Nitrates and migraine

The Surprising Connection Between Migraines and Nitrates

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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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Image by Colin Behrens from Pixabay.

Angela A Stanton, PhD, is a Neuroeconomist who evaluates changes in behavior, chronic pain, decision-making, as a result of hormonal variations in the brain. She lives in Southern California. Her current research is focused on migraine cause, prevention and treatment without the use of medicines.

As a migraineur, her discovery was helped by experimenting on herself.

She found the cause of migraine to be at the ionic level, associated with disruption of the electrolyte homeostasis, resulting from genetic mutations of insulin and glucose transporters, and voltage gated sodium and calcium channel mutations. Such mutations cause major shifts in a migraine brain, unlike that of a non-migraine brain. A non-migraineur can handle electrolyte changes on autopilot. A migraineur must always be on manual guard for such changes to maintain electrolyte homeostasis.

The book Fighting The Migraine Epidemic: How To Treat and Prevent Migraines Without Medicines - An Insider's View explains why we have migraines, how to prevent them and how to stay migraine (and medicine) free for life.

Because of the success of the first edition and new research and findings, she is now finishing the 2nd edition. The 2nd edition is the “holy grail” of migraines, incorporating all there is to know at the moment and also some hypotheses. It includes an academic research section with suggestions for further research. The book is full of citations to authenticate the statements she makes to be followed up by those interested and to spark further research interest.

While working on the 2nd edition of the book she also published academic articles:

"Migraine Cause and Treatment" Mental Health in family Medicine, November 23, 2015, open access
"Functional Prodrome in Migraines" Journal of Neurological Disorders, January 22, 2016, open access
"Are Statistics Misleading Sodium Reduction Benefits?", Journal of Medical Diagnostic Method, February 3, 2016, open access
“A Comment on Severe Headache or Migraine History Is Inversely Correlated With Dietary Sodium Intake: NHANES 1999-2004” Angela A Stanton PhD, 19 July 2016 DOI: 10.1111/head.12861 not open access, membership required to read it.

Dr. Stanton received her BSc at UCLA in Mathematics, MBA at UCR, MS in Management Science and Engineering at Stanford University, PhD in NeuroEconomics at Claremont Graduate University, and fMRI certification at Harvard University Medical School at the Martinos Center for Neuroimaging for experimenting with neurotransmitters on human volunteers.

For relaxation Dr. Stanton paints and photographs. Follow her on Twitter at: @MigraineBook

14 Comments

  1. This is very interesting. No one can figure out my migraines it seems(20yrs). I wake with migraines around 4 in the morning almost everyday. Some are debilitating for hours or even days. Waking with them and going to bed with them sometimes. There are only a handful of days I do not wake with them in a month. I thought my pattern of them were around anytime there was fluctuating hormones(44yrs old). But I don’t understand the 4 in the morning migraines. Do you have any advice? I can get them other times depending. Especially smells, hormones etc. Is this article meaning no carbs? I don’t eat a lot now, mainly from fruit. Thanks!

    • Dear Gypsy,

      Thanks for your comment. I see that you have joined my Facebook migraine group since you posted this comment. So you will learn everything you need to know about migraines.

      The morning migraines are usually always sugar crash associated. You need not be eating junky carbs to get sugar crashes.
      The 4-am waking for a migraine is so typical that it is noted in my book as well.

      See you in the group for further discussions.
      Angela

  2. Wow, this was very interesting. I just came out of a migraine that was untypical for me. Not associated with menstral cycle and more in my temples forehead and overall not feeling well. Temp was normal. I even took a COVID test thinking it could be that. Then I realized the only thing I did differently was take 2 Tbls of beet/carrot juice (1 beet and 1 carrot that I split between 2 days). Thought this might help with gastric troubles and chronic constipation. I try to eat 2 kiwis a day to help as well. Had the juice Mon/Tues. Did not have yesterday when headache was the worst, but today (Thurs) I feel much better. I’ve always had low blood pressure 90/60 and have long dealt with migraines. I thought the carbohydrate relation was interesting since I remember feeling really great when I did the Whole30 diet. So interested to learn more. Thank you

