Daniel: Sure. Well, migraine is actually classified as a disease state. And not many people realize that. So with regard to migraine, there are a multitude of neurologic and metabolic abnormalities that happen within the brain. So with migraine, you find that patients who suffer migraine have extreme chemical and food sensitivities. They’re at a risk of suffering cervicogenic headaches, so most people with migraines are at a higher risk of suffering cervicogenic headaches, whereas those with cervicogenic headaches don’t really tend to suffer migraines because migraines is more of an inheritable genetic disease.

Cervicogenic headache is pain in the head or face that is a result of a nociceptive input irritation, inflammation arising from the neck. And classically what you’d see is changes in active range of motion on the neck. Or if the clinician was to palpate, a patient with cervicogenic headache along the structures to the neck, that would give rise to referred pain into the head around the eyes, symptoms like that. Whereas in migraine, 20% percent of the patients will tend to experience migraine with aura, which involves visual, auditory hallucinations, tingling numbness in the face, even to the extremities. But also they’ll tend to develop photophobia, phonophobia, so extreme of light and sound sensitivity prior to the migraine attack or during the migraine attack.

So they’re the key differential symptoms between cervicogenic headache and migraine. But those with migraine have higher susceptibility to experiencing a cervicogenic headache because the increased sensitivity in the trigeminal vascular system or the spinal trigeminal nucleus that sits in the lower brainstem becomes very sensitized. And the information arising from the neck also synapses into that area and, therefore, if there’s a minor subluxation or a joint disarrangement in the neck migraineurs will tend to experience more frequent cervicogenic headaches. But those with cervicogenic headaches don’t necessarily experience migraines because migraines is more of an inheritable genetic disease.

Andrew: And we’ve also got like cluster headaches. I mean, you can go off on so many tangents here. You know, in children, they’ve noted abdominal migraines. I don’t even know how to approach that one. So I think there are so many. Can I just ask, before we move on, the cervicogenic headaches, are those the ones that…when you’re talking about pressure at the rear of the head, having orbital pain, presenting an orbital pain, is this where you basically palpate around the base of the skull, from the rear, from the occiput round towards your ears, and there’s that sort of the bottom of the mastoid process around there is that there, or you’re talking about the actual backbone?

Daniel: Well, classically, cervicogenic headache, the source of pain is referred from…classically, in 70% of patients C2, C3 regions. So classically, 70% of your patients with cervicogenic headache will have a biomechanical dysfunction, derangement, also arthritis, irritation to the capsule in the associated passive structures, somewhere in between C2 to C3. Whereas higher up in the occipital mastoid region, you’d find that you can get biomechanical compensation up in the occipital areas where the mastoid is C2 or a C1 and generally the compensations can also give rise to like a secondary hyperalgesic response as well.

So it’s not a classic technical situation where it’s just C2, C3 palpable tenderness, it can also spread into the areas of the upper neck as well, especially when you have that sternocleidomastoid attached into the mastoid. So, classically, you will find also those areas can be quite tender as well.

Andrew: Gotcha. And are these the patients that tend to have that tenderness down the side of the neck, top of the clavicle, that sort of front of their collarbone and that sort of issue?

Daniel: Yeah, so they have the overlying muscle hypertonicity and hyperalgesic response. So a hyperalgesic response meaning that, for example, the use of the pinwheel, which tests more your spinothalmic pain pathways, they almost feel as if that’s more of like a knife-like sensation. So that’s that hyperalgesic response. You’ll tend to feel a lot of these patients in the SCM, scalene, subclavius some and even sub-accesibles [SP] develop quite exquisite hypersensitivity with palpation in those areas. And there’s a big biomechanical influence as well.

Andrew: I hate the word you’re using, exquisite. So let’s get back onto migraine because that’s really the focus of our talk. But I think just answering that belies just how complex this issue of pain is, and that’s just only in the head, let alone neuropathic pain and all the arthralgias and things like that. So let’s talk about migraine for a tick. Can you take us through the pathophysiology of migraine? Because there’s a biphasic response there, right?

