[HN Gopher] The metabolic face of migraine - from pathophysiolog...
       ___________________________________________________________________
        
       The metabolic face of migraine - from pathophysiology to treatment
        
       Author : DanielleMolloy
       Score  : 76 points
       Date   : 2021-05-07 14:13 UTC (8 hours ago)
        
 (HTM) web link (www.nature.com)
 (TXT) w3m dump (www.nature.com)
        
       | yolobouquet wrote:
       | I suffered from migraines for many years, always after a night's
       | sleep. I had sleep studies and they determined I was not getting
       | enough oxygen. I had surgery for a deviated septum and tissue in
       | my nasal passages and throat was scoured back. I continued to get
       | migraines and was given a CPAP. The headaches continued. I was in
       | my 40s when my dentist asked me if I got headaches in the
       | morning. She said I was grinding my teeth and I needed to start
       | wearing a mouth guard at night or I was going to crack a molar. I
       | still get migraines but they are much less frequent than they
       | used to be.
        
         | TheSpiceIsLife wrote:
         | This leads me to ponder if the _cause of the tooth grinding_
         | could be resolved, would the frequency of migraines reduce
         | further still?
         | 
         | Have you tried taking a magnesium di-glycinate based magnesium
         | supplement. Magnesium can help relax the small fast twitch
         | muscles in the jaw.
        
       | JoeAltmaier wrote:
       | They talk of how migraine might be adaptive. But isn't it
       | possible that migraine is a side-effect of another adaptive gene
       | for a different effect? Nature doesn't care if we're miserable.
       | Just that we survive (as an individual or community) and
       | reproduce.
       | 
       | Imagine if miserly consumption of some chemical was calorie-
       | adaptive or saved for emergencies, but the same gene meant
       | migraines at other times. The gene would still proliferate, with
       | no need to explain the negative effects as adaptive?
        
         | dillondoyle wrote:
         | If have a bad enough migraine can't go hunt or gather food.
         | 
         | Though sex or orgasm can help with headaches in my experience
         | so maybe that's a driver :)
        
           | fallingfrog wrote:
           | In my experience an orgasm only makes a migraine go away for
           | 3 or 4 seconds. It's like a brief moment of relief then you
           | feel the pain come rushing back.
        
       | svcrunch wrote:
       | Fascinating work, thank you for sharing. Here's a link to the
       | full paper:
       | 
       | https://orbi.uliege.be/bitstream/2268/247255/1/Gross%20et%20...
        
         | DanielleMolloy wrote:
         | Thanks for the link! I must have been logged in via my
         | institution and didn't realize the article wasn't public.
        
       | lazypenguin wrote:
       | One of my relatives suffers from migraines and they are seriously
       | debilitating with sensitivity to light and intense nausea. There
       | are strong meds that can help prevent them but they always
       | intrinsically knew that certain foods were a trigger for them. It
       | seems over the years that the connection between migraines and
       | nutrition has been strengthening. I could not access the journal
       | but I would have loved to know what their conclusions and
       | recommendations were. Especially the part related to diet
       | modification.
        
         | TheSpiceIsLife wrote:
         | One medical scientist I know has been banging on for over 25
         | years that the liver _always plays a role in headaches &
         | migraines._
         | 
         | This also helps explain why hormones, especially oestrogen, can
         | be a problem for migraine sufferers, as it's the liver-gut-
         | gallbladder axis that detoxifies hormones from the body.
        
         | wayoutthere wrote:
         | I do too; they have at times been debilitating. I've found no
         | prescription drug works better than marijuana.
         | 
         | There is also a significant hormonal component to migraines.
         | Women have 2-4x as many migraines as men -- an effect that is
         | also seen in trans women who are taking estrogen, which
         | indicates that it's probably hormones rather than genetic. Not
         | ruling out a dietary component, but it's obviously a complex
         | set of symptoms with likely dozens of contributing factors.
        
           | nickclaw wrote:
           | After trying some prescription drugs I've also found
           | Marijuana works the best for me. It's the difference between
           | lying on the bathroom floor waiting to throw up and being
           | semi-functional (I am pretty stoned, so not totally
           | functional) around the house.
           | 
           | I don't think it's a cure so much as a great way to manage
           | the pain while the migraine is at its peak, unfortunately the
           | migraine hangover still lasts for days.
        
