Vitamin B12 – why it is important and which form to choose

Vitamin B12 is an essential water-soluble vitamin, often highlighted for its role in energy production, red blood cell formation, DNA synthesis and prevention of pernicious anaemia. But, beyond the fact that it can be lacking in plant-based diets and should be consumed regularly, what do we really know about how this crucial nutrient functions within the body?

With an important role in so many metabolic reactions, B12 deficiency was uncovered in the mid-18th century. A diagnosis once deemed fatal, it was soon discovered that a diet rich in liver could largely ameliorate the condition. Nowadays, B12 related fatalities are rare, however a ‘sub-clinical’ category of B12 deficiency is on the rise.

While B12 deficiency has primarily been identified in people who are under-nourished and in those with the autoimmune condition pernicious anaemia; more recent discoveries have identified several sub-clinical factors which can contribute to a reduction in B12 status. These include malabsorption issues – which may occur with increasing age or in those with gastrointestinal impairments, genetic factors; vegetarian and vegan diets and even certain medical interventions.

As such, with a broader understanding of the factors which can contribute to low B12 and with knowledge of the severe consequences which can result from deficiency, it has become more important than ever to raise our awareness around B12 status.

In this blog, we discuss why B12 is so important and what factors can contribute to low levels. Furthermore, we will explain the various forms of B12 and the current methods of B12 testing available.

Skip to Key Takeaways

So, why is B12 important?

B12 participates in the metabolism of every cell in the human body. It contributes to normal nervous system functioning through its role in the synthesis of myelin (the fatty layer which surrounds our nerve cells); supports the maturation of red blood cells in bone marrow, as well as acting as a cofactor in fatty acid and amino acid metabolism and DNA synthesis.

For this reason, deficiency can lead to widespread signs and symptoms, including:

  • Pale skin
  • Weakness, fatigue and light-headedness
  • Constipation, diarrhoea or gas
  • Loss of appetite
  • Nerve issues like tingling, numbness and muscle weakness
  • Impaired vision
  • Hormonal and mood imbalances
  • Sleep disturbance
  • Reduced immunity
  • Cognitive impairment
  • Problems with balance

Absorption of B12

The absorption of B12 in the body is a highly complex process which can be divided into three key phases: the gastric phase, the intestinal phase and the mucosal phase.1 Food-bound B12 must be released through an extra step before it can be absorbed in the ileum; as supplements are already in their free-form, they do not require this stage.

Gastric Phase Free-form (supplement): B12 binds to a plasma carrier protein known both as haptocorrin or transcobalamin I. This glycoprotein is secreted by the salivary glands and protects B12 from the acidic environment of the stomach. The B12-haptocorrin complex then moves towards the duodenum for the next step.

Protein-bound B12 (food): unlike free-form B12, protein-bound B12 must first undergo proteolytic cleavage in the stomach to be released from its protein carrier before it can bind to haptocorrin.2,3 Proteolytic cleavage refers to the digestion of protein by pepsin in the stomach, which frees B12 for binding. Adequate stomach acid is vital to trigger the conversion of pepsinogen into the functionally active pepsin.

The parietal cells in the stomach release intrinsic factor which will bind to B12 in the duodenum.

Intestinal Phase As the B12-haptocorrin complex enters the second part of the duodenum, protease secreted by the pancreas degrades the haptocorrin complexed to the B12. It is here in the duodenum that the B12 binds to intrinsic factor to create a B12-instrinsic factor complex which will be carried toward the ileum of the small intestine.
Muscosal Phase Upon entry to the ileum, the B12-intrinsic factor complex is absorbed via the enterocytes (cells which line the small intestine) and binds to transcobalamin II; making it active B12. Generally, around 50% of this active B12 is delivered directly to the liver for storage, while the rest is circulated for use in the body tissues.


