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carnitine or NAC for those with CBS+, NOS+, COMT+, SUOX+ ??

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
NAC is problematic for people with histamine intolerance, also. The symptoms vary widely individual to individual. If you respond badly to NAC, check out the article by Maintz in the American Journal of Clinical Nutrition. I'm not saying it's not methyl trap, but it is cited in the article as a source of histamine, for those of us who struggle with that issue.

Hi Critterina,

I'm not saying it's not methyl trap, but it is cited in the article as a source of histamine,

Methyltrap gives every appearance of increasing histamine. It causes widespread inflammation, asthma, MCS, allergic responses, IBS, skin rashes, and all sorts of hyper sensitive responses.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Hi Critterina,

I'm not saying it's not methyl trap, but it is cited in the article as a source of histamine,

Methyltrap gives every appearance of increasing histamine. It causes widespread inflammation, asthma, MCS, allergic responses, IBS, skin rashes, and all sorts of hyper sensitive responses.
Yes, we know that, Freddd. Some of us have histamine intolerance without having methyltrap, (which I'm still awaiting a biochemical explanation of, you may remember). You just have to allow for the possibility that there can good medical evidence of a reaction that has nothing to do with your pet theory, yet shares some of the same symptoms.
 

knackers323

Senior Member
Messages
1,625
What would be a rough max for doses of these supplements where it would probably lose its effect? I ask because I can seem to take any amount I wish with no ill effects
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Yes, we know that, Freddd. Some of us have histamine intolerance without having methyltrap, (which I'm still awaiting a biochemical explanation of, you may remember). You just have to allow for the possibility that there can good medical evidence of a reaction that has nothing to do with your pet theory, yet shares some of the same symptoms.

Hi Critterina,

There are a number of possible causes. There are more ways to make things go wrong than to go right. That is why I specified the grouping of descriptions of symptoms that go with methyltrap. I was being very specific so that there would be no misunderstanding. If the specific enzymes involved in breaking down or getting rid of histamine require ATP for powering the transaction at any stage or methylation or ATP involved in making the enzymes it could very well fit right into right into the deadlock quartet hypothesis. If that's the case, then there might be a testable hypothesis there. It would depend upon what all your non-histamine related symptoms are that might tell the story.

The 4 way deadlock has thousands of cascading mysterious problems resulting.

I don't know what the thousands of breakdown pathways are when enzymes are blocked by insufficient ATP, and why which specific ones. I don't know anybody who does. The body's triage methods for allocating scarce resources are not yet described.

It's hardly a pet theory. And I do NOT ignore "good medical evidence". It has to fit in. There is a difference between "good medical evidence" and understanding or explaining it correctly. I work with an evolving working hypothesis. I don't care about the hypothesis or theory or whatever semantic nitpicking you want to use. It is whatever it needs to be. I walked in the door here 6 years ago with a very different working hypothesis. The facts and responses haven't changed but the explanations have. Histamine intolerance is a result, not a cause. Who knows how deep the cause is buried.


http://ajcn.nutrition.org/content/85/5/1185.full Article containing the below image.
Added: http://ajcn.nutrition.org/content/85/5/1185/F2.large.jpg

Methylation is involved in disposing of histamine via the HNMT pathway by SAM-e. So, one possible conclusion is that some sort of partial methylation block might be involved in Histamine Intolerance. It's that pesky SAM-e getting involved.

Determination of the HNMT activity is based on transmethylation of histamine by S-adenosyl-l [methyl-14C] methionine (126). Furthermore, the total histamine degradation capacity can be measured (69).
 
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Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
What would be a rough max for doses of these supplements where it would probably lose its effect? I ask because I can seem to take any amount I wish with no ill effects

Hi Knackers,

Your question is completely unanswerable as it sits. Some have a negative effect if too much. It's all about combinations, balance and individual needs.

