… How to choose the right type of B12 for depression and anxiety, methylcobalamin for depression, bipolar, anxiety, too much methylation bad for anxiety   

How to choose the right
type of B12
for Depression Anxiety and Bipolar 

  Choosing the right type of B12 can make a difference and help you achieve your health goals, understanding the different properties of the 4 different types of B12 can help you choose which one to use. 
Best type of B12 for depression and anxiety
B12 comes in 4 different types
  • Methylcobalamin, Methyl-B12
  • Adenosylcobalamin, Adenosyl-B12
  • Hydroxocobalamin, Hydroxo-B12
  • Cyanocobalamin


The 1st thing that should come to mind when you think of methyl B 12 is methylation, it’s in the name methyl cobalamin it’s the type of cobalamin that donates methyl molecules called methyl groups to the body. Methylation is a chemical reaction whereby methyl groups are added or removed from other molecules to change them, methylation is needed for over 50 chemical reactions and is occurring continuously in every cell of your body, including the manufacture neurotransmitters, the breakdown of inflammatory homocysteine which is associated with increased brain degeneration and ageing and what is called DNA methylation which controls the expression of every gene in the body; having poor DNA methylation can have widespread effects causing diverse health problems in many parts of the body.
Methyl B12 is mainly found in the blood, brain and cerebrospinal fluid. Methyl B readily crosses the blood-brain barrier as opposed to adenosyl B12 that is mainly found in the mitochondria see below. The way methyl B12 is concentrated in the brain and cerebrospinal fluid suggests that it is the form of B12 most involved in brain health and consequently mental health.
The methyl molecules that methyl B12 donates to the brain are used both to manufacture neurotransmitters and to break down after they have been released into the synapse, as well as being involved in neurotransmitter balance methylation is critical lowering and maintaining healthy levels of homocysteine and inflammation. Imbalanced neurotransmitters, homocysteine and inflammation levels are all involved in depression and in my clinical experience methyl B12 is the form of B12 that has the greatest therapeutic effects against depression. However having said that there are some very rare individuals have a metabolic system that tends to over methylate and for these people supplementing large amounts of methyl B12 may make them feel worse, either more anxious or depressed and they will need to either take alternative forms of B12 or take only a little methyl B12 and counterbalance it with niacin; I discuss this below and elsewhere in more detail see How to Deal with over Methylation Using Niacin.
B12 and Neurodegeneration
Methyl B 12 also protects nerve cells from a loss of myelin insulation (demyelination) that occurs in neurological diseases such as Multiple Sclerosis, neurological degeneration may also present itself as visual or balance disturbances. Super high doses of 25,000 mcg daily by intramuscular injection slowed down the progression of Lou Gehring disease[i], adenosyl B12 is another form of B12 that protective against demyelination. I specialise in treating mental health problems not neurological diseases but I would advise that if you have a neurological disease and you are going to try supplementing high doses B12 you should 1st have your DNA tested to see if it could
Methyl B12 requires glutathione to work
Methyl B12 metabolism requires glutathione and if your glutathione levels are inadequate you won’t get any beneficial results from supplemental methyl B 12, you can glutathione levels with NAC cysteine or more expensive is sublingual glutathione.
As a methyl donor methyl B12 works in tandem with methylfolate (the natural methylating form of folic acid) and to for optimum wellness your methylfolate levels must also be adequate; as you may already know your methylfolate levels will not be adequate if you have the MTHFR gene mutation. Therefore to restore and maintain balance when you have the MTHFR gene mutation you will probably need to supplement both methylfolate and B12, however you do not start by supplementing methylfolate as this may produce toxic healing reactions. Before introducing large amounts of methylfolate into a body with the MTHFR gene mutation you start by ensuring the detoxification pathways will be able to cope with the extra workload they will receive, you introduce a micro dose of lithium orotate to improve B12 utilisation, then introduced B12 including at least some methyl B12 as it is the primary methyl donating form and eventually progress to directly supplementing methylfolate.
For a more detailed description see MTHFR Treatment for Depression Anxiety and Bipolar
How to Test If You Need More Methyl B12
To test if you are methyl B12 deficient you can have blood tests but they are not particularly effective way to work out if you are deficient. The standard test of measuring methyl B12 levels in blood serum can be misleading, it does not indicate the level of B12 in the cells. More useful would be measuring MCV and MCH, these are basically methods of the average size of your red blood cells and the concentration of haemoglobin per red blood cell.
If these tests show that your B12 levels are below the medical reference range then you definitely B12 deficient but if these tests show your B12 levels are just within the normal range that doesn’t inform you whether or not you could benefit by taking more, as I’ve said many times elsewhere an individual may have an above average need or benefit from an above average intake of a specific nutrient; furthermore nutritional supplements can be used not just to bring the levels to within normal reference range, they can be used in higher doses as a medicinal substance remedy.
I’m suggesting you can work out how much B 12 to take by supplementing it and seeing if it improves your condition. For example let’s say that your B12 levels look normal but you experience more energy and less depression when you supplement it, or your levels look normal but your homocysteine levels are too high and when you supplement B12 it lowers your homocysteine.
If you have problems depression or low energy you will be able to tell for yourself if methyl B12 supplements are helping you, if you’re taking it to lower homocysteine you will need to monitor your homocysteine levels with blood test, if you don’t have any health issues but are simply taking it to prevent deficiency because you are vegan for example you could take 1000 or 2000 mcg a day for a month to compensate for any pre-existing deficiency and then take this dose once or twice a week for maintenance. 