Daniel: Yeah. So essentially we have like a prodrome and aura migraine attack, and then you have the postdrome. So essentially, what happens is, there’s some particular type of trigger. And a trigger could be a particular food antigen, it could be a chemical sensitivity. There could be many, stress, things like that. And basically what happens is you have a reduction in cerebral ATP, and oxygenation as a result, and you get…essentially what happens is oxidative stress, inflammation. And then what you have is the phenomenon called a cortical spreading depression. And that cortical spreading depression usually arises from the occipital lobe, and then it continues all the way down through the brainstem areas.

And then essentially, what happens is the trigeminal vascular system, so the spinal trigeminal nucleus releases calcitonin gene-related peptide and Substance P, which then travels through the vasculature of the head and neck. And the vasculature is innervated by cranial nerve fibre, and trigeminal nerve, and that in itself sets up a sterile inflammatory response. And essentially, that’s where most of their perceptions originate from, the perception of pain and their throbbing postural headache.

So generally, that’s, you know, in the most general sense, that’s the pathophysiology of migraine. And essentially, what can happen over time with chronic migraine is that prolonged cortical spreading depression is very much…so if they don’t have good bioavailability, or energy substrate, or ATP for many reasons, the cortical spreading depression lasts longer, and over years, they become chronic migraineurs. But then having said that, what happens is the periaqueductal grey in the midbrain, which is the area that helps descend down into the cords to inhibit incoming pain signals, that becomes an increase in iron deposition into the power periaqueductal grey.

Now I question whether opioids, which is used as a means of inhibiting pain, it can’t target the power periaqueductal grey because of the iron deposition and the pathology surrounding that structure. And so you find a lot of people will develop an inability to descend…to be able to inhibit pain because they’re descending influences had been somewhat lost as a result. So that locked down-modulation of pain becomes really, really affected over time, and so that becomes a big problem. But what’s interesting is that those…just prior to the migraine, the cerebral ATP stores must be maintained for the resolution of migraine to occur.

And so what happens is, insulin resistance is pretty much…occurs in all other tissues other than the brain. So you have your glutathione receptors, which is where insulin binds to in the brain, and it ensures that there’s increased intracellular lipolysis and ketogenesis to be able to make sure that there’s increased ATP and energy substrate availability to ensure that the cortical spreading depression occurs and is resolved. And so essentially, that’s something between migraine attacks we need to optimize and really consider the person as a whole from a functional medicine perspective, which during the time in which when they suffered a migraine attack, the phase of which the cortical spreading depression, and the prodrome won’t be as long-lasting. But you can never truly stop the migraine attack itself from actually happening.

Andrew: Right, right. Just talking about that pathophysiology for a sec. So when we’re talking about a breakdown in mitochondrial energy, if we’re thinking about the electron transfer chain, iron is integral in the first section of that?

Daniel: Yes.

Andrew: Like the complex 1, 2, 3, or something. So if we’re talking about a deposition of iron in those neural tissues, are we talking about damaged mitochondria and the iron leaked about, or are we talking about…

Daniel: Yes.

Andrew: Ah, okay.

Daniel: Yeah, definitely. So, yeah, there’s definitely increased mitochondrial reactive oxygen species as a result. So essentially, over time, you can get mitochondrial dysfunction as a result from, as you mentioned, the superoxide states as a result from iron deposition in the midbrain. So that’s something to be really, really considerate of, and I know a lot of people tend to wanna supplement with nitric oxide synthase to induce more vasodilation, but the concept of migraine it’s not a vasoconstrictive disorder or disease. So it’s really, really important to understand that the vascular insufficiency has been, for long now, rejected as the aetiology of migraine. And so they found out…

Andrew: So I’m way out of date.

Daniel: No that’s okay. Yeah, and so what nitric oxide actually does, it actually inhibits cytochrome c, I think oxidase 4 subunit in the mitochondria. And that in itself can also perpetuate the migraine cycle, too. And I can actually share with you that paper to be able to put on the website for those interested in reading as well. Yeah,

Andrew: Oh, yeah, please. So is there something wrong with the first few complexes? Is that where the sort of damage or the fragility is in the mitochondria?

