Migraine and Insulin Resistance

What Every Migraineur Should Know

Indeed, no one tells migraineurs the biggest risk of all: insulin resistance (IR) and type 2 diabetes (T2D). Why don’t doctors tell them? Most likely because they don’t know. As some of you know, I specialize in migraines because I am a migraineur (I should say “I was” since I can prevent every migraine now) and because I am a scientists, so I am in a perfect spot for conducting migraine research–on people and not lab rats.

I have a hard time accepting lab rats with migraines where a migraine is caused by scientists so they can study migraines. Not because they are rats and we don’t actually know what they feel when they experience a migraine (if they even can experience that), but because migraine is not just a pain in the head and it is not possible to cause a migraine in a brain that is not preset to be a migraine brain. This needs a tad more explanation that you can read here, in an article I wrote in May of 2017.

Ironically rats and all wild animals have “migraine brain” setup but they don’t experience migraines for a reason: they need to use that brain the right way with all of its sensitivities and special features. All wild animals have a sensitized hyper alert brain (like migraineurs do–this is explained in the article I linked to) else they are food for another animal. I have trouble with scientists causing pain to anyone who has not consented to such, even if that is a lab rat. Furthermore, since migraine is a series of events that fall like dominoes, ending up in a migraine, the scientists causing pain to rats are not really causing migraines just a headache.

IR and T2D Shake Hands with Migraineurs

Just about every scientific journal article on migraines connects migraines with metabolic syndrome (both IR and T2D are part of that syndrome), but they always write “mechanism not yet understood.” However, the mechanism is actually quite clearly understood–at least by me. So let me share just the basics now as the whole concept is going to be explained in great detail in the extended edition of my original book (which I am told is missing page numbers now after I fired my publisher–sorry about that; the new extended edition will have page numbers).

In short: migraineurs have a different brain; it is always on alert; it is hyper sensitive with its sensory organs (hence the sensitivity to smells, sounds, light, etc.,); it uses more voltage (that is bigger voltage and more often); it needs a different electrolyte concentration to make it function; and it sports over 1000 genetic variances, of which the first 40 or so are related to the brain’s voltage control mechanism (ionic channels), ATP issues with solute carriers variance (this is glucose), insulin issues (here is the IR connection), and mitochondrial variations (some more energy difference).

Thus migraineurs are predisposed to not handle eating glucose or fructose (in other words not just sugar but fruits, vegetables, nuts, legumes, and all grains are trouble foods for migraineurs) very well. When migraineurs stop eating these foods, their migraines vanish! Eating foods high in glucose and fructose for easy access (candies and sweets) or those types of carbs that very fast convert to glucose (grains, starches–rice, potatoes, tapioca, all underground-grown veggies, legumes), high sugar containing food (fruits, juices, and prepared foods of any kind), are all trouble for migraineurs because of their genetics. In my migraine group on Facebook I recommend to all of my migraineurs to use a glucose meter and to run an initial test to see if they have glucose problems–so far every migraineur who tested does have at least IR and some T2D. I also have a second migraine group where we use the ketogenic diet for migraine. In that group both glucose and beta hydroxybutyrate (blood ketones) must be tested regularly.

Most medicines that migraineurs get cross the blood brain barrier. They all cross using the glucose metabolic processes that are not functioning well in migraineurs. Therefore, the medicines migraineurs receive end up causing IR and then later T2D. Unfortunately all medicines that are prescribed for migraines will do this, including those that are cardio vascular, such as Propranolol, because these also cross the blood brain barrier.

I am starting a series on HormonesMatter about IR and T2D and though the series will not be specific to migraineurs, it is important for all migraineurs to also read it. When the first of the series airs I will post a link here for all to read.

Comments are always welcome!


About Angela A Stanton, Ph.D.

