Does tryptophan help prevent seizures?

[googly389]

If tryptophan helps prevent seizures? The reason I'm asking is because over thanksgiving I are leftover turkey for at least four days and I felt like I had the most clarity and calmness in my thinking than I have ever had! If anyone knows that would be helpful, thanks!

[joan]

I found this on epilepsy.com. Maybe it just proves diet has a larger hand in it all than many think.
joan*

PAOLOM...tryptophan, serotonin and epilespy. A new approch to control seizures

Hello,

I’m Paolo Mainardi, I’m a chemistry and I work on epilepsy in the Neurological Clinic of University of Genoa since 1982. I had a lot of experience on amino acids and peptides in plasma and CSF in different neurological diseases.
In ’90 I found decreased plasma levels of Tryptophan and the other Large Neutral Amino Acids (LNAAs) in epileptics respect controls (Lunardi G, Mainardi P, Albano C in Allegri Flippini G et al eds, Tryptophan and Epilepsy in Recent advances in tryptophan research Plenum Press, New York). Tryptophan (trp) is the only brain precursor of serotonin and by our results I can estimate a 30% reduction of trp brain uptake in epileptics respect controls. In the same years we started clinical studies on Selective Serotonin Reuptake Inhibitor drugs, largely used as anti depressant. These drugs was wrongly believed to be pro-convulsants, but our results shown their able to help the seizure control (Favale E, Mainardi P, Albano C. Neurology 45: 1926. 1995; Favale E, Albano C. Seizures 12: 316. 2003). In agreement with our results Jobe and Browing (Jobe PC, Browining RA. Epilepsy Behav 7: 602. 2005) put forward a theory ) about the presence in the brain of exterior defensive shields. In their view, both epilepsy and affective disorders have different intrinsic fabricators, i.e. neuronal circuits which actually initiate and sustain dysfunctional episodes. However, they share common exterior defensive shields which are made up of circuits using noradrenaline and serotonin and protect the system from a deranged function of the intrinsic fabricators. This may lead to either the epileptic pathology or affective disorders, such as depression, according to the particular fabricator involved.

Therefore an increase in brain serotonin level has both anticonvulsive and antidepressant effects.

The decrease in the amount of tryptophan which arrives to the brain is likely to result in a corresponding decrease of brain serotonin synthesis and in a diminished serotonin control. A des-metabolic gastro-intestinal absorption of LNAAs could be a concomitant cause of epileptic pathogenesis.
Because in the gastrointestinal system LNAAs (trp included) compete to the same carrier, like to BBB, I thought that a protein rich in trp and poor in the other LNAAs is able to increase trp/LNAAs plasma ratio I think better than only trp.
Unfortunaly Tryptophan is the limiting amino acid in most sources of proteins, then these cause a decrease in plasma Trp-LNAAs ratio and are therefore not suitable for supplementation of tryptophan.
Finally I found alpha-lactalbumin (ALAC), a whey protein, naturally occurring in human milk, with the highest Trp-LNAAs ratio of all quantitatively relevant, food-derived proteins.
It is shown that ALAC can increase plasma Trp-LNAAs ratio of up to 48% compared to casein. By ALAC I developed Serplus (Giofarma Srl) a serotoninergic food supplement. In a pilot trial on 18 drug resistant epileptic patients we had a good clinical outcome in 10 out 18 (Albano C, Leonardi A, Mainardi P. 7th European congress on epilottology, Helsinki 2006). The mean percent seizures decrease was 48% ± 36% min= 0%, max= 100%. After Serplus in 13 patients, the seizures were milder; 5 pts referred a marked amelioration of mood. In 1 pt body weight was reduced; in 1 pt turned up a sleep improvement.
In these days a local multicenter trial is starting. The patients who have had a good clinical outcome ( 10 out 18 ) still now, after a year, have a good control of the seizures.

[RobinN]

This thread on the subject is interesting:
5-HTP

[drarvindr]

I really don't know. Not a nutritionist. Maybe , i suppose , since serotonin (5-Hydroxytryptophan) is made from trypto. I suppose the definitive test is to look for people who have epilepsy AND carcinoid syndrome ( it's a tumor that makes a LOT of serotonin) , so if the carcinoid tumor reduced their seizures , it could indicate that trypto can help. Then again , certain SSRIs(drugs like sertraline , clozapine and Prozac) can induce seizures in some patients and while they don't make serotonin , they prevent you from destroying the serotonin you have (increasing the amount of serotonin in your blood). So i'm not sure about "SSRIs were wrongly believed to be pro convulsants" since there are many many conflicting studies, and for every study that says they are safe there's one that says they aren't. Every study , even the ones which have claimed they are safe have said that seizures were worsened in at least some patients , so there is definitely a risk in some portion of the population . Whether this risk is genetic or environmental remains to be seen, as there is no clear consensus regarding the safety of SSRIs in epilepsy.

