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Help with B12 confusion

Messages
28
Hi,

After getting genetic testing done and identifying several mutations I've started supplementing. I've started using @Freddd's protocol as my primary reference and have seen some results although overdid it a bit with 5-MTHF (see other post, lesson learnt).

My confusion now comes from having processed my 23andme data through a site called NutraHacker. That has given me a table for my results and suggestions for what to take and what to avoid.

For some mutations I'm told to encourage Hydroxy B12 and avoid Methyl B12, Methyl donors.

For others I'm told to encourage Methyl B12 and TMG which is a Methyl donor.

I'm definitely seeing benefits from taking Methyl B12 and have also been taking some TMG and feel good when I use it and notice something is missing on the days I don't.

Should I also be looking to take Hydroxy B12? It is recommended against COMT genes (rs4633 and rs4680).
 
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Messages
15,786
@Enigmatic - Fredd's protocol is primarily based on his own experiences, and he categorically refuses to recognize that different people might respond differently. Hence his refusal to have his own relevant SNPs tested, even when people have offered to pay for it.

Yasko and associated groupies are of the opinion that certain SNPs, which result in slower use of methyl groups, will result in reduced tolerance for supplements containing methyl groups. This is a logical and sensible possibility, but it has never been proven scientifically that a poor tolerance for MethylB12 is due to specific SNPs or genes.

At the end of the day, if you feel good taking MethylB12 and aren't having issues with potassium or other side effects, then there's no reason to switch. If you are having any problems on MethylB12, or are worried about potential potassium issues, then HydroxoB12 is a safe alternative.

Do what works best for you, and don't worry too much about the various ideologies, especially when those ideologies are lacking scientific support.

There are two forms of B12 which the body actively uses. One is MethylB12 and the other is AdenosylB12. MethylB12 is used in methylation, and AdenosylB12 is involved in energy production in the Krebs Cycle. HydroxoB12 is the version stored in the liver, and is readily converted to either of the active forms. The active forms will convert to HydroxoB12 if they're being stored instead of used, such as probably happens if supplementing more than your body can immediately use.
 

xchocoholic

Senior Member
Messages
2,947
Location
Florida
Thanks for keeping up with this info @Valentijn.

I agree with you on taking whichever supplement meets your needs. I've found that I could tolerate various supplements for periods up to a year or two but then developed an intolerance to them.

My reaction to Adenosyl b12 was interesting because I actually felt physically stronger when I took it. That didn't last tho.

I first felt energized by sublingual mb12 but it didn't last. I had 1 injection of mb12 + 2 other b's that gave me the energy I'd had as a child. It lasted for about 4-6 hours. I crashed the next day tho.

I suspect that because I'm a celiac and can't digest food properly my body needed all these nutrients due to untreated celiac disease. I went gfcfsf, etc in 2005. 15 years post me/cfs onset.

But later I developed intolerances (chemical taste in mouth and smell on skin) to these due to chronic leaky gut and taking them everyday. I've tried to re-introduce these multiple times but they make me feel toxic.

Nowadays, I get my B's from real food, including fresh juices, and Vitamin water xxx. The xxx gives me a boost I can't get from foods including fresh homemade veggie juice.

Sorry for the book. Tc .. x
 
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caledonia

Senior Member
You can get a starting point from looking at genes, but you will still need to do trial and error.

The influence of all genes is not equal. Some are major players and some are minor players. The more mutations you have in a particular gene or group of similar genes, the more influence it can have.

Yasko has a nifty table at her Simplified Roadmap page, about halfway down the page, which suggests types of B12 for your COMT/VDR combination. http://www.scribd.com/doc/132017201/Dr-Amy-s-Simplified-Road-Map-to-Health

It would be nice if Nutrahacker came up with a way to measure the various genes' influence on each other, so it wasn't so confusing, but I'm guessing the research isn't there yet - someday hopefully it will be....
 

Martial

Senior Member
Messages
1,409
Location
Ventura, CA
There is differing views on this issue depending on other people. I could tell you about my own experiences or what helped me but better to find out yourself. I would try picking up both and see how you feel. Personally I think it is bogus to say that methyl b12 and Hydroxy b12 cause different reactions, genes affect difference. Methyl b12 is just the bio available form, Hydroxy needs to first be converted to Methyl b12 before used by the body. If anything I suspect some people are sensitive to Methyl b12 and Hydroxy being less immediately active helps with those symptoms.
 
Messages
67
I wonder if several of you guys are realising that the body stores a small amount of B12 ready for use in the liver, so if you have a deficiency, there is going to be a big difference in: 1. taking whichever version of B12 when your body has none in store, and 2. stopping B12 when your body does in fact have it in store, a kinda time lag. (and I guess all the complex chemistry going on as well)
 
Messages
28
Thankyou all for the responses @Valentijn, @xchocoholic, @caledonia, @Martial and @Coolie.

