#97 Elena Gross


Originally published at: https://ketowomanpodcast.com/97-elena-gross-transcript/

This transcript is brought to you thanks to the hard work of Debbie Mitchum.

Welcome Elena to the Keto woman podcast. How are you doing today?

Hello Daisy. Thanks for having me. I'm actually very excited to finally talk to somebody about migraines. Who knows what migraines are herself, which is really cool. 

Oh yes, absolutely. 

There's nothing better than introspective when you talk about a disease. You actually know what it is like, right.

For sure. We've been trying to record this for ages, funnily enough we were laughing about this before. We've both had to cancel due to migraines at some point, which is kind of funny. But we're, we're finally here and it's fantastic to be speaking to you. 

Yeah, it's certainly also been my fault for having to finish the PhD thesis and lots of things going on. So, my thesis in two weeks, I'm still a little bit stressed, but fairly migraine free, so it's all good. And I've been looking forward to this since you asked me like months ago. Yes. 

Yes. It was quite a long time ago when we started talking about it. But the timing worked out quite well in a way because yes, like you say, it's good to finish your thesis first.

Yeah. And you even skim read it. I'm well proud of you and honored. 250 pages. Well done.

Well I was, I was very interested in, there were, there were all sorts of things in there that we've chatted about a little bit before we start, so we'll have to remember to bring up all the points in our actual recording.

Okay, great. I guess you have a list. Otherwise I'll pull out the thesis again and we can go through it.

So, let's start by hearing about you and how you got into keto, how you got into your migraine research.

Yeah. So, as you can imagine, and as I already mentioned, I'm a migraine patient myself. It's, I think it started about when I was about 14 maybe half a year after I started the contraceptive pill, which is very interesting because having talked to a lot of patients within the course of my study now there seems to be a connection to starting the contraceptive pill and migraine onset or migraine worsening. But I just went to several doctors, nobody knew what was going on, psychologists and whatever brain scans. And finally, I diagnosed myself using the internet actually with migraine and from them then on is basically continuously gotten worse. So despite trying everything, and you know when you're 16 you're trying to go out with your friends or have a drink here and there and the least you want is really have a stable lifestyle of going to bed at the same time and not eating all these triggering foods. And, but I really tried and despite all efforts, alternative and medicine or pharmacological therapies, it just got worse. So after I think it was June, my bachelor's degree, I was always interested in the brain, but I started reading psychology and my bachelor's degree and my migraines actually became chronic and that's something where you have more than 15 days per month of migraines or at least eight of those have to be migraines. The rest can be headache and just really crippling. Your migraines are starting to control life. You cannot go anywhere with that pain. I mean you know that when you have a bad migraine you can't really control or ignore pain in the brain. Really. It's a, it was quite tough, and you never knew whether you could take exams or whether you would have a migraine that day and plus social life. It was really bad. People don't understand and so well by the end of the degree I realized that I couldn't be doing a normal job with these migraines anyway. So, I decided I'm going to change my career path and not become a psychotherapist but go and read neuroscience instead and maybe within my lifespan, figure out more about what is a migraine and what can we do to actually treat it. So more looking into what might be the root causes, where is it coming from and why? Because I went to so many specialists and nobody actually answered that question, what is a migraine, why are we getting it? And of course, you can't treat it.

Yeah. Cause if you want to really properly treat something, you've got to find that root cause.

Exactly. And not just treat the symptoms, not just treat the pain. And as we discussed earlier before this recording,  with triptans, those acute migraine medication or even with analgesics, you cannot take them more than like 10 to maximum 15 but that's already pushing it days per months without getting medication overuse headache or this risking to get one of those. Because your brain basically adapts and then it adapts to having these chemicals around. And if you don't have them around, then you get something like a rebound headache. So, your body is anticipating what these triptans do to your serotonin receptors because their serotonin agonists and if you don't have those around, there's not enough serotonin anymore to basically endogenously activate those receptors. So, then you get a migraine when you don't take those drugs, which is even worse. Right? So, it's like a vicious circle. So, I was stuck in that situation where half the time I could not take anything against the pain and that basically means you're out for days in your dark room and you can't do anything. So very unsatisfying. And  this is why I then went into neuroscience and I was lucky enough to have an open neurologist in Oxford who took me on and I did two of my masters, both master's projects or thesis in migraine research with chronic migraine patients was one in neuro imaging. 

And the other one was STEM cell IPS, CS induced pluripotent STEM cell research with migraine neurons basically, which was also interesting. But for me it was most fascinating to be close to the patients in that neuro imaging. And there was this one incident and I still remember very clearly where the scanner broke down for one patient and she had to come back and she comes back into the lab the second time and I almost didn't recognize her. She was walking up straight, she was smiling, she's lost weight, she was like a completely different person. Back then I already started forming my theory that migraines are at least in part an energy deficit syndrome of the brain. She comes back and I asked her, what did you do? And she told me she'd been fasting for two weeks and that completely shocked me. He says, oh my God, she's not eating for two weeks. And we know that not eating is one of the most potent migraine triggers. Right.

Typical triggers.

Exactly. And she was having a glass of red wine every night and it was fine. She had not a sandwich and I was like, wow, I couldn't believe it because this is Oxford medical school or psychology medical school both together and the neuro-science in Oxford. We did not learn that the brain can metabolize anything else than glucose. Right. So, I didn't even come across ketone bodies during the whole year of my studies there. And I was shocked, and I didn't understand it. And I went about, and I chose the end of the degree. I was procrastinating in the library again as usual and was flicking through a nature magazine and it had an epilepsy special in there. And one of the articles was actually on the oldest treatment for epilepsy, the ketogenic diet. 

And I read upon the mechanisms and this was like the, I think this was the best aha moment I've ever had in my life. I was like, okay, this explains his incident with a patient, and this could also be the solution because reading upon the mechanisms, they were all migraine relevant. And few people know that actually migraines and epilepsy are genetically related. So, some kids would grow out of epilepsy and into migraines. It's almost very similar pathophysiological mechanisms. The two, so some kind of parts of epilepsy are kind of like more severe versions of a migraine attack in a way you could end a lot of epilepsy patients even have migraine.

That's interesting. How does that work? Why is the link though?

They see epilepsy as a migraine. It's a hyper-excitable brain. It's problems with your ion channels in the brain that make your brain super hyperexcitable and this can be exacerbated by energy deficits and when neurons fire in synchrony and they all fire at the same time, you basically get an epileptic seizure. That's your seizure, uncontrollable firing, right, and a migraine CSD or Chronicle critical spreading depression, which is the correlate of the aura phase in migraine, which is this phase of visual. It could be visual but could be any other sensory deficiency that precedes the headache for about an hour and can be anything between five minutes and 60 minutes long. Basically patients go black on one side of the visual fields or you some go paralyzed. Some could also be like a aura of the body. Or you lose speech or something like this. But that's also basically in the back of your head. This is basically a cortical spreading depression means that neurons fire in synchrony go over the cortex in a wave and that's followed by no activity. And that's basically when you then lose sight or lose control partly of body or loose speech, wherever that wave is traveling to basically. 

