Exploring the Gut-Brain Connection and Photosensitivity

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BTW, nicotine does get oxidized in the body, but it does not turn into niacin. It turns into cotinine. The process happens mostly in the liver through the action of the P-450 cytochrome (an enzyme).

Yes, I did mention that earlier. There is also a link to the rest of the process of nicotine's metabolism in the body, probably two or three pages back. It turns into rather a number of things before it's stored and evacuated. Unfortunately, none of those things is niacin.
 
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kirsten, I agree, let food be thy medicine. I'm especially interested in the low carb diets, resistant starches, fermented foods and intermittent fasting. These and the ketogenic diet have been discussed in this thread.

Oh, dear. No, the evidence I'm referring to doesn't talk about magic diets but healthy diets, i.e. those that give us all the vitamins and minerals and fat and protein we need. I'd hate everyone to think I was saying that intermittent fasting (http://whatstheharm.net/detoxification.html) and low carb diets had more evidence of efficacy than supplements. That's entirely another kettle of fish. Not so much evidence on that score (we do have some evidence for keto diets in epilepsy.)
http://www.sciencebasedmedicine.org/more-evidence-that-routine-multivitamin-use-should-be-avoided/

And if you're actually questioning my humility, I can't blame you as that's exactly how I feel about the pompous medical establishment continuously treating epilepsy from the neck up

Spending 14 years of study, decades of practice with 20 actual patients daily, 210 days a year, spending several years on each study and developing treatments that meet stringent safety and efficacy standards based on the evidence they find, to collectively formulate a field that now brings remission in 70% of epilepsy patients, instead of doing it Keith's way, is pompous?
Make no mistake, the medical field has looked into and studied the link between the gut and the brain. That's where all your studies come from. Their results have never been statistically significant or repeatable or translatable from animal to human trials, and they've never demonstrated anything useful enough to create a new tier of useful epilepsy treatment, so they continue to treat epilepsy as a brain thing. Funny, that.

This whole thing is kinda like trying to turn my bedroom light on by flushing the toilet, and when that doesn't work, trying out the light switch, and when that works, going back to always flushing the toilet every time I need light. It sucks trying to read in the dark, but I'm sticking by my belief in the plumbing-electricity connection.

Now I'm really bowing out.
 
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Yes, I did mention that earlier. There is also a link to the rest of the process of nicotine's metabolism in the body, probably two or three pages back. It turns into rather a number of things before it's stored and evacuated. Unfortunately, none of those things is niacin.

Please read my post earlier detailing how nicotine converts to nicotinamide (niacinamide) via cotinine which is what niacin converts to naturally in the body. So it seems nicotine conversion skips a step from niacin to niacinamide and converts directly to niacinamide. That's a good thing, except when one has too much of a good thing as is the case in chronic smokers . . . associated with diabetes and cancer.

And how does this relate to gut microbes? Tryptophan metabolism to niacin and serotonin, hence melatonin, is dependent on microbial balance.
http://books.google.com/books?id=9z...nepage&q=tryptophan gut flora indole&f=false

"A subset of enteric bacteria express tryptophanase, which converts tryptophan to indole, pyruvate, and ammonia."
http://www.pnas.org/content/106/10/3698.long
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC235931/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209837/
http://mic.sgmjournals.org/content/159/Pt_2/402.full

Here's some discussion we had on the forum two years ago:
http://www.coping-with-epilepsy.com...tophan-help-prevent-seizures-5183/index5.html
 
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Beginning to learn something more about nitric oxide (NO) in epilepsy and how levels may be regulated by microbes:

NO is made in the body from citrullene (high in foods such as watermelon) via arginine:
http://www.sciencedaily.com/releases/2008/06/080630165707.htm

There are contradictory roles for nitric oxide (NO) in epilepsy, but this study found inhibiting NO anticonvulsant: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1915743/

Nitrogenous compounds and sulfur in red meat a culprit feeding NO production? Who's making it? "Most remarkably, when cysteine or starch were excluded, NO concentrations reached significantly lower levels . . . To our knowledge, no literature is available on the direct influence of cysteine, starch or any of these compounds on microbial NO production. As the results were most remarkable for cysteine, this compound was chosen for further investigation elucidating the NO formation mechanism."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821680/?report=classic

Everything placed in our mouths is a prebiotic.
Nitric Oxide Production by the Human Intestinal Microbiota by Dissimilatory Nitrate Reduction to Ammonium
http://www.hindawi.com/journals/bmri/2009/284718/citations/

Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice.
http://www.ncbi.nlm.nih.gov/pubmed/23188422

