migraine brain

Migraine Energy Metabolism: Connecting Some Dots

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migraine, brain energy, thiamine

I have been reading some of the fascinating posts by Angela Stanton PhD concerning her research in migraine headaches. I regard the substance of her discussions as somewhat like dots on a chart that need to be connected. I learned a great deal about the chemistry involved in migraine. One of her comments that involves ion homeostasis in brain metabolism is fascinating. She noted that “serotonin is created by a normally functioning brain. Why it decreases or increases in the brains of migraineurs has always puzzled me. Should we not try to find out why?” That simple three letter word is the heart and soul of research and I believe that I may be able to add some information that might provide an answer.

Ehlers Danlos and Migraine

In one of Angela’s posts she discusses a subject which has been of interest to me for many years, the overlap of symptoms in disease. She noted that 60% of migraineurs have one type of Ehlers Danlos syndrome (EDS) and 43% of EDS have minor changes in DNA (SNPs) found in migraineurs. She concludes that they must be related. Over 70% of migraineurs have Raynaud’s disease and there is an overlap with EDS and Raynaud’s. Therefore, she concludes that these three diseases are variants. In  fact, there is an association between EDS, Postural Othostatic Tachycardia Syndrome (POTS) and a group of conditions known as mast cell disorders. EDS-HT, (one of the manifestations of this disease), is considered to be a multisystemic disorder, involving cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic and psychiatric manifestations, including joint hypermobility. Many non-musculoskeletal complaints in EDS-HT appear to be related to dysautonomia, consisting of cardiovascular and sudomotor dysfunction. Many of the clinical features of patients with mitral valve prolapse can logically be attributed to abnormal autonomic function. Myxomatous degeneration of valve leaflets with varying degree of severity is reported in the common condition of mitral valve prolapse.

A woman, with what was described as a “new” type of EDS, died after rupture of a thoracic aortic aneurysm. Autopsy revealed myxomatous degeneration and elongation of the mitral and tricuspid valves. Patients with POTS, a relatively common  autonomic disorder, may have EDS, mitral valve prolapse, or chronic fatigue syndrome and are sensitive to various forms of stress, as depicted in the clinical treatment of a dental patient affected by the syndrome. Dysautonomia has been described in the pathogenesis of migraine, featured by nausea, vomiting, diarrhea, polyuria, eyelid edema, conjunctival injection, lacrimation, nasal congestion and ptosis. In general, there is an imbalance between sympathetic and parasympathetic tone.

Energy Metabolism and Migraine

Technological studies have confirmed the presence of deficient energy production together with an increment of energy consumption in migraine patients. An energy demand over a certain threshold creates metabolic and biochemical preconditions for the onset of the migraine attack. Common migraine triggers are capable of generating oxidative stress  and its association with thiamine homeostasis suggests that thiamine may act as a site-directed antioxidant. It strongly suggests that migraine is a reflection of an inefficient use of brain oxygen.  An intermediate consumption of oxygen between deficiency and excess appears to be a necessity at all times. In fact,” moderation in all things” is an important proverb

Backing up energy deficiency, two cases of chronic migraine responded clinically to intravenous administration of thiamine. However, the authors are in error when they state in the abstract that “nausea, vomiting and anorexia of migraine may lead to mild to moderate thiamine deficiency”. An otherwise healthy 30-year-old male acquired gastrointestinal beriberi after one session of heavy drinking. Nausea, vomiting and anorexia relentlessly progressed. He had undergone 11 emergency room visits, 3 hospital admissions and laparoscopy within 2 months but the gastrointestinal symptoms  continued to progress, unrecognized for what these symptoms represented. When he eventually developed external ophthalmoplegia (eye divergence), he received an intravenous injection of thiamine which reversed both the neurologic and gastrointestinal symptoms within hours.

In other words it is important to be aware that nausea, vomiting and anorexia are primary symptoms of beriberi due to pseudohypoxia in the brainstem where the vomiting center is located. Chronic migraine has a well documented association with insulin resistance and metabolic syndrome. The hypothalamus may play a role. One of Angela’s comments concerns ion homeostasis in migraines. Thiamine triphosphate (TTP) can be found in most tissues at very low levels. However, organs and muscles that generate electrical impulses are particularly rich in this compound. Furthermore, TTP increases chloride (ion) uptake in membrane vesicles prepared from rat brain, suggesting that it could play an important role in the regulation of chloride permeability. Although this research was published in 1991, the exact role of TTP is still unknown. It has been hypothesized that thiamine and magnesium deficiency are keys to disease.

Angela wondered why serotonin might be increased or decreased in migraineurs. I strongly suspect that it is due to brain thiamine deficiency as the ultimate underlying cause of the migraine. In a review of thiamine metabolism, it was pointed out that metabolites could be high or low according to the degree of the deficiency. Victims of beriberi were found to have either a low or a high potassium according to the stage of the disease. If they were found to have a low acid content in the stomach, treatment with thiamine resulted in a high acid content before it became normal. If the stomach acid was high it would become low before it became normal. Since low and/or high potassium levels may be found in the blood of critically ill patients, thiamine deficiency should be a serious consideration in the emergency room or ICU Thiamine deficiency may be the answer for the fluctuations of serotonin observed in migraine.