Factors which may contribute to low B12 status

Due to the complexity of B12 absorption and synthesis within the body, low levels can often be observed even when there is adequate dietary intake. Some factors which can contribute to low B12 status include:

  • Age: B12 deficiency is very common among the senior population with estimates suggesting that at least 20% of people over the age of 50 may have low levels.4 Malabsorption due to reduced enzyme and stomach acid activity or a lack of cobalamin transport proteins are potential factors, as well as dietary insufficiency, prescription medications or pernicious anaemia.4
  • Dietary preferences: vegan and vegetarian diets can easily be lacking in B12 as it is primarily bound to animal protein. While vegetarians may fare better as some B12 can be found in dairy and eggs, levels should be monitored to ensure adequacy if attaining B12 through diet alone.
  • Parietal cell damage: intrinsic factor is secreted by the parietal cells and is needed for B12 absorption. Parietal cell damage occurs as a result of autoimmunity (leading to pernicious anaemia), hypochlorhydria, gastritis and in those with a history of high alcohol intake.
  • Hypochlorhydria (low stomach acid): sufficient stomach acid is required to release B12 from food. Several factors such as old age, radiation for gastric cancer, the use of anti-secretory medications (PPI’s, H2 blockers), antacids, hypothyroidism and Helicobacter pylori infection can all contribute to impaired stomach acid production.5
  • Nitrous oxide: can irreversibly convert active B12 into its inactive form, thus preventing use in the body. Nitrous oxide is used in a number of dental and surgical procedures.
  • Intestinal malabsorption: B12 is absorbed in the small intestine and so conditions such as ulcerative colitis, Crohn’s or coeliac disease which can cause damage to these cells could impede B12 absorption.
  • Genetics: genetic polymorphisms affecting genes including TCN, FUT2 and MTR/MTRR can disrupt the transport, use and recycling of B12 in the body.
  • Medication: in addition to some of the medications mentioned above, other prescription drugs such as metformin and neomycin can impair B12 absorption.
  • Surgical intervention: a significant loss in the number of cells which produce hydrochloric (stomach) acid and intrinsic factor can result from gastric bypass surgery. In addition, partial or full removal of the ileum drastically reduces the surface area available for absorption of B12.

Forms of B12

B12 belongs to the cobalamin family of compounds as it has a cobalt atom at its centre. The structure of B12 is quite intricate, consisting of a corrinoid ring with an upper and lower ligand which attaches to a cyano, hydroxy, methyl or adenosine group.

6Form Natural or synthetic? Biologically active? No. of conversion steps required Sustained release? Unique properties
Cyanocobalamin Synthetic No 4 Average None
Hydroxocobalamin Natural No 3 Very good Detoxification of cyanide & nitric oxide
Methylcobalamin Natural Yes 0 Average DNA, brain, nerves, blood, detoxification
Adenosylcobalamin Natural Yes 0 Average DNA, brain, muscles, energy



Conversion: cyanocobalamin -> hydroxocobalamin  -> methylcobalamin <–> adenosylcobalamin.

This is both a synthetic and inactive form of B12; produced with the addition of a cyanide donor. The cyanide molecule has a strong attraction to cobalamin, making it a very stable form of the vitamin. With that said, the presence of cyanide can make absorption more difficult as a methyl donor is required to detoxify the cyanide from the body.

While cyanocobalamin has historically been the chief form of B12 used both medically and commercially, it has received criticism of late for the following reasons:

  • Potential for toxicity as cyanide can be produced during cyano breakdown – of particular concern for those experiencing detoxification issues such as in smokers or patients with liver or renal damage
  • Requires reduction across four metabolic steps before it can be used
  • The conversion of cyanocobalamin to active B12 can be prevented by a number of genetic and metabolic abnormalities


Conversion: hydroxocobalamin -> methylcobalamin <–> adenosylcobalamin.

