Serotonin / PUFA Drive Migraine

[haidut]

The role of serotonin in migraines is becoming more recognized every day. Unfortunately, SSRI drugs are still being used to treat migraines, but more recent studies found that serotonin antagonists like cyproheptadine or mianserin are much more effective.
The study below found that linoleic acid levels are highest in patients with current migraine attack, and linoleic acid is a potent liberator of serotonin from platelets and, of course, a prostaglandin precursor (also implicated in migraines). Thus, aside from drugs like cyproheptadine and aspirin (which affect both serotonin and prostaglandins) another easier OTC remedy could be taking a bigger dose saturated fat like coconut oil, or palmitic/stearic acid in order to block the effects of linoleic acid. Vitamin E could work as well as it has also been shown to directly destroy linoleic acid.

Role of individual free fatty acids in migraine. - PubMed - NCBI
"...Total plasma free fatty acids, platelet serotonin content and plasma stearic, palmitic, oleic and linoleic acids were estimated in 10 migraine patients before, during and after a migraine attack. Total and individual plasma free fatty acid levels rose and platelet serotonin content fell in most patients. The highest rise was observed in linoleic acid, which is known to be a potent liberator of platelet serotonin in vitro and is the only precursor of all prostaglandins in the body. It is suggested that the rise in plasma levels of linoleic acid in migraine could be responsible for the platelet serotonin release observed during the attack. At the same time, it may also serve as a source of increased prostaglandin E1 synthesis, which has a powerful vasodilating effect. It is realized that both suggestions have to be confirmed by relevant investigations, as outlined in the body of this paper."

 

[Peatful]

The serotonin AGONISTS (sumatriptans) work nearly every migraine for me without fail and quickly. SSRIs did not, thankfully.

Why does the serotonin agonist work?
More specifically, what does that say about the etiology of my migraine?

 

[tara]

The serotonin AGONISTS (sumatriptans) work nearly every migraine for me without fail and quickly. SSRIs did not, thankfully.

Why does the serotonin agonist work?
More specifically, what does that say about the etiology of my migraine?

I'm interested in this too. Triptans (usually sumatriptan) are usually effective for me as nothing else has been. I've not used SSRI's. I would guess I have chronically high serotonin, but that's just guessing, not measured.
(I'm finding topiramate somewhat effective as a preventive in reducing the duration of migraines by making them more responsive to the triptan - but they have not reduced the frequency.)

Large amounts of saturated fat has not been obviously helpful - possibly made it worse. Small amounts maybe OK in context of a suitable small meal, but not obviously positive at that stage. I do eat some saturated fat regularly as part of my diet, and try to keep PUFA low but general standards, but not extreme.

Vit-e seemed negative. I'm not sure, but I wondered if it might have messed with mineral/electrolyte balance or something at a delicate stage.

 

[Constatine]

Aspirin does wonders for my migraines. No matter how bad one may be just pop a couple aspirins and its completely gone.

 

[tara]

Aspirin does wonders for my migraines. No matter how bad one may be just pop a couple aspirins and its completely gone.

Lucky you. :)
I heard of others who have that experience, too, and those who find small daily doses prevent them effectively, as well.
Sure worth a try for any migraineur who hasn't given it a go yet.

 

[Koveras]

The serotonin AGONISTS (sumatriptans) work nearly every migraine for me without fail and quickly. SSRIs did not, thankfully.

Why does the serotonin agonist work?
More specifically, what does that say about the etiology of my migraine?

I'm interested in this too. Triptans (usually sumatriptan) are usually effective for me as nothing else has been. I've not used SSRI's. I would guess I have chronically high serotonin, but that's just guessing, not measured.
(I'm finding topiramate somewhat effective as a preventive in reducing the duration of migraines by making them more responsive to the triptan - but they have not reduced the frequency.)

Large amounts of saturated fat has not been obviously helpful - possibly made it worse. Small amounts maybe OK in context of a suitable small meal, but not obviously positive at that stage. I do eat some saturated fat regularly as part of my diet, and try to keep PUFA low but general standards, but not extreme.

Vit-e seemed negative. I'm not sure, but I wondered if it might have messed with mineral/electrolyte balance or something at a delicate stage.

Triptan

"Triptans are selective agents for 5-HT1B and 5-HT1D[23] and have low or even no affinity for other types of 5-HT receptors.[14]"

I believe some of the 5HT1 receptors are involved in the negative feedback pathway for serotonin, so they may reduce overall serotonin synthesis. There could be some direct effect of the drug on the blood vessels through the 5HT1 receptors as well (as wikipedia mentions) - which are not what you would see with serotonin itself which would bind to every available receptor.

