Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by GenDylan, Jun 15, 2013.
Ah,see, The l-methionine is what raised my histamine. No chance I'm touching that again.
This could be a streeeetch, but I did read on an extremely comprehensive article about methylation that higher levels of SAMe inhibits the MTHFR enzyme and that high levels of 5mthf inhibits the conversion of SAMe into sarcosine (with glycine) via the GNMT enzyme. I believe this is supposed to operate as a sort of pendulum effect where the lower one's SAMe is then the the less MTHFR gets inhibited and the opposite when SAMe is high that 5mthf isn't overproduced so that SAMe doesn't build up. Taking methionine supplements MAYBE causes higher SAMe which then leads to a backup of the the 5mthf precursor due to MTHFR inhibition which in turn inhibits THF production and reconversion during Methyl transferase (THF, which is responsible for histidine breakdown) in effect causing higher levels of histadine and histamine. I will look for that article talking about the relationship between MTHFR and GNMT. I'll attach a pic of the GNMT enzyme I'm talking about. I have taken methionine and had no issues, but then again I have never had any histamine related issues in my life. My theory seems contradictory considering I originally read that SAMe is supposed to break down histamine but which effect would be great, MTHFR inhibition resulting in higher histamine vs SAMe methylation of histamine, I don't know.
Edit** I found the article, but it was one I printed out and I couldn't find an accessible one on google. Title is "One-carbon metabolism in psychitric illness". It says:
"The major regulators of methylation potential are glycine N-methyltransferase (GNMT) and MTHF reductase. GNMT binds 5-MTHF and high 5-MTHFR levels inhibits its activity. Conversely, high SAM concentrations inhibit MTHF reductase, reducing the concentration of 5-MTHF and releasing the inhibition of GNMT, which then reduces SAM levels. If SAM concentrations fall, MTHF reductase activity increases, producing more 5-MTHF which... inhibits GNMT preserving SAM for other essential transmethylation reactions."
Wow pgoody that's great info!!!!
So,if I'm not mistaken(which this brain fog may make me)I should supplement 5MTHF? !
If I'm mistaken,someone just please help me
I cannot give you an experienced perspective as I have only tried methionine for no longer than a week, and it also depends on your objective. The fact that you are supplementing with L-methionine tells me you are trying to increase methylation, I am guessing. Methyl folate can increase methylation, as long as there are enough precursors along the path to pass the methyl group onto homocysteine. Ben Lynch has a good video that goes through most of the pathway (the part you are concerned about at least) on his site: http://mthfr.net/
The part I am talking about begins around 33 minutes. Low activity of the MTHFR enzyme has a few causes I believe. 1) genetic alterations in the enzyme genes, 2) methyl trapping due to low b12 3) perhaps low b2?, 4) SAMe buildup? (my last post). Supplementing with 5mthf, methyl b-12, and TMG are all other ways to enhance methylation. I think some form of b12 is good to take before methyl-folate because it methylates and ensures you are not methyl trapping yourself. It would allow the flow of methyl from methyl folate (5mTHF) to produce homocysteine and allow the THF part of 5 mTHF to go on and break down histidine. At the same time taking 5mTHF might be good as well as it will provide the needed THF and methylation simulatenously (given enough b12 is present).
Wow, I great info. I know very little about methylation . I started supplementing L-methionine to lower my histamine levels, that's all! And it completely backfired on me. I knew nothing about methylation, only that - if you have high histamine, you're under methylated. And l-methionine lowers histamine. Welp, backfired. I didn't know that there are so many variables in methylation!!
After ur last post,I'm thinking of supplementing both mb12 and 5mtf,starting tomorrow. Do you think I'll get methyl trapped? Assuming my case is mtfhr inhibition causing low mtfh..
