Causes of migraine: what fills your bucket

A bucket that is too full

Picture your body as a bucket. Low-grade inflammation, a disrupted microbiome, nutritional deficiencies, hormonal fluctuations, sleep loss - they fill that bucket drop by drop. As long as there is room, you notice little. But one day you drink a glass of wine, skip a meal, or the weather turns unstable - and the bucket overflows. That is your migraine attack.

The question is not: which trigger causes my migraine? The question is: why is my bucket already so full?

The answer sits deep in your brain, at the basic unit: the neuron. Neurons are specialized nerve cells that process electrical and chemical signals day and night. They are incredibly active - and therefore also vulnerable. A neuron needs at least five things to function well:

• Fuel - mainly glucose, but also ketones and lactate. Your brain is only 2% of your body weight yet uses 20-25% of your total energy (Raichle & Gusnard, 2002).
• Electrolytes - sodium, potassium and calcium in exactly the right proportion. That balance decides whether a neuron can fire correctly (Bean, 2007).
• Oxygen - essential to convert fuel into usable energy.
• Antioxidants - energy production generates free radicals. Without enough antioxidants, that damage accumulates.
• Balanced neurotransmitters - glutamate, serotonin, dopamine, GABA. Too much or too little disrupts the communication between neurons.

Every shortage fills your bucket a little more. When enough of these pillars wobble, the neuron is already on edge. It becomes overstimulated and releases an excess of glutamate - a substance that activates surrounding neurons. They in turn become overstimulated, and so a wave of hyperactivation arises, followed by sudden silence: cortical spreading depression. This is the storm before the calm. When that wave reaches the membranes of the brain, the trigeminal nerve is activated, which releases inflammatory substances (including CGRP) and causes the typical migraine pain (Charles & Baca, 2013; Pietrobon & Moskowitz, 2014).

Sensitization: why it keeps getting easier

Picture the connections in your brain as paths in a forest. The first time you have a migraine attack, you clear a narrow little path. But the more often you walk that path, the wider it becomes. After dozens of attacks it is a paved road - your brain chooses it automatically, even at small stimuli.

This process is called sensitization. With each attack, three things happen:

• The neurons become more sensitive - glutamate accumulates, oxidative stress increases, and the threshold for a new attack drops.
• The trigeminal nerve becomes irritated and reacts faster and faster to stimuli, including external ones - cold wind, smells, light (Burstein et al., 2010).
• Your brain remembers the pattern - it links more and more stimuli, symptoms and even emotions to the migraine attack. Over time, the fear of an attack alone can set one off (Borsook et al., 2016).

I therefore like to make the distinction between migraine that is not yet sensitized (for example one attack a month that lasts a few hours) and sensitized migraine (frequent attacks that are triggered more and more easily). Chronic migraine is always sensitized. But the hopeful part is this: thanks to the neuroplasticity of your brain, sensitization can also be reversed - if you address the right building blocks (Goadsby et al., 2017).

The building blocks: what fills your bucket

Migraine has few direct causes - apart from a handful of exceptional genetic variants. No one gets migraine because they have gut complaints or because they sleep badly. What we do know: there are factors that make your neuron more vulnerable. I call these factors building blocks.

The more building blocks apply to you, the lower your threshold - and the faster a trigger leads to an attack. Each building block gets your neuron into trouble in a different way: through an energy shortage, an electrolyte imbalance, oxidative stress, a neurotransmitter disruption, or a combination of these.

Low-grade inflammation

One of the most underestimated building blocks is chronic low-grade inflammation. This is not inflammation you feel as fever or swelling, but a subtle, smouldering activation of your immune system that can persist for months or years.

Why is this so relevant for migraine? Because an active immune system does three things that directly affect your neuron:

• Cytokines activate the trigeminal nerve - Inflammatory messengers circulating in your blood can directly activate the trigeminal nerve and blood vessels in the membranes of the brain. With sensitized migraine that is a shortcut: the typical headache is triggered without a neuron having to get into trouble first (Edvinsson et al., 2019).
• Mitochondria are suppressed - Your immune system holds back the power plants of your cells. Less energy, more oxidative stress, neurons that exhaust faster (Bristot et al., 2019).
• Neurotransmitters become dysregulated - Chronic inflammation lowers, among other things, serotonin production, which lowers your stimulus threshold further (Miller et al., 2013).

Where does that inflammation come from?

The most common sources in people with migraine:

• A disrupted gut barrier (leaky gut) - bacterial toxins leak into your bloodstream and activate the immune system
• Dysbiosis - a disrupted gut microbiome that produces pro-inflammatory substances
• Nutrition - ultra-processed food, sugar, trans fats and an excess of omega-6 fatty acids
• Visceral fat - belly fat actively produces inflammatory messengers
• Chronic stress - prolonged sympathetic activation shifts the immune system toward inflammation
• Sleep loss - insufficient sleep raises systemic inflammatory markers

The good news: chronic inflammation is highly modifiable. Through nutrition, omega-3 fatty acids, gut restoration and stress reduction, you can lower the inflammatory load significantly.

