Abstract
Introduction:
Migraine is a common type of headache, but its pathogenesis is still not fully understood. Triggering factors may vary in migraine patients with a particular importance of certain food intake. In this study, the efficacy of limiting certain migraine- triggering foods in the prevention of migraine attacks was investigated.
Methods:
Patients diagnosed with migraine without aura according to the International Classification of Headaches were enrolled. Fifty migraine patients stating that migraine attack started after the intake of certain foods were evaluated. The patients were randomly divided into 2 groups. The migraine-triggering foods identified by the patients were excluded from the diet in both groups 1 (n=25) and 2 (n=25). Monthly attack frequency, attack duration, and attack severity (using the visual analogue scale) were recorded before starting the diet restriction and 2 months after the diet restriction. Diet restriction was relaxed in group 1 after the second month and continued in group 2. In the fourth month, the monthly attack frequency, attack duration, and attack severity (using the visual analogue scale) were determined in both groups.
Results:
A total of 50 patients comprising 9 males and 41 females were evaluated in this study. In both the groups, in the second month after diet implementation, monthly attack frequency, attack duration, and attack severity were found to have decreased to a statistically significant extent compared to those in the period before diet implementation [group 1 (p=0.011, p=0.041, and p=0.003, respectively) and group 2 (p=0.015, p=0.037, and p=0.003, respectively)]. In the evaluation in the fourth month, it was observed that this significant decrease was maintained only in group 2.
Conclusion:
The results of the study reveal that if migraine-triggering foods are identified by migraine patients, restricting their intake can be an effective and reliable method to reduce migraine attacks.
Keywords: Migraine, headache, food, diet, elimination
INTRODUCTION
The pathophysiology of migraine, which is a primary headache disorder, is still not fully understood. Migraine attacks emerge with various features such as autonomic, gastrointestinal, and neurological symptoms. Symptoms such as increasing desire to consume some foods, mental slowdown, sleepiness, difficulty in concentrating, tiredness, and uneasiness occur primarily in the premonitory phase (prodrome) and can also be seen in the post-headache phase. Migraine is a common type of trigeminovascular pain that negatively affects the activities of daily living of individuals and has a high social impact. Migraine appears more often in the first three decades with a female preponderance that is based on hormonal changes (1,2,3,4,5).
Many factors triggering migraine attacks have been identified. The commonly reported ones include environmental factors, menstruation, sleep disorders, changing stress levels, changes in the air, smells, and foods (6,7,8,9). There are non-pharmacological therapy approaches for migraine treatment, such as medical treatment, psychotherapy, biofeedback, and cognitive behavior treatment. On the other hand, pharmacological treatment is used for acute attacks and as a prophylactic measure. Although simple analgesics, non-steroid anti-inflammatory agents, ergot alkaloids, triptans, and opioids are used to treat acute attacks, propranolol, metoprolol, flunarizine, amitriptyline, valproic acid, topiramate, and melatonin are preferred for the prophylactic treatment. The side-effect profile of the drugs used in the acute attack and prophylactic treatment is quite wide. Apart from their side effects, they interact with drugs in a potentially dangerous way and new treatments are needed (4,5,10,11,12).
It has been discussed for years whether food factors play a triggering role in migraines, and the first few studies on this issue reported that restricting the intake of some foods is effective in preventing migraine attacks and symptoms. Although some foods are known to be triggering in migraine patients, this issue is still being discussed (13,14). The objective of this study was to investigate whether restricting the intake of foods that trigger migraine attacks prevents such attacks.
