The Relationship Between Food Allergens and Migraine Among Patients With Migraine Referring to Shahid Mohammadi Neurology Clinic

,

investigated the correlation between migraine severity and IgE level in peripheral blood. The IgE level was recorded for all 212 participants and then scrutinized for the clinical signs of allergic rhinitis (AR). The prevalence of AR in migraine patients and the degree of allergic sensitivity were examined in this study. According to the findings, there was a 78.3% prevalence of AR among migraine patients. The IgE level in the peripheral blood was significantly higher among migraine patients with RA compared with people who did not have migraine. There was also a significant relationship between the intensity of AR (higher levels of IgE) and the severity of migraine attacks. However, no significant relationship was observed between AR intensity and other factors. Ultimately, the researchers concluded that inflammatory mediators play a key role in triggering migraine attacks. Hence, the effective treatment of AR is crucial in the treatment and prophylaxis of migraine headaches (6).
In another descriptive cross-sectional study, Rosario et al examined the relationship between allergic sensitivity with the prevalence of migraine and its accompanying disability. The serum IgE level was recorded for 100 male and female outpatients who were diagnosed with migraine. Moreover, migraine severity was evaluated with the Migraine Disability Assessment scale. It was detected that elevated levels of IgE were accompanied by more severe headaches which required longer treatments. Considering the findings, it was concluded that migraine is more prevalent among females and younger individuals (7).
Given the prevalence of migraine in Bandar Abbas and controversial reports regarding the relationship between migraine and serum IgE level, the present study sought to investigate this potential relationship through measuring the serum IgE level during the acute phase of migraine headache for patients who had been referred to the neurology clinic in Shahid Mohammadi Hospital in 2019. It is believed that the findings would have diagnostic, therapeutic, and prophylactic utility for the management of migraine headaches.

Materials and Methods
The population of this cross-sectional descriptiveanalytical study involved all patients who had been referred to the Neurology Clinic of Shahid Mohammadi Hospital in Bandar Abbas with the complaint of headache, for whom the diagnosis of migraine was confirmed. The minimum sample size was calculated as 230 individuals who were selected through purposive sampling. The inclusion criteria were having signed the informed consent form, being in the group age of 18-65 years, and having a confirmed diagnosis of migraine. On the other hand, the other types of headaches such as tension or cluster headaches, history of secondary headache disorders due to conditions (i.e., cerebral aneurysm or tumors), and chronic medical disorders such as malignancies or renal failure in addition to pregnancy and its concomitant migraine were considered as the exclusion criteria.
The patients' demographic information such as age, gender, marital status, and other data such as a family history of headache, frequency, and duration of each headache in a given month were recorded in a questionnaire by the assistant physician. The quantitative data distribution was examined using the Kolmogorov-Smirnov test, and then the data were analyzed through statistical tests such as chi-square and Mann-Whitney.