Daniel: Yeah, I’m not too sure. It’s getting pretty deep. It’s something for me to look into or it’s something that I think, you know, there might be defective mitochondrial genes or people with snips that could certainly be looked upon. And I’m sure that’s something that’s of great value in-depth because there are things we can do to support mitochondrial health, which would be very, very useful to look into. So…

Andrew: But it’s really interesting. Like I was thinking, my first thought when you mentioned iron deposition was can we use, say, zinc as an antagonist to iron, but then I was thinking, “Hang on, if that’s not the cause, really, you’re just chasing your tail, and there’s more iron being deposited all the time.

Daniel: Exactly.

Andrew: We’ve got to look at causality in helping to rejuvenate tissues.

Daniel: Exactly, exactly. So it gets really, really complex. And I think it’s really important to look…now iron is, you know, because of the dopamine and the feeds in the biochemical pathway as well. So that’s important. But then, again, is the iron being, you know, as you said, it’s being deposited as a result from the pathophysiology, not from a result from…if I take exogenous iron, and is that gonna further worsen the scenario, and things like that? So it gets tricky. It gets tricky.

Andrew: Well, tricky. Indeed. Because I was then thinking about, “Okay, if we’re talking about in the biopterin pathway, because we’re talking about Bs and folate and things like that methylation. Is this perhaps where…poor biochemistry here, is this perhaps where you know riboflavin comes in as a potential treatment?

Daniel: Definitely and that’s just been shown in the research paper that B2 or riboflavin actually is a very important in trying to resolving the migraine process. And especially, obviously, during the, you know, you’re able to support the mitochondria through B2, B3, that’s absolutely essential. And that’s one of the key areas of treatment that we can provide and utilize.

Andrew: Gotcha. Okay. All right. So when we’re talking about migraine, you know, we’ve got to think about when patients find us or you in this case. So are the patients that seek you out the people that have been to everyone, seen everyone, tried everything, and they’re just sick and tired of everything? They’re the breakthrough migraineurs. And so you get these sort of, you know, let’s say, a biased sample of the failures of orthodox medicine. Do you get those people trickling through? Or do you get just normal, first time, sort of…not first time, but early treatment seekers?

Daniel: Yeah, it’s so many combinations. So you definitely have the ones who’ve been referred due to, you know, I’ve been renowned as being a bit more in-depth, a bit more integrated. So certainly, you get that referral, that word of mouth. And those patients come to me because they’ve been everywhere. Or, classically, in my industry, within the chiropractic profession, a lot of the chiropractors, just look at a single source of the problem, which is just purely biomechanical. And if it’s a neck source, if the source of the issue is lying in the neck, and outside of that, there’s really not much scope, should I say. Well, there’s not much, I think, willingness to explore outside the scope.

So I do find a lot of these patients, you know, coming to me, and it’s not just a purely biomechanical case, you know, and that’s what’s led me to go down the path of functional medicine and functional neurology, because you can’t separate the two, they’re very, very, very intertwined. And, you know, metabolic support is huge. I mean, for example, like, you know, for the most part, a lot of female migraineurs tend to have extreme chemical sensitivity. They may have pathogenic yeast overgrowth, like pathogenic candida overgrowth. And what we know about candida is that it actually hijacks the…so what happens is it produces acetaldehyde, it converts pyruvate to acetaldehyde unless pyruvate gets shunted into the mitochondria to make ATP.

And if you have ATP, that’s obviously less as a result, then that’s gonna affect energetics as well. So that’s the one thing that’s also really, really important. We need to look at the gut, address the gut, and just overall look at the whole system

Andrew: Got it. So when you’re talking about female migraineurs, and just a point, what I thought was interesting was there was a neurologist based in South Sydney, St. George area who…correct me if I’m wrong, but he was so sick and tired of having disgruntled patients not getting complete resolution or near-complete resolution of their migraines that that’s what drove him to source or to look into functional medicine, integrative medicine as a means to just nip off the bud. He didn’t swap over, he was using it in combination with medicines, but pharmaceutical medicines. But there was quite a substantial group of patients that were just not satisfied with the reduction in migraines that they were getting.

So what’s really interesting about this movement, even of quite orthodox neurologists to investigate herbs and nutrients in helping migraineurs.

Daniel: Certainly, I mean, especially when a lot of the neurologic cases, a lot of the cases that are presented to neurologists, they’re not classic textbook neurology cases you’d find, you know, during med school. I mean, for the odd occasion of the one who presents with a space-occupying lesion, or tumour, or they might have, say, for example, you know, herpes simplex virus, you know, invading the trigeminal nerve. You know, it’s not typical, these are atypical cases that they present with.

