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Commentary: Research on Potential Migraine Triggers, January 2023

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January's theme is migraine triggers. We'll take a look at three recent studies that have tried to better determine the nature of specific triggers for headache.

One of the most common and reportedly consistent migraine triggers is exposure to alcohol, and the International Classification of Headache Disorders (ICHD-3) includes alcohol-induced headache as a secondary headache. Little is known regarding the association between migraine and alcohol. Vives-Mestres and colleagues investigated the alcohol intake of people using a digital health diary for headache. They specifically looked at the 48 hours preceding a migraine attack and whether alcohol was consumed, and also the number of beverages consumed. This was further adjusted for sex, age, and average weekly alcohol intake.

The N1-Headache Tracker is a digital headache diary that patients use to track their daily headache symptoms and inform them of potential migraine risk factors. Over a 90-day period, this study followed patients that did not meet the criteria for a diagnosis of chronic migraine. They also reported on their intake to the platform that they regularly consume alcohol. Of note, persons who never tracked alcohol consumption were excluded from this study. On intake to the platform, alcohol exposure was characterized both as whether daily consumption of alcohol was occurring and as the total daily number of alcoholic beverages.

The primary outcome of this study was migraine attack 1 day after alcohol consumption. Participants were specifically asked if their headaches were diagnosed as migraine by a physician. Migraine attack onset was considered binary, and a logistic model was used to estimate the probability of having a migraine attack on any given day with the association of alcohol intake for up to 48 hours prior to that day.

A total of 487 people with migraine were included in this trial and they collectively contributed over 43,000 diary days; almost 6000 were first days of a migraine attack. Overall alcohol consumption was not considered high and was noted to vary between groups; people with lower frequency migraine tended to have higher rates of alcohol intake. No significant correlation was observed between the presence of migraine attacks within 48 hours after alcohol consumption. This did not vary among different probability models; a population-level model showed that the probability of a migraine attack 2 days after alcohol intake was 25% lower than the probability of an attack with no alcohol consumption. This was also true after adjustment for age, sex, and average number of alcoholic beverages per week.

The association between migraine and alcohol is complicated, and the concept of migraine triggers in general is very complex. Although over 70% of people with migraine say that they have a consistent trigger, and alcohol is consistently at the top of the list of those reported triggers, there does not appear to be a direct correlation between migraine and alcohol exposure. The greatest caveat of this study is the fact that people with chronic migraine were excluded. Further research should specifically investigate triggers such as alcohol in this population.

The use of proton pump inhibitors (PPI) has been shown in previous studies over the past few years to be associated with a number of neurologic events and risks, including impaired hearing, vision, and memory, as well as migraine occurrence. The specifics of this association are not well known — specifically, whether the duration of use is the main factor, or whether it is acute exposure to a PPI medication that is a trigger. Kang and colleagues reviewed data in the Korean national database and developed a case-control model to study this association specifically.

The migraine and control groups were equally matched: They had the same demographics, smoking status, alcohol consumption, blood pressure range, fasting glucose, and total cholesterol. Past and current PPI use and comparisons of migraine occurrence were further differentiated among patients who were exposed to PPI medications for < 30 days, 30-365 days, and > 365 days.

The use of PPI treatments was noted to be linked to increased migraine regardless of duration, and regardless of the acute presence of the PPI. Even a history of prior PPI use was noted to increase the odds ratio of migraine development. This was significant among all subgroups, independent of age, sex, and other comorbidities. There was no difference in the presence of aura associated with migraine.

As we noted above, the concept of migraine triggers is overall poorly understood. This is even more the case when it comes to historical exposures. Although the use of PPI medications appears to be associated with the occurrence of migraine in this population, these medications are necessary in many instances, including in patients with severe gastritis and gastroesophageal reflux refractory to diet changes. It remains to be seen precisely how PPI medications would potentially lead to a higher incidence of migraine.

Among many of the triggers discussed, specific foods are commonly thought to be associated with migraine. Although there is scant evidence for a specific diet to improve migraine frequency, many patients are very interested in potential dietary changes that may help them. Prior studies and reviews have looked at gluten-free, dairy-free, low-carbohydrate, low-tyramine, and elimination diets — all of which were not associated with a significant improvement in migraine frequency or severity. Bakıran and colleagues sought to investigate an antioxidant-rich diet that included polyphenols and carotenoids — substances that may improve systemic inflammation, glucose metabolism, and oxidative stress.

Phytochemical-rich foods include fruits and vegetables (excluding potatoes) as well as nuts, whole grains, pulses, and olive oil. The phytochemical index is a tool used by dietitians and nutritionists to assess the phytochemical content in a diet.

A total of 90 patients who had a diagnosis of episodic migraine by a neurologist were enrolled. Individuals were excluded if they had a body mass index > 40 or < 18 or had other significant chronic comorbidities, such as hypertension, diabetes, hepatic or renal disease, or other neurologic conditions. Participants filled out a headache diary over 3 months; the Migraine Disability Assessment (MIDAS) questionnaire was also followed in order to assess migraine-related disability. Diet quality was cataloged as per patient records; patients also filled out a 3-day nonconsecutive food diary. This information was added to a food software program that calculated specific nutrients, including the phytochemical index.

Participants were divided into groups with good diet quality and poor diet quality based on their phytochemical index. No differences were seen in migraine frequency or disability between these groups, although mean attack duration was lower in those with poor diet quality. Severity was noted to be higher in those with poor diet quality; 75% of participants with poor diet quality experienced severe attacks.

Overall, the results of this study are very mixed. Participants on the recommended high phytochemical diet were seen to have lower severity of migraine but a prolonged duration of attack. There also was no correlation between this diet and either frequency or disability. This was a small study, and further research should focus on this among other diet changes that have the possibility to improve the quality of life of people with migraine.

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