Introduction
Migraine is a complex interplay between neurotransmitters, cytokines and the “trigeminal”. The trigeminal nerve, also called the fifth cranial nerve, is an important nerve in the head and face. It has three main branches that carry sensory information from the skin, muscles and mucous membranes of the face to the brain. This nerve plays an essential role in regulating sensations such as pain, touch and temperature in the face and mouth. Excessive stimulation and sensitivity of the trigeminal nerve is an important factor in migraine attacks. When the trigeminal nerve is overstimulated, cytokines are produced that set off an inflammatory response.
In this article we try to explain, in an understandable way, why you may be sensitive to this. Note that this is only an overview of possible factors and is not exhaustive. Every patient is different and will have a different cocktail of factors.
Methylation problems
Methylation is a chemical process that plays a crucial role in many bodily processes, including building or breaking down certain neurotransmitters, detoxification, the breakdown of oestrogens and many others. A reduced capacity to methylate can result from missing (co)factors such as B12, folate (B9), B6 and choline, or from genetic variations in certain genes such as MTHFR or COMT.
If you have chronic stress, for example, this can put a strain on your methylation capacity, because the large amount of stress hormones produced also has to be broken down again. Since that capacity is not unlimited, this can have a negative effect on other processes in your body that require methylation.
So if this process doesn’t run well, or comes under too much pressure, you get, among other things, a build-up of toxins in your body. One of these “toxins” is the pro-inflammatory forms of oestrogen, which often cause problems such as “oestrogen dominance” and even breast cancer. These toxins can penetrate the blood-brain barrier and/or activate the trigeminal nerve. Once the blood-brain barrier has been penetrated, an inflammatory response follows which, besides triggering migraine, may make the barrier even more permeable to other toxins, so that you end up in a vicious circle. When they “only” stimulate the trigeminal nerve, this too triggers the production of, among other things, the neurotransmitter CGRP, resulting in inflammation and migraine.
Insulin resistance
The liver is responsible for detoxification: making substances harmless. These substances can be produced in your own body, or come in through food, through the skin, through your lungs… Methylation is one of the ways the liver can do this.
When you are insulin resistant, your liver can no longer detect how much energy is present in your blood. In response, it starts releasing and/or producing glucose itself, to make sure your brain doesn’t run out of glucose. But this costs the liver a lot of energy, and it doesn’t have enough energy to carry out all its tasks at once, so it has to set priorities. Because blood glucose is crucial for survival, while a toxin usually doesn’t kill you immediately, priority often goes to producing glucose. If this is short-lived, it is not a problem, but if you have become chronically insulin resistant, you can also chronically have a larger amount of toxins in your body as a result. As described above, these toxins can in turn penetrate the blood-brain barrier and/or overstimulate the trigeminal nerve.
The brain’s energy supply
We said it already: blood glucose is crucial for survival. Although your muscles can manage without glucose for a while (you feel that when you are ill and can barely climb the stairs), your brain cannot. This dependence on glucose makes the brain vulnerable to energy deficits when glucose levels drop. Such an energy deficit can activate the trigeminal nerve and initiate “cortical spreading”, which leads to aura and migraine.
You may notice such an energy deficit yourself when you get an afternoon slump. Brain fog also falls under this. When your metabolism has become used to a constant supply of carbohydrates, it becomes inflexible, and you get dips in your blood glucose a few hours after eating. At that moment your brain gets less energy, and this energy deficit is an important step towards migraine. A flexible metabolism can also feed your brain with ketones and lactate, which makes it less vulnerable when less glucose is available. Ketones are also anti-inflammatory, so they can have a healing effect on an earlier inflammatory response.
Hyperexcitability of the brain
Early stress in the first 1,000 days of your life (including pregnancy) can put you in a state of constant vigilance for the rest of your life. This can lead to excessive production of the neurotransmitter glutamate. Glutamate activates your NMDA receptors, which simply means that it has a very activating effect in the brain. In other words, your brain becomes hyperactive, or “hyperexcitable”. These large amounts of glutamate are neurotoxic. On top of that, neurons use far more electrolytes when they are hyperactive. When these become depleted or are no longer in the right balance, neurons can get into trouble, which can be an important factor in developing an attack.