Redefining Disease Models

According to the present medical model, each disease is described as a constellation of symptoms, physical signs and laboratory studies, each with a separate etiology. The overlap discussed by Angela suggests that the various conditions nominated have a common cause and that they are indeed nothing more than variations. If energy metabolism is the culprit, it would make sense of the infinite variations according to the degree and distribution of cellular energy deficiency. EDS-HT, described above is reported as a multi-system disease, exhibiting cardiovascular, autonomic gastrointestinal, hematologic, ocular, gynecological and psychiatric symptoms as well as the joint mobility. It seems to be impossible to explain this multiplicity without invoking energy deficiency as the cause. People with prolapsed mitral valve and a patient with a “new” form of EDS, reportedly have myxomatous degeneration as part of their pathology and it is tempting to suggest that such an important loss of structure might well be because of energy deficit.

The controls of the autonomic nervous system are located in the lower part of the brain that is particularly sensitive to thiamine deficiency and beriberi is a prototype for thiamine deficiency in its early stages. Dysautonomia is frequently reported as part of many different diseases, offering energy deficiency as the etiology in common. Yes, it is true that thiamine is not the only substance that enables the production of ATP. Nevertheless, it seems to dominate the overall picture of energy metabolism. It has long been considered the essential focus in the cause of beriberi, even though all the B complex vitamins are found in the rice polishings. Milling and the consumption of white rice was the prime etiology of the disease when it was common in rice consuming cultures.

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This article was published originally on June 22, 2020.

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Migraine: Do We Have It All Wrong?

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Migraine brain

The combined APS (American Physiological Society) and EB (Experimental Biology) conference was full of excitement for me. This was my first migraine-associated presentation to scientists, MDs, and premed students. I have never presented a poster at any conference—I have usually given lectures. I was concerned. Will my posters catch any interest? Then I arrived at Chicago’s McCormick Conference Center and was shocked by its size and the size of this conference. There were 1500 poster boards, each with new posters every day for three days, in addition to booths and lectures. I took a deep breath.

Here I share with you what I presented and some of the questions attendees asked, answers I provided, and offer a more comprehensive explanation of what migraine is. I am also including one of the two posters I presented.

The first day, I presented a poster under the EB session so most visitors were curious about the biological aspects of migraine. The second was presented under the Electrolyte Homeostasis session, which brought very different visitors and very different questions. I find it important to define what migraine is and then continue with my hypothesis, which is drawn in the middle of the poster, and I highlight it here for easier viewing.

What is Migraine?

The answer is not pain. I found that the majority of those who have no migraines or never met anyone with migraines know migraine as a pain in the head. The truth is pain is just one – and not even mandatory – aspect of migraines. For me, presenting the real definition of migraines equals to explaining the conclusions of my many years of research.

Migraine is the manifestation of an energy (voltage) shortage in the brain, caused by insufficient electrolyte quality. This actually makes migraine into a symptom. The insufficient electrolyte mix is caused by certain genetic variances that result in some electrolyte mineral deficiency. Therefore, the electrolyte imbalance is also a symptom. The direct cause of migraine lies hidden in critical genetic variances that should operate the voltage gated channels of neurons but cannot. Why not? This is the heart of migraine: migraineurs are glucose sensitive with a brain that lacks capability to handle the huge electrolyte disruption when glucose enters the brain cells. As we know, adaptation is an important part of evolution. It seems that a very large percentage of the human population was able to adapt to the dietary circumstances of contemporary life but people with the migraine-brains could not. I call the migraine brain an ancient brain that is not able to utilize glucose. Modern carbohydrate-rich diets overload this ancient brain with glucose. Migraineurs are not the only ones with this problem. People with seizures, multiple sclerosis, Alzheimer’s disease, and many more conditions, have very similar—if not the same—problem. Not every human can eat birthday cakes, potatoes, and toast for breakfast. Migraineurs cannot.

The Migraine Brain Difference

sensory neuron comparison

Image copyright by Angela A. Stanton, Ph.D.©

Figure 1. Neuron: non-migraineur vs migraineur

The top image represents a single neuron in an average human brain, highlighting an enlarged section showing the receptors and the neurotransmitters in the circled region. The bottom image is the same for a migraineur. The two are obviously very different—look at the density of the receptors and neurotransmitters (the layer of black dots under red). The questions one must ask:

  1. Why do the migraineur’s neuron contain so many more receptors and neurotransmitters?
  2. Does that have anything to do with pain? And if so how and why?