  3. Wonderful article to make things clear to me. Thank you for your positive research and research. I appreciate you.
    Marion

  4. Hi Angela,

    I “talked” to you once a few yrs ago through email. My son is a such a mess. He is better than he has been since we realized he has dysautonomia and deal with the low blood pressure. It took yrs to realize every system seemed to be messed up. He started as a small child with headaches daily that became migraines ( he had non pain migraine with visual and auditory aura for 4 yrs before pain came.) at age 9 and then had migraines 3 to 7 times a week for 9 yrs. He also had several types of non convulsive seizures since 6 months of age ( stares and muscular twitching in sleep with spells of tensing, followed by hyper-relaxation.). So, neurologists were puzzled – several thought I was making it up even though he had abnormal eeg’s and video. I think he had multiple migraine types and auras which stressed his body increasingly, causing seizures. I think he just had a low seizure threshold. He finally performed a convulsion for them, but they still didn’t know what to do. So, at 17 the migraines stopped suddenly and instead he developed drop seizures and what we came to realize yrs later, syncope. He suffered broken bones and many injuries, even with helmets, body armour, and wheel chairs. Giving up on dr’s we worked with scientists and, unfortunately, his advice nearly killed him. Long story. By then we knew he had tachycardia and it took many yrs to journal and discover blood sugar issues, no tolerance at all to sugar ( it caused reactive hypoglycemia), and later that slow gastric motility was causing the blood sugar issues, tachycardia, and low blood pressure. We had been talked into trying a keto diet and it nearly killed him. Unbelievable nightmare. We didn’t realize yet that he had the gastric issues and could not tolerate meat or much fat at all. Journaling helped me realize it later and then we put it all together when we learned about dysautonomia. So, my son is one of the atypical ones with seizures, migraines, and dysautonomia (POTS). You had told me when I wrote that you didn’t think migraines and seizures were related. I wish in his case it were not true. So, anyhow, after not having migraines for 10 yrs the headaches started back up now and then. I think he has some aura sometimes – visual stuff. Several times he has had the start of a migraine and had one tonight. Bad pain and wanting to vomit, but thankfully did not. Not full blown. So, you speak of carbs, but he cannot eat but very little meat. I am so grateful we were able to get him on a little meat, but I have to use the “nitrite free” lunchmeat for some meals because he struggles to digest regular meat. But that celery…. I made him a dinner tonight and used celery salt, something i rarely use with him and I am wondering if this caused overload with the lunchmeats ( turkey and beef – 2 0z 3 times a day and then he usually has regular chicken or fish 2x, also 2 0z. He eats 5 meals a day) , which I believe use celery as a natural nitrite. He is so thin and can eat so little meat or fat that if he did not eat carbs he would not make it. But I think I will try to grind meats. You wouldn’t believe all the dietary restrictions I have to deal with for him. And speaking of potassium, we give him 1/4 tsp of salt with 4 meals along with 1/8th cream of tartar for potassium. He can’t eat many vegetables with the slow motility. He gets magnesium glycinate throughout the day ( 800 mg a day) which really helped his migraines yrs ago, I think, and he can’t seem to live without it. It is hard to know how to balance anything with his diet. I communicated with Dr. Lonsdale about B1, but we have yet to be able to try this again because he just had too many issues going on, but we may get to soon. We are working on a few other ideas – like deep breathing and so forth to help vagal nerve function. Slowly, slowly. Midodrine has given him more quality of life than he has had in so many yrs, combined with Propranolol ( tiny dose.) and he no longer has tachycardia or syncope. He is walking about 3 to 4 blocks a day, or more, in 2 sessions. I am just really concerned about the migraines trying to come back. Tonight was not low blood pressure. I am glad I found this article and will rethink the celery derived products.