         | AuryGlenz wrote:
         | I'm a man and had occasional but regular migraines until I got
         | low testosterone diagnosed and treated. Just throwing it out
         | there, even though I might be a unique situation.
        
         | podgaj wrote:
         | Hey, seriously, check out riboflavin and see my other comment!
         | 
         | https://onlinelibrary.wiley.com/doi/full/10.1111/jcpt.12548
         | 
         | The nausea is most likely from high serotonin which cannot be
         | metabolized by MAOA when in riboflavin deficiency.
        
         | binarymax wrote:
         | I'm triggered by sulfates and pistachios. I found this out
         | through a combination of pure luck and semi-structured
         | observation. I haven't had one in several years.
         | 
         | I consider myself very fortunate to have found these, and I
         | encourage anyone who experiences migraines to keep a food diary
         | (write down what you ate and drank the day before, including
         | all ingredients). You may be able to find trigger ingredients
         | at some point, and then avoid them the rest of your life.
        
           | coldcode wrote:
           | I had severe migraines in high school through my early 20's,
           | in addition to a 1 month bout of cluster headaches (you don't
           | want those!), my triggers were MSG (yes I know people say its
           | perfectly fine, but I experimented and was able to show it
           | affected me, all those years of studying Chemistry...) and
           | bright sunshine reflections. I made sure I ate food with
           | little or no MSG, and always wore strong sunglasses outside,
           | which helped reduce them a lot.
           | 
           | The connection to MSG is clearly controversial given how much
           | the food industry loves using it to smooth out taste in
           | prepared foods, but it seems to not affect most people, so it
           | didn't bother me as long as I could identify its inclusion.
           | 
           | In the the past 30+ years they have decreased in frequency
           | and severity; now other than the aura (20 minutes of weird
           | vision) the headache is at most a simple Tylenol one.
           | 
           | Triggers can be almost anything that affects the brain in
           | some way; given this research it's clear that what affects
           | people with migraine potential does not affect those with
           | different genetics. Very often genetics plays a large role in
           | how your body reacts to stimulus and food and diseases, but
           | also that many genetic adaptations have both good and bad
           | sides, so perhaps migraines gave our ancestors some benefit,
           | and we pay the price lying on the couch in the dark.
        
             | WorldMaker wrote:
             | MSG was the first taste bud science was able to isolate on
             | the tongue because MSG is a messaging enzyme in
             | neurochemistry and it turns out that the taste bud very
             | physically resembles the brain receptors. In a similar way
             | to caffeine, the brain requires a moderate amount of MSG to
             | function, but can easily be over-stimulated.
             | 
             | The reason for all the "perfectly fine" "controversy" with
             | MSG is that there's still no known allergy to it, and the
             | early proponents of "MSG allergies" were quacks using bad
             | science for racist reasons (despite it being a naturally
             | occurring substance, and a required enzyme in the brain).
             | 
             | So overall it is much less controversial to say that MSG is
             | a known migraine trigger in some people. It's still "safe",
             | migraines so far as we know are rarely life-threatening
             | even if sometimes you do feel like you are going to die.
             | You mostly just need to acknowledge that as a trigger it
             | varies greatly among people.
             | 
             | The analogy to caffeine is an extremely useful one as
             | caffeine is also "generally recognized to be fine/safe/not
             | an allergy", but too little caffeine and too much caffeine
             | (and caffeine withdrawal) can all be migraine triggers or
             | migraine relievers depending on what side of it you are on.
             | (Most over-the-counter "migraine medication" if you check
             | the ingredients is just a dose of generic Tylenol and a
             | shot of caffeine because the most common migraines in
             | America are often the withdrawal state or the too little
             | state and it isn't likely to make it worse if you are in
             | the too much state already, unless too much is on the edge
             | of a caffeine OD and you have more life threatening
             | problems.)
             | 
             | It plays the other way sometimes too: sometimes I crave
             | foods high in MSG when I have a migraine and that will
             | settle the migraine some.
        
