# Proper balance of serotonin and dopamine lead to Crohn's disease remission



## David

> Abstract
> Purpose:
> 
> This paper reviews the clinical course of a case of severe Crohn’s disease and discusses the scientific ramifications of a novel treatment approach.
> Patients and methods:
> 
> A case study of a 37-year-old male with a 22-year history of Crohn’s disease whose clinical course had experienced no sustained remissions. The patient was treated with a protocol that utilized serotonin and dopamine amino acid precursors administered under the guidance of organic cation transporter assay interpretation.
> Results:
> 
> Within 5 days of achieving the necessary balance of serotonin and dopamine, the patient experienced remission of symptoms. This remission has been sustained without the use of any Crohn’s disease medications.
> Conclusion:
> 
> In Crohn’s disease, it is known that there is an increase of both synthesis and tissue levels of serotonin in specific locations. It is asserted that this is prima facie evidence of a significant imbalance in the serotonin–dopamine system, leading to serotonin toxicity. The hypothesis formulated is that improperly balanced serotonin and dopamine transport, synthesis, and metabolism is a primary defect contributing to the pathogenesis of Crohn’s disease.


Source


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## Jam300

Incredible!

David, do you happen to know of any other studies like this one that have been conducted? There must have been some research that promted this study to take place in to begin with...

I wonder how simple a task it is balancing both serotonin and dopamine...


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## David

Jordan, at the bottom of that paper are all the studies and sources that they reference.  That should be a good starting point 

I personally think that various nutrient and vitamin/mineral deficiencies such as magnesium and vitamin D play a critical role in the pathogenesis of Crohn's disease.  Both of them are very important players in the serotonin/dopamine ballgame.  Just a theory of course


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## SarahD

We should be wary in that this paper is only a case study on a single individual and results may not be generalisable. That said the result sounds amazing!


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## David

Good point Sarah, thanks for bringing that up.


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## Jam300

David said:


> Jordan, at the bottom of that paper are all the studies and sources that they reference.  That should be a good starting point
> 
> I personally think that various nutrient and vitamin/mineral deficiencies such as magnesium and vitamin D play a critical role in the pathogenesis of Crohn's disease.  Both of them are very important players in the serotonin/dopamine ballgame.  Just a theory of course


Thank you David, i'll give them a read.

I wholeheartedly agree with you, I had a fairly awful diet as a child and didn't really enjoy going out too much, as a result i'd imagine that from ages 5-16 I was most likely defficient in everything.


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## PaulPhoenix

I'd love to know how long their remission lasted or is lasting!

I guess it could have just been lucky.  It's a pity they couldn't have treated five or ten people at the same time.  That'd give a lot more confidence...


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## mf15

This is insane, looks to be semi easy,of course it is complex,trying to wade through it to see how it applies to UC.  One question is how did these ratios get out of whack in the first place.
This quys remission was over 2.5 years and still going.
They also did this on others,but this was the worst case they could find to write the paper on.  Does not seem to be a cure,still need to take the aminos to stay in remission.

Old Mike


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## kiny

To recap if I got this right.

A person with crohn's disease became refractory and was not in remission on LDN or diet. (he tried many other medications before this)

He was given precursors to dopamine and serotonin, namely *L-tyrosine* and *5-HTP*.

(he was also given 1000 mg of vitamin C, 220 mg of calcium citrate, 75 mg of vitamin B6, 400 μg of folate, 4500 mg L-cysteine, and 400 μg of selenium)

At _1500 mg_ L-tyrosine and _150 mg_ 5-HTP, once in the morning, once in the afternoon, there was no change.

They increased the dosage to 3x per day instead of 2x per day and his crohn's disease symptoms improved and said it was _"the best treatment he had experienced during the course of his 22-year illness"_

They increased the dosage to 4x per day.

Serotonin went from 5150.7 μg to 12,611.1 μg  / 1 g creatinine
Dopamine went from 206.4 μg to  741.3 μg / 1 g of creatinine

6 weeks later all aminos and medication were discontinued

5 months later he came back for checkup without symptoms, he was given the same protocol.

26 months after he is still fine

The GI said that he took care of the patient for 10 years and for the first time his crohn's disease was in remission.


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## David

kiny said:


> He was given precursors to dopamine and serotonin, namely *L-tyrosine* and *5-HTP*.


http://www.vitaglo.com/108.html?utm...medium=adwords&id=38924399594&utm_content=pla

http://www.vitaglo.com/sn0190.html

The $20.00 OTC cure long term remission inducer for Crohn's?