Interesting point , though.
Btw,
Re: the above study , a sample of 10-18 people isn't nearly big enough to prove significance. Need a full abstract to draw meaningful conclusions , although i still feel finding a correlation in 10 people isn't statistically significant.

P.S. Now they're doing it backwards. Years ago , epileptic patients who also had depression had their depression lessened when they had seizures. That's why some brainiac decided to simulate seizures in non epileptic suicidally depressed patients - TADA! Electroconvulsive therapy. Now they're using this as a rationale for giving serotonin in epilepsy. Hmmmm.

[stilldancing_98]

Now that is interesting. You should make being a nutritionist a part of being a neurologist. That would be very helpful to your patients. Are you going to be working with children or adults?

[Bernard]

If tryptophan helps prevent seizures? The reason I'm asking is because over thanksgiving I are leftover turkey for at least four days and I felt like I had the most clarity and calmness in my thinking than I have ever had! If anyone knows that would be helpful, thanks!

This thread on the subject is interesting:
5-HTP

Robin beat me to it. You could always try experimenting with a 5-HTP supplement (available at any vitamin store) and see how it goes.

[epileric]

to see if it helped my seizures but it seemed to make them more frequent & more intense

[googly389]

to see if it helped my seizures but it seemed to make them more frequent & more intense

What type of seizures do you have? I believe mine are coming from one of my temporal lobes, so the case might be different. Anyhow, I might just get on the GARD diet which allows turkey I believe, as opposed to taking supplements. Thanks everyone for the help!

edit: I do wonder if it may be just the fact that it promoted better sleep since in the past when I had my complex partial seizures, they seemed to be triggered by a poor night of sleep and nothing else. Just a thought.

[epileric]

My seizures are mostly partials as long as I'm on my meds. They discovered that they were caused by a lesion on the hypothalimus in the brain so it is possible that tryptophan would effect you differently.

If you do try it let us know how it effects you.

[Junebug]

There really is not much Tryptophan in turkey compared to foods that you eat everyday. Most of the Tryptophan in turkey = sleepyness is a myth. Typtophan is also in other foods that you eat everyday.

Turkey meat and drowsiness
One widely-held belief is that heavy consumption of turkey meat (as for example in a Thanksgiving or Christmas feast) results in drowsiness, which has been attributed to high levels of tryptophan contained in turkey.[48][49][50] While turkey does contain high levels of tryptophan, the amount is comparable to that contained in most other meats.[15] Furthermore, postprandial Thanksgiving sedation may have more to do with what is consumed along with the turkey, in particular carbohydrates and alcohol, rather than the turkey itself.

It has been demonstrated in both animal models[51] and in humans[52][53][54] that ingestion of a meal rich in carbohydrates triggers release of insulin. Insulin in turn stimulates the uptake of large neutral branched-chain amino acids (LNAA) but not tryptophan (trp) into muscle, increasing the ratio of trp to LNAA in the blood stream. The resulting increased ratio of tryptophan to large neutral amino acids in the blood reduces competition at the large neutral amino acid transporter resulting in the uptake of tryptophan across the blood-brain barrier into the central nervous system (CNS).[55][56] Once inside the CNS, tryptophan is converted into serotonin in the raphe nuclei by the normal enzymatic pathway.[51][53] The resultant serotonin is further metabolised into melatonin by the pineal gland.[9] Hence, these data suggest that "feast-induced drowsiness," and in particular, the common post-Christmas and American post-Thanksgiving dinner drowsiness, may be the result of a heavy meal rich in carbohydrates which, via an indirect mechanism, increases the production of sleep-promoting melatonin in the brain

[drarvindr]

Just a word of warning , should any person with depression come across this post:
If you are on any of the following drugs :
Azilect, Eldepryl ,Emsam ,Marplan ,Nardil ,Parnate or Zelapar
DO NOT TAKE MORE TRYPTOPHAN IN YOUR DIET.IT COULD BE POTENTIALLY FATAL. MAO inhibitors (drugs listed above) increase the metabolism of tryptophan into catecholamines (stuff like adrenaline) and you could go into a hypertensive crisis (the so-called "cheese reaction").

