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Methylation - hb12 making me feel bad

Messages
9
Hi guys,

I have A1298C ++, and I was advised by my doc to take methylfolate, mb12 and hb12. So I started taking the hb12 in smaller doses, and boy did I feel a difference......a NEGATIVE IMPACT -> it made me down in the dumps for a few days. I tried this 3 times over the next couple weeks, with the same result. Does anyone know why I could be getting this reaction?

I don't have the guts to move onto methylfolate and mb12 as I'm worried I won't be able to cope at work..

I have high serotonin in urine, and blood. As well as high histamine in my blood.

According to my 23andme results I have the following +/+ in addition to the MTHFR A1298C:

DHFR CC +/+
GAD1 TT +/+
GAD1 GG +/+
MTHFD1 C105T CC +/+
MTHFR AA +/+
MTHFR TT +/+
MTHFR GG +/+
MTHFS CC +/+
MTRR GG +/+

As well as MAO-A R297R T + . Could this explain my high levels of serotonin? Many of the specialists and GP's I've seen were stuck as to why I have high levels....

Any comments would be greatly appreciated because I'm stuck myself as to what to do next...

Thank you.
 

Helen

Senior Member
Messages
2,243
Hi guys,

I have A1298C ++, and I was advised by my doc to take methylfolate, mb12 and hb12. So I started taking the hb12 in smaller doses, and boy did I feel a difference......a NEGATIVE IMPACT -> it made me down in the dumps for a few days. I tried this 3 times over the next couple weeks, with the same result. Does anyone know why I could be getting this reaction?

I don't have the guts to move onto methylfolate and mb12 as I'm worried I won't be able to cope at work..

I have high serotonin in urine, and blood. As well as high histamine in my blood.

According to my 23andme results I have the following +/+ in addition to the MTHFR A1298C:

DHFR CC +/+
GAD1 TT +/+
GAD1 GG +/+
MTHFD1 C105T CC +/+
MTHFR AA +/+
MTHFR TT +/+
MTHFR GG +/+
MTHFS CC +/+
MTRR GG +/+

As well as MAO-A R297R T + . Could this explain my high levels of serotonin? Many of the specialists and GP's I've seen were stuck as to why I have high levels....

Any comments would be greatly appreciated because I'm stuck myself as to what to do next...

Thank you.

Hi,
With your three MTHFR homozygote mutations you do need to support with methylfolate . You just write MTHFR? Which are they? I guess, but would know ;-). Did you start taking methylfolate or just hydroxycobalamin?

I think your methylation is blocked due to these mutations AND the MTRR ++ that increases your need for vitamin B12. Then taking hydroxycobalamin that has to be methylated to the bioactive methylcobalamin will put more demand on the methylation that already is decreased. If you feel worse of alcohool this could be a sign of decreased methylation.

I would start with methylcobalamin and increase to a high dose. Injections would probably be the best though. Where you tested for B12 deficiency? Homocysteine or better methylmalonic acid (spelling?)? There are no valid B12 lab tests, but a deficiency may show up in these tests.

Then start with methylfolate and titrate the dose. www.MTHFR.org.

There are a lot more about cofactors to methylation and supplements for the Kreb´s cycle that you might benefit from, but I think this would be a good start.

Best of luck
 
Messages
9
Thanks for your response Helen.

Here's is a list of all my MTHFR results using the app on MTHFRsupport:

Gene & Variation rsID # Risk Allele Your Alleles Results
MTHFR 03 P39P rs2066470 A GG -/-
MTHFR A1298C rs1801131 G GG +/+
MTHFR A1572G rs17367504 G AA -/-
MTHFR C677T rs1801133 A GG -/-
MTHFR G1793A (R594Q) rs2274976 T CC -/-
MTHFR rs12121543 A AA +/+
MTHFR rs13306560 T CC -/-
MTHFR rs13306561 G AA -/-
MTHFR rs1476413 T TT +/+
MTHFR rs17037390 A GG -/-
MTHFR rs17037396 T CC -/-
MTHFR rs3737964 T TT +/+
MTHFR rs4846048 G GG +/+
MTHFR rs4846049 T TT +/+
MTHFS rs6495446 C CC +/+

I haven't started taking any methylfolate or methylb12 - just tried hydroxyb12 on its own...it wasn't a nice feeling to say the least.