Like I say, I was more confused about the recommendation to both avoid and take different forms.

Thanks to these responses and stuff I since found I should be OK with taking all forms (confirmed by table in link provided by @caledonia. Understand results may vary but I will now get some Hydroxy B12 and try it.

I've found posts by @Fredd where he is quite specific as to why he doesn't believe Hydroxy B12 should be used but everyone is different so I will try it and see what it does for me as that is the most valid test.

@Valentijn I have experienced some side effects since introducing the full protocol but I've yet to confirm exactly what is wrong. I know I took too much 5-MTHF but have scaled this back to only what I get in a B Complex capsule for about a week now.

I still do not feel right and have been having problems with my sleep again plus I have varying results with going to the toilet swinging between bunged up and very loose.

I am wondering if perhaps I have done something wrong with the introduction of L-Carnitine Fumarate but I cannot find anything about side effects for this and should perhaps switch to trying the Jarrow Liquid carnitine at a lower dose.

@caledonia The report from NutraHacker suggests a Genotype Freq of 48.7173% (COMT rs4633) and 48.2074% (COMT rs4680 ) for the genes requiring Hydroxy B12. For the ones requiring Methyl B12 they provide 34.2065% (MTR rs1805087), 19.7362% (MTRR s1801394) and 42.7445% (MTRR rs1802059).

@xchocoholic I'm looking forward to the day I can get everything I need from food but for now I know I have issues with stomach acid and bile production and general absorption of proteins and fats.
 

Freddd

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

After getting genetic testing done and identifying several mutations I've started supplementing. I've started using @Freddd's protocol as my primary reference and have seen some results although overdid it a bit with 5-MTHF (see other post, lesson learnt).

My confusion now comes from having processed my 23andme data through a site called NutraHacker. That has given me a table for my results and suggestions for what to take and what to avoid.

For some mutations I'm told to encourage Hydroxy B12 and avoid Methyl B12, Methyl donors.

For others I'm told to encourage Methyl B12 and TMG which is a Methyl donor.

I'm definitely seeing benefits from taking Methyl B12 and have also been taking some TMG and feel good when I use it and notice something is missing on the days I don't.

Should I also be looking to take Hydroxy B12? It is recommended against COMT genes (rs4633 and rs4680).

Hi Enigmatic,

HyCbl will possibly block the MeCbl effectiveness and cause partial methylation block all by itself. I find that the recommendations from the genes to be worse than useless, even damaging, in many case. They are basing these on tests that have validated partial methylation block as normal. HyCbl is less than 1% as effective as MeCbl, 100 to 10000 times less effective. HyCbl does not prevent 90% or so of MeCbl/AdoCbl deficiency symptoms. Those have become our mystery diseases. You can certain try it HyCbl but be sure you watch carefully what it does. The first thing it does to me is cause acne type lesions first on my scalp and face, and then spreading over the body the longer continued. Then my neurology starts worsening. In 3 days many of my B12 deficiency symptoms arte on their way back. I would stick with success and use the clues you are already getting from TMG and MeCbl and follow the path of healing.

HyCbl is damaging until 1% approximately is converted to MeCbl and to AdoCbl in total. It is only useful after that conversion.
 
Messages
28
Thanks for replying @Freddd.

I've ordered some but will hold off taking any. As per other topic you replied on, I will keep supplements to basics and treat with the quartet. I will wait until I'm firmly back on track before adding any changes in.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
I wonder if several of you guys are realising that the body stores a small amount of B12 ready for use in the liver, so if you have a deficiency, there is going to be a big difference in: 1. taking whichever version of B12 when your body has none in store, and 2. stopping B12 when your body does in fact have it in store, a kinda time lag. (and I guess all the complex chemistry going on as well)

Hi Coolie,

Despite years of researchers talking about the hypothetical "store" of b12 in the liver it doesn't exist, at least the way people think of it. HTC III transports waste cobalamins back to the liver where they are "stored" in the sewage lagoon until excreted in the bile. A sewage lagoon is not a water reservoir. The other large amount of b12 in the liver is working B12 in the liver being used to make ATP and enzymes for detoxing all sort of things. When the liver cells start breaking down, they release B12 into the serum. High serum B12 without supplementation is often a flag of liver disease and breakdown. This transport of junk cobalamins (like CyCbl, GlutationylCbl, NitroCbl and plant cobalamins in general) that get in the way competing for transport and gets them out of the body as part of the refinement process.
 
