Does tryptophan help prevent seizures?

Keith

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Hi Andrew, I'm far from expert, but what I've been discovering is how people, including health professionals, believe the source of crucial nutrients is dietary. Also, it's thought fats such as PUFA in the diet are to blame for inflammation. But the real source is microbial enzymes responsible for biosynthesis of vitamin B6 and PUFA. Bacterial enzyme deficiency is underestimated and overlooked, especially in the intestines and liver. It's also biosynthesized in plants. I believe diet is secondary to flora. B6 deficiency is known in gut dysbiosis among other B vitamins which is one good reason to use probiotics. Here are some links about B6 biosynthesis:
http://www.bio-pro.de/magazin/wisse...l?lang=en&artikelid=/artikel/02669/index.html

http://www.jbc.org/content/280/7/5242.short

http://jb.asm.org/content/108/3/1001.short

http://www.ncbi.nlm.nih.gov/pubmed/15242009

even the so called bad guys make it (maybe they're not really bad, just overgrown): http://mbio.asm.org/content/1/3/e00112-10
 
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Keith

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Andrew, thanks for sharing that, way over my head, obviously, especially the question to Fermilab! I've been there a number of times, by the way, as a Chicagoan. You must be following the big news at CERN re: breaking speed of light. Not sure if it's been debunked. Also, the Higgs Boson story I wish I understood for even a moment.

So, I assume you've had genetic testing to confirm the mutation? Are you aware of how gene-microbe interaction can cause mutation? Over generations, it explains the fact that sanitation-challenged India suffers a full 60% of the world's heart disease based on 4% of the population carrying genetic defect. There's no return from mutation, so probiotics to shift flora in the right direction making B6 bioavailable wouldn't apply . . . I'm only theorizing and really haven't a clue. However, it's known microbes switch genes on and off including their own.
 
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Keith

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Tryptophan is thought to be only a dietary factor when it's well known to be made by microbes such as bacteria and yeast via biosynthesis. When in balance, I believe our gut flora likely has the enzymes necessary to create tryptophan. There's a lot of research since the 1960s on E.coli producing tryptophan, yet I can't seem to find anything about gut flora producing our tryptophan (it's all about eating turkey and cashews to modern science).
http://rnajournal.cshlp.org/content/13/8/1141.full

Serotonin is well studied in gut disease such as IBS; here's a study about tryptophan depletion in IBS and gut-brain connection:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774304/

Interestingly, there's 400x more melatonin (converted from serotonin which is made from tryptophan) in the gut than the brain's pineal gland. Most people assume all melatonin is made in the brain:
http://www.ncbi.nlm.nih.gov/pubmed/12395907

Perhaps the most important factor about tryptophan is how it's converted to niacin in the liver via microbial enzymes. Niacin deficiency is associated with the "4 Ds" —dermatitis, diarrhea, dementia, and death. Niacin is also antimicrobial, regulating microbial metabolism, lowers cholesterol and modulates H3 histamine receptor (important in hypothalamus function). Niacin also boosts innate immunity to help balance gut flora.

I just don't understand why tryptophan is thought to be about diet when microbes make it. When our intestines are out of balance, however, it seems tryptophan depletion is possible regardless of diet. This study shows how tryptophan is consumed (metabolized) by flora, likely the case in bacterial overgrowth, i.e., SIBO: http://www.pnas.org/content/106/10/3698.long

5-HTP may help bring serotonin levels up, but for some folks with gut malfunction, serotonin is a problem causing spasm in IBS. Also, I understand 5-HTP cannot be made in the the body into niacin.
 

Keith

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I've thought the reason fasting seems to halt seizure activity is simply via allowing the gut to rest, especially since intestinal innervation (nerve fibers and bundles) are the most extensive in the body. I didn't think it was about ketones and still don't, though I obviously have much to learn about ketones.

But there are also interesting dynamics regarding tryptophan and fasting. One of them is tryptophan levels in the pancreas rise during fasting and lower in serum. Apparently, tryptophan levels change quickly upon eating. http://www.springerlink.com/content/g527627x24378n42/

And because tryptophan is the precursor for niacin, apparently niacin is released more efficienty during fasting:
http://www.ncbi.nlm.nih.gov/pubmed/4260741

Fasting also appears to induce significant increase in melatonin in both serum and gastrointestinal tract:
http://books.google.com/books?id=m_...Q6AEwBg#v=onepage&q=melatonin fasting&f=false

So, between pancreatic tryptophan, niacin and melatonin increased during fasting, there's improved glucose and lipid control along with antimicrobial and powerful antioxidant activity.

But how is serotonin affected by fasting? It's depleted in fasting, apparently a good thing in the case of gut dysbiosis where too much serotonin is a problem. But fasting is said to increase serotonin levels in the brain and maybe that's a good thing. So, there's an inverse relationship in brain and gut serotonin during fasting.
http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.1984.tb16495.x/abstract

There's a growing science behind the practice of intermittent fasting (IF) and several variants of the diet. The one I think makes sense is allowing oneself a daily eight hour eating window, i.e., noon-8pm.

Some nice IF references here associated with brain health:
http://healthyagingreview.com/featured/does-fasting-decrease-aging

Please accept what I'm saying here "with a grain of salt" as I'm really just learning aloud . . . here's a brand new paper released last week stating "gut-derived serotonin" is increased during fasting which leads to better fat absorbtion (I've read fat malabsorption is the real cause of gut symptoms in Celiac disease). They state this also leads to improved glucose regulation. http://www.sciencedirect.com/science/article/pii/S1550413112003981
 
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Bernard

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... Thank to them, ALAC is entry in the screening of new drugs at NIH. ...
I was curious this morning and did some searching around. Some of those studies have been published now (both done on rodents):

http://www.ncbi.nlm.nih.gov/pubmed/21458955 (2011)

http://www.ncbi.nlm.nih.gov/pubmed/23000629 (2012)

I also saw this study headline (title) which I thought interesting:
The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism.
http://www.ncbi.nlm.nih.gov/pubmed/23955123
 

masterjen

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I wouldn't chalk the problem up to genetic defect so quickly given how genes are turned on and off like light switches by microbes and microbial metabolites. We're not necessarily our DNA because our lifestyle regulates DNA.
On what basis do you draw this conclusion? Do you have evidence to challenge what these researchers have found? Is there a flaw in their research methodology and consequent evidence?

