ABSTRACT
The migraine headache is a disease related to the neurovascular system, which affects 10%–20% of people, worldwide. Recent evidences suggested a relation between thiamine status and migraine headaches. The current study was undertaken to assess dietary intake of the thiamine in migraine patients and to evaluate its association with the frequency of migraine attacks. In a case-control design, the current study was performed on 50 migraine patients and 50 healthy people, 20–60 years old in Isfahan, Iran, in 2017. Information about dietary intake was collected by Food frequency questionnaire and analyzed using the Nutritionist version 4 (N4) software (Tinuviel Software). Information about the history of disease was collected by demographic questionnaire. Analysis of covariance and independent t-test were used for data analysis and p value less than 0.05 was considered significant. Mean age, weight, height, and body mass index of participants were 35.1 ± 9.8 years, 65.3 ± 10.4 kg, 162.5 ± 8.4 cm, and 24.7 ± 4.0 kg/m2, respectively. Dietary intake of thiamine among the migraine patients was lower than that in the healthy participants (p < 0.001). Migraine patients with the high frequency attacks had significantly lower intake of thiamine compared with moderate frequency attacks group (p = 0.010), however, it was not significant after adjusting for energy intake (p = 0.410, p = 0.240). Dietary intake of thiamine in migraine patients was not significantly different in comparing with healthy subjects. In addition, no significant correlation between thiamine intake and the frequency of migraine attacks was observed.
-
Keywords: Diet; Thiamine; Migraine disorders; Frequency
INTRODUCTION
Migraine is known as a chronic disease related to brain neurovascular system [
1]. Migraine is estimated to be the third cause of disability, according to the Global Burden of Disease 2015, in individuals under the age of 50 [
2]. Also, migraine can increase the risk of nervous disorders, such as stroke, and lead to reduce the quality of life [
3,
4].
According to the International Headache Society (IHS) criteria, migraine has 2 subtypes due: migraine with aura and without aura that this classification is associated with the presence or absence of transient disturbance in motor function, visual, language, or sensory. However, the most migraine patients have migraine without aura [
5,
6]. One of the current symptoms of the migraine is recurrent headaches that may be followed by gastrointestinal disorders, like nausea and vomiting [
7,
8]. Also, these symptoms can be affected by environmental factors, like light and noise [
9].
The major mechanism about the pathophysiology of migraine is not completely clear, but studies showed that various factors, such as diet and lifestyle, may play an important role [
10,
11]. It seems the B vitamins group as an important part of diet affects clinical symptoms of the migraine [
12,
13].
According to previous studies, thiamine supplementation may lead to an improvement in migraine headaches in Wernicke-Korsakoff syndrome. Nausea, vomiting, and anorexia may contribute the lower intake of thiamine among migraine patients with headaches, this can describe the relation between migraine headaches and thiamine status.
Low thiamine intake leads to increased risk of the Wernicke-Korsakoff and frequent headaches [
14,
15,
16]. Thus, the relation between thiamine status and migraine headaches has suggested the necessity of study about dietary intake of the thiamine in migraine patients. Also, there are many studies related to the B vitamins group status and migraine headaches [
13,
17], but the studies about thiamine are limited. Thus, the main purpose of this study is to compare the dietary intake of thiamine in migraine patients and healthy people, and its relation to the frequency of migraine attacks.
MATERIALS AND METHODS
Based on the case-control design, current study was conducted on 50 migraine patients in Isfahan, Iran, in 2017. Patients were included based on: 1) Being in the range of 20 to 60 years; 2) Interested in participating in the study; 3) Suffering migraine; and 4) Not receiving drugs for certain diseases, such as stroke, renal, and heart diseases.
Confirmation of migraine diagnosis was carried out using the IHS criteria [
5] by an expert neurologist.
The inclusion criteria were as follows: 1) Having a migraine history since 4–5 years or more and recurrent migraine attacks for one year duration (at least 12 attacks per year); and 2) Having migraine attacks, when participating in the study. The frequency of migraine attacks was determined for each migraine patients. The high frequency of the migraine attacks was defined as more than 10 attacks per month [
18].
Control group included 50 healthy subjects, age and sex-matched to the patient group. The sample size was determined with the confidence level of 90 percent. In addition, this study was approved by the Institution Ethics Committee, of the Isfahan University of Medical Sciences (Ir. May. Rec. 1395.3.405) and consent form was signed by all participants.
