Confused B12, Folate

I read a post on the thyroid group that until B12 is high that folate should not be supplemented. Is this correct?

I have had my blood tests and am waiting for GP call back following her speaking to a haematologist for advice (she is now off ill for min of 2wks) so I am supplementing with B complex as I didn't want to wait. I had thought that it was better to have the complex as all B vits work synergystically together. So a lot confused.

The supplement I am now using as don't want to wait without is a probiotic fermented liquid B complex - so supposed to be the best bioavailable as the B vits are produced by bacteria as they naturally would be in our intestines. But B12 is only 263mcg (DV 4,383%) Folate 1000mcg (DV 250%)

Serum B12 392 pmol/L (range: insufficient 140-250)

B12 Active 209.6 pmol/L (range: 25.1-165)

Folate 24.88 nmol/L (range: 8.83-60.8)

So total B12 is low but the active is a high percentage of that total. Which could mean that active is not getting into cells and so building up in blood or maybe not.

My questions are:

Should I not be taking a complex - but just be taking B12? But my folate looks low? But according to my GP it fluctuates meal to meal so not interested in.

Or should I continue with complex and take additional B12?

Does anyone recommend patches? I hate added ingredients to supplements because I have to be gluten free. A year or more ago I used to get a B12 powder from Holland as was just B12 in sugar, nothing else. But it stopped being available.

Which lozenges does anyone recommend? Most don't often state all the added ingredients let alone whether Gluten Free Genetically M etc

28 Replies

  • Total B12 is not low. Almost 400 pmol/L is 2.5 times he stated lower limit. Your active B12 is 8 times the lower limit. Your folate is three times the lower limit.

  • When B12 is quoted to be 500 + being the absolute min for restorative healing sleep or 9-1000 quoted to be required to heal nerve damage symptoms. Is that a different reference range? when I said low, I wasn't referring to lab ranges more what I need to get rid of symptoms and heal. Mainstream lab ranges are often not ideal eg. TSH, vitD, ferritin, to just pluck three out of mid air.

    So are you saying that it is ok to take a B complex containing folate, and it won't cause the damage implied because my B level is above that concern.

    Is it correct that folate shouldn't be taken if very low B12 as in lower than range (which I know that I am not) but just wanted to know re the function and process?

    Because I have a further dilemma re symptoms and a too high a active B12 that, B12 is prevented from getting into cells and that is why it is building up in the blood.

    In which case let's say it is not getting into cells, so B12 would be very low in cells. Is it then ok to take a vit B complex with folate in it or not? Would I be better just taking B12. But I had thought we needed folate for B12 or is folate just needed for absorption from the digestive tract.

    Why is it dangerous to take folate when B12 is low?

  • personally not a great fan of the statements about optimal levels for vitamins and minerals that proliferate on the TUK forum. The reality is that human beings vary and what is right for one person is not necessarily right for another. the levels quoted as 'optimal' are based on averages - and perpetuating them as being right for everyone is repeating the same mistake that results in normal range being used to rule out a deficiency.

    As fbirder says the levels you quote for serum B12, active B12 and folate are not indicative of a deficiency. Interpreting tests is much more difficult if you have been supplementing as this will have skewed the underlying results - to get decent readings on the tests for B12 you would need to avoid supplementing for 3- 6 months. Evaluation should include looking at your symptoms - which can be difficult in the case of thyroid conditions because there is a significant overlap with thyroid problems


    unless you are highly symptomatic of B12 deficiency I would be inclined not to waste my money on supplements which are unlikely to be of any help at all.

    It is symptoms not numbers that come back from tests that count.

  • personally not a great fan of the statements about optimal levels for vitamins and minerals that proliferate on the TUK forum. The reality is that human beings vary and what is right for one person is not necessarily right for another. the levels quoted as 'optimal' are based on averages - and perpetuating them as being right for everyone is repeating the same mistake that results in normal range being used to rule out a deficiency.

    I can understand why giving set levels to people and saying "There, that is what you should aim for" might be upsetting, and might not be the best science around.

    But what is the alternative? Saying to someone "Oh, your vitamin D level isn't very good is it?", and not saying anything else?

    People need something to aim for, otherwise they wouldn't know where to begin the process of getting better, they are just left flailing around not knowing what they should do.