A migraine brain’s sensory neurons are hyper sensitive (1) and hyper alert in comparison to the sensory neurons of a non-migraine brain. More alertness is explained by the more receptors (2) and neurotransmitters. But why do migraineurs have more receptors and hyper sensory brains? To answer this question I present a few hypotheses:

Hypothesis 1: If you look at many mammal species in the wild, you find they are always on alert for predators. If they are not on alert, they are likely to become food. For these species the hyper-sensory alert brain is the default. The migraine-brain is a hyper-sensory alert brain.

Hypothesis 2: If hyper-sensory brain can be the default then such a brain, the migraine-brain, is the default mammalian brain that all human ancestors must have had at one time. Since this brain is still very prevalent in the human population (15%), it must have represented a significant survival advantage in ancient times. Today, however, the majority of humans do not have this brain type.

Hypothesis 3: While the majority of humans were able to adapt to more modern lifestyles and food supply, some could not; their brain remained unchanged, still holding onto the ancient traits and retained hyper sensory organs. These then are today’s migraineurs.

Hypothesis 4: The tendency for electrolyte imbalance is a sign that the migraine-brain is greatly compromised under modern nutritional challenges. While the majority of humans adapted to the use of carbohydrates for fuel during our recent evolution, migraineurs did not. Up until about 15,000 years ago carbohydrates formed minimal part of the human diet.

Hypothesis 5: The ancient brain (in some of its traits) may go back as far as the Euarchontoglires (100 million years ago), the first common ancestor to all mammals and primates. The early mammals had a few special traits that appear to be connected to migraine-brain. Two of these are the Ehlers-Danlos Syndrome (EDS) and Raynaud’s Syndrome. Both of these are highly connected to migraine and to each other and are ancient traits that some small mammals still carry today—and apparently a very large percentage of migraineurs do as well, although in the general population the percentage is minuscule.

Hypothesis 6: Migraine is a neurovascular condition (not a disease) that is an evolutionary throwback. Neuro because it is neuron voltage energy generation problem and vascular because of the different vascular structure migraineurs have from non-migraineurs. Both EDS and Raynaud’s are vascular in nature and EDS is also associated with hyper mobility and being disjointed, which was a very important adaptation in early mammals and still are in many, such as cats, often referred to as floating shoulders. Having a different vascular system allows for more flexibility without vascular damage.

Hypothesis 7: Migraineurs have a very different vascular system from non-migraineurs. I propose the vasculature segments are shorter and more numerous. This can often be seen on the skin of people with EDS because they also have very thin and transparent skin. Shorter vascular regions allow for more flexibility along with the hyper flexibility of those afflicted with EDS.

Hypothesis 8: Migraine brain is of the era when being disjointed and having different vascular system was an evolutionary benefit. From evolutionary throwback perspective then it makes sense that migraineurs are glucose sensitive and carbohydrates intolerant, since at that time, carbohydrates and glucose were not consumed.

Support for the Hypotheses

Support for these hypotheses come from genetics, which shows us that the migraine brain has different voltage gated ionic channels for calcium, ATPase, the sodium/potassium pump, sodium channel, and potassium pump, implying that all electrolyte modulation for a migraineur is different from a non-migraineur, in addition to glucose and insulin regulatory variances. See below the top few genetic variances. I used GeneCards database to find all gene variance associated with migraines—sorted by importance called “score”—and removed some that are not relevant to my point:

GeneCards Migraine Genes
GeneCards Migraine Genes

I only listed 16 gene variances from the 1293 currently associated with migraines (highlighted important words), though as more research is conducted, this number is certain to grow. Some variances that have low score—such as insulin resistance—will likely move to higher scores since migraineurs are associated with a very high incidence of metabolic disorders, specifically migraine is associated with insulin resistance (3) as a result of being glucose sensitive.

Migraines, Drugs, Nutrition

Pharmaceutical companies have spent much of their migraine-allocated time developing drugs that block migraineurs’ voltage gated channels that are different from that of the standard population, without any concern why they are different. As a result, these channels cannot work at all when medicated. Of course, just as there is no point in medicating blue eyes, a genetic variance, so is medicating a type of voltage gated channel is futile. It takes a bit of understanding why. At the conference I spent eight hours a day for two days explaining this to doctors, scientists, and even representatives of big pharma. It took me 10 years to figure it out.

Since “…serum Na+ falls by 1.4 mM for every 100-mg/dL increase in glucose, due to glucose-induced H2O efflux from cells” (4) (page 4), you can immediately see that as glucose enters the cells, sodium (Na+) falls and water (H2O) leaves the cell, causing major electrolyte disruption.

Regular human brains that have adapted and are able to reset electrolyte homeostasis with ease have no trouble. The migraine brain cannot because all associated voltage gated ionic pumps and channels are in their ancient forms, where carbohydrate consumption was too minimal to matter in electrolyte dysregulation. The long epoch in which the hyper sensory mammalian brain was still the dominant variant of humanity, sugar and grains were not part of the diet at all and very little if any carbohydrates were consumed.