Dietary assessment
Dietary intake of the participants was assessed by an expert Nutritionist, using a valid semi-quantitative 168-item food frequency questionnaire (FFQ) [
19]. Usual dietary intake was assessed using a validated 168-item semi-quantitative FFQ. A trained dietitian administered all the questionnaires. The questionnaire consisted of a list of foods with standard serving sizes commonly consumed by Iranians. Participants were asked to report their frequency of consumption of a given serving of each food item during the previous year on a daily (e.g., bread), weekly (e.g., rice, meat), or monthly (e.g., fish) basis. The reported frequency for each food item was then converted to a daily intake. Portion sizes of consumed foods were converted to gram using household measures. Total calorie and nutrients intakes were calculated using Nutritionist version 4 (N4) software (Tinuviel Software, Warrington, UK).
Data were analyzed by SPSS software (version 18;SPSS, Chicago, IL, USA). Independent sample t-test was used to compare thiamine intake between different groups, i.e., migraine patients and healthy subjects, or 2 migraine patients based on frequency of headache. Thiamine intake had been adjusted for energy intake, using analysis of covariance. The p value less than 0.05 was defined as statistically significant.
RESULTS
Fifty patients with migraine (12 men and 38 women) and fifty healthy people (12 men and 38 women), were enrolled in the study, as the case and control groups, respectively. Mean of the participants' age, weight, height, and body mass index was 35.1 ± 9.8 years, 65.3 ± 10.4 kg, 162.5 ± 8.4 cm, and 24.7 ± 4.0 kg/m2, respectively.
Dietary intake of the energy, thiamine, folate, and fat were significantly lower, among migraine patients than the healthy people (p < 0.001) (
Table 1). However, the intake of energy-adjusted thiamine was not significant between case and control groups (p = 0.410) (
Table 2).
Table 1 Demographic and dietary characteristics in migraine and healthy subjects
Table 1
|
Variables |
Migraine patients |
Healthy subjects |
p value |
|
Age, yr |
36.14 ± 9.80 |
34.00 ± 9.80 |
0.280 |
|
Weight, kg |
66.20 ± 10.50 |
64.30 ± 10.30 |
0.370 |
|
Height, cm |
162.46 ± 8.10 |
162.54 ± 8.85 |
0.960 |
|
Body mass index, kg/m2
|
25.00 ± 3.70 |
24.50 ± 4.30 |
0.500 |
|
Energy, kcal |
2,032.47 ± 656.86 |
2,479.99 ± 758.33 |
< 0.001 |
|
Thiamine, mg |
1.68 ± 0.60 |
2.10 ± 0.75 |
< 0.001 |
|
Carbohydrate, g |
311.95 ± 258.33 |
336.71 ± 100.91 |
0.530 |
|
Fat, g |
65.01 ± 31.01 |
88.42 ± 40.94 |
< 0.001*
|
|
Protein, g |
104.36 ± 57.49 |
113.94 ± 44.05 |
0.350 |
|
Riboflavin, mg |
2.19 ± 0.71 |
2.48 ± 0.91 |
0.080 |
|
Niacin, mg |
22.51 ± 6.88 |
24.70 ± 7.28 |
0.120 |
|
Pyridoxine, mg |
1.91 ± 0.57 |
2.17 ± 0.81 |
0.060 |
|
Folate, µg |
329.81 ± 137.35 |
429.13 ± 151.85 |
< 0.001*
|
|
Cobalamin, µg |
3.10 ± 2.38 |
2.80 ± 1.84 |
0.480 |
Table 2 Difference of dietary intake* between case and control group or according to the different frequency of headache attacks
Table 2
|
Variables |
Case-control group |
Migraine frequency groups |
|
Migraine |
Healthy |
F |
df |
p value†
|
Moderate frequency |
High frequency |
F |
df |
p value†
|
|
Thiamine, mg |
1.86 ± 0.05 |
1.92 ± 0.05 |
0.68 |
1.97 |
0.410 |
1.73 ± 0.07 |
1.58 ± 0.10 |
1.43 |
1.47 |
0.240 |
|
Carbohydrate, g |
343.50 ± 24.58 |
305.17 ± 24.58 |
1.16 |
1.97 |
0.280 |
