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A Little Poisoning Along the Road to ME/CFS
Looking at my symptoms, many of which are far less these days and some are gone, it would be easy to figure that I'd just been dealing with some heavy-duty menopausal issues.
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depression, mthfr and gut dysbiosis

Discussion in 'General Symptoms' started by Kimsie, Sep 6, 2013.

  1. Kimsie

    Kimsie Senior Member

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    Hi everyone!

    I am not and ME/CFS person, but I have found so much help on this site for other problems that I just have to post to say thank you and tell a little bit of what I have discovered because of our own problems that might help some of you on this site, too. I think my 17 year old son might have ended up with CFS, but I have reason to believe that we are succeeding in nipping it in the bud (after 2 years). One problem he had was fatigue due to the MTHFR 677 gene mutation, but methylfolate has taken care of that now. He still has problems from gut dysbiosis that we are working on.

    This is about some causes of depression and/or anxiety type symptoms that may have relevance for some people with CFS. I know that you people here are wise to things like BH4 and gene mutations, but I wrote it originally for another site, so some of it will seem elementary. I imagine that excess histamine from gut dysbiosis could contribute to some of the other symptoms that people on this forum have, also, besides causing depression and anxiety.


    Depression can be caused by a variety of factors, so my comments here will not apply to everyone who is depressed, but I want to share them because they should be helpful for some people. These comments and theories are based on my experience with my husband and my son with a lot of research that I did on the internet. These comments will be much more likely to apply to a person who has trouble remembering their dreams (unless they take melatonin for sleep) than a person who usually remembers their dreams.

    Warning: You should not take 5-htp if you are on drugs for depression because it can lead to serotonin syndrome. If you believe that you are depressed due to dysbiosis and high histamine then you need to work with your doctor on this.

    My husband has suffered from mild depression for nearly his whole life. We have learned in the past year that he has one copy of the MTHFR A1298C gene mutation, which lowers his ability to maintain levels of BH4, or Tetrahydrobiopterin, which is a co-factor in the conversion of tryptophan to 5-htp. 5-htp is what your body uses to make serotonin, so if your levels of 5-htp are low, your serotonin levels will be low, too. Persons with two copies of this mutation will presumably have a deeper depression. BH4 is also needed for other purposes in the body such as for dopamine and getting rid of ammonia from the breakdown of protein, so people who have this mutation may be able to improve other problems in addition to low serotonin by taking 5-htp and freeing up more of their scanty supply of BH4 for other purposes. They should probably not be on high protein diets if at all possible, too.

    In this case long term 5-htp supplementation is the logical solution, since the gene mutation can't be changed and 5-htp should only be needed at low doses. 5-htp is well absorbed sublingually, and from our experience I believe that less is needed and more gets to the brain when you take it sublingually. We cut open a capsule and pour out the amount we want onto a plate or even straight in the mouth. If you swallow a capsule it seems that more of the serotonin gets produced in the gut leading to increased motility of the gut and diarrhea. If you are constipated this might be a good thing. You might need to take a little P5P (B6) which is a co-factor in the 5-htp to serotonin pathway. You should notice a difference within 15 minutes after taking it sublingually, assuming that you have enough B6 and that you have taken enough 5-htp for your needs. With one copy of the mutation 25 mg or less will probably be enough unless there are complicating factors. If you take too much, you will get sleepy as a side effect, and maybe have loose stools. Many people take it at night because of the sleepiness side effect.

    The MTHFR A1298C gene mutation is very common. This type of depression is not associated with anxiety; one possible cause of depression with anxiety or panic attacks will be addressed below.

