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List of Biochemical Causes for Irritability

Discussion in 'Cognition' started by Hip, Apr 17, 2011.

  1. Hip

    Hip Senior Member

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    Irritability (a low threshold for annoyance) is a common symptom in many ME/CFS patients. I have been collecting information on possible biochemical causes of irritability.

    Here is my list of biochemical causes for irritability as it stands so far:

    Acidosis.
    Systemic acidosis is when the body is too acidic.
    Possible treatment: an alkalizing diet; a quarter teaspoon of sodium bicarbonate daily, taken away from meals.

    Lactate build-up in muscles.
    Possible treatment: as above: an alkalizing diet; a quarter teaspoon of sodium bicarbonate daily, taken away from meals.

    High TNF-alpha
    Possible treatment: supplements that lower TNF-alpha include: cat's claw (potent), vinpocetine (potent), taurine (potent), evening primrose oil, ginger, chondroitin sulfate, magnesium, fish oil, and many others.

    High IL-10.
    Possible treatment: none found.

    Low serotonin due to the Interferon-induced breakdown of tryptophan.
    Low serotonin can cause depression or irritability. Tryptophan is needed to make serotonin. Tryptophan is broken down by the enzyme IDO (indoleamine-2-3-dioxygenase). Interferon stimulates the activity of the IDO enzyme, causing increased tryptophan breakdown. Hence interferon can cause depression or irritability. Since interferon gamma is generated when the immune system is in Th1 mode, the use of Th1 boosting supplements may also cause increased tryptophan breakdown, leading to depression or irritability.
    Possible treatment: Stop taking supplements that boost the Th1 mode, such as Astragalus, inosine, beta sitosterol, and transfer factor. Aspirin, propolis, resveratrol and lemon balm reduce tryptophan breakdown, so may increase serotonin and thus reduce irritability. Serotonin boosters like high dose inositol (15 grams daily) or saffron may help.

    Hyperthyroidism (overactive thyroid).
    Possible treatment: antithyroid medicines are used for mild hyperthyroidism.

    Low iodine.
    Iodine deficiency can cause irritability symptoms. Ref: 1.
    Possible treatment: kelp or some other iodine-containing supplement.

    High prolactin.
    Possible treatment: pantethine can reduce prolactin, as can chasteberry (agnus castus) herb, and zinc with vitamin B6.

    Low testosterone.
    In men, low testosterone may cause irritability. Ref: 1.
    Possible treatment: tribulus terrestris herb will boost testosterone production; nettle leaf herb will increase the amount of free testosterone (the active form of testosterone).

    High DHT (dihydrotestosterone).
    High DHT can also cause a loss of hair.
    Possible treatment: astaxanthin, saw palmetto extract or beta sitosterol will lower DHT.

    High cortisol.
    Possible treatment: phosphatidylserine works well to reduce cortisol levels. Holy basil herb (Ocimum tenuiflorum) also lowers cortisol. The anti-fungal ketoconazole is a potent reducer of cortisol, but doctors are prescribing this less now, due to liver damage side effects in rare cases.

    Low blood sugar.
    This typically occurs first thing in the morning
    Possible treatment: presumably a snack of slow burning carbs.

    High histamine
    High histamine levels can cause irritability.
    Possible treatment: antihistamine tablets.

    High follicle stimulating hormone (FSH) and high luteinizing hormone (LH) levels can cause irritability.
    Possible treatment: progesterone cream can lower the amount of FSH and LH hormones released.

    High sodium levels can cause irritability. High sodium may come from high levels of salt (sodium chloride) in the diet; or perhaps from high amounts of supplements like sodium ascorbate or sodium bicarbonate.
    Treatment: reduce sodium intake.

    Vitamin B2 (riboflavin) deficiency can cause irritability.
    Treatment: supplement with vitamin B2.

    Vitamin B6 deficiency can cause irritability.
    Treatment: supplement with vitamin B6.

    Vitamin B12 deficiency can cause irritability.
    Treatment: supplement with vitamin B12.

    Magnesium deficiency can cause irritability.
    Treatment: supplement with magnesium.