The migraineurs’ exaggerated reactions to carbohydrate consumption shows that they have a problem with glucose metabolism. With this major negative, is there a way to prevent migraines without the use of any medicines? Absolutely. Before I detail the proper migraine nutrition, I would like to answer a question I received from some doubters during the conference. Facing a skeptic is great, it forces the scientist to come up with the appropriate answers.

The most common comment (particularly from those representing pharmaceuticals) was that “whatever is done without medicine must be placebo”. This was extremely easy to defend by the simple logic that goes as follows:

If A > B AND B > C then A > C 

This applies to pharmaceuticals since their clinical trials for medicines are placebo tested. Therefore, migraine medicines, M, are proven to be better than placebo, P. M > P. The medicine-free treatment available is MF. Given that the MF treatment has been successful for thousands of migraineurs who also quit taking all their migraine medicines and remained migraine free, we can state the following:

If MF > M AND M > P then MF > P – that is medicine free is better than placebo.

Medicine & Migraine Free

So what is medicine free and migraine free? It is quite simple: since migraineurs cannot use glucose as energy and if they try they end up with major electrolyte disruption as a result, it implies that by stopping the consumption of carbohydrates migraines can be prevented. Certain amount of protein also converts to glucose (gluconeogenesis) so controlling protein amount is also important but less critical.

Can migraineurs eat any carbohydrates? Yes, they can but minimal and highly fibrous. Carbohydrates of up to 5 net carbs grams (total carbs – fiber = net carbs grams) per meal seems to be tolerable by all migraineurs. For example, a migraineur can eat green leafy salads, cucumbers, zucchini, avocado, and many similar foods. However, she cannot eat a slice of bread, an apple, or drink smoothies, fruit juices, or soft drinks. See below the poster I showed in Chicago, summarizing what I just wrote and also showing what a migraineur should or should not be eating.

Image copyright by Angela A. Stanton, Ph.D.©

Conclusion

So we are dealing with a brain that is not used to eating carbs and this leads to glucose sensitivity, leading to major reaction to glucose with edema and sodium leaving cells. This leads to electrolyte dysregulation. Migraineurs on the Stanton Migraine Protocol®, LCHF, or the ketogenic diet, slowly taper off their medicines, their insulin reverts to normal and migraines typically vanish.

Sources

  1. Schwedt TJ (2013) Multisensory Integration in Migraine. Curr Opin Neurol:248-253.
  2. Wei Y, Ullah G, & Schiff SJ (2014) Unification of Neuronal Spikes, Seizures, and Spreading Depression. The Journal of Neuroscience:11733-11743.
  3. Fava A, et al. (2014) Chronic migraine in women is associated with insulin resistance: a cross-sectional study. European Journal of Neurology 21(2):267-272.
  4. Longo DL, et al. (2013) Harrison’s Manual of Medicine 18th Edition (McGraw Hill Medical, New York).

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This article was published originally on May 3, 2017. 

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Migraine as a Metabolic Disease

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Migraine as a Metabolic Disease

Migraine is assumed to be a disabling neurovascular disease with various manifestations that affect the vasculature as well as the physiology of the brain. Migraine is categorized either as episodic headache (<15 pain days a month) or chronic (>15 pain days a month). It is also understood that migraine is associated with hyper sensory sensitivities and that about 15% of migraineurs suffer aura migraines. Migraine is strongly associated with metabolic disease1-9. Based on many studies, migraine leads to metabolic disease—either because of migraine prevention medicines or because of dietary lifestyle. Genetic factors also strongly underlie why migraineurs end up with metabolic syndrome. Before we investigate what these genetic factors are and how a migraine sufferer can avoid metabolic syndrome,  we first need to understand what migraine is.

So, What is Migraine?

The current scientific understanding of migraine ignores many key factors because most doctors only see migraineurs when they are in pain or have aura, and most research is, therefore, only focused on pain or aura. However, every single migraineur experiences migraines without pain—silent migraines. Silent migraines are usually associated with aura migraines but cyclic vomiting syndrome, irritable bowel syndrome (IBS), and restless legs syndrome (RLS) can also be present. These other syndromes are often precursors of the migraine-brain development (particularly in children) and they come without migraine-pain. If one can have pain-free migraines, it means the pain in migraines is only a symptom. A symptom of an underlying condition that my research and publications have been identifying and describing.

I have written many blogs about migraine and its genetic connections, see here and here and have published a book that details all genetic, neurovascular, and metabolic connections to migraine, which you can find here. In these publications, I discuss how even 2-year-olds can have migraines, how cyclical vomiting, IBS, RLS, and anxiety often precede the presentation of migraine pains by years. Because of this, migraine can appear as “not migraine” for many years and these seemingly independent symptoms may end up being treated separately. In my research, working with thousands of migraineurs over the years in my FB migraine group, I have found that nearly all of them have some form of insulin resistance (IR), which may be exhibited by hyperglycemia (HG) or reactive hypoglycemia (RH), all of which nearly always remain undiagnosed for a very long time. This is particularly important, since contrary to non-migraineurs with metabolic syndrome, migraineurs sport low blood pressure and are often very thin—meaning several commonly used key factors for the classification of metabolic syndrome are not present, based on which medical professionals would even consider testing for metabolic syndrome.