For starters, most MeCbl that you have tried may have very little of the effects you need. Slow down. Relax. This is a "game" of skill. You can't "win" by trying to blast through.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
There are a number of possible causes.
Thank you for acknowledging that. And thank you for speaking English this time, and not using undefined acronyms. As you may remember, last time I couldn't tell what the FFF you were talking about. (Example of one of your UAs)

If the specific enzymes involved in breaking down or getting rid of histamine require ATP for powering the transaction at any stage or methylation or ATP involved in making the enzymes it could very well fit right into right into the deadlock quartet hypothesis.
It would be rather short list of metabolic pathways that ATP is not involved in, don't you think? And each has a myriad of other things that can go wrong.

If that's the case, then there might be a testable hypothesis there. It would depend upon what all your non-histamine related symptoms are that might tell the story.
On a stable methylation protocol, prescribed for me, my symptoms are stable until I do one of the following:
Eat a breakfast of oatmeal and cinnamon
Eat a breakfast of cottage cheese and blueberries
Eat any amount of tomato, pepper (bell, chili, paprika), spinach
Eat any cooked and refrigerated meat (the longer the refrigeration, the worse the symptoms)
Drink over-fermented kombucha (violent reaction)
Take NAC, 600 mg, 3x/day (also severe reaction)

Symptoms are immediate nasal blockage and decreased lung capacity, down to 80% as tested by spirometry. With continued use of the above substances, more extensive edema and inflammation.

The symptoms may subside, or I may choose to use a short course (3-5 days) of steriods to reverse them. Trouble arises when I can't or don't avoid histamines. My protocol already includes twice daily antihistamines. Since I've been living in a hotel since Sept 8, my control over my food has not been wonderful. Sometimes I take 2 more benedryl at lunch, for 3 times a day.

I have had extensive lab tests during the past year. All my non-histamine related symptoms except early-onset obesity are described in the article Diagnosis of Adrenal Insufficiency in the Annals of Medicine, 2003 and they seminar "Adrenal Insufficiency" in the Lancet, 2003. That's probably how deeply the cause is buried. Cortisol opposes histamine and cortisol is largely undetectable in my lab tests, and it's precursor, progesterone, is completely undetectable.

The 4 way deadlock has thousands of cascading mysterious problems resulting.
And thus many thousands of ways of being confused with other things.

I don't know what the thousands of breakdown pathways are when enzymes are blocked by insufficient ATP, and why which specific ones. I don't know anybody who does. The body's triage methods for allocating scarce resources are not yet described.
I would submit that possibly different people, depending on genome, environment, and lifestyle, may have bodies that use different methods to triage.

It's hardly a pet theory. And I do NOT ignore "good medical evidence". It has to fit in. There is a difference between "good medical evidence" and understanding or explaining it correctly.
Then why can't I find a good, peer-reviewed article on either paradoxical methylfolate insufficiency or methyl trap? You refer to "many studies", but double-blind, placebo-controlled studies are the hallmark of "good medical evidence" in the US, double-blind, non-inferiority studies substitute in Japan because of the different balance in ethical treatment vs. hard science. I don't see the publications, and it appears that you are doing investigations on human subjects that don't meet the standards of good clinical practice, thus subjecting the study results to misinterpretation. (Not to mention liability issues.)

Absent clinical evidence that would withstand scrutiny, I would settle for "understanding or explaining it correctly". Thank you for publishing link to the HI article. My doctors have copies. Links to methyl trap articles would be more welcome.
 

knackers323

Senior Member
Messages
1,625
Hi guys when I take relatively big doses of NAC my symptoms increase within a few hours. Do you know any way to tell if this is due to the methylation cycle, histamine intolerance, breaking down biofilms or anything else?

I am able to take l-carnitine which gives me energy. Again in pretty big doses.
I always seem to need bigger doses than the average to see an effect with most things I take.

I also seemed to be able to take liposomal glutathione and felt better on it. Again big doses.

As a side question any idea on why I need to take big doses to see effects?

