It is a common belief that taking too much folate can cause “overmethylation” leading to symptoms such as anxiety. While taking too much folate isn’t a good idea and it is possible to have a state of overmethylation, I believe that there are some incorrect ideas circulating that need to be examined.
I have been modifying my hypothesis, and I am hoping that some of you here will respond by giving me helpful criticism of my ideas so that I can continue to improve them. I will respond by either modifying my hypothesis or by defending my ideas, as it seems appropriate to me.
Myth #1. Niacin helps symptoms of overmthylation by mopping up methyl groups.
Niacin does mop up methyl groups, especially in the niacinamide form, but normally if the levels of neurotransmitters get too high they are quickly degraded by enzymes such as MAO. Without sufficient niacin (NAD) for the aldehyde dehydrogenase enzyme reaction, MAO will become inhibited – leading to an excess of neurotransmitters. So if a person has sufficient niacin in the body, they will not get a buildup of neurotransmitters (assuming they do not have some other block in that pathway). Magnesium is also used in this pathway. The common symptoms of overmethylation are caused by niacin deficiency, so niacin or niacinamide relieves them. Notice that I am saying there is a deficiency of NAD here, something I have said before in other posts. Obviously this is important for energy production because if a person does not have enough NAD for the MAO pathway then they don't have as much as they need for the TCA cycle either.
I realize that a number of people here have problems taking niacin or niacinamide. I believe that this must be due to insufficient amounts of other substances, such as vitamins or minerals, or other factors that are interfering with normal pathways in the body. By examining the symptoms an individual has, it may be possible to figure out what is going on and compensate.
Myth #2. Too much folate can cause a person to have too much SAM-e, leading to overmethylation.
Although MTHFR, which is the rate controlling enzyme for the methionine cycle which produces SAM-e, can be inhibited by a lack of folate there are several feedback mechanisms which normally control the amount of SAM-e produced regardless of folate availability, such as high levels of SAM-e inhibit MTHFR. The liver has a mechanism for getting rid of too much SAM-e through the glycine N-methyltranferase enzyme which requires glycine. The body makes glycine using SHMT, a folate enzyme. So an increased need for glycine might increase production of SAM-e. Insufficient glycine could be the cause of high SAM-e. Other possible causes might be found in the MTHFR feedback pathways of the individual person.
Note: I don't think the answer is taking glycine. More about that later.
I think this is enough to get a conversation started, if anyone is interested. I can put up lots of references and diagrams if anyone wants to see them, but I don’t have enough time today. I have a lot of other ideas that I would like to discuss but if I try to put everything into one thread it would be too long and complicated so I am planning to gradually start other threads about them.
I have been modifying my hypothesis, and I am hoping that some of you here will respond by giving me helpful criticism of my ideas so that I can continue to improve them. I will respond by either modifying my hypothesis or by defending my ideas, as it seems appropriate to me.
Myth #1. Niacin helps symptoms of overmthylation by mopping up methyl groups.
Niacin does mop up methyl groups, especially in the niacinamide form, but normally if the levels of neurotransmitters get too high they are quickly degraded by enzymes such as MAO. Without sufficient niacin (NAD) for the aldehyde dehydrogenase enzyme reaction, MAO will become inhibited – leading to an excess of neurotransmitters. So if a person has sufficient niacin in the body, they will not get a buildup of neurotransmitters (assuming they do not have some other block in that pathway). Magnesium is also used in this pathway. The common symptoms of overmethylation are caused by niacin deficiency, so niacin or niacinamide relieves them. Notice that I am saying there is a deficiency of NAD here, something I have said before in other posts. Obviously this is important for energy production because if a person does not have enough NAD for the MAO pathway then they don't have as much as they need for the TCA cycle either.
I realize that a number of people here have problems taking niacin or niacinamide. I believe that this must be due to insufficient amounts of other substances, such as vitamins or minerals, or other factors that are interfering with normal pathways in the body. By examining the symptoms an individual has, it may be possible to figure out what is going on and compensate.
Myth #2. Too much folate can cause a person to have too much SAM-e, leading to overmethylation.
Although MTHFR, which is the rate controlling enzyme for the methionine cycle which produces SAM-e, can be inhibited by a lack of folate there are several feedback mechanisms which normally control the amount of SAM-e produced regardless of folate availability, such as high levels of SAM-e inhibit MTHFR. The liver has a mechanism for getting rid of too much SAM-e through the glycine N-methyltranferase enzyme which requires glycine. The body makes glycine using SHMT, a folate enzyme. So an increased need for glycine might increase production of SAM-e. Insufficient glycine could be the cause of high SAM-e. Other possible causes might be found in the MTHFR feedback pathways of the individual person.
Note: I don't think the answer is taking glycine. More about that later.
I think this is enough to get a conversation started, if anyone is interested. I can put up lots of references and diagrams if anyone wants to see them, but I don’t have enough time today. I have a lot of other ideas that I would like to discuss but if I try to put everything into one thread it would be too long and complicated so I am planning to gradually start other threads about them.
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