Results
The participants' demographic information indicated that out of 230 subjects, 121 (52.6%) were females and 109 (47.4%) of them were males. The mean age of the patients was 40.59 ± 13.80. Among them, 62.2% were married and 62.2% had a family history of migraine. The average number of headaches per month was 4.20 ± 3.13, and the duration of each was 3.52-4.24 hours.
Eating allergen foods (Table 1) cause or exacerbate migraine. According to the findings, sausages (55.7%), carbonated beverages (52.2%), peanut (45.2%), veal or beef (45.2%), and canned food (41.7%) were the most common foodstuff that could trigger or exacerbate migraine headaches, respectively. On the other hand, chicken, strawberry, rice, and wheat had the least potential in this regard.
The relationship between the potential of consumed food in the initiation or exacerbation of migraine headaches based on the gender of patients was examined through the cross-tab command by the chi-square test ( Table 2). The results indicated that cantaloupe was the only fruit that had a significant relationship with migraine exacerbation (P < 0.05). This was more evident among women.
According to the obtained results, the chi-square test revealed that none of the intended foodstuffs had a significant relationship with the migraine onset or deterioration in terms of family history (P > 0.05) ( Table 3).
Based on data analysis, the egg was the sole food that could significantly initiate or worsen migraine headaches (P < 0.05) with a presumably higher degree among married patients compared with single ones ( Table 4).
The data in Table 5 represent the relationship between the potential of eaten foodstuff on migraine initiation or exacerbation based on the participants' age. Due to the abnormal distribution of the participant's age, Mann-Whitney non-parametric test was applied to examine this relationship. According to the findings, none of the foodstuffs had a significant relationship with migraine initiation or exacerbation based on age (P > 0.05).
Due to the abnormal distribution of patients' headache hours, Mann-Whitney non-parametric test was applied to examine the relationship between the consumed Agha Negahi et al hmj.hums.ac.ir http foodstuff on migraine onset and intensity. According to the findings, there was a significant relationship between the intake of traditional or industrial cheese and headache hours (P < 0.05) ( Table 6). In other words, patients who are non-allergic to cheese experience considerably less intense headaches.
Since the number of patients' headaches did not have a normal distribution, Mann-Whitney non-parametric test evaluated the relationship between the foodstuff and migraine intensity. It was found that eating shrimp had a significant relationship with migraine (P < 0.05) ( Table 7). It is apparent that patients who are non-allergic to shrimp suffer from less severe migraine headaches.