I would definitely recommend starting slow and titrating. Look around this forum for a clear protocol as opposed to just winging it. Taking straight supplements isn't always 100 percent safe. For example, a lot of people on here also take potassium along with methyl b12 since methyl b12 will deplete it, and potassium isn't something you want to be low on. Not to scare you, but you can die from low potassium if you don't know the signs and let it progress too far. Knowing the symptoms of low potassium would be a good thing to know and having some of it around might not be a bad idea. Maybe read some of the top posts in this forum, such as freddd and rich vank's protocols it should be discussed in there. Otherwise just do a search on the search bar for it. Some people are really sensitive with methyl groups and slow and steady definitely wins the race. Supplementing methyl groups isn't like popping halls vitamin C pills, or even supplemental vitamin c for that matter. Even too much vitamin c can be bad for you. I'm just saying, be more careful and have a more strategic approach to the methylation thing vs just going and buying some supplements and trying them.
Damn,I really don't know which supp to start fist - normally, methyl b12 should be started before 5mthf.BUT, assuming my 5mthfr is being inhibited, then supplementing with 5mthf should take care of the problem. SHOULD take care of the problem, but what if I have low b12 playing into this . I would then methyl trap myself by supplementing with 5mthf before mb12.
Going straight for the 5mthf is really tempting me, because my histamine is so unbearably high.
I think it's also very possible that I have low b12. I had my b12 tested while I was on a all protein diet, my b12 was a point away from the max. This could mean that I have a b12 absorption problem, and I'm low on the b12 that actually counts.
I'm so new to this methylation stuff. This is only my 2nd day of good learning,,, I just thought that was obvious . This is a disclaimer. Lol
GenDylan: Can't commet on whether B12 or Folate should be supped first, or at all. One way to know, I've read, if you have a serious B12 deficiency is by getting an MMA blood test. You could look into that. I am. But in the mean time I am also staying the heck away from all methyl-donors for the time being. I'm going to keep working on rebalancing my copper/zinc imbalance first. Also, after some histamine reading last night, I took some B6. It helped a lot. I finally got some decent sleep. Histamine issues seem to have their root in an issue with poor copper metabolism. Copper + Vitamin C + B6 (plus likely some others?) are co-factors in the DAO enzyme which degrades histamine. (I'd get your copper from normal diet unless you know you are low as copper toxicity/biounavailability is a real thing.) But maybe try B6?
Ya I've been thinking that I might have really low b6,because I how low zinc,which makes b6. I've been trying to get my DAO up by DRINKING olive oil, 'tis not pleasant. I've been hesitant to take b6 because I've heard it can raise histamine or assist methionine or something. But I think you're right, it's vital to DAO and I probly should be taking it. I'll probly buy some p5p today.
I'm willing to try anything to get my histamine down. I'm going to try metafolin and hydroxyb12. I'll keep the antihistamines within reach,for sure.
Well, idk. I have VERY high histamine - my allergies are the worst my allergist has ever seen, and the only methylation supplement that sets them off is niacin. Niacin sets everyone off but for those of us who are sensitive the reaction is very severe and long lasting. Presumably not dangerous except it will ruin your day and scare th ecrap out of you. P5P is SO good for you - it also protects your kidneys from glycation caused by blood sugar and Life Extension says a huge percentage of those with kidney disease could have avoided it with P5P. It is considered an important life extender for that reason.
As for me, I have experimented for a few days now and it looks like taking an extra 50mg P5P in the evening (I already took a 50mg in the morning) prevents me from having anxiety problems even if I dial down my dose of DHEA to more normal levels. I have a CBS +/+ and a CBS +/- and I believe it takes BOTH DHEA (possibly the testosterone made from it) AND P5P to regulate that correctly. It might be possible to regulate that w/o the DHEA but then the dose of P5P would likely be astronomical if it worked at all. I don't like takig astronomical anything so I am happy with my regimen tweak so that I can take normal doses of everything.