METHODS
The patients who were diagnosed with migraine without aura according to the International Classification of Headache Disorders 2004 were included in this study (15). Patients, with normal physical and neurological examinations, who were aged between 18 and 60 years, and who had a migraine attack frequency of 4 or more times a month were consecutively selected. Patients with secondary headaches were excluded. In case of patients using prophylactic medication, on admission, the medication was not changed during the study period. According to the International Classification of Headache Disorders 2004, the following patients were excluded from the study: ones with medication overuse headache, who started therapy in addition to their current migraine therapy in 6 months before the beginning period of the study, who underwent the Botulinum Neurotoxin Type A treatment for a medical purpose in 6 months before the beginning period of the study, who underwent non-pharmacologic treatment, who had other primary headache history apart from migraine, who had a malignancy history and had undergone cranial surgery, who were pregnant or in the breast-feeding period, who had uncontrolled hypertension, who had uncontrolled diabetes mellitus, who had suffered chronic liver failure, who had suffered chronic renal failure, who had suffered congestive heart failure, who had hypophyseal and hypothalamic dysfunction, who had consumed 500 mg/day or more caffeine in the last 1 month, and who had a major psychiatric disorder.
According to the inclusion and exclusion criteria of the study, a total of 57 patients comprising 10 males and 47 females among 247 migraine patients evaluated and whose migraine attacks were determined to be related to the intake of certain foods by implementing the food sensitivity questionnaire form (Table 1) in migraine patients were included in the study. Informed consent was obtained from all participants. Examining 1-month headache diaries of all patients before treatment, the monthly attack frequency, attack duration (hourly), and pain severity (using the visual analogue scale) were recorded. The patients were randomly divided into 2 groups. The identified triggering foods were excluded from the diet of the patients in groups 1 (n=29) and 2 (n=28). Because 4 patients in group 1 and 3 patients in group 2 could not maintain the inclusion criteria during the study, the study was completed with 50 patients. Before diet implementation and in the second month after diet implementation, the monthly attack frequency, attack duration (hourly), and attack severity (using the visual analogue scale) were recorded. After the second month, the diet restriction was relaxed in group 1 patients but continued in group 2 patients. In the fourth month, the monthly attack frequency, attack duration (hourly), and attack severity (using the visual analogue scale) were recorded in both groups. All data were obtained by evaluating headache diaries.
Table 1.
Food sensitivity questionnaire
| Veal | Cabbage |
|---|---|
| Lamb | Cauliflower |
| Turkey meat | Broccoli |
| Fowl | Artichoke |
| Chicken | Apple |
| Sardine | Pear |
| Salmon | Mandarin |
| Shrimp | Orange |
| Oyster | Plum |
| Anchovy | Banana |
| Tuna fish | Apricot |
| Sujuk | Grape |
| Sausage | Raisin |
| Salami | Strawberry |
| Cows’ | milk Kiwi |
| Goat’s milk | Melon |
| Yoghurt | Pine apple |
| Butter | Mango |
| Cheese | Avocado |
| Cream cheese | Date |
| Parmesan cheese | Pumpkin |
| Kosher cheese | Coconut |
| Mozzarella cheese | Huckleberry |
| Roquefort cheese | Mushroom |
| Egg | Olive |
| Honeydew honey | Sesame |
| Flower honey | Thyme |
| Thyme honey | Cumin |
| Wheat | Curry powder |
| Rice | Clove |
| Lentil | Saffron |
| Corn | Starch |
| Oat | Vanilla |
| Soy | Ginger |
| Potato | Carob |
| Onion | Maple Syrup |
| Garlic | Sunflower seed |
| Tomato | Nut |
| Pepper | Peanut |
| Cucumber | Almond |
| Carrot | Walnut |
| Radish | Chocolate |
| Lemon | Pickle |
| Parsley | Tea |
| Mint | Turkish coffee |
| Dill | Nescafe |
| Garden Rocket | Sage tea |
| Eggplant | Fennel |
| Zucchini | Fruit juice |
| Leek | Alcohol |
| Other foods : |
Statistical Analysis
Data analysis was performed using the Statistical Packages for the Social Sciences (SPSS Inc; Chicago, IL, USA) for Windows 15.0 package. Descriptive statistics were shown as a mean Å} standard deviation for continuous variables and as case number and percentage for nominal variables. Whether the distribution of continuous variables was near normal was investigated using the Kolmogorov–Smirnov test. In comparison with the pre-treatment, whether statistically significant changes occurred in the second and fourth months after treatment were compared using the Wilcoxon signed-rank test. The differences between groups were examined using the Mann–Whitney U test. Operating power was found to be 80%. Results showing p<0.05 were accepted to be statistically significant.