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## wildbill_52280

very interesting.

there could be some debate as to whether they fully understand why this happened as they are downplaying the role of the 4500mg l-cysteine they also gave the patient. they also did not define the term, "cofactors" that they also gave the patient, so that is an issue of objectivity, if i cant define what a "cofactor" is, i cant exactly reproduce the experiment in a fair way, to be precise they state "4500 mg l-cysteine with co factors" i know what l-cysteine is, but not a cofactor, that is not a specific physical thing it is an abstract general concept with some degree of subjective interpretation if not well defined.

so it is also possible some other mechanisms are also responsible, such as, extra l-cysteine affecting the antioxidant system, as l-cystiene is a precurser to glutathione. i have read that part of the inflammation that is chronic in IBD to be due to low levels of butyric acid levels from bacterial fermentation, leaving intestinal redox systems in a state of oxidative stress, and this is what leads to higher levels of inflammation. so the L-cysteine could also correct this state of oxidative stress, lowering levels of inflammation and related cytokines, like tnf-alpha.  

therefore, their explanation of why this patient reached remission, is still a little biased and theoretical, and may not be the real reason why remission was achieved.

EDIT- also, the serotonin precursors 5-htp could also be increasing melatonin production as well, which has also been shown to protect against experimental colitis in rats, and one human study where remission was also achieved this way. im still betting on the l-cysteine and selenium.


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## kiny

I think he's talking about cofactors and precursors to glutathione. L-cysteine or NAC, vitamin C and selenium are needed to raise glutathione, since giving glutathione in pure form doesn't help because it's not bioavailable.

Glutathione will help against ROS damage in the intestine, it's an intracellular antioxidant that's very powerful, but to increase it you need to use the right cofactors and precursors.


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## wildbill_52280

kiny said:


> To recap if I got this right.
> 
> 
> 
> (he was also given 1000 mg of vitamin C, 220 mg of calcium citrate, 75 mg of vitamin B6, 400 μg of folate, 4500 mg L-cysteine, and 400 μg of selenium)
> 
> .



ahhhhh, see, i did not find the part where they stated the selenium, or the other vitamins. im a little tired right now, but nice work to you Kiny!!!!

the selenium and l-cysteine could help balance the state of oxidative stress and lower inflammation reaction by increasing the levels of glutathione, IF that is why inflammation is enhanced in ibd that is, and this would be another alternate explanation for the results of the protocol, and not the levels of serotonin or dopamine, which undoubtedly seemed to change, but i dont agree were the therapeutic mechanism.


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## Trysha

SarahD said:


> We should be wary in that this paper is only a case study on a single individual and results may not be generalisable. That said the result sounds amazing!



Hi Sarah
You echoe'd my thoughts!
One swallow does not make a summer.
However it is a good paper and bears much thought and follow up.
Thanks David.
Trysha


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## kiny

that's a lovely expression trysha, never heard that


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## mf15

Here is a little bit more on the subject.
In the paper they did say they treated others with crohn's but this was
the worst case.
Old Mike
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355850/


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## David

Interesting that they utilized 400mcg of Selenium.  That's the Upper Tolerable Limit.


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## Trysha

It's an old English expression Kiny.
In England one day of sunshine, and no rain used to constitute summer!
Mostly rains all the time hence verdant pastures...
Flocks of Swallows arriving  herald the summer
Trysha


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## Igor_Passau

hi did you find any new studies?


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## mf15

ok here is something, not to say any DDS induced mice/rat colitis is like human UC.

http://www.sciencedirect.com/science/article/pii/S0016508509014565



Ok human UC study,just found one,checking metabolites of serotonin and melatonin,have not even read it yet.

http://cornetis.pl/pliki/GP/2009/5/GP_2009_5_358.pdf

more
http://farncombe.mcmaster.ca/documents/Ghiaetal.2009.pdf

transmitters.
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2982.2005.00673.x/pdf
more
http://www.nature.com/ctg/journal/v3/n4/full/ctg20128a.html

meals
http://www.ncbi.nlm.nih.gov/pubmed?term=12499331

dentric cells
http://www.ncbi.nlm.nih.gov/pubmed/21281798
Old Mike


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## kiny

there are the ones I found by doing a simple search






.
.
.
.


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## mf15

Here is a simplified explanation of what is going on with the amino acid dosing.
Old Mike
http://www.steinorthopedic.com/pdf/aminoacidtherapy.pdf


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## mf15

I would think that this article would support the concept that gut hormones are important in

the pathogenesis of IBD.

Old Mike

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940144/


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## nogutsnoglory

I am a little skeptical because while I do believe the gut is our "second brain" there are many CD and UC patients on SSRI's, myself included! 