And I’m actually dealing with a patient at the moment who has celiac disease, yet presents with an orthostatic tremor and a whole host of other neurologic-type symptoms. And you really got to address the energetics. You’ve got to address the gut, you’ve got to sort of eliminate the total inflammatory burden. And I think that’s really, really important. I think there’s a really big push into the integrative functional medicine aspect. Because how I look at it is if, you know, the vagus nerve is 80% afferent. And, you know, you know we have alpha-synuclein, you know, released into the vagus nerve that transfers up into, you know, the brainstem and cortical related areas and that’s where you have your Parkinsonism and your various other types of movement disorder pathologies that can result from perhaps maybe a long-standing gastrointestinal problem, maybe we don’t know.

But it’s definitely something where the, you know, I think the research is quite clear, it’s now heading into, you know, investigating potential pathogenic species in the gut, and the effects of which can cause long-term and in the presence of intestinal permeability and in various other factors. And so that’s certainly not to be overlooked.

Andrew: Gotcha. Okay. So are there any key considerations that we have to be aware of, with, I guess, especially female migraineurs, they do suffer migraines more than men, but it’s not restricted to only women, obviously?

Daniel: Yeah, I think the young female, you know, 30 to 35, especially on the contraceptive pill. Those who have benign hypermobility or a collagen abnormal…so for example, like a collagen disorder or Ehlers-Danlos, and many of the others. So if your structural support system is not good, and you’re on the pill, and you may have elevated homocysteine levels, then you put all those three together and you now need to consider whether you believe that a manipulative technique is necessary at that particular time. And so I think that’s really, really important to address.

Andrew: What I’m picking up here is that we’re really talking about an almost metabolic fragility here, you know, you’ve got genes then you’ve got, you know, potential gut issues, potential gluten sensitivity. So you’ve got snips related to that as well. La, la, la. So we’re going all around here. What about, forgive me, including the hormones as well, and not just looking at the OCP, but potentially things like polycystic ovarian syndrome. Do you have a PMS, things like that?

Daniel: Yep. 100%. So they’ve even shown that two to five days after the menses, that if your estrogen levels are significantly reduced, that’s also a risk factor for migraine or the increase in frequency of migraine attacks. So that’s really, really important, especially for women with estrogen dominance syndrome even, you know, estrogen and progesterone can be quite neuroprotective. So that’s an avenue that you need to kind of look into. And I guess even hypo cortisol states, so very low cortisol.

So if you have very low cortisol, that’s going to be a potential drive-in chronic unresolved inflammation. And so that’s a really important step. And especially and it’s been shown that, you know, having low very low cortisol, essentially can operate like NF-kB, which can drive someone with autoimmunity or a pre-existing autoimmune disease and pretty much causing a flare-up. So we need to adjust cortisol and various other hormones as well. I think that’s very, very important. Very, very important.

Andrew: Right. So they’re obviously, those low cortisol people, they’re sort of, you know, on their last legs, they’ve been through the high cortisol, and they’re worn out.

Daniel: Yes, they’ve been through the stages.

Andrew: I mean, we need to really address this, and I’ll cover up what supplements you use, and you find a merit later, but in the meantime, things like assessments. Do you do any…forgive me you were mentioning before you were showing us on the video, forgive our listeners, but you’re gonna miss out on this, and you were showing us basically where you’re palpating for the cervicogenic type headaches. What sort of other physical assessments can tell us or give us clues about metabolic fragility for instance?

Daniel: Yeah, sure. So one thing you can do is you can use your opthalmascope if you have one in your practice and just shine…obviously, dial down the intensity if they’re…during the migraine or between migratory episodes, so you don’t wanna get them in and be able to perform an extensive evaluation once we have the migraine attack. But if you shine the light into their eyes at a very low intensity and see how the latency in their capillary constriction and whether it holds or not, and to which extent…how long after it holds does it re-dilate.