Messages
67
Hey @Freddd

Can you help interpret this if possible, my blood serum results for B12 and Folate: Serum vitamin B12 level XE2pf: Result 558 ng/L (normal range 211.0 -900.0)

Serum Folate level (42US.) 22.9 ug/L (normal range 4.0 - 20.0) ABOVE HIGH HREFERENCE LIMIT

The thing is - I didn't go to the doctor for these test until I had undergone all the numerous changes explained in my other forum posts including but not limited to my hair growing back and neurological changes such as my eyes staying in focus, and changes (some good and some bad) with my IBS. And all this was after a few weeks of supplementation. So.....


My doctors conclusion was that I will not know for sure if I was in fact low on B12 because the results show ok.

Actually I'm only taking a bog standard B COMPLEX which is responsible for my Folate being way over and the B12 is showing only pretty normal despite being on HIGH DOSE B12, which I then subsequently changed to Methyl after these tests.

I would like to hear your opinions as you know quite a bit about it from the sounds of it?

By the way, the separate liver function test showed as OK.
 

whodathunkit

Senior Member
Messages
1,160
Freddd said:
High serum B12 without supplementation is often a flag of liver disease and breakdown.
Hmmm. This is really interesting. Just quoting because it might help me remember and it's worth pointing out.
 
Messages
28
High serum B12 without supplementation is often a flag of liver disease and breakdown.

@Freddd, my serum B12 was 468 pmol/L and climbed to 600 pmol/L; this was prior to starting any B12 supplementation. My ALT is now close to double what it was just a month ago at 46 U/L and is outside the upper limit of the range (5-40).

My B6 is being supplemented for my Pyroluria but the result is very high at 1100 nmol/L.

Something isn't working right.
 
Messages
4
I am new to this forum and have never posted before, however I have (for decades now) had a serum b12 that is either very high or 'out of range' (now over 2000). My liver function tests are all ok according to the NHS (unfortunately I've lost all faith in our medical system-not fit for purpose).
I have ME/CFS and pernicious anemia so therefore have methylcobalamin injections and also discovered methylfolate a definate advantage for me. I found the NHS administered hydroxycobalamin were useless, however I was given no choice with this (usual for NHS).
I managed to 'cure' years of being hypothyroid (couldn't use thyroxine, had to go with a dissicated) by addressing methylation and now have a perfectly functioning thyroid (no meds required at all-big shock for me).
I wondered if years of multivitamin supplements with cyanocobalamin could be the culprit. I avoid cyano now (as well as folic acid) however I still have a high serum b12 and would love to find out if there is anything else I could do to lower it?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
@Freddd, my serum B12 was 468 pmol/L and climbed to 600 pmol/L; this was prior to starting any B12 supplementation. My ALT is now close to double what it was just a month ago at 46 U/L and is outside the upper limit of the range (5-40).

My B6 is being supplemented for my Pyroluria but the result is very high at 1100 nmol/L.

Something isn't working right.

Hi Enigmatic,

Something isn't working right

Well, whatever it is, your B12 isn't high. They are speaking of 3000-10000 pg/ml without supplementation. Yours is right around the area that Japan classes as the lower acceptable limit (550pg/ml). A rise of 132pmol/L (a slightly different measurement, can be converted, using a conversion factor of 1.35 pg/ml = 1 pmol/l) can be caused by a mcg or two absorbed in a meal. It is "low normal", not that even the "high limit" (no such thing, a statistical aberration) signifies much. Studies have shown that people can have responsive to MeCbl peripheral neuropathies at over 1500pg/ml with the average in a study of over 700pg/ml to start with. In that study 62% of the MeCbl responsive people would have been excluded from the study based on "normal" test results except that they used symptoms as the qualifiers, not test results. In other words the "normal" tests would have kept almost 2/3 of people responding to treatment from being treated.

I would estimate that it would take 15,000pg/ml to even approach asymptomatic and that assumes a decent level of l-methylfolate and other factors.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hey @Freddd

Can you help interpret this if possible, my blood serum results for B12 and Folate: Serum vitamin B12 level XE2pf: Result 558 ng/L (normal range 211.0 -900.0)

Serum Folate level (42US.) 22.9 ug/L (normal range 4.0 - 20.0) ABOVE HIGH HREFERENCE LIMIT

The thing is - I didn't go to the doctor for these test until I had undergone all the numerous changes explained in my other forum posts including but not limited to my hair growing back and neurological changes such as my eyes staying in focus, and changes (some good and some bad) with my IBS. And all this was after a few weeks of supplementation. So.....


My doctors conclusion was that I will not know for sure if I was in fact low on B12 because the results show ok.