I have been on Prozac before even being diagnosed with crohns. Granted I'm not on any dopamine meds but Prozac has in no way helped my disease symptoms. It does help with anxiety which probably does make it easier to live with a very depressing and anxiety provoking chronic illness though.


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## Igor_Passau

Hi,
I want to try it  (L-tyrosine and 5-HTP +  1000 mg of vitamin C, 220 mg of calcium citrate, 75 mg of vitamin B6, 400 μg of folate, 4500 mg L-cysteine, and 400 μg of selenium)

it was intravenous injection?
What kind of firm produce it L-tyrosine and 5-HTP with high quality?
Regards
Igor


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## mf15

IGOR: As far as I can tell this is an oral approach.
These supplements are easy to get in the USA.
Look on amazon.
Please be aware if something goes wrong,bad results.
Here is the worst case, I would think of the approach,if it somehow got out of control. I am not sure if you really need all the cofactors?
Old Mike

Death:

http://en.wikipedia.org/wiki/Serotonin_syndrome

http://en.wikipedia.org/wiki/Serotonin

You may want to read my thread on healingwell,few more studies.
http://www.healingwell.com/community/default.aspx?f=38&m=2621363


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## David

Be careful about supplementing 75mg of vitamin B6.  Too much B6 can lead to a whole host of problems including peripheral neuropathy and 75mg is a high supplemental dose and nearing the tolerable upper intake.  If you're getting a lot of B6 from diet as well, then problems could arise.  If you're not, then it should be ok but I don't think I'd do it long term. Read this for more information.

My biggest suggestion, if you are going to do this, is to do it under the supervision of a good physician.  Let them monitor you and offer guidance.  For example, they could routinely test your B6 levels to make sure you don't get too much.


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## mf15

There was a UK study on food intake prior to UC,B6 popped up,don't know if it was an artifact or not.  B6 drives the tryptophan pathway towards making niacin.
Old Mike


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## superzeeman

David, where o where can we find GI's that will try more novel approaches other than the normal Humira, Remicade, Prednisone etc? I am in remission thanks to surgery but I know that someday that will not be the case and would LOVE to find someone that would take a proactive approach in a novel way.


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## David

I wish I knew the answer to that.  Unfortunately, I do not.  I think connecting with others in this community with GIs who have been willing to try more novel approaches is obviously one way, but others here may have better suggestions.


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## nogutsnoglory

superzeeman said:


> David, where o where can we find GI's that will try more novel approaches other than the normal Humira, Remicade, Prednisone etc? I am in remission thanks to surgery but I know that someday that will not be the case and would LOVE to find someone that would take a proactive approach in a novel way.


I know you asked David but I figured I'd pitch in. You could work with a facility doing IBD clinical trials or a naturopathic doctor for a more natural route.


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## superzeeman

I live so far away from anywhere that would put on a clinical trial for anything but that is a good idea. I live 1.5 hours from a Mayo Clinic and I am sure that they do stuff but getting off work for a day to get gets fianancially prohibitive.


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## nogutsnoglory

Have you searched on clinicaltrials.gov? They aren't all major facilities, sometimes small doctors offices carry research.


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## superzeeman

I will check that out. Maybe I will get lucky and find something,. Thanks!


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## sammies

I am working with a naturopath who has suggested this treatment. In the next three weeks, I plan to check in with my kidney and liver docs and my GI.  Hoping they all give it a GO.  Anyone hear of this treatment with Ostomy folks? I am without my entire colon, rectum, anus.  We are looking into this but any advice would be appreciated.

Must get back to reading all these studies!


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## David

That's awesome sammies!  Please keep us updated as to your progress.


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## xmdmom

When I read the abstract, a couple of authors' names  (Marty Hinz and Al Stein) rang a bell.  They have promoted amino acid supplements for ADHD and other "mental/emotional" issues. "Dr Marty Hinz is President of Clinical Research, Neuro-Research Clinics, Inc."  The FDA has filed an injunction against Hinz's company because it made unsubstantiated claims about its nutritional supplements. http://www.startribune.com/business/129808958.html?refer=y  It had received warning letters before.

I'm not questioning the case report, but do believe there may be something shady about the authors' business practices.


