Which B12

Hello all

I have Hashi's, Candida and gut bacterial overgrowth problems. When I had my 23andme test last year it came back that I was MTHFR etc., and my then FD said I needed to take Hydroxycobalmin, not the methyl that I was taking. My levels are all in my profile,arn't too bad so I cut down on taking every day, but my levels have been up and down like a yo yo for a long time

When I had my OATS test done recently (changed to another FMD a few months ago, it says I have a high methylmalonic acid marker which is seen in poss vit B12 deficiency or defective absorption. She has me on this B complex but I feel there is too much of something in it and makes me feel jittery

My now nutritionist says I need methyl and not hydroxy. She also said that the 23andme reports are becoming more and more unreliable by the day

Confused.com - I have no idea what to take.

The OATS report markers also mention that my B6 and B5 levels are a little low

44 Replies

  • What was the reasoning given for hydroxo vs methyl B12? I followed you over from the TUK forum and looked at your lab history. With what you've provided, I can't see a reason to switch, but you do definitely need more B12.

    You may also need more of certain cofactors. The B complex is helpful, but may not be adequate. You may need more B2, B6, TMG, B1, or molybdenum. It might be helpful to do a Genova Diagnostics NutrEval test to see. And were any aminos out of range in your OAT test?

    Which MTHFR SNPs do you have? Homo or heterozygous? What about other genes... TCN1/2, MTR, MTRR, MTHFD1, DHFR, BHMT, CBS, SUOX, COMT, etc.? These may definitely alter what your body is doing - we're all unique, so someone else's dose may not work for you.

    But, most importantly, you need to get rid of candida. The best way would be a rotation of Diflucan and Nystatin overs couple of months, along with a strict anti candida diet and a good probiotic. The candida creates a slimy coating on your insides, impairing nutrient absorption.

    While you're doing that, sublingually or injections of B12 would be most helpful. You can mix the types of B12, my doctor has me inject methylB12 3x a week and hydroxoB12 once every 10 days and I take methyl and adenosyl B12 orally. Stay away from cyanocobalamin, though.

  • s1036.photobucket.com/user/...

    SNP Summary:

    CYP1a1, 1A2 --Phase 1 detoxification in the liver, which impair clearance of Estrogens, Xenobiotics (foreign chemical substance-like metals)

    GPX1, GSTP1--Decreased ability to use glutathione to neutralize toxins

    COMT-Decreased Cathechol-O-methyltransferase activity-

    this enzyme is used to break down catecholamines in a normal, heatlhy fashion. Cathecholamines are adrenali, norepinephrine and dopamine. If you don't clear this normally, they PERSIST and exert their stimulatory effects for longer than is normal

    Decreased COMT activity also impairs Phase II detoxification in the liver. Phase II is where toxins etc are attached to things like Glutathione, Suflate, Glycine or Glucuronic Acid.

    COMT SNP's can be worsened by excess methyl donors

    GAD1- Decreased ability to make GABA, an inhibitory/calming neurotransmitter. There are 3 main places where GABA has high expression: Basal Ganglia, Cerebellum and Pancreas. People with low GABA are really prone to anxiety, worry and an overly high firing Brain. But can also show problems with hyperactivity, balance, coordination, car sickness

    NRC31--Abnormal receptor for Cortisol. This can lead to chronic fatigue, high cortisol and side effects from high cortisol (decreased memory, trouble going to sleep, insulin resistance)

    VDR-Abnormal receptor for Vitamin D - you could have normal levels, but not benefit form those normal levels. In addition, these SNPs can be made worse by excess Methyl donors.

    BCMO1-Decreased levels of Vitamin A. Vitamin A is very important for the health of epithelial tissues (skin, GI tract, Respiratory tract); also for retinal and macula health in the eye; normal function of thyroid hormone receptor.

    SOD2, SOD3--Decreased levels of Superoxide Dismutase 2, which protects your mitochondria (energy power plants in every cell) from being damaged

    You are heterozygous C/A for the MTHFR A1298C SNP – which can mildly elevate homocysteine

  • Interesting. That doesn't look too bad... I don't see any other folate or methionine cycle SNPs on your list, so it may be that you just gave a malabsorption problem due to candida and gut inflammation, so work on that. I don't see a reason not to use MB12, but doing both MB12 and HB12 may give you a good balance.