337.20 ± 40.67 |
258.32 ± 136.55 |
1.11 |
1.47 |
0.290 |
|
Fat, g |
73.52 ± 3.54 |
79.91 ± 3.54 |
1.55 |
1.97 |
0.220 |
62.72 ± 4.40 |
69.86 ± 6.55 |
0.77 |
1.47 |
0.380 |
|
Protein, g |
114.68 ± 5.74 |
103.61 ± 5.74 |
1.77 |
1.97 |
0.190 |
106.40 ± 8.60 |
1.03 ± 12.80 |
0.16 |
1.47 |
0.690 |
|
Riboflavin, mg |
2.35 ± 0.10 |
2.33 ± 0.10 |
0.03 |
1.97 |
0.870 |
2.31 ± 0.11 |
1.95 ± 16.00 |
3.07 |
1.47 |
0.090 |
|
Niacin, mg |
23.97 ± 0.78 |
23.25 ± 0.78 |
0.40 |
1.97 |
0.530 |
23.11 ± 0.87 |
21.23 ± 1.30 |
1.39 |
1.47 |
0.240 |
|
Pyridoxine, mg |
2.08 ± 0.07 |
2.00 ± 0.07 |
0.60 |
1.97 |
0.440 |
1.97 ± 0.07 |
1.77 ± 0.10 |
2.35 |
1.47 |
0.130 |
|
Folate, µg |
362.73 ± 14.62 |
396.20 ± 14.62 |
2.50 |
1.97 |
0.120 |
343.71 ± 17.74 |
300.26 ± 26.40 |
1.77 |
1.47 |
0.190 |
|
Cobalamin, µg |
3.25 ± 0.30 |
2.66 ± 0.30 |
1.81 |
1.97 |
0.180 |
3.15 ± 0.42 |
3.00 ± 0.63 |
0.04 |
1.47 |
0.840 |
Patients with the high frequency of migraine attacks, showed significantly lower thiamine intake than the moderate frequency group (p = 0.010) (
Table 3), while intake of the energy-adjusted thiamine was not significantly different, between high and moderate frequency groups (p = 0.240) (
Table 2).
Table 3 Comparison of dietary intake in patients with the different frequency of headache attacks
Table 3
|
Variables |
Moderate frequency |
High frequency |
p value |
|
Energy, kcal |
2,179.51 ± 659.20 |
1,719.99 ± 439.35 |
0.020*
|
|
Thiamine, mg |
1.83 ± 0.60 |
1.36 ± 0.50 |
0.010*
|
|
Carbohydrate, g |
360.53 ± 298.30 |
208.72 ± 74.30 |
0.050 |
|
Fat, g |
67.12 ± 34.54 |
60.52 ± 22.03 |
0.490 |
|
Protein, g |
113.18 ± 60.20 |
85.62 ± 47.70 |
0.110 |
|
Riboflavin, mg |
2.37 ± 0.72 |
1.83 ± 0.55 |
0.010*
|
|
Niacin, mg |
24.13 ± 6.73 |
19.08 ± 6.05 |
0.010*
|
|
Pyridoxine, mg |
2.06 ± 0.55 |
1.60 ± 0.48 |
0.000*
|
|
Folate, µg |
362.98 ± 142.06 |
259.33 ± 97.13 |
0.010*
|
|
Cobalamin, µg |
3.16 ± 2.34 |
2.99 ± 2.53 |
0.820 |
DISCUSSION
The current study showed that mean of thiamine intake among migraine patients is lower than the healthy subjects.
Migraine is a complex disabling neurological disease, and is accounted as 19th reason of disability during life, based on The World Health Organization report [
20]. This disease imposes high health care cost to the patients, and has a substantial negative effect on the patient's quality of life [
21,
22].
The B vitamins group contains several substances that may help prevent or threat migraine. Regular supplementation may have additional benefits in lowering the incidence of migraine attacks [
23].
Vitamins also act as antioxidants and work effectively in oxidative stress to slow down the disease progression. B vitamins group is one of more concerns, however exact mechanism of thiamine deficiency in the pathogenesis of migraine is not clearly understood.
The etiology of migraine is multifactorial, with genetic components and environmental interactions considered to be the main causal factors. Some researchers postulate that deficits in mitochondrial energy reserves can cause migraine [
24].
At the other hand, some studies have shown an association of hyperhomocysteinemia with migraine as well as the roles of vitamins B
6, B
9, and B
12 in lowering the levels of homocysteine in patients with hyperhomocysteinemia [
12,
25,
26]. There is also evidence that riboflavin (vitamin B
2) reduces the frequency of migraine attacks [
24].