    When I was really, really ill, and was getting no help from doctors, I needed to be spoon fed. I needed a goal, I needed to be told what to do, and I needed to be told what I should be aiming for.

    I simply wasn't well enough to make these decisions for myself.

  • this forum is not a substitute or medical advice.

    I do my best to be honest about the limitations of averages and ranges both ways and that is what I would hope that others will do. statements about optimal ranges are misleading when it comes to B12 - I really can't comment on other minerals and vitamins and how much they vary as I haven't looked into it.

    People do not need something to aim for - they need to understand the facts and to understand where there are uncertainties, however, unpalatable that may be.

    Encouraging people to continually dose themselves up with huge amounts of supplements is not the way to go. At best it is a rally to wasting huge amounts of money if the supplements aren't need. At worst raising B12 levels in serum to unnecessarily high levels, is not without potential risks (eg functional B12 deficiency). Whilst the consequences may be inevitable if you have a B12 absorption problem and a resulting deficiency that needs treatment they are not inevitable and I would really rather people didn't end up finding themselves in a situation where they needed to consume really high levels of B12 to stay well, just because they had supplemented unnecessarily.

  • Hi, are you inferring, when referring to 'functional B12 deficiency' in your post that if we supplement with vit B12 when it is 'not required' by our own individual system, but just as a proactive preference that we could be heading for trouble because? possibly the body will prevent the methylation process from functioning properly, because there is so much B12 access re the supplementation?

    I have symptoms which is why I became concerned, started to research and all symtoms point to B12 deficiency. I remembered reading functional doctor/ pshychiatrist Dr DanielAmen's book (he's the guy who developed using Spect Scans to see what is going on in the brain and created the term 'Brain Envy') where he states that you never want to be bottom of the class when it comes to B12 - that it needs to be up there at the top of the range for good brain health. Ditto with specialist Dr Datis Kharrazian, whose books I have read. And who knows seriously in this country what is 'within range' In the Uk we have the lowest range of most other countries - is this a way for the NHS to save money through the back door! The Japanese min acceptable B12 level is 500 (range 500-1300) couldn't be why the Japanese have the lowest heart attack risk could it. Please do not tell me that B12 has nothing to do with heart attack risk! From a functional perspective every pathway influences every function, the body works as a whole functioning system as I am sure you know. But if you question - see Dr Tom O'Bryan's work - his father died too early in life from a sudden heart attack. Because Dr Tom is who he is and tenacious he would not let it rest at autopsy until the cause of his father's heart attack was determined. Under normal circumstances the cause would not have been persued to such an extent. It was eventually found that his father died of a heart attack brought on by an unrecognised B12 deficiency. He states that his father died unnecessarily for the sake of an injection that costs pence.

  • I am certainly not going to tell you that B12 isn't a risk for heart attacks - but telling people to supplement or not supplement purely on the basis of B12 serum score and to tell them that they need to have levels at 1000 is potentially harmful. Symptoms are an important part of evaluating the status of someone who may or may not have a B12 deficiency - so at least ask if they are symptomatic.

    Functional deficiency is about transportation to cells and doesn't have anything to do with methylation beyond the fact that if you don't have B12 getting through to your cells then there isn't anything for the cells to convert to methyl B12.

    Cells actually use two types of B12 - methyl and adenosyl and there are documented cases of people who can't convert methyl to adenosyl so actually advising people to use methyl has its risks as well.

    Yes, the UK could do with better guidance on using normal range and it could do with amending but only if cliniical evaluation is taking place as well as the blood test. Not much mentioned but if we just used the normal range and didn't use any other indicators then 5-10% of people would actually be treated when they didn't actually have a B12 deficiency - just underlines how limited it is as a single diagnositic tool

  • Thanks Gambit - I appreciate your knowledge base. So is it when converted to Adenosyl that B12 gets transported into cells? So methyl reqires converting to Adenosyl to get into cells? or the 2 types coexist and either are transported into cells?

    So the Active B12 that should be approx 20-30% of the total serum B12, when measured in serum is attached to the transport protein TC11 ready to be taken up and used in the cell. Is that made up of either methyl or adenosy or both ?