This form of B12 is one of the predominant forms found in food. While it is also inactive, it does not contain a cyanide molecule and in fact aids the excretion of cyanide in the urine. Interestingly, hydroxocobalamin is commonly used as an antidote in cases of cyanide poisoning.7

Hydroxocobalamin has been found to have a higher affinity to plasma protein, as well as a longer half-life than cyanocobalamin. In a study which investigated the nasal absorption of hydroxocobalamin in older adults, it was found to be so effective that researchers suggested it as a possible alternative to intramuscular injections in some individuals.8

It is safely administered to those experiencing tobacco amblyopia,9 a condition related to cyanide metabolism. Patients with B12 deficiency optic neuropathy are also prescribed hydroxocobalamin in the UK.9 Hydroxocobalamin has demonstrated a distinct ability to inhibit nitric oxide above other cobalamin forms.10 High levels of nitric oxide can contribute to oxidative stress. However, in pregnancy nitric oxide aids the control of fetoplacental circulation.11 For this reason, methylcobalamin and/or adenosylcobalamin may be a better option during pregnancy.


Conversion: methylcobalamin <-> adenosylcobalamin (the body can convert to either of these forms depending on need).

As one of the two active forms of B12, methylcobalamin is required for several essential processes including:

  • Conversion of homocysteine to methionine (thus lowering homocysteine concentrations) as part of the methylation cycle
  • Generation of S-adenosyl methionine (SAMe) – an important methyl donor involved with over 200 enzymes required for cell growth, maturation and specialisation
  • Supplying methyl groups required for various reactions, including generation of acetyl-CoA
  • The only cobalamin which can regulate sleep and wake cycles12

Studies have demonstrated an increased utilisation of methylcobalamin within the body when compared with cyanocobalamin,13 possibly due to the fact that it does not require conversion as it is already in its active form. While serum levels were similar in a comparative study between oral doses of cyanocobalamin and methylcobalamin, high doses of cyanocobalamin resulted in increased urinary excretion of B12, while methylcobalamin appeared to replenish the body’s stores.13

Methylcobalamin has been noted for its role in neuroprotection. This cobalamin form supports the restoration of myelin sheath which results in improved neural conductance; with ongoing investigations into its application in nerve injury models. Furthermore, methylcobalamin demonstrated a distinct analgesic effect in patients with trigeminal neuralgia. Intravenous injections resulted in a reduction of paroxysmal pain, continuous spontaneous pain and allodynia (central pain sensitisation).14 It is highly likely that these therapeutic applications are associated with the positive effect methylcobalamin has on nerve action and regeneration.15


Conversion: adenosylcobalamin <-> methylcobalamin

This is a less well-known form of active B12. As it is involved in the Kreb’s cycle (creation of ATP or cellular energy), it is often referred to as the mitochondrial B12. During the Kreb’s cycle, adenosylcobalamin aids the conversion of methylmalonyl-CoA to succinyl-CoA.   If this cycle is not functioning properly, fatigue and increased cellular ageing can ensue.

Most liver stores of B12 are as adenosylcobalamin and only convert to methylcobalamin as needed. While this conversion is straightforward for most people, certain genetic abnormalities can reduce the body’s ability to synthesise adenosylcobalamin.

As well as energy production, adenosylcobalamin is required to reduce levels of methylmalonic acid which can cause nerve damage at high levels. Furthermore, adenosylcobalamin plays a role in the catabolism of important amino acids and hormones such as valine, threonine, isoleucine, methionine, thymine and cholesterol.

Adenosylcobalamin is a good form to consider in cases of chronic exhaustion, muscle weakness, liver damage and hepatitis, where low B12 is suspected. In an Italian study where B12 was administered in the treatment of viral hepatitis, adenosylcobalamin was found to have a significantly greater effect on normalising total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase values compared to cyanocobalamin.16

Getting tested: how to measure your B12 status

A serum blood test is the standard method to assess B12 levels. This looks at total B12 or haptocorrin (transcobalamin I); the inactive plasma B12 binding protein. Within the cells, B12 is generally bound to transcobalamin II and so levels of total B12 are not necessarily indicative of the levels being assimilated into cells for use by the body. For this reason, B12 levels could be within a normal range in the blood, but the body may be unable to use it.

