Migraine is a highly prevalent and debilitating neurological disorder, affecting more than 1.5 billion people worldwide, with a higher prevalence in women (1–3). The most common symptom of a migraine is a throbbing headache that comes on repeatedly. Other symptoms include light or sound sensitivity, nausea, and vomiting (4, 5). These debilitating symptoms not only cause significant suffering for patients but also result in substantial economic burdens due to absenteeism and reduced productivity. In the U.S. alone, the direct and indirect costs associated with migraines are estimated to exceed $20 billion annually (6). While the precise pathophysiological mechanisms underlying migraines are still unknown, an increasing body of research indicates that oxidative stress is a major factor in the etiology of migraines (7, 8). Free radicals and the body’s antioxidant defenses are out of balance, which leads to oxidative stress, and can lead to cellular damage, inflammatory responses, and abnormal vasoconstriction and vasodilation, which are thought to trigger migraines (9, 10). Studies have shown that oxidative stress markers are elevated in individuals with migraines, while antioxidant levels tend to be lower (11). Therefore, nutrients with antioxidant properties, such as carotenoids, may potentially exert a protective effect by reducing the occurrence or severity of migraines.

Carotenoids are natural pigments found in plants that possess strong antioxidant and anti-inflammatory properties. Their physiological functions are primarily achieved by scavenging free radicals, reducing oxidative stress, and enhancing immune function (12, 13). Multiple research studies indicate that carotenoids have a negative correlation with the likelihood of developing chronic illnesses such as cardiovascular diseases, specific forms of cancer, and age-related macular degeneration (14–16). One example is the significant association between elevated serum levels of β-carotene and a decreased likelihood of developing cardiovascular disease (17). Additionally, Carotenoids like lutein and zeaxanthin have been shown to protect the eyes, particularly by defending against age-related ocular diseases (18). Although these health benefits are well-established, the specific relationship between carotenoid levels and neurological disorders, including severe headaches and migraines, remains insufficiently understood.

Our research aims to analyze the correlation between levels of serum carotenoids and the prevalence of severe headaches or migraines using data from the 2001–2004 NHANES, offering new insights into the potential role of nutritional interventions in migraine management.

The research indicated a significant inverse relationship between the prevalence of migraines and serum levels of α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, and total carotenoids. Among the carotenoids studied, β-cryptoxanthin exhibited a unique L-shaped association, suggesting that its protective effect may plateau after reaching a certain concentration. In contrast, lycopene did not show a significant association with migraines, indicating that different carotenoids may have varying effects. Subgroup analyses confirmed the robustness of the study’s findings.

This suggests that individuals with higher serum concentrations of these carotenoids are less likely to experience migraines. The protective effect of these carotenoids is primarily attributed to their strong antioxidant activity. Reactive oxygen species (ROS) production is elevated in migraines due to oxidative stress, leading to neural tissue damage and impaired vascular function, which are known contributors to the pathophysiology of this condition (24, 25). Carotenoids, as effective scavengers of ROS, may help neutralize these free radicals, thereby protecting the brain and vasculature from oxidative damage (7). Additionally, carotenoids possess anti-inflammatory properties, which may further explain their protective role in migraine prevention (26). Frequently linked to neuroinflammation, migraines are triggered by inflammatory cytokines including tumor necrosis factor-α and interleukin-6 (27, 28). Carotenoids, particularly lutein and β-carotene, have been shown to downregulate these inflammatory mediators, potentially reducing the inflammatory processes that lead to migraine attacks (29). The observed L-shaped relationship between β-cryptoxanthin and migraines suggests that while increasing β-cryptoxanthin levels initially provides a protective effect, this effect may reach a plateau beyond a certain point. This may indicate a threshold for the bioavailability or metabolism of carotenoids, where the body can only utilize a limited amount of β-cryptoxanthin for its antioxidant and anti-inflammatory effects. Beyond this threshold, further increases in serum levels do not provide additional protection, highlighting the need for future research to determine the optimal carotenoid levels for migraine prevention.