Do you think i should try the methylb12 on its own, increase it slowly and then introduce the methylfolate? I've got all the supplements in my cupboard ready to go, but I'm just a little worried about taking them.

I haven't had a drop of alcohol all year, in an attempt to improve my health, but yes when I did drink, I did tend to get more affected quicker, and overall unwell feeling over the last couple years.

I've had my serum b12 tested, and it was within range for the lab. No tests for Homocysteine or BMA completed. But will request.

Thanks again,

E
 

Helen

Senior Member
Messages
2,243
@Earlyshine

I am sorry I am not used to see the MTHFR SNP`s more than in the methylation panel by Yasko or GeneticGenie, so I don´t know what the rs numbers correspond to. Glad to see that your MTHFR C677T , is ok though as this is the SNP that is supposed to be the most important to look at concerning methylfolate.

Yes, as an answer to your question! I understand you are hesitating due to earlier reaction, but in some way you have to try to add B12 (first) . Hope you have a good brand of MCbl. The reaction could also depend on a reaction to methylation so if you are ready with some niacin to "cool down" a methylation that you eventually can´t tolerate, you would be as safe as possible when you test. You experience from alcohool makes sence. Many people need a high dose to get an effect from B12 so going slow might take a long time before you notice any result. Best of luck!
 
Last edited:
Messages
9
Thanks Helen! I really appreciate your responses.

I've just taken my first mb12 oral tablet this morning, following breakfast - 1mg from Thorne Research.

Will update this thread with how I go with it. I'm sure there are others out there that will come across hb12 issues as well.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Thanks Helen! I really appreciate your responses.

I've just taken my first mb12 oral tablet this morning, following breakfast - 1mg from Thorne Research.

Will update this thread with how I go with it. I'm sure there are others out there that will come across hb12 issues as well.

Hi Earlyshine,

When swallowed absorption is about 1% + up to 10mcg. When taken sublingually or under lip for 45-120 minutes the range of absorption is 10%-33% and typically 15-25%. So far the most effective brand is Enzymatic Therapy B12 Infusion. And the Anabol Naturals Dibencoplex 10mg, one can use a small part of the contents of the capsule between the lip and gum for AdoCbl, for mitochondria, nerve repair and control inflammation. Good luck.
 
Messages
9
Thanks for the advice Freddd. Ive just ordered the Enzymatic b12.

Do you suggest i bump up the dosage to 2 tablets after a couple weeks?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Thanks for the advice Freddd. Ive just ordered the Enzymatic b12.

Do you suggest i bump up the dosage to 2 tablets after a couple weeks?

Hi Earlyshine,

I prefer to make changes by the clues. So for MeCbl, the neurological brightening was an incredibly important clue for me. It got going with 1 tablet. I had a bunch of starts and stops because of ineffective brands. The Enzy product went backordered all over the USA in less than a month after announced my results. So then I ordered 10 brands and started the study with 5 persons hypersensitive to MeCbl differences to pick out the most effective brands. So after I found a suitable replacement I had fresh startup all over again. It was really depressing to have my burning bladder and tongue which had 99% recovered all come back in weeks. The backorder condition lasted about 3 months. After that I found that a combination of 2 or 3 different brands, each at least 3 stars and at least 1 5 star brand were more effective than a single brand. I also found that 1 tablet several times per day maintained higher levels of healing until I reached equilibrium, which took about 9 months. When the neurological brightening faded regardless of the sublingual dose I started the next thing I had found, AdoCbl. Keeping the neurological brightening going turned out to be my best guide to healing. I didn't crank it to the max, but rather just kept it going which worked until about 15mg sublingually a day after which more made no difference until I added AdoCbl. Then Metafolin became available. It took me 5 years to work out the deadlock quartet in practice, including potassium. Since then it has been about adding in the various modifiers and balance. That all went on after I was trying to heal the damage from the glutathione trial.
 