So we know that with an increase in fatigue stress average an increasing catecholamine response or epinephrine that can sensitize the pain response. And so it’s one thing to look at or to gauge capillary dilation. If the pupil constricts at a very, very…if the light sees very, very, very, very, very minimal, and it constricts only a tiny bit, and then re-dilates that have increased fatigue ability, potentially, you have to look at other things as well, but potentially increased fatigue will response in that the midbrain is just being wound-up, potentially. So if the midbrain is being wound-up…

Andrew: Yeah, wound for survival.

Daniel: Exactly right. Exactly right. So that’s one little thing that you can do. You can also use like a neurotip and apply it to the side of the neck while you concurrently looking in their pupil. Now if the pupil dilates, a significant increase, as a result of the pinprick, you know that there’s an increase in sympathetic tone of sympathetic response because you get the superior survival ganglion, which increases the sympathetic response as a result from that, on that mechanical impulse. So there’s like little… there are two things that you can kind of utilize. Of course, you’d want to also…which you could…I mentioned this in the dysautonomia webinar as well, is that you could place the pulse oximeter on their finger and provide a high-frequency sound emitted from a tuning fork into their ears, one ear, or the other, and see if that actually elevates their heart rate response.

Andrew: Wow.

Daniel: And so if it does, you know that… Yeah, because within the midbrain, you have the superior and inferior colliculi, one that responds to, like light, emitting light, and auditory sound. So if they have a dysregulated midbrain that’s just wound-up you can probably find the heart rate escalate with some sound, especially when it’s a high-frequency sound, or you shine the light in their eye and their heart rate jumps up. So these are the like, small, you know, things that you can do at the bedside, that can give you an indirect, you know, assessment as to well, they’re really wound-up now you don’t wanna probably treat them right now, you might have to kind of reduce the stress levels a bit and then go in and find what you think is most appropriate. So they’re two things that you can do at the bedside.

Andrew: Wow, that’s really interesting.

Daniel: Yeah, yeah.

Andrew: Oh, I think that’s brilliant. Absolutely brilliant. Okay, so what about other assessments? You’re mentioning, NF- kB being raised. So, you know, do you look at things like…, not ESR, CRP? Do you look at ferritin, things like that?

Daniel: Oh, yeah, so we look at a complete blood count, the plate differential, we look at homocysteine levels. Ferritin is for your arm storage, your CRP, and your ESRs, very important for the acute inflammatory response. And I think it’s also good to look at, you know, the 24-hour salivary cortisol as well, I think that should actually be a standard part of the assessment for someone who’s been to every different doc and they can’t resolve as to why they have migraines.

So I think that’s really, really important. Your B12, you know, B2, and your full iron count as well, which is really important. So standard blood VADs with added functional systems on the side is very much, I think, necessary. And of course, if you feel it’s necessary, to look at the methylation status as well, which I think can be quite important.

Andrew: Gotcha.

Daniel: So yeah, there are quite a few things that we can do.

Andrew: Okay, brilliant. And so we’ve mentioned riboflavin, we’ve mentioned, you know, well, forgive me, we’re talking about mitochondrial health before, and what was going through my mind with complex 1, 2, 3, was CoQ10. So what sort of nutraceuticals and indeed herbs do you use for helping people to reduce migraines? And when are they applicable to use? Like can you take them during a migraine? Or is it really over a longer period of time to decrease the frequency and severity?

Daniel: I think it’s over a longer period of time to decrease the severity and the frequency. I think between migraine attacks, if we can establish a pattern or a time period of which it happens, I think the best intervention is the one between the attacks, I think. But that doesn’t go to say that you can’t use high-quality you know, EPA or DHA during the migraine process to resolve the inflammatory cascade. I like to optimize energy. So I like to use Coenzyme Q10, Alpha Lipoic Acid, resveratrol, high-dose curcumin, ginger, so you know, upping your phytonutrients as well. So I think you need to look at, A, you know, downregulating inflammation, but also then, you know, improving mitochondrial health.

So I think that’s really, really important. Magnesium citrate, or magnesium malate. And then you could also use…I forget what other herbs you can think about, but basically, you wanna look at…

Andrew: Feverfew.

Daniel: Feverfew extract, yeah, yeah, there’s some good data on that.

Andrew: There’s a number, you know, that I have used.