Your gut and your brain

Your gut and your brain communicate constantly through the vagus nerve, the immune system and the metabolites your gut bacteria produce. Disruptions in this gut-brain axis play a fundamental role for many people with migraine (Arzani et al., 2020).

The microbiome as an ally

Your gut microbiome plays a crucial role in, among other things, the regulation of histamine. Certain bacteria in your gut - especially bifidobacteria - have the ability to break down histamine before it reaches your bloodstream. You may not be genetically strong at breaking down histamine yourself, but the army in your gut can catch this for you.

But the other side of the coin is just as important: when your microbiome is disrupted and you have too few bifidobacteria, the histamine problem gets much worse. You not only lose that bacterial help, but some other bacteria actually produce histamine. It is as if your allies disappear and your enemies multiply.

Histamine

Histamine is a substance that promotes blood vessel dilation and neuroinflammation - exactly what you do not want with migraine. People with reduced histamine breakdown (due to a shortage of the enzyme diamine oxidase, DAO) can get attacks after eating histamine-rich foods: aged cheese, wine, sauerkraut, smoked meat (Maintz & Novak, 2007). Courses of antibiotics, stress, pesticides and acid-suppressing medication can reduce your bifidobacteria and so worsen histamine problems.

Serotonin: largely made in your gut

About 95% of your serotonin is produced by cells in your gut, not in your brain. Serotonin plays a key role in the migraine mechanism - triptans work precisely through this system. If your gut microbiome is disrupted, this can dysregulate serotonin metabolism and make you vulnerable to attacks.

Energy and mitochondria

Mitochondria are the power plants of your cells. They produce ATP - the fuel that drives every cellular process. Your brain is by far the largest energy consumer in your body. When mitochondria do not function optimally, the brain is the first organ to get into trouble.

More and more research points to people with migraine having reduced mitochondrial function (Terrin et al., 2022; Yorns & Hardison, 2013). In a well-functioning system, free radicals - the by-product of energy production - are neutralized by antioxidants. With mitochondrial dysfunction, the production of free radicals increases and detoxification decreases. The result: oxidative stress that both damages the mitochondria further and promotes neuroinflammation.

A shortage of antioxidants, insufficient nutrients or an active immune system that suppresses your mitochondria - they are all roads to the same problem: a brain that has too little energy to stay stable (Fila et al., 2019).

Hormonal fluctuations

The fact that migraine is three times more common in women than in men is no coincidence. Estrogen plays a central role - not so much the level, but the fluctuations in it. Every drop in estrogen can trigger a migraine attack, because estrogen influences, among other things, the fluid and sodium balance, which directly impacts your neurons (Stachenfeld, 2008).

Menstrual migraine

About 60% of women with migraine experience a link with their menstrual cycle. The attacks typically occur around menstruation, when estrogen drops sharply. This affects serotonin production, CGRP sensitivity and prostaglandin balance - each a factor that makes your neuron more vulnerable.

Contraception and perimenopause

The pill-free week with the combined pill causes an artificial estrogen drop that can set off attacks. Continuously taken pills or progestogen-only contraception give more stable hormone levels. Perimenopause is for many women the worst period in terms of migraine: the estrogen fluctuations are unpredictable and intense. After menopause, migraine improves in the majority.

Nutrition and lifestyle

Blood sugar and metabolic flexibility

Your brain runs largely on glucose. But what if that glucose supply is unstable? With a blood sugar peak followed by a rapid drop, your neurons get into trouble: too little fuel. Skipping meals, sugar-rich food or chronic stress - all of it can cause blood sugar fluctuations that lower your migraine threshold (Di Lorenzo et al., 2022).

What makes the problem worse: many people have lost their metabolic flexibility. In a healthy system, your brain can switch between glucose, ketones and lactate. But because of a modern diet with a constant carbohydrate supply, the alternative transporters are underdeveloped. Your brain is then fully dependent on glucose - and extra vulnerable at every dip (Gross & Schoenen, 2019).

Dehydration and electrolytes

Even mild dehydration disrupts the electrolyte balance your neurons need to fire correctly. Sodium and potassium must be present in exactly the right proportion. A shortage of sodium - or an imbalanced ratio with potassium - can set off migraine (Harrington et al., 2006). Drinking enough, with attention to electrolytes, is one of the most underestimated basic interventions.