Messages
9
Hi Freddd, when you say neurological brightening, you mean removal of brain fog, right?

What glutathione trial caused you damage. I have some NAC on order at the moment, recommended by my doctor to assist with Glutathione. Should i be weary?

Thank you for sharing your insight. :)
 

Helen

Senior Member
Messages
2,243
@Earlyshine
I would first concentrate on increasing the dose of MCbl. There is a lot of experience of treatment with only B12 and folate at a ME-clinic close to where I live. Including my own experince and lots of others. People start with injections, 10 mg of methylcobalamin, and very few have bad reactions on that. MCbl is very safe even in very high doses. If any reaction, it will not do long-time harm. So, if you don´t have any bad reactions on the B12 so far, I should increase as soon as possible. At least 2000 mcg has been found to be necessary, but we never know about uptake from intake. With your MTRR mutation you might need high, daily dose, or frequent injections.

Then you have all your MTHFR mutations that have to be compensated for. Methylfolate should not be overdosed. Richvank wouldn´t go higher that 400 mcg (half of it folinic acid). If I rememer right, Dr. Ben Lynch recommends a maximum of 800 mcg. I would titrate with the Mega B folate from Yasko . One drop 67 mcg and an increase every third day e.g.

I would be a bit careful with glutathione. Some people have reacted bad to it, and if you get your methylation going the glutathione production should start by itself. Glutathione as supplement now might mess everything up for you. Your mutations, and your need, is so clear. But, some people feel bad when they add methylfolate and some have felt better with a little glutathione as it might decrease at the beginning of a methylation protocol (B12+folate).

There are researchers, like Richvank, who don´t recommend more than 300 mcg NAC if you have amalgam fillings.

I do hope you will feel a lot better when you are on adequate doses of B12 and methylfolate.They are the core supplements. I would add supplements separately and with a few days between so that you can keep track of reactions, good or bad. Hope this can be of some help though my bad language. Don´t make it more complicated than this when you start, is my opinion. Later on you can try to adjust if it won´t work well for you. Also, a good B-complex is a base to be sure that you have enough of the most important co-factors. Good luck!
 

caledonia

Senior Member
I found out recently I don't tolerate hydroxycobalamin. But my reaction was different - a revved up, over stimulated feeling, and it didn't do any of the things that methylcobalamin does for me (metal detox and improvement in MCS).

Are those your only methylation mutations? Do you have COMT, CBS, etc.? Can you post your whole methylation panel?
 
Messages
9
Thank you for your support Helen. I agree, simple and slowly is best. Its easy to get impatient sometimes, when all you try doesnt improve things...and often get worse.

Its amazing how little people down here in Sydney know about Methylation. Chatting to you and Freddd has been a breath of fresh air. My test results; elevated histamine in blood, elevated serotonin in blood and urine, high creatinine level in urine only...basically left doctors unsure what the problem could be. Then learning more about methylation I find that the high histamine is likely due to undermethylation. My serotonin levels are probably due to my MAO-A + gene(apparently called the warrior gene). Although still not sure about my high creatinine levels from my 24 urine sample...maybe my body is expelling something -> on Jan 1st this year I stopped all alcohol, smoking(after 15 years), and eating mainly organic. I think my cycle may have gone into shock from going so clean after a below par lifestyle.

Reading through other peoples experiences has been very helpful on a number of different levels :)

When you say a good b-complex, it should be one without folic acid, right?
 