Methyl 12 for depression
If you are under-methylated either because your diet is deficient of methyl donors especially methyl B and folate or you have the MTHFR gene mutation compromising your methylation it’s going to affect the health of your brain and could cause depression.
I’ve yet to see anyone with depression make a full recovery from just B12 therapy alone but if you suffer from depression and you are vegan or have a poor diet or any digestive issues that can interfere with the absorption of B12 including low stomach acid, small intestinal bacterial overgrowth and more it would be perfectly valid to presume that you are B12 deficient and until you correct this problem you are may not be able to make 100% recovery; furthermore studies have shown that low folate, B12 and high homocysteine (a combination definitively indicating a lack of methylation) is associated with non-responsiveness to antidepressants[ii] and higher B12 levels are associated with better treatment outcome with major depression[iii].  
It shouldn’t be a disappointment to you to hear that taking B12 is unlikely to be the hundred percent cause of the problem and hundred percent cure for the problem; there is a new understanding that depression a condition in the brain whereby structures and neuro circuits that control mood suffer a loss of function and that what causes this diminished function is when our brains ability to maintain and repair itself (neuroplasticity) becomes overwhelmed by damage and wear and tear from inflammation, oxidative stress, nitrosative stress (see hydroxo B12 if you haven’t heard of nitrosative stress). Inflammation levels become increased when we have diminished methylation from a lack of methyl B12 and folate as well as from deficiencies of other key nutrients primarily B3, magnesium, EPA, and prolonged exposure to elevated levels of psychological stress. I What Really Causes Depression Beyond Neurotransmitters elsewhere.
The bottom line is overcoming depression involves repairing the structures in the brain control mood by eliminating or at least diminishing the destructive forces that break the brain down and increasing ideally maximising the restorative neuroplastic mechanisms in the brain; don’t try to look for rely on one single monotherapy approach but rather instead combine multiple treatment approaches together including supplementing B12. Think of using B12 and other supplements in 2 ways firstly to eliminate actual deficiencies and secondly you can use in much higher amounts like medicines to enhance or amplify specific processes that treat your problem.
Methyl B12 for Bipolar
When you read that methyl B12 enhances methylation, increases neurotransmitter production and be helpful for depression you would be right to question is this a good idea if you have bipolar disorder and a problem with overproducing dopamine, norepinephrine and glutamate.
Well it turns out methylation doesn’t only increase the production of neurotransmitters it is also used to break down neurotransmitters in the synaptic cleft including dopamine, so far I have not had a case of methyl B12 provoking mania, indeed a lack of methylation is a consistently found feature of bipolar disorder[iv], however we should always be safe and I do not recommend anyone with bipolar take a high doses of methyl B12 on its own without having multiple anti mania safeguards in place especially anyone with the. COMT +/+ mutations which compromises the ability to break down dopamine and norepinephrine. I always prescribe lithium orotate for bipolar disorder which is not only a protection against manic episodes it also appears to enhance B12 utilisation and methylation in the bipolar brain.
If you want to learn how to use supplements to balance the bipolar brain I’m available for consultations my London clinic or via Skype for people that live too far away.
If you do have an adverse reaction A quick way to antidote over methylation is to take a high dose of niacin (B3 to deplete the availability of methyl groups, but balancing bipolar disorder is much more involved than simply B12 niacin.
Methyl B12 for Anxiety
Online you often see people claiming B12 deficiency can cause anxiety but I’ve never found B12 to have any useful therapeutic effect for any of my patients with anxiety nor can I find anything in the medical literature substantiating such claims. Conversely what I have seen occasionally and I really mean only very occasionally is high doses of methyl B12 and other methylating supplements making anxiety symptoms temporarily worse. Some people suffer from over methylation as opposed to under methylation and when they take high doses of methylating supplements they will feel worse, if this happens to you you can quickly antidote it by taking large amounts of niacin which reduces the availability of methyl groups.
If you want to experiment to see if under methylated all over methylated by a bottle of methyl B12 sublingual and niacin and see if either one makes you feel better or worse. I’ve been in practice for 30 years and I would guess the number of people I’ve seen that found niacin supplements therapeutic is less than 1 in 700 or maybe even closer to 1 in 1,000 (that’s just a guess) the point I want to make is it rare. Having said that for those few individuals that niacin helpful they found it incredibly helpful, literally life changing. They all said the benefits began very quickly some within hours others within days so it’s very easy to work out if niacin can be a useful remedy for you. If you don’t feel any benefits within a few days if not for you, conversely if it makes you feel worse than now would indicate that you have a problem with under methylation and you can quickly test this with methyl B12 and SAM-e supplements.
There is currently no precise laboratory test to determine exactly what affects if any supplementing methyl B12 will have on an individual bipolar brain and until there is we have to rely on personal experimentation. Some people improve their health by increasing methylation with methyl donating supplements, in others this can produce over methylation, to quickly antidote over methylation you should have Niacin B3 supplements for safety when you first experiment with methyl 12 See How to Treat with Over Methylation Reactions using Niacin.