             | Tarragon wrote:
             | > bout of cluster headaches (you don't want those!)
             | 
             | Oh, now you tell me...
             | 
             | "Cluster headache is among the most severe pains known to
             | mankind." [1]
             | 
             | Cluster headaches to generally thought to be neurological
             | compared to migraines which are generally considered
             | vascular. I guess by this article, indirectly vascular.
             | 
             | Cluster headaches are significantly rarer than migraines.
             | Only a very very few get both. You should have gotten a
             | lottery ticket that month. Glad it faded.
             | 
             | [1] https://www.practicalpainmanagement.com/pain/headache/c
             | luste...
        
             | ses1984 wrote:
             | Are you triggered by foods that naturally contain msg?
        
         | DanielleMolloy wrote:
         | Next to what other users said it gives very specific supplement
         | recommendations, riboflavin (B2) far above the daily
         | recommended value, as well as Q10 and Magnesium. I've made some
         | good experiences with the latter and will give the others a
         | shot too.
         | 
         | They recommend ketogenic food too (I never noticed an effect on
         | my migraines though).
        
         | svcrunch wrote:
         | Full text:
         | https://orbi.uliege.be/bitstream/2268/247255/1/Gross%20et%20...
         | 
         | Lots of excellent recommendations starting from page 6 onward
         | ("Theraputic studies")
         | 
         | An incomplete list of long term strategies presented in the
         | paper:
         | 
         | - aerobic exercise
         | 
         | - b-vitamin supplementation (several different ones are
         | mentioned), and magnesium supplementation
         | 
         | - ketogenic diet (train the brain to use non-glucose sources of
         | energy)
         | 
         | - sleep management (are you getting enough?)
         | 
         | Given the root-cause analysis of migraines presented in the
         | paper, there's one additional treatment which I'll experiment
         | with: milk thistle supplementation. Milk thistle boosts levels
         | of glutathione in the liver, which appears to have a bearing on
         | migraines.
        
       | mdip wrote:
       | I started getting Migraine headaches in the late spring at age 17
       | and continued to get them in the spring/fall weekly for about two
       | decades[0]. I remember the age and the season because, up to that
       | point, I had headaches. What happened that day resulted in a trip
       | to the emergency room, on my insistence; I thought my brain was
       | bleeding[1]. After 4 hours, I was sent home with a note to take
       | two extra strength Tylenol. And for the 20 years that followed,
       | that was about the quality of treatment I received.
       | 
       | Everything, for me, is solved with a medication that is very
       | rarely prescribed for Migraine. My issue is that I cannot take
       | the usual medications (imitrex, etc). They are effective, but I
       | lack a gene that is required to flush them from my system
       | correctly. So 30 minutes after taking the pill I'd be the
       | happiest I've ever been in my entire life, and about 1.5 hours
       | later, I'd be miserable. It was _comical-if-they-weren
       | 't-happening-to-you_ mood swings, which almost killed me[2].
       | 
       | I've seen several doctors for this. After a mess of semi-
       | unrelated circumstances around that event which almost killed me,
       | I ended up on a prescription for Depokote. It's a very old
       | medication, originally prescribed for seizures and I now commonly
       | used off-label for bipolar. It was prescribed to me with the
       | endorsement of "a few of my patients responded well to this, none
       | of them had side effects, and this is where we're at on the list
       | of choices" ... basically, the guy had no confidence it would
       | work, so I didn't either. It was prescribed mid-summer, and I
       | noticed after about a week that I felt like I was carrying around
       | _zero_ anxiety[3], and a number of other fantastic side-
       | effects[4]. By the end of the following spring, I was convinced
       | it worked -- completely. It was the first year I had gone any
       | season without a single Migraine headache. Interestingly, I 'd
       | get the "aura", on occasion, but it would never melt into
       | horrifying pain.
       | 
       | The whole time, regardless of specialist, there wasn't anyone who
       | could give me a really good idea of just what the hell was really
       | going on in my skull. I'll admit, after reading this, I'm
       | wondering if I really have Migraine or if I don't have some other
       | thing (cluster was ruled out). My triggers are seasonal; and I
       | have bad days when there has been a large shift from high->low or
       | low-> high. Interestingly, though, if I get a migraine, I am
       | pretty much insulated from getting another one for about a week,
       | which implies some sort of biological process that is serving
       | some function, since multiple repeats of that trigger, or even
       | much stronger ones, will not cause a second migraine for several
       | days after one already landed.
       | 
       | [0] Varying lengths but until I learned to cope with the
       | symptoms, it at least destroyed the entire rest of the remaining
       | day once it hit. Often remained a day after, as well.
       | 
       | [1] I really, _really_ , hated hospitals as a kid. My parents
       | took me on my insistence because they knew I would only demand to
       | go if I seriously thought I was dying ... even though it was a
       | headache.
       | 
       | [2] A combination of medications related to Migraine which I took
       | during an attack (as prescribed) resulted in my serotonin levels
       | sending me to the hospital. It. Was. Bad.
       | 
       | [3] I never thought of myself as anxious, and it's never been an
       | issue in my life -- that I know of -- that has held me back. But,
       | holy cow, the difference was _stark_.
       | 
       | [4] For medications with "brain affecting" side-effects, I _do
       | not_ read the label. My wife takes that responsibility. My
       | thinking is: (1) placebo /nocebo effect is really strong when the
       | thing it effects is emotional/personality. (2) I can't trust my
       | brain to evaluate what is happening to itself -- it's compromised
       | by the medication.
        