Thank you
 
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Messages
99
Location
London, UK
NAC is problematic for people with histamine intolerance, also. The symptoms vary widely individual to individual. If you respond badly to NAC, check out the article by Maintz in the American Journal of Clinical Nutrition. I'm not saying it's not methyl trap, but it is cited in the article as a source of histamine, for those of us who struggle with that issue.

I definitely do. I have strikingly similar symptoms to you whenever I eat what you mentioned: cinnamon, berries (especially strawberries; they give me hives in addition to the asthmatic symptoms I get with all the others), tomato, pepper (bell, chili, paprika), spinach, any cooked and refrigerated meat. I always keep antihistamines handy because of the reactions I get.
 

btdt

Senior Member
Messages
161
Location
Ontario
I have been trying to sort out what is going on within this page.... I will admit I do not understand everything people are talking about in this thread. What I would like to have is an answer... to the original question in plain english please...
carnitine or NAC for those with CBS+, NOS+, COMT+, SUOX+ ??
I have taken NAC if I take it long enough I can't breath so I now mostly avoid it unless I am having a bad reaction ... not sure why but it is one of the supplements listed to treat MCS multiple chemical sensitivity just to clarify the acronym. Again this was from a layperson who had lessened her symptoms greatly and mcs may have many faces like me we may not all be the same exactly variations are bound to exist.
From what I can recall from 23 and me I have issues with all those genes except maybe NOS I don't recall seeing it.
I know this thread too a bit of bad turn there which may have lessened peoples interest in this topic. All I can say about that is lets try to be nice to each other nobody here is a doctor we all know that and there may be as many different answers as there are people... well maybe not that many.
I no longer take NAC ... never say never.
I tried carnitine twice both times it seemed helpful.

I have not had a tomato or other things on your list in a a long time. dx with cfs way back in the 80 feel I had it long before then... have read the idea that mcs is a progression of cfs if you have cfs long enough you will eventually get mcs... not sure about anything... curious about these genes.
 

btdt

Senior Member
Messages
161
Location
Ontario
http://www.drdebe.com/articles/l-5-mthf-new-supplement-that-could-save-your-life
The importance of L-5-MTHF involves more than its role in promoting proper genetic expression, DNA synthesis and repair. L-5-MTHF also plays a role in dopamine, epinephrine, norepinephrine, histamine, L-DOPA, serotonin, and estrogen metabolism. Not surprisingly, folic acid deficiency is a consistent finding in depression. L-5-MTHF plays a role in forming S-adenosylmethionine (SAM or SAMe), which is the compound that directly donates methyls to DNA and to serotonin and dopamine. Like L-5-MTHF, SAM is available in supplemental form. SAM is a popular remedy for depression and arthritis. It is likely that individuals who respond to SAM are actually in need of L-5-MTHF. It makes sense to try L-5-MTHF before SAM because it is much less expensive.

from what I can recall SAME was bad for me and has been sent to my never take again box of supplements.... so this does not hold true for me.. to the best of my thinking and my thinking is hit and miss.

Since histamine is a player in the methyl trap problem perhaps everybody is right.. it is both



https://academic.oup.com/ajcn/article/85/5/1185/4633007

Thus, histamine intolerance seems to be acquired mostly through the impairment of DAO activity caused by gastrointestinal diseases or through the inhibition of DAO, but the high interindividual variations in the expression of DAO in the gut and the association of SNPs in the DAO gene with gastrointestinal diseases provide evidence for a genetic predisposition in a subgroup of patients with histamine intolerance (27)

last but maybe most important...

Histamine exerts its effects by binding to its 4 receptors: H1R, H2R, H3R, and H4R on target cells in various tissues. Histamine receptors are located all over the body and have many important functions including:

  • H1 receptors: Smooth muscle and endothelial cells affecting skin; blood vessels (Benadryl and Claritin block activity of these receptors)
  • H2 receptors: Cells in the intestines control acid secretion, abdominal pain, and nausea; heart rate
  • H3 receptors: Central nervous system controlling nerves, sleep, appetite and behavior
  • H4 receptors: Thymus, small intestine, spleen, colon, bone marrow and white blood cells; inflammatory response
The DAO gene is also involved in the metabolism of glutamate, an excitatory neurotransmitter found to be elevated in those with schizophrenia and bipolar disorders. ,,
I have a DAO SNP! What now?
Histamine becomes a problem when we have metabolic disturbances that do not allow us to effectively metabolize histamine properly specially for DAO. If DAO is inhibited, histamine will accumulate in the blood and would result in intolerance.

