Research Review by Gary Maguire©

Date Posted:

September 2010

Study Title:

Diet restriction in migraine, based on IgG against foods: A clinical double-blind, randomized, cross-over trial


Alpay K, Ertas M, Orhan EK et al.

Author's Affiliations:

Department of Neurology, Anadolu Health Centre, Gebze, Kocaeli Turkey

Publication Information:

Cephalalgia 2010; 30(7): 829-837.

Background Information:

The exact pathophysiology of migraine headaches remains unclear. Many theories exist with varying degrees of supporting evidence, from different genetic mutations to profound evidence of the role of meningeal inflammation. There is also evidence that there are numerous environmental triggers as well as other factors that may trigger the occurrence of migraine attacks. Food is one such trigger.

However, as with most elements of migraine, the evidence is inconclusive with research findings vulnerable to the influence of the individuality of each migraine patient. Readers should bear this in mind as they continue reading here. Some foods commonly thought to trigger migraine attacks are: cheese, chocolate, wine or food additives (triclorogalactosucrose or aspartame). Diets with low-fat intake have also been shown to reduce headache frequency.

There is strong evidence that hidden food allergies are linked to triggering migraines with studies to date revealing the following:
  1. Migraine patients can improve when put on an elimination diet;
  2. IgE- specific food allergy has been shown to be related to migraine, supported by the success of individualized diets in controlling migraine attacks;
  3. Non-IgE antibody mediated mechanisms have also been proposed in food allergy;
  4. There is evidence of a pro-inflammatory effect of food intake; and
  5. There is preliminary evidence that IgG-based elimination diets can successfully control migraine without requiring medication. As a result of this IgG could be one of the markers to identify food which causes inflammation and could therefore cause migraines in predisposed individuals.
The focus of this study was to evaluate the efficacy of a diet based on specific total IgG antibodies against 266 food antigens in controlling migraine attacks (conducted as a double-blind, randomized, controlled, cross-over clinical trial).

Pertinent Results:

Thirty patients (28 females, 2 males; mean age 35 ± 10yrs) participated in the study with an average migraine history of 13 ± 10 years (so, long term migraine sufferers). All patients were using acute medication for migraine attacks with 50% using preventive medication.

  • From the IgG antibody tests there were 732 reactions against 266 food allergens (40% were low, 46% moderate, 10% high and 4% were very highly graded).
  • During the elimination diet period (compared to both the baseline period and provocation diet period): There was a statistically significant reduction in attack count, number of headache days, number of attacks with acute medication and total medication intake, while no significant change occurred between the provocation diet period and the baseline period. It was also noted that attack severity and attack duration did not change significantly between all three phases.
  • There was a significant reduction of migraines when comparing percentage differences from baseline, in the elimination diet period, attack count, number of headaches, number of attacks with acute medication and total medication intake compared to the provocation diet period.
  • Testing of the effect of order of diet consisted of dividing the two groups in to two subgroups (15 patients with elimination diet in the ‘first diet phase’ and 15 patients with elimination diet in the ‘second diet phase’).
  • Calculation differences were performed on the following: elimination diet period and the baseline, provocation diet period and baseline, provocation diet period and baseline and elimination diet period and provocation diet period for attack count, number of headache days, and number of attack with acute medication, total medication intake, median attack severity and mean attack duration for each subgroup.
  • Analysis of these parameters with the two subgroups did not show any significant difference in any of the comparisons, indicating that, whether the elimination diet was in the first diet phase or second diet phase, the order of elimination period had no significant effect on the outcome (calculations were also performed for preventative medicine usage and there were no significant change in parameters between preventative medicine users and non-users).
  • Calculations were also performed to determine if the patient showed at least a 30% reduction and at least a 50% reduction for attack count and number of headache days using elimination diet compared to provocation diet and to the baseline period.
  • Elimination and provocation phase comparisons (parameters of the number of headache days and attack count) revealed a reduction of ? 30% in 16 and 16 patients respectively, and reduction was found to be ? 50% in 7 and 6 patients, respectively.
  • When looking at the comparison between elimination and provocation phases, reduction was ? 30% in 15 and 12 patients, respectively, and reduction was determined to be ? 50% in 6 and 4 patients, respectively.