What is Metabolic Syndrome?

If three of the following five categories are met (based on the new revision of the ranges; see original article here), the person is said to have metabolic syndrome.

  1. Waist circumference > 40 in (males) or >35 in (females)
  2. Fasting glucose ≥ 100 mg/dl
  3. Triglycerides ≥ 150 mg/dl
  4. HDL cholesterol < 40 mg/dl (males) or <50 mg/dl (females)
  5. Systolic blood pressure >130 mmHg or diastolic blood pressure > 85 mmHg

I repeat here the same in bold striked out the ones that migraineurs don’t typically have:

  1. Waist circumference > 40 in (males) or >35 in (females)
  2. Fasting glucose ≥ 100 mg/dl (true for a few)
  3. Triglycerides ≥ 150 mg/dl (true for a very few)
  4. HDL cholesterol < 40 mg/dl (males) or <50 mg/dl (females)
  5. Systolic blood pressure >130 mmHg or diastolic blood pressure > 85 mmHg<.strike>

As you see, migraineurs don’t meet three (and often none) of the above to qualify for a metabolic syndrome examination. Yet, when I ask for an at-home 5-hour fasting blood glucose test, checking for blood sugar fasted, pre-breakfast, 30 minutes after breakfast, and then every 30 minutes after that for 5 hours, I find some very complex IR and RH cases. Below find two common examples:

Hyperglycemia
Hyperglycemia

Hyperglycemia (high glucose)—note that the “normal” may appear low to you but my migraineurs are on a low carbohydrate diet where the maximum blood sugar spike should not exceed 20 points. The above hyperglycemia graph shows both an overly large blood glucose spike and a significant delay in the spike, suggesting serious insulin resistance.

Reactive Hypoglycemia Example
Reactive Hypoglycemia Example

Reactive hypoglycemia is represented by blood glucose level that drops significantly after a meal.

Note that both of the above graphs come from people on a low carbohydrate diets, where breakfast is usually eggs with bacon with perhaps some raspberries with yogurt or a mix of nuts with cottage cheese. So the spike at the 2-hour mark usually represents the conversion of egg whites’ protein to glucose—hence, the spike at 120.00 minutes for the RH and a delayed spike for the HG. Some of the RH migraineurs ended up with such low blood glucose that they were close to fainting (two of them so far reached low 50s). Yet, because they don’t meet the “minimum three” criteria from the five listed above, many doctors flatly refuse to test them for metabolic syndrome. Some even disregard the at-home 5-hour blood glucose test as silly—not sure why, after all, there is no better method currently available. This just shows why migraineurs are never considered as having metabolic disease until it is late in the game, even though there are hundreds of academic articles showing the connection.

Given that migraineurs end up with metabolic syndrome (with most of the five points eventually) later in their lifetime, and since they are undiagnosed prediabetics for a very long time, could it be that migraine is actually a metabolic disease? Since IR, HG, and RH are part of metabolic syndrome and nearly all migraineurs have them from a young age, shouldn’t we investigate what the connection may be?

Observing that migraineurs end up with metabolic syndrome is one thing; finding if migraineurs have predisposition to metabolic diseases as a result of their genetics that includes metabolic gene variants within their migraine gene variants, would be an entirely different thing. Shall we go and find these genes?

The Genetics of Migraines

As a migraineur who is also a scientist, finding out as much as possible about migraines was easier for me than for those researchers who never had migraines. I knew what to ask and what to look for and could also tell what made sense and what didn’t. While most everyone’s first instinct is to say, “what works for one person may not work for another,” hold that thought! In the case of migraineurs this isn’t true. Over the many years of research, I found that migraineurs are like siblings. Nearly all of their symptoms and reactions to treatments are identical. If you want to fully understand why, you need to look at the genetic variances of migraineurs—all of these variances are identical or at least very similar to each other among migraineurs. How do I know this? Many migraineurs had genetic testing and shared their genetic data with me so I could compare their genetic variances with those “average” variances listed for migraine-genes.