Thiamine helps the body produce cellular energy from food and is essential for the functioning of several enzymes in mitochondria, the cells power center. Despite the role of mitochondria in neural energy production, little direct research has been conducted on thiamine and migraine [
23].
Mean of thiamine intake was significantly different between patients with the moderate and high frequency of migraine attacks. However, the differences was not significant, after adjusting for energy.
In addition, one of the hypotheses related to thiamine-migraine association is a mitochondrial dysfunction theory. Thiamine, as an important coenzyme in energy production (Krebs cycle), in mitochondrial metabolism, may related to migraine disease. Mitochondrial dysfunction, leading to oxygen metabolism impairment may associate with migraine pathogenesis [
27]. Studies suggest that B vitamins group may involve in aerobic respiration reactions, which may relate to the migraine prophylaxis [
26,
28].
In addition, thiamine has an important role in neuronal cells. Thiamine gets involved in neuro degeneration preventing and its deficiency results in apoptosis and severe cellular deficit [
29,
30].
Few studies have investigated a relation between thiamine status and migraine headache. In the current study, we failed to find a significant difference between thiamine and energy intake, with the frequency of migraine attacks, while Prakash et al. [
16] reported 2 female patients with chronic migraine, having a low blood thiamine concentration, in which thiamine supplementation led to a migraine attacks frequency reduction. The interrelation between migraine and thiamine deficiency is unknown, however Prakash et al. [
16] suggested nausea, vomiting, and anorexia of migraine may lead to mild to moderate thiamine deficiency.
However similar studies, assessing other B vitamins group supplementation approved our results. Conflicting findings may be due to differences in daily dietary intake, physical activity, mental states, and genetic factors of the participants.
To support results of the previous studies, the low blood level of B vitamins group can be caused by the low food intake which occurs due to gastrointestinal disorders, such as vomiting and nausea, in migraine patients [
16].
Hyperhomocysteinemia is caused by abnormal methionine biosynthesis due to deficiencies in folate, vitamin B
12, and vitamin B
6. Also, Menon et al. [
31] showed that the supplementation of pyridoxine, folate and cobalamin could not be effective on the frequency of migraine attacks, while Lea et al. [
12] reported that the intake of pyridoxine, folate and cobalamin led to low frequency of the migraine attacks.
To the best of our knowledge this is the first case control study about dietary intake of thiamine in migraine patients in Iranian people. In addition, adjusting for the dietary intake of energy led to increasing reliability of results.
There are several limitations that should be taken into account, when interpreting our findings. First, the sample size was not particularly large, which may lead to insufficient power, to detect the thiamine-migraine association. Secondly, although thiamine intake was assessed by 168-item FFQ that was validated with the same population, recall bias cannot be excluded. Third, subjects were collected from a single hospital and the generalization of the findings is limited.
CONCLUSION
Our findings cannot suggest a significantly lower thiamine intake, among migraine patients, compared to the healthy people. The same conclusion was achieved, regarding patients with the high frequency of migraine attacks, compared to moderate group. Considering the safety, well-tolerated properties and cost-effectiveness of thiamine supplement, it is reasonable that more investigations should be conducted, before excluding thiamine supplementation as a potential efficient treatment for migraine. Randomized controlled trials are needed to prove this result.
NOTES
-
Conflict of Interest: The authors declare that they have no competing interests.
ACKNOWLEDGEMENTS
The current article is part of the Master Thesis, registered at Isfahan University of Medical Sciences with the code of 395405. We would like to thank all participants for their cooperation.
REFERENCES
- 1. Hougaard A, Amin FM, Christensen CE, Younis S, Wolfram F, Cramer SP, Larsson HB, Ashina M. Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura. Brain 2017;140:1633-1642.
- 2. Steiner TJ, Stovner LJ, Vos T. GBD 2015: migraine is the third cause of disability in under 50s. J Headache Pain 2016;17:104.
- 3. Inaloo S, Dehghani SM, Farzadi F, Haghighat M, Imanieh MH. A comparative study of celiac disease in children with migraine headache and a normal control group. Turk J Gastroenterol 2011;22:32-35.
- 4. Monteith TS, Gardener H, Rundek T, Elkind MS, Sacco RL. Migraine and risk of stroke in older adults: Northern Manhattan Study. Neurology 2015;85:715-721.