[stilldancing_98]

Do you have other names for those drugs?Cheese reaction. Please explain.

[brain]

Since my deceased father was a Chief
Pharmacist for years, and I have knowledge
in the Pharmacology area - I can answer these
questions for you:

Brand Name is first (Generic)

• Azilect (Rasagiline) - Neurological (usually for Parkinson's)
• Eldepryl / Carbex (Selegiline / Selegiline HCL) - Neurological
• Zelapar / Eldepryl (Selegiline Hydrochloride) - Neurological
• Emsam (Selegiline Transdermal System {Patch}) - Anti-depressant
• Parnate (Tranylcypromine) - Anti-depressant
• Nardil (Phenelzine) - Anti-depressant
• Marplan (Isocarboxazid) - Anti-depressant

=============================

What the Doctor was in reference to the "Cheese"
effect - because "Cheese" is often aged, and aged
products will cause serious problems. This ALSO
includes: Fermented Products and Aged Meat too!
And I hate to imply this - but PICKLES will be a
"No-No" here as well as well as YEAST products!

[stilldancing_98]

That was very informative! Thank you Brain. But is it just those meds? Or would it include other antidepressants.I take celebrex. So would it include all of those?I'm getting confused. sdkjf! it's those meds again. I feel kind of dumb and giggly all day.Now if I could only lose about 15 lbs.

[brain]

That was very informative! Thank you Brain. But is it just those meds? Or would it include other antidepressants.I take celebrex. So would it include all of those?I'm getting confused. sdkjf! it's those meds again. I feel kind of dumb and giggly all day.Now if I could only lose about 15 lbs.

Celebrex (celecoxib) - is a NSAID which is known as:
Nonsteroidal Anti-inflammatory Drug

You should not take this if history of allergic reaction
to aspirin, sulfa drugs, or other NSAIDs.

NSAID unfortunately has a Drug-Drug reaction with
other drugs including OTC (Over-The-Counter), even
with Ibuprofen, Motrin, for examples.

If you're experiencing issues / problems - you are
none the wiser to pick up the phone and call the
Doctor's Office and have a "Drug Review" consultation,
but whatever you do - DO NOT STOP YOUR MEDS
ON YOUR OWN!

ADDENDUM:
I did some research online and found that Celebrex
should not be used with Lithium at all! So if anyone
is on Celbrex and Lithium ~ it's a high time that you
pick up the phone and have a serious talk with your
Doctor!

[drarvindr]

No . the cheese reaction and hypertensive crises only occur in patients on Monoamine oxidase inhibitors (selegiline , Rasagiline,Phenelzine,Isocarboxazid). These drugs affect the metabolism of tyramine and tryptophan. When you eat too much tyramine you get hypertensive because the tyramine becomes catecholamines. The tryptophan gets converted into large amounts of serotonin which causes hypertension , flushing , and diarrhoea. People on these drugs should lay off meat extract drinks like Bovril , also stay away from aged cheese and other products high in tyramine and tryptophan.
It's also a good idea to wear a medic alert bracelet that you're on these drugs

[brain]

No . the cheese reaction and hypertensive crises only occur in patients on Monoamine oxidase inhibitors (selegiline , Rasagiline,Phenelzine,Isocarboxazid). These drugs affect the metabolism of tyramine and tryptophan. When you eat too much tyramine you get hypertensive because the tyramine becomes catecholamines. The tryptophan gets converted into large amounts of serotonin which causes hypertension , flushing , and diarrhoea. People on these drugs should lay off meat extract drinks like Bovril , also stay away from aged cheese and other products high in tyramine and tryptophan.
It's also a good idea to wear a medic alert bracelet that you're on these drugs

Okay, let's have a Science Class today!



Permit me to translate what the Doc was saying, as
I am positively sure that many of you are left with


First of all let's find out what MOAIs is. MOAIs is an
abbreviation for Monoamine Oxidase Inhibitors.

Now what is a MOAIs? Like many of you are familiar with
"Benzos" (Benzodiazepines) which is a "Family" or a "Class"
of medication - which includes Diastat, Valium, Klonopin,
etc. MOAIs is a "Family" or "Class" itself - of powerful
anti-depressants. While often used to treat Parkinson's
Disease, it has other uses as well; such as social anxiety,
non-typical and atypical depression (I'm unsure if they
use the word "non-typical depression" anymore), migraines,
etc. Which in turn we know it as "Off Label" usage, which
is also know as 'multi-purpose' drug.