True migraines start with a hormonal disruption as a result of overstimulation of the sensory neurons and end in electrolyte dysfunction that prevents action potential in some part(s) of the brain, which results in what is referred to as cortical spreading depression. This is well understood by studying the genetic template of migraine, where the first 30 or so genetic variances are all associated with ionic channels operating electrolyte management and maintenance. Other key genetic variants of importance among migraine genes are glucose transport, renin-angiotensin-aldosterone system (RAAS)10; see variants associated with RAAS as AGT, AGTR1, AGTR2 and BDKRB2 in the migraine genes and here the same associated with type 2 diabetes and here with hypertension, ATP binding, glucagon receptor, and several mitochondrial variants all with very high score in migraine genetic variances. These variants collectively lead to one key problem all migraineurs eventually face: metabolic syndrome5,11. Is it possible then that migraine, while it is clearly genetic, with its metabolism and energy associated variances, is actually a sign (symptom) of metabolic syndrome? In other words, does the genetic makeup of migraineurs lead directly to metabolic syndrome? The answer to this is likely yes. The reason? When migraineurs change their nutritional regime by excluding or greatly reducing all carbohydrates, they reverse their metabolic health condition, achieve full remission, and with that their migraines also disappear.

Clearly, migraineurs’ genetic makeup is such that factors responsible for type 2 diabetes are major components of their migraines. What are those factors? Metabolic syndrome in migraine is not diagnosed until the migraineur had the disease for many years because as we described, migraineurs don’t carry three out of five typical metabolic syndrome traits. The one common variable is chronic insulin resistance (CIR). While academic literature is quite a war zone when it comes to the causes of CIR, in migraineurs the cause is very simple to determine and the condition is easy to reverse.

Reversing Chronic Insulin Resistance in Migraineurs

All people with chronic insulin resistance have common symptoms when they are late with a meal or skip a meal: feeling grumpy, nervous, ravenous, sometimes shaky, sweaty while cold, anxious, and may even faint. Feeling hungry when blood glucose levels are above the body’s preferred 99 mg/dl (about 1 teaspoon of glucose in the entire body) is not normal but those with hyperglycemia feel hungry even when their blood glucose levels are way over 100. To understand the importance of this, we should understand what hunger actually is. I am not covering the biochemical and hormonal elements of hunger. Hunger is a state in which the body is running short of glucose for whatever reason. If the blood glucose level is way above normal, feeling hunger is not warranted. This sort of hunger actually signals insulin resistance because while the blood has plenty of glucose to feed the organs that need glucose, glucose doesn’t get there. It cannot get there because insulin is resistant—meaning it is not sensitive enough to pick glucose up to carry it to the cells. Therefore, eating when hungry while the level of blood glucose is still high, causes more trouble and the hunger will not be sated.

Reversing this type of insulin resistance (hyperglycemia) is very simple: stop eating and keep on checking your blood glucose levels. My migraineurs are asked to not eat until their blood glucose levels dips well below 99 mg/dl—preferably between 70 and 95 mg/dl. Getting down to this low blood glucose may take several days of not eating! If a migraineur is not on any psychotropic or heart medicines, the ketogenic diet I specifically formulated for migraineurs is the best option.

If the migraineur has reactive hypoglycemia, fasting is not an option, since their blood glucose level can drop below healthy minimum levels, endangering their lives. In this case, the migraineur moves to the zero carbs diet (all meat and fat, ratio dependent upon certain factors). Without any exogenous easy glucose, the liver must convert glucose from protein for all of the body’s glucose needs and this reduces insulin, since insulin is not spiked by glucose in this case.

Normal hunger is *just hungry* and no urgency. Normal hunger is healthy, and you can continue being hungry for several days without eating without any problems. That’s normal. A normal hunger doesn’t affect your blood sugar in any shape or form, because the liver manufactures the proper amount of glycogen via gluconeogenesis and ketones for the ketogenic metabolic process. Migraine is 100% preventable by a metabolic process that doesn’t use carbohydrates at all or only in minimal amounts. Since a large body of science suggests that metabolic syndrome is driven by excess carbohydrate intake12 (see here and here and here), and it is reversible by carbohydrate restriction (not caloric restriction), it follows that migraineurs recover from their migraines because they are able to reverse their genetic predispositions to carbohydrate intolerance and glucose sensitivity.

Since migraineurs are carbohydrate intolerant and glucose sensitive, they end up with metabolic syndrome if they continue to consume the – for them – offensive substances. This also suggests that each migraineur should be scrutinized by medical professionals to eliminate all opportunities for the development of metabolic syndrome by educating them to remove carbohydrates from their diet.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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Additional Sources

1          Bhoi, S., Kalita, J. & Misra, U. Metabolic syndrome and insulin resistance in migraine. The Journal of Headache and Pain 13, 321-326, doi:10.1007/s10194-012-0416-y (2012).

2          Casucci, G., Villani, V., Cologno, D. & D’Onofrio, F. Migraine and metabolism. Neurological Sciences 33, 81-85, doi:10.1007/s10072-012-1047-4 (2012).

3          Fava, A. et al. Chronic migraine in women is associated with insulin resistance: a cross-sectional study. European Journal of Neurology 21, 267-272, doi:10.1111/ene.12289 (2014).