So synchronized uncontrolled firing is basically the underlying physiological correlate of an epileptic attack.  Migraines have that component to at least to some degree also antiepileptic drugs or the preventative drugs that are probably the most effective or among the most effective in migraine. So, if you reduce your excitability in the brain, you can help a migraine attack. And there's also the link between hyperexcitability and energy metabolism because basically what makes a neuron fire the firing of a neuron is called an action potential. And there's something called a resting membrane potential between a neuron and the outside of the neuron, which basically determines how likely the cell is to fire. Simply put, it's almost like a wall between say the ocean and the land, the wave are the action potentials. If you have a high wall, the wave is unlikely to go over the wall onto the land, so you're unlikely to get an action potential, which means your brain is calm. The lower the wall and the wall would be this resting membrane potential. The lower the wall, the more likely the waves are coming out to come over the wall. And whenever the waves come over the wall, the neuron will fire. Keeping this wall high or keeping the membrane potential high, which in the neuron is done by basically carrying out ions against a concentration gradient to basically keep this potential is an electric difference between inside and outside. In order to do that, you need to spend a lot of energy. So, 50% of the brain's energy demand actually goes into caring ions across their potential difference in the brain, 50% it's massive. So, if you have reduced energy in the brain, of course this wall is going to come down. When the wall comes down, your neurons are more likely to fire. What does that do? Well, first of all, you might get a migraine attack. But also, most migraine patients have some kind of sensory sensitivities. 

So hypersensitive to light, to noise, to smells.  Why? Because it needs much less of a trigger for the neurons to fire. If the wall comes down, they fight easily. So, life becomes much brighter and noise becomes much louder.  So, I think that's how you can explain those other issues that come with a migraine attack before and during an attack as well could also be explained by this energy deficiency and by these neurons that are firing more likely. And the genetic predisposition here is a shared one between epilepsy and migraine would be, and there's so many different ion channels in the brain that basically carry ions across membranes. That's a function. Right. And if you have some that are predisposing you for a lower wall already or an increased tendency to fire and you put yourself in an energy deficient environment by only eating carbs. Right. Or you have mitochondria damage, then basically those two come together and you get a migraine or, you get more migraines. And I didn't want to distract from the personal story, but maybe we could come back to this later. I believe that migraines, one says that chronic pain has lost as one in function. That's what'd you say? Acute pain. Everybody knows it's very important for evolution and once it becomes chronic, people say it's lost the wanting function. We just need to treat the pain. But I doubt that. I think that pain always has a warning function. A migraine is a very potent warning of our brain that it's in an energy deficit, that it's, the oxidative stress is too high. It's a very, very powerful means for the body to force us to stop what we're doing to rest, to go in a dark room, we’re nauseated. We don't want to move. That's one of the most migrant symptoms. Movement makes it worse. Light makes it worse so you basically you shut up all sensory input, you conserve the energy you have until the homeostasis in the brain is restored and then a migraine stops and very interestingly during the migraine attack, early studies about 50 years ago and they've completely been forgotten about, showed that during a migraine attack, irrespective of what people are eating, ketone bodies are calling up and like policies is going up so it's like a counter reactive response of the brain saying Oh we have an energy deficit now we need to ramp up some kind of energy that we can actually use. I now know that my migraines are trying to protect me from something and knowing that also helps you to kind of accept what you have. In a way I guess it's not your body forcing this migraine onto wanting something bad is actually trying to protect you from something that is super harmful. It might increase your risk for Alzheimer's in the long run or for some kind of brain damage in the long run because there is migraine stroke in patients that have migraines with aura. Typically for a very long time. I've been working in neuro imaging as I mentioned before, for some time you find this micro lesion in the brain. People usually say a migraine doesn't leave a mark, but it actually does, so the more you get them, you actually do get to see it in the brain. Even with like a very course neuro image of like one square millimeter, which a on a on a much finer level, you'd probably see other things as well. Ions accumulate in the brain and all sorts of things.

Yes, I have read that actually and it makes complete sense.  If something is happening that your body is warning you against, it's likely to leave a mark of some kind. 

Yes, and it hasn't lost its warning function. It's just that our environment has become so maladaptive to our migraine warning genes that say that people have it chronically, and of course it's debilitating, but that also means that they probably have some kind of oxidative stress level in the brain or constant energy deficit. And that's something you can also measure in migraine with neuro imaging these days, they have about a 20% on average ATP lack in the brain compared to controls, even between attacks. 20% less energy that's not benign, and that’s episodic patients. That's not even chronic patients. So, I don't want to know how much lack of energy in the brain a chronic patient would have, and all the body can do. It cannot talk to you. It can send you pain signals, It turns these ancient mechanisms on, it turns the pain cause Kate on to force you to, to stop whatever you're doing, to change something and tell you, hey, we're not doing okay. There's something wrong here. Right? That's what pain tells you. And then in chronic patients it's just that their genetic load is so high, and their mitochondrial functioning might be this bad. And there is other environmental situation with regards to food and energy might be this bad that they are constantly reaching the migraine threshold, the warning migraine threshold basically that the brain is always in such a state that it thinks it needs to warn them. Back to the personal story, just to finish that off, basically I stumbled across ketosis. I was like, this is it. I started self-experimentation. It went very wrong at the beginning because I had no idea what I'm doing and what a cute Jenny died is triggered like the worst migraine ever. I think it was fasting and I wasn't in ketosis for like 10 days, which is crazy. My body completely had forgotten about how to make ketones or how to get them anywhere. But when I finally got it right, it was pretty amazing. Lots of self-experimentation followed. And then I knew that I wanted to do this in my PhD and nothing else. That turned out to be fairly tricky because everybody was like, Oh, you can come here but you do what we want you to do. I mean, as a pre PhD student, nobody believes you and it was fairly risky project, but then in Basel, and this is why I turned on Oxford in the end, is in Basel they said, if you come here, you can do it as a side project, and then before even starting my supervisor, he has said he has to leave to Germany. He's, he's leaving, he's gone. So, my funding went, but that was basically the possibility then to say, okay, I'm going to make this my major project. I'm going to leave neuro imaging. 