    If your SOD2 SNPs are homozygous for the risk variants, you may want to look at NT Factor for mitochondrial membrane health.

    A functional medicine trained doctor would be useful to consult.

  • I am on my second FD and she wants me to start a third protocol for the Candida and gut dysbiosis but there is too much stuff she wants me to take, it's ridiculous.

    I wonder whether I should take certain B's separately

  • I'd recommend Dr Datis Kharrizian's books "Why do I still have Thyroid Symptoms, when my Lab Tests are normal" and, "Why isn't my Brain Working". He is a leading neurologist and researcher into the gut/brain connection and it's link to autoimmune diseases. He lectures post graduates and is quoted by many of the functional doctors in the US.

    His books are very readable to the layman. One of his recommendations is a gluten free diet and he confirms that you don't necessarily have to test positive for coeliac or have obvious gastric symptoms to be sensitive to gluten.

    Foods high in gluten can damage the microvilli (little hairs) that line our intestinal system and make it harder to absorb vital nutrients like vitamin B12, D3, selenium, magnesium, etc. leading to other problems.

    PS He mentions in his books that many patients are taking too many unnecessary supplements....

  • jefner, the reason you were told to avoid methyl B12 is the COMT variant. The MTHFR variant that you have has no appreciable impact on B12.

    Find it a bit difficult to follow the results on your profile as they don't all have the year by them.

    Have you supplemented B12 and/or folate at all?

  • Gambit62

    Thanks for replying hon. My results are from last year and this year. I supplemented with standard B12, then moved onto the methyl as advised by the Thyroid Group, then Hydroxy by my FMD in the States, now back to Methyl by my current FMD. The Folate is in this which my current FMD has me taking although I am only taking half a cap as I am not sure there is too higher something in there that is bothering me metabolics.com/b-complex-po...


  • the tablets you are currently taking contain methylcobalamin (and adenosylcobalamin) and methylfolate. The dose isn't particularly high, so what you are experiencing could be the interaction between using methylcobalamin and having the COMT variant - particularly the jittery comment. Is this something that started/got worse when you switched to the new tablets.

    If your B12 levels were high when you had the OATS test then that could be iindicative of a functional deficiency - the result of a response to having high levels of B12 in your blood that tries to stop it getting through to your cells (second main stage in metabolising B12) ... MTHFR etc is the third stage - how B12 gets processed in your cells.

    Do you know if you were taking higher doses previously when you were taking hydroxocobalamin?

    Thanks for clarifying he period covered but it doesn't really help with following the results - there are two that are dated december and the last one is dated december but follows ones dated January and february so I can't see clearly which results are earlier/later than others.

    What symptoms did you have and when and what were your B12 levels at the time. What symptoms of B12 deficiency do you currently have?


  • Gambit 62

    Results are in order ie. latest ones first.

    B12 last year I was just taking a basic one from Sainsburys and then I was recommended the thornes Basic B Complex some time ago via the Thyroid group which I tried but after a couple I noticed my anxiety went through the roof so I was told they may have been too strong so I went back to the basic one from Sainsburys.

    My FMD in the States (after having 23andme done last September time) said I should be on methyl B12 which I then switched to the latter part of last year, one by Swansons, around 1000mg. Then when I started with my current FMD a few months ago she put me on the Metabolics but I was also supplementing Swansons Hydroxy 500mg for a while.

    Just on the Metabolics now

    My OATS test result says the following "High methylmalonic acid marker is seen in B12 deficiency, in defective absorption or transport of it, and in the genetic disease methylmalonic acidemia"

    My current FMD doesn't want me adding any more B12 for some reason, but did want me to double my B complex dose BUT she doesn't know that I was only take half a cap a day anyway because I wasn't sure whether they are still too strong for me.

    Not sure what symptoms relate to B12 because I am a complex case of depression, anxiety, post meno symptoms, low thyroid, Hashi's, gut Candida and gut bacterial overgrowth

  • appreciate that unravelling symptoms given the overlap with other conditions is very difficult.