Daniel: There’s a number on them. There’s a number on them. And I think even L-carnitine as well, I mean, especially during that process of which the cortical spreading depression is occurring, where you have that migraine episode. It actually can…if you can increase ATP generation. So lipolysis you have…or even if you look at, say, beta-hydroxybutyrate, like exogenous ketones, just anything to increase the energy bioavailability so that the frequency or the duration of the attack is potentially gonna lessen. So, things like that. And I don’t know, maybe, like, you have endogenous ketones, you have exogenous, but I really don’t know if exogenous is gonna make a big difference. But yeah, it’s just a consideration, a thought based on that yeah.

Andrew: So what dose of carnitine do you use?

Daniel: To be honest with you, I just go off just the prescription on the back. So, you know, if it’s a powder form, I like to use one to two scoops, you know, three or four days, if you can predict when the migraines…if they have an aura leading up into the migraine, then I’d like to have at least two or three scoops of L-Carnitine, you know, once or two times a day three or four days before the actual migraine episode. But that depends on how long the aura lasts for. And everyone’s really different, so…

Andrew: Yeah. So we’re talking gram dosages, certainly. You mentioned also suddenly before about…forgive me, something that was going to be affecting BDNF. And so I was thinking about, you know, the good things that we know, positively affect BDNF, and that was things like exercise, but sometimes strenuous exercise can bring on a migraine. So how do you navigate that one?

Daniel: Yeah, very interesting. So, you know, so really, we’re exploring the concept of readiness. Like, when am I ready to exercise? When am I ready to move about? So I think if you have…I mean, there are a lot of heart rate variability apps that you can download, that can kind of gauge your readiness as to when to exercise. If weather changes are a trigger in your migraine attacks, you know, you might not wanna exercise in unstable conditions. But I guess it really comes down to establishing baseline physiological data, and then getting a percentage of that, that’s not going to tip you over the edge.

So I would certainly suggest that you know, exercise shouldn’t be strenuous, it shouldn’t be too intense, light to moderate. And obviously, throughout that process, it’s really important to, you know, induce, or be able to do some biofeedback with some, you know, heart rate variability before and after exercise so you can somewhat maintain a pseudo level of homeostasis.

Andrew: Gotcha, brilliant. So just one other point we were talking about with CoQ10. So, do you tend to…because we’re talking about mitochondrial sufficiency here, do you tend to go, you know, quite punchy doses? I mean, I’ve seen you know, 1000 milligrams, for instance, used in Parkinson’s. But do you tend to go high and heroic or low and slow? And sorry, the last question…well, not the last question. But one of the other questions was, you’re also mentioning the people with low cortisol, the people that are just worn out, do you use you know, adaptogenic herbs, there like, you know, the Withania, the Astragalus, the immune thing?

Daniel: Licorice root.

Andrew: Licorice root.

Daniel: Yeah, licorice root is, you know, Glycyrrhiza glabra. That certainly has its place definitely. So I like licorice root. I haven’t really explored too much into the others, but that’s something that I advise my patients to use.

Andrew: Gotcha. And with the CoQ10, high and heroic or low and slow?

Daniel: I like low and slow. So I like to start with 350 to 400 milligrams…

Andrew: Okay, that’s quite decent.

Daniel: …and then work your way out to 750 to 1000 maybe really depending on the patient, but yeah.

Andrew: Wow okay. That’s cool. We got some great tips today, Daniel. Thank you so much.

Daniel: And it really depends on that. No worries.

Andrew: Now can I also ask have you done any webinars on this?

Daniel: No.

Andrew: We need to get you teaching people.

Daniel: I’d love to.

Andrew: This is fantastic information. It really is.

Daniel: Oh, you enjoyed it. Wow, great.

Andrew: Yeah, it’s wonderful. Daniel, thank you so much for taking us through just some really nice practical tips today on helping people with migraine and pain. Pain is huge I get it. So we didn’t really go into neuropathic pain and things like that. But thanks so much for taking us through headaches and migraine today and what we can do to help patients.

Daniel: Glad to be here. Thank you so much.

Andrew: And thank you for joining us today on “Wellness by Designs.” You can find all the other podcasts and the show notes for this podcast on the Designs for Health website. This is “Wellness by Designs.” And I’m Andrew Whitfield-Cook.