    My son has experienced a cause of depression that I believe is also very common. Over two years ago he had several rounds of antibiotics leading to a gut dysbiosis and now he has bacteria in his gut that produce more histamine than his body can neutralize. I don't actually know if the gut dysbiosis has caused him to not be able to produce as much DAO as he used to produce or if his new gut flora is producing more histamine than the old flora did. I am not going to go into how I know this or how I tracked this down because it would take too long so you will have to take my word for it that his depression is caused by histamine caused by organisms in his gut. If the body does not have enough DAO to get rid of the histamine, it has to find other routes to get rid of it. It produces adrenaline to get rid of the histamine, so this leads to anxiety type symptoms. In my son this only produced a feeling of uneasiness, but in some people this leads to symptoms such as panic attacks, anxiety and difficulty sleeping. When the serotonin problem is bypassed by taking 5-htp this adrenaline, which the body is still making adrenaline to get rid of the histamine, makes the person feel excited and “high”, and the person can have trouble sleeping in this case, too, from the adrenaline.

    However, in this case the 5-htp does not address the underlying problem, and it can be difficult to find a balance depending on how much excess histamine they have unless you at least mitigate the underlying problem. But before I get to that I will explain my current theory on how high histamine levels cause depression. Also, some people with high histamine problems do not have depression, and I believe that it is because their particular set of genes and gene mutations allows them to bypass the problem with 5-htp production.

    The purpose of histamine in the body is to produce inflammation in order to lead to healing. When histamine is introduced into the body from an outside source, such as from intestinal bacteria in this case, the inflammation is not helpful. Inflammation leads to the production of the highly reactive hydroxyl radical (OH.) 1,2, a very damaging substance which your body must get rid of. We had long noticed that vitamin C to bowel tolerance helps our son tremendously. It turns out that not only does vitamin C degrade histamine in the body, it also is a hydroxyl radical scavenger to help get rid of the damage. However, the body has another hydroxyl scavenger seven times as effective as vitamin C. Can you guess what it is? 5-htp!3 So if a person has very high histamine levels creating hydroxyl radicals and no other pathway sufficient to remove the hydroxyl radicals they will have to use 5-htp to deal with the hydroxyl radicals leading to lower serotonin and depression. This type of depression can be extremely severe. I have seen my son go from nearly a catatonic state, lying on his bed staring at the ceiling, to being able to get up and do things 45 minutes after a 15 gram dose of vitamin C. However, when the condition is extreme like this he can't feel very good just with vitamin C alone; he can reach a functional level, but not a happy level. The addition of 5-htp brings him to a much higher level and feeling good, but when he has a lot of histamine being produced it takes very high levels of 5-htp and it's hard to get enough to the brain without causing diarrhea from high levels of gut serotonin. Taking the 5-htp sublingually helps to some degree to avoid diarrhea. Also, if the histamine is not dealt with he still has high levels of adrenaline causing symptoms as the body is trying to get rid of that histamine, but at least he feels good emotionally.

    The answer is to get the histamine production in the gut in line with the ability of the body to produce DAO to get rid of it.

    In our experience the organisms producing the histamine thrive on complex carbohydrates. Multiple times we have brought the levels down with the GAPS diet (which does not allow complex carbs) only to find that the symptoms returned when we tried to reintroduce starches, even when he was taking oil of oregano to combat the organisms. We have also learned that if he fasts, he feels great emotionally, and although eating fruit or vegetables doesn't make him feel worse. he feels worse within a couple of hours after eating high protein foods which give the organisms histidine, the amino acid used to produce histamine. Fasting for 24 hours might be a good way to figure out if gut produced histamine is causing your symptoms. Just don't eat from the time you get up and if you feel pretty good at dinner time other than feeling hungry, there is a pretty good chance this is your underlying problem. Then eat some protein for dinner and see how you feel 2 or 3 hours later. Some people might only have the bacteria in their colon and not small intestines so they might not react as quickly as my son does.

    We have found that there is a little bit of a conflict eating the high protein GAPS diet, but in the long run GAPS reduces the offending organisms to the point where he can be symptoms free, except that if he eats sauerkraut it causes symptoms because of the histamine in it, so we are doing GAPS without kraut. There may be other ways of lowering the population of histamine producing organisms to the point where the symptoms may be easily controlled, but I haven't figured out what those ways are. These organisms release high levels of histamine while they die, so taking oil of oregano or probiotics with soil bacteria such as bacillus subtilus increases symptoms greatly, but you can use vitamin C and 5h-htp to mitigate the symptoms.