    Personally suspect that the reason for the high MMA is the or transport of it rather than anything to do with absorption as it looks as if your levels got very high and guessing that was when the test was done.

    Supplementation makes interpreting tests relating to B12 very difficult - not that serum B12 is an easy test to interpret in the first place.

    People vary a lot in how they respond to different forms of B12 and it most definitely isn't the case that methyl is a better form of B12. For some people it causes problems - and that would seem to be the case for you. I really think you should go back to your FMD and try and find an alternative to the tablets you are on that doesn't contain high doses of methyl B12 - if you felt better on the hydroxo then go back to that - but may be at a lower level.

    Really think it would be incredibly useful for both yourself and your FMD to go back over the last couple of years and try and map out what types of B12 you were taking when and how you felt on them.

  • Gambit62

    I am currently looking for another FMD as not happy with her to be honest. The new protocol she wants me to start is an absolute overload of stuff. That will be my third one :( Problem is that I feel ill every day so can't tell which B12 suits me and which doesn't and even by two so-called specialists, I have been told the opposite.

    Are there any tell tale symptoms/signs that one or the other wouldn't suit me?

  • Gambit62

    I have high anxiety, blurry vision, I can tell my cortisol levels are high again, brain fog, poor concentration and memory. Can't string a sentence together half the time but those could also be symptoms of anxiety. I just don't know what the hell I am supposed to be taking as regards B12 as my blood says I am OK but my OATS test says otherwise

  • jefner - think responses have crossed.

    There are 3 main stages to B12 metabolism

    a) absorbing it from your food (which gets it into your blood)

    b) getting it from your blood into cells

    c) using it in your cells for a number of processes

    The OATS test coming back with high MMA is an indication that something may be going on at any or all of these stages.

    Serum B12 only really tells you what is going on at the first stage.

    You only need to use very high does of B12 if you have a problem with the first level - if you don't then the supermarket supplement is going to be enough.

    Using high dose supplements can actually cause problems at the second stage resulting in an auto-immune response that basically stops B12 getting from your blood and into cells, and leaving you with a functional B12 deficiency. Flooding the system with B12 can get over this (I think of it as being like keeping the water behind a dam so high that enough trickles over the top) but that may not be the best option for you

    Problems at step C tend to be genetic in origin - some combinations of MTHFR variants can cause problems at this point but as I understand the genetics (and I'm far from being a specialist) the variant you have isn't one that should have a significant impact).

    Because the metabolism of B12 being so complex serum B12 really doesn't work as a single indicator of B12 deficiency and symptoms end up being key - though that's really difficult if you have multiple conditions with overlapping symptoms. The normal range is based on averages and tends to miss 25% of people who are B12 deficient but it would also pick up 5% who aren't deficient but their serum levels are still below the bottom of the range. Supplementation with high doses (or treatment with injections) makes serum B12 even less useful as a guide to whether people actually have enough B12.

    Think that looking for another FMD is probably a good idea. Suggest that you ask new candidates if they have heard of functional B12 deficiency and also ask them how they rate different types of B12 - if they tell you that methyl is the best form then I'd personally steer clear of them. If they tell you that the best form of B12 varies from individual to individual then that would be another tick.

    In terms of which form of B12 is better for you - really it is a question of try it and see.

  • sometimes it's better to take an approach that isn't trying everything all at once but to look at things in turn and might even be better to look at leaving B12 for a while and sort out other things one by one - would certainly make it easier to see what is affecting what symptoms.

    What you really want out of new FMD is one that is going to work with you and allow you to go at a pace that suits you

  • Gambit62

    Thanks hon. Sorry I am just feeling so unwell and brain fogged today, think I have read too much and can't take it in. The supermarket supplement I was using is just a standard low dose B complex with no B12 in. I was taking the Swansons 1000mcg Hydroxy sublingual but as my levels appeared to be reasonable I didn't take it every day.

    I don't know what to do :( just too distraught. I just wish I knew the root cause of my Hashi's. Been so unwell now for 18 months

  • As above - try getting the thyroid sorted out first and then take it from there - one issue at a time.