Results and Discussion
Migraine is a type of primary periodic headache which is accompanied by a combination of neurologic gastrointestinal and autonomic symptoms (1). Other symptoms include photophobia, nausea, vomiting, constipation or diarrhea, weight gain, ataxia, dizziness, hypertension, and fluid retention, followed by urination (2).
The findings of this study indicated that the most On the other hand, chicken, strawberry, rice, and wheat had the least effect on the initiation and exacerbation of migraine. Cantaloupe had a significant relationship solely with gender (P < 0.05) so that it could trigger migraine mostly in women. According to the results, none of the foodstuffs had a significant relationship with family history (P > 0.05). In a study conducted in Gilan, Iran, the prevalence of migraine was investigated using an AR questionnaire among different age groups. It was concluded that the prevalence was 14.3% and 28.2% in the age groups of 6-7 and 12-13 years, respectively (8). Based on our findings, a significant relationship was found between cheese consumption and patients' duration of headaches in terms of hours (P < 0.05). In other words, patients who are allergic to traditional and industrial cheese suffer more intense migraine headaches.
The results of this study also revealed a significant relationship between eating shrimp and migraine onset or deterioration. It is apparent that patients who are non- The scratch test is most commonly used to justify the relationship between allergen foods and primary headaches (9), and an elimination diet is then recommended based on the results. Most studies in this regard have reported a relatively high success rate.
There were other triggers as well (34.4%). Ultimately, it was concluded that migraine triggers among Indians were the same as those for other populations; however, they were mostly linked with dietary factors (10). According to the report of Wöber et al, knowledge of dietary stimulants for migraine would decrease their frequency of consumption (11).
In the same study, Yadav et al considered wine, chocolate, fruits, and vegetables (P < 0.05) as the stimuli reported by patients with migraine and tension headaches. However, hunger was an exception since the personal experience was more extensive than theoretical knowledge in this regard (12)(13)(14)(15)(16)(17)(18)(19).
Immunological mediators such as IgE and histamine tumor necrosis factor (TNF-alpha), calcitonin genedependent peptide, intestinal vasoactive peptide, prostaglandins D2 and F2, interleukin 1, and tryptase, as well as most cell activation and nitric oxide secondary release, were observed in both migraine and allergy (13). Moreover, migraine patients considered variations in weather (83%), season change (75%), and exposure to allergens (62%) as headache triggers (7). In another study in a rhinology tertiary care center, Perry et al found that the incidence of migraine was 58% among patients with headaches who had normal radiology and endoscopic findings (14). Ku et al evaluated individuals who were above 40 years of age and had a positive radioallergosorbent test, at least one of the common inhaled allergens, and at least two positive answers to the 6 questions regarding AR (nasal congestion, rhinorrhoea, sneezing, snoring or mouth breathing, pharyngeal discharge, and itchy and watery eyes). The other investigated individuals in their study had one of the symptoms of AR on examination (pale or swollen turbines, mucous secretions in the nasopharynx airways, dark rings around the eyes, and the backline of the nose). The control group included non-atopic patients who had been referred to internal medicine and pediatric clinics (15).
A meta-analysis in 2001 reviewed studies conducted between 1996 and 1999 on the relationship between migraine and immune system function. It was concluded that the impact of the immune system on intensifying migraine headaches due to the potential impact of atopic disorders on migraine is still debatable. Since 1996, about 45 studies considered immune system function changes in migraine patients; they were all revered by Kemper et al. The variations of serum complement levels and immunoglobulins, histamine, cytokines, and immune cells have been identified in some of these studies, but have not been confirmed in most cases. The abovementioned study demonstrated that there is no definite proof for immune function disorders in migraine. Nonetheless, the likelihood of this relationship is not ruled out totally. The variations in the findings are partly due to the differences in the sampling methods linked with the timing of migraine attacks. In this regard, the findings of this study represented that sampling times should be precisely defined based on immune system function in migraine patients (16). Pradalier and Launay studied the immunological aspects of migraine and observed alterations in immunoglobulins, especially IgE, complement function, mediators, cytokines, and inflammatory cells. However, conclusive remarks about the role of the immune system in the pathophysiology of migraine are assigned for further studies (17).
Özge et al examined 186 migraine cases for the relationship between migraine and atopic diseases in the department of neurology of a university in Turkey. They concluded that 41.4% of migraine patients had at least one atopic disorder, which may indicate a positive relationship between such disorders and migraine headaches (18). Evidently, different studies expressed varied findings regarding the relationship between migraine and allergens, along with the impact of the immune system on migraine. The measurement time of the immune system factors, study groups, and headache time would explain the discrepancies in the findings. For instance, in some studies, the measurement time was during the intervals between migraine attacks, while in other studies, it was at the onset of the attack. In other cases, the measurement time was not defined at all. On the other hand, some studies selected their control group from healthy individuals, while in others, patients with Research has identified different causes of migraine, including foods, stress, depression, anxiety, hormones, barometric pressure, light, cigarette smoking, and headache medications. However, the researchers have not yet figured out how to determine the specific etiology of headaches. Those who study migraine and diet mostly face problems such as the headaches which develop after eating a triggering substance but are actually the result of other substance deposits. The other reason for the inconsistency of findings in migraine studies is their lack of definite diagnostic criteria. Most of them simply claim that the participant had been diagnosed with migraine without stating the applied diagnostic criteria. The third underlying reason for the incompatibility in such studies would be their lack of or indefinite participant inclusion criteria, which would be absolutely misleading. The fourth explanation for divergent results is the methodological differences. In the studies with blinding methods, the given dose, number of administered doses, and measurements were different. In some cases, insufficient information regarding the methods expanded the ambiguities. Last but not least, some authors' reluctance to use inferential statistics for data analysis increase the obscurity. Although inferential statistics lead to more definitive conclusions, only a few studies take this advantage.
It is evident that the methodology is directly impacted by the intention of the study. A challenging study should be performed given that the goal of a project is to evaluate a biochemical mechanism associated with food. However, a therapeutic study must be conducted if the intention is treatment. It is recommended that research on therapies should be performed through double blinding rather than non-blind eating challenges. Accordingly, any impact could be easily attributed to the foodstuff per se instead of other non-specific factors.
Although diet-induced migraine is a common phenomenon that affects many people, it is not yet fully clarified which foodstuff becomes a trigger or under which conditions they change. Learning to detect migraine-triggering foods and the influencing conditions, as well as identifying susceptible individuals leads to effective headache management. For future studies, it is suggested that the present project be modified with more participants. Furthermore, through intervention and elimination of allergens from individuals' diets, the role of specific allergens could be clarified more accurately. It is high time that we take actions to prevent disease through changing people's lifestyles.