    Would you know where the TC11 protein becomes attached to the B12 - is it in the intestines where absortion or other factors could affect?

    Or does the process of becoming bound to the TC11 protein happen once B12 is absorbed into the blood?

    I read that the inflammatory process (aka me) can affect or block the uptake/or was it function of the TC11 protein and so resulting in deficiency of B12 in cells because it cannot or is not being transported across into cells. This is denoted by a build up of transport protein bound Active B12 building up in the blood?

    I have within range but a still low total B12 in my opinion, but instead of a 20-30% of my total being active/transport bound - I have a 50-60% percentage which was graded as abnormal high by the lab. This situation is seen in cancer patients, because of the innflammation.

    I have RA and consequently am permanently battling with inflammation. Although I had got my CRP down to within normal range the last time tested. My iron levels are I believe affected in this way, I have a high normal but top of the range ferritin (not too healthy and so was hoping to donate blood to bring ferritin levels down as they have shot up now that i no longer bleed/ have periods) but low available serum iron and abnormal low transferrin percentage (whivh is really not good) So it seems that my body feels I am under threat of pathogens because of the inflammatory process and uses the hormone Hepcidin to store iron rather than release it for my cells to use.

    So perhaps a similar protective mechanism is happening with B12 TC11 transport. If so I cannot understand why leaving the active B12 in the blood stream would be protective, as in serum there is pathogen access. Unless pathogens cannot access te B12 when it is bound to the transport protein?

    I really do not know how to move fwd at this point and my GP's referral to haematology has been rejected on the basis of my serum B12 levels being in normal range. I need to say that the haematologists don't even know their own or refer to their own guidelines.

    Sorry for the long post - I am just appealing to your greater understanding :)

  • Sounds like there are a lot of things that are getting confused. Gluten intolerance can cause inflamation in the gut which can prevent adequate amounts of B12 being absorbed from your food in the gut.

    TCII, or holo-T is B12 bound to a protein once it has been absorbed in the ileum - but the protein binds to all types of B12 - your blood will also contain B12 that is bound to another protein which has protected it from being degraded by stomach acid whilst travelling in the gut to the ileum. What is being looked at in the active B12 test is the ratio of TCII in your blood to TCi. The form of B12 that is bound at this point will vary and could be methyl, hydroxo or cyano if you are supplementing and depending on which you are using.

    It is processes that occur in the cell that actually convert the form of B12 into the one that is needed for whatever the cell is trying to do - which could be methyl or adenosyl.

  • Thanks for the enlightening information

  • Re: "what is being looked at in the active B12 test is the ratio of TC11 in your blood to TCi"

    Can you tell me what is TCi. I had thought it determined the ratio of active, bound to the transport protein ready to move in to cells compared to the free unbound in the Total

    B12 found in the blood?

  • Once our body absorbs B12 from the gut, or from an injection site, the B12 - in any of the common forms, cyano, hydroxo, methyl, adenosyl - enters the blood where it can bind to one of two proteins - TC and HC (the proteins previously known as TC(I) and TC(II).

    TC is the only form that can enter the cells. This is what is called holotranscobalamin, or 'active' B12.

    The 'active test measures B12 bound to TC. It does not measure a ratio, but the absolute amount.. The normal serum test measures B12 bound to both TC and HC. For the majority of people the B12-HC is about 4 times higher than the B12-TC.

    That is why you'll hear it said that only around 20% of B12 can get into the cells. Some might even say, incorrectly, that this is why the serum test is useless. However, the people devising the tests know about this 4:1 ratio and the ranges for the tests take into it account.

    Once the B12-TC is taken into the cell the TC is removed and the B12 (still in whichever form was administered) is passed on to an enzyme called MMACHC. This enzym removes the top ligand (the hydroxo, cyano, methyl, or adenosyl group) to leave something called cobal(II)amin.

    At this stage all different types of B12 have been converted to just one intermediate.

    Once the MMACHC has done its job the cob(II)alamin gets passed on to wherever it's needed in the cell, to get converted to methylcobalamin or adenosylcobalamin.