Here is my regimen:
Thorne Basic B 2x/day
50mg P5P 2x/day
1g TMG 2x/day
800 mcg mfolate 1x/day
50mg DHEA 1x/day
10,000 D3 5x/week
500mg potassium 1x/day
2g mineral ascorbates 1x/day
1g/ d-alpha tocopherol 1x/day (you take gamma, don't do as I do)
MK-7 Now small dose 1x/day (1/week I take 15mg MK-4 instead)
50mg zinc (my allergies need this and so does methylation and also it is an alpha reductase inhibitor so helps me retain soe testosterone for CBS)
LEF cruciferous veggie supplement (makes my hormones come out right, including a 5 alpha reductase inhibitor for testosterone metabolism and I3C / DIM for estrogen metabolism)
etc( other supplements)
That Mk-7 above is from NOW brand (which is what I meant by saying "now") and the MK-4 is that Canadian brand OAR(?) OR(?) - it is the only one I could find in a high enough dose to use to clear the blood stream.
Interesting stuff triffid113 . I'm buying p5p today, it's necessary to for the dao enzyme to work, which breaks down histamine.
I can't wait to do my 23andme testing. My neurotransmitter levels suggest a possible CBS problem. I'm 21 and I've had the same,very unhealthy symptoms since I was 5. For sure methylation has something to do with it.
P5P is lowering my histamine !!!! At least I think so! My body doesn't feel feverish to touch. I haven't had a hot flash. So far I've taken 100mg of p5p. I'll take some more tonight.
I believe I'm deficient in zinc,which would make me deficient in p5p. My dao enzyme has life is coming to life I believe!
God if this continues it'd be so great. Lower histamine means less anxiety. Thus because Adrenaline is a main counter to histamine.
Wow that's interesting. I had a high blood histamine level (even though I said I have never had histamine reactions to anything), and I have been having a lot of issues with high adrenaline as well. I'd really like to know if you continue to notice positive results with the b6.
Gen, I also have a question about the symptoms you have relating to high histamine other than itching and hives. You mentioned a sort of hot flash and feverish sensation. I was wondering if this was specific to your skin or if this feeling made your body completely hot? I am asking as I had this high histamine blood test and show no signs of allergies or reactions, however I am a very "hot" individual. I must sleep with a fan on every night otherwise I cannot sleep. I have anxiety and such and my guess is this is from pumping out too much adrenaline?
I found a small description of B6 in lowering histamine at: (http://histamino.wordpress.com/2010/02/26/relief-from-histamine-intolerance/
"Vitamin C is well-known for its anti histaminic activity, a lot of cases blood histamine levels are directly correlated to the vitamin C levels, and that the intake of vitamin C will lead to less histamine in a matter of days.It functions as a cofactor of DAO, just like vitamin B6 does. Diamine oxydase, the enzyme that breaks down histamine in the blood and the gut, depends on vitamin B6 to function, so if a shortage of B6 arises, the enzyme is practically useless. The intake of vitamin B6 often leads to a higher activity of DAO, at least in vitro."
This reminds me about a different study I was reading in relation to high histamine individuals. As it is stated in this link I sent you, Vitamin C did a great job of lowering histamine. I will try to find that article again and link it to you. If you are having good results with b6 alone that is great, b6 and vitamin C might be an even better combination.
Here it is: (http://jn.nutrition.org/content/110/4/662.full.pdf). If you want to take a peak at this you can skip right to the charts and tables. The tables show that people with low plasma ascorbic acid (vit C) have higher blood histamine levels. Table 2 shows the change in blood histamine levels in supplementing 1g of vitamin C for 3 days. The change was pretty significant for all of the individuals, lowering it by 2 or 3 times.
The image below is a fairly simple depiction of the histamine pathway indicating two different ways of breaking down, one being through DAO the other being through SAMe methylation. It also shows the location of the various Histamine receptors throughout the body.
So glad to hear the B6 helped you too, GenDylan! My histamine reactions are now totally gone after only three days of supping with B6. (Note: They weren't an issue before the methylation supps, so I doubt B6 will be a cure-all for everyone with histamine problems.) I've been messing with p5p and regular B6 and both seem to help equally for me.(Though it may not be that way for people with trouble converting.) I've been lightly supping Vitamin C (500mg) so that might've helped as well. Enjoying the increased dream recall. Hope you get to the bottom of your health issues Dylan. I suspect, like me, you have a zinc/copper imbalance at the root of your problem (copper destroys B6 on contact, or so I've read, along with Vitamin C...and it antagonizes molyb and zinc and chromium, among others) which may take precedence over jumping straight into the B12/Folate methylation support. My basic understanding from Yasko's book is that those with CBS mutations (like me) need to correct their mineral imbalance with molybdenum and possibly zinc before they go after their methylation issues, or else things like methyl donors might cause problems. Which has certainly been my experience! Good luck.