       | mancerayder wrote:
       | I get a devastating headache every few weeks lasting a few days
       | from the base of my skull inside, and it feels like the type of
       | headache that you get from drinking something cold too fast, a
       | bit milder, and lasting a few days. It seems to be triggered from
       | sitting in front of the PC (I try to always stand), doing
       | something dumb at the gym (benching and pushing my neck into the
       | bench so I no longer bench), sitting awkwardly for too long (like
       | a train seat), or looking at a slight angle down while working.
       | It feels like nerve impingement and it travels sometimes to just
       | one side of my face, and even hurts above my eye. Sometimes I
       | feel nauseous too. I've had this for many years. It's more likely
       | to happen if I've slept poorly or get stressed.
       | 
       | What's the difference between that and migraine? I hear people
       | all the time saying they suffer from migraines, and I'm told it's
       | connected to a 'quadrant' type of pain. Are people being
       | diagnosed with migraines maybe suffering from a similar nerve
       | issue that I have? And by the way, that I have a nerve
       | impingement is purely my own hypothesis, and difficult to
       | prove/disprove I think.
        
       | podgaj wrote:
       | Riboflavin!
       | 
       | https://onlinelibrary.wiley.com/doi/full/10.1111/jcpt.12548
       | 
       | The link to the mitochondria is through FAD, a metabolic
       | derivative of Riboflavin, which is used in the electron transport
       | chain.
       | 
       | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447943/
        
         | boffinism wrote:
         | Didn't work for me. I think it's easy to come up with a pet
         | theory ("migraines are caused by X, and therefore prevented by
         | Y"), especially when there is some science to support you. But
         | when you dig into it, you learn that while some treatments are
         | wildly effective for a few people, no treatment is widely
         | effective. If it were, migraines wouldn't be such a thing in
         | the developed world.
         | 
         | So by all means, let people know that Riboflavin might help
         | them, but be wary of prescribing it to all and sundry when in
         | truth, it will only help a minority.
        
       | mmastrac wrote:
       | It will be interesting to see the next phase of migraine
       | treatments - psilocybin, CRGP inhibitors, etc. It really feels
       | like we're getting close to understanding what a migraine truly
       | is.
       | 
       | I believe "cortical spreading depression" is a fairly recent
       | discovery and has opened up a lot of avenues of research vs the
       | past belief that migraine was purely vascular.
       | 
       | This video was a pretty good update on state-of-the-art
       | treatments, including those in trial:
       | https://www.youtube.com/watch?v=LB9nYDvpfbA
        
         | podgaj wrote:
         | everyone always makes it complicated. How about riboflavin?
         | 
         | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447943/
         | 
         | I have seen the effect of this first hand.
        
           | mmastrac wrote:
           | Riboflavin and the other nutraceuticals are in this paper. Co
           | Q10, magnesium, etc all have promising prophylactic effects.
           | 
           | We still need research and treatments for those who get
           | migraines despite the prophylactics.
        