It's interesting, but it's too far away from the solution. I want to do this Keto and migraine full time. And in order to get a grant that funds a full phase two clinical trial, which is fairly extensive, we decided to go the exogenous ketone round route, which is basically changing one variable only adding ketone bodies and find out what does the presence of ketone bodies change in a migraine patient with regards to potential mechanisms. And is this enough to show a significant clinical effect in those patients in terms of migraine day reduction and other outcome measures. And that's been going on for like four years now. I think with the planning and everything and we're in the last half a year. Last patient cohort is currently, in the study and then hopefully by next year we'll have the results of that. But that's basically the journey I've been. Now I'm towards the end of my degree and I was able to deep dive into ketone migraine, which is amazing if you can make your disease your passion, it's kind of cool.

Exactly. So, you not only diagnosed yourself, but you're going on to find the best treatment for yourself and for others at the same time. Yes, exactly. And we'll talk a little bit about what your Keto looks like later because I know having had a conversation with you before we started recording, it's going to play into something to do with what we're going to talk about. So, I think it'd be better put that in a little bit later, right? Yeah, sure. You have spoken about already a little bit about what migraines are, but perhaps you could just talk a little bit more about that and also the connection you found with all the different triggers associated with migraines.

Yeah. So, migraines typically aren't. That's kind of, I maybe one more funny anecdote with regards to what a migraine actually is. Because when I was five or six years, I had a favorite movie called poom tin and Anton, it's a German movie. And uh, I used to watch it on rainy Sundays with my friends. And in there the protagonist's mother has migraines and her friend asked the dead, what are migraines? And he says migraines are headaches that don't exist as in like she's making this up. So, for the next 10 years following, I actually believe that migraines are a term for a headache that doesn't exist for a made of headache. And then I had to, once I got there myself, I found out that they're very real. So, migraines are not headaches that don't exist. They're actually even more than a bad headache. Typically, they're from the headache, from moderate to severe quality pulsating.  They're typically unilateral meaning they only appear on one side of the head. Typically, it could be some people have it strictly only on the right always and for some people it swaps. But typically, you have a preferred side where it happens, at least at the beginning. Eye pain is very frequent. Then you have kind of a premonitory phase, which precedes the headache attack up to one day or even more. And there you typically have associated symptoms, neurological symptoms like nausea, light sensitivity, noise sensitivity, smell sensitivity. Sometimes moving makes it worse and you have this like feeling of doom. Some people get really agitated. Other people get super tired and super fatigued and those symptoms can last throughout the headache phase. And then they will also typically last for the prodrome phase, which is basically the postdrome phase. Sorry, the phase that follows the headache. There could also be days even while you're typically very fatigued and sometimes you have gastrointestinal symptoms. Most people have a lot of yawning. Maybe they pee more or increased appetite. It's like your brain sensing there's something wrong and now you need to eat as much as possible before the attack comes. A lot of people throw up. It's much worse than a headache because you can't ignore it. With a headache it's like a pressure type of a pain and it's your whole head typically and moving makes it better in migraine moving any kind of movement makes it worse.   pool sating sometimes stabbing quality is also fairly common. Does that summarize, I mean you could even, you could tell us, would you mind going, it feels like it's fairly, it's a fairly individual. This would be like more typical summary. 

 Duration wise, the diagnostic criteria says between 4 hours and 72 hours. So, between 4 hours and 3 days, which is quite correct. Typically, if I have a migraine that’s longer than three days, it swaps sides. So, I know, okay, next attack is starting. It's not the same. 

You’ve got another one. 

Exactly. So, if that's how you can tell and some people have an aura phase, you already touched upon this, about a third of migraineurs will have the phase of a visual or whatever, a sensory, defect. It will change. So, it's only there for about an hour and then it will proceed, it could be a paralysis, it could be typically as visual, so visual disturbances, zag lines, blackout, whatever, these kinds of things. But it could be any sensory quality, losing speech as well. 

That's fascinating to me because I used to have these incidents when I was younger, and they've always been a mystery always. And I may be had about half a dozen in total, but it was my late teens, early twenties. I thought it might be something to do with some type of epilepsy, you know, one of the really sort of low-grade forms of it. I just wasn't sure. And the reason I didn't investigate it was because I basically, I didn't want to have my driving license taken away,  which someone told me if they start investigating thinking you might have epilepsy  that's going to happen, but it never happened in any way like that. And I always had some kind of warning it was coming, but what happened was that I would kind of black out but stay conscious. Yeah. So, my vision would go completely. That's a typical aura. My hearing would become muffled and the best thing I could do was just to sort of curl up in a fetal position. Terrifying. It happened once after a very stressful event where it was when I was at university in Liverpool and it happened just, actually on the phone to my mother and I think I terrified her because I said, I've got to go, I think I'm going to pass out. And I managed to get myself in the lift. I was on the 11th floor and then it happened. I couldn't see, I could hear a little bit and luckily my, my roommate was either in the lift or was that, I think I managed to hit the right floor or was there when I got there and I said, you're going to have to guide me to my room because I can't see.

Yeah, it's so scary. It's so scary.

And it was very, very strange. It was, and I had no idea what that was, and I've never associated it with migraines at all.

So, the interesting bit is that all phases of the migraine attack can happen on their own. So, you can have an aura without the headache following. You can have the headache without the aura. You can have premonitory phases without the headache as well. So, people can have isolated auras, which is basically almost like a small epileptic attack. And depending on where this wave is traveling to. So, you have to imagine, right? We said that keeping your resting state with membrane potential upright takes 50% of the brain's energy. Imagine there's now a wave of electricity traveling over your cortex at the same time and you then have to rebalance all the minerals in your brain. That takes a lot of energy. I think it increases energy demand by like 200% or whatever and oxygen demand and everything. So it takes some time to basically get those neurons back into a state where they can fire again. If your neuron can't fire, you can't see, feel or hear anything. So basically, what probably has happened is that this wave was traveling across your visual cortex in the back because all your vision is basically centered in the back of the head. So that means if something troubles over there and basically enables all these neurons to do anything, that means it's all vision is gone. That's very interesting. The studies on the, I think, Second World War, First World War,  British soldier had these very weird helmets that would basically stop at the back of their head. So, you'd have a lot of, or quite a few soldiers coming back that has a wound or a shot into the back of their head and they would lose selective parts of vision depending on where the bullet has hit. So, if something would have hit all of your visual cortex in the back, then you just can't see because the neurons, they are not working anymore. So, brain function, at least in some regards is localized in the brain.

Oh, how interesting. 

Would you probably have it as an is an aura, a prolonged or maybe even so then you can see it for patients, typically when they have it the first time it's, it's terrifying. They think they have a stroke. But the good thing is about an aura phase and that’s, where people shouldn't be too terrified or worrying too much. That typically function comes back within the hour. So, it is more energy demanding. It does create more oxidative stress, which is probably why often aura phase of migraine headache starts because of all the oxidative stress, all the metabolic strain it puts in your head. Right. I mean, it now has to rebalance all these things after this electrical wave of activity. And that takes a lot of energy. It takes a lot of electrolytes. It takes a lot of oxygen and it takes a lot of things to get back on track, but it usually does. So your vision will come back and you’re feeling in your arm. Will come back and all these things, but it’s a fairly terrifying event. And that will be a prime example for an aura. Quite a bad one.

