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.