What on earth is Selegiline? It is a drug - and it is often used
commonly for Narcolepsy, Parkinson's, Depression, and other
"Off Label" usage - as it has 'multi-purposes'. It is a powerful
drug.

Now the next phase he posts I have already posted below,
are the drugs (both brand and generic - alongside with
their purpose). See Post #13

Which before I bring up the next issue, we will talk about
SEROTONIN - because it is very important to know about
this for it's critical and will result serotonin toxicity which
is very serious! And some of the partial list below is an example
Cognitive effects: mental confusion, hypomania, hallucinations,
agitation, headache, coma.
Autonomic effects: shivering, sweating, hyperthermia,
hypertension, tachycardia, nausea, diarrhea.
Somatic effects: myoclonus (muscle twitching), hyperreflexia
(manifested by clonus), tremor.

What exactly is serotonin anyway? This here will provide you
all the explanation and references to SEROTONIN (click on
the link - for it is very interesting reading and learning
about your brain, and all the nerves and tidbits and
it's functionality. The Neurotransmitters, Neurons, CNS
(Central Nervous System), Receptors, and so much more.
{You're going to feel like you're in University now!}

So once having understanding of this end, now we
can move on to the other two:

Tyramine, which I am going to quote because it has the
best description than I can type it:

Tryamine is metabolized by the enzyme monoamine oxidase.

Foods containing considerable amounts of tyramine include meats that are potentially spoiled or pickled, aged, smoked, fermented, or marinated (some fish, poultry, and beef); most pork (except cured ham); chocolate; alcoholic beverages; and fermented foods, such as most cheeses (except ricotta, cottage cheese, cream cheese), sour cream, yogurt, shrimp paste, soy sauce, soy bean condiments, teriyaki sauce, tofu, tempeh, miso soup, sauerkraut; broad (fava) beans, green bean pods, Italian flat (Romano) beans, Chinese (snow) pea pods, avocados, bananas, eggplants, figs, red plums, raspberries, peanuts, Brazil nuts, coconuts, processed meat, yeast, and an array of cacti.

Then the next one would be what is Tryptophan? It is merely
one of the many standard amino acids. And I am going to
once again quote:

Tryptophan is a routine constituent of most protein-based foods or dietary proteins. It is particularly plentiful in chocolate, oats, bananas, mangoes, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas, sunflower seeds, pumpkin seeds, and peanuts. It is found in turkey at a level typical of poultry in general.

Congratulations Class, you've now graduated!

[borgolibero]

http://en.wikipedia.org/wiki/Alpha-lactalbumin is for Doctor Paolo Mainardi of Genoa University a natural anticonvulsivant.... he published in Medical Hypotheses a study, "Potentiation of brain serotonin activity may inhibit seizures". http://www.epilepsy.com/blogentry/966921 is an article of Mainardi on ''tryptophan, serotonin and epilepsy''. I talk to Mainardi . It seems very important. Also because Serplus is sold now online and is in test in Italy (in my town too) with good result on epilepsy in wich seizures are not well controlled by valproate or carmadiazepine.

[paolomainardi]

I thank Borgolibero and Joan who introduce my project in this very important forum.

The idea born on my results on amino acid anaylisis in blood of epileptic pts: I found all large neutral amino acid (LNAAs) levels to be lower respect controls. Tryptophan (trp) is an LNAAs, it's the only precursor of brain serotonin, and its brain uptake rate depend on trp/LNAA plasmatic ratio. On my data I evaluated 1/3 reduction of trp brain uptake in epileptic pts respect controls. Recently, Chugani by PET demonstred that the brain serotonin synthesis depend on the aumount of trp uptaked in the brain.
To potentiate brain serotonin was wrongly believe to be pro-convulsant, in fact antidepressant SSRIs drug were reported to be pro-convulsants. In '90s our clinical results (Albano C) domenostred SSRIs are anticonvulsants, and in 2005 Jobe wrote tha at low doses, as used as antidpressant drugs, they are anticonvulsants, at higher doses, as used in experimental models, they are pro-convulsants. Jobe have a lot of experience on serotonin and epilepsy and in this paper reported a role of serotonin as brain controller, with the aim to keep isolated bad function neurons. If this controller system fail, these neurons are used in neuronal cyrcuits and epilepsy or depression come out, depending where are localized these bad function neurons.
The original idea was to increase trp/LNAA plasmatic ratio to increase trp brai uptake and brain serotonin synthesis.

starting '70s, a lot of papers reported good anticonvulsive response in animals by trp injections in blood, but clinical studies in humans with oral adminsitration carry out controversial results both in epilepsy and depression.


