The Surprising Connection Between Migraines and Nitrates

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Nitrates and migraine

Do Nitrates Have Anything to do with Migraines?

A recent article published found that higher levels of nitrates correlate with migraine. This research intrigued me. Many migraineurs I work with in my migraine group on Facebook announce shortly after joining the group that nitrates in their food causes migraines for them. This is very odd because human saliva contains an abundant amount of nitrates (1). I wondered why so many migraineurs would be concerned about nitrates when nitrates occur naturally in their saliva.

Though the research is clear, most folks do not realize that all produce, organic or otherwise, contains nitrates. In fact, anything grown in soil contains nitrates. There is a list of foods high in nitrates here but let me include a few for examples. Let me first say that the nitrate content in foods depends on the soil in which it is grown. The soil in some regions is higher in nitrates than in others, and thus, produces crops with higher nitrate content. Overall however, root vegetables are exceptionally high in nitrate. So, if you eat potatoes, sweet potatoes, carrots, radishes, onions, or yams, you are eating nitrates and your saliva will likely measure high concentrations of nitrates. Celery is very well known for its nitrates and many migraineurs eat celery regularly. And since organic prepared foods often use vegetable nitrates like celery juice, they too are high in nitrates, even though they advertise themselves as “nitrate free”.  Lettuce, beets, carrots, green beans, spinach, parsley, cabbage, radishes, and collard greens are also all high nitrate foods. Fruits have lower nitrate contents. This makes sense since they are not part of the plant per se.

Since nitrates are naturally occurring and we eat them in fresh produce every day, one must wonder if there is anything behind the theory that nitrates cause migraines. On the surface it certainly doesn’t appear so. Could there be something behind this association, beyond a chance correlation?

When this topic was presented to me for research, at first I thought… urgh… nah… there is not much here. Lots of researchers have worked on this and the results are conflicting at best. And given the nitrate content in foods, I thought the correlations observed were incidental. Then, a light bulb when off. Maybe there is something to this correlation, but I would dare say it is not what I thought it would be. Let me take you through the series of connections I made while researching this topic.

The Light Bulb Moment

It is important to start with a fact: our saliva contains nitrates. People with more nitrates in their saliva have more cavities. Many tests have been done to evaluate if salivary nitrite and nitrate (forming nitric oxide) can be used as biomarkers to estimate the likelihood of gingivitis. The correlation found was insignificant. While we all have varying levels of nitrates in our saliva, based on the gingivitis research, nitrates have nothing to do with migraines because not everyone with gingivitis has migraines and not everyone with migraines has gingivitis.

Another type of nitrate research is focused on the area where the esophagus and the stomach meet. Would nitrates have a role in GERD? Some migraineurs have GERD; could there be a connection?  Possibly, but again, unrelated to the cause of migraine because not all migraineurs have GERD and not all people who suffer from GERD have migraines. Then suddenly I found some amazing articles that hit me in the heart. Here is a title that started my heart beating a bit faster: “Dietary Nitrate Provides Sustained Blood Pressure Lowering in Hypertensive Patients” (3). Aha! I can now see a connection. Soon after finding this article, several other articles popped up with similar subject and the connection suddenly became clear.

Migraine, Low Blood Pressure, and Nitrates: The Missing Connection

It is little known that migraineurs, when not in pain, have clinically sub-normal low blood pressure, see hereherehere, and here. When new migraineurs join my migraine group, they frequently sport a blood pressure of 90/50 (normal ranges are 100-139 in systolic and 70-85 in diastolic) or up to 100/60 but rarely ever go over 110/70. What might happen if a chemical compound, such as nitrate, which lowers blood pressure, is given to or consumed by a migraineur? With the drop in blood pressure that follows taking nitrates (in food), and the vasodilating effect of that nitrate has on blood vessels (4), migraineurs are in trouble. Such drop in blood pressure can cause serious hypotension, which is associated with electrolyte disturbance, and that I believe, is the real cause of migraine.

