Help! How can we keep our methionine from draining?

[Kimsie]

I just came to the realization today that our son, who has high histamine due to gut dysbiosis, is losing his substrate in the methionine cycle through the CBS pathway. He does have CBS upregulations, but I think the main reason he is losing his methionine, or homocysteine, or SAMe, whatever you want to call it, is that when you have high levels of methionine and or SAMe it causes CBS to increase the enzyme levels but my son needs high levels of SAMe to degrade the large amount of histamine being produced as we try to deal with and kill of his bad gut bacteria. Every time he eats it only takes about 1/2 hour before his symptoms start to get worse, so the bacteria must be high in his gut, or else maybe he is having an allergic reaction to his high protein GAPS diet, but he gets this no matter what protein he eats, whether it is broccoli or beef or chicken or rabbit or duck or goose. The only things that don't cause it are fruit and fats. When we push the cycle with b12, folate, and methionine he feels good, because when he has enough SAMe it gets rid of the histamine, but then we have to give more and more to keep him feeling good. I think that if we could put the breaks on the CBS it would solve the problem, but the only ways I have seen would be counter productive, either cutting off his B6, which would put the breaks on dopamine production, or by cutting off methionine in the diet, which would defeat my purpose.

Does anyone have any suggestions? I think I will have to start giving him large doses of vitamin C again. Maybe that will make it so he can feel good without needing such high levels of SAMe. Vitamin C alone needs very high doses all day with bowel tolerance to keep the histamine down, but maybe a combination will work acceptably while we are working on getting his gut bacteria under control. I thought when I started giving him these things and he felt so good that every thing was going to be smooth sailing, but It looks like we have hit another bump in the road.

 

[Critterina]

@Kimsie ,
Have you put him on a low histamine diet? That has been huge for me. It's not the type of protein (except no fish or shellfish), but that you only cook it right before you eat it. If you have to keep it overnight, you need to freeze it. And no tomatoes, peppers, spinach, cocoa, cinnamon, cheese, yogurt, or anything aged or fermented. Let me know if you want more info.
I don't know if he has the BHMT 08 mutation, but if he does, TMG is helpful in recycling homocysteine back to methionine. I'm hoping to do enough with the methylfolate, methylB12 and TMG that next time I test, my methionine will be back up to normal. I also use 400 mg SAMe and enzymes (to digest the protien)...I have a ways to go, but I'm better than I've been in 22 months since starting low histamine.

 

[Kimsie]

Hi Critterina,

We did try TMG, but it didn't make a difference. If the pool of homocysteine is small it doesn't have much to draw on.

I know all about the low histamine diet. Even when his food is cooked right before he eats it, if it has any protein in it he feels worse after about half an hour. It has to be either a reaction to the food or that bacteria are using the protein to produce histamine. It used to take two hours before he felt worse. I suspect that on the GAPS diet the bacteria have been creeping up his intestines looking for food. When I started giving him lactoferrin about 3 weeks ago the first day his symptoms were much better so it must have hit the bacteria hard and made them stop producing histamine, but after 2 days the symptoms were back but all the time, even before eating in the morning when usually he feels fine in the morning before he has any protein, so I think that it was from die off. This leads me to think that it must be bacteria as I have suspected all along, and not a food reaction.

 

[Critterina]

Hi Kimsie,

That's too bad. Have you added H1 and H2 histamine blockers with his meals? I don't know much about them, but I understand they are things like benedryl and zantac. Maybe someone can eludicate and better educate me.

Maybe you are right about the gut bugs. Have you tried restricting natural protein from his diet and using pure supplements of the free or branched chain amino acids to meet his nutritional requirements? Not sure that would help...I'm sort of grasping at straws here.

Have you tried the 4-R gut rebuilding program. I'm sorry I don't remember the official name of it.

 

[Kimsie]

Hi Critterina,

I tried using Quercetin yesterday, which blocks the release of histamine, and it didn't do any good. We haven't tried Benedryl, my son doesn't like the idea of using drugs and I couldn't get him to take anything like that (I tried, but he is 17 years old and I think he should have some say in this), but I really think his problem is from draining the SAMe to get rid of the histamine, and not from histamine getting into the receptors, anyway.

When he first got sick he was on a low protein diet and he still had the symptoms, the symptoms improved when he went on GAPS, which is a high protein diet, I think that was because it raised his methionine levels. We did try using the amino acid powders to give him a protein free diet, but that wasn't working either. I think now that that was because there was histadine in the mix and the bacteria turned it to histamine. At the time I didn't realize that it was histamine that gave him his symptoms, I just knew it was something made by bacteria in his gut.

Today our plan is to only give him fruit and fat for part of the day and let him have protein later after he gets most of his work done. He usually feels good until he eats something with protein in it.