RESULTS
In this study, 247 migraine patients were evaluated, and it was completed with 50 patients. The foods triggering migraine attacks were identified (Table 2). The average age of the patients was 36.28 years in group 1 and 36.48 years in group 2. There were 21 (84%) female and 4 (16%) male patients in group 1 and 20 (80%) female and 5 (20%) male patients in group 2. There was no statistically significant difference between groups with regard to the average age and distribution of women and men (p=0.969 and p=0.987, respectively).
Table 2.
Foods identified to trigger migraine attacks
| Type of food | The number of people affected by the food | ||
|---|---|---|---|
| Group 1 | Group 2 | Comparison of groups, p value* | |
| Wheat | 13 (52%) | 14 (56%) | 0.8125 |
| Orange | 10 (40%) | 12 (48%) | 0.6281 |
| Egg | 11 (44%) | 9 (36%) | 0.6274 |
| Nescafe | 9 (36%) | 8 (32%) | 0.8115 |
| Cheese | 9 (36%) | 7 (28%) | 0.6257 |
| Chocolate | 7 (28%) | 7 (28%) | 0.9920 |
| Milk | 7 (28%) | 8 (32%) | 0.8111 |
| Sujuk | 6 (24%) | 7 (28%) | 0.8104 |
| Sugar (beet) | 6 (24%) | 6 (24%) | 0.9920 |
| Red Meat | 6 (24%) | 5 (20%) | 0.8094 |
| Pickle | 6 (24%) | 5 (20%) | 0.8094 |
| Alcohol | 5 (20%) | 5 (20%) | 0.9220 |
| Mushroom | 4 (16%) | 5 (20%) | 0.8087 |
| Corn | 3 (12%) | 4 (16%) | 0.8076 |
| Tea | 3 (12%) | 3(12%) | 0.9919 |
| Onion | 2 (8%) | 1 (4%) | 0.8045 |
| Garlic | 1 (4%) | 1 (4%) | 0.9917 |
Mann–Whitney U test (nonparametric test). If p value is >0.05, the difference between the medians is not significant.
Although there was a statistically significant decrease in the monthly attack frequency, attack duration, and attack severity in the second month after treatment compared to that during pre-treatment in group 1 (p=0.011, p=0.041, and p=0.003, respectively), there was no statistically significant decrease in the monthly attack frequency, attack duration, and attack severity values in the fourth month after treatment compared to that during pre-treatment in group 1 (p=0.426, p=0.758, and p=0.128, respectively). There was a statistically significant decrease in the monthly attack frequency, attack duration, and attack severity in the second and fourth months after treatment compared to those during pre-treatment in group 2 (p=0.015, p=0.037, and p=0.003 and p=0.007, p=0.022, and p=0.003, respectively) (Table 3).
Table 3.