DAO deficiency can be caused by genetic factors (primary deficiency) when certain sequence variants (polymorphisms) in the DAO gene lead to a significantly reduced DAO enzyme activity. Individuals with a DAO gene mutation may have a tendency towards high histamine.

Having a polymorphism doesn’t mean you will have expression of the SNP and therefore histamine intolerance, but you are pre-disposed, particularly if your environment (food, stress, toxin exposure, gut function) are affecting the expression of the gene. In that case, given that histamine is present in our daily diet, we need to be careful what we’re consuming every day.
Copper and Vit C are crucial components of the DAO enzyme and B6 is a key cofactor that enables DAO to degrade histamine.

Copper deficiency is another possible cause for low DAO activity, as copper is a central atom of the DAO and thus essential for its function. Because copper is essential to DAO function, copper levels should be monitored in patients with low DAO activity to avoid further DAO deterioration. Zinc levels should be checked at the same time, as zinc prevents intestinal copper absorption.

DAO vitamins and minerals

  • Vitamin C is well-known for its antihistaminic working. In a lot of cases, blood histamine levels are directly correlated to the vitamin C levels, and 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. Vitamin C can be taken at doses of up to 3,000 mg to reduce histamine levels. Taking large amount of vitamin C is known as Megadosing.
  • DAO depends on vitamin B6 to function. If there is shortage of B6, the enzyme is practically useless. The intake of vitamin B6 often leads to a higher DAO activity. According to the NIH, doses of up to 2 mg should suffice for lactating mothers.
  • Magnesium is important in the histamine metabolism. A shortage increases the activity of histidine decarboxylase in some tissues. Histidine decarboxylase is the enzyme that makes histamine from histidine. While at the same time, a lack of magnesium intake leads to reduced DAO. The NIH recommends doses of up to 400 mg and Magnesium can be bought over the counter as 500 mg tablets.
  • Copper is another cofactor of DAO and able to reduce histamine levels. It’s not often recommended to supplement.
  • Zinc inhibits the release of histamine from mast cells. Supplementation is recommended.
  • Manganese also inhibits the release of histamine from mast cells much like zinc.
  • Many different diuretics, hormone replacement drugs, statins (and others) reduce the amount of these nutrients, causing “medication induced SNP.” This kind of SNP can happen in the absence of an actual gene SNP, because the medication is acting worse than the homozygous polymorphism.

    Drugs that influence DAO

    The changed production of DAO enzyme can be as a consequence of certain medications:
    • Non-steroidal anti-inflammatory drugs (ibuprofen, aspirin)
    • Antidepressants (Cymbalta, Effexor, Prozac, Zoloft)
    • Immune modulators (Humira, Enbrel, Plaquenil)
    • Antiarrhythmics (propanolol, metaprolol, Cardizem, Norvasc)
    • Antihistamines (Allegra, Zyrtec, Benadryl)
    • Histamine (H2) blockers (Tagamet, Pepcid, Zantac)
    Some studies suggest considering the herb HOPS and quercetin (about 250 to 500 mg taken three times daily) in order to reduce histamine levels.
There is a lot more but this is all for me today....

DAO Deficiency and Histamine: The Unlikely Connection
https://www.mthfrsupport.com.au/dao-deficiency-and-histamine-the-unlikely-connection/
 

btdt

Senior Member
Messages
161
Location
Ontario
DAO more...
L-theanine and allergy
Science Score:

★ ★ ★ ★ ★


Thanks, John. L-theanine’s “mechanism of action” is quite interesting.