Yes. How interesting. And it's, and it's what I realized that it would pass fairly quickly. It was anything from, you know, 10, 20 minutes. I just knew that, yeah, if I just lay down, I mean, it's the safest thing to do, isn't it? Sit down, lie down somewhere.

It's the best for you brain as well. You rest, you're not spending energy on walking, for example. That would again, expand energy that your brain would need to restore itself. So, it’s kind of intuitively you do the right thing. How interesting. You've solved a mystery. Yeah, yeah. I mean there's other things I've been wondering about and it's like little puzzles that you can solve along the way. It's kind of nice if you can explain your symptoms looking back. Because you always end up going to a medical doctor typically doesn't help because I don't have explanations as to why things happen. They only have a symptom treatment response. Typically for an aura, there's some drugs you can take, but it reduces the aura frequency by like 20% or whatever. It's really not worth it, but it's good to know that when it happens rest, lie down, don't do anything. Maybe have some magnesium’s and minerals, maybe if you can get something down.

It kind of makes sense that it happened at that period in my life. Maybe where, you know, a lot of things are changing with your body because it doesn't seem to have carried on. That was something that happened within a period of a few years.

Yeah. So, your threshold would have been much lower because if you're stressed, and that's something that was very interesting to me because there's psychological stress and there's physical stress and we always think that these are different things. But actually, they're fairly similar in terms that all of these stressors or stresses, irrespective whether it's physical or mental, is basically causing oxidative stress. And oxidative stress is the common denominator of all migraine triggers, irrespective of how unrelated they seem to feel. So, fasting, skipping a meal of course causes hypoglycemia, stressful, oxidative stress, increases stress, mental, physical, aerobic exercise, any kind of exercise. And that's why migraines typically have an intolerance to exercise, causes a lot of oxidative stress. And if oxidative stress exceeds your antioxidant capacity, so your body's ability to buffer this oxidative stress, then it will do a lot of harm. So, if your exercise is triggering a migraine, it's actually doing harm and you shouldn't be exercising, or you shouldn't be exercising at this intensity. 

Because what oxidative stress also does is it's damaging your DNA, it's damaging your protein, it sets you up for all sorts of potential chronic diseases long term. So, you really don't want that. Then sleep changes, oxidative stress. Again, you can see that in nurses, in people that change their circadian rhythm, those come with more migraines and metabolic diseases or varying hormone changes. Female hormone changes during this cycle will increase oxidative stress also, and that's where the pill comes in. I said that was a correlation between pill and a contraceptive pill, which is basically given out like candy to any teenager. I found publications that show that pill onset increases oxidative stress even in athletes by 50% but 50% more oxidative stress. So now if you have a migraine genetics in your underlying system, then taking the pill might be enough to set you off with migraines for life basically.

And talk a little bit about what you were saying about triggers being like a bucket because it really explains, doesn't it, how some people get them a lot and some people get them rarely.

Yeah, so there's a few more alcohol, sensory triggers. People have weather changes as a trigger even that makes sense. Because of atmospheric pressure. It decreases or increases the oxygen as in the air and you have alcohol and sensory triggers will also increase oxidative stress, especially blue light for example, is increasing oxidative stress not only in the eyes but also through the skin. So, we can see that all of these migraine triggers that we know are basically working on a similar pathway. Now if something targets a similar pathway, that basically means that you are adding up the stressors and you can think of a migraine threshold maybe as a bucket full of water. Some of us will have the bucket half full already when they're born because they have migraine prone genetics. Then you're getting the pill for example, right? So, your migraine bucket is becoming increasingly fuller. 

And then on this bucket you're now adding, as a female adding this as a cycle in hormones. For example, estrogen is very antioxidant. So, one during the time of your period when it's high, you're less likely to have this water bucket overflowing because it's kind of buffering. It's a bit like the estrogen is letting out a little bit of the water and increasing your migraine threshold. So, this explains why some triggers like a glass of wine might be fine during some parts of the months. Whereas if you have other stresses at the same time so you haven't slept well, all of these things you haven't eaten, you've done exercise, you've had some alcohol depending on your genetics and your environment and how full your bucket already is. These individual triggers might then set off a migraine, have the bucket overflowing or not. Basically, a full bucket means migraine attack and all these trigger factors together will maybe cause a migraine attack at some point and not at the other point. 

But if you're born with a bucket that is already full, you'll have a migraine all the time. Or if you're born with a, with a bucket that is half full, but then you're on this worst diet or you have mitochondria dysfunction because of toxins or other things and that sets off that your bucket is full, then you also have a migraine all the time. So, it's always an interplay between the genetic water load and your environmental water load, and when those two are added together, and environmental could be several different triggers, so many different things coming together. But if both of those come together and make the bucket full, then you have a migraine attack. From evolutionary perspective, it makes sense that some of us have these hyper excitable migraine genes because typically you're already during attacks. You don't have this habituation phenomenon, which basically means habituation is a way for the brain to conserve energy, which means that typically one of the rules is that your brain only encodes for change. 

So that means we're not like a computer, we're not firing all the time. Basically, a brain is only set up to fire when things change. So, if a normal healthy person looks at a checkerboard, let's say, or a wide wall and it's not changing, the brain will just stop firing. But in migraine brain will keep firing. It doesn't have habituate, so it's spending more energy, but it's also basically alerted all the time. And you'll see that in migraine patient typically is this perfectionist person and always kind of a little bit more sensitive to light noise and on all those things, even between attacks slightly. But if you think about a tribe of people, every seventh person has migraines in the world. There's like a billion of us. If you think about a tribe being made of, Oh I don't know, 20 people, you would have three migraine genetic people in there. 

And they would be the first ones to hear when a lion is coming at night because they have light sleep, they pick up very small sensory cues. So those would be the ones that might be saving the tribe from lion because wake up first. There must have been some kind of evolutionary advantage to having these migraine genetics around because if a population is affected, 15% of the population are affected by a certain genetic combination and genotype. There's no way that didn't have an evolutionary advantage at some point in time. So that just means that all the environment has changed so much that we're now at a disadvantage with those genes. But otherwise it would not have stuck around that 15% of the population have this. So migraine really must have had some evolutionary advantage and that was probably maybe on the one hand, and that's very speculative, but saving the tribe from things that require somebody to be alert all the time, even during sleep, more or less like being hyper-responsive. 

