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Preventing Methyl-Sensitivity by limiting Supplemental Vitamin B2 (Riboflavin) Intake to 35-50 mg/da

aaron_c

Senior Member
Messages
691
Hi Everyone,

In a nutshell, I seem to be having success limiting methyl-group sensitivity by limiting my daily riboflavin-5-phosphate (R5P—the active form) supplemental intake to about 35 mg. This does not seem to work via limiting 5-MTHF synthesis via MTHFR, as taking even large amounts of 5-MTHF has not causes “overmethylation” symptoms. Perhaps methyl groups are the usual limiting factor in the synthesis of some catecholamines, but having added extra methyl groups R5P becomes the limiting factor? Here is the only salient study I could find, reporting that “Riboflavin deficiency induced decreases in liver epinephrine and norepinephrine, and in brain norepinephrine, but not in the adrenal glands or spleen.”

I am interested to hear if anyone else finds this to be true. Perhaps this is the reason that people on Freddd's protocol do not suffer from “overymethylation” (he recommends limiting R5P to 50 mg per day, I believe).*

Here is the longer story, for those interested: I recently “stepped down” from using large amounts of mB12 and 5-MTHF, more or less according to Freddd's protocol. Part of this protocol involves keeping B1, B2 and B3 supplementation under 50 mg per day. I had experienced some benefits, but I wanted to experiment with higher levels of magnesium supplementation, and the magnesium seemed to be interacting with the B12 unfavorably. In attempting to find a lower amount of methylfolate and methylb12 that I would take, I accidentally found that taking the multi-B complex I had used while on Freddd's protocol prevented overmethylation symptoms (alertness without extra physical energy stores, followed by insomnia and exhaustion but still with a “caffeinated” feeling.) I added B1 without inducing over-methylation symptoms, which only left B2 as the culprit, as all other vitamin intakes had been the same when I got overmethylated and when I was not.

Assuming this works roughly like I suggest, there would be further questions to answer: Where are the extra methyl groups going? Are we at risk of over-methylating genes? Do the answers to these questions depend on COMT status? Although I feel I a need to point out the possible risks, I should also say that this discussion probably overlaps with discussion on possible risks of Freddd's protocol.

Having acknowledged some of the risks involved, I would also like to point out the advantages I see: This allows me to use as much lecithin as I would like, both for liposomal nutrients and to repair my gut and mitochondrial membranes in general. It allows me to add more methylfolate and b12 into the mix, which does seem to improve my general wellbeing up to a point. In sum, it eliminates the precise balancing act I had been subject to in regard to methyl groups, and allows me to take (more of) some helpful supplements.

I am very curious to hear from anyone suffering from methyl sensitivity who tries or has experience with this (I believe Pure Encapsulation's B-Complex Plus should limit b2 to an acceptable amount.) But as stated, I am unsure of the medium-to-long-term consequences of this.** Finally, I wonder if anyone has insight into what mechanism might be driving this (assuming that this works as I imagine, and I have not missed something!)

Hooray for you if you have gotten this far, and thank you so much from me.
Warmly,

Aaron C


*This could also, as Rich Van K pointed out, be attributable to increased conversion of sarcosine into glycine and THF into 5, 10 methylene-THF via SDH. Or perhaps they arrived at an entirely different conclusion? I haven't read much on that particular question.
** I am not a medical practitioner in any way, just a person with ME.
 

amaru7

Senior Member
Messages
252
I couldn't read the thread thoroughly because I'm not doing that well, but I can tell you over methylator is connected to comt polymorphisms.

As for Riboflavin I don't know the connection, generally I came to the point that I don't do well with supplements, never had big improvements over the years and some supplements left me feeling even worse off.

As for overmethylation, methyl donors are to be avoided like big doses of methylfolate, methylcobalamin, SAMe etc.and I had bad experiences with these in the past due to comt double mutations. You might read Amy yasko, I think she started the term overmethylation and she's an expert in nutrigenomics

Hope that's any helpful to you
 

npeden

NPeden, Monterey, CA
Messages
81
Hi Everyone,

In a nutshell, I seem to be having success limiting methyl-group sensitivity by limiting my daily riboflavin-5-phosphate (R5P—the active form) supplemental intake to about 35 mg. This does not seem to work via limiting 5-MTHF synthesis via MTHFR, as taking even large amounts of 5-MTHF has not causes “overmethylation” symptoms. Perhaps methyl groups are the usual limiting factor in the synthesis of some catecholamines, but having added extra methyl groups R5P becomes the limiting factor? Here is the only salient study I could find, reporting that “Riboflavin deficiency induced decreases in liver epinephrine and norepinephrine, and in brain norepinephrine, but not in the adrenal glands or spleen.”