L-theanine has shown some promise as a modulator of allergic reactions. (R) A major event in allergic reactions is the secretion of histamine from immune cells known as mast cells. Mast cells can be thought of as the first responders of the immune system, they are constantly sensing the environment and when they detect something potentially harmful they secrete a wide range of factors to kick start the immune response. When mast cells detect something as harmful (even if it’s harmless) this causes an allergic reaction. (R) Theanine inhibits histamine release from mast cells.

Interestingly, this inhibition of histamine also ties in with L-theanine’s glutamate inhibitory activities as well. Histamine can induce glutamate release (R), which as we’ve established above, is an excitatory neurotransmitter our bodies need. Excess histamine may cause an unhealthy build-up of glutamate, although there is some evidence that there is an upper maximum of glutamate build-up associated with histamine (R).

L-theanine mechanism of action
Science Score:

★ ★ ★ ★ ★


So the interesting questions then becomes how does L-theanine link all these together, and is there a single gene or SNP which is of particular interest?

Lets look at histamine first, a major gene involved in histamine metabolism is AOC1, which encodes for the enzyme Di-amine Oxidase (DAO – pay attention to that abbreviation as it’s the cause of much confusion). In health DAO functions to break down histamine following its release from mast cells, curtailing the immune response. There are several SNPs within AOC1 which are associated with reduced DAO activity, resulting in histamine intolerance, which is characterized by symptoms often associated with allergy such as headaches, flushing of the skin and irritation (R).

The benefit of L-theanine here is clear. By suppressing histamine release from mast cells (R), it is prevented from building up to harmful levels, even in those with reduced DAO activity.

We’ve already described how L-theanine can inhibit stress by blocking glutamate receptors (R). As excess histamine can lead to the buildup of glutamate there’s a clear mechanism for impaired DAO activity leading to increased histamine, leading to increased glutamate. L-theanine works by both preventing histamine release, and also blocking glutamate activity as well.

AOC1/DAO and DAO/DAAO
There’s a nice indirect mechanism linking DAO, histamine and glutamate.

However, if you read around on the internet, you may find articles discussing a direct action for DAO interacting with glutamate. While there may be evidence linking them directly I’ve not come across it; rather I think it’s a case of confusing DAO the enzyme with DAO the gene. DAO is encoded for by the AOC1 gene and functions to breakdown histamine (R). There is however a DAO gene which confusingly encodes for an enzyme called d-amino acid oxidase (DAAO), which is involved in glutamate metabolism (R).

See also: You say DAO, I say DAAO

Quite why it seemed a good idea for DAO to be encoded for by AOC1 and DAAO to be encoded for by DAO I’ll never know, but I think this is the basis for much confusion. So be careful when you’re trying to interpret your genetic results!

L-theanine dosage and complementary supplements
Ok, taking the mic back from Aaron for some closing thoughts.

I have found L-theanine to be an effective nootropic that produces a calm focus. For me, it’s an effective tool for writing, meditating, creative bursts, and even to unwind and get to sleep at the end of the day. I also like it socially.

If you’re using theanine as an anti-anxiety supplement, the calming effects for me were greatest when paired with GABA and valerian. Keep in mind that both GABA and valerian can upset the stomach, so start slow. I also don’t recommend this stack for daily use over extended periods of time, best to cycle on and off.

As we discussed, theanine lowers blood pressure. Because there can be side effects, I would encourage everyone to experiment with different doses to see what amount of theanine suits them best. Some will tolerate 200mg quite well, while others may want to dose more in line with the studies that used 50mg.

Choosing a theanine supplement
If you’ve read thus far and want to add theanine to your supplement stack, I’ve included a short section below that gives a tour around some of the best theanine products on the market, standalone supplements, as well as a couple blends that have positive reviews and are made with good manufacturing practices from brands I trust.
https://www.mygenefood.com/experience-l-theanine-dose-benefits-side-effect
not sure about this but found it decide for yourself