Gastroenterologic studies reported that free amino acids are not absorbed by intestine, they cross intestinal membrane thanks carrier systems and all LNAAs compete with the same carrier as at BBB. In spite of about 14 million of people using trp, i found only one paper on metabolic fate of trp in humans, but the authors had to inject in blood to see an increase in blood level!
In fact, gastroenerologic studies report that the best way to increase free amino acid plasma levels is by proteins, among them why protein carry out an higher increase, because they don't precipitate in acids of stomach and demolished to peptides freely cross the intestinal membrane.
Unfortnately all protein of our diet have a low trp/LNAA ratio, then they carry out a decreasing in this plasmatic ratio.
I found alpha-lactalbumin, a whey protein of milk, in human milk, too, it have a high trp/LNAA ratio and markus studies reported it able to increase trp/LNAA ratio in blood.
In 2006 started a open study on this protein in 18 drug resistant epileptic pts, the results were very good: 5 don't responder, 7 have an 50% of decreasing of seizures, 4 more of 80% and 2 go free from seizures.
After these results I contacted prof Perucca (Pavia, Italy) vice-president ILAE that help me a lot. Thank to Perucca, prof De Sarro, Catanzaro, tested ALAC on different experimental models, more than 500 animals, more than 1 year of study. These results were very good, also in pilocarpine model (ALAC is effective both in chronic and acute seizures of this model) and they let ALAC to entry in NIH screening tests as new drug.

The De Sarro's results confirmed the need to chronic administrations to have anticonvulsant effect. A single dose was not effective at any dosage, at least 5 days of repeated adminstrations were needed to have anticonvulsant effect, no dose depending in many experimental models.

On the basis of these evidences I start a new idea: to obtain an anticonvulsant effect is not enought increase trp/LNAA ratio, but it have to keep elevated for many days, in this way the neuroendocrine system carry out the stimulation of brain synthesis of neuropeptides, as NPY. Studies on NPY direcly injected in brain of animals showed an high anticonvulsant action, in fact it's named "endogenous anticonvulsant".

Neuroendocrine system link intestinal brain to brain, it's a control system and it give high and sudden response to prolonged stimuli. They are: fasting, as reported in Bible to control seizures, intesinal nutrients as fats, ketogenic diet, triglycerid, expecially medium chain T, the MCT diet, or trp and/or serotonin.

Then, SSRIs surely increase intestinal serotonin before reach brain, many anti-epileptic drugs increase trp and/or serotonin in intestine, and ALAC increase intesinal trp.

The new idea is about the possibility to act on intestine to promote brain synthesis of neuropeptides, as NPY, leptine, norephineprine. All of them are showed to be anticonvulsants and antidepressants.
The mechainsm of action of neuopeptides are different from those of neurotrasmitters, they act on neurogenesys and sinaptogenesys, in this way they make more easy to keep isolated the bad function neurons, in agrrement with Jobe's theory, making new neuronal circuitations in our brain.

It's my opinion more easy use endogenous system to control seizures, by gut-brain axes, than directly act on ionic channels of neurons. Moreover often we lost that any drugs when orally adminsiterd surely act on intestinal brain.

[Bernard]

Hi Paolo, welcome to the forum.

You have touched on a lot of topics (tryptophan/serotonin, gut brain, blood brain barrier, etc.) that have been discussed here in the forum in various places, but not brought into a cohesive picture before.

Neuroendocrine system link intestinal brain to brain, it's a control system and it give high and sudden response to prolonged stimuli. They are: fasting, as reported in Bible to control seizures, intesinal nutrients as fats, ketogenic diet, triglycerid, expecially medium chain T, the MCT diet, or trp and/or serotonin.

If I'm understanding you correctly, you are saying that the reason the ketogenic diet works (and, I'm guessing by extension the Modified Atkins and LGIT) is because they increase the trp/LNAA ratio in the gut? Is reducing dietary intake of simple carbohydrates enough to affect the trp/LNAA ratio?