Haidut has posted about some of the risks they still have however

Btw, FDA just added a few extra black-box warnings for opiates and one of them is increasing the risk of serotonin syndrome when taken with SSRI drugs.
http://www.painmedicinenews.com/Web...Warnings-Safety-Labeling-for-IR-Opioids/35699
"...These warnings include the risk for serotonin syndrome resulting from opioid drug interactions with antidepressants and migraine-specific medications in the triptan class. Serotonin syndrome occurs when high levels of the chemical build up in the brain, resulting in toxicity. Signs and symptoms of serotonin syndrome include agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, and/or nausea, vomiting or diarrhea. Onset of symptoms ranges from several hours to a few days after taking an opioid along with another medicine that affects serotonin; dose increases also can trigger serotonin syndrome."

So, opioids either inhibit MAO-A or act like an SSRI themselves, both of which are obviously undesirable effects. The FDA warning also indicates that drugs like sumatriptan are also serotonergic and dangerous. The pharma industry has denied for decades that the triptans are serotonergic, opting instead for the more nebulous "mixed agonist-antagonist" or the fancier Serotonin Modulator and Stimulator (SMS) label. But if something can cause serotonin syndrome its effects are largely serotonergic.

 

[tara]

Thanks Koveras.
I probably did read that from Haidut and forgot.
I think Haidut is warning that they likley do have serotoinergic effect, which doesn't sound good, but you are saying they may actually reduce serotonin sythesis, ids that right? If so, your interpretation would make me a lot happier about using them. Since I haven't found anything else yet that stops them.

 

[Mito]

Vitamin E could work as well as it has also been shown to directly destroy linoleic acid.

I knew that Vitamin E mitigates damage from PUFA by oxidizing the lipid peroxide radical which prevents the lipid peroxide chain reaction. But I didn’t know Vitamin E could directly destroy linoleic acid?

 

[Koveras]

Thanks Koveras.
I probably did read that from Haidut and forgot.
I think Haidut is warning that they likley do have serotoinergic effect, which doesn't sound good, but you are saying they may actually reduce serotonin sythesis, ids that right? If so, your interpretation would make me a lot happier about using them. Since I haven't found anything else yet that stops them.

I e-mailed Ray about stuttering and mentioned Paul Stamets and the psilocybin mushrooms. These mushrooms are 5-HT1a agonists. Ray's response was that the 5-ht1a is the negative feedback pathway for serotonin, which reduces serotonin, and asked if I had ever tried Cyproheptadine.

The drug Flibanserin for "Hypoactive Female Sexual Desire Disorder" is based around these observations - that a lot of the negative effects of serotonin are mediated through 5-HT2 and some of the positives through 5HT1(a). Flibanserin is a 5HT2 antagonist and a 5HT1a agonist - and by those mechanisms reduces serotonergic tone and increases dopaminergic tone - and thereby libido.

I wonder if it would be good for migraines.

I think there are some potential negatives to some of the other 5HT1 receptors (b/d? - I'd have to do some digging).

 

[Tarmander]

Thanks Koveras.
I probably did read that from Haidut and forgot.
I think Haidut is warning that they likley do have serotoinergic effect, which doesn't sound good, but you are saying they may actually reduce serotonin sythesis, ids that right? If so, your interpretation would make me a lot happier about using them. Since I haven't found anything else yet that stops them.

Did you ever try the magnesium, B2, feverfew for a few month protocol?

 

[tara]

Yes, thanks for thinking of those. I've tried all of them for months.
I'm aiming to keep the Mg (400mg +) and small dose B2 (10-20mg - tried high dose for a while, did not seem better than low dose).
Feverfew did not reduce frequency, so I stopped it after nearly a year. It was doing something short-term. Had withdrawal issues, but then no worse.

 

[Lejeboca]

I'm aiming to keep the Mg (400mg +)

Coffee helps me : It has Mg and acts as anti-spasmodic for me.

small dose B2 (10-20mg - tried high dose for a while, did not seem better than low dose)

I'd go even 'homeopathic' for B2... I've actually experienced a "B2 proofing" (in homeopathoic sense): Started taking B2 for something else (joints) but started having low-grade migraines, which are stopped as soon as I stopped B2. (No effect on joints from B2). I was taking about 5mg of B2 as far as I remember.

 

[Waynish]

Anyone try lisuride for migraines?

 

[cardochav]

Haidut, are you aware of any similar studies on the roll Individual fatty acids and epileptic seizures?

 

[Hgreen56]

i never experience headache from high tryptophan food.
even not in the days when i consume 60-80 gr whey protein powder.
Orange juice in the other hand give me massive headaches.