    One of the best treatments I have found for irritability is very low dose amisulpride (12.5 mg to 25 mg daily). Amisulpride in very low doses is used as an antidepressant. Other effective anti-irritability supplements I found were: vinpocetine 20 mg (must be taken with food), royal jelly 3000 mg, vitamin B2 100 mg, estriol 0.2 mg (estriol comes as a cream you can put on the skin).

    Severe irritability is a common symptom in autism, and the main treatment for this is atypical anti-psychotic drugs such as amisulpride, risperidone (Risperdal) or aripiprazole (Abilify).

    Some research has shown that N-acetyl-cysteine can help the irritability in autism, but this is not quite as effective as atypical anti-psychotics.
     
    Last edited: Dec 31, 2014
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  2. sensing progress

    sensing progress Senior Member

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    I often get irritable after eating anything with sugar in it, however I'm fairly certain its not from hypoglycemia. Any idea what other mechanism it could be? I believe I also have Leaky Gut Syndrome and that it may be related to this.
     
    oceiv likes this.
  3. Hip

    Hip Senior Member

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    Not sure. I'll have to think about it. Are you positive it is not some rebound hypoglycemia? You could test this easily by buying a low cost digital blood sugar level meter (you can get these amazingly cheaply), and testing your blood sugar say every 15 minutes after eating sugar, to see if there is some elevation and then rebound reduction in blood sugar level.

    The other thing I can think of is that the sugar is feeding some bad gut bacteria you may have, and causing an adverse reaction?
     
    oceiv likes this.
  4. sensing progress

    sensing progress Senior Member

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    Fairly sure. The reason I say that is I have a lot of experience with hypoglycemia and that irritability is like a crankiness but it can be controlled if I try hard. This other irritability I sometimes (but not nearly always) get when I eat certain sweet treats is a more profound irritability that feels different and more intense (hard to explain).

    That is a good idea and I think a distinct possibility. Any others have experience with this?
     
    oceiv likes this.
  5. merylg

    merylg Senior Member

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    Over-accumulation of Iron can cause irritability.

    Can occur from over supplementation with Iron and/or Vitamin C.
    Can be due to consumption of Iron fortified food.

    Can be due to Hereditary Hemochromatosis.
    http://www.haemochromatosis.org.au/symptoms.htm
     
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  6. SickOfSickness

    SickOfSickness Senior Member

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    I get irritable from hormonal stuff like birth control pills.

    I get irritable from benzos including benadryl which is similar to a benzo. And other CNS depressants.
     
  7. taniaaust1

    taniaaust1

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    You could have hyperinsulinemia (abnormally high insulin spikes/level). That can cause some to get very irritable (it can affect my moods if I eat carbs so badly that Ive actually smashed car windows.. I think Im extra sensitive to my own abnormally high insulin levels due to also having MCS?, so the combination of these two together appears to be quite bad for me).

    It is possible to have hyperinsulinemia without also having hypoglycemia and it would explain getting irritable after sugar (and possibly other forms of carbs too).

    Hyperinsulinemia is tested by 2 hr Glucose tolerance testing but with the insulin levels included. If you do have high insulin... it can also make other symptoms worst too eg I get less sore throats etc now that my doctors have got me on extremely low carb diet. Things like GERD, bloating if you have those, can also be caused solely by this issue.
     
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  8. taniaaust1

    taniaaust1

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    PMS tends to be worst in ME/CFS people. That of cause can cause a lot of irritability. (I think we are far more sensitive to all our homones).
    .....

    Food intollerence reactions can also cause irritability. (one sees that a lot in kids and I guess it probably causes some of us issues too).
     
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  9. alice111

    alice111 Senior Member

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    @Hip the first thing you mention is acidosis,how can you tell if this is the problem? also, does potassium bicarb work the same as sodium bicarb? thanks!
     
  10. SDSue

    SDSue Southeast

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    Glad this thread has been revived. Thanks for another well-researched, clearly written summary @Hip !
     
    oceiv likes this.
  11. Gingergrrl

    Gingergrrl Community Support Volunteer

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    Not sure if this has already been said (and I haven't read the entire thread yet) but I had irritability and agitation as part of an over-methylation reaction, dehydration/electrolyte imbalance, hypoglycemia, and as part of the delayed reaction to a horrible reaction to IV saline.
     
