Migraines are a complex neurological condition that can be triggered by a variety of factors, including changes in metabolite levels. Metabolites are small molecules that are produced as a result of various chemical processes in the body, such as digestion, energy production, and cellular metabolism.
Migraines are a headache and a hip pocket pain, but newly discovered genetic causes by QUT researchers could pave the way for new preventative drugs and therapies.
Professor Dale Nyholt and his Ph.D. students Hamzeh Tanha and Anita Sathyanarayanan from the QUT Centre for Genomics and Personalised Health published the results of their genetic analyses in The American Journal of Human Genetics.
Professor Nyholt said the team identified causal genetic links to three blood metabolite levels that increase migraine risk:
- lower levels of DHA, an omega-3 known to reduce inflammation
- higher levels of LPE(20:4), a chemical that blocks an anti-inflammatory molecule
- lower levels of a third, currently uncharacterized metabolite, named X-11315.
Fatty acids are composed of more complex lipids that aid in cell signaling, cell membrane composition, and gene expression, all of which influence disease risk. Lower DHA levels are linked to inflammation, cardiovascular and brain disorders such as depression, all of which are linked to migraine risk.
Professor Dale Nyholt
Professor Nyholt believes that future research and clinical trials could target these genetic links to develop and test compounds that influence metabolite levels and prevent migraine. He stated that migraine is estimated to cost the Australian economy $35.7 billion per year and that current treatments fail up to 50% of migraine patients.
“Observed relationships between genetic factors influencing blood metabolite levels and genetic risk for migraine suggest an alteration of metabolites in migraine patients,” Professor Nyholt said.
Metabolites are substances made or used when the body breaks down food, drugs, or chemicals during metabolism. “Variations in blood levels of metabolites can be due to diet, lifestyle, and genetics, but they are easy to measure and may be modified using diet planning and supplementation,” Professor Nyholt said.
Professor Nyholt said people with migraine had higher levels of shorter-length fatty acids except for docosahexaenoic acid (DHA), a very long-chain omega-3 that protects against migraine.
“Fatty acids are composed of more complex lipids that aid in cell signaling, cell membrane composition, and gene expression, all of which influence disease risk,” he explained. “Lower DHA levels are linked to inflammation, cardiovascular and brain disorders such as depression, all of which are linked to migraine risk.”
According to Professor Nyholt, LPE(20:4) is a chemical compound that inhibits the production of an anti-inflammatory molecule known as anandamide. “If LPE(20:4) is controlled to allow more anandamide to be produced to reduce inflammation, this could potentially prevent migraine,” he explained.
Lower blood levels of a third metabolite, X-11315, increased the risk of migraine, according to Professor Nyholt, and characterizing it is an area of future research.
Overall, while alterations in metabolite levels can contribute to the development of migraines, the exact mechanisms involved are complex and not fully understood. Further research is needed to better understand the role of metabolites in migraine pathogenesis and to develop more effective treatments for this debilitating condition.