Serum B12 levels between 150 and 400ng/L are considered borderline for deficiency, with less than 180ng/L potentially causing pernicious anaemia and/or peripheral neuropathies.  In these cases, a holotranscobalamin (transcobalamin II) blood assay will often be suggested, which looks at active B12 levels only.

If signs of B12 deficiency are present but total B12 levels are within normal range, it can be useful to seek functional assessment. Testing for methylmalonic acid via the blood or urine (high when adenosylcobalamin is low) and/or homocysteine in the blood (high when methylcobalamin is low) in conjunction with total or holotranscobalamin can create a much clearer picture of overall B12 status.17

Finally, genetic testing can also be helpful in assessing what form of B12 is most suitable. For example, methylcobalamin may be particularly useful for those with certain MTR or MTRR polymorphisms (genetic mutations). The MTR enzyme uses methylcobalamin and zinc in one of the steps to convert homocysteine to methionine and so adequate levels are vital in order for this reaction to take place. The MTRR enzyme is involved in regenerating methylcobalamin after this reaction and so must also be considered.

Key Takeaways

  • Vitamin B12 is an essential water-soluble vitamin which plays a role in the metabolism of almost every cell in the body; including normal nervous system functioning and DNA synthesis.
  • Deficiency can lead to widespread symptoms including fatigue, blurred vision, numbness, tingling, muscle weakness, sleep disturbance and hormonal imbalance.
  • The absorption of B12 is a complex process which can be broken into three key phases: the gastric phase, the intestinal phase and the mucosal phase.
  • There are several factors which can contribute to low B12 status including age, dietary preference, use of certain medications and digestive integrity.
  • Cyanocobalamin is an inactive form of B12, often used in supplements, which contains a cyanide molecule. It is therefore not recommended for those with liver or renal issues. Those who smoke should also be cautious as cyanide may not be eliminated effectively.
  • Hydroxocobalamin is an inactive form of B12 found predominantly in food. This is a good option for B12 deficient patients with tobacco amblyopia (a condition related to cyanide metabolism), cyanide toxicity and/or B12 deficiency optic nerve atrophy.
  • Methylcobalamin is an active form of B12 with a methyl group and is the only form able to cross the blood brain barrier without further metabolism. This form is a good option for the majority of the population due to its distinct neuroprotective effects. It is also recommended for those with certain genetic polymorphisms.
  • Adenosylcobalamin is the mitochondrial form of B12 and co-factor for a metabolic enzyme involved in energy production. It is a good option for those experiencing severe fatigue or with certain genetic polymorphisms reducing their ability to synthesise adenosylcobalamin in the body.
  • B12 status is most commonly tested via total B12 levels in blood serum. As this can be an unreliable indication of cellular B12 levels, it is recommended to consider holotranscobalamin, homocysteine, methylmalonic acid and/or genetic testing in conjunction with this, in order to create a more accurate picture of B12 status.

If you have any questions regarding the topics that have been raised, or any other health matters please do contact me (Amanda) by phone or email at any time., 01684 310099