And to future TMG / Folate / Methionine histamine reaction googlers: I think I made a mistake when I tried niacin during my extreme 2 day reaction. It provided temporary relief once the flush was through, but I think it extended my reaction in the long run. Try B6 or p5p first.
pgoody whenever I get really excited, I get the histamine symptoms. Also when I go outside and it's really hot out, I get histamine symptoms, always when I get in a super hot car I get super itchy. Not only do I get itchy, I get hot. Also I get remarks on my body where I haven't even itched, my forehead and neck particularly . It always starts out with just a feeling of heat,that gets increasingly overwhelming.
Cortisol and adrenaline are histamines main counters, my histamine would not be a problem if I had sufficient cortisol. But I don't, my cortisol is flatlined I believe.ill be testing this week, and then taking hydrocortisone. In the mean time while my cortisol is low, adrenaline is all I got to counter the histamine. I get a rush of adrenaline on command, butterflies in my stomach. I'm paranoid and nervous about everything, ridiculous general and social anxieties. This constant surging of adrenaline leaves me fatigued, including my brain - I've had 24/7 brain fog for at least about 2 years,,,along with the fact that my energy is so low I could be bedridden. My body doesn't want to stand, my legs want to give out. My body's high need for adrenaline is also depriving me of dopamine,because dopamine converts into epinephrine(adrenaline),my dopamine is constantly being converted and being robbed from me. The low dopamine and high adrenaline causing ADHD and a super wiredness,while being physically SO tired.
So, histamine is a big,big key for me.once I start having adequate levels of cortisol in me, I want my histamine to be manageable for just the cortisol. If my histamine is too high to where my cortisol can't get rid of it, then my adrenaline will still be higher than I'd like. FYI, I once took a cortisol suppressing supplement at night(seriphos) , once it kicked it in I got a histamine reaction. Major hot flash. I knew not of hot flashes until LMethionine..
And The reason that I'm now reluctant to use Vitaman C to lower my histamine ,is because I recently read that VitC helps a lot with the conversion of Dopamine to Nonepinephrine. Although VitC is GREAT at lowering histamine , I can't stand to lose any more dopamine. My dopamine is so low, I can't focus, I'm depressed with ZERO motivation,not even to brush my teeth,,,and I get euphoric at anything that makes me happy. I'm so sensitive to dopamine because I'm so low. Btw,depression with low motivation is typically dopamine,not serotonin ,actually new studies say dopamine is much more important than serotonin /serotonin is overrated in terms of depression.
Btw I've had all of these symptoms,since I was 5 years old, they've just progressed significantly. And I didn't know histamine was a problem until I started LMethionine. I suspect I've always had low cortisol and methylation problems..
dishwashsoap 1st of all I'm very happy for you that your histamine issue has resolved.i wish stress upon nobody. Also, it is veryyy encouraging that b6 has helped you so much. Thanks for pushing me this direction, really appreciate it.
I too believe that I could have a copper problem. Thus because I believe I have low zinc and high estrogen. high estrogen because I have man boobs w/o working out or having much fat on my body. Low zinc because I didn't flush during the niacin histamine test, I did get hot tho, and this was before LMethionine which raised my histamine. I've read that you need zinc to flush from Niacin..
I really can't wait to do my 23andme test , the price is amazing.
