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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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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