And on the other hand, it's a preserve mechanism that shows you something's wrong in your brain where an energy deficit, oxidative stress is too high. We now need to rest. And it's very interesting how you can, and this is described in this nature and neurology paper that I sent you that was in my thesis. Basically, we cannot even mechanistically explain how we get from attack triggering to the resolution of the attack once. Why adaptive behavioral changes. We are forced to rest and do everything. So that homeostasis is basically conserved. And that is done by via molecule, one of them and neuropeptide that is causing pain called CGRP. And CGRP is basically what now Novartis and Eli Lilly and other pharma companies are blocking with their CGRP monoclonal antibodies, which is these injection-based treatments that have just come out recently. And they call it the migraine with [inaudible]. 

I think it's an injection you get once per month. This is basically blocking the action of this molecule, but this molecule also seems to be part of mitigating the attack because it's very antioxidant. Yeah. It's basically the body sending out a pain signal and the solution in the same time. It's stopping you from doing things, but at the same time it is kind of treating the initial problem. And another thing that is going on, like the third pillar of the whole migraine attack thing is the metabolic changes that happened during the attack. One of the things that can fairly reliably or was shown like 50 years ago, again to fairly reliably trigger a migraine attack in about 50% of cases is a giving a glucose tolerance test. You get 50 to a hundred grams of pure glucose to migraine patient and 50% of them will develop an attack in the coming hours, like 8 hours. 

It's always delayed for the eight hours. And if you look at those that develop an attack and those that don't and their metabolic responses, fatty acids, lipolysis and ketone bodies only go up in the ones that get a migraine attack and they're eating normally they're eating the same as the control group basically. If you want to trigger a migraine you give them sugar and then you see that there is a metabolic response. Basically, our body is trying to help us to save us there really because a, it's changing your metabolism. It's providing the brain with an alternative energy source because it is increasing glycolysis, increasing ketogenesis. It is sending out this molecule that is antioxidative and other molecules to seizure a piece, just one of them. But at the same time, this molecule also hurts because that's the only way we would be stopped from running around and doing more damage for the brain. Expanding more energy.

Let it work. Yeah

That's a long explanation. Sorry, I think I'm rambling on too long. 

No, no, it's fascinating. And I remember what you cited in the migraines used to be referred to as hypoglycemic headaches. So that makes perfect sense. It's that crash afterwards. 

Yes. About a hundred years ago. And then, you know, modern studies came along, pharma came along and then this was completely forgotten about for 50 years, almost a decade. And people have thought migraines might be a vascular problem and then it was neurogenetic and now it's hyper excitable. And yeah, those things do play into the picture. But a hundred years ago this neurologist was treating his patients already with a low carb diet very successfully.

And it makes perfect sense then. And that's the way I've always felt with this stacking system. With the bucket being full of the different triggers that by changing your diet you empty a load of water out of that bucket straight away. Yeah, exactly. Lower your threshold right down because there were all sorts of things that used to be reliable triggers for me for migraines. You know, things to do with the weather, surf, it was really hot or if a storm was coming, smell was one of the biggest things for me. If I walked past someone who was wearing some perfume or cigarette smoke. I could guarantee that I was going to get a migraine straight away. They do still happen, but nowhere near as often and so it makes total sense that by changing that big thing, changing my diet has dropped that threshold down.  It makes sense. What you were saying earlier about the problem when you're  having the migraine is that lowering in ATP function and elsewhere, you talk about with ketone bodies that they're capable of increasing relatively speaking to glucose that they can, you can produce more ATP. So, it makes sense. Yes. That by treating, if you like migraines with ketones, you’re getting that energy balanced back in place.

Yeah. You have a more effective energy source there. That's true per oxygen molecule consumed. Basically, you also circumnavigate any problems or a lot of the problems with glucose metabolism and transport. So dude, one transport is might be deficient, which is the officially the transport system that gets glucose into the brain and, and insulin, insulin is also needed for, for glucose metabolism and ketone bodies are completely independent of these two issues. And then there's more that comes with this dietary change, right? You also have less hypoglycemia. You have a more constant supply because you can use your fat stores now, which you were not able to use before. You might have more micronutrients in your diet as well. When you clean it up, you have less processed foods, less processed foods mean less oxidative stress again. So just getting ketones high is not the answer. 

We saw this very recently with a study on one of the first ones on cancer, brain cancer and ketone bodies. They were put on this very nasty Nestlé shake product, which is like the worst ingredients that you could ever give to anybody like rap seed oil and processed oils in there. But participants were in very high ketosis, like five millimoles and they would still die as quickly as a control group. There was no change at all from being in ketosis, which is why I stress so much. The quality of your ketogenic diet is key. It's not just about having ketone bodies presence. You also need the antioxidants, the minerals, the vitamins. You need to make sure that you don't add trans fats or any crappy fats, which would make matters maybe even worse. A high quality, real food ketogenic diets adapted to your micronutrient needs and to your antioxidant need. 

I think that's the key. Also checking whether dairy is a problem for a lot of migraineurs. Dairy can be problematic, especially casein. Playing around with a non-dairy, more like paleo ketogenic diet can help.  But there's a lot of things that this diet can set right. One of them is a mitochondrial functioning. Ketone bodies are antioxidative on their own, so the antioxidants and when you burn them you produce less oxidative stress, which again puts less metabolic strain on already damaged mitochondria. And you have the transport issue, you increase mitochondria biogenesis, so you have more powerhouses in the cell. Ketone bodies are able to reduce brain hyperexcitability via very many different, I think at least four mechanisms are now known. So that's also another issue that is key for epilepsy and migraine is that you reduce or increase the inhibitory transmitters in the bright and reduces hyperexcitability, which again will empty your buckets of water is one of the ways. 

And, and its anti-inflammatory inflammation plays a role in almost any chronic disease. So again, that's water out of the buckets. And the nice thing about this ketogenic diet approach or ketosis in general, maybe even in part exogenous ketones, we will have to find out. But is that it targets so many migraines rather than mechanisms, even the gut microbiome. There are about eight migraine mechanisms that we know are targeted or potentially targeted by ketosis. And migraine is a very multigenic disease as any chronic disease. So that means that many different pathways and things are probably involved in an individual migraine patient’s migraine, you cannot treat a chronic disease with a one target drug approach because there's not one target in a chronic disease. And the beauty about ketosis and ketone bodies is that it targets all of these different mechanisms individually or together and migraine that might be completely different in one person to the migraine mechanisms in another person. 

Both of them might profit because some of their migraine causing mechanisms are effected by ketone buddies and the other person's as well because they just have such a big variety of metabolic and signaling action signaling being like they change your gene expression or they change hyperexcitability so they're the signaling and metabolite at the same time alternative energy substrate, but also changing all these other pathways in a favorable fashion. And I think this is why there could be such a potent migraine and even as a neurological disease strategy because they target so many of the known chronic disease or neurological disease pathways that are involved all with one molecule basically. It's quite fascinating. 