  • Thank you so muc fbirder. For the first time, I think, I actually understand the process and terminology and the different supplements offered. Can't thank you enough :)

  • as fbirder correctly points out - Active B12 isn't looking at a ratio - but it is measuring the amount of B12 that is bound in TC - whilst 12 in blood can be bound to both TC (transcobalamin) and HC (Heptacorrin) - and I had temporarily confused this heptacorrin with transcobalamin)

  • Hi Gambit, thanks for replying :) I do have symptoms. Some that I hadn't really picked up on/ignored for ages and others hit with a bang at New Year. So that is why I am worried and logically trying to sort this out instead of panicking which I did at first, or I'd never get any sleep and that's part of the crucial issue for healing and repair.

    Yes I did supplement with B complex for 3 days only in 8months. And the 3rd day was just rinsing the empty bottle out. I panicked and took, then realised re tests and had test 3 weeks later. I did ask the lab (Blue Horizon) and they said test is just a snap shot in time, blood levels at that moment.

    I don't understand what people mean by skewed. It doesn't mean that the results are turned upside down/chaotic and totally unreadable, just that the result may read a higher level of B12 than would be in the blood if hadn't been supplementing - so not a good base line to judge what your everyday diet would provide or show as low as possible in order to fulfill requirements for injections. My 2/3 days of supplementing 3 weeks prior, can't have made much more difference than having eggs for breakfast, shrimps for lunch and liver for tea for a few days immediately before the blood test.

    The point is, my blood test shows that the percentage of active within the low/grey zone B12 total is too high - not 20-30% but 50-60%. Which implies active B12 is not getting into the cells but building up in the blood because it is unable to get into cells. Which then creates a deficiency and then symptoms. I do not know how I am going to move forward with this, and maybe my symptoms are not caused by B12. But nevertheless something strange is happening with my B12 metabolism so to me as my symptoms are typical B12 deficiency symptoms, deficiency is what I presume is happening. And B12 supplementation seems to be the only course of action I can take. Apart from which, my total B12 is too low to stop sleep disturbance and promote healing sleep and is no where near 900-1000 suggested on this forum, to initiate healing the nerve damage

    I was just concerned about a post that stated folate (so I suppose that would be a complex) should not be taken until B12 gets high enough. My question is Why? Is this because as I once read, and never knew whether correct or not - that folate and B12 have to balance in the blood and so if folate is high in the blood then B12 will be drawn out of cells in to the blood to balance and so exacerbate the deficiency.

    My question: but we all have folate in our diet, absorbed into our blood and I had thought folate was required for correct B12 metabolism.

    So should I be taking a complex? And in addition take B12? And which B12 supplements would people advise. Has anyone found patches effective?

  • Better to click onto green reply button below Gambit62 's post otherwise she won't see it 😊

  • Hi,

    There's a lot of skepticism about methylation but it might explain your issues. b12 requires folate to work at the cellular level. There are gene snps that interfere with this b12/folate metabolism in a variety of ways, for instance the mechanism that transports b12 through the cell wall fails so you read high in serum but are still symptomatic. There are other co-factors in the cycle like the hormone vitamin d, Sam e, minerals, other b vits. Epigenetics suggests that you're restarting methylation by supplementing b12. So if you low in other factors, maybe malabsorption issues?, adding them in might boost things along. The reading I've done indicates this is very much trial and error. Folks who report success doing this have kept detailed records of their responses and keep tweaking. Start small. I take a low dose b complex, vitamin d, a mineral complex. I'm tweaking folate. My daughter can't drive her d above 30 unless she takes 10,000 iu. But huge difference when she did in her fatigue. The differences in our responses can be attributed to the interaction of snps which turn off and on in response to diet, exercise, stress, toxin load etc. which explains why it's possible to have bad genes but be perfectly healthy, or have good genes and be ill. Or be really healthy when young and fall apart in our forties. Just read of a researchers reversing mental retardation in a strain of mice using epigenetics. Thalassemia major has been cured! This is still early days in this field, but what hope for the future!

  • not sure that what is going on with LynneG's blood results has anything to do with methylation as that is something that is going on at the cell level whereas one of her concerns is around the build up of transcobalamin2 in her blood.