Angela A Stanton, PhD, is a Neuroeconomist focusing on chronic pain--migraine in particular--physiology, electrolyte homeostasis, nutrition, and genetics. She lives in Southern California. Her current research is focused on migraine cause, prevention, and treatment without the use of medicine. As a forever migraineur from childhood, 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 variations of all voltage dependent channels, gates, and pumps (chanelopathy) that modulate electrolyte mineral density and voltage in the brain. In addition, insulin and glucose transporters, and several other variants, such as MTHFR variants of B vitamin methylation process and many others are different in the case of a migraineur from the general population. Migraineurs are glucose sensitive (carbohydrate intolerant) and should avoid eating carbs as much as possible. She is working on her hypothesis that migraine is a metabolic disease. As a result of the success of the first edition of her book and her helping over 5000 migraineurs successfully prevent their migraines world wide, all ages and both genders, and all types of migraines, she published the 2nd (extended) edition of her migraine book "Fighting The Migraine Epidemic: Complete Guide: How To Treat & Prevent Migraines Without Medications". The 2nd edition is the “holy grail” of migraine cause, development, and prevention, incorporating all there is to know. It includes a long section for medical and research professionals. The book is full of academic citations (over 800) to authenticate the statements she makes to make it easy to follow up by those interested and to spark further research interest. It is a "Complete Guide", published on September 29, 2017. Dr. Stanton received her BSc at UCLA in Mathematics, MBA at UCR, MS in Management Science and Engineering at Stanford University, PhD in Economics with dissertation in neuroscience (culminating in Neuroeconomics) at Claremont Graduate University, fMRI certification at Harvard University Medical School at the Martinos Center for Neuroimaging for experimenting with neurotransmitters on human volunteers, certification in LCHF/ketogenic diet from NN (Nutrition Network), certification in physiology (UPEN via Coursea), Nutrition (Harvard Shool of Public Health) and functional medicine studies. Dr. Stanton is an avid sports fan, currently power weight lifting and kickboxing. For relaxation (yeah.. about a half minute each day), she paints and photographs and loves to spend time with her family of husband of 45 years, 2 sons and their wives, and 2 granddaughters. Follow her on Twitter at: @MigraineBook, LinkedIn at https://www.linkedin.com/in/angelaastantonphd/ and facebook at https://www.facebook.com/DrAngelaAStanton/
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6 Responses to Migraine and Insulin Resistance

  1. Great article!! Could you go more in depth on the meds crossing the blood brain barrier? I’m curious about the biochemistry (I know… A bit nerdy, sorry!) I was also wondering, you mentioned Propranolol as one med that crosses, so I was wondering if newer generation beta blockers like metoprolol also cross and cause IR and T2D? Thanks again for a fantastic read. 😁

    Liked by 1 person

    • Hi Melissa,

      Yes, Toprol (Metoprolol) crosses the blood brain barrier (BBB) as well–I found that out the hard way! I was on it for heart arrhythmia for ages and then when I went on the ketogenic diet, it started to work against the very thing I took it for. Rather than reducing arrhythmia, it increased it. No one among my doctors new what was going on. My cardiologist doubled the dose–that made it worse! Suddenly my blood pressure, which is normally low, was all over the place on the higher end. I even went through 1 week of permanent heart monitor glued to me before and ER cardiologist friend (from another state), Dr. Phinney (the keto genius), and I figured out that it was Metoprolol that suddenly started to work as an antagonist.

      So what actually happens on the exact molecular level is too complex to explain but basically all medicines that cross the BBB (with a few exceptions, like so far it seems that Benzodiazepines don’t act up) use the “glucose” pathway. What I mean by that is that in order for them to function the way they were intended, they need to take part in the metabolic process of carbohydrates, which include (and I am just saying this number for magnitude comparison) 36 steps. In that 36 steps, each medicine bails out at a different level. The many steps allows them to use the particular step and location where they are supposed to be absorbed–see further down the absorption types and location references–in bold.

      When you are on the ketogenic diet that uses fat for fuel, again just a magnitude comparison here, the number of steps to convert fat to fuel is ~6. So there are way fewer steps to bail out and act on a particular organ in a certain way than in the carbohydrate metabolic cycle. As a result, the “metabolites” of the drug end up being different from what they were designed to be–this is particularly true for lipophilic drugs (they dissolve in lipids).