       | gadders wrote:
       | This was a good podcast on the subject of migraines that I
       | listened to last week:
       | 
       | "Throbbing head, nausea, dizziness, disturbed vision - just some
       | of the disabling symptoms that can strike during a migraine
       | attack. This neurological condition is far more common than you
       | might think, affecting more people than diabetes, epilepsy and
       | asthma combined.
       | 
       | While medications, to help relieve the symptoms of migraine, have
       | been around for some time, they haven't worked for everyone. And
       | what happens in the brain during a migraine attack was, until
       | recently, poorly understood.
       | 
       | Peter Goadsby is Professor of Neurology at King's College
       | London's Institute of Psychiatry, Psychology & Neuroscience and
       | is a true pioneer in the field of migraine.
       | 
       | Over the course of his career, he has unravelled what happens in
       | the brain during a migraine attack and his insights are already
       | benefiting patients - in the form of new medications that can not
       | only treat a migraine, but also prevent it from occurring.
       | 
       | Peter shares this year's Brain Prize, the world's largest prize
       | for brain research, with three other internationally renowned
       | scientists in the field."
       | 
       | https://www.bbc.co.uk/programmes/m000vp2z
        
         | alexreds wrote:
         | There are a bunch of recently approved new migraine medicines
         | that block CGRP instead of serotonin. I have suffered migraines
         | since my teens and while Sumatriptan provides some relief, it
         | is not great and has to be taken as soon as I get an auora to
         | be at all effective. Stress and high fructose corn syrup, which
         | is in EVERYTHING, are my triggers. I have not yet tried the new
         | meds, but I am hopeful.
         | https://cureheadaches.org/2020/07/15/new-migraine-medication...
        
           | podgaj wrote:
           | Serotonin is metabolized by MAOA, witch needs riboflavin
           | (FAD) work effectively.
           | 
           | https://ars.els-
           | cdn.com/content/image/1-s2.0-B97804446412500...
        
       | plutonorm wrote:
       | Translation: People with highly sensitive nervous systems get
       | migraines because they are overstimulated. It can also be caused
       | by mutations in mitochondria which reduce energy output. Both of
       | these cause mismatches in the amount of energy being consumed and
       | the amount of energy being expended.
       | 
       | I can confirm that my migraine frequency has doubled since having
       | children.
        
       | nickclaw wrote:
       | This is fascinating, I've suffered occasional migraines for 15
       | years, and while I've found over time that it's highly connected
       | to my diet combined with other stressors (like intense exercise,
       | lack of sleep, high stress, etc...), I've never seen the
       | mechanism described so clearly as "a mismatch between the brain's
       | energy reserve and workload."
       | 
       | I wonder if the "migraine hangover" is also part of the brains
       | process to "restore brain energy homeostasis" or is just an
       | unfortunate side effect.
        
       | fallingfrog wrote:
       | I once got a migraine with aphasia. I was noticing that the
       | visual alligator crack rainbow lightning stuff was finally going
       | away and I decided to check Facebook. I found that while the
       | letters snd words looked normal, it was all gibberish. I tried
       | saying something out loud and I found that all that came out was
       | a mess of random phonemes. It lasted about half an hour.
       | 
       | It looks like this if you want to see:
       | 
       | https://youtu.be/IG7NuH5QTdE
        
       | pugworthy wrote:
       | I rarely get the headache side of migraines, but I do get the
       | visual aura fairly often. If over-stimulation is a factor, then
       | certainly they are a bit self regulating since I have to just
       | stop using the computer, stop reading, stop looking at my phone,
       | etc. until it's gone.
       | 
       | If you've not had the visual migraine effect before, the impact
       | is a bit like if you looked a bright light, then tried to read
       | something.
        