4          Guldiken, B. et al. Migraine in metabolic syndrome. Neurologist 15, doi:10.1097/NRL.0b013e31817781b6 (2009).

5          Sachdev, A. & Marmura, M. J. Metabolic Syndrome and Migraine. Frontiers in Neurology 3, 161, doi:10.3389/fneur.2012.00161 (2012).

6          Salmasi, M., Amini, L., Javanmard, S. H. & Saadatnia, M. Metabolic syndrome in migraine headache: A case-control study. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences 19, 13-17 (2014).

7          Shaw, S. W., Johnson, R. H. & Keogh, H. J. Metabolic changes during glucose tolerance tests in migraine attacks. J Neurol Sci 33, 51-59, doi:10.1016/0022-510X(77)90181-2 (1977).

8          Sinclair, A. J. & Matharu, M. Migraine, cerebrovascular disease and the metabolic syndrome. Annals of Indian Academy of Neurology 15, S72-S77, doi:10.4103/0972-2327.100015 (2012).

9          Winsvold, B. S. et al. Migraine, headache and development of metabolic syndrome: An 11-year follow-up in the Nord-Trøndelag Health Study (HUNT). PAIN® 154, 1305-1311, doi:https://doi.org/10.1016/j.pain.2013.04.007 (2013).

10        Atlas, S. A. The Renin-Angiotensin Aldosterone System: Pathophysiological Role and Pharmacologic Inhibition. Journal of Managed Care Pharmacy 13, 9-20, doi:10.18553/jmcp.2007.13.s8-b.9 (2007).

11        Bhoi, S. K., Kalita, J. & Misra, U. K. Metabolic syndrome and insulin resistance in migraine. J Headache Pain 13, doi:10.1007/s10194-012-0416-y (2012).

12        Volek, J. S., Fernandez, M. L., Feinman, R. D. & Phinney, S. D. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res 47, doi:10.1016/j.plipres.2008.02.003 (2008).

 

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Migraine Brain as a Survival Advantage: Connecting the Dots with Angela A. Stanton

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migraine radio show

On February 2nd, 2017, Thursday morning at 10 am Central time, I will be on ONE RADIO NETWORK (see schedule here). On this talk show I will present my views about the causes of migraines. The talk show invites advance emailed-in questions to email@oneradionetwork.com, as well as live call-ins during the show at: 888.663.6386. Here is the page where you can listen to the archived recording on the Internet (one hour talk show). If you are in Austin, Texas, you can listen on the radio.

Migraine Brain as a Survival Advantage

For a while we have known that the human body contains approximately 20 thousand genes, although this number seems to be a moving target as technology improves. The latest studies have reduced it to 19 thousand. From the 19 thousand, so far 1254 genes have been associated with migraines. Such a huge number of genes – associated with a condition that plagues nearly 30% of the population – begs for an explanation.

Could it be that migraine at one time in human history provided a survival advantage? A benefit that helped those endowed with this set of genes to survive? The answer to this question must be “yes” because the migraine-brain has survived in the population for so long. It has not been bred out of human populations over the millennia of our evolution. Health conditions disadvantageous for survival normally get deleted from our genome.

The question “why migraine hurts” has a simple answer based on this theory: pluck a group of people with a special adaptation from its natural habitat and place it into a different environment, and what was an advantage suddenly becomes a disadvantage. There are many examples for this in nature.

Greenland Inuit, Canadian Inuit and the Native American populations all have glucose (simple sugar into which all carbohydrates, including fruits and vegetables, grains, nuts, seeds, and some percent of proteins convert) intolerance genes. Fructose (a sweet substance that is approximately half of table sugar; found in fruits, vegetables, and syrups like honey, maple syrup, and of course high fructose corn syrup) can also be problematic. Many of us are born without the necessary enzymes to absorb fructose. The inability to digest sugar can cause diarrhea. In medical parlance, this is called “malabsorption” but the question remains: if so many people are born without the ability to absorb sugar, would that be considered a “malabsorption” or is sugar absorption an adaptation that occurred later in time?  I am not the first one to ask this question.

Now returning to migraine: it is found in at least as large fraction of the population as it is for the inability to absorb sugars, like glucose or fructose. The set of adaptations for the more sensitized brain to danger (that migraineurs today still possess) at one time may have been present in all of our predecessors. Some percent of the ancient population likely never lost this highly sensitized brain adaptation because in the ancient environment it would have provided a survival benefit. However, in our modern life, the highly sensitized brain has become a painful burden, whereas a large percent of the population adapted to modern life, reduced their brain sensitivity and they feel no pain. This is likely similar to how the majority of the population adapted to digest and absorb sugar; only a minority retained their inability to do so, and they still experience painful health conditions as a result.