- 5. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013;33:629-808.
- 6. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8(Suppl 7):1-96.
- 7. Goadsby PJ, Lipton RB, Ferrari MD. Migraine--current understanding and treatment. N Engl J Med 2002;346:257-270.
- 8. Irwin S, Barmherzig R, Gelfand A. Recurrent gastrointestinal disturbance: abdominal migraine and cyclic vomiting syndrome. Curr Neurol Neurosci Rep 2017;17:21.
- 9. Mollaoğlu M. Trigger factors in migraine patients. J Health Psychol 2013;18:984-994.
- 10. Kowa H, Yasui K, Takeshima T, Urakami K, Sakai F, Nakashima K. The homozygous C677T mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for migraine. Am J Med Genet 2000;96:762-764.
- 11. Camboim Rockett F, Castro K, Rossoni de Oliveira V, da Silveira Perla A, Fagundes Chaves ML, Schweigert Perry ID. Perceived migraine triggers: do dietary factors play a role? Nutr Hosp 2012;27:483-489.
- 12. Lea R, Colson N, Quinlan S, Macmillan J, Griffiths L. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics 2009;19:422-428.
- 13. Menon S, Lea RA, Roy B, Hanna M, Wee S, Haupt LM, Oliver C, Griffiths LR. Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation. Pharmacogenet Genomics 2012;22:741-749.
- 14. Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007;6:442-455.
- 15. Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome: under-recognized and under-treated. Psychosomatics 2012;53:507-516.
- 16. Prakash S, Kumar Singh A, Rathore C. Chronic migraine responding to intravenous thiamine: a report of two cases. Headache 2016;56:1204-1209.
- 17. Gaul C, Diener HC, Danesch U. Migravent® Study Group. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. J Headache Pain 2015;16:516.
- 18. Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology 2001;56:S20-S28.
- 19. Hosseini Esfahani H, Asghari G, Mirmiran P, Azizi F. Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran Lipid and Glucose Study. J Epidemiol 2010;20:150-158.
- 20. Linde M, Steiner TJ, Chisholm D. Cost-effectiveness analysis of interventions for migraine in four low- and middle-income countries. J Headache Pain 2015;16:15.
- 21. Bloudek LM, Stokes M, Buse DC, Wilcox TK, Lipton RB, Goadsby PJ, Varon SF, Blumenfeld AM, Katsarava Z, Pascual J, Lanteri-Minet M, Cortelli P, Martelletti P. Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS). J Headache Pain 2012;13:361-378.
- 22. Taşkapilioğlu Ö, Karli N. Assessment of quality of life in migraine. Noro Psikiyatri Arsivi 2013;50:S60-S64.
- 23. Hickey S. The vitamin cure for migraine. Laguna Beach (CA): Basic Health Publications; 2010.
- 24. Shaik MM, Gan SH. Vitamin supplementation as possible prophylactic treatment against migraine with aura and menstrual migraine. BioMed Res Int 2015;2015:469529.
- 25. Di Rosa G, Attinà S, Spanò M, Ingegneri G, Sgrò DL, Pustorino G, Bonsignore M, Trapani-Lombardo V, Tortorella G. Efficacy of folic acid in children with migraine, hyperhomocysteinemia and MTHFR polymorphisms. Headache 2007;47:1342-1344.
- 26. Bianchi A, Salomone S, Caraci F, Pizza V, Bernardini R, D'Amato CC. Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine prophylaxis. Vitam Horm 2004;69:297-312.
- 27. Yee AJ, Schoenen J. Effectiveness of high-dose riboflavin in migraine prophylaxis. Neurology 1999;52:431-432.
- 28. Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G. High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre. Eur J Neurol 2004;11:475-477.
- 29. Bâ A. Metabolic and structural role of thiamine in nervous tissues. Cell Mol Neurobiol 2008;28:923-931.
- 30. Mkrtchyan G, Aleshin V, Parkhomenko Y, Kaehne T, Di Salvo ML, Parroni A, Contestabile R, Vovk A, Bettendorff L, Bunik V. Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis. Sci Rep 2015;5:12583.
- 31. Menon S, Nasir B, Avgan N, Ghassabian S, Oliver C, Lea R, Smith M, Griffiths L. The effect of 1 mg folic acid supplementation on clinical outcomes in female migraine with aura patients. J Headache Pain 2016;17:60.
