BBQ season is a time-honoured tradition, synonymous with sunny days, casual banter, ice-cold beers and hotdogs. Whilst a mouthwatering treat for some, hotdogs and the chemicals they contain can be a nightmare, sending a migraineur home with their head between their hands. New research suggests that it may not just be the chemicals in hotdogs that are responsible for the onset of migraines, but the tiny organisms living inside the body as well.

Certain foods, such as processed meats, leafy vegetables and chocolate and food additives consist of nitrate-containing compounds. These dietary nitrates, naturally occurring chemicals containing nitrogen and oxygen, significantly contribute to nitric oxide formation in the body, a chemical which has been linked to the development of migraines (1).

Produced by many cells in the body, nitric oxide is vital for blood vessel health, smooth muscle relaxation, immune system modulation, vasodilation and cell signaling just to name a few (2). As per the old adage, there can be too much of a good thing. Too much nitric oxide in the brain of a person sensitive to the chemical has been shown to induce to migraines (3).

For example, one of nitric oxide’s functions is to open veins wider, increasing blood flow and bringing in more oxygen. While great for most athletes, increased levels of nitric oxide seen after intense exercise might not be so great for those sensitive to the chemical, many of whom go onto suffer migraines shortly after their workout (4).

Another way nitric oxide is implicated in migraine is through the enzyme nitric oxide synthase which catalyses the production of nitric oxide. It’s been shown that inhibition of this enzyme for treatment of spontaneous migraine attacks is effective in 60% of patients (5)

Now that we know there’s a correlation between nitric oxide and migraines, where do microbes fit into the picture?

A study conducted by Rob Knight and his team (6) looked into the types of microbes in the mouth and the levels of nitric oxide they produce.

Certain bacterial genes such as nitrate reductase, nitrite reductase and nitric oxide reductase are involved in the modulation of nitric oxide. Healthy participants submitted oral and faecal samples for sequencing. A connection was determined between the presence and abundance of nitrate, nitrite and nitric oxide reductase genes in the samples and the self-reported migraine status of participants. Results showed that migraine sufferers had a higher amount of these genes than non-migraineurs indicating that nitrate-reducing bacteria in the mouth could be contributing to migraine-triggering levels of nitric oxide in the body.

Whilst causal evidence is still required to determine the link between nitrate-, nitrite-, and nitric oxide-reducing bacteria and migraines, these correlation studies suggest an explanation for why some people are more susceptible to migraines than others and why particular foods act as migraine triggers. In the future, treatments may involve altering the balance of bacteria in the mouth in order to prevent migraines, a type of “probiotic mouthwash” so to speak.

It is intriguing to speculate that such small organisms living in our bodies could be responsible for one of the worst pains known to humans. Whilst the mechanistic connection between nitrates, gut microbes and migraine is yet to be determined, one thing is clear – if you’re at a BBQ serving hotdogs and are prone to migraines, opt for the chicken skewers instead.

Brigid xx

References

(1) Gallai, V., Sarchielli, P. Nitric oxide in primary headaches. J Headache Pain 1, 145–154 (2000). https://doi.org/10.1007/s101940070036

(2) Henderson, William R., and Neil H. Raskin. “”Hot-dog Headache”: Individual Susceptibility To Nitrate.” The Lancet, 1972, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(72)92591-3/fulltext. Accessed 7 April 2021.

(3) S. Moncada and E. A. Higgs, “Endogenous nitric oxide: physiology, pathology and clinical relevance,” European Journal of Clinical Investigation, vol. 21, no. 4, pp. 361–374, 1991.

(4) Davis, Jeanie Lerche. “Does Exercise Trigger Your Migraines?” WebMD, 2001, https://www.webmd.com/migraines-headaches/news/20010702/does-exercise-trigger-your-migraines#:~:text=Even. Accessed 7 April 2021.

(5) Nitric oxide synthase inhibition in migraine. Lassen, L H, et al. 1997, Lancet, p. 349.

(6) Knight, Rob. “Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort.” mSystems, vol. 2, no. 2, 2017, pp. 17-23, https://msystems.asm.org/content/1/5/e00105-16.