Nutrients to Improve Mitochondrial Function to Reduce Brain Energy Deficit and Oxidative Stress in Migraine

The mechanisms of migraine pathogenesis are not completely clear, but 31P-nuclear magnetic resonance studies revealed brain energy deficit in migraineurs. As glycolysis is the main process of energy production in the brain, mitochondria may play an important role in migraine pathogenesis. Nutrition is an important aspect of migraine pathogenesis, as many migraineurs report food-related products as migraine triggers. Apart from approved anti-migraine drugs, many vitamins and supplements are considered in migraine prevention and therapy, but without strong supportive evidence. In this review, we summarize and update information about nutrients that may be important for mitochondrial functions, energy production, oxidative stress, and that are related to migraine. Additionally, we present a brief overview of caffeine and alcohol, as they are often reported to have ambiguous effects in migraineurs. The nutrients that can be considered to supplement the diet to prevent and/or ameliorate migraine are riboflavin, thiamine, magnesium ions, niacin, carnitine, coenzyme Q10, melatonin, lipoic acid, pyridoxine, folate, and cobalamin. They can supplement a normal, healthy diet, which should be adjusted to individual needs determined mainly by the physiological constitution of an organism. The intake of caffeine and alcohol should be fine-tuned to the history of their use, as withdrawal of these agents in regular users may become a migraine trigger.

Old Habits Die Hard: Dietary Habits of Migraine Patients Challenge our Understanding of Dietary Triggers

Introduction: Migraine is a multifactorial neurological disorder with a major metabolic facet. Dietary approaches represent a commonly implemented lifestyle modifying strategy in headache clinics, yet the precise relationship between diet and migraine is still a matter of debate.Materials and Methods: The study consisted of two parts: first, in a cross-sectional design, we compared alimentary habits of migraine subjects and a control group of healthy volunteers. For the second part, we prospectively evaluated patients' daily consumption of various potentially migraine-triggering foods over a two-month period in order to examine their possible association with the occurrence of a migraine attack.Results: Most migraine patients reported avoiding at least one potentially migraine-triggering food/drink from their diet. In spite of that, with the sole exemption of citrus fruits, there were no statistically significant differences with respect to consumption patterns between migraine patients and controls (including wine and chocolate). Consumption frequency over time was proportional to intake of potentially migraine-triggering foods the day before a migraine attack.Conclusion: Our results underline the need of performing trigger challenges in order to avoid falling into an association-causation fallacy when attempting to identify possible alimentary migraine triggers. Indeed, it is possible that intake of certain foods like chocolate before attacks is a consequence of pre-attack cravings or a simple coincidence facilitated by previously established dietary habits.

Are some patient-perceived migraine triggers simply early manifestations of the attack?

Objective To study the agreement between self-reported trigger factors and early premonitory symptoms amongst a group of migraineurs in both spontaneous and pharmacologically provoked attacks. Methods Fifty-three subjects with migraine with and without aura, with ≤ 22 headache days/month, with spontaneous premonitory symptoms associated with migraine attacks were recruited nationally. A detailed history was taken by a study investigator to confirm diagnosis and extended phenotyping was performed to identify patient-reported triggers for migraine attacks, premonitory symptom phenotype and headache characteristics, using a standardised physician-administered questionnaire. The same subjects were exposed to a 0.5 mcg/kg/min nitroglycerin infusion over 20 min, to determine if similar migraine symptoms could be triggered. The triggered attacks were phenotyped in the same way as spontaneous ones. Percentage agreement and Cohen’s kappa measure of agreement were used to identify concordance between patient-reported triggers and the corresponding spontaneous and triggered premonitory symptoms. Percentage agreement of > 60% and/or a kappa value > 0.3 with P < 0.05 were considered significant. Results There was statistically significant agreement between perception of light as a migraine trigger and spontaneous premonitory photophobia; perception of sound as a trigger and triggered premonitory phonophobia; skipping meals as a trigger and spontaneous premonitory food cravings; and food triggers and spontaneous premonitory food cravings. There was good agreement between stress and premonitory triggered mood change. Conclusions At least some patient-reported triggers, such as light, sound, foods and skipping meals, may represent early brain manifestations of the premonitory phase of the migraine attack.

A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

Aim To use an animal model of migraine to test whether migraine headache might arise from a brainstem-trigeminal nucleus pathway. Methods We measured evoked and spontaneous activity of second-order trigeminovascular neurons in rats to test whether the activity of these neurons increased following the induction of cortical spreading depression or the imposition of light flash – two potential migraine triggers, or headache provokers. We then tested whether drugs that could activate, or inactivate, neurons of the nucleus raphe magnus or the periaqueductal gray matter, would affect any such increases selectively for the dura mater. Results Injection of sodium glutamate (a neuronal excitant) into these two nuclei selectively inhibited the responses of trigeminovascular second-order neurons to dura mater, but not to facial skin, stimulation. Injection of lignocaine (a local anaesthetic) into these nuclei selectively potentiated the responses of these neurons to dura, but not to facial skin, stimulation. Furthermore, injections into either nucleus of glutamate inhibited the increase in the ongoing discharge rate of these neurons produced by cortical spreading depression and light flash. Conclusions These results provide indirect evidence that trigeminovascular nociception may be tightly controlled by these two nuclei, whereas cutaneous trigeminal sensation may be less so. These nuclei may be relays of one possible brainstem-trigeminal pathway that could mediate migraine headache. Modification of neuronal activity in these two nuclei produced by migraine (headache) triggers may lie behind the pain of a migraine attack, at least in some cases.

