Migraines are headaches so severe that the World Health Organisation regards them as a form of temporary disability. A throbbing, often unilateral headache lasts from several hours to days and may be accompanied by nausea or a combination of photophobia and phonophobia. In ~20% of cases it is preceded by an aura. Estimated to afflict 15% of Australians, migraines vary considerably in characteristics but are identifiable by internationally classified criteria. The causes of migraine are thought to include both cerebrovascular and neuronal mechanisms to which individuals are genetically or hormonally predisposed. Women are 2-3 times as susceptible as men, particularly during menstruation and perimenopausally, when migraine without aura may result from sudden changes in circulating estrogen, other hormones or prostaglandins. Hormone replacement therapy or phytoestrogen supplementation may help in some cases, although the evidence is weak and mechanisms are unclear. 

Supported by an HMRI grant, we have pioneered research into the effects of resveratrol, a phytoestrogen, on brain function and, in a recent discovery (patent pending), have observed mood and cognitive benefits in postmenopausal women that are linked to improvements of circulatory function in the brain assessed by transcranial Doppler ultrasound examination of cerebral arteries. We have shown that resveratrol acts by enhancing endothelial vasodilator function, which has led others to suggest that resveratrol in red wine may be a cause of migraine. However, biogenic amines and nitrite sources in foods and wine which are thought to trigger migraines act directly on arterial smooth muscle, not indirectly through the endothelium. We have now conducted four intervention trials of resveratrol and have never recorded a single incidence of migraine. Indeed, we hypothesise that resveratrol, by facilitating the regulation of arterial tone, may suppress acute vasomotor changes associated with migraine and alleviate symptoms. 

We now seek to extend our groundbreaking research on cerebrovascular and cognitive benefits of resveratrol in postmenopausal women by examining, for the first time, its potential protective effects in women of reproductive age, about 40% of whom suffer migraine. We will evaluate prevalence and severity of headaches and migraine initially then after taking resveratrol both acutely and chronically (twice daily through three menstrual cycles). At each stage, we will evaluate static and dynamic measures of cerebrovascular function.  We anticipate that 1) neither acute or chronic resveratrol administration will cause migraine; 2) chronic treatment will suppress migraine incidence in susceptible women; 3) this benefit will be associated with improved cerebrovascular responsiveness to both physiological and cognitive stimuli assessed bilaterally.

The HMRI grant will be used to seed this project and by supporting the initial phase comprising a baseline comparison of the abovementioned outcome measures in migraineurs versus non-migraineurs. We will also obtain DNA from baseline blood samples for genotypic profiling by expert collaborators at the QUT which will enable us to assess the relative importance of vascular and neuronal mechanisms predisposing women to menstrual migraine. We expect this fundamental evidence will enable us to secure the support of industry partners to evaluate the potentially protective role of resveratrol in migraine.

Researchers 

Prof Peter Howe, Dr Rachel Wong, Prof Lyn Griffiths

Research Area 
Project type 
Project Grant
Year of funding 
2017