I am sure P5P is lowering your anxiety. It appears it is lowering your itchiness. (This is not a symptom I ever had because I have taken 100mg B6 my whole life). I do NOT BELIEVE it is lowerig your HISTAMINE. I have EXTREMELY bad allergies and they are not phased AT ALL by any methylation supplement in any dose. The only "allergic" symptom that is cured by methylation is itching from bug bites - a mere skin allergy...it does NOTHING for systemic allergies. So...the story is a lot more complicated than you make it appear and you cannot say that it lowers histamine w/o testing to prove it.
You should get your hair analyzed before you jump to conclusions about copper. estrogen helps women absorb copper, for example. Men and women are usually high/normal in copper when they are young due to hormonal help. You can get a tracelements.com hair analysis here:
btw, I find this study about zinc:
Biomedical and Life Sciences
Volume 22, Number 6 (2009), 1031-1040, DOI: 10.1007/s10534-009-9254-z
Comparison of inhibitory activities of zinc oxide ultrafine and fine particulates on IgE-induced mast cell activation
Kouya Yamaki and Shin Yoshino
The effects of ultrafine and fine particles of zinc oxide (ZnO) on IgE-dependent mast cell activation were investigated. The rat mast cell line RBL2H3 sensitized with monoclonal anti-ovalbumin (OVA) IgE was challenged with OVA in the presence or absence of ZnO particles and zinc sulfate (ZnSO4). Degranulation of RBL2H3 was examined by the release of β-hexosaminidase. To understand the mechanisms responsible for regulating mast cell functions, the effects of ZnO particles on the levels of intracellular Zn2+, Ca2+, phosphorylated-Akt, and global tyrosine phosphorylation were also measured. IgE-induced release of β-hexosaminidase was obviously attenuated by ultrafine ZnO particles and ZnSO4, whereas it was very weakly inhibited by fine ZnO particles. The intracellular Zn2+ concentration was higher in the cells incubated with ultrafine ZnO particles than in those with fine ZnO particles. Consistent with inhibitory effect on release of β-hexosaminidase, ultrafine ZnO particles and ZnSO4, but not fine ZnO particle, strongly attenuated the IgE-mediated increase of phosphorylated-Akt and tyrosine phosphorylations of 100 and 70 kDa proteins in RBL2H3 cells. These findings indicate that ultrafine ZnO particles, with a small diameter and a large total surface area/mass, could release Zn2+ easily and increase intracellular Zn2+ concentration efficiently, thus decreasing FcεRI-mediated mast cell degranulation through inhibitions of PI3K and protein tyrosine kinase activation. Exposure to ZnO particles might affect immune responses, especially in allergic diseases.
Ok, here's a study that shows what is happening to you regarding skin allergies:
Effect of vitamin B6 deficiency on an antibody production in mice
DOKE S.; INAGAKI N.; HAYAKAWA T.; TSUGE H.
To investigate the effects of vitamin B6 (B6) deficiency on an antibody production in BALB/c mice, the production of specific immunoglobulin (Ig) E antibody against dinitrophenylated ovalbumin (DNP-OVA) were measured by the methods of enzyme linked immunosorbent assay. The mice fed on on a B6 deficient diet for 4 weeks were immunized intraperitoneally with DNP-OVA absorbed to aluminum hydroxide gel. The contents of anti DNP-IgE antibodies in sera of B6 deficient mice significantly increased compared to that of control mice fed on a diet containing B6. In addition, Interleukin-4, which was known to induce IgE production in allergic reactions from splenocytes of B6 deficient mice, was approximately four-fold higher than that in control mice. According to the recovery test to the B6 deficient mice, that is feeding the control diet for 21 days, all values in terms of the body, thymus, and spleen weight, total serum protein, IgG, and anti DNP-IgE content, regained almost the same levels as those of control. These results suggest that B6 deficiency in mice would have relation to the stimulation of specific IgE antibody production against DNP-OVA.
Note that it affects IgE (which is skin allergies like you have) not IgG (hayfever like I have). Either of these will cause histamine production.
Oh, sorry, I don't want to imply that I know more about allergies than I do. There are many different Ig's and IL-'s involved in allergic responses and I don't really know which one causes what...just that some things suppress one or another or a handful but not all.
You can also try a Google Site Search
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