This new article about NO in gastrointestinal health looks interesting, still reading: http://www.aor.ca/wp-content/uploads/2014/03/Nitric-Oxide-and-Gastrointestinal-Health.pdf

Relationship of NO to glutamate:
http://www.medsci.org/v07p0147.htm

Flora shift via lowering nitric oxide which decomposes into nitrates feeding "bad" bacteria out of balance: http://www.ucdmc.ucdavis.edu/publish/news/newsroom/7462

Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite
http://www.sciencedirect.com/science/article/pii/S1089860305001266

Review article: nitric oxide from dysbiotic bacterial respiration of nitrate in the pathogenesis and as a target for therapy of ulcerative colitis
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2008.03612.x/abstract

Nitric Oxide Can Alter Brain Function
http://www.sciencedaily.com/releases/2008/11/081126133403.htm

"Summing up, in the present state of knowledge the only reasonable conclusion is that NO behaves as a neuromodulator with dual - proconvulsive or anticonvulsive - action." http://www.ncbi.nlm.nih.gov/pubmed/21999730

Zinc inhibits nitric oxide formation in response to lipopolysaccharides which are microbial endotoxins causing hypothalamic inflammation. http://www.sciencedirect.com/science/article/pii/S0014299997014167

It seems some people may be too high in NO and some too low based on flora balance.
Sleep and epilepsy: A key role for nitric oxide?
http://www.ncbi.nlm.nih.gov/pubmed/10897149

Dual role:Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models
http://www.scielo.br/scielo.php?pid=S0100-879X1997000800010&script=sci_arttext
 
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It seems likely that too much nitric oxide (NO) is the prevalent problem in epilepsy due to NO inhibiting glutamine synthetase which would otherwise clear glutamate. Which microbes may be responsible for excess NO leading to glutamate toxicity? http://www.sciencedirect.com/science/article/pii/S0197018613001708
http://link.springer.com/article/10.1007/s13105-010-0054-2
http://www.sciencedirect.com/science/article/pii/S000689939800064X
http://www.ncbi.nlm.nih.gov/pubmed/16869530
http://www.sciencedirect.com/science/article/pii/S0197018603000391

"This study demonstrated the up-regulation of citrulline-nitric oxide cycle enzymes and may contribute to enhancing recycling of citrulline to arginine to support the increased production of nitric oxide in epilepsy. The decreased glutamine synthetase may increase glutamate in chronic epilepsy and may lead to neurodegeneration."
http://file.scirp.org/Html/1-2400238_46646.htm

The relationship of NO and glutamate toxicity in eyes is also troubling.
http://online.liebertpub.com/doi/abs/10.1089/10807680151125555
http://journal.frontiersin.org/Journal/10.3389/fendo.2013.00048/full
http://www.sciencedirect.com/science/article/pii/S0014483500908406

The relationship between insulin and nitric oxide is especially interesting. If fasting increases NO which inhibits insulin secretion, this may explain how fasting halts seizure activity via balancing blood sugar and avoidance of hypoglycemia. "We conclude that both high glucose concentrations and fasting increase islet total NO production (mostly iNOS derived) which inhibit insulin secretion."
http://www.sciencedirect.com/science/article/pii/S0167011511001893
 
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More on photosensitive seizure potentially caused by nitric oxide in eyes exposed to light:

Ultraviolet B Irradiation of the Eye Activates a Nitric Oxide-dependent Hypothalamopituitary Proopiomelanocortin Pathway and Modulates Functions of alpha-Melanocyte-stimulating Hormone-responsive Cells
http://www.nature.com/jid/journal/v120/n1/full/5601715a.html

"The vitreous NO initially increased rapidly to flicker, but then decreased as the flicker continued. We found that the diurnal change of NO in the vitreous depended on the ambient light condition."
http://www.sciencedirect.com/science/article/pii/S0304394003007171

http://www.sciencedirect.com/science/article/pii/S004269891000502X

http://news.ucsc.edu/2012/05/nitric-oxide.html

As discussed in the previous post, NO inhibits glutamine synthetase which raises glutamate. In earlier posts, we discussed glutamate release in eyes exposed to light inhibiting melatonin.
 
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But this excess nitric oxide (NO) as cause of seizure including photosensitive seizure is thought to feed intestinal microbial imbalance, a vicious circle of gut dysbiosis. NO collides with superoxides to form nitrates which feed certain bacteria such as E. coli. Then the situation shifts to low NO seen in type-2 diabetes, itself associated with seizure.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927936/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657953/

Here's an explanation for low NO in diabetes: a vicious circle where intestinal microbial overgrowth feeds on nitrates formed when NO collides with superoxides:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004111/
https://www.sciencenews.org/article/inflammation-feeds-e-coli
(E. coli is strongly associated with diabetes)

Association between seizures and diabetes mellitus: a comprehensive review of literature.
http://www.ncbi.nlm.nih.gov/pubmed/23590576

Note to Shelley, thanks for your research and interest. We're going to have to agree to disagree on the facts.
 