Note that glutamate can also be found in foods as a flavour enhancer, in the form of MSG. Many people with migraine know that this works as a trigger for them.
Mitochondrial dysfunction
Mitochondria are the energy factories in our cells, both in our body and in our brain. When they don’t work optimally, you logically get problems with the energy supply of the neurons. Mitochondrial function weakens when too many oxidants have built up and there are too few antioxidants to clear them away. We call this “oxidative stress”, and besides triggering inflammation, it also makes your energy factories work less well. These oxidants are produced precisely when you need to produce a lot of energy, so when your brain is very active. They are necessary and unavoidable, but they must always be neutralised in time.
So you can probably see that a cocktail of a hyperexcitable brain, poorly functioning mitochondria, a shortage of glucose and perhaps even a shortage of electrolytes can create a perfect storm.
Leaky gut
A permeable gut, popularly known as “leaky gut”, can have several causes. Stress, for example, opens up your gut “by default”, to pull in as much water, glucose and sodium as possible so that your body is fully ready to attack or run away (the fight-or-flight response). Short term, that is not a problem, but chronically it is. Other causes of a leaky gut include gluten and other specific proteins in foods. A gut infection can also temporarily make your gut leakier.
When your gut is “leaky”, proteins, pathogens and toxins from your food can travel through the gut wall into the bloodstream. Of course you still have an immune system and a liver to deal with this, but you can see that when this is chronic, that system comes under pressure. Your immune system is constantly activated, so it demands more energy. Energy that is drawn away from your brain. Your liver again puts its priority on producing glucose to supply the immune system with energy, instead of making toxins harmless. The result is even more toxins in the blood. We are now in the phase of “low-grade inflammation”. This is an important route to chronic insulin resistance, as mentioned earlier.
When these toxins have entered through the gut and are circulating in the blood, they also reach the blood-brain barrier. An intact blood-brain barrier will hold out against them for a while, but when it is already permeable, for example because of an earlier migraine attack, it won’t be able to stop everything, and a new attack is lurking around the corner.
Protecting the trigeminal nerve
The trigeminal nerve is surrounded by myelin. Myelin is a kind of insulating layer around the nerve. Myelin has several functions, but what is important to remember is that myelin means less energy is needed to conduct electrical signals through the nerve, and that myelin protects the nerve against damage.
When the myelin of the trigeminal nerve is damaged, the nerve is more prone to irritation. When the barrier of your face, nose or mouth is also not optimal, toxins can stimulate the trigeminal nerve directly through that route. These barriers can be more permeable because of certain genetic variations, but also, for example, because of using aggressive face creams, corticosteroid inhalers, …
Building myelin properly requires the right nutrients. Methylation, a process that depends among other things on your underlying building blocks, is also an important step in building myelin.
Conclusion
We have listed a number of important factors here. Although this list is incomplete, it should already be clear that these factors also clearly reinforce each other. Poor methylation capacity, for example, leads to a weaker myelin sheath, more stress, more toxins… But insulin resistance in turn leads to poorer methylation capacity and to the lack of extra backup energy in the form of ketones and lactate.
At the Functional Migraine Clinic we turn this to our advantage. If several factors can reinforce each other, it also means we have choices when it comes to interventions to resolve those factors. These interventions are also inherently health-promoting, and you will soon notice that they can not only help you get your migraine under control, but that other complaints can disappear too, complaints you often weren’t even aware of any more.
Want to get started?
At the Functional Migraine Clinic, our mission is to help you get your migraine under control. By looking at your life and complaints as a whole, across your entire life course, and where useful adding DNA testing through the DNA Migraine Blueprint, you can identify which building blocks can lead to migraine in your case. With both quick wins and structural, personally tailored changes, you can drastically reduce your sensitivity. Every day you win back is a moment of joy for us.
Start with the Building Block Analysis to map out your migraine profile and get started in a targeted way.