Studies have shown that oxidative stress markers are elevated in migraine patients, while levels of endogenous antioxidants, such as glutathione, are decreased, indicating an impaired ability to neutralize ROS in these patients. Similarly, some studies have reported that individuals whose diets are rich in carotenoids, particularly β-carotene and lutein, have a lower risk of neurological disorders, including migraines (30). For instance, adherence to the Mediterranean diet—which is high in fruits and vegetables that contain carotenoid—was linked to a lower incidence of migraines, according to a study by Bakırhan et al. (31). This complements the current findings, as the measurement of serum carotenoid levels provides an objective biomarker of dietary intake and antioxidant status, further supporting the protective role of these compounds in migraine prevention. The non-linear L-shaped relationship observed in this study between β-cryptoxanthin and migraine risk is similar to findings in other health conditions, such as cardiovascular disease. Huang et al. found a similar L-shaped association between β-cryptoxanthin levels and cardiovascular disease risk, where moderate levels provided the greatest protection, but higher levels did not offer additional benefits (17). This suggests that the protective effect of β-cryptoxanthin may be dose-dependent, with an optimal range for its beneficial effects. Results from a study in the future indicated that being exposed to numerous serum carotenoids was linked to a decreased likelihood of mortality from any cause, cardiovascular disease (CVD), and cancer. These results imply that consuming a diverse range of carotenoids in one’s diet may provide extensive health advantages (17, 19). Research by Wang et al. indicated an inverse correlation between serum carotenoid concentrations and the prevalence of CVD, with the protective effect being more pronounced for heart disease and stroke (32). Higher dietary antioxidant index scores have been associated with a lower prevalence of severe headaches or migraines (33). Additionally, Research has indicated a negative correlation between the prevalence of chronic obstructive pulmonary disease and carotenoid levels, with lutein, zeaxanthin, and α-cryptoxanthin being the main contributors to this inverse association (34). Research conducted by Heqing Zheng and colleagues indicated that the potential link between zinc consumption and migraines could be attributed to the antioxidant and anti-inflammatory characteristics of zinc. Furthermore, this negative association was more pronounced in participants aged 20–50 compared to those over 50 (35). In this study, there was no significant link between lycopene and migraines. This difference may be due to the way carotenoids accumulate and function in different tissues. While lycopene effectively protects against oxidative stress in the prostate and cardiovascular system, it may not have the same protective effect in the brain, where other carotenoids, like lutein and β-carotene, are more prevalent (36, 37).

The presence of serum carotenoids may be linked to the prevalence of migraines. Carotenoids are known for their capacity to counteract reactive oxygen species (ROS) and decrease oxidative stress, which is a significant factor in the development of migraines. Migraines are frequently connected with heightened oxidative damage, particularly in neural tissue, which is highly vulnerable to oxidative stress because of its high metabolic requirements (24, 25). By mitigating oxidative damage, carotenoids may help in preventing or reducing the frequency and severity of migraine attacks.

The study has multiple notable strengths. To begin with, it utilizes a sizable, nationally representative sample from the NHANES dataset, enhancing the generalizability of the findings to a broader U.S. population. The utilization of NHANES ensures high-quality data collection, including serum carotenoid level measurements conducted using advanced laboratory techniques, thereby providing accurate and objective biomarkers of antioxidant status. This research emphasizes serum carotenoids rather than self-reported dietary intake, mitigating biases associated with misreporting or inaccuracies common in dietary surveys. Furthermore, this research is among the initial inquiries into the correlation between various specific carotenoids and the frequency of migraines. Previous studies have primarily concentrated on overall dietary patterns or general antioxidant intake. By examining individual carotenoids, this research offers deeper insights into how specific antioxidants may influence migraine risk. The L-shaped relationship observed between β-cryptoxanthin and migraine risk contributes novel information to the existing literature on antioxidants and migraines, suggesting that the carotenoids exhibit dose-dependent protective effects.

Despite these strengths, this study also has several limitations. Firstly, the cross-sectional design of the NHANES dataset constrains our ability to establish causality. This study remains uncertain whether higher carotenoid levels reduce migraine risk or if individuals with fewer migraines exhibit different dietary habits or lifestyles that contribute to elevated carotenoid levels. Longitudinal studies are necessary to more accurately assess the directionality of this relationship. Secondly, the self-reported nature of migraine diagnosis may introduce recall bias or misclassification. Finally, although this study examined multiple carotenoids, it did not investigate potential interactions between carotenoids and other nutrients, which may play synergistic roles in mitigating oxidative stress and inflammation. Future research should explore how combinations of antioxidants influence migraine risk and whether specific carotenoids are more effective when consumed alongside other nutrients.

The results of this research indicate that there is a negative correlation between serum levels of α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, and total carotenoids and the probability of experiencing migraines. Notably, an L-shaped relationship exists between β-cryptoxanthin and migraine risk. Increasing the intake of carotenoid-rich foods may represent a straightforward and feasible strategy for enhancing antioxidant defenses and alleviating the burden of migraines.