I have a genetic disorder, and tryptophan (among other neurotransmitter-based medications) has been shown to improve my seizures. So are you saying it's my fault I have this genetic disorder and my lifestyle would have prevented development of this genetic condition? If so, based on what you are saying than changing my lifestyle should "readjust" my DNA so I no longer have this condition. Many specialists over the years have yet to cure me . . . are you saying you can? Tell me how to change my lifestyle to do this, I'll retake the genetic test and we'll see if I no longer have the faulty genes.
 

Keith

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jen, have you ever researched how genes can change over time? I'm not at all saying the research is faulty. In fact, I think it's great evidence. And I'm not saying your genetic disorder is your fault. Which gene was found mutated? Or are you just assuming your condition is genetic? It could be, you may have been born that way.

What I am saying is that we do have some control over our genes. Genes are quite commonly viewed in this way these days. Celiac gene testing, for example, will show genes positive for the disease, then negative after gluten-free diet within weeks. And there's a lot we have to learn about gene-microbe interaction. Bacteria are known to have similar tryptophan genetic pathway, ACMSD, as humans. http://www.ncbi.nlm.nih.gov/pubmed/17288562

I don't know your history or much about your epilepsy, so wouldn't know how to make suggestions. Do you have any gastrointestinal symptoms? I see on your profile you say largely nocturnal seizure, so any history of hypoglycemia? There's much people can do in attempt to resolve epilepsy. My construct, if it applies to you, is about shifting gut flora through diet and supplements, addressing both gut and brain. What have specialists done to address your gut?

If tryptophan is helping, you might consider testing niacinamide before bed as that's an important part of tryptophan metabolism to raise NAD.
 
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Keith

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to see if it helped my seizures but it seemed to make them more frequent & more intense
Perhaps tryptophan raised serotonin which is an excitatory neurotransmitter in both gut and brain. CO2 is supposed to put serotonin where it should be, but I don't know the details.
 
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Interesting thread. I think it would be a good idea to talk to my GP about this.

Could be helpful.
 

Keith

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What's really interesting is how certain microbes that are overgrown in the gut can cause tryptophan imbalances. Microbes make and break tryptophan. For example, overgrowth in Proteobacteria may degrade too much tryptophan leading to a deficiency of brain serotonin . . . which can dysregulate the glutamatergic system leading to excitotoxicity such as seizure.

Microbes also make other amino acids which compete with tryptophan to cross the blood-brain barrier.

Many things about gut microbiota implicate altered tryptophan metabolism as cause of gut-brain problems.

Paolo Mainardi's work about ALAC is very interesting, especially when considered as prebiotic.
 

Keith

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This ALAC paper looks interesting related to nocturnal seizure:
Evening intake of α-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention
http://ajcn.nutrition.org/content/81/5/1026.full

And this one from year 2000:
The bovine protein α-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress
http://ajcn.nutrition.org/content/71/6/1536.full

I don't think ALAC is available on the shelf. Maybe it's in some infant formulas and some whey products.
 

Keith

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This paper seems to implicate Clostridium overgrowth with amino acid imbalances:
The Role of Microbial Amino Acid Metabolism in Host Metabolism
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425181/
Furthermore, the addition of BCAA (valine, leucine, and isoleucine) to trypticase yeast extract has been shown to increase the yield of BCFA in Clostridia [64]. These observations provide evidence that several amino acids can be used for SCFA production as well as for BCFA production by gut bacteria.

Gut bacteria generally contain a higher proportion of BCAA relative to other amino acids [32]. Whether this may indicate increased BCAA synthesis and/or uptake, or decreased BCAA breakdown, and if this influences host BCAA availability remains to be determined.
ALAC is about raising the ratio of tryptophan to LNAAs in order to allow more tryptophan into the brain to increase serotonin. But too much serotonin may also be a problem, known as Serotonin Syndrome. Serotonin is also excitatory in the gut associated with diarrhea. BCAAs are a type of LNAA, so microbial uptake and synthesis of BCAAs appears to greatly affect neurotransmitter balance.
 

Keith

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We also know BCAAs are raised by the ketogenic diet, likely due to flora shift such as reduced Clostridia and raised Bacteroides, also known.
High plasma branched-chain amino acids:aromatic amino acids ratio in children on the ketogenic diet: a mechanism in controlling epilepsy.
http://www.ncbi.nlm.nih.gov/pubmed/15217184
 

Keith

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So, if someone had high Clostridia as known in autism and other conditions, then microbial uptake of BCAAs might raise dopamine. Clostridia produce HPHPA known to inhibit conversion of dopamine to norepinephrine which is anticonvulsant.
A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function.
http://www.ncbi.nlm.nih.gov/pubmed/11875637

Interaction between dopamine, serotonin and the endocannabinoid system is interesting stuff.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612120/
 

Blonde Angel

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Never thought I'd get interested in the amino acid metabolism stuff.
So, it seems this could be important in that if one doesn't have any tryptophan available one isn't going to make serotonin.

The brain makes all these neurotransmitters like GABA, dopamine, nor-adrenaline, melatonin and yes serotonin.
It relies on the digestive tract to supply these goodies.
 
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