Two Forms of B12 at Once = No Absorption?

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Hello all,

After identifying my B12 deficiency via an MMA test (623) we tried methyl shots with methylfolate but found I was having neuropathy. Stopping both methyls cleared up the neuropathy and using an hydroxy b12 1000mcg/Folinic acid lozenge in the AM along with an Adensoyl b12 1000mcg later in the afternoon was able to get my MMA down to 420.

At this point we switched to a blended Hydroxy/Adensoyl/Folinic acid lozenge (2000mcg) but after retesting two months later and several vertigo/fatigue issues, the MMA was back up to 607.

What could cause the same overall dosage and forms to make my MMA go back up? It’s like my body is not absorbing.

Is it that you can’t take two different forms of b12 at the same time or something where the body blocks more b12 because my serum b12 is over 2000? My folate recorded at greater than 20.

Regards,
K.
 

drmullin30

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Hello @K980 do you have Single Nucleotide Polymorphisms (SNPs) around b12 and folate metabolism? Those would provide a lot more insight into what might have caused your problem.

Without knowing that, my guess is that it was the use of hydroxocobalamin or folinic acid that killed your methylation or caused paradoxical folate and b12 deficiency and caused your MMA to rise. Your high folate and b12 numbers are very strong indicators of paradoxical folate and b12 deficiency.

The neuropathy could have been numerous things (not necessarily the folate and b12) including a start up symptom (neurological healing), oxalates, induced hypocalcemia (calcium deficiency) from sudden high dose b12 or if you have the wrong SNPS the folinic acid itself could have caused a folate deficiency.

I can't handle even trace amounts of folic acid or folinic acid because of my many methylfolate SNPS and hydroxocobalamin will totally stop methylation in certain people.
 

Pyrrhus

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Is it that you can’t take two different forms of b12 at the same time or something where the body blocks more b12 because my serum b12 is over 2000? My folate recorded at greater than 20.
There shouldn't be any problem mixing different forms of B12 at the same time. But be aware that, however you take B12, the body will only retain a fraction of the amount that you take.

For lozenges, the amount absorbed depends upon how long you hold the lozenge under your tongue. There is a slow absorption through the vascular tissue on the bottom of the tongue. If you immediately chew the lozenge to mix it with the haptocorrin in your saliva and then swallow it, then the amount absorbed will be limited by the amount of intrinsic factor in your gastrointestinal tract.

Even if you inject the B12, the amount retained in the blood will be limited by the amount of transcobalamin you have in your blood. If you already have high B12 levels in your blood, then there may be no more transcobalamin to hold onto any more B12.

using an hydroxy b12 1000mcg/Folinic acid lozenge in the AM along with an Adensoyl b12 1000mcg later in the afternoon was able to get my MMA down to 420.
You probably don't need the Adenosyl-B12. Your body only uses a very tiny amount of Adenosyl-B12, and as long as your glutathione levels are high enough, your body should be able to convert Hydroxy-B12 to any other form of B12. Glutathione is absolutely essential for the proper utilization of B12 in the body.

There are different ways to boost your glutathione levels, but the most common way is to take cysteine in the form of N-Acetyl-Cysteine (NAC). But be aware that NAC can come with some difficult start-up effects:
https://forums.phoenixrising.me/threads/glutathione-confusion.77255/#post-2222623
https://forums.phoenixrising.me/threads/glutathione-causing-anxiety-irritability.81246/#post-2304206

Hope this helps.
 
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Thank you for the feedback. I thought MMA was directly tied to Adensoyl b12. I take extra glutathione per day. I am COMT++ and MTHFR C277 double.

Any ideas why my MMA would go up when taking a hydroxy/Adensoyl/Folinic acid lozenge all in one (I always leave it under the tongue until it dissolves.

I had tried methylfolate but I gave me neuropathy (Comt ++) so I switched to folinic acid and folate levels are good without the neuropathy.

I feel weak, my ears are ringing, vertigo and no clue why the b12 combos aren’t working. Potassium and other levels came back great and I take a good amount of the other Bs.
 
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Hello @K980 do you have Single Nucleotide Polymorphisms (SNPs) around b12 and folate metabolism? Those would provide a lot more insight into what might have caused your problem.

Without knowing that, my guess is that it was the use of hydroxocobalamin or folinic acid that killed your methylation or caused paradoxical folate and b12 deficiency and caused your MMA to rise. Your high folate and b12 numbers are very strong indicators of paradoxical folate and b12 deficiency.

The neuropathy could have been numerous things (not necessarily the folate and b12) including a start up symptom (neurological healing), oxalates, induced hypocalcemia (calcium deficiency) from sudden high dose b12 or if you have the wrong SNPS the folinic acid itself could have caused a folate deficiency.