I am interested to hear if anyone else finds this to be true. Perhaps this is the reason that people on Freddd's protocol do not suffer from “overymethylation” (he recommends limiting R5P to 50 mg per day, I believe).*

Here is the longer story, for those interested: I recently “stepped down” from using large amounts of mB12 and 5-MTHF, more or less according to Freddd's protocol. Part of this protocol involves keeping B1, B2 and B3 supplementation under 50 mg per day. I had experienced some benefits, but I wanted to experiment with higher levels of magnesium supplementation, and the magnesium seemed to be interacting with the B12 unfavorably. In attempting to find a lower amount of methylfolate and methylb12 that I would take, I accidentally found that taking the multi-B complex I had used while on Freddd's protocol prevented overmethylation symptoms (alertness without extra physical energy stores, followed by insomnia and exhaustion but still with a “caffeinated” feeling.) I added B1 without inducing over-methylation symptoms, which only left B2 as the culprit, as all other vitamin intakes had been the same when I got overmethylated and when I was not.

Assuming this works roughly like I suggest, there would be further questions to answer: Where are the extra methyl groups going? Are we at risk of over-methylating genes? Do the answers to these questions depend on COMT status? Although I feel I a need to point out the possible risks, I should also say that this discussion probably overlaps with discussion on possible risks of Freddd's protocol.

Having acknowledged some of the risks involved, I would also like to point out the advantages I see: This allows me to use as much lecithin as I would like, both for liposomal nutrients and to repair my gut and mitochondrial membranes in general. It allows me to add more methylfolate and b12 into the mix, which does seem to improve my general wellbeing up to a point. In sum, it eliminates the precise balancing act I had been subject to in regard to methyl groups, and allows me to take (more of) some helpful supplements.

I am very curious to hear from anyone suffering from methyl sensitivity who tries or has experience with this (I believe Pure Encapsulation's B-Complex Plus should limit b2 to an acceptable amount.) But as stated, I am unsure of the medium-to-long-term consequences of this.** Finally, I wonder if anyone has insight into what mechanism might be driving this (assuming that this works as I imagine, and I have not missed something!)

Hooray for you if you have gotten this far, and thank you so much from me.
Warmly,

Aaron C


*This could also, as Rich Van K pointed out, be attributable to increased conversion of sarcosine into glycine and THF into 5, 10 methylene-THF via SDH. Or perhaps they arrived at an entirely different conclusion? I haven't read much on that particular question.
** I am not a medical practitioner in any way, just a person with ME.
Rick, I take Pure Encaps B complex plus, have COMT and am methyl sensitive. (I do fine on it and I am wondering if this is all the folate I will get for my MTHFR). The Pure encap has 400 mcg. of mehthyl b12. I have been taking it with another methylcobalamin, 1000 mcg. with lithium 5 mg. And it has done wonders for my depression.

Today my ND started me on hydroxycobalamin and it sucks. I am anxious and depressed. I too would like to find a way around methyl sensitivity, too. I take about 800 mg. of magnesium a day and did not see a problem with the methyls.

I am not familiar with Fred's Protocol. Will look into it. Meantime, I too am looking for a way to "go around" methyl sensitivity. Thanks, np
 

aaron_c

Senior Member
Messages
691
Hi @npeden

At this point, I also wonder how much of methyl sensitivity is just taking time to "get used" to a higher dose of methyl groups. Because while methylation of monoamines is one function of SAMe, it is not the only use of methyl groups, and I suspect that finding the best level of methyl donors may not correlate with how many methyl donors initially prevent insomnia, et. I wonder if histamine levels, at least in those of us without DAO mutations, might ultimately be a better indicator of methylation status.

Since beginning to limit my B2, I have had used both a high and medium amount of methyl B12/methylfolate, and when I was raising the amounts, there has always been a period of "overmethylation," ie insomnia and feeling "cracked out." Over time, however, this has receded. For what it is worth, soon I will try to add methyl groups in order to help with my high histamine.