Actually I'm only taking a bog standard B COMPLEX which is responsible for my Folate being way over and the B12 is showing only pretty normal despite being on HIGH DOSE B12, which I then subsequently changed to Methyl after these tests.

I would like to hear your opinions as you know quite a bit about it from the sounds of it?

By the way, the separate liver function test showed as OK.

Hi Coolie,

In Japan, 550pg/ml is the lower limit for b12 and the official b12 is MeCbl. Japan has 1/5 the Alzheimer's rate of the USA. The 160-210pg/ml "lower limit" in various countries ignores a lot of deficient people It is a pathetic lower limit. It could be that low because of a low amount of l-methylfolate. Unconverted folic acid can come out as "high" folate. It's sad that B12 is so poorly understood. In much research it is stated over and over that the only way to know if any specific person is going to benefit from B12 is to see if they benefit from a trial, then the docs want to ignore the benefits. Clearly you are benefiting from MeCbl. I would keep on benefiting. The "reference limits" these days include chronic low b12 and folate as "normal". So an MCV of > 92 would have been alerted 50 years ago, > 96 10 years ago and > 102 (not all, some labs) now. MCH has also risen and all the other "borderline" symptoms of b12/folate deficiencies are now ":normal". I was dying with "normal" tests. My doc said "sickest normal person he had ever seen".
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Hi Coolie,

In Japan, 550pg/ml is the lower limit for b12 and the official b12 is MeCbl. Japan has 1/5 the Alzheimer's rate of the USA.

Not disputing your B12 info, but the Japanese do seem to have a generally much healthier diet than the 'West', based largely on plants and fish. They have longer lifespans and generally better health, I believe.

They also have significantly different incidences of various SNPs, I understand.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Not disputing your B12 info, but the Japanese do seem to have a generally much healthier diet than the 'West', based largely on plants and fish. They have longer lifespans and generally better health, I believe.

They also have significantly different incidences of various SNPs, I understand.

The point is that the only country using MeCbl as the official B12, is also the only country with the highest lower limit set based on the effectiveness characteristics of MeCbl instead of CyCbl/HyCbl. The Alzheimer's is maybe connected 2 ways; low CSF cobalamin levels in those with Alzheimer's as research has shown and also through the correlation (correlation is not causality) with more MeCbl used to maintain higher serum levels of B12 correlates with lower level of Alzheimer's in the population. Their cultural profile of diseases is quite different from the USA and UK for many reasons including diet and genes. Japanese folks who grow up in the USA and eat an American diet have the local American disease profile pretty much. The Japanese research also has looked at these various neuropsych diseases and test high dose (50mg/day) MeCbl and direct injection of MeCbl into spinal fluid. They ask some of the questions that become relevant with some experience and knowledge of MeCbl.

The Japanese were very interested in neurological damage from their mercury disaster in the 50s and how to possibly treat it and went off in an entirely different research path than the USA and UK.
 
Messages
28
Hi Enigmatic,

Something isn't working right

Well, whatever it is, your B12 isn't high. They are speaking of 3000-10000 pg/ml without supplementation. Yours is right around the area that Japan classes as the lower acceptable limit (550pg/ml). A rise of 132pmol/L (a slightly different measurement, can be converted, using a conversion factor of 1.35 pg/ml = 1 pmol/l) can be caused by a mcg or two absorbed in a meal. It is "low normal", not that even the "high limit" (no such thing, a statistical aberration) signifies much. Studies have shown that people can have responsive to MeCbl peripheral neuropathies at over 1500pg/ml with the average in a study of over 700pg/ml to start with. In that study 62% of the MeCbl responsive people would have been excluded from the study based on "normal" test results except that they used symptoms as the qualifiers, not test results. In other words the "normal" tests would have kept almost 2/3 of people responding to treatment from being treated.

I would estimate that it would take 15,000pg/ml to even approach asymptomatic and that assumes a decent level of l-methylfolate and other factors.

@Freddd Thanks again for the response. In the few weeks since I've posted that message, I've noticed a significant increase in my general well being following your core protocol. I stripped everything back to basics and have been slowly increasing my Liquid Carnitine dose and also my Methyl Folate.

I'm going to see my GP next week and will be asking him to perform some blood tests as I am keen to see how my B12 level is now plus my liver panel.

I also believe that now I'm taking B12 my digestion is starting to improve but this is just a feeling/assumption. Not quite sure how to test it and prove it.

The only negative currently is that I appear to have a return of Ulcerative Colitis. I'd been symptom free and in remission for over 2 years but it appears to have come back despite huge changes in diet to reduce the chances of it returning. I'm hoping this is just part of the healing process and will pass.