  • Gambit62

    Not able to get my thyroid straight because of the Candida and gut issues which affect it. I know I don't convert well hence the addition of some T3 last November but when I went up to 20mcg I went over range on the T3 so dropped back to 15mcg and still my T3 levels too low in range so tried 20mcg again. Last week I had a terrible crash with severe anxiety and shaking. Still trying to understand why because there was no real reason. Doing another thyroid test tomos as a possible suggestion is that I have had a Hashi flare

  • Hi Hefner. How were you doing before you added t3? I ask this because t3 can cause all those problems. It may not be your b12. My system can't handle t3. It's too strong. You are on t4 also, right? T4 may be enough. T3 could be pushing you over the edge. I had a thyroid storm because of t3 and too much t4.

  • jpar

    No my T3 is low even with added T3 with my Levo

  • Gambit62

    Should I just stick to the Metabolics B complex then

  • personally I'd ditch the metabolics and go for something that doesn't contain methyl B12 - either cyano or hydroxo.

    However, I'm not a substitute for good medical advice.

    Looking back over your results you weren't clearly B12 deficient when all of this kicked off - though having gut problems may mean you have an absorption problem - your levels do seem to drop when you aren't supplementing but that doesn't necessarily indicate an absorption problem either.

    Did your fist FMD have you on a combination of vitamins or just on B12?

    Think top priority is finding an MD you can work with.

  • Gambit62

    First FMD in the States said back in September to have this "Perque Activated B12 Guard - yes have found it here but it's rather expensive and isn't 2000mcg a little high? functionalnutritionsuppleme..."

    But I questioned it being too high a dose and suggested this one which he agreed to healthmonthly.co.uk/swanson...

    I found an email and I remember saying to him that when I started supplementing on the 1000mcg methyl after my levels looked low from blood tests, it shot up dramatically into the 800's within a couple of weeks. If you look at my results in June and July 2016 you will see the dramatic difference

  • if levels went up that quickly then 2000mcg probably is more than you need.

    if the swanson worked for you I'd suggest going back to that - but have you tried just stopping supplements for a while to see what that does. If you don't have an absorption problem then much lower doses - should be sufficient to keep levels where they need to be for you.

  • So confused lol

  • Many of us with Hashi's and other autoimmune diseases find a gluten free diet helps. Dr Datis Kharrazian, believes that 'leaky gut' and the gut/brain connection the root cause of autoimmune problems. He is a leading neurologist, researcher and lecturer and I'd recommend his excellent books, written in layman's language 🤗 "Why do I Still have Thyroid Symptoms?" and "Why Isn't My Brain Working?".

    I personally find Jarrows Methylcobalamin 5000 mcg, taken sublingually very effective (available from Amazon with good reviews) and you can't overdose.

    This latest BMJ research document has a useful summary and important information re. blood tests once you begin supplements or injections (bottom of page 4 under 'how is response to treatment assessed'):

    "Cobalamin and holotranscobalamin levels are not helpful because they increase with vitamin B12 influx regardless of the effectiveness of treatment and retesting is not usually required."


    I hope things improve for you very soon Jefner.

  • Gambit62

    Sorry I updated my profile with my latest results but it didn't show. Ok now

  • Do you have any references for the warning about methylcobalamin and COMT mutations? Of the 16 COMT SNPs listed by Promethease I am heterozygous for 11 of them!

    It could explain why I felt quite terrible the one time I injected with methylcobalamin (and would indicate that the patches, lozenges, sprays, etc. that I'd tried, mostly methylcobalamin, were not absorbed to any extent).

  • it was a trail that I followed some time ago over noticing methyl B12 being contra-indicated on a genetic report.

    Where I got to was the role of B12 in recycling neuro-transmitters and the possibility that COMT variants meant that this was a very delicately balanced process that having too much methyl B12 could interfere with sending it into overdrive - which can be as problematic as it working too low.

    These are the references that I have book marked but the biochemistry was very complex and I can't guarantee that I have followed it properly





    (and if anyone has used a 'will' when they should have used a 'can', eg the US National Library of Medicine in their genetics site, please take it up with them :) )

  • Wow! It's going to take me quite a while to go through that first one.