Messages
9
Hey Caledonia,

In addition to the above i have

ACE Del16 +/-
ADD1 G460W +/-
BHMT +/-
COMT H62H +/-
COMT V158M +/-
DAO +/-
NOS2 +/-
NOS3 +/-
PEMT +/-
SHMT1 +/-
VDR BSM +/-

CBS is all -/-

Yeah hb12 appears to just make me more anxious right now, as well as just making me feel really flat. I plan to give it another shot once i get my cycle going with mb12 and methylfolate.
 

Helen

Senior Member
Messages
2,243
Thank you for your support Helen. I agree, simple and slowly is best. Its easy to get impatient sometimes, when all you try doesnt improve things...and often get worse.

Its amazing how little people down here in Sydney know about Methylation.

Chatting to you and Freddd has been a breath of fresh air. My test results; elevated histamine in blood, elevated serotonin in blood and urine, high creatinine level in urine only...basically left doctors unsure what the problem could be. Then learning more about methylation I find that the high histamine is likely due to undermethylation. My serotonin levels are probably due to my MAO-A + gene(apparently called the warrior gene). Although still not sure about my high creatinine levels from my 24 urine sample...maybe my body is expelling something -> on Jan 1st this year I stopped all alcohol, smoking(after 15 years), and eating mainly organic. I think my cycle may have gone into shock from going so clean after a below par lifestyle.

Reading through other peoples experiences has been very helpful on a number of different levels :)

When you say a good b-complex, it should be one without folic acid, right?

Hi again,

I can tell it is the same in Sweden. Some doctors know about one-carbon metabolism or mono-....instead of methylation.
Show them the excellent figure that Amy Yasko has on her homepage :). Maybe it will be a wake-up. Cancer doctors know that their treatment might increase the need for methylfolate.

Your high creatinine level might have to do with your muscles. Are you loosing strength and/or muscle mass? it can have to do with an affected Kreb´s cycle that is connected to the methylation. There are supp´s to support.. Check figure of the Kreb´s cycle by Yasko or Rich van Konynenburg. I think they will show

Yes, about your high histamine. Could be quite right.

Alcohool needs to be methylated - unfortunately. Hope you have had some benefits going clean..

Yes, about a good B-complex - no folic acid. Thorne has got one good with folinic and methyl folate. Good, I think when you have found out your need for bioactive folates, but maybe a bit low doses of the other B´s. Freddd had one good brand in a post recently. No folates at all.

By, for now :)
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
Hi Earlyshine,

I prefer to make changes by the clues. So for MeCbl, the neurological brightening was an incredibly important clue for me. It got going with 1 tablet. I had a bunch of starts and stops because of ineffective brands. The Enzy product went backordered all over the USA in less than a month after announced my results. So then I ordered 10 brands and started the study with 5 persons hypersensitive to MeCbl differences to pick out the most effective brands. So after I found a suitable replacement I had fresh startup all over again. It was really depressing to have my burning bladder and tongue which had 99% recovered all come back in weeks. The backorder condition lasted about 3 months. After that I found that a combination of 2 or 3 different brands, each at least 3 stars and at least 1 5 star brand were more effective than a single brand. I also found that 1 tablet several times per day maintained higher levels of healing until I reached equilibrium, which took about 9 months. When the neurological brightening faded regardless of the sublingual dose I started the next thing I had found, AdoCbl. Keeping the neurological brightening going turned out to be my best guide to healing. I didn't crank it to the max, but rather just kept it going which worked until about 15mg sublingually a day after which more made no difference until I added AdoCbl. Then Metafolin became available. It took me 5 years to work out the deadlock quartet in practice, including potassium. Since then it has been about adding in the various modifiers and balance. That all went on after I was trying to heal the damage from the glutathione trial.