      Here is a quote from an academic article describing drug metabolism:

      “The transport of drugs across membranes involves one or more of the following processes: 1) passive diffusion, 2) filtration, 3) bulk flow, 4) active transport, 5) facilitated transport, 6) ion-pair transport, 7) endocytosis, and 8) exocytosis. Drug absorption also depends on a number of physicochemical factors, the two most important of which are lipophilicity and solubility. The membrane of the gastrointestinal epithelial cells is composed of tightly packed phospholipids interspersed with proteins. Thus, the transcellular passage of drugs depends on their permeability characteristics to penetrate the lipid bilayer of the epithelial cell membrane, which is in turn dependent on the lipophilicity of the drugs. Although correlations have been established between lipophilicity and increased permeability, lipophilicity is not always predictive of permeability.”

      This then modifies drug excretion, half-life, and all metabolites that are created in the process of the metabolism. Thus a drug that dissolves in lipids well will react very strongly in a highly lipid environment (such as a ketogenic) and depending on some genetic factors and variances associated with P450, this can lead to terrible results. So this also implies that not everyone will react the same way depending upon how fast one metabolizes a drug. Fast metabolizers (I happen to be one of those) go through a time release drug as though it was not time release–I used to take the extended release–and that probably makes things worse if Metoprolol happens to also love the lipid environment (which apparently it seems it loves). And so it ended up (probably) overdosing in several magnitudes causing major trouble. However, as you can see from above, the exact mechanism is not yet understood.

      In general, drugs that act on receptors that are in the brain (GABA, serotonin, dopamine, etc.,) and histamine receptors cross the BBB. If you look at Propranolol, it is a “non-selective” beta blocker (look in wikipedia for ease of finding) and so it ties both H1 and H2 receptors down–these are 2 histamine receptors. Because it ties both down, it can also be fatal for an asthmatic so it is not only the ketogenic environment that is troublesome.

      Metoprolol only ties only one histamine receptor and not both down so it is what is called a “selective” beta blocker. However, since it affects a histamine receptor, it crosses BBB with disastrous results.

      Here is another little paper full of good info and here is a quote

      “Lipophilic drugs
      More likely to be metabolized, creating metabolites that are likely more polar, and then more easily excreted.
      • Phase 1 = Convert lipophilic molecules into more polar molecules (hydrolysis, oxidation, reduction)
      • Phase 2 = Further convert lipophilic molecules into more polar molecules through conjugation with glucuronic acid, sulfuric
      acid, acetic acid, or amino acid.
      If reabsorbed and recirculated, then this may increase half-life
      • Increased tubular reabsorption
      • Enterohepatic recirculation” (page 1 toward the bottom)

      So as you can see drugs the cross the BBB AND are lipophilic are affected by the ketogenic diet and must be stopped. Perhaps the reason why benzos seem OK is because they are not lipophilic–not sure since I never checked but it seems, based on reports by many that they are not affecting changes and are not affected by the change in diet type. When I discovered the problem, I was switched to another drug for heart arrhythmia (Atenolol or in brand name Tenormin), which doesn’t cross the BBB. I had a headache for about 10 days after the switch–that was the drug withdrawal I suppose from my brain and then after that it is bliss.

      One of my patients asked her psychiatrist if there is any psychotropic drug that is NOT using the glucose pathway and the answer was a definitive NO. All do. So if you want to get a medicine that doesn’t cross the BBB you have some home work to do since most doctors don’t know enough about the pharmacology of a particular drug to know. I give you one example that will make you fall off the chair: Tylenol. It uses the cannabinoid receptors in the brain. Would you ever have thought that 1) Tylenol crosses the BBB? and 2) that it acts like a cannabis on the brain?

      And in terms of insulin and T2D: absolutely! All meds that use the glucose pathway do cause IR and T2D. Also all drugs with hormones, like corticosteroids, estrogen, progesteron, steroids of all types.. I think it may be easier to list the ones that don;t cause IR or T2D!

      So major homework… indeed!

      Hope this helps (and doesn’t scare you more than it scares me!! I am running away from all drugs!).

      Best wishes,


  2. Dawn Woodes says:

    Waiting with anticipation for more.

    Liked by 1 person

  3. Kristin Ingram says:

    Excellent article … looking forward to the rest of the series! 🙂

    Liked by 1 person

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