The evaluation of the changes in clinical measurements before and after treatment in groups and between groups
| Group 1 | Group 2 | Group 1 vs. Group 2 | |||
|---|---|---|---|---|---|
| Mean±SD | pa | Mean±SD | pb | pc | |
| VAS | 13 (52%) | 14 (56%) | 0.8125 | ||
| Beginning | 89.80±5.7 | 90.20±8.5 | 0.517 | ||
| 2 months later | 72.80±20.9 | 0.003* α | 72.20±19.9 | 0.003* α | 0.868 |
| 4 months later | 86.80±9.6 | 0.128 β | 71.40±20.1 | 0.003* β | 0.006* |
| Number of attacks | 9 (36%) | 7 (28%) | 0.6257 | ||
| Beginning | 6.08±1.7 | 5.96±1.7 | 0.759 | ||
| 2 months later | 4.84±1.9 | 0.011* α | 4.68±1.9 | 0.015* α | 0.806 |
| 4 months later | 5.96±1.7 | 0.426 β | 4.64±1.8 | 0.007* β | 0.013* |
| Pain duration | 6 (24%) | 6 (24%) | 0.9920 | ||
| Beginning | 29.44±21.8 | 30.56±22.3 | 0.953 | ||
| 2 months later | 22. 2±15.2 | 0.041* α | 23.52±18.1 | 0.037* α | 0.829 |
| 4 months later | 28.96±20.0 | 0.758 β | 22.88±18.4 | 0.022* β | 0.138 |
Paired test (Wilcoxon) ffor comparisons in Group 1 between pre-treatment (beginning) and post-treatment (2 and 4 months later),
Paired test (Wilcoxon) for comparisons in Group 2 between pre-treatment (beginning) and post-treatment (2 and 4 months later),
Unpaired test (Mann-Whitney U test) for comparisons of the changes between Group 1 and 2, VAS: visual analog scale; SD: standard deviation
Comparing group 1 and group 2, the decrease in both groups was identified to be proportionately similar in terms of the monthly attack frequency, attack duration, and attack severity values in the second month. It was statistically insignificant (p=0.806, p=0.829, and p=0.868, respectively). Although the proportional decrease in the attack frequency and attack severity was observed to be statistically significant in group 2 in the fourth month compared to group 1 (p=0.013 and p=0.006, respectively), the proportional decrease in pain duration was statistically insignificant (p=0.138) (Table 3).
DISCUSSION
According to the findings of the study, more than one triggering factors related to food were identified for all the patients. This situation was observed in approximately 1/5 patients with migraine. The foods identified as triggering were restricted from the diet of all patients, and in the second month, migraine attacks and symptoms of all patients decreased. Food restrictions applied to group 1 were relaxed in the second month to test the effectiveness of this method. The patients continued their diet as it was before the implementation, and the well-being was observed to continue in this group. On the other hand, food restrictions were continued in group 2. The restrictions were found to be effective in decreasing the attack frequency, attack duration (hour), and attack severity of migraine after treatment at the end of the fourth month compared to that during the pre-treatment and that in group 1.
In this study, the elimination of foods identified as triggering factors in migraine patients gave good results in reducing migraine attacks and symptoms. In recent studies, the importance of food intolerance and food sensitivity in many painful cases, such as primary headaches, especially migraine, were concentrated upon and treatment strategies were developed. Treatment strategies were the methods used to prevent food restriction and other triggering factors in the treatment of migraine and other primary headaches (16).
In the study conducted by Grant (16), the relationship between food allergies and migraine was examined, and the foods causing common reactions were excluded from the normal diet of 60 migraine patients for 5 days. A significant decrease was detected in the monthly number of headaches and full painlessness was observed in 85% of the patients. It was stated that immunological and non-immunological mechanisms could play a role in migraine pathogenesis resulting from food intolerance. Egger et al. (17) reported in their double-blind controlled studies including 88 children that there was a serious decrease in migraine attacks using an oligoantigenic diet.
In their prospective studies, including 61 episodic and chronic migraine patients and completed with 39 patients, Rees et al. (18) reported what the decrease in migraine attacks was, with a 6-point scale (0=no benefit, 5=high benefit), when they excluded the foods with IgG increases by monitoring serum food-specific IgG levels of the patients within a 2-month period. At the end of the second month, 38.2% of the patients indicated a serious benefit (4–5 points) in terms of migraine symptoms, 32.4% of the patients saw few to no benefit (0–1 points). When they started their normal diet again, a serious increase in strong migraine attacks was observed in 26.9% of the patients.