Yes. I was going to ask you about inflammation because I've read the migraine is potentially an inflammatory disorder, but it would make sense if you’re causing this damage. 

But that's again too simple, right? 

Yeah, exactly.

People say it's a hyper-excitability problem. The, I would say it's primarily inflammatory. The other people say, Oh, it's vascular. The other people say, Oh, but it's purely energetics. It's too simple. And also, there's probably migraine subtypes that we just can't distinguish because the phenotype, so what we see is fairly similar, but this maybe there's a thousand different migraines. Right. 

And are these also maybe secondary issues? Like what you were saying when we were talking about the triptans, and you just touched on it there, the migraines were thought of as a vascular disorder. Yeah. But your argument is that that's just a secondary thing that happens because of it. 

See is, you know when you ask a migraine patient, they have this pulsating pain, right? So pulsating pain basically means that some kind of vascular receptors must be involved. Right. So, so when I had migraines 10 years ago, they told me, well, it's basically that your arteries in your brain are dilating, they're pressing against the skull and it hurts. 

But that's the symptom rather than the cause. Yeah. In the dilation. Now they know that the dilation, it doesn't correlate at all 

the dilation of the arteries and the pain onset is not, the timing doesn't fit at all. There's definitely not a vascular disease, definitely not. But the dilation could be the brain trying to get in more blood, more blood meaning more nutrients and more oxygen. Right. So, you have a delayed dilation in the brain. I could just be a secondary effect. As you say, it's probably not causative, but also the triptans are targeting receptors on arteries. But also, that is a just one thing that we know they do, and they probably do other things as well. They could also inhibit a neuropeptide that is involved in pain for example, or work via completely misunderstood mechanism. We don't fully understand why triptans are working at all. Really. 

So similarly, to what you were saying earlier, actually part of this pain response that you're getting but packaged up with that is a potential treatment. So, it symptoms of the cause, but actually what's happening in your body is helping treat that original cause, treating that migraine and actually by treating those symptoms, potentially you're dampening the treatment that's just happening naturally in your body. 

Not with a migraine and not with the triptans necessarily or the analgesic. I would definitely say don't necessarily suffer through an attack and be like never going to take triptans or ibuprofen or aspirin., I don't do that because it's just unnecessary pain and suffering. So I still take those because I know that those don't target the CGRP, but I think I would personally not do this injection based treatment of CGRP, monoclonal antibodies because I know CGRP, this neuropeptide is also expressed very highly in the gut and it's not a selective treatment so you basically just block the action of one peptide in the body, which I think is kind of crazy. There's not a lot of side effects yet, but if you do that for a long time, I'm really not sure what it does because we're also inhibiting other bodily functions and we don't really know so I'm going to wait and see, but I know that for some people it really is a life changer in the sense that their pain is gone. 

For others it doesn't work at all. I think it really depends on what kind of neuropeptide cocktail is responsible for your personal migraine pain, but you need to remember you are blocking the pain and the same goes for triptans. You can see it as a center in the brain and the brainstem that basically lights up. When you get a migraine, you can see that that is still ongoing while you're taking the triptans, which means the migraine is still there. Triptans do not abort the migraine. It's just not true. The same as analgesics and this rebound, migraine is not a rebound migraine. When the triptans wear off, the attack is just there and it's going to be there for that much longer. If you take the triptans and then you go to work and you do your whole stressful day and maybe even do exercise and you're not resting at all, I will not do that either. You need to be aware that the pain might be gone, but the migraine is still there, so you need to take care of yourself during this attack. If you don't want it to come back, he would still rest and do things a bit more slowly, in my opinion. So that would be my advice. 

Yes, that's a good point. So, you're taking something to get rid of the pain, but you should remember what you would have done where you not to take it, which is exactly that lie down in a dark room. Exactly. 

Don't endure the pain if you don't necessarily have to and you can tolerate those drugs quite well.  At least are under 10 days a month I would say. You really shouldn't be taking them more often day wise let's say. But yeah, don't forget that you have the migraine in the first place. That's a very good tip. Remember what it would be like or what you would be doing if you were still have this attack and it probably wouldn't be running. You're going to work, doing the laundry at the same time, picking up the kids and cooking and shopping and everything and like these hours of migraine, probably not. 

Yes. It's actually still do what you would have done and talking about different ways that you can help. Maybe you could talk about some ofthe preventative treatments you've listed in your thesis. There weresome different vitamin supplements, all sorts of different things, including the ketogenic diet. 

Yeah. It's quite interesting. There are some studies that show that antioxidants basically can help migraines, quite a lot as good as drugs actually. And it's those could be CoQ10 300 milligrams, that could be riboflavin.  Riboflavin is vitamin B2 400 milligrams, so high dose, but also just a good complex, B vitamin and magnesium can help. Also, it's responsible for 300 enzyme function and we tend to be too low. So, a good mineral supplement can help and there's also alpha lipoic acid that has been shown to be my one protective, which is a strong antioxidant. There's other antioxidants astaxanthin. There has not been a study, but it goes into the similar lines. So that's something one could think about as well. If one wants to figure out the migraine. A best thing would be actually, I mean these things are just done an edit to the patients. 

I mean CoQ10 you could always do, but there might be other minerals or essential vitamins that are lacking. So I would always try and advise too, if you have the funds, do a blood test, minerals must be checked in full blood and vitamins, you can also check and see whether you might be lacking some of the things or even more. And then you can add a broad spend, high quality multivitamin or selectively take the things that you're lacking could be zinc as well and that will improve your mitochondrial functioning and mitochondrial functioning is at the key for migraines. And you can add a ketogenic diet if your mitochondria are not working because you are lacking some vitamins or you're completely toxic, for example. You can add ketones almost as much as you want. It won't help much because also ketones need to have mitochondria that are producing your ATP. 

It's like, okay, so in a car, right. It's a bit like if you are calm and tolerant, if your glucose metabolism isn't well, it's like a Petro car and you're feeding a diesel all the time, it won't run well. Right. But if you are now giving diesel to a diesel car but the diesel car doesn't have an engine, it's still not going to run. So the engine is your mitochondria, you can swap the fuel, but if you don't have an engine in your car, you can swap the fuel as much as you want. The right fuel won't do anything. You need an engine that can make energy that can power your car. Right? So, the first step is to get your engine right and then you can change the fuel. So that’s what I was also referring to in this paper that you were talking about is get your mitochondria as best as you can. Antioxidants, whole food diets and supplement either if you have the funds selectively, if you don't have the funds with a good broad spec multivitamin in a way that has everything that we need. 

And something like magnesium is, is a kind of thing that you can take without doing harm. It's very obvious when you've taken too much, isn't it? 

