aaron_c
Senior Member
- Messages
- 691
Hi Yall,
A discussion on this thread started veering into BH4 territory, so I thought I'd move it over here. I hope yall don't mind, but I do think it might be partinent.
You would be correct about NOS if it mostly operates in the direction you have indicated. Some people (Amy Yasko at least, and really anyone who buys that excessive ammonia can cause a depletion of BH4) believe that at least for people with our diseases, excessive ammonia can cause NOS to run in the opposite direction more often than it normally would, and that when it does so, it somehow uses up BH4. As I said, I at least do not know the mechanism, however, I have used BH4 to alleviate, in a dose-dependent manner, symptoms that would seem to have come from excessive ammonia. Perhaps after so many cycles BH4 becomes BH2, like methylcobalamin in methionine synthase, and the issue is simply that our excessive ammonia is using the enzyme much more than it would have otherwise been used? Here is a link to a longer explanation of my experiences with BH4, if you are interested.
In terms of folates being involved in the recycling of BH2 to BH4, here is an excellent explanation of how that happens (or doesn't) by Nandixon. One argument for folate cycling being involved in BH4 levels has to do with the idea that MTHFR can run "backwards" and recycle BH4, which it seems is not likely in vivo.
However, I found a second way 5MTHF might influence BH4 and NOS in this article, which is new to me. It would seem to indicate that 5MTHF interacts with NOS and BH4, probably to prevent BH4 from becoming BH2 (and thus preventing NOS from becoming uncoupled, where it produces more superoxide) But the article is from 2000, so perhaps the understanding is a bit old? What is your take @nandixon?
Also, DHFR, which converts both "folic acid" and dihydrofolate to tetrahydrofolate, also converts BH2 to BH4 using NADPH. So taking synthetic folic acid--which cycles through DHFR slowly--might slow this down and lower one's BH4/BH2 ratio.
@oh_noes: I realize I am coming to this discussion quite late, and you may have gotten your answers by now, but:
1. If the above paper is correct, BH4 does require methylfolate to work well
2. I have never heard that methylfolate was contraindicated for those with sulfur issues. There is the issue of methyl sensitivity, but for what it is worth, my experience with methyl donors (including methylfolate) is that it took a little while to get used to a higher dose, but I did get used to it. My understanding is that methyl sensitivity has to do with how quickly we can recycle catecholamines with COMT and how sensitive our bodies are to them. (I think through the vitamin d receptor, assuming heartfixer guy is right. Which it seems he is not always.) The theory as I understand it is that if one has mutations in the COMT or VDR genes, like I do, then taking more methyl groups will produce more catecholamines that we inactivate slowly (COMT mutations) and that our bodies will be more sensitive to (VDR mutations) which will end up causing insomnia, et. But my body, at least, was able to adapt over time, and I now do quite well with fairly high doses of methyl donors.
My understanding is that, since "methyl-sensitivity" is theorized to be related to genes having to do with neurotransmitters and not SAMe directly, and since our bodies seem to be able to adapt to these changes, we actually want to get our bodies used to taking higher amounts of methylfolate--although how high anyone should go is a matter of some discussion.
A discussion on this thread started veering into BH4 territory, so I thought I'd move it over here. I hope yall don't mind, but I do think it might be partinent.
If the B2 was helping me make nitric oxide, I would have felt better, not worse. I assume, then, that I'm missing a co-factor, which could be T4, or B3, or both, or....
You would be correct about NOS if it mostly operates in the direction you have indicated. Some people (Amy Yasko at least, and really anyone who buys that excessive ammonia can cause a depletion of BH4) believe that at least for people with our diseases, excessive ammonia can cause NOS to run in the opposite direction more often than it normally would, and that when it does so, it somehow uses up BH4. As I said, I at least do not know the mechanism, however, I have used BH4 to alleviate, in a dose-dependent manner, symptoms that would seem to have come from excessive ammonia. Perhaps after so many cycles BH4 becomes BH2, like methylcobalamin in methionine synthase, and the issue is simply that our excessive ammonia is using the enzyme much more than it would have otherwise been used? Here is a link to a longer explanation of my experiences with BH4, if you are interested.
Low MeB12, means poorer folate cycling. This leads to lower amounts of BH4 (an essential requirement for NOS).
In terms of folates being involved in the recycling of BH2 to BH4, here is an excellent explanation of how that happens (or doesn't) by Nandixon. One argument for folate cycling being involved in BH4 levels has to do with the idea that MTHFR can run "backwards" and recycle BH4, which it seems is not likely in vivo.
However, I found a second way 5MTHF might influence BH4 and NOS in this article, which is new to me. It would seem to indicate that 5MTHF interacts with NOS and BH4, probably to prevent BH4 from becoming BH2 (and thus preventing NOS from becoming uncoupled, where it produces more superoxide) But the article is from 2000, so perhaps the understanding is a bit old? What is your take @nandixon?
Also, DHFR, which converts both "folic acid" and dihydrofolate to tetrahydrofolate, also converts BH2 to BH4 using NADPH. So taking synthetic folic acid--which cycles through DHFR slowly--might slow this down and lower one's BH4/BH2 ratio.
@oh_noes: I realize I am coming to this discussion quite late, and you may have gotten your answers by now, but:
1. If the above paper is correct, BH4 does require methylfolate to work well
2. I have never heard that methylfolate was contraindicated for those with sulfur issues. There is the issue of methyl sensitivity, but for what it is worth, my experience with methyl donors (including methylfolate) is that it took a little while to get used to a higher dose, but I did get used to it. My understanding is that methyl sensitivity has to do with how quickly we can recycle catecholamines with COMT and how sensitive our bodies are to them. (I think through the vitamin d receptor, assuming heartfixer guy is right. Which it seems he is not always.) The theory as I understand it is that if one has mutations in the COMT or VDR genes, like I do, then taking more methyl groups will produce more catecholamines that we inactivate slowly (COMT mutations) and that our bodies will be more sensitive to (VDR mutations) which will end up causing insomnia, et. But my body, at least, was able to adapt over time, and I now do quite well with fairly high doses of methyl donors.
My understanding is that, since "methyl-sensitivity" is theorized to be related to genes having to do with neurotransmitters and not SAMe directly, and since our bodies seem to be able to adapt to these changes, we actually want to get our bodies used to taking higher amounts of methylfolate--although how high anyone should go is a matter of some discussion.
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