  • Gambit62

    Just updated profile again, for some reason it isn't accepting some of the text I put in but the dates should be better. The bottom one is December 2015, when I discovered I had Hashi's

  • If I didn't have brain fog before I read this I certainly do now. This b12 journey is oh so complicated isn't it.

    I'm having a particularly poor day with loud tinnitus and wonky vision that's either causing or caused by high anxiety.

    I truly wish there were better tests and treatment for this situation accessible to everyone.

    The knowledge you guys seem to have is truly unbelievable.

    I've never even heard of an oats test until now.

    This thing Is so life destroying.

  • not really sure of what OATS stands for either - just looked it up and appears to be Organic Acids Test ... which would make sense if it picked up MMA - almost certainly not an NHS thing.

  • Gambit52

    Can email you the OATS report if that helps. Have already linked my 23andme reports in the thread

  • no - don't need to see the OATS report - MMA is likely to be the only thing on it relevant to B12 deficiency.

  • Gambit62

    what is MMA please

  • methylmalonic acid - which you noted as being raised - its a by product of one of the processes that B12 is used for that builds up if there isn't enough B12 to recycle it into a useful building block - hence it is a potential marker that you don't have enough B12 at the cell level. It can be raised by other things.

  • Gambit62 If i dont have enough at cell level then i dont know which one to take hun?

  • think your problem may be too much B12 in your blood leading to a functional deficiency. 2 ways of treating that - let levels drop and see what happens then or just take high doses of B12 and keep levels in your blood high - possibly higher than you have managed to get them so far. suggest you use either hydroxo or cyano but avoid methyl.

    Really though you need to find a FMD you can trust and who really knows about B12.

    Sorry no clear answers

  • Thank u, i havent had any for a couple of weeks. Did thyroid test today so should have results in day or so. Will restart the hydroxy. Prob is my b complex has small amount of methyl. What symptoms might i experience if not taking the right one?

  • your cells need both methyl and adenosyl B12. the problem with a lot of genetic variants is that they tend to be 'could cause' rather than 'will cause'. I am most definitely not an expert but my understanding is that the COMT variants affect how efficient one particular process that uses methionine is. This seems to be a particular problem when it comes to the processes that the body uses to reset neuro-transmitters. methyl B12 can be a problem because it donates its methyl to the process and with some COMT variants this sends the process into overdrive - recycling the neurotransmitters too fast so signals get scrambled. This can lead to neuro psychiatric problems like depression, anxiety, paranoia ... but in terms of general neuro symptoms can cause numbness, pins and needles, shooting pains. This could fit with the jitters that you mentioned.

    Your body will convert hydroxo and cyano to methyl by combining the B12 with methyl that is already stored in your body. The problem with using methyl as a source of B12 if you have a genetic variant that is supercharging the methionine process would be that you are introducing extra methyl into your body. It might also be a good idea to avoid methylated forms of folate as well - but really you need to be taking advice from someone who has a lot more medical information than I do - and also bear in mind that this is only going to beone small element of how your body works.

  • Gambit62

    thanks hon for all your time and explanation. I don't understand much about it. One FD says I need hydroxy and the other says methyl. On reflection I haven't supplemented with B12 alone for weeks now as I just relied on the small amount in the B complex she gave me which is methyl. I think I am just going to try 2-3 doses a week of the hydroxy that I have and stick to a basic supermarket b supplement until I can find a new nutritionist

  • Gambit62

    Is there a proper B12 test I could do which would tell me exactly what I need to be taking?

  • unfortunately there isn't any test that I'm aware of - think its unlikely - although the metabolisation of B12 is a fascinating and complex subject it isn't one that gets a lot of research asscociated with it. The genetic test you had implies that methyl is probably a form of B12 you should avoid ... and whilst MTHFR gets a lot of coverage and gets linked with using methyl there actually isn't much evidence that methyl works any better.

    Think trying the hydroxo and just using an over the counter for others is probably the way to go until you manage to find a FD that you can work with.

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