  • long term supplementing folate will mask any macrocytosis and as such can delay a diagnosis of B12 deficiency (though that shouldn't be the case as macrocytosis shouldn't be being used as a definining characteristic but is a reflection of reality)

    Short term treating a B12 deficiency with folate carries a risk of precipitating SADC - sub-accute combined degeneration of the spinal chord - though this is based on a few isolated and probably extreme cases where the B12 deficiency was severe - so the recommendation is that treatment with B12 should start 24-48 hours before treatment with folic acid.

    If it weren't the case that B12 is generally stored in the liver in good quantities and the quantities you were taking for a normal person amount to 400x RDA (ie more than a years worth of B12) then it would be the case that supplementing for a few days would not skew the results but that just isn't the case. I am not sure that dismissing the supplementation as equivalent to having had eggs for breakfast is really valid in this instance - it might work for folate and other vitamins that aren't stored in the way B12 is but I don't think it is valid for B12, even allowing for limitations in the amount of B12 that can be taken up in the gut.

    If you wish to pursue further testing you probably need to look at MMA and homocysteine to clarify whether enough B12 is actually getting through to cells. Serum B12 and even active B12 are unlikely to be of any use at this point.

  • I read a post on the thyroid group that until B12 is high that folate should not be supplemented. Is this correct?

    I don't know which post you read that in, but this is what prompted the concern about supplementing folate before getting at least a little bit of B12 on board :

    Read section 2 in this link :

    Also see :

    Quote :

    If someone is deficient in vitamin B12 and folic acid, the vitamin B12 deficiency must be treated first to avoid precipitating subacute combined degeneration of the cord (giving folic acid first will turn the remaining B12 into methylcobalamin which will not be able to participate in fatty acid metabolism).

  • There is no reference given for that wikipaedia comment.

  • Possibly because it's not true.

    Well, the warning is correct, but the proposed reason sounds wrong. I shall look into it.

    I never trust a Wikipedia 'fact' that doesn't have a link to back it up.

  • Yes, I thought it smelt fishy. The body just doesn't work like that.

    Here's what really happens:

    Normally there is a folate cycle where folic acid gets converted to dihydrofolate which gets converted to tetrahydrofolate (THF), which gets converted to methylenetetrahydrofolate which gets converted to methyltetrahydrofolate (MTHF) which passes its methyl group to B12 to make methylcobalamin and THF which goes back into the cycle. Phew!

    The step where methylenetetrahydrofolate gets converted to MTHF is irreversible. And the only way to get rid of the MTHF is by making methylcobalamin.

    If there isn't enough B12 then not all of the MTHF will get used up, so MTHF levels will rise and THF levels will fall (because it's not being made from MTHF). Most of the body's folate ends up trapped as MTHF.

    THF is important in other biochemical processes important in the production of myelin - which is why a lack of it can cause SACDC.

  • Damn. That snippet is in at least two places on Wikipedia. Looks like I'll need to find the time to do some editing.

  • Thanks so much :)

  • Hi LynneG. Just a quick thought...has any body suggested that you get an MMA and homocysteine blood test? These can be useful in telling if your body has a problem with B12 at a cell level (they will be raised if your body is not processing B12 properly - something that serum B12 and active B12 tests cannot tell you).

    Take care with B12 complex...they often contain high levels of B6 and too much B6 can cause peripheral neuropathy (certainly don't take more than 100% RDA - and that is too much for some people).


  • Thanks Foggyme - Yes research told me. have not had MMA - didn't include with my active B12 test as I was unaware at the time. Have my Homocysteine checked regularly and was at nearly 10 (not good) but proactively got it down to 8.3 so Homocysteine doesn't seem an indicator?

  • Sorry for late replys have not been well and stressed.

    I took all info and help onboard from this group, and so I was well informed re symptom based clinical guidelines from this group I managed to get my GP onside - now having blood test for Intrinsic Factor ab's this Friday. My GP did a referral to a haematologist at the same time, saying that I had more understanding of this than she and I would be better speaking directly to a haematologist. (which is great, I just want to talk to someone with a depth of understanding) My GP had a tel conv with a Haematologist before referral and he suggested we look at a 'film' of the blood cells which will determine more - hence the up and coming blood test and referral

    Unfortunately my referral has gone through and been rejected on the basis that my Total B12 serum levels are within normal range on my last bood test. Don't they even look at their own clinical guidelines!

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