Amanda Williams and the Cytoplan Editorial Team


  1. Busti AJ and Herrington JD (2015) ‘The Mechanism of Absorption of Vitamin B12 (Cobalamin) in the GI Tract’, Retrieved from:
  2. Lieberman M et al (2013) ‘Marks’ Basic Medical Biochemistry : A Clinical Approach’, Wolters Kluwer Health, 7(40), pp 744-759
  3. Institute of Medicine (1998) ‘Standing Committee on the Scientific Evaluation of Dietary Reference Intakes; Panel on Folate OBV; Subcommittee on Upper Reference Levels of Nutrients; dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B₆, Folate, Vitamin B₁₂, Pantothenic Acid, Biotin, and Choline’, National Academy Press
  4. Andrès E et al (2004) ‘Vitamin B12 (cobalamin) deficiency in elderly patients’, CMAJ, 171(3), pp 251-259
  5. Fatima R and Aziz M (2018) ‘Achlorhydria’, StatPearls Publishing, Retrieved from:
  6. Roth JR et al (1993) ‘Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium’, J Bacteriol, 175(11), pp 3303-3316
  7. Thompson JP and Marrs TC (2012) ‘Hydroxocobalamin in cyanide poisoning’, Clin Toxicol, 50(10), pp 875-885
  8. Van Asselt DZ et al (1998) ‘Nasal absorption of hydroxocobalamin in healthy elderly adults’, Br J Clin Pharmacol, 45(1), pp 83-86
  9. BNF: British National Formulary – NICE (2018), Retrieved from:
  10. Weinberg JB et al (2009) ‘Inhibition of nitric oxide synthase by cobalamins and cobinamides’, Free Radic Biol Med, 46(12), pp 1626-1632
  11. Lyall F, Young A and Greer IA (1995) ‘Nitric oxide concentrations are increased in the fetoplacental circulation in preeclampsia’, Am J Obstet Gynecol, 173(3), pp 714-718
  12. Mayer G, Kröger M and Meier-Ewert K (1996) ‘Effects of Vitamin B12 on Performance and Circadian Rhythm in Normal Subjects’, Neuropsychopharmacology, 15(5), pp 456-464
  13. Okuda K et al (1973) ‘Intestinal absorption and concurrent chemical changes of methylcobalamin’, J Lab Clin Med, 81(4), pp 557-567
  14. Xu G et al (2013) ‘A Single-Center Randomized Controlled Trial of Local Methylcobalamin Injection for Subacute Herpetic Neuralgia’, Pain Med, 14(6), pp 884-894
  15. Okada K et al (2009) ‘Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model’, Exp Neurol, 222(2), pp 191-203
  16. Medina F and Vitali D (1968) ‘Controlled clinical research with cobamamide in the treatment of viral hepatitis’, Clin Ter, 46(2), pp 139-144
  17. Spence JD (2015) ‘Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke’, Nutr Res, 36(2), pp 109-116

Last updated on 20th October 2022 by cytoffice


33 thoughts on “Vitamin B12 – why it is important and which form to choose

  1. I found this the best post I have read on B12 so far. Very useful, especially the reference to Methylcobalamin ‘s role in reducing homocysteine which is now know to be an independent risk factor for Heart attacks and stokes. I have a prescription for folic acid, but favour methylfolate and methylcobalamin as a better option for reducing homocysteine

  2. Very interesting and well explained to this lay reader. I was especially interested in the downside of cyanocobalamin which I started taking in the 1970s!

  3. A good blog but doesn’t indicate that neuropathy can result from B12. An elderly lady I know was not diagnosed as B12 deficient in time to prevent permanent nerve damage in her feet and lower limbs. Most deficient (elderly) people have several injections of B12 per year as even supplements may not be sufficiently absorbed.

  4. Have you tested the impact of your two sublingual B12 products on patients with FUT2 and MTR/MTRR Snps? It would be good to know how effective these sublingual supplements have been in clinical practice/trials at correcting B12 deficiency and also lowering homocysteine. Many thanks!

    1. Hi Justin,

      Thank you for your question. You may be interested in the results of this very recent study (published this month) that compared sublingual B12 and intravenous B12 and concluded that sublingual was more effective at raising serum B12 and should be the method of choice for vitamin B12 deficiency – available to view here.

      As you say certain SNPs can increase the need for B12, and symptoms along with testing will indicate a particular individual’s B12 status and the impact the SNPs may be having.


  5. I had part of my ileum removed 20 years ago due to Crohns and experience balance issues but these seem to be getting more regular. I now see this could be down to not absorbing enough B12. Is it worth taking oral supplements as I have seen nasal sprays recommended for this situation?

    1. Hi Sue,

      Thank you for your comment. I have not found any studies comparing sublingual supplements to nasal sprays. However, similarly to nasal sprays, sublingual can bypass the need for intestinal absorption if allowed to dissolve under the tongue. See the research paper above comparing sublingual to injections.

      If you suspect you have a B12 deficiency I recommend that you visit your GP for a blood test before you start taking oral B12 (which can affect the results).