I can't handle even trace amounts of folic acid or folinic acid because of my many methylfolate SNPS and hydroxocobalamin will totally stop methylation in certain people.
I am suspecting I need to try methylcoblamin again given your comment on the hydroxy. I am COMT++ and when I stopped the methylfolate the neuropathy went away. For a while, when using hydroxy/Folinic in the AM and Adensoyl in the PM my MMA went down to 420 but using the combo of all three in one it has skyrocketed
 

drmullin30

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But be aware that NAC can come with some difficult start-up effects:
I would also advise caution when using NAC to boost glutathione. If you have SNPs around sulfur or glutathione metabolism (CBS, CYP1xx, CYP2xx, GSTP etc.) and/or problems with the sulfation cycle, NAC can cause major problems.

In addition, glutathione won't penetrate into cells if you are toxic with sulfites. Many other things interfere with the effectiveness of glutathione (free radicals, inflammation, mercury, oxalates, viruses, mold etc.) and it's a bit of chicken and egg problem when trying to increase b12 utilization and glutathione. You may also need glycine and glutamine in addition to cysteine to synthesize glutathione. Sometimes, but not usually the glycine or even less likely glutamine can be a limiting factor. Finally, if your methylation cycle isn't functioning correctly glutathione won't work correctly either.

Also, I know @Pyrrhus doesn't agree, but some people have found that NAC will cause a crash by driving b12 out of the cells and cause paradoxical folate deficiency but this is based on mainly anecdotal evidence but seems to be true in my case.

I have found the best way to raise glutathione is through alpha lipoic acid along with Vitamin E and C. Although alpha lipoic acid can be even more risky than NAC if you are mercury toxic or have sulfur metabolism issues.

I have also had huge success with coffee enemas for raising glutathione production in the liver.

Transcobalamin function can be compromised by SNPs on the TCN gene or lithium deficiency or other cofactor deficiencies which just adds to the problem of getting bioavailable b12 (cobalamin) into the cells.
 
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I would also advise caution when using NAC to boost glutathione. If you have SNPs around sulfur or glutathione metabolism (CBS, CYP1xx, CYP2xx, GSTP etc.) and/or problems with the sulfation cycle, NAC can cause major problems.

In addition, glutathione won't penetrate into cells if you are toxic with sulfites. Many other things interfere with the effectiveness of glutathione (free radicals, inflammation, mercury, oxalates, viruses, mold etc.) and it's a bit of chicken and egg problem when trying to increase b12 utilization and glutathione. You may also need glycine and glutamine in addition to cysteine to synthesize glutathione. Sometimes, but not usually the glycine or even less likely glutamine can be a limiting factor. Finally, if your methylation cycle isn't functioning correctly glutathione won't work correctly either.

Also, I know @Pyrrhus doesn't agree, but some people have found that NAC will cause a crash by driving b12 out of the cells and cause paradoxical folate deficiency but this is based on mainly anecdotal evidence but seems to be true in my case.

I have found the best way to raise glutathione is through alpha lipoic acid along with Vitamin E and C. Although alpha lipoic acid can be even more risky than NAC if you are mercury toxic or have sulfur metabolism issues.

I have also had huge success with coffee enemas for raising glutathione production in the liver.

Transcobalamin function can be compromised by SNPs on the TCN gene or lithium deficiency or other cofactor deficiencies which just adds to the problem of getting bioavailable b12 (cobalamin) into the cells.
thank you. Given this, what forms of b12 and how much should I take? Should I switch to Methylcoblamin again?
 

Pyrrhus

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I would also advise caution when using NAC to boost glutathione. If you have SNPs around sulfur or glutathione metabolism (CBS, CYP1xx, CYP2xx, GSTP etc.) and/or problems with the sulfation cycle, NAC can cause major problems.
Do you have any scientific evidence to back up this claim?

In addition, glutathione won't penetrate into cells if you are toxic with sulfites
Do you have any scientific evidence to back up this claim?

some people have found that NAC will cause a crash by driving b12 out of the cells and cause paradoxical folate deficiency but this is based on mainly anecdotal evidence but seems to be true in my case.
Do you have any scientific evidence to back up this claim?

I have found the best way to raise glutathione is through alpha lipoic acid along with Vitamin E and C.
Do you have any scientific evidence to back up this claim?
 

drmullin30

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Sorry @Pyrrhus you're right, I don't have any clinical studies to back this up but nobody is going to fund these types of studies because they aren't based on pharmaceuticals and very few doctors have even heard of nutrigenomics.