    • Hi Joan,

      I am glad you gave more detail. A couple of things caught my eyes as I read your story. One if the cream of tartare, which is basically potassium supplement. Supplementing potassium can be dangerous. I wrote about it here in the past. There are high potassium foods that he may be able to eat. Meat, such as beef, or fish, such as salmon, are naturally very high in potassium. I am confused about is GI issues. Normally GI issues disappear from eating only animal products. Our stomach acid cannot do anything with carbs, just take the glucose out of it. The fiber moves on for gut flora for limited fermentation. There are not much nutrients in carbs, and whatever is there, is not available for digestion becuase it is blocked by plant “nutrients” that are anti-nutrients for humans.

      I work with many migraineurs with GI issues and once on an all animal diet, their gastric issues all resolve. So I am unclear about what is giving a hard time for your son. A meat-diet is also great for motility-to be honest, so far everyone I have talked to who used to have constipation on the fiber-heavy diet became completely regular once the fiber was removed–including me.

      I am glad he can now exercise a little. His migraines would ease up if you could remove the carbs. So it’s a dilemma to solve what you do and how. But for growth, bone strength and muscles, he needs to eat animal protein. Bone is 40% protein and calcium cannot adhere without protein to build bone! And only animal protein is complete protein–with the exception of soy, but soy is a goitrogen, so harmful for the thyroid.

      It sounds like you are doing a good job in keeping a diary and helping him improve! So keep on going. 🙂

      Best wishes,
      Angela

  5. I just suffered one of the worst migraines in years ,the day before I ate two large roasted beets, I had roasted broccoli and had eaten celery. I also have low blood pressure. I woke up at 3:30 am with my head splitting, by 9 am I was throwing up. Scary because the first thing that went into my mind was COVID. My temperature was low 96. Something (can’t remember). I did have a shot and my sweet husband made me chicken rice soup. Your article is very useful thank you.

    • Dear Diana,

      Your migraine is not likely associated with Nitrates–though the celery has Nitrates but the amount you ate is minimal and not concentrated enough. Likely it is from having eaten the two beets full of carbs and potassium. Migraine starts as a result of electrolyte imbalance that is caused by carbohydrates and also here the high potassium. To prevent migraines, be sure to consume salt after a high-carbs meal and also you need to balance sodium and potassium in your meals. And grains (rice is a grain) will definitely get you. Join my Facebook migraine group to learn how to abort and prevent a migraine.

      Best wishes,
      Angela

  6. I am intrigued, and glad I found this article. I have low blood pressure and occasional migraines. However, the migraines are returning with my recent consumption of fresh celery juice—which I’m discontinuing.

    Thank you for your research.

  7. I suffer from Hypertension and get occular migraines. I have had more relatively recently and been looking for a trigger … The best I can do at the moment is raw carrot, hence why I found this (“search on migraine and carrot”). My BP, even treated is around 120/85. My father also had high BP and he too suffered migraines. Does this cause issues with your theory? Incidentally I suffer from Occular migraines.

    • Dear Dave,

      Migraineurs are carbohydrate intolerant and glucose sensitive, so carrots are not the best choice to eat for anything. Carrots are high carbs veggies. Your experience doesn’t cause trouble to my “theory” since one can have high blood pressure as a result of the wrong diet (such as eating lots of carrots) as well as medications. The consumption of a high carbohydrate diet can cause hypertension. There are genetic reasons for hypertension as well. It is not typical for migraine sufferers to have high blood pressure, provided they are not eating he wrong food, but it need not exclude people who have migraines and high blood pressure. Only it’s not typical.

      In terms of triggers: knowing what causes migraines gives information about the nature of the triggers and why; on the flip side, knowing the triggers can tell us about the cause of migraines. Triggers are always associated with:

      –foods that are high carbs, are out of potassium to sodium balance,
      –things that are too stimulating for the sensory neurons–such as bright light, loud noises, strong odors, etc. These are all sensory neuron stimulants.

      If you read up on the differences between migraine brain and other brains, there is lots of research now showing that the migraine brain has more neuronal connections among sensory neurons. Here is the latest study on this “Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study“.

      So if you look at all the research, you will see that my “theory” (I note it in quotes because really something that has been proven to work for thousands of people is really no longer a theory) is totally supported. 🙂

      Best wishes,
      Angela

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