Exactly. And CoQ10 is the same. Ubiquinol is the preferred version. There are two versions of CoQ10 which might be worth mentioning. Ubiquinol is the reduced one. You'd ideally want that without maybe a hundred milligrams is enough. If you have Ubiquinol then you probably need to take 400 milligrams because it still has to be converted with the minerals and the or the vitamins more. Always try and take the active version and for example, there’s four different versions of B12 and cyanocobalamin is even toxic. So please also don't go to the supermarket and take the cheapest multivitamin you find, it's probably going to do much more harm than it does good because if you have non-active vitamins you liver  needs to detox them again, your liver is already busy with all other toxins and oxidative stress. So yeah, don't save on that. It's probably better to take nothing then take a bad supplement. And then there's other things that you can do. So we talked about vitamins and minerals, we talked about getting antioxidants in your diet, which is basically colorful vegetables if you can. And it could also be in supplement form. 

This brings us quite neatly to a conversation we were having before where I touched upon earlier asking you what your keto diet looks like. We were talking about a few things clicked in in my mind again about what happened when I did my carnivore challenge and one of the things that increased a lot were migraines. I had other issues too with hot flushes and acid reflux and my mood was bad as well. But when I mentioned that to you earlier, your eyes lit up and you said yes it was something that was very common and the people doing a ketogenic diet if they suffer from migraines, need to be aware of and that's where the importance of these micronutrients might come in. Perhaps you could talk a little bit about that cause you just touched on it there with the fruits and vegetables of different colors. 

Yeah, so basically, I figured out for myself that a very restrictive ketogenic diet that only basically has green and white vegetables wasn't really cutting it and I mean carnivore would just be unthinkable. I think I did it for a week, it was horrible. There's something called an ORAC index and that basically measures the antioxidant content in foods, the foods and even coffee has antioxidants. The darker or the more colorful a food is basically the more antioxidants it has. Like blueberries is super high, chocolate, coffee and then other colorful fruits and vegetables and basically if you think about, a migraine patient typically on a regular basis exceeding their antioxidant capacity. So oxidative stress is a good thing in moderation, but whenever oxidative stress exceeds your body's capacity to fight it, it's bad. And if you take out all the foods and fats and proteins, they don't have a lot of antioxidants. 

This ORAC index is very, very low. So basically, that means that likely, even though they have some ketone bodies present and there is somewhat antioxidative, they will still be lacking potentially, or they will still do better with increasing antioxidant via their diet to help the mitochondria fight oxidative stress. I figured I'm doing much better having more food and vegetable colorful because I wasn't even eating carrots or tomatoes or peppers that really can help getting more of those in it. For me it did. And for some patients also, so then you can either add exogenous ketones or MCT oils or, maybe it's even enough to just be in ketosis some of the times. Some intermittent fasting might help. A lot of patients also struggled with the fasting because there's something called glycogen resistance that has been found in migraine. It's basically the opposite of insulin resistance. 

Glycogen resistance means that you will not turn on ketogenesis and gluconeogenesis as much because you're resistant to glycogen, which is basically the hormone that tells your body when you're fasting to produce more energy. And if you're resistant to that, you get more resistant by fasting. You basically need to do the opposite than an insulin resistant person. You need to eat more to get this fixed. So that's another interesting aspect in a migraine that is different to other metabolic diseases basically. But yes, so increasing antioxidants can be done with supplements, but also you can use the power foods that come with micronutrients that come with all these polyphenols and flower needs and these things that can be beneficial for migraines. Actually. And for mitochondrial functioning. 

So, you've worked your way to, you were saying before we started recording that your ketone levels are lower, but you feel a lot better. You've gone through a sort of stricter keto diet to now including, 

and I can still be in ketosis that said though it needed about, and that's something we find in epilepsy too. It needs about two to five years in an epilepsy kid on a strict ketogenic diet. And then whatever gene expression changes and therapeutic effects they had during the ketogenetic diet is outlasting the duration of ketosis. So basically, if a kid has 80% reduction of seizures, that will be a point in time where they can stop a ketogenic diet completely. And these kids sadly go back to Western diets and it will still have 80% reduction and that might be something that's happened to me as well. I was in higher ketosis for two and a half years and then was this point where I could go away and still have this reduction in migraine from like I had 20 days on average and I'm now down to maybe three a month. 

I'm not sure if that was the major driver, but even during this stricter ketosis, I would feel better generally. I also like energy-wise in to body ache and like, you know, burning muscles. The more carbs from, not from the grains, I'm not doing any of this or even legumes. I can only beans again and stuff, but I wouldn't recommend that. But just from more colorful vegetables and having some fruits really helped me. And the only explanation for me is it's not the carbs, but it's the things that come with the carbs of fruit and vegetables that you cannot get with the meat. 

Very interesting. And what do you feel about treating when you do have a migraine treating it with exogenous ketones and that, just is a question actually about the trials that you're doing, are they taking exogenous ketones sort of on a daily preventative basis or are they taking them as a treatment for a migraine? 

It's prevention. You need to think about, you need to basically on a chronic basis, empty the bucket with the ketone bodies. It's like it's my migraine is a cascade of events, right? It could be and I don't have much evidence and for me it's hard. It's work sometimes and sometimes not. If you catch a migraine super, super early and the pain cascade hasn't started, maybe you can abort it with exogenous ketones. But really what you need to do is increase the threshold or lower the water in the bucket on a regular basis. So, we're using them as a preventative, increasing the threshold, reducing the frequency. 

Your mimicking what other people are doing with a diet. 

Exactly. If you think about a migraine as a process, like a stone sitting on top of a mountain rolling from a mountain, once the stone gets rolling and it becomes full speed, it's almost impossible to stop that stone. And it's a bit like that in a migraine. Once the pain cascade has started, once these newer peptides that caused the pain in your brain have been released, you can take all the exogenous ketones you want. More energy is not going to stop the peptides from being around. Right. It might make the attack less long, less prolonged. It might make it less strong, but it's probably not going to, it's not a painkiller. It's not going to stop the pain because pain basically is these peptides being around and the receptors being activated. So it will be very interesting to see and I would really love to do that trial with patients that are very experienced and can have this like feeling of when the migraine is coming, if they take enough ketones early enough in the whole process, whether it could abort an attack even. 

But we don't have that data. I only have patients coming to me saying that it's worked for them and that's really interesting. Also like on this a ketogenic diet from the conference from Dominic D'Agostino. I had several patients that have seen a video before or read my poster and they've done that, and they say it works. But I don't know if this is a regular occurring thing. I cannot reliably make it work. Sometimes it would, sometimes it wouldn't, but I'm also now I'm doing so many things. I'm also on the road and I don't have them with me all the time, so I think I'm taking it too late when it doesn't work, when the pain is there already, it's too late. It won't do anything, 

But it's kind of something that's maybe worth a try. It's just something that I’ve mentioned in my Facebook group. Yeah, and some people have tried and really found it helps. So for me anything like that. Are they taking the racemic or the D, do you know?  Just a racemic type one that you can buy on Amazon, that kind of type exogenous ketones. 