Supplementing methyl B12
Methyl B12 is readily available in sublingual lozenges, oral sprays and liquids, See B12 Supplements 4 Things You Need to Know about Absorption and Dosage for more information.


When I think of adenosyl B12 the 1st thing I think of is cellular energy production. Adenosyl B12 found mainly concentrated in the mitochondria which are structures within every cell in our body, the mitochondria are the places we make the majority of the energy our body uses for everything from manufacturing neurotransmitters and hormones to contracting the muscles that pump blood around our body and move our body around.
I think of trying adenosyl B12 before methyl or hydroxo B12 for conditions characterised by a lack of energy such as chronic fatigue syndrome and also for people that have a very low tolerance to physical exertion, when exercising they suddenly run out of energy and feel worse after exercise.
Adenosyl B12 is actually manufactured in our mitochondria from methyl B12 so you might think why not just take methyl B12 as the parent molecule this would give the body the methyl groups donated from methyl B12 and what it needs to manufacture adenosyl B12, the problem is that some people have enzyme deficiencies due to variations in the COMT genes that compromise their ability to manufacture the adenosyl B12 from methyl B12; thankfully we can take adenosyl B12 as a supplement to circumnavigate problem.
How to Test If You Need More Adenosyl B12
There are basically 3 ways you can work out if you may be having a problem with the conversion of methyl B12 to adenosyl B12:-
  • the 1st is you can simply buy a bottle of sublingual adenosyl B12 and try between 1000 to 5000 mcg per day and see if it has a therapeutic effect on your energy deficit, mood or homocysteine levels
  • the 2nd technique is you can have your genes tested and see if adenosyl B12 is suited to your COMT V158M and VDR Taq variations
  • the 3rd technique you can use to determine adenosyl B12 levels is to test for urinary methylmalonic acid (MMA). If MMA levels are elevated and especially if your homocysteine levels are also elevated supplement adenosyl B12 and either a high dose or just a small dose of methyl B12 to bring both MMA and homocysteine levels down.
The COMT gene is also involved in the detoxification of spent oestrogen and supporting the COMT gene deficit with adenosyl B12 may be helpful for anyone vulnerable to oestrogen dominant cancers such as some types of breast cancer it is also worth trying if you have a buildup of oestrogen premenstrual the with symptoms such as fluid retention, fatigue and alterations in mood at this time.
Supplementing adenosyl B12
Adenosyl B12 is readily available in sublingual lozenges, oral sprays and liquids, See B12 Supplements 4 Things You Need to Know about Absorption and Dosage for more information.