I've already admitted this was anecdotal. It's also very individual based on your genetics and epigenetics so I'm honestly not sure how you would perform a typical clinical study on the effectiveness of a personalized nutrigenomics program other than implement it in clinical medical practice which is what Yasko and Roberts have done.

I'm speaking from my direct experience with sulfur toxicity, NAC crashes and the work done by Dr. Yasko and James C. Roberts. Also, Fred's study is very convincing. The consistent symptomology and b12 dumping they measured in urine seems to be pretty good scientific evidence in my mind even if it is only a sample size of 9 or 10 but as I said, this could all apply only to certain genotypes.

When I was using NAC, my urine sulfites and sulfates were off the charts, as was my ammonia levels and my glutamate levels (which is inconsistent with sufficient glutathione). I had terrible fatigue, depression anxiety, acne, joint pain, heart palpitations and brain fog. Those symptoms all reduced or stopped when I removed NAC from my regimen based on Fredd's advice. Call my reaction detox or startup if you want but I had zero improvement using NAC and I used it for years.

It makes sense to me that if a cell is already filled with sulfur molecules to the point of toxicity it's not going to permit more into the cell no matter what form it's in whether it's glutathione, cysteine, sulfate, SAMe or other. That's a simple logic and bears out in mine, and other people's experience and is supported by Yasko and Roberts work. If your trans-sulfuration pathway is overloaded, adding more sulfur doesn't seem to make much sense.

As far as alpha lipoic acid goes, the evidence there has been gathered by the Lester Packer lab and is detailed in the Antioxidant Miracle and is evidenced anecdotally by my continuing reduction in b12 and folate doses as well as inflammation and an excellent increase in energy and drive since adding it into my regimen on a regular basis.

You can wait around for clinical studies if you want. I don't have time to wait. I'm 45 years old and I'm in better physical and mental health than I have ever been and I was a very sick individual. I was firmly on the Asperger spectrum, I had regular bouts of PEM, arthritis in my knees, hips and shoulders, OCD, panic attacks, suicidal depression and brutal arrhythmias that on occasion would wake my wife up from the bed literally bouncing in time with my heart. If I had listened to what doctors told me all these years I would be dead now.
 

drmullin30

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thank you. Given this, what forms of b12 and how much should I take? Should I switch to Methylcoblamin again?
I'm sorry @K980 I honestly have no idea based on what little information you provided. I take methylcobalamin and adenosylcobalamin and avoid hydroxocobalamin but I made that decision based on a thorough understanding of my genome and epigenetic and symptomatic history.
 
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Maybe this would help:

- Had an MMA of 623 and a doc gave me methyl shots and a methylfolate sublingual. MMA went down to 411 but neuropathy started

- Referred to another doctor who found that beyond my MTHFR C77 double snp, I am COMT++. Stopping the methylfolate cured my neuropathy. At this time we were trying a liquid cynacoblamlin but my MMA stayed around 489 to 500

- Started hydroxy/Folinic acid lozenge with Adensoyl in the PM each day and MMA came down to 423

- Thought that switching to a hydroxy/Adensoyl combo lozenge with a separate lozenge of Folinic acid would be the same as its both forms and the same daily amount (2000mcg). MMA came back at 607
 
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Do you take the methyl and Adensoyl on the same day or rotate them out of curiosity? I read another forum post that said you need to space out the different forms or else they compete for the cell.
 

drmullin30

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Do you take the methyl and Adensoyl on the same day or rotate them out of curiosity? I read another forum post that said you need to space out the different forms or else they compete for the cell.
I take both everyday in what most would consider insanely large doses. I've never heard of or had any problems taking both at the same time and have found they are more effective together. In the past, I've also taken hydroxo and methylcobalamin together and didn't have any major issues. I'm not sure why they would interfere with one another they are used in different pathways.

In order to get cobalamin into the cells and functioning you need to make sure you're not deficient in many other things. Including, pyridoxine (B6), selenium, carnitine, riboflavin (B2), folate, iodine and molybdenum as well. Not to mention ALL of the other b vitamins.

Your COMT SNP can cause a treatment conflict with methyl donors like methyl folate and methylcobalamin and can cause anxiety. I have never read anything about COMT causing neuropathy. I have this SNP too and methylcobalamin has caused me to have anxiety and adrenaline problems if methylation isn't functioning well all the way around the cycle. I have my methylation functioning fairly well now and this keeps my SAMe to SAH (methionine to homocysteine) ratio higher so the COMT enzyme can work optimally. I also avoid other things that can slow this down like green tea.

For me, this is a much bigger issue than just b12 and folate. Methylation is a complex cycle that occurs millions(?) of times a day in each and every cell and every individual's methyl cycle is unique and requires unique solutions.

