The relationship between toxic heavy metal exposure and migraine and the modulatory role of an anti-inflammatory diet: A population-based cross-sectional study

The influence of chronic, low-level environmental toxic metal exposure on migraine is poorly characterized. This study aimed to investigate the association between blood cadmium and lead levels and risk of migraine and how the inflammatory potential of dietary modified this association among United States adults. This cross-sectional study recruited 10,763 participants aged ≥ 20 from the National Health and Nutrition Examination Survey. The concentrations of blood cadmium and lead were measured using atomic absorption spectroscopy. The dietary inflammatory index (DII) assesses the inflammatory potential of diets and categorizes them into 3 groups: anti-inflammatory diets, low-intensity pro-inflammatory diets, and high-intensity pro-inflammatory diets. Migraine was diagnosed when participants reported that they had severe headaches or migraines during the past 3 months. Weighted multivariable logistic regression and restricted cubic spline models were used to determine the association of blood cadmium and lead levels, DII categories, and risk of migraine. The study included a total of 10,763 participants, of whom 2202 (20.5%) were diagnosed with migraine. After multivariable adjustment, blood cadmium levels were independently associated with an increased odds of migraine in a linear dose-response manner (odds ratio 1.18, 95% confidence interval 1.06-1.31, P = .004, P for nonlinearity = 0.064). Compared with participants having blood cadmium levels ≤ 0.3 μg/L, those with levels ≥ 0.7 μg/L had 21% higher odds of migraine (odds ratio 1.21, 95% confidence interval 1.01-1.46, P = .035). Mechanistic exploration analysis suggests that blood cadmium levels were associated with an increase in system inflammation response index and systemic immune-inflammation index, which reflect systemic inflammation, in migraineurs. Blood lead levels were not related with migraine, system inflammation response index, and systemic immune-inflammation index. Stratified analysis by the DII categories showed that the association between blood cadmium levels and odds of migraine remained significant only in the low-intensity pro-inflammatory diet subgroup, but disappeared in the anti-inflammatory diet and high-intensity pro-inflammatory diet subgroups. Higher blood cadmium levels are associated with an increased probability of suffering migraine, which could be mitigated by anti-inflammatory diets. Further studies are needed to clarify how cadmium triggers migraine attacks and to ascertain whether dietary interventions reduce risk of migraine in high-exposure populations.