Migraine trigger factors

In second-century Rome Galen of Pergamon suggested that migraine was triggered by yellow bile irritating the brain and meninges. Today atmospheric, nutritional, hormonal, physiological, and pharmacological triggers have been investigated in numerous clinical studies. A trigger for migraine is any factor that upon exposure or withdrawal can lead to the development of a migraine attack. According to the International Headache Society, trigger factors increase the probability of a migraine attack usually within 48 hours. Thus, a trigger factor is not regarded as a necessary causative agent in migraine, and therefore the presence of a trigger factor may not always induce an attack. The majority of studies on trigger factors are retrospective surveys hampered by recall bias, multiple significance errors, and questionnaire design, which may explain differences between studies. There are only a limited number of prospective studies, with conflicting results. In this chapter the present knowledge on migraine triggers is presented and described, highlighting both facts and myths. In addition, we will discuss the clinical implications of identifying triggers, and whether there is any rationale for avoidance of triggers, which has been a classic strategy, and recommendation for migraine treatment.

Circadian Variation of Migraine Attack Onset: A Review of Clinical Studies

Several studies suggested that migraine attack onset shows a circadian variation; however, there has not been an overview and synthesis of these findings. A PubMed search with keywords “migraine” AND “circadian” resulted in ten studies directly investigating this topic. Results of these studies mostly show that migraine attacks follow a monophasic 24-hour cyclic pattern with an early morning or late night peak while other studies reported an afternoon peak and also a biphasic 24-hour cycle of attacks. The identified studies showed methodological variation including sample size, inclusion of medication use, comorbidities, and night or shift workers which could have contributed to the contradictory results. Several theories emerged explaining the diurnal distribution of migraine attacks suggesting roles for different phenomena including a morning rise in cortisol levels, a possible hypothalamic dysfunction, a circadian variation of migraine triggers, sleep stages, and a potentially different setting of the circadian pacemaker among migraineurs. At the moment, most studies show an early morning or late night peak of migraine attack onset, but a significant amount of studies reveals contradictory results. Further studies should investigate the arising hypotheses to improve our understanding of the complex mechanism behind the circadian variation of migraine attacks that can shed light on new targets for migraine therapy.

Aerobic exercise training for migraine prevention: A trigger-based analysis

Background: Although aerobic exercise has been recommended for migraine management, no study has yet explored the effects of regular aerobic exercise on migraine triggers profile. Objective: To evaluate the effects of a 12-week aerobic exercise intervention on migraine triggers profile. Methods: We conducted a secondary, post hoc analysis of a randomized, controlled clinical trial. Triggers were recorded in a paper-based headache diary with a formal list including 8 common migraine triggers. Results: Twenty-five patients concluded the protocol and were analysed (exercise: n = 12; waitlist: n = 13). In the whole cohort, the most common triggers were stress/irritability (60 %), sleep deprivation (60 %), fasting (28 %), and foods (28 %). Most patients (52 %) had ≥ 3 triggers. The exercise group showed a higher baseline proportion of patients with ≥ 3 triggers (69 %) compared to waitlist group (25 %) (p = 0.041). After intervention period, there was no difference in the proportion of patients with ≥ 3 triggers between waitlist (16.6 %) and exercise (30 %) groups (p = 0.502). The exercise group showed greater numeric reductions (from group’s sum) than waitlist group for triggers stress/irritability (-14 vs -9), fatigue (-12 vs -6), and menstruation (-9 vs -5). This seemed to reflect the reduced number of attacks in the exercise group [mean (CI95 %): -2.5 (-3.7, -1), p = 0.002] vs waitlist [0.9 (2.4, -0.8), p = 0.341]. Conclusion: Tracking migraine triggers during exercise interventions may help to unravel specific clinical effects of regular exercise. Trial registration: #NCT01972607.

Clinical profile and triggers of migraine: an Indian perspective

Background: Primary headache disorders are among the most ubiquitous disorders affecting people worldwide. Migraine headache is one of the commonest syndromes of primary headache. There are few studies regarding clinical profile of migraine and migraine triggers in India. The objective this study was to study the gender, age distribution, frequency, severity of migraine attacks and other associated symptoms in patients presenting with migraine. To study in detail about triggers of migraine in present study population.Methods: About 222 patients who presented with history suggestive of migraine with or without aura defined according to International classification of headache disorders 2, fulfilling the study criteria were included. The study duration was fifteen months from March 2017 to May 2018. Details were collected using a proforma.Results: In this study, incidence of Migraine is higher in females (169,76%) than males (53, 24%). Majority of migraine patients were between age group of 18-29 years constituting about 77 patients (34.65%). Frequency of migraine more commonly observed was 3-4 per month was observed in 64 patients (29%) and chronic migraine was seen in 19 patients (8.4%). Migraine without aura is most common type observed in this study. Many patients had more than one trigger. More common triggers identified were sun exposure (85, 38.3%), sleep deprivation (83, 37.4%), stress (84, 37.8%) and travel (80, 36%).Conclusions: Migraine is more common in females than males with majority being in between age group of 18-29 years. Many had frequency of 3-4 episodes per month. Most had more than one trigger.