      Once you have had the blood test, you could take some oral B12 and see how your symptoms are (blood tests are not always reliable so even if you are in the ‘normal’ range I would recommend a trial of some additional B12 and monitor the impact on your symptoms). I would also recommend an all round multivitamin and mineral, for example our CoQ10 Multi which is in capsule form to increase your intake of all the B vitamins (as well as other micronutrients).

      You may also be interested in our free health questionnaire service. If you complete a health questionnaire we will send you some written diet and supplement recommendations, availble here.

      I hope this helps.


  6. I have got a pin hole internal bleeding from my gut and cause me to have anemia specialist from the hospital been advised me of taking an iron tablet every day. Will that work with B12. Is it likely to cause me any problems. Would like your advice please.

    1. Hi Jacqueline,

      Thank you for your comment. A B12 tablet is ok to take alongside your iron tablet. I would recommend that you take an all-round multivitamin and mineral – for example our CoQ10 Multi has good levels of B12 (200mcg) plus other vitamins and minerals. An all round multivitamin and mineral is always a good place to start, rather than taking individual nutrients, and then individual nutrients can be added if needed. You can take start with one CoQ10 Multi for 7 days, then increase to 2. It is very low in iron but has other nutrients (including B12) that are needed for red blood cell production.


  7. I have seven of the above symptoms that could indicate I may be deficient in B12.
    I already take your 50+ supplements which include B12 but would I benefit from extra B12 supplements or would that be overkill and possibly dangerous?

    1. Hi Aileen,

      If you suspect you may have a B12 deficiency then in the first instance I would suggest that you visit your GP for testing. You will need to stop the 50+ for 7 days prior to the test, otherwise the B12 in the product could affect the result. If you would like to email me ( with your symptoms I can give you some further advice. We do also offer a free health questionnaire service – if you complete and return a health questionnaire we will send you some written diet and supplement recommendations.


  8. Just a quick note it was always difficult to understand a vitamin it’s importance and lack of.
    With someone like myself who has enlish Danlos Sybdrome fibro CFS and PTSD, plus I am recovering from severe pneumonia.
    I am so glad I found your firm.
    I have made a small order but as I run out I look forward to purchasing from you thankyou

    1. Hi Sandra,
      Yes I have found a paper referring to B12 bringing on seizures, although the paper suggests this is an unusual manifestation of deficiency. Given its importance for the nervous system, it is not surprising that it could be a contributory factor in seizures for some people. Obviously there are many other possible reasons and causes for seizures and we would always recommend visiting your G.P. with such symptoms for proper investigation of causes and diagnosis.
      Best wishes,

  9. Can vitamin B12 help with muscle cramps, muscle tingling etc. I have pelvic floor dysfunction due to tight muscles in my pelvic floor and wondered if this would help me. Thank you

    1. Hi Shirley,
      Thanks for your comment.
      I would try magnesium for your muscle cramps / tight muscles – you could take Biofood Magnesium – 2 per day. If you are taking any blood pressure medication be aware that magnesium can have a blood pressure lowering effect, so start with 1 per day for a few days and monitor the effects on your blood pressure.
      The tingling you describe – is this muscles or could it be nervous system? An all-round multivitamin and mineral would be a good place to start – I suggest our CoQ10 Multi which has a good level of B12 in it, alongside other B vitamins and nutrients which are also important.
      You may also be interested in the free health questionnaire service that we offer – if you complete and return a health questionnaire we will send you some written diet and supplement recommendations.
      Finally, if you haven’t discussed these symptoms with your G.P. then I would recommend a visit so they can carry out any necessary investigations.
      Best wishes,

  10. An excellent explanation of a complex subject. I do have a question.
    Suffering from debilitating fatigue my doctor decided to give me a B12 injection despite bloods tests showing levels to be within reference. The injection seemed to help so I then put myself on high doses of sublingual methyl and Cyanocobalamin. I’m so much better now.
    Conversely my partner suffering from sudden onset fatigue, nerve pain, optical disturbances, and permanent excruciating headaches has no detectable B12 in his blood tests. Despite having three injections weekly for over two months. As the injections are hydroxycobalamin perhaps they are not effective for these symptoms. His symptoms have improved greatly since taking mega dose sublingual B12 ( methyl and Adenosylcobalamin) but blood tests still show no B12.
    I understand blood levels of B12 may not be the best indicator of stored B12. My question is, as B12 is water soluble but is also stored in the liver what would be maximum safe dosages bearing in mind the potential low absorption rate. Can we overdose on B12?

