New theory about migraine triggers published

“Migraine breakthrough as scientists discover the process that triggers EVERY symptom – paving the way for a cure!” the Daily Mail over-optimistically reports. While a new theory about the cause(s) of migraines is plausible, it is also unproven.

The new study involved looking at previously published research about 22 things thought to trigger migraines. The researcher thought these triggers may all involve “oxidative stress”.

Read about things that trigger migraines. 

Oxidative stress could be seen as a form of “biological rust”. Oxidised molecules – free radicals – have the ability to interact with a range of other molecules inside cells. This can cause a kind of “wear and tear” damage to DNA, proteins, membranes and other cell structures.

It is thought to be a cause of many diseases and is also associated with the ageing process.

The researcher found that some of the most common and well-established migraine triggers, including alcohol, infection, stress and the sweetener aspartame, have been shown to cause oxidative stress in a number of ways. Other studies were found that indicated a number of potential triggers that might also cause oxidative stress in some circumstances, including dehydration, noise, disturbed sleep and chemicals found in certain foods like red wine and aged cheese.

If the theory holds true, it would open up the possibilities of treating migraines with antioxidants, which are drugs that help neutralise free radicals. However, this prospect needs more research.

Where did the story come from?

The study was carried out by a single researcher from the University of Maine. It had no external funding. 

The study was published in the peer-reviewed medical journal Headache on an open-access basis, so it’s free to read online.

The Daily Mail overstated the certainty of the findings, and the possibility of a cure, based on antioxidants, as a result. The researcher himself makes the point that “such a role for antioxidants has not been established and requires further research”.

The newspaper also exaggerated the number of studies included in the review, which was 261, not 2,000.

However, their report does rightly warn that antioxidant supplements may have health risks. For example, the antioxidant beta-carotene has been linked to an increased risk of lung cancer in smokers.

What kind of research was this?

This study was a narrative review and synthesis, which means the researcher trawled through existing research already published on migraine triggers, looking for information about whether they could cause oxidative stress. The results of this literature review are less reliable than those of a systematic review, as it does not include all relevant studies – just a few example studies for each trigger.

What did the research involve?

The researcher searched for papers about oxidative stress and a variety of reported triggers for migraines. Those of interest were picked out and the results summarised. The triggers were given a star rating from one to three, based on the amount and strength of evidence linking them to oxidative stress in the brain, and if so how that might happen.

The search was carried out using the terms “oxidative stress” and “brain” along with 22 triggers. Where possible, studies in living animals rather than studies done in test tubes in the laboratory were chosen. There is no good way to measure oxidative stress in living brains, meaning there are few human studies on this.

What were the basic results?

The researcher said the migraine triggers he reviewed “are capable of generating oxidative stress” through a number of mechanisms.

These included:

• causing the mitochondria (energy sources) in cells to work very hard
• poisoning cells
• changing the way the cell membranes worked
• inflaming nerve cells 
• overloading cells with calcium

All of these pathways could increase the production of oxidised chemicals, which can build up and cause oxidative stress.

There was greatest evidence that the following triggers can cause oxidative stress: alcohol, aspartame, infection and stress. The second group with some evidence included water deprivation (dehydration), monosodium glutamate, noise, weather and pollution, oxygen deprivation, a disrupted sleep cycle, “daily hassles” and the drug nitroglycerin. Less evidence was found for the food chemicals tyramine, beta-phenylethylamine, flavonoids and nitrates, or for the effect of a reduction in oestrogen levels, low blood glucose or mental overwork.

How did the researchers interpret the results?

The researcher said that: “underlying each of the traditional migraine triggers is their propensity to generate oxidative stress”. The researcher said the theory was “physiologically plausible”, unified the known triggers and “provides an explanation for how triggers can summate”, meaning why a migraine is more likely to be brought on by a number of triggers together than any one separately.

He said the theory “raises the possibility” of using antioxidants to prevent migraine, but warned that such a role “has not been established and requires further research”.

Conclusion

The study brings together evidence in support of a plausible theory about the causes of migraine. However, the evidence is very mixed in quality. Although the author says all triggers have the potential to cause oxidative stress, the link for some triggers is quite weak. For example, he says in the study it is unclear whether excessive mental work can cause oxidation, and that the role of oestrogen is not clear. Because of the difficulty of showing the effects of oxidative stress on the brain, most of the evidence is from animal studies on mice or rats, or studies of what happens to cells in test tubes or petri dishes, rather than in the human body.

Triggers for migraine have been mainly identified by people who experience them. This is not always a reliable way of identifying a cause of migraine, because it’s easy to muddle a trigger with an early symptom. For example, if you always get a migraine after eating chocolate, you might actually have a craving for sugar as an early migraine symptom, but you would probably identify the chocolate itself as a trigger. Also, the triggers studied here have many effects, in addition to any effect on oxidative stress. The author has not ruled out the possibility that other effects are the true cause of the migraine.

It’s an even bigger leap to say that certain antioxidants, such as vitamins, could prevent migraines.

We need further research to find out whether antioxidants could be beneficial for people with migraines.

In conclusion, the theory presented by the study is interesting and biologically plausible. It now needs to be proved (or disproved) by experimentation on the potential role of oxidative stress in triggering migraines. 

Links To The Headlines

Migraine breakthrough as scientists discover the process that triggers EVERY symptom – paving the way for a cure. Daily Mail, December 22 2015

Links To Science

Borkum JM. Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis. Headache. Published online December 7 2015