In their randomized double-blind studies, including 35 patients diagnosed with migraine without aura, Alpay et al. (19) studied the IgG levels developed against 266 food antigens after 6-weeks of normal diet using the ELISA method, and reported a decrease in the number of painful days, attack number, and rate of drug use (30% decrease in the number of attacks, 50% decrease in the number of painful days) after 6-weeks since they had excluded foods with high IgG levels from the diet; but, they reported no change in attack severity and attack duration. After a 2-week normal diet, the patients were given a provocative diet generating high IgG levels, and all the parameters of the patients during the provocative diet were at similar levels with the base values. Thirty patients completed the study. It was stated that diet restrictions based on IgG antibodies could be used as an effective strategy to minimalize migraine attacks (especially for the attacks resistant to therapy) (19).
Mitchell et al. (20) divided 167 patients with migraine and intolerance to one or more foods into 2 groups; they gave a normal diet to one group and gave a diet to another group created by excluding the intolerant foods as observed with the ELISA method. While a significant decrease was detected in the number of migraine pains in the fourth week, no significant decrease (as in the fourth week) was observed in the 12th week. In these studies, the elimination of the foods identified as triggering factors in migraine was used as a treatment method, and it was observed that variable results related to its effectiveness were obtained (20).
In this study, a wide food intolerance evaluation was performed with the food questionnaire form including foods triggering migraine attacks and other triggering foods apart from them, without using the ELISA method. The antibodies for a specific number of foods were determined with ELISA methods. The food questionnaire form enables evaluation of a larger number of foods. The treatment efficacy obtained with diet restriction applied to the patients as evaluated with a food questionnaire form was similar to the treatment efficacy obtained from food restriction with food intolerance identified using high-cost methods such as ELISA.
As a result, some foods can both show individual differences and trigger migraine attacks. When personal food triggers are determined, restricting the intake of these foods contributes to the prevention and minimization of migraine attacks. As detected in group 2 in this study, an effective response obtained with continuing the diet implementation is possible over the long-term. Results show that this method can be used as an additional strategy in migraine prevention treatment and decreasing symptoms. Randomized, double-blind, placebo-controlled, and long-followed studies that include a large number of patients are necessary to accurately reveal the efficacy and power of this strategy in migraine treatment.
Footnotes
Ethics Committee Approval: Ethics committee approval was received for this study from the ethics committee of Gülhane Military Medical Academy.
Informed Consent: Written informed consent was obtained from patients who participated in this study.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept - AÖÖ, ÖK; Design - AÖÖ, ÖK; Supervision - AÖÖ, ÖK; Resource - AÖÖ, ÖK; Materials - AÖÖ, ÖK; Data Collection and/ or Processing - AÖÖ, ÖK; Analysis and/or Interpretation - AÖÖ, ÖK; Literature Search - AÖÖ, ÖK AÖ; Writing - AÖÖ, ÖK AÖ; Critical Reviews - AÖÖ, ÖK AÖ.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study has received no financial support.
