1636 replies to this topic

[ForLyla]

So Ive been thinking. I have SIBO. I have withdrawal syndrome. I've come to realize that mostly all of my symptoms are due to histamine intolerance from one or the other or both conditions. When I take a regular non-drowsy antihistamine, I usually feel great afterward for a couple days. Makes me wonder how many more are like me. These are exactly all my symptoms.

Symptoms of histamine intolerance:

Hypotension (drop in blood pressure)

Tachycardia (increased pulse rate, “heart racing”)

Symptoms resembling an anxiety or panic attack

Chest pain

Nasal congestion and runny nose

Conjunctivitis (irritated, watery, reddened eyes)

Some types of headaches that differ from those of migraine

Fatigue, confusion, irritability

Digestive tract upset, especially heartburn, "indigestion", and reflux

[fishinghat]

 
lot of ways to treat that including DAO, vitamin b6 in low dose and antihistamines.

[ForLyla]

I know I said I'd never take supplements again but I started taking quercetin and dao digestive enzymes. I'll also keep taking the non drowsy anti histamines once or twice a week. I don't think there's any known interactions with any of those and duloxetine.

[fishinghat]

Not that I am aware of. If you start developing stomach issues it may be the dao digestive enzymes.

[ForLyla]

I'm obstaining from all supplements for now. Having a bad reaction. Will need to revisit sibo treatment when I heal. Hope this doesnt set me back long.

[invalidusername]

You'll be lucky to buy any the way the world is carrying on...!

[fishinghat]

Unluckily Lyla you are in a catch 22 situation. Until you get the sibo under control you probably will not progress. If you take something to control the sibo then you will undoubtedly have a set back due to the toxic effects of the dead bacteria.

[ForLyla]

FH I dont think that my cymbalta withdrawal and sibo are all that related. I was feeling pretty good for about a week in February before I took lansoprazole. I've also probably had sibo for 15 years, just that it's gotten worse with my flare up from the flu.

I imagine I'm feeling bad right now because of histamine flare up from probiotics. Also, garlic and enzymes etc likely have an effect on serotonin and absorption of cymbalta. I imagine in a couple months I should be feeling back to normal wd wise. In a way this is a blessing as I now know why I've had acid reflux all these years and problems with anxiety, fatigue etc. Likely all related to SIBO.

From your knowledge, does anyone get MS or other immunological diseases from withdrawal?

[fishinghat]

The sibo and the Cymbalta are only related in the fact that both are stressful so treating the sibo will cause gastric issues and that added stress will make the Cymbalta withdrawal worse.

"From your knowledge, does anyone get MS or other immunological diseases from withdrawal?"

The only thing I am aware of is a subjective opinion that Cymbalta can produce a set of symptoms similar to Parkinson's (but not fatal). There is a section on this in the ebook with medical references and comments.

[ForLyla]

I had some blood work done and my RBC, WBC and Hemoglobin all dropped quite a bit but are still at the low end of normal. Top this on top of my crazy symptoms right now and the villous atrophy and I'm pretty scared. I read that having a villous atrophy can cause lymphoma so that makes me wonder. 

[fishinghat]

That would take a far smarter person than me to know. Sounds like time for a specialist.

[ForLyla]

I feel like doctors are useless. It feels good to be supplement free again though. Hopefully it will only be another month or two before I feel ok again. I'd much rather feel better withdrawal wise and just live with the sibo.

[ForLyla]

Not sure why this happens sometimes but I'm in an odd phase of withdrawal where I feel functional for most of the morning and afternoon and the waves are hitting me later in the day around 5 or 6pm and last the rest of the night. Usually my windows and waves are the opposite where I feel like crap until 6 and better later in the evening. 

 

I don't know about you guys but people are coronavirus crazy here in Toronto. How are things where you are Gail?

[ForLyla]

Just to touch base on my last message. Wondering if I feel like crap later in the day because the cymbalta is working against me now. Could my doses be sending me into waves now?

[fishinghat]

One way to find out if it is the Cymbalta is to switch the time of day you take it by 12 hours.

 

By the way in most diseases the symptoms are worse in the evening because serotonin id decreasing and melatonin is increasing. When this is flipped it is often, but not always, due to the time certain medication or specific food is eaten.

[ForLyla]

The more I read about it, I wonder if histamine intolerance is the reason why SNRI withdrawal is so terrible. Cymbalta is known to block DAO. FH are there any known interactions of DAO with Cymbalta? It breaks down histamine in your intestine so I'm assuming it works in the same way as taking an h2 blocker like Zantac? I'm trying to reduce my gut histamine levels as much as possible.