    1. Hi Angela,

      Thanks for your query. As well as blood tests looking at serum B12, there are functional tests that can provide an indication of B12 status. For example MCV (mean corpuscular volume) is a measure of the size of red blood cells – if the red blood cells are larger than normal then one reason is insufficient B12. Also levels of methylmalonic acid (MMA) can be measured in blood or urine – if this is raised, it can indicate a need for B12. You mention that your partner’s symptoms have improved since taking a sublingual supplement but that the blood test still shows no B12, the improvement in symptoms is a good guide that the dose being taken is sufficient (what dose is your partner taking?). I would discuss with the GP whether some indirect testing is also possible. Have any underlying reasons for low B12 been investigated – other health conditions which may affect absorption? Prescription medications which, again, can affect absorption?

      With regard to safe upper levels, the European Expert Group on Vitamins and Minerals (2003) concluded that there was insufficient data to set a safe upper limit and that vitamin B12 has low toxicity. On the other hand you only want to be taking higher therapeutic doses for the time that they are needed and reduce to maintenance doses when possible.

      You may be interested in Sally Pacholok’s book “Could it be B12?”.

      If you would like some more individual advice, please email me with further details of which supplements are being taken, any medications and a brief summary of medical history and symptoms.

      I hope this helps.

  11. My sister will love this. She get B12 injections but I just take your daily sub-lingual – I’m mostly vegitarian so don’t get a great deal from food.
    thanks for this interesting blog.

  12. For me something very difficult to understand, because in my view it’s a contradiction is: how can it be to have a normal level of B12 in your blood but still be diagnosed with Pernicious anemia. If the intrinsic factor wouldn’t work then surely it would show up in the blood and therefore the B12 would be low, but it’s not, it’s normal. Thank you for this article.

    1. Hi there – thank you so much for your comment. It does seem strange, but often what is most important with B12 is its ability to function within cells, serum levels of B12 are only half the picture. B12 needs to be methylated for it to be active within the body. Some people possess genetic mutations known as single nucleotide polymorphisms or SNPs, some specific SNPs can mean that you have a reduced function of the enzyme which methylates B12, therefore most B12 does not become “active” and doesn’t function as normal in the body.

      Generally pernicious anaemia is only diagnosed in conjunction with low B12 but it may be that homocysteine has tested high which is also a sign that there may be problems with methylation, or methylmalonic acid which is another sign it is not being utilised.


      It has also been noted that certain antibodies can interfere wit B12 testing which can give falsely high serum B12 results.

  13. Very informative article.i stopped taking B12 years ago because my energy level was high from strenuous activities; but with increasing age and I recently had hip replacement surgery and was feeling fatigue and tired , I am now back to taking a B12 capsule and slowly regaining energy and feeling calmer and less anxiety.
    Question : is it best to take in morning with meals or at night before bed time?

    1. HI Olivia – as B12 can energise, it is best taken in the early part of the day. It is best taken on an empty stomach – say ½ hour or so before eating. Many thanks for your comment on our blog.

    1. Hi Rose-Mary – If you are supplementing with B12 at the time of a blood test you can indeed get higher blood readings than are necessarily representative of tissue levels. Also if you are unable to convert B12 to a methylated and useable form you could indeed be deficient but still show high blood levels. However this can be identified by a test for methylmalonic acid which if high will tend to indicate that B12 is not being properly metabolised. It is also possible to get a high B12 blood test that is not representative of actual levels in cases where red blood cells are being broken down in the body, as with some blood cancers.