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Agreed, the bodybuilding forums can be good ways to learn, however, they're clueless about the importance microbial balance. And so is most of the world.

The point I'm making is nitric oxide levels are regulated by intestinal microbial balance.
 
... Make no mistake, the medical field has looked into and studied the link between the gut and the brain. That's where all your studies come from. Their results have never been statistically significant or repeatable or translatable from animal to human trials, and they've never demonstrated anything useful enough to create a new tier of useful epilepsy treatment, so they continue to treat epilepsy as a brain thing. ...

This isn't entirely true. It's only been relatively recent that renewed interest in diets came to be (largely thanks to the Abrahams and their Charlie Foundation). Dr. Kossof was doing a lot of good work studying diets (MAD, LGIT, etc.) and Paolo Mainardi has also contributed some interesting ideas.

I think the real problem with diets as a treatment option is that many patients don't have the discipline or determination to implement them. It's only the folks are "refractory" (meds won't work) that get serious about it.
 
Keith, your links are all single incidents and to be accepted in science an experiment has to be repeated with similar results as well as being done on a large human population (not rats or mice). Some of your links even appear to be describing the same study. One of them even refers to the incidence as very rare. Another of your links is so vague that it doesn't even say what was done or what it has proved, another is someones opinion (no indication if he has medical training) and another even says:
The syndrome of abdominal-visceral epilepsy is reviewed and reappraised. It is concluded that the syndrome does exist.

This is not something the scientific community can take seriously and without proper studies showing they shouldn't.

I can't help but believe that the neurologists don't see the gut/brain issue as a 2 way street have good reason not to so far.
 
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There aren't really any good sources for the definition of abdominal epilepsy, given that it's a diagnosis that isn't commonly accepted in neurology circles and it doesn't appear in authentic medical dictionaries, so in trying to come to your side of the fence for a while, I had to use WebMD. Here is what abdominal epilepsy is said to be:

Abdominal epilepsy is an exceptionally rare syndrome of epilepsy that's more likely to occur in children. With abdominal epilepsy, seizure activity causes abdominal symptoms. For example, it may cause pain and nausea. Anticonvulsant medications can improve the symptoms.

Abdominal epilepsy is so uncommon that some experts question whether it exists.

http://www.webmd.com/epilepsy/guide/abdominal-epilepsy-in-children-and-adults

All the definitions I find say the same thing: The focus in the brain causes the gastrointestinal symptoms, and anticonvulsants (which act on the brain) are effective in treating it. The same is seen in your papers.

This is what a seizure focus looks like. As you can see, it is in the brain, and not the gut.
2008_09_30_14_38_21_240_09_07_3933_01b_resized_zpse839056b.jpg


You've misunderstood the meaning of abdominal epilepsy. Abdominal epilepsy does not add to your premise. HOWEVER, if it's abdominal epilepsy that you're talking about in this thread, you're speaking about an exceptionally rare syndrome, and not about the sort of epilepsy most epilepsy patients have. If you are talking about abdominal epilepsy, you should say so in your signature so that the rest of us, and most of CWE, are aware that what you're discussing doesn't apply to us.

The brain affects the autonomic functions of the body (digestion, blood pressure, core body temperature etc). It does have an impact, in other words, on digestion. That doesn't mean that a seizure can immediately cause gastrointestinal symptoms, but it does mean that the brain can, in the case of autonomic neuropathy, cause diarrhea. It does not mean that diarrhea can cause neuropathy, or seizures.

In other words, the papers you've linked to say that the epileptic brain is causing the problem. The gut is not causing the problem. If they were decent papers, they would disprove your premise.

But it is important to remember that not all science is equal. Cherrypicking research that confirms your bias–that’s not science. Giving equal weight to everything that is written–that’s not science. Thinking that a researcher is an expert because they have a degree or qualifications in another area–that’s not science.
And these aren’t up for debate, because there is no debate, unless someone thinks that undue weight, given to bad science, is considered important evidence.
It’s important to remember that just because the science doesn’t support your point of view doesn’t mean it’s wrong. It means your point of view is wrong.
The TL;DR version:

Only high quality articles, published in peer reviewed, high impact factor scientific journals count in a discussion about science.
Expertise matters, and it’s not self-proclaimed nor is it established by a few letters after your name. It’s established by the amount and depth of respect from peers.
Not all science is equal. And the best research is a systematic review which shows a clinically significant effect.
Giving false balance or undue weight to fringe beliefs that are unsupported by the vast breadth of research in that area is inappropriate and can be ignored.