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  12. Hip

    Hip Senior Member

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    Not sure how acidosis is measured. You might consider trying a ¼ teaspoon of sodium or potassium bicarbonate each day (either is fine), and seeing if that improves you irritability symptoms. (Bicarbonate by the way seems to dramatically reduce post-exertional malaise: see this thread).

    I went through all these potential causes of irritability by trial and error, taking each of the treatments in turn to see if they would improve my irritability symptoms. The only treatments in my above list of that I found reduced irritability a bit was taking DHT inhibitors, and TNF-alpha inhibitors.

    DHT can cause male pattern baldness hair loss (androgenic alopecia), incidentally, so inhibiting DHT (and/or inhibiting the enzyme 5-alpha-reductase that makes DHT) can also help reduce this type of hair loss.

    My protocols were:

    Anti DHT & 5AR protocol:
    Astaxanthin 8 mg
    Saw palmetto 320 mg
    Biotin 2 mg
    Zinc 22 mg

    Anti TNF-alpha protocol:
    Cat's claw (15:1 extract) 200 mg
    Chondroitin sulfate 500 mg
    Vinpocetine 20 mg
    Ginger 1200 mg


    However, by far the best treatment for irritability I found was very low dose amisulpride (just 12.5 mg daily, which is very economical). I have taken this daily for several years now, and I still swear by it. It has other benefits too, like reducing sound sensitivity. If I stop taking it, within two days my grumpy irritability returns.
     
    Last edited: Dec 31, 2014
    oceiv likes this.
  13. alice111

    alice111 Senior Member

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    @Hip Thank you so much!
    How did you know that your DHT was high?

    Also, if possible could you explain how amisulpride works? I checked on wiki.. It's a little too much for my foggy brain.. Is it like an antidepressant? Or a benzo?
     
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  14. Hip

    Hip Senior Member

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    I didn't know, and still don't know, if my DHT is high, but I found that DHT lowering medications improved my irritability symptoms a bit. I did not do any testing, I just tried out all the above anti-irritability treatments to see which helped and which didn't.

    Amisulpride at very low doses acts as an antidepressant. At normal doses it acts as an anti-psychotic. The reason it acts differently at different dose levels is a little complex to explain, but basically at very low doses amisulpride activates the dopamine D2 and D3 receptors in the brain (via an autoreceptor mechanism), but at normal doses it does the opposite and blocks the dopamine D2 and D3 receptors.

    There may be some risks linked to amisulpride (see the thread), but these I hope will be minimized due to the very low doses used.
     
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  15. Gondwanaland

    Gondwanaland Senior Member

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    Question: why do mB12 and protease cause mood swings and extreme irritability?
     
  16. Gondwanaland

    Gondwanaland Senior Member

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    I had extreme low blood pressure from as little as 30mg potassium bicarbonate. @Sidereal reported the same reaction. OTOH I don't get this reaction from sodium bicarb.
     
  17. Hip

    Hip Senior Member

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    I am not really sure, but I have read that vitamin B12 can raise histamine, and high histamine can cause irritability.
     
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  18. alice111

    alice111 Senior Member

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  19. Hip

    Hip Senior Member

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    @alice111
    I cannot see any direct measure of DHT (dihydrotestosterone) in that report, but 5AR (5-α-reductase) is measured, and 5AR is the enzyme that converts testosterone into DHT, so 5AR levels might possibly give some indication of DHT levels, but I don't know for sure.
     
  20. alice111

    alice111 Senior Member

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    @Hip I am wondering if you wouldnt mind taking a look at my latest hormone tests?
    I don't really know what to make of it, and it seems like you are really knowledgeable on pathways and enzymes etc
    it would seem to me that something is messed up, and i have an overactivity or underactivity of some enzymes... although i cant make head or tails. what is particularly strange is that I am supplementing with progesterone but it seems to all be converting down the wrong path!
    here is where I posted my test results : http://forums.phoenixrising.me/inde...-help-me-interpret-results.35784/#post-566050
    ps totally understand if you dont have the time to look, and no worries , just thought id throw it out there!
    thanks so much for all your help with everything you have replied so far :)
     
    oceiv likes this.

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