Sleep and circadian rhythm

Sleep and migraine share the same control center: the hypothalamus. This brain region regulates both your sleep-wake rhythm and your pain processing. Chronic sleep loss raises inflammatory markers, lowers your pain threshold and reduces mitochondrial function. But too much sleep or an irregular schedule can also set off attacks - what matters is the regularity. A consistent sleep-wake schedule, including on weekends, is one of the most effective non-pharmacological interventions.

Unrest and stress

"Stress" may be the most misused word in healthcare. You have too much stress, you need to slow down. As if you have to downsize your life and then everything is solved. It is not that simple - and that is not the message here.

When I talk about stress, I do not mean that you work too hard or have too much on your plate. I mean that your nervous system is in a state of chronic alertness. That can come from a busy job, yes - but just as much from chronic pain, a disrupted gut microbiome, sleep loss, an unsafe childhood, or a personality that is always alert. Everything you read in the previous sections - inflammation, gut problems, energy shortage - is also a form of stress on your nervous system. They are communicating vessels.

Accelerator and brake pedal

Your autonomic nervous system has two branches. The sympathetic branch is your internal accelerator: it gets you ready for action. Your heart goes faster, your breathing speeds up, adrenaline and cortisol are released. The parasympathetic branch is your brake pedal: it takes care of recovery, digestion and relaxation. Without that brake pedal, hormones cannot be restored, inflammation cannot be calmed and brain cells cannot be fed.

In many people with migraine, the accelerator is permanently pressed. That does not have to come from a busy job or financial worries - it can just as well come from an unsafe childhood, a traumatic experience, or simply a body that is already so loaded on so many fronts that the nervous system can no longer come to rest. Your brain has adapted to that state of alertness. Not because it is weak, but precisely because it was strong enough to survive. Only: that adaptation costs energy, and your nervous system runs at a higher speed than you actually want.

The safety balance

In my practice I work with the concept of the safety balance. Signals of safety (a stable relationship, financial security, a supportive network) weigh against signals of insecurity (conflict, uncertainty, chronic pain). When insecurity predominates, your nervous system stays in a heightened state of vigilance - and your migraine threshold drops (Porges, 2022).

An interesting fact: migraine attacks often occur not during stress, but rather in the relaxation phase afterward. On the weekend, on holiday, after a deadline. As long as cortisol is high, it suppresses your immune system and holds things together. But as soon as the stress falls away and cortisol drops, your body finally gets the room to react - and the migraine strikes (Houle et al., 2014).

Triggers vs. building blocks

Many people with migraine are focused on avoiding triggers: chocolate, red wine, bright lighting, weather changes. But a trigger is not the same as a cause. A trigger is the final push that nudges your neuron over the threshold. But that push can only set off an attack if your threshold is already lowered by underlying building blocks.

This explains why the same trigger - a glass of wine, a busy day - sometimes causes an attack and sometimes does not. It is not the wine. It is the state of your nervous system at that moment: how many building blocks are active? How low is your threshold?

A solution-focused approach therefore does not aim at avoiding that final push, but at addressing the building blocks: less inflammation, more stable hormones, a healthier microbiome, better mitochondrial function, more resilience in your stress response. The more building blocks you address, the higher your threshold becomes - and the more triggers you can tolerate without an attack following.

That is a liberating perspective: instead of organizing your life around avoiding triggers, you can work on increasing your resilience. The result is not only fewer attacks, but also more freedom.

Conclusion

The causes of migraine are rarely clear-cut. Genetic predisposition determines how big your bucket is, but it is the building blocks - inflammation, gut health, mitochondrial function, hormones, lifestyle and the state of your nervous system - that determine how full it is. With repeated attacks, sensitization develops, lowering the threshold further and further.

The distinction between triggers and building blocks is crucial. Avoiding triggers is treating symptoms; addressing the underlying building blocks is the road to structural improvement. In my practice I therefore work on two tracks at once: on the one hand the biochemical side - nutrition, gut restoration, targeted interventions, sleep hygiene - and on the other hand the mental track. Sensitization means your brain chooses the migraine path faster and faster. But you can use that same neuroplasticity to your advantage: by consciously activating and strengthening new neural paths, you help your brain choose a different path. In people with chronic migraine who combine the biochemical track with this mental track, I see the most dramatic drop in attack frequency.

The message is one of hope: you are not at the mercy of your genes or your diagnosis. By understanding which building blocks are at play for you and addressing them systematically, you can considerably reduce the frequency and severity of your attacks.

Want to take a first step? The Building Block Analysis maps which building blocks play a role for you. Or read more about migraine medication and where it fits into the bigger picture.

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Disclaimer: This article is written for information purposes and does not replace medical advice. Always consult your doctor or neurologist before making changes to your treatment. The Functional Migraine Clinic works complementary to conventional medicine.