I realize I haven't given an answer, exactly. But I would love to hear how things progress. I am particularly interested if you try to add methyl donors to know if you also find that the overmethylation symptoms subside with time.
 

aaron_c

Senior Member
Messages
691
@npeden

I'm afraid I have to backtrack just a little on what I said about histamine. Here is Rich Van K on the histamine-methylation connection and more:

Histamine is made from histidine, and tetrahydrofolate is needed to metabolize histadine to glutamate. When there is a partial methylation cycle block, tetrahydrofolate is not being produced at a normal rate by the methionine synthase reaction (this is what produces the elevated Figlu on a urine organic acids test). It may be that more of the histidine goes into forming histamine when the conversion to glutamate is impeded by low tetrahydrofolate.

The other aspect to consider is the breakdown of histamine. If this is slow, histamine can build up. There are two main pathways for this. One is a methyltransferase pathway, and a partial methylation cycle block would be expected to interfere with it. The other is diamine oxidase, which requires vitamin B6 (actually its active form, P5P) and copper. If either of these is deficient, it could slow the breakdown of histamine and produce higher levels of it.

What can be done? Well, together with your physician, you might check the levels of copper and B6, and supplement if low. If copper is supplemented, zinc should also be supplemented at a dosage that is a factor of 10 or 15 higher, to keep them in proper balance. It's also important not to overdo the copper, because it can produce oxidative stress via the Fenton reaction.

EDIT: The methyltransferase pathway he mentions is the main one in the brain, and it uses SAMe as the methyl donor.

The THF deficiency would only be an issue in a folate deficiency or methyltrap situation (where one's folates are trapped as methylfolate.) Assuming that one has taken the correct supplements to avoid those situations, methylation mostly lowers histamine levels in the central nervous system, but not elsewhere. Which makes me wonder if a histamine blood test will have much bearing on methylation status.

At best, it seems like CNS histamine could be a decent measure of methylation status, particularly if B6 and copper levels were well within norms. But since a spinal tap is painful and expensive, symptoms might be the only guide. Perhaps we could expect insomnia that is mitigated by substances that lower histamine to become less severe as methylation status improves?

I realize I am probably just ruminating. But I do hope you find something that works for you,

Aaron C
 
Last edited:

npeden

NPeden, Monterey, CA
Messages
81
Hi @npeden

At this point, I also wonder how much of methyl sensitivity is just taking time to "get used" to a higher dose of methyl groups. Because while methylation of monoamines is one function of SAMe, it is not the only use of methyl groups, and I suspect that finding the best level of methyl donors may not correlate with how many methyl donors initially prevent insomnia, et. I wonder if histamine levels, at least in those of us without DAO mutations, might ultimately be a better indicator of methylation status.

Since beginning to limit my B2, I have had used both a high and medium amount of methyl B12/methylfolate, and when I was raising the amounts, there has always been a period of "overmethylation," ie insomnia and feeling "cracked out." Over time, however, this has receded. For what it is worth, soon I will try to add methyl groups in order to help with my high histamine.

I realize I haven't given an answer, exactly. But I would love to hear how things progress. I am particularly interested if you try to add methyl donors to know if you also find that the overmethylation symptoms subside with time.

Well, I was just thinking of upping my riboflavin for my hi bp, with ND's help....I take a very limited amount now, 5 mg, but that may be a lot for an MTHFRer.

BTW I am green for DAO (DAO rs2070586 A GG -/-).

I am actually feeling better than I have in a long time. ND put me on passion flower (harmaline) for my MAO A and it has really helped my depression. I am also upping my intake of hydroxycobalamin. (Yasko has a good one I will order today as the one my ND sells take 40 to 60 drops to get me to 2-3k mcg. we are seeking.

Now we are working on the sleep but he hasn't proposed anything yet.

Sleeping pretty well on 1200 mg. of gabapentin and three squirts of organic, home made pot tincture. But I would like to get off both. I hope we can find something in my genes that can be appeased. My whole family has sleep difficulties. None of them will be tested.
 
Last edited:
Messages
76
Location
Southwest
I have recently started a trial of high-dose B2/Riboflavin to help with migraine prevention. I am taking 400mg to 600mg a day, and I have not noticed any ill-effects so far. There has been no over-methylation symptoms.

Cheers,
Silverseas2014