smoking status, coronary heart disease, and hypertension.

The current study also has a few limitations. First, establishing a causal relationship between OBS and depression is challenging due to the cross-sectional nature of the study.As a result, there is a requirement for more studies with prospective designs to illustrate the effectiveness of OBS.Second, the inclusion of all OS-related dietary and lifestyle exposures in OBS was challenging due to limitations in the database. Many components, such as flavonoids, were limited in availability.Third, the current study operates on the assumption of a linear correlation between all pro-oxidants and antioxidants with oxidative stress. This overlooks the threshold effects of antioxidants, and certain antioxidants, like copper and carotenoids, have demonstrated potential pro-oxidant activity at elevated doses or under specific conditions.Lastly, the study did not consider the relationship between migraine medications and oxidative stress. This confounding factor related to the use of migraine medication was not accounted for due to data limitations.

In conclusion, findings from a nationally representative sample of US adults indicate a robust negative association between OBS and migraine.It was demonstrated that elevated OBS, indicative of greater antioxidant exposure than prooxidant exposure in diet and lifestyle, correlated with reduced odds of migraine.Therefore, a diet rich in antioxidants and a healthy lifestyle are crucial for the prevention and treatment of migraines.

Ethics statement

The survey plan and study procedure have been approved by the National Center for Health Statistics' Ethics Review Board, and the participants/patients have given their written informed consent. We conducted a study that was exempt from institutional review since it involves secondary data analysis from the National Health and Nutrition Examination Survey.In the future, there is a need for more extensive investigation into the causal relationship and precise mechanisms underlying the association between OBS and migraines.

Funding

Health and Technology Capacity Enhancement Project in Jilin Province, in China(2022lc085).

CRediT authorship contribution statement

Jing Su is the primary author who drafted the manuscript, obtained references, performed most of the data analysis, and helped with the conceptualization of the study. Liming Liu,Dexi Zhao and Zihan Wang both performed data analysis with the regression models, obtained background information for references, and proof read the manuscript drafts. Xinna Wang, Ruonan Wang,Qiaoli Xu, Qingyuan Wang and ChunYu Shen also performed extensive background research, as well as proofed all drafts of the manuscript and helped created fgures and tables.

Declaration of competing interest

None.

Data availability

The National Health and Nutrition Examination Survey (NHANES). (https://www.cdc.gov/nchs/nhanes/index.htm) provided the data for this investigation.

Acknowledgements

We appreciate Dr. Jie Liu of the Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital for statistics, study deign consultations and editing the manuscript.

Author Contribution

J.S. is the primary author who drafted the manuscript, obtained references, performed most of the data analysis, and helped with the conceptualization of the study. L. L.,D. Z. and Z. W. both performed data analysis with the regression models, obtained background information for references, and proof read the manuscript drafts. X. W., R. W.,Q. X., Q. W. and C.Y. also performed extensive background research, as well as proofed all drafts of the manuscript and helped created fgures and tables.

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Tables 1 to 4 are available in the Supplementary Files section.

No competing interests reported.

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Association between Oxidative Balance Score and Migraine among American Adults: National Health and Nutrition Examination Survey

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Abstract

Background

Methods

Results

Limitations:

Conclusions

Figures

1. Introduction

2. Materials and Methods

2.1 Study population

2.2. migraine assessment (outcome)

2.3 Oxidative balance score (exposure)

2.4. Covariate assessment

2.5. Statistical analysis

3. Results

3.1. Baseline Characteristics

3.2. Relationship between OBS and Migraine

3.3. Association between the dietary OBS/lifestyle OBS and migraine

3.4. Analysis of restricted cubic spline regression

3.5. Additional analysis

4. Discussion

5. Strengths

6. Limitations

7. Conclusion

Declarations

References

Tables

Additional Declarations

Supplementary Files

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