http://www.skepticalraptor.com/skepticalraptorblog.php/how-evaluate-quality-scientific-research/
This is going to sound snarky, but it's actually a question I'd really like you to answer. Please do comment. You don't answer most of questions in this thread, so I've made the questions red to make it clear which questions I'm asking you. I'm also asking that you answer them in words and not studies, please. You're free to add studies to support your case, but simply copying and pasting a bunch of studies is not really answering a question. :

When I almost drowned as a toddler, and got epilepsy as a result, how did the near drowning affect my gut in those two minutes, in order to affect my brain, giving it a seizure focus, in order to cause seizures for the rest of my life? Did the lack of oxygen have no effect on my brain, but a rather dramatic effect on my gut. In those two minutes, did my gut microbial balance go out of whack, or become leaky, or whatever, and then did that effect travel up to my brain and carve out my seizure focus? Or did the lack of oxygen damage my brain and give me a seizure focus?

Or, more simply, (and please answer this too) in our member who got epilepsy from surgery, when the doctors cut into his brain, did his gut go out of whack as a result, and cause an effect on the brain such that a scar was formed exactly where the surgeon's scalpel was cutting, giving him epilepsy? Or did the surgeon's cutting cause a scar that gave him epilepsy?
 
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I don't think that Keith is arguing that ALL new onset seizures have gut issues as a primary cause. (Keith -- correct me if I'm wrong).

But if you have a lower seizure threshold due to head injury, hereditary metabolic abnormality, etc., then gut issues can certainly play a contributing role as a secondary trigger, in the same way that fatigue or others stresses can.

There are some seizures that do have metabolic triggers (though it's important to note that these seizures may or may not be classified as epilepsy). Metabolic issues that can provoke a seizure:
-- Electrolyte disturbances (altered levels of sodium, calcium, or magnesium)
-- Hypoglycemia or hyperglycemia
-- Renal failure (kidney disease) with uremia
-- Hepatic failure and elevation of associated toxins
-- Hypoxia (lowered oxygen delivery to the brain)

As for the gut-brain connection, Keith -- it's okay to "think aloud", but please remember to emphasize that the science is new, inconclusive and/or speculative. Some animal studies do suggest "that gut microorganism can activate the vagus nerve" (see http://www.ncbi.nlm.nih.gov/pubmed/24997031), but how those mechanisms apply to seizures is yet to be determined.
 
I think every epilepsy patient on this green earth has experienced secondary triggers first hand, so none of us would argue against their existence. Lack of sleep, cerebral edema, sodium imbalances, low blood pressure, caffeine/guarana/etc...these are all secondary triggers I've experienced directly. And the reason they are secondary triggers is that they act on the brain.

Currently, the sweeping statements in this thread are saying 'epilepsy is of gut origin' (see first five pages of the thread, and probably the few around page 16) which is not the same as saying 'abdominal epilepsy is of gut origin', or ' idiopathic epilepsy is of gut origin'. He has also claimed that schizophrenia, bipolar, glaucoma, diabetes, some sort of cardiac disorder, and autism, among others, originate in the gut, and with babies who are born with epilepsy, it is the gut in-vitro that causes it. Keith has said in the past that he's not suggesting that we abandon the brain's role, but these sorts of statements need to be reworded correctly, but that view is always turned upon and we go back to square one where epilepsy is of gut origin. This isn't a website with the primary purpose of opinion-based research. People with epilepsy come here for help. I have followed your suggestions and those of other members on this site. I have made direct changes to my medication, bringing it down, taking different tests, as a result of suggestions I received here. I have stopped taking medication as a result of what was suggested here. Others do it too. I believe that gives the entire community a responsibility to keep our language accurate, and free of advice that should only come from a doctor.

This particular thread is, I think, problematic, because there is a blend of doctor/scientist-sounding writing, doctor/scientist looking research, doctor/scientist level of confidence in treating, and a layperson's capacity to research. It's a fatal mix, but not for the writer. To untrained eyes, this is *the* thread to learn how to treat epilepsy, and it has 15 000 plus views. This is why I keep harping on about language, asking about exactly 'gut origin of epilepsy' means, and trying to hone in on the truth of that view. Thus far, we've not moved past 'gut origin of epilepsy' into more realistic territory, so it's gut origin of epilepsy that I discuss. I'm aware that the goalposts have been moved back and forth, but at this point, we're where I have to ask about how an eating plan can erase or cause a scar.

I've been reading the thread from its inception--all the studies, the whole shebang. Give it a go, Nak. It'll give you a round view of the view.
 
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