         | greatgib wrote:
         | Very very interesting topic.
         | 
         | I was also used to suffer from the visual migraine as you
         | describe it.
         | 
         | For another exemple, it is like looking at the phone in
         | complete darkness with the phone brightness set to the maximum;
         | but that effect in daylight with the screen set to low/normal
         | brightness level.
         | 
         | Maybe I'm wrong, but the deductions I did from my issues was
         | that it might be related to work conditions. For example, I
         | used to have the computer screen at 90deg of a window. And
         | there was probably constantly a little bit of light reflexion
         | on my screen. So it is not so much to be noticable or annoying,
         | but for a full day it will exhaust my eyes and brain. And I
         | would regularly have the issue at the end of the day.
         | 
         | Then, I changed of work and of light conditions, and I almost
         | never got the issue anymore. (Still once in a while, but very
         | very rarely compared to before)
         | 
         | Also, I discovered that there are a lot of good advice
         | regarding the work environment that you should try to respect:
         | 
         | - no excessive room temperature (>21)
         | 
         | - no sun or light directly in front. No light reflexion from
         | the back or side.
         | 
         | - room ambiant light the closest possible to the brightness of
         | the screen
         | 
         | But, a point that could support the theory of this publication
         | is that, when the issue arrived, it was often that I was
         | feeling hungry for sweets and desperately looking for a snack.
        
         | davmar wrote:
         | I have the exact symptoms as you - no headache but visual aura.
         | 
         | I think my triggers are a lack of food/hydration and bright
         | lights.
        
           | mjklin wrote:
           | I've seen a doctor for this and he mentioned stress and foods
           | containing tyramine (pickled and fermented foods, preserved
           | meats and aged cheeses, asparagus, red wine, chocolate) as
           | possible triggers.
           | 
           | See: https://www.webmd.com/migraines-headaches/tyramine-and-
           | migra...
        
         | auslegung wrote:
         | I recently learned about ocular migraines, and what you're
         | describing could be that. https://www.mayoclinic.org/diseases-
         | conditions/migraine-head...
        
         | BrandoElFollito wrote:
         | I do not usually get the headache part either but the visual
         | part is epic.
         | 
         | The first time I got it, a few years ago, I thought I was
         | having a stroke.
         | 
         | The visual area gets ripped in two by the diagonal, the two
         | pieces move away and are replaced with a silver band. The
         | picture stays more or less complete, but broken in two. The
         | image kind of pulsates, or rather waves.
         | 
         | I was terrified the first time, then visited the
         | ophthalmologist, did a tomography of my head and ended up at a
         | neurologist. He was a specialist of migraines and told me that
         | about 30% of migraines are without headaches.
         | 
         | My father has migraines, my younger brother too and both have
         | headaches.
         | 
         | I had some other extasy-like migranes and I am usually
         | exhausted afterwrds and sleep 10 to 12 hours straight.
         | 
         | I am lucky to have only a few cases a year.
        
           | tonyedgecombe wrote:
           | > The first time I got it, a few years ago, I thought I was
           | having a stroke.
           | 
           | That was my reaction as well.
           | 
           | It reminded me of looking through a kaleidoscope.
           | 
           | Luckily I've only had it occur a couple of times.
        
       | alfiedotwtf wrote:
       | Migraine sufferer here. Know your triggers!
       | 
       | I used to suffer migraines at least once a months, and head aches
       | at least once or twice a week. But then I found my triggers...
       | 
       | So the Philae Lander landing on a comet on a Wednesday night, at
       | sometime like 3am, and the next morning I had a really bad
       | migraine. It was right then and there that I realised I only ever
       | got migraines on Saturday and Sunday. Why did I all of a sudden
       | get on then? Lack of sleep! I started experimenting, and
       | eventually found that if I had under 4 hours of sleep for 3 days
       | in a row, surely enough on the fourth day I would most likely
       | have a migraine! It was an awesome epiphany.
       | 
       | I've also managed to dramatically reduce headaches too - by
       | having at last 6 hours sleep, I will have most likely staved away
       | my usual tension head aches.
       | 
       | I'm also under the suspicion that my headaches are effected by a
       | lack to serotonin, but haven't had my bloods checked for that
       | yet.
        
       | juskrey wrote:
       | I had no headaches for a straight year on strict low carb diet
        
         | wayoutthere wrote:
         | I honestly had the opposite; I tried Keto and had headaches for
         | a month. They went away about 15 minutes after I ate a
         | chocolate bar.
        
       ___________________________________________________________________
       (page generated 2021-05-07 23:01 UTC)