Freddd was your MB12 trial using equivalent doses of the different brands? Does taking more of a 3 star brand equal the Enzymatic Therapy? I'd like to raise my dose of MB12 but the Enzymatic Therapy only being in 1mg tablets does get rather expensive when taking multiple tablets daily. So for example could 1 tablet of 5mg 3 star brand replace say 2 or 3 tablets of the 1mg enzymatic therapy?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi Sea,

No, taking more of a 3 star brand doesn't replace a 5 star. I do want to say, that 1mg or the Enzymatic Therapy does more than any other current brand. However, a mix of the Enzy and another one might work a little better or penetrate a little deeper than the ENZY alone. Good luck. Try it and tell us what the results were.
 
Messages
9
Took my first cap (half of a 1mg cap, threw the other half out) of methylfolate this morning...started feeling edgy, hands were a little shaky, and an all round nervousness..however, i then drank a bunch of coconut water, and 20 minutes later i felt like i was back to normal. Potassium did the trick! I read this advice somewhere in one of Freddds' posts I think!
 
Messages
9
**UPDATE**

Hi, so I have been supplementing methylfolate and mb12, and I am feeling better.

However, I had a bunch of blood tests done over the weekend, and all were ok except now my liver AST and ALT have spiked tremendously.

AST 182 (should be less than 40)
ALT 185 (should be less than 40).

I had these previously tested and they were fine. So something I've been taking recently has caused the spike.

I also take P5P, Magnesium, and Zinc. Nothing at excessive levels.

My doctor recommends that I stop all supplements as it looks like something is throwing it out. I was just wondering, does this spike sound normal? Has anyone else experienced such a situation?

I don't particularly want to stop the methylfolate and mb12, but I need to get my levels down before I damaged my liver (if in fact it is due to the supplements). I'm at a crossroads...
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
**UPDATE**

Hi, so I have been supplementing methylfolate and mb12, and I am feeling better.

However, I had a bunch of blood tests done over the weekend, and all were ok except now my liver AST and ALT have spiked tremendously.

AST 182 (should be less than 40)
ALT 185 (should be less than 40).

I had these previously tested and they were fine. So something I've been taking recently has caused the spike.

I also take P5P, Magnesium, and Zinc. Nothing at excessive levels.

My doctor recommends that I stop all supplements as it looks like something is throwing it out. I was just wondering, does this spike sound normal? Has anyone else experienced such a situation?

I don't particularly want to stop the methylfolate and mb12, but I need to get my levels down before I damaged my liver (if in fact it is due to the supplements). I'm at a crossroads...

Hi Earlyshine,

It is estimated that 50% of the body's B12 is in the liver, most of it being used to make ATP and enzymes needed for detoxing things. This could also be one of those way behind type things that is so common at startup. Nobody though has ever had tests and we are barely beginning to trace out the actual healing path and collecting any clinical data. Everything was in some kind of terrible meta-stable balance until methylation is started. Then everything becomes unbalanced but works towards a new balance with everything healing quicker. I have to say I have no idea what goes high and only some of the things that go low.

Here are things to consider. This should be watched. I don't see how MeCbl and L-methylfolate could cause that unless it is a strictly temporary spike dealing with the accumulated products of cell death that hadn't been cleaned out in a while, and this is wild speculation at best. It is based on the assumption that with the b12/folate the liver is becoming more functional and somehow this is a result.

http://en.wikipedia.org/wiki/Liver_function_tests
AST/ALT elevations instead of ALP elevations favor liver cell necrosis as a mechanism over cholestasis. When AST and ALT are both over 1000 IU/L, the differential can include acetaminophen toxicity, shock, or fulminant liver failure. When AST and ALT are >3X of normal but not > 1000 IU/L, the differential can include alcohol toxicity, viral hepatitis, drug induced, liver cancer, sepsis, Wilson disease, post-transplant rejection of liver, autoimmune hepatitis, and steatohepatitis (non-alcoholic). When AST/ALT elevated are minor it may be due to rhabdomyolysis among many possibilities.

http://www.medicinenet.com/liver_blood_tests/page3.htm
for more information of more specific types.