The connection between migraine, nitrate, and low blood pressure has not been mentioned before in the scientific literature; at least I could not find it. Nitrates indeed cause trouble for migraineurs but not because of the harmful effects of nitrates as chemicals themselves, as is believed. After all, nitrates can be life saving for hypertensive patients. Nitrates cause problems for migraineurs because they lower their already low blood pressure, which sets off the cascade of events leading to migraine. This is the light bulb moment. This is the real reason for the correlations found in the article cited above and others. Unfortunately, much confusion still exists in this field of research.

Migraine and MTHFR Mutations: More Connections

Let us unpack the article’s results a bit more and see if we can shed some more light on the migraine-nitrate connection. Returning to the original article by Gonzalez et al., who stated the following:

“Using high-throughput sequencing technologies, we detected observable and significantly higher abundances of nitrate, nitrite, and nitric oxide reductase genes in migraineurs versus nonmigraineurs in samples collected from the oral cavity and a slight but significant difference in fecal samples” (see in abstract)

Suddenly this makes sense, but again, not for the reasons researched in the above article. They were comparing gut microbes and other interesting data but the real important stuff is in the saliva. The nitrate content of saliva is genetically predetermined by the SLC17A5 gene. Migraineurs carry the MTHFR C677T variant, and thus, migraine is genetically determined. Since migraineurs have sub-normally low blood pressure but higher than normal levels of nitrates in their saliva, perhaps there is a genetic connection. If there is a variant of the SLC17A5 gene in migraineurs in addition to the MTHFR gene variant, which we already know migraineurs have, there may be a genetic connection between migraineurs’ low blood pressure and higher nitrate levels in their saliva. If nitrates are given to hypertensive patients to reduce blood pressure, that makes sense, and it suggests that for the hypertensive, consuming foods with nitrates maybe helpful. We cannot state the same for migraineurs where nitrate consumption would reduce blood pressure. The consumption of nitrates would spiral migraineurs into a dangerously low blood pressure and induce the electrolyte imbalance responsible for most migraines!

Thus, the connection between nitrates and migraine is not a chemical one as suggested by Gonzalez et al., it is not similar to chemicals like MSG that many people are sensitive to (which has its own controversy). Rather, nitrates lower blood pressure and the low blood pressure initiates the migraine by two interrelated mechanisms:

  1. Reducing blood pressure relaxes arteries and muscles and thus reduces the volume of the blood available to carry oxygen and other vital nutrition around the body. A blood pressure of 90/50 has a significantly more difficult time pushing blood all the way up to the brain of a migraineur and increases the likelihood of reduced oxygen and reduced electrolyte, which then prevents action potential.
  2. As vasodilation creates the appearance of a reduced blood volume by widening the blood vessels’ diameter, migraineurs may experience dizziness, nausea, may faint and can have serious discomforts, all well-know prodromes of migraines.

While this article is in no way in conflict with any research that has ever been done on the connection between migraine and nitrate consumption, it clearly points to a new cause for the problem and suggests direction for new research. Nitrates may indeed have serious effects on migraineurs by their blood pressure lowering effects.

Sources

  1. Granli T, Dahl R, Brodin P, & Bøckman OC (1989) Nitrate and nitrite concentrations in human saliva: Variations with salivary flow-rate. Food and Chemical Toxicology 27(10):675-680.
  2. Kapil V, Khambata RS, Robertson A, Caulfield MJ, & Ahluwalia A (2015) Dietary Nitrate Provides Sustained Blood Pressure Lowering in Hypertensive Patients; A Randomized, Phase 2, Double-Blind, Placebo-Controlled Study. Hypertension 65(2):320.
  3. Kukovetz WRH, S; Romain, C; (1987) Mechanism of vasolidation by nitrates: role of cyclic GMP. Cardiology 74(Suppl 1):7.
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