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## kiny

he owns patents too registered under some lab under his name

we should peer review this section before anyone posts in it, I have posted things in the past that I didn't think I should have posted because there were too many conflicts of interest, although I always try to look over the conflicts of interest and look up who they are, which studies they have posted, how long the review time was between acceptance and publication etc

the latest study I posted I already sort of regret posting, because I know chamberlin and others in that study have some bias, but on the other side of the spectrum Van Kruiningen has bias too, would be nice if we peer-reviewed the section and the study goes up for review and a few people are allowed to vote on it before it goes live


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## sammies

I started the protocol 2 days ago.  I'm taking NeuroReplete (5 HTP plus vit C, vit B, folate,calcium, l-lystine, l-tryrosine) and CysReplete (l-cysteine plus folate, selenium). Had just been to a conference on food and the brain, optimal nutrition for the brain.  lots of buzz pn the dopamine-seratonin relationship.

Here's hoping!


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## David

Best of luck sammies!  Please keep us updated either way.


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## sammies

In my fourth week of the protocol.  Just added D5 Mucuna twice a day.  Felt really good the first two weeks and not as great the last week but it was a very stressful work week.  Developed skin rash two weeks ago.  Looks like Humira rash folks describe.  I've been on Humira a year but had yet to see a rash.  Also had very bad edema for several days.  Naturopath doc reminded me that once started on the protocol, patients often see more side effects front their regular meds.  Not sure why.  Still I will ask kidney doc for blood test.  See GI next Wed.  He is still talking surgery.  I want to give this protocol at least 8 weeks. I also want to try remicade, cimzia, tysarbi, and a whole host of things before I consider losing more intestine (I have a permanent ileostomy.  I
Had total proctocolectomy in 2009.)

Anybody else on this protocol? I read through the thread on the UC page but this is the only other thread I can find.  Would love to hear some anecdotes.


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## mf15

Go here for another person doing it,he is doing well.
I usually hang out on the healingwell UC forum,but also post here.
Old Mike
http://www.healingwell.com/community/default.aspx?f=38&m=2689559


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## sammies

THANKS OldMike! I went right away and joined the conversation there as well.  S


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## mf15

Here are a few more thoughts on IBD and neurotransmitters.
Old Mike
While reading through my old thread and looking for the reasons for neurotransmitter imbalances,one of my statements is.


What I think I know on diet is this.

First you cannot make serotonin without trypotphan,and possibly melatonin not sure on that.

If you eat a lot of protein you get tyrptophan,but will not be absorbed well,because it competes with the other amino acids.

But if you eat carbs at the same time then you get an insulin spike,then you get an increased ratio of tryptophan to other aminos and then it can be absorbed into the brain at least.

So to lower tryptophan my guess is not to combine carbs with protein.

But in UC there may also be someting wrong with SERT in the gut,possibly due to inflammation.



So food combining the way many normally eat may be causing the problem in the first place, that nice steak sandwich my son used to eat 10 oz or so of beef on a 12 inch roll,pre UC.

The great old american standard meat and potatoes,how about beef stew,the great american sandwichs of all types. Pizza,thankgiving dinner,turkey,bread filling,mashed potatoes,then through in some bread,pie.

Bacon and eggs might be fine,but then you add toast and home fry's.

Or how about a McDonalds breakfast sandwich.

Seems the american/western diet pushes for an unusually high tryptophan absorption,combine this with

some high serotonin foods such as bananas,walnuts others.

What if????

Oh my.



Also butyrate in the colon down regulates SERT,somewhat of a paradox since butyrate is a food for colon cells.



This perhaps a reason SCD and Paleo works on some people,high protein low carb=less tryptophan being absorbed,but you are still eating some carbs and probably both at the same time,which leads to tryptophan being absorbed. Perhaps these diets would work much better if you eat protein and carbs at different times.

Will look more into food combining and neurotransmitters,hopefully will find real science as opposed to junk.

Looks like I have a thread on this in the past,might have to start trying this.

http://www.healingwell.com/community/default.aspx?f=38&m=2632924


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## Volcano

Just started to enter the hormone and neurotransmitter side of Crohn's and it's increasingly looking like dopamine addiction is at the root.


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## JMC

This is why I posted this, I think the brain, bowel, immune system connection is still being established: http://www.crohnsforum.com/showpost.php?p=869491&postcount=1


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## David

Volcano said:


> Just started to enter the hormone and neurotransmitter side of Crohn's and it's increasingly looking like dopamine addiction is at the root.


Do you mean you're being treated for this or you're researching it?


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## MarkC

@David or whomever else.

I went through this treatment with both these doctors. It was an interesting experience.  I have Crohn's-Colitis. 