The cause of migraines is not the pain—the pain is one of many symptoms. Just like medicating children to be able to eat an ice cream makes little sense, so is medicating migraine pain by blocking certain brain functions makes little sense. That is the only thing that the medicines are able to do and they are dished out to migraineurs like candy. Here are three of the most common (and most dangerous) medications given to migraineurs as “preventive” and what they block: Propranolol (blocks cardiac and neuronal voltage-gated sodium channels), Topamax (blocks voltage gated calcium and sodium channels), Amitriptyline (blocks or initiates many channels out of sync, causing major heart damage and sometimes death). Would we put ourselves at these types of risks in order to be able to eat a piece of sugar if we lacked the enzymes to digest them? I think the real problem is the lack of understanding of the true nature of migraines.

Migraines and Salt

Migraine starts with prodromes that are signals of an impending migraine. These prodromes precede a cascade of events that lead to the pain, which starts with the initiation of an alarm status that leads to fight-or-flight from danger. A migraineur can easily be triggered into a migraine by noise, odor, a specific light intensity, and even taste that is above or below the norm. Migraineurs have hyper sensory organ sensitivities (1), more sensory neuronal connections than the norm (2), and this is how perfume can trigger a migraine because that scent is above the norm. A migraineur will start a migraine unless voltage is re-established. Why voltage? Migraineurs use more voltage (3, 4) as a result of the more sensitive sensory organs. Voltage is generated by the sodium/potassium pumps that are located in cell membranes, facilitating voltage differential exchanges between the inside and the outside of the cell. Since more voltage use requires more salt, migraineurs need to consume more salt (sodium chloride). Migraineurs tend to pass more sodium in their urine as a result (5).

The modern Western diet is forever reducing its salt recommendation for the general population, ignoring that a large percent of that population needs more salt than what is recommended. In general, I found that migraineurs need approximately 50% more salt in their diet than non-migraineurs.

Migraines and Sugar

Another factor is sugar. While there is no academic research on migraineurs lacking enzyme to absorb fructose or that they are genetically lacking glucose absorption (although there are many research papers hinting at their possibilities–here is a review of some), it seems, based on the several thousand migraineurs I studied, that migraineurs are either sugar intolerant or are hyper sensitive to sugar—and all forms of carbohydrates. Indeed, migraineurs usually become insulin resistant. It would be quite educational to provide genetic testing to all migraineurs to find out what may drive their intense reaction to carbohydrates. Most migraineurs can completely prevent all migraines by completely avoiding refined carbohydrates, reducing complex carbohydrates to near the low carbs high fat (LCHF) diet levels, and increasing dietary animal fats (not oils).

Myelin is made from fat and cholesterol; it is the white matter in the brain, responsible for insulating the neurons’ axons, the parts that transmit voltage. Since migraineurs transmit voltage more often, their myelin is more likely to get damaged. Glucose seems to aggravate nerves in general in all central nervous systems conditions. The ketogenic (high fat, very low carbohydrate) diet may be ideal for migraineurs since it appears to repair the myelin damage glucose causes. Myelin can be replenished by eating a proper, high in natural fat (not man-made oils) diet and by ensuring that a migraineur retains a healthy insulin response. As expected, migraine is highly correlated with the incidence of insulin resistance (6-8), diabetes mellitus (7), obesity (9), and cardiovascular disease (10).

If migraine were a true disease, dietary changes would not be able to change the brain response in a way that all migraines become preventable and abortable without medications. Since they can be prevented and aborted with the proper migraine-brain diet (an ancient type diet that is void of simple sugars and complex carbohydrates in excess), it follows that migraine is an unintended consequence of the modern Western diet and it is not a disease.

Sources:

  1. Schwedt TJ (2013) Multisensory Integration in Migraine. Curr Opin Neurol:248-253.
  2. Tso AR, Trujillo A, Guo CC, Goadsby PJ, & Seeley WW (2015) The anterior insula shows heightened interictal intrinsic connectivity in migraine without aura. Neurology:1043-1050.
  3. Liu H, et al. (2015) Resting state brain activity in patients with migraine: a magnetoencephalography study. in The Journal of headache and Pain, pp 16-42.
  4. Tessitore A, et al. (2015) Abnormal Connectivity Within Executive Resting-State Network in Migraine With Aura. Headache 55(6):794-805.
  5. Campbell DA, Tonks EM, & Hay KM (1951) An Investigation of the Salt and Water Balance in Migraine. British Medical Journal:1424-1429.
  6. Bhoi S, Kalita J, & Misra U (2012) Metabolic syndrome and insulin resistance in migraine. The Journal of Headache and Pain 13(4):321-326.
  7. Guldiken B, et al. (2009) Migraine in Metabolic Syndrome. The Neurologist 15(2):55-58.
  8. Sachdev A & Marmura MJ (2012) Metabolic Syndrome and Migraine. Frontiers in Neurology 3:161.
  9. Bigal ME, Liberman JN, & Lipton RB (2006) Obesity and migraine: a population study. Neurology 66.
  10. Tana C, et al. (2013) New insights into the cardiovascular risk of migraine and the role of white matter hyperintensities: is gold all that glitters? The Journal of Headache and Pain 14(1):9.

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