  14. I recently had fbc and have have high homocysteine and high MCV and my level is 700 odd. I supplement with your methylcobalamin sublingual but am vegetarian. However I also have the genetic blood disorder hemachromatosis. Is there any research which shows a link to this condition? I know if I stop taking my supplement my symptoms return as I have run out several times and then suddenly felt unwell. Each time, I have started to take my tablets again and felt back to normal. On another note, it said in my results that the normal reading could be anything from 174 being the lowest acceptable level. How can this be? Is that not telling anyone that is deficient that their reading is normal. I read somewhere that in the US the lowest acceptable level was 400? You don’t mention in your article what the lowest acceptable level is. People need to know that their levels are deficient. Could there be another article including lowest acceptable levels published. I tell people all the time but they would rather listen to their doctor than me. Thanks for any advice on the hemachromatosis. My mum has the same, her B12 levels are 1000 but the doctor will not listen to her although her homocysteine and MCV is high like mine. Is it possible to take too much as she is supplementing with sublingual like me and has no feeling in feet or front of legs. Also she is on a low dose of omeprazole which we know causes less B12 absorption too. This is also something which needs massive awareness raising.

    1. Hi Becky,

      Thank you for your comment. There can be multiple factors that affect both homocysteine and MCV. As you are already taking methylcobalamin, which is an essential nutrient in the methylation cycle, it is unusual to have high homocysteine. However folate and B6 also play an essential role. Many people can have genetic polymorphisms that mean that you are unable to methyl folate and therefore require folate in the l-methyl-folate form. It may be useful to do a genetic test to determine if this is the case. I would recommend switching from B12 to Methyl Factors to fully support the methylation cycle for 2 months and see if this has an effect on your homocysteine levels, it still contains methyl cobalamin but there are other nutrients which also support the clearance of homocysteine. I do not know of a mechanism where hemochromatosis is related to homocysteine but this doesn’t mean there is not a connection but no research I can find. However hemochromatosis will contribute to high MCV.

      UK B12 recommendations are 115 to 1000 pmol/L (picomols per litre), US is in different units 200 ng/ml to 900 ng/ml.(nanograms per ml)- these conevert to roughly the same

      The normal range for vitamin B12 (total) is between 200 – 1100 ng/L (nanograms per liter), 200 – 1100 pg/mL (picograms per milliliter), or 148 – 811 pmol/L (picomoles per liter). The normal range for active vitamin B12 (holoTC) is around 20 – 134 pmol/L (picomoles per liter).

      The trouble is with serum levels of B12, it is not demonstrating if B12 is getting into cells and exerting action, some people have high serum B12 and high homocysteine as they are unable to methylate B12 to make it active, so I don’t fine serum reading particularly helpful anyway.

      Looking at zinc and copper status is important in hemochromatosis as they complete with iron for absorption, so it could be a good idea to add in 1 x Zinc and Copper,other than that it is to avoid adding in additional iron.


  15. Hi! I’ve just found your article. My genetic test indicates I have hemochromatosis. A couple years ago, a different doctor told me I likely had the MTHFR mutation after seeing high homocysteine and high B-12 in my lab results. I began taking methyl B12 and folate – but am now wondering if I should not take the B-12 given my hemochromatosis. Everything I read says to stay away from B-12 and Vitamin C with hemochromatosis. Do you have a perspective on this?

    1. Hello Rhonda,

      Thank you for your query. Both B12 and iron as essential for red blood cell production and function. Therefore, it is extrapolated that B12 contributed to excess iron. Haemochromatosis is excess iron and independent of B12 levels. In fact, it is often recommended to supplement B12 as haemochromatosis is sometime associated with low B12. Vitamin C can increase iron absorption, therefore it is best to avoid high supplementation with vitamin C. However, it would be best to do a genetic test to determine if you do have an MTHFR or other methylation SNPs – although it does seem likely. It would also be good to test homocysteine again, following B12/folate supplementation.

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