    Large doses of vitamin C can chelate copper which is needed to produce DAO so you should take 2 mg of copper a day if you are taking a lot of C unless you know for certain that you have enough copper. There are many multivitamins that have 2 mg of copper.

    Also, you should not take 5-htp if you are on drugs for depression because it can lead to serotonin syndrome. If you believe that you are depressed due to dysbiosis and high histamine then you need to work with your doctor on this.
    1. Histamine as a marker for hydroxyl radicals (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365656/)

    1. The iron-binding and hydroxyl radical scavenging action of anti-inflammatory drugs (http://informahealthcare.com/doi/abs/10.3109/00498258809041682?journalCode=xen)

    3. 5-hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C (http://www.ncbi.nlm.nih.gov/pubmed/15617538)
     
    Sherlock and Gondwanaland like this.
  2. AbbyDear

    AbbyDear

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    Thanks for the info. I am curious, do antihistamine, or sudafed, or Histame (DAO) help at all ?
     
  3. Kimsie

    Kimsie Senior Member

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    We haven't tried any antihistamines because we don't like to use drugs. However, I doubt that they would work if my theory is correct because antihistamines work by blocking the receptors, not by getting rid of histamine. Vitamin C gets rid of histamine and that works in very large doses but since the histamine is constantly produced and vitamin C has a very short half life, it's hard to keep taking enough to keep the symptoms away. My theory is that histamine causes depression by causing an increase in the hydroxyl radicals and the 5-htp gets diverted to get rid of the hydroxyl radicals instead of making serotonin so if that is correct blocking the receptors would not help free up the 5-htp for serotonin production.

    We tried some DAO but I think the dose is way too low even taking 5 or 6 of them. I mean way too low when there are a lot of bacteria producing histamine in the gut, I have heard that it helps for people when they eat foods with histamine.
     
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  4. Gondwanaland

    Gondwanaland Senior Member

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  5. Kimsie

    Kimsie Senior Member

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    You must be referring to other posts of mine, I don't think I mention my son with schizophrenia in this thread!

    I read Pfeiffer's ideas many years ago when my son with schizophrenia first became ill, and we were seeing an orthomolecular doctor. I think these different groups all actually have the same underlying cause, except for the cerebral allergy group, but the differences such as the high or low histamine are caused by genetic variations, as are the schizophrenia symptoms themselves.

    I am having more success helping my son now, both sons, this thread is over a year old.

    The orthomolecular doctor we were seeing didn't have any success with him, even though he consulted Abram Hoffer, who is one of the founders in the same group as Pfeiffer. They are correct in saying that niacin and B6 is required, but they missed other things, so they only had success with some people and not with others, and no one has been able to design a study, not that very many have been done, that can show that these supplements can help schizophrenia.
     
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  6. Sherlock

    Sherlock tart cherry etc. for joints, insomnia

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    Czechosherlockia, USA
    I'm glad it popped up again, thanks. I wonder why I'd never heard of C reducing histamine levels before.

     
    Tunguska likes this.
  7. Sherlock

    Sherlock tart cherry etc. for joints, insomnia

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    Czechosherlockia, USA
    I'll mention that fasting also leads to increased dopamine, which makes a person feel on, so to speak, since it is meant to encourage food-seeking behavior instead of laying around. (Dopamine knock-out rats will starve to death with a bowl of food nearby.)

    @Kimsie there is a Mast Cell forum which would deal with endogenous histamine: http://forums.phoenixrising.me/index.php?forums/mast-cell-disorders-mastocytosis.126/

    E.g. I am high histamine (likely from MTHFR 677) but have never detected any bad effects from ingested histamine. There is a Soviet/Canadian doc who treats high histamine with ingested histamine. (I'm sure Kimsie knows all of this.)
     
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  8. Sherlock

    Sherlock tart cherry etc. for joints, insomnia

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    @Kimsie I've never felt any benefit from C despite trying several times through the years. Any idea why not?

    I'll start another test today, with copper.
     

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