Potential Link Between Positive Food-Specific IgG Antibodies and Migraine Identified

Study results point to a potential link between immunoglobin G (IgG) antibodies and migraine frequency, severity, and comorbidities.

Findings of a cross-sectional clinical study published in the Journal of Pain Research revealed migraineurs with positive food-specific immunoglobin G (IgG) antibodies reported worse migraine, anxiety, and gastrointestinal symptoms.

“Migraine attacks can be associated with a variety of factors, including dietary consumption,” the authors explained, while “allergies mediated by food-specific IgG antibodies can cause chronic aseptic inflammation in many systems of the body.”

Previously, researchers hypothesized IgG may serve as a biomarker to identify foods related to enhanced inflammatory responses in vivo. In addition, proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) can induce visceral pain. Increased serum levels of these cytokines have also been observed in migraineurs.

To better understand the effects of food-specific IgG antibodies on headaches, gastrointestinal symptoms, anxiety, depression, and other factors, the researchers conducted a cross-sectional study of patients with a neurologist-confirmed migraine diagnosis.

All participants were recruited from a health center in China between October 2020 and February 2021 and were between the ages 18 and 62. A trained survey coordinator collected demographic and past medical history information via a general health questionnaire, while individuals also filled out the Migraine Disability Assessment questionnaire (MIDAS) and completed a visual analogue scale to assess headache pain.

An additional 5 questionnaires were administered to participants to assess the impact migraine has on daily activity and quality of life. The researchers also assessed blood samples in addition to food-specific IgG antibodies (measured via enzyme linked immunosorbent assays) and IL-6, interleukin-10, and TNF-α.

Of the 89 patients included, the majority were female with a mean (SD) age of 40.3 (9.2) years and an average body mass index (BMI) of 23.5. “Those who had 1 or more food-specific IgG antibodies ≥ 50 U/mL were classified into the IgG-positive group, which was then further divided into subgroups based on differing numbers of food allergens,” the authors explained.

Analyses revealed:

  • The top 2 most prevalent food allergens were eggs and cow’s milk; among the 67 participants in the positive group, 43.3% had positive egg-specific IgG and 26.9% had positive cow’s milk–specific IgG
  • Participants in the positive group were more likely to have longer time elapsed since migraine diagnosis, more frequent and severe migraine, a higher risk of developing anxiety and gastrointestinal symptoms, and higher IL-6 and TNF-α levels
  • A significant positive association was observed between not only MIDAS scores but also Gastrointestinal Symptom Rating Scale scores and the positive IgG concentration
  • Subgroups with more food allergens generally had worse conditions
  • After adjusting for the inflammatory cytokines, the effect of IgG was reduced

According to the researchers, study participants residing in this region of China are exposed to both milk and eggs early in life and consume the products with frequency. These factors combined “leads to the ability to accumulate high levels of serum IgG antibodies in the body and produce chronic antigen antibody reactions.”

Because consumption of sensitized allergenic foods can trigger certain IgG antibodies produced by the immune system, in combination with allergens from an immune complex, this process could activate multisystem inflammatory reactions such as migraine, sleep disorders, or other conditions, the authors explained.

Overall, in the current study, “migraineurs with an increased number of positive food allergens and/or higher overall positive IgG concentration had poorer disability measurements and greater related functional impairments, quality of life, disability questionnaire results, and slightly greater odds of having chronic migraine, likely related to inflammation triggered by food-specific IgG antibodies and a variety of inflammatory factors produced in this process,” they said.

A small sample size marks a limitation to the investigation, in addition to its cross-sectional nature. “We expect to conduct an interventional study in the future to explore the effect of eliminating IgG-positive foods on migraine and the related comorbidities,” the researchers concluded.


Zhao Z, Jin H, Yin Y, et al. Association of migraine with its comorbidities and food specific immunoglobin G antibodies and inflammatory cytokines: cross-sectional clinical research. J Pain Res. 2021;14:2359-2368. doi:10.2147/JPR.S316619