REFERENCES
- 1.Bussone G. Pathophysiology of migraine. Neurol Sci. 2004;25(Suppl 3):S239–41. doi: 10.1007/s10072-004-0295-3. [DOI] [PubMed] [Google Scholar]
- 2.Ferrari MD. Migraine. Lancet. 1998;351:1043–1051. doi: 10.1016/S0140-6736(97)11370-8. [DOI] [PubMed] [Google Scholar]
- 3.Martin VT, Behbehani M. Ovarian hormones and migraine headache:Understanding mechanisms and pathogenesis-part 1. Headache. 2006;46:3–23. doi: 10.1111/j.1526-4610.2006.00309.x. [DOI] [PubMed] [Google Scholar]
- 4.Silberstein SD, Sapel JR, Freitag FG. Migraine:diagnosis and treatment. In: Silberstein SD, Lipton RB, Dalessio DJ, editors. Wolff's headache. 7th ed. Oxford university pres; 2001. pp. 201–203. [Google Scholar]
- 5.Karada ş, Odabaşı Z. An Open-Label Clinical Study on the Efficacy of Melatonin Prophylaxis in Migraine:A Preliminary Report. Arch Neuropsychiatry. 2012;49:44–47. [Google Scholar]
- 6.Kelman L. The triggers or precipitants of the acute migraine attack. Cephalalgia. 2007;27:394–402. doi: 10.1111/j.1468-2982.2007.01303.x. [DOI] [PubMed] [Google Scholar]
- 7.Martin PR, Reece J, Forsyth M. Noise as a trigger for headaches:relationship between exposure and sensitivity. Headache. 2006;46:962–972. doi: 10.1111/j.1526-4610.2006.00468.x. [DOI] [PubMed] [Google Scholar]
- 8.Goadsby PJ. Recent advances in the diagnosis and management of migraine. BMJ. 2006;332:25–29. doi: 10.1136/bmj.332.7532.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Vaughan TR. The role of food in the pathogenesis of migraine headache. Clin Rev Allergy. 1994;12:167–180. doi: 10.1007/BF02802353. [DOI] [PubMed] [Google Scholar]
- 10.Loder E, Biondi D. General principles of migraine management:the changing role of prevention. Headache. 2005;45(Suppl 1):S33–47. doi: 10.1111/j.1526-4610.2005.4501002.x. [DOI] [PubMed] [Google Scholar]
- 11.Karadaş Inan LE, Ula ş, Odabaşi Z. Efficacy of local lidocaine application on anxiety and depression and its curative effect on patients with chronic tension-type headache. Eur Neurol. 2013;70:95–101. doi: 10.1159/000350619. [DOI] [PubMed] [Google Scholar]
- 12.Inan LE, Inan N, Karada ş, Gül HL, Erdemoğlu AK, Türkel Y, Akyol A. Greater occipital nerve blockade for the treatment of chronic migraine:a randomized, multicenter, double-blind, and placebo-controlled study. Acta Neurol Scand. 2015;132:270–277. doi: 10.1111/ane.12393. [DOI] [PubMed] [Google Scholar]
- 13.Van den Bergh V, Amery WK, Waelkens J. Trigger factors in migraine:a study conducted by the Belgian Migraine Society. Headache. 1987;27:191–196. doi: 10.1111/j.1526-4610.1987.hed2704191.x. [DOI] [PubMed] [Google Scholar]
- 14.Downing D, Davies S. “Allergy:Conventional and alternative concepts”. A critique of the Royal College of Physicians of London's report. Journal of Nutritional Medicine. 1992;3:331–349. [Google Scholar]
- 15.Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders:2nd edition. Cephalalgia. 2004;24(Suppl 1):1–160. doi: 10.1111/j.1468-2982.2003.00824.x. [DOI] [PubMed] [Google Scholar]
- 16.Grant EC. Food allergies and migraine. Lancet. 1979;1:966–9. doi: 10.1016/s0140-6736(79)91735-5. [DOI] [PubMed] [Google Scholar]
- 17.Egger J, Carter CM, Wilson J, Turner MW, Soothill JF. Is migraine food allergy?A double-blind controlled trial of oligoantigenic diet treatment. Lancet. 1983;2:865–869. doi: 10.1016/s0140-6736(83)90866-8. [DOI] [PubMed] [Google Scholar]
- 18.Rees T, Watson D, Lipscombe S, Speight H, Cousins P, Hardman G, Dowson AJ. A Prospective Audit of Food Intolerance among Migraine Patients in Primary Care Clinical Practice. Headache Care. 2005;2:105–110. [Google Scholar]
- 19.Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, Baykan B. Diet restriction in migraine, based on IgG against foods:a clinical double-blind, randomised, cross-over trial. Cephalalgia. 2010;30:829–837. doi: 10.1177/0333102410361404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Mitchell N, Hewitt CE, Jayakody S, Islam M, Adamson J, Watt I, Torgerson DJ. Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Nutr J. 2011;10:85. doi: 10.1186/1475-2891-10-85. [DOI] [PMC free article] [PubMed] [Google Scholar]