[fishinghat]

This is a different situation as a H2 blocker. The H2 blocker works on the histanmine receptors but D-amino acid oxidase is a histamine scanvenger. This means it chemically reacts with the free histamine in the body to destroy/change it. It does not react with the histamine receptor that I know of.

 

I could find no studies on the interaction of Cymbalta and D-amino acid oxidase for what ever that is worth,

 

D-amino acid oxidase effects nearly all amino acids and systems in the body.

 

FDA has not approved this compound for medicinal use except in research/studies.

 

D-amino acid oxidase is an enzyme and as such is probably not removed by the liver but reused until it naturally degrades.

Therapeutic treatments
D-amino acid oxidase is used in therapeutic treatments such as regulation of hormones, regulation of hypertension, treatment of schizophrenia, treatment of psychiatric and cognitive disorders, and possible pain reduction. Changing the amount of D-amino acid oxidase transporters with the use of drugs has therapeutic effects on schizophrenia. D-amino acid oxidase regulates D-Aspartate, which regulates the secretion of melatonin, prolactin, testosterone, luteinizing hormone and growth hormone. By regulating D-amino acid oxidase, D-Aspartate can also be regulated and control hormone secretion. Increased D-amino acid oxidase activity has been correlated with psychiatric and cognitive disorders, so reducing D-amino acid oxidase can have therapeutic effects on these disorders. D-amino acid oxidase helps produce L-6-hydroxynorleucine, which then generates Omapatrilat. Omapatrilat inhibits angiotensin-converting enzyme and neutral endopeptidase and effectively reduces hypertension. D-amino acid oxidase also may have an effect on pain stimuli, but it is not confirmed yet.
Wiki

FYI

https://www.ncbi.nlm.nih.gov/gene/1610
Histamine and Histamine Intolerance
Abstract
Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.

[ForLyla]

Here's what I found. Diamine oxidase (DAO) is a digestive enzyme produced in your kidneys, thymus, and the intestinal lining of your digestive tract. Its primary function is to break down excess histamine in your body. Not sure if this concerns me or not as antacids also have the same effect and work to breakdown histmaine in the gut. FH isn't it reasonable to assume that because Cymbalta inhibits DAO that perhaps it inhibits it in order for it (cymbalta) to absorb properly? 

 

Anyhow, I took my first DAO pill today. Feeling very sleepy. Maybe a little shaky but that could just be my head. Acid seems to be better but haven't given it enough time. 

[fishinghat]

You know when I went to school (back before God made dirt) abbreviations were not allowed. Technical terms had to be spelled out. Now I understand the dilemma. Originally you mentioned DAO which represents D-amino acid oxidase (as does DAAO) BUT now I find that it also can represent Diamine oxidase which is what you mentioned and it is not the same compound as D-amino acid oxidase. So I need to start from scratch in the morning. Sorry for the confusion.

[ForLyla]

Haha sorry Hat. Yes diamine oxidase. Feeling super tired and out of it after taking it. However my acid reflux is great! I'm hoping this is something I can keep taking but I'm nervous! It's so hard to find any information on this enzyme.

[fishinghat]

I will dig into it later in the morning. Tied up right now. Sorry

[ForLyla]

Ok thanks HAT. Your research is appreciated as always.

I dont know about the validity of this publication but I found this on garlic. https://www.ncbi.nlm...les/PMC2792615/

[fishinghat]

I did not find a lot of info. The last article is a good read that you might find interesting.

https://pubmed.ncbi....dase&from_pos=2
The amine oxidase DAO, formerly called histaminase, is found in various tissues, but is especially active in the intestinal mucosa. Its function is the oxidative deaminating of several polyamines, essential substances for cell proliferation.
DAO is normally present in very small amounts in the circulation.

https://pubmed.ncbi....ge=2&from_pos=1
Daily Variations of Serum Diamine Oxidase and the Influence of H1 and H2 Blockers: A Critical Approach to Routine Diamine Oxidase Assessment
Serum diamine oxidase levels showed no significant daily variations and no significant sex differences. Antihistamines had no influence on diamine oxidase activity except for cimetidine, which caused 25% inhibition at the highest dose tested , dihydralazine 68% inhibition and diphenhydramine, which caused 19% increase of enzyme activity.