I have had Crohn's-colits for approximately 12 years now.  I have a very severe and more so aggressive case.   Flare's can hit and I can be up to 30+ times a day in the washroom with blood and mucus within a week of onset. It hit's me that fast.  Severe pain as well.   Pred & antibiotics always took me out of a flare.  Remicade worked to a high degree and I actually landed in "clinical remission" but with IBS symptoms remaining.  However I built up antibodies to it and had to stop after two years.  Methotrexate helped a little, Imuran seemed to not have much effect or maybe on par with Methotrexate.  And the list goes on..   So I basically spent a solid 12 years in and out of intense flares.  

So I went down this treatment path as I was heading towards surgery.  

Upon starting this treatment I was sort of up and down for a while and experienced some initial improvements. It's very hard to describe in a lot of ways.  I slept forever though... that's for sure.  Extreme tiredness was a side effect that eventually wore off over time.   There was a specific point that there was definitive "click" upon a dosage adjustment.  I remember this day very clearly.  All of a sudden there was a dramatic relief in my gut... Certain food tolerances also improved.  That being said, I made some more dosage adjustments and my mucus production got out of control.  Eventually I reached a point where I had to call it quits.  It was to much.  I was simply passing pure mucus and in extreme pain by the end. I could not wait out another dosage adjustment at this point. 

I spoke with the doctors and informed them.  I said to myself if I didn't get better somehow I may return to it in the future but I needed meds to get control of the situation, and fast. 

I went to the meds (Pred and Imuran) and then went a slightly different path - somewhat alternative again and sure as $hit I landed in essentially complete remission.  I have been this way for almost two years now.  Crazy.  

Anyway - I have never been able to find someone that can confirm the treatment works...  So find someone in full remission from it.  I would suggest maybe trying to find someone that has seen success before diving in.  It's expensive.   

----------- 

I will point out one thing though:

The premise of this treatment and theory is that there is a defect in OCTN1 and 2 and this in turn effects the re-uptake of seratonin and dompaine at nerve endings in the gut... this in turn induces an imbalance and certain specific amino acids at specific dosages can influence/address this balance.   Specifically the idea that dopamine levels are low - or the real problem is on the dopamine side in those with IBD so the treatment revolves around balancing the dopamine side of things. 

Keeping that in mind - if one is able to accept there is a possibility that MAP (Mycobacterium Avium Subspecies Paratuberculosis) can play a role in Crohn's one way or another - then then you soon realize that MAP effects the nerve endings in the same area where this theory suggests - and more than likely leads to the same imbalances presented through swelling and damage. 

Somethign just to keep in mind...   

To get a little further into it in regards to SERT expression and 5HT etc in relation to both IBD/IBS and MAP perhaps start here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168579/?tool=pubmed

I would be more tempted to suggest someone first be tested for MAP and perhaps try to treat if positive versus trying to approach it from the amino acid therapy side of things.

Hope this helps...

EDIT:  In relation to all this there is a paper that I have always found intriguing that may be of interest:  It is called Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense http://www.ncbi.nlm.nih.gov/pubmed/23303993


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## InstantCoffee

I've been reading a lot into the serotonin / dopamine effects on Crohn's as well as related treatments, and it's interesting to find someone mention the OCTN1 & 2.

Last week I began an intermittent fasting diet. Fasting has an effect on your body's hormonal balance, largely the serotonin production in the gut as well as release of catecholamines which contain dopamine.  

The results on the first week of the diet were great, I began to gain weight and feel a lot better with minimal other variables to account for. 

Since trying to incorporate breakfast / lunch back into the mix hoping that the other supplements I started at the same time as the fast, results have not been so good. 

I've been looking at ways to effect serotonin / dopamine more directly.

There was a story posted on here of a guy that juice fasted for over a month and believes it put his Crohn's into remission. It's also possible this could have worked in any number of ways including bowel rest and starving out antagonistic bacteria.


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## Crusty007

Hi there..gonna try this out.

Instantcoffee, I've done 2 fast (one 10, one 15 days) in the past 18 months. Do you have some links on the connection between fasting and hormonal rebalancing? 
TIA
Crusty


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## InstantCoffee

Crusty007 said:


> Hi there..gonna try this out.
> 
> Instantcoffee, I've done 2 fast (one 10, one 15 days) in the past 18 months. Do you have some links on the connection between fasting and hormonal rebalancing?
> TIA
> Crusty


Check out post #5 in my log, I link to this study

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696514/

Keep in mind all things I discuss are theories that I have built on or changed over time. 

I no longer advocate the long term use of fasting in Crohn's maintenance due to its altered effect on gut bacteria. I believe it can cause healing, but a better long term plan to balance neurotransmitters without sacrificing your diet would be to find a supplemental method.


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