That being said here are a number of question to consider if you are trying to treat CFS/ME with supplementation and diet:

When you say neuropathy do you mean pain, tingling or numbness?
What's the status of your MTRR, MTR, CBS, ACAT, TCN, DHFR, BMHT MTHFS MOCS, VDR genes? (this is a small subset of the potentially impactful genes)
With the MTHFR C677T SNP if you were having issues with folate you might have high homocysteine. Have you had this measured?
What are your primary symptoms?
What other supplements are you taking?
What pharmaceuticals are you taking?
What's your diet like?
Do you have Celiac disease?
Do you have a problem with oxalates?
Other food allergies e.g. dairy nuts, fish, salicylates?
Do you have thyroid issues?
Do you have other autoimmune issues?
Do you have kidney problems?
Have you had your cortisol and other hormones checked?
Do you have estrogen dominance?
What's your cholesterol status?
Do you get PEM?
Do you have joint pain?
Are you overweight/underweight?
Are you toxic in mercury, aluminium, cadmium or copper?
Are you deficient in calcium, magnesium, zinc or potassium?

Again this is a subset of things that are important to know. Knowing what I know now, I wouldn't even start without having most of this information at my disposal. If I'd had all of this information in the beginning I could have saved a significant amount of time and money. I have it now, and I'm applying it with success. Better late than never I guess.
 
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Thank you for all your assistance with this complex (more than I thought it would be) issue:

When you say neuropathy do you mean pain, tingling or numbness?

Numbness/pain in legs (no gone since stopping methylfolate)

What's the status of your MTRR, MTR, CBS, ACAT, TCN, DHFR, BMHT MTHFS MOCS, VDR genes? (this is a small subset of the potentially impactful genes)

I have not had these checked

With the MTHFR C677T SNP if you were having issues with folate you might have high homocysteine. Have you had this measured?

Yes, it was last a little above 10

What are your primary symptoms?

Vertigo, especially when walking, poor digestion, weakened, some sleep issues, energy, increased Tourette’s when eating protein

What other supplements are you taking?

Zinc, D3 and K2, Magnesium, DIM, Fish Oil, Megaspore

What pharmaceuticals are you taking?

Northera, clonazepam, florinef

What's your diet like?

Gluten free, mostly lean proteins, veggies, fruits and rice cereals

Do you have Celiac disease?

No

Do you have a problem with oxalates?

High oxalates

Other food allergies e.g. dairy nuts, fish, salicylates?

basil, congested drinking milk

Do you have thyroid issues?

no

Do you have other autoimmune issues?

mitochondrial issues, CIRS

Do you have kidney problems?

no

Have you had your cortisol and other hormones checked?

yes, functional cortisol was a bit on the low side but my doc said it’s related to my gut/health issues and once we fix those that would be fixed

Do you have estrogen dominance?

No

What's your cholesterol status?

in range

Do you get PEM?

no

Do you have joint pain?

no

Are you overweight/underweight?

neither, in a good spot.

Are you toxic in mercury, aluminium, cadmium or copper?

no

Are you deficient in calcium, magnesium, zinc or potassium?

no, recent labs showed great
 
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Potential Ah Ha! About 6 weeks ago I ran out of the organ meats I was taking (high in Riboflavin). With me having the MTHFR C77T double, thinking that I am not converting the folate I have to match up with the b12 (thus the high folate and high b12), as it’s not getting used because you need the right folate but without B2 it won’t bind properly to make that conversion happen
 

drmullin30

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Potential Ah Ha! About 6 weeks ago I ran out of the organ meats I was taking (high in Riboflavin). With me having the MTHFR C77T double, thinking that I am not converting the folate I have to match up with the b12 (thus the high folate and high b12), as it’s not getting used because you need the right folate but without B2 it won’t bind properly to make that conversion happen
@K980 absolutely riboflavin is essential for folate and b12 to function. I take up to 100 mg per day of B2.
 
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Thanks for all your help on this. I will up the intake and see the results. Will try to post here once I have enough time to see the results.
 
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Started having leg cramps and increased nausea. I am upping my potassium intake in the hopes that b12 is finally getting into my cells.

Is it normal to feel much worse when b12 is actually getting absorbed?
 

Judee

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If you have an infection hiding in your body somewhere, you may be feeding the bad guys.

SIBO doc on YT said bacteria need methyl donors too. I'm truly beginning to suspect that is why so many of us have deficiencies even when we supplement in large doses or consistently and why we feel worse when we do.

I am working on getting my bacteria load down and after years of hair that I could have threaded through a drinking straw when wet, it feels thicker now. My nails also seem to be growing faster than usual. I think killing the bad bacteria is leaving more nutrients for my body to use.