https://academic.oup.../5/1185/4633007
INTRODUCTION
Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. The main enzyme for metabolism of ingested histamine is diamine oxidase (DAO) (1–5). An impaired histamine degradation based on a reduced DAO activity and the resulting excess of histamine may cause numerous symptoms mimicking an allergic reaction. Ingestion of histamine-rich food (6), alcohol (7–9), or drugs (10–13) that release histamine or block DAO may provoke diarrhea, headache (14), congestion of the nose, asthmatoid wheezing (6, 8, 15), hypotension, arrhythmia, urticaria (16, 17), pruritus, flushing, and other conditions in these patients. Approximately 1% of the population has histamine intolerance, and 80% of those patients are middle-aged (18). Because of the multifaceted symptoms, the existence of histamine intolerance is frequently underestimated, or its symptoms are misinterpreted. Clinical symptoms and their provocation by certain foods and beverages appear similar in different diseases, such as food allergy and intolerance of sulfites, histamine, or other biogenic amines (eg, tyramine). Therefore, the differentiation of the causal agent in adverse reactions to food, alcohol, and drugs is a difficult challenge. There is poor evidence of adverse reactions to these agents based on double-blind, placebo-controlled (DBPC) provocations (19). However, a better understanding of the pathophysiology, clinical picture, trigger factors, and diagnostic tools may help to clarify the confusing debate surrounding histamine intolerance.




 

[ForLyla]

Thanks FH. I've decided I need to get rid of my sibo once and for all. I'm going to try the antibiotics (rifaximin) with garlic (allicin) as well. Your research showed Rifaximin to be safe with duloxetine. I cant imagine how an antibiotic would work on the same receptors as duloxetine but who knows.

Here we go again. Wish me luck!

[fishinghat]

I think that is a good idea. By the way garlic tablets upset some peoples stomachs. You may have some digestive issues as the bad bacteria die but that will fade as the issue resolves. I think in the long run you will be netter off.

[ForLyla]

FH I hope so unless it doesnt work. I really hope it doesnt affect the absorption.

[fishinghat]

Prayers for you Lyla.

[ForLyla]

Captains log... day whatever. So although it's much too early to tell, my initial reaction to garlic and Rifaxmin hasn't been too bad. I actually feel pretty good today. I know this doesnt mean much as it will take a good week to see if this negatively affects me but it is at least somewhat encouraging that I dont feel miserable right out of the gate. Oddly enough, my skin hasn't been super dry or flaky since I started this. Not sure if that's a good sign but I guess I'll take it.

[ForLyla]

Not having a good day today at all. Feeling very nauseous, brain fog, terrible vision issues, and just general ill feeling. Usually I love the sun but it feels way too bright for me to stand it. Not sure if this is from die off of SIBO or due to an interaction of what I'm taking with the duloxetine. 

 

FH did you see my link a couple posts ago regarding garlic? Do you have any take on whether it would be bad with the duloxetine? 

[fishinghat]

Lyla
I couldn't find any link to Cymbalta. Garlic is broken down by digestive enzymes and Cymbalta by CYP enzymes,. Totally different. I woiuld expect most of those symptoms with the bacteria die off except for the vision issues. The sensitivity to light comes with many antibiotics.

What kind of vision problems you having?

Well well well, look what I finally found...

What all this means is that rifaximin interacts with the same CYP enzymes as Cymbalta.

 

https://dailymed.nlm...81-cc259c0be2f1
7.3 CYP3A4 Substrates
An in vitro study has suggested that rifaximin induces CYP3A4 [see Clinical Pharmacology (12.3)]. However, in patients with normal liver function, XIFAXAN at the recommended dosing regimen is not expected to induce CYP3A4. It is unknown whether rifaximin can have a significant effect on the pharmacokinetics of concomitant CYP3A4 substrates in patients with reduced liver function who have elevated rifaximin concentrations.

Metabolism
In an in vitro study rifaximin was metabolized mainly by CYP3A4. Rifaximin accounted for 18% of radioactivity in plasma suggesting that the absorbed rifaximin undergoes extensive metabolism.

In in vitro drug interaction studies the IC50 values for rifaximin was >50 micromolar (~60 mcg) for CYP isoforms 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, and 2E1. In vitro IC50 value of rifaximin for CYP3A4 was 25 micromolar. Based on in vitro studies, clinically significant drug interaction via inhibition of 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 by rifaximin is not expected.

https://www.drugs.co...h/cymbalta.html
Clinically Important Drug Interactions
Because both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism, potential exists for clinically important drug interactions when duloxetine is concurrently administered with CYP1A2 inhibitors, CYP2D6 inhibitors, and CYP2D6 substrates.