Yeah. Interesting. Interesting. Because the lower blood glucose, the racemic so it's interesting. 

So yeah. Great. Yes, I mean it seems to me that if you can help with something like that as supplement rather than taking any kind of pain meds, it's worth a try. Oh, certainly. That's something that I want to try myself. 

Because yeah, all these pain medications, again, it puts quite a strain on your liver and your liver is already super busy in a migraine patient typically. Any medication has to be detoxed and we typically underestimate how quickly you can kill yourself with ibuprofen because it leads to liver failure. It's like I don't know what, you take six of them or eight of them at one go and you can kill yourself. It's like, it won't kill you if you take two, obviously, but that doesn't mean that taking two on a regular basis is not going to somehow negatively impact your liver with time. Right. So if you can find a natural approach to that by all means and a ketones, if even if it's, if it's a D BHB, even better because as the endogenous version, the human identical one because then you only have things around that are human identical. So that won't have any side effects because it's something that is around anyway. They're harder to get hold of. Right, they're harder to get hold of still we're working on it. I'm working on it because I wanted it for myself. So maybe one day hopefully. But yes, until then, I mean racemic if you don't take it for like 10 years, there's also safety data for the racemic is not going to kill you. Certainly not. All right. It's if it helps by all means.

Perhaps you could round up with what you call the four-step approach to improving mitochondrial functioning and energy metabolism in migraines towards the end of your thesis. I read that the recommendations that you have for everybody who suffers from migraines. 

Oh yeah, certainly. We've kind of touched upon the first two, right? The first one we talked about is a individualized supplementation of the micronutrients. And this could also be hormones, so not only vitamins and minerals, but also some people have menstrual migraines which get really bad two days before their period, which is basically the time where your estrogen plummets and you don't have this oxidative stress protection, your insulin sensitivity changes during that time. So sometimes people with menopause get really bad migraines and maybe they would profit from some human identical. Again, that's the key. Don't take synthetic hormones. They're not the same ones that your body makes. It needs to be bioidentical; hormones can help. So basically, getting the base right, getting your engine working, getting your engines in the body, working, getting the base, giving the body everything, it needs, all the ingredients for good function first. And the second step will then be increasing antioxidant capacity. So that could be with food, with supplements and also would using oxidative stress and that could be toxins. Smoking, too much alcohol. Actually, it's really interesting if you tolerate alcohol well, it's basically the best test to see whether your liver is doing fine. If you have alcohol intolerance, that basically means your liver is struggling. It's kind of nice to check in with yourself sometimes. Can you tolerate alcohol? If yes, your liver is probably doing okay. If not, you might have to increase your antioxidants. The third pillar is stabilizing blood glucose, and this is essential for migraine patients that often get a migraine in the middle of the night because blood sugar plummets. If you have easy carbs like in a glucose tolerance test, typically what comes after is a delayed insulin response that is exaggerated, which then needs to reactive hypoglycemia, which you want to avoid, so basically low GI diet would be essential, so get rid of any. 

Of course, that's where that one of the biggest triggers is skipping a meal. Exactly. You can just see how eating ketogenically is really going to help so much with that pillar. 

That point doesn't even have to be ketogenic, that could be low carb. Low carb can stabilize your blood glucose very well. 

Anything you can do just to stabilize it. Stopping several highs and lows. 

The fourth pillar, the final pillar is that if that doesn't help, then providing your brain with an alternative energy substrate might be key and that's the ketogenic diet. Potentially if you struggle and your liver isn't making enough ketones, or you have to put more vegetables into feel better. This is why exogenous ketones could come into the picture and MCT oil if you tolerate it, but if that has not helped yet, then you really need this alternative energy. Then you run better on ketones than you do on carbs due to transport issues or whatever it might be. So that's when you really should go strictly on a ketogenic diet or get other sources of ketones in if you can. So that would be the four-step approach that I summed up my thesis with. 

Something that just dawned on me  just going back to the beginning when you started talking about those different steps, if somebody has a regular, like with time of the month when they always get migraines, they can reliably know that they're going to get migraines. Like you were saying that the couple of days before their period say, and that happens every month despite all the other things that they've done. Would that be a good example of when you were talking about taking exogenous ketones more as a preventative way or right at the top of that pain cascade getting in there before the pain starts, would it may be good for somebody like that to say take exogenous ketones for those few days when they get migraines every month certainly as a preventative measure.

 For example, before your period, for some people,  period is stressful, estrogen plummets if you have menstrual migraine, it might well be worth experimenting, adding exogenous ketones in two days before the period starts because they know they will get a migraine and seeing if that helps things. That's exactly what you can do for like a targeted approach where you know, or when you're extremely stressed, and you know you didn't sleep well, and you know you're bound to get a migraine. Maybe not wait for the first symptoms. Just take high dose exogenous ketones and see how you're doing. 

 Because if you're saying that for it to be effective, you need to get in there before the pain starts. Exactly. That just suddenly dawned on me. That might be a good way to do it. I would definitely recommend that. It's been wonderful talking to you, and I could go on all day. Likewise, but I know you have to go. Perhaps you could round us up with a top tip. 

If there's a numberone tip that I would recommend, and that's something that I had to learn quite painfully because I was one of those perfectionist migraineurs who's always listened to everybody else and I took all these, general advice on board, like, sport is good for everyone. Do sports, don't do that. Don't do that. Whatever the number one thing you can do and really learn is listen to your body. Your body will tell you what it means. Once you get rid of your addictions or whatever, the best thing you can do is listen to your body. Does this feel good? Does exercise feel good? Does it trigger a migraine? Does cheese feel good to me? Does whatever? Does a very strict ketogenic diet few good or does something else feel good to me? Don't think because it works for somebody else it's going to work for you. 

It was so individual, nothing even the color red is going to look different to every one of us. There's nothing that is basically assured to be the same with you then to somebody else. So, the only person who knows you have to become your own doctor. You have to take care of yourself and your health yourself and listen to your body. It's going to send the right cues if you listen to it. And the migraine is one of those cues. So, the migraine is telling you something and you need to change things in your environment until you figure out what is good for you. And this could even be getting rid of toxic relationships that chronically stress you and put water in your bucket. So, you really have to sort out through not only your diet, but also your supplements, your relationships, all of these things that stress you and that you might have not been aware of. All these things will make your bucket full in order to get water out of the migraine bucket. If there's one advice is listen to your body while doing it.


Thank you so much. Yeah. 

 It's been a great pleasure. 

Thank you, Daisy. Have a good day. 

And you