Clinical Application & Conclusions:

Due the effect of various foods as trigger mechanisms for migraine attacks a diet that is aimed at restriction of IgG antibodies might be an effective strategy in reducing the frequency of migraine attacks and could be implemented for therapy-resistant patients.

There is growing evidence that inflammation plays a role in the pathogenesis of migraine headaches, with gene-related peptide and nitric oxide as participants in this immune and inflammatory response mechanism (1).

Within the context of this current evidence, readers should keep in mind that some patients report that certain foods only trigger migraines in conjunction with stress or extended physical exercise (both of these trigger mechanisms cause the release of inflammatory cytokines).

If inflammation caused by food could create the pro-inflammatory milieu necessary for the induction of migraine headaches by other triggers, then the focus on inflammation induced by food requires the identification of a specific marker.

All IgG subclasses (except IgG4) lead to an inflammatory response when in contact with its respective antigen. The ideal tool to develop a dietary approach would then determine specific IgG subclasses within a larger number of foods, enabling a modification of nutritional habits in order to prevent chronic inflammation and onset of migraine headaches in sensitive patients. Such an approach would be quite advanced for the average manual medicine provider, so inter-professional collaboration may be necessary.

Study Methods:

The study was set up as a double-blind, randomized, controlled, cross-over clinical trial using patients (recruited from headache out-patient clinics) diagnosed with migraines without aura (utilizing the criteria of the International Classification of Headache Disorders, 2nd edition).

Inclusion criteria consisted of:
  1. having had at least 4 attacks and 4 headache days/month within the last few months;
  2. age 18-55 years;
  3. having been treated with acute attack medication only or with preventative medications (unchanged for at least 3 months); and
  4. the ability to understand an cooperate with the study requirements.
The study consisted of 3 main phases (baseline, first diet and second diet phase).
  1. The baseline consisted of: completion of a 6 week headache diary, monitoring their daily diet, and providing venous samples for detection of IgG antibodies against 266 food antigens.
  2. Phase one: Allocation was to either the randomization schedule either excluding (elimination diet) or including (provocation diet) specific foods. Following the end of the phase and turning in their diary patients were allowed to return to their usual diet (2 weeks without journaling).
  3. Phase two: Those on the elimination diet from the first phase were given a provocation diet for 6 weeks and vice versa. During this timeframe a headache diary was completed.
IgG antibodies against 266 food antigens were detected using a commercially available enzyme linked immunosorbant assay (ELISA) test with positive reactions rated as low, moderate or high (values above 7.5mg/l were considered positive).

Diets were arranged by IgG antibody results and assembled by a dietician who also educated patients about diet adherence. The elimination diet consisted of a defined panel of IgG-negative food and the provocation diet consisted of a panel of IgG-positive and IgG negative food necessary to comply with a balanced diet.

Study Strengths / Weaknesses:

The authors of the study accurately point out that due to a small sample size, caution should be taken when translating these results into daily practice. The strategy does provide an area of research where monitoring migraine patient’s diets, keeping a journal and being able to identify IgG antibodies may assist in the reduction of the frequency of migraine attacks. Further research is necessary to determine the mechanism of IgG positive, food-induced migraine and its relation to other triggers.

The study does provide a table of positive test results (frequent IgG positivity) food categories for those who may want to gain further understanding of food type trigger mechanisms. Additional information is also provided on identification of all 266 food allergens tested.

Additional References:

  1. Geppetti P et al. CGRP and migraine; neurogenic inflammation revisited. J. Headache Pain 2005; 6: 61-70.