I'll take a look at that gut rebuilding program. We are using GAPS, and it did heal his leaky gut so that as long as he has his zinc, he no longer has food reactions. However he hasn't been making any progress lately, but I think it may be because with GAPS you are supposed to eat yogurt and kraut and we stopped the kraut months ago but he was still eating yogurt but we stopped that a couple of days ago in case the yogurt keeps seeding more histamine producing bacteria into his gut. If that doesn't help within 3 weeks or so we might try a different program to deal with his gut problems.

 

[Kimsie]

I think I figured this one out! His histamine has been fluctuating so much that his body can't regulate the amount of SAMe it makes. His levels are low in the morning and go up after he eats so they are high all day and low for a few hours during the night.

We need to keep his histamine levels constant, which we will do by provoking more die off with lactoferrin, and make sure he has sufficient amounts of methylfolate and B12 and then it will take a couple days after the histamine is constant for his body to make the adjustment. I will report later if this works in case anyone else ever has a similar problem.

This would account for the reason why sometimes people feel good for a couple of days after starting the supplements, and then it stops working while the body is adjusting to the new levels of enzymes it needs to make.

 

[Critterina]

Hi Kimsie,

I really hope that helps him. That seems to be such a tough problem, reacting to all protein.

What is the mechanism of the SAMe getting rid of the histamine? Maybe more SAMe will help me. My NP had me on 1500 mg methionine, and when I told her I wanted to replace the methionine with SAMe, she said to use 400 mg sublingual. It seemed like a reduction in dose. (Quercetin didn't have a big effect on me, either, and it took a couple weeks for me to notice it. After two months, now, I'm not sure I'll buy more.)

Here's a thread that talks about the 4R gut rebuilding, if you choose to try that sometime:
http://forums.phoenixrising.me/index.php?threads/the-4r-gut-rebuilding-program-summary.25761/

I have only followed it loosely, but when I got to it, the enzyme/probiotic combo by American Health, taking it 3 times a day with meals, did not bother my histamine intolerance and did darken and form my stools after about 4 weeks. Every place I look has been out of it recently.

 

[Kimsie]

Hi Critterina,
I realize now that what is happening is that he isn't exactly reacting to the protein, it's that the bacteria in his gut is making histamine, and because his histamine is higher during the day when he eats, and considerably lower during the night, his body is having trouble regulating the amount of SAMe. I think I have figured out a way to fix the problem, and I will post about it in a day or two if it works. It should only take about 2 days to re- set his SAMe to the amount he needs from what I have been observing in the past 2 weeks.

SAMe is used by histamine N-methyltransferase as the methyl donor to degrade histamine. If you don't have enough SAMe, you won't be able to degrade all of it quickly. However, I don't think that it is very effective taking SAMe supplements, it's better to get your methionine cycle going to make the amount you need. I guess I will tell you my ideas about helping my son because I think it is important here.

Why do some people react negatively to methyl groups and others are not affected? I can take tons of methylfolate and methyl B12 (even an injection) and I feel nothing. Some people become anxious or feel like they are bouncing off the walls. I believe the answer is that the ones who are "overmethylators" are actually low in niacin.

The needs of the body for SAMe vary through the day, yet the mechanism for changing the amount of SAMe produced by the body takes more than 24 hours to significantly change the amounts of the enzymes that are responsible for recycling homocysteine into SAMe: methionine synthase and methylenetetrahydrofolate reductase. This is based on my personal observation of my son and how long it took to change his ability to respond to higher doses of B12 - it took more than one day and less than two for him to stop responding to B12. If the levels of SAMe rise too high, then methionine synthase and MTHFR are inhibited, and CBS is increased. So how do we maintain levels of SAMe that are high enough for our highest daily needs without triggering the inhibiting response during the part of the day when we need less? I would suggest that one unacknowledged function of niacin is to be a methyl sponge to keep the levels of SAMe from getting high enough to trigger the inhibition. If free niacin floating in the blood isn't harmful, and I believe that it isn't (There have been cases of liver damage from high doses of slow released niacin, but none from regular niacin or niacinamide.) in the amounts that are needed for the methyl sponge function (perhaps up to 1.5 grams a day), then I think that metabolism of niacin is a sufficiently low priority job for SAMe that it does its other more important jobs and then the excessive SAMe is used up getting rid of the extra niacin.

So I am trying this on my son and within a day or two I should know if it works. If you have trouble with histamine every day then perhaps it would work for you, too. For instance, for my son I am giving 500mg of niacinamide 3X a day and 2 mg of methylfolate 2x a day and 5000mcg of methyl B12 about 5 times a day. After he is feeling good we will experiment with lowering the doses because I think I am over shooting on the amounts, but as long as he has the niacinamide to mop up the excess, that shouldn't be a problem.