Hydroxo B12 has 3 notable features:
Firstly it protects the body including the cells and myelin sheath in the brain from oxygen free radical and nitrosative free radical damage or stress as it’s called, basically it absorbs or mops up reactive oxygen species[v] and excessive nitric oxide[vi]. We usually think of nitric oxide as a desirable thing especially from a cardiovascular health point of view, however excessive amounts of nitrous oxide can produce a type of free radical damage called nitrosative stress, if you haven’t heard of nitrosative stress before it’s like oxidative free radical damage but stemming from nitric oxide and excessive protein consumption.
Nitrosative and oxygen free radicals directly damage brain cells and the myelin sheath membranes that insulates them, this damage then provokes inflammation in the brain which causes further damaging effects. It is now know that inflammation in the brain is a cause of mental health problems, perhaps the leading or definitive course, if you are not yet aware of this you need to update your understanding. See Beyond Neurotransmitters Inflammation Causes Mental Health Problems . Briefly what inflammation does is it can directly interfere with neurotransmitter production [ref] and cause a breakdown of synaptic connections and dendrites so that we literally have less synapses to ‘carry’ neurotransmitters. A new frontier in treating mental health problems is to target inflammation in the brain, the pharmaceutical industry is looking at drugs to achieve this goal, in my practice I’m doing this with already by identifying and targeting the original sources of inflammation combined with using natural remedies with anti-inflammatory effects and anti-inflammation diets.
I think of trying hydroxo B12 when I meet a patient with signs of elevated free radical damage causing premature ageing in the brain characterised by loss of cognitive and/or other mental functions and premature ageing skin characterised by the kind of greyish, haggard, small dry fish scales appearance to the skin that you see in heavy drinkers and smokers which exposes the body and skin to massive amounts of free radical damage.
If can try hydroxo B12 and it produces noticeable improvements in your health within a few weeks you could suspect that oxygen and nitrosative free radical damage from excess uncontrolled nitric oxide was part of your problem; switching to a vegan anti-inflammation diet and taking a stack of additional supplements that quench free radicals may also further improve your health.
In terms of diet the ketogenic and Palaeolithic diet produce a lot of nitrosative damage because they are so high in protein and nitrogen, initially these diets can stimulate neuroplasticity but after a prolonged period such diets can increase inflammation in the brain which works against neuroplasticity; so although these diets supply plenty high B12 containing foods they could be made healthier with supplemental hydroxo B12. The vegan diet is noted for containing less nitrogen in producing less nitrosative stress, however it contains practically zero B12 and therefore B12 supplementation is essential and not optional.
Secondly hydroxo B12 have a kind of natural time-release effect, it persists in circulation after ingestion including by injection giving it a natural sustained or prolonged effect.
Thirdly hydroxo B12 may be the most well-tolerated form for all types of COMT V158M and VDR Taq variations.
Hydroxo B12 can be readily converted into methyl B12 and then into adenosyl B12, however in terms of supporting methylation metabolism the neurotransmitter and DNA methylation methyl B12 is the superior form.

There’s a theory that mitochondrial dysfunction oxidative stress is involved in the mental health problems including schizophrenia and bipolar… Oxidative stress

Supplementing hydroxo B12
Hydroxo B12 is readily available in sublingual lozenges, oral sprays and liquids, See B12 Supplements 4 Things You Need to Know about Absorption and Dosage for more information.

Cyanocobalamin is a cheap synthetic form of B12 that you will still often see used in multivitamins but anyone who knows what they’re talking about no longer recommends and supplement manufacturers should stop using, one of the things we want to obtain from B12 is for it to donate a methyl groups (simple carbon molecule needed for methylation metabolism) but cyanocobalamin requires us to give up a methyl group to convert it into the active form. I tried supplementing several thousand mcg of cyanocobalamin via the efficient sublingual route and found it completely failed to deliver any of the noticeable health benefits I receive from methyl B12.

In Summary

  • Methyl B12 (the brains B12) good for mental health problems also for methylation.
  • Adenosyl B12 (the mitochondrial B12) support energy production, good for fatigue.
  • Hydroxo B12 combats nitrosative free radical damage from elevated uncontrolled nitric oxide, sustained release.
  • Choosing the Best Type of B12 for Absorption How to Supplement B12 Efficiently
Further reading:-
I specialise in treating and coaching people with mental health problems how to obtain better mental health with natural remedies and self-help techniques. If you would like me to look into your individual case and develop a tailor-made programme of natural remedies, dietary advice and brain training exercises I’m available for private consultations at my London clinic and online for people that live too far away.
I also run regular meditation classes in London and online.
Click on the 
bookings tab to make an appointment.
I’m passionate about treating mental health and I’d be very happy to work with you.
[i] Izumi Y and Kaji R. [Clinical trials of ultra-high-dose methylcobalamin in ALS]. Brain Nerve. 2007 Oct;59(10):1141-7
[ii] Am J Psychiatry. 1997 Mar;154(3):426-8. Folate, vitamin B12, and homocysteine in major depressive disorder. Fava M, et. al PMID: 9054796 DOI: 10.1176/ajp.154.3.426
[iii] BMC Psychiatry. 2003; 3: 17. Published online 2003 Dec 2. doi:  10.1186/1471-244X-3-17 PMCID: PMC317314 PMID: 14641930 High vitamin B12 level and good treatment outcome may be associated in major depressive disorder Jukka Hintikka, et al
[iv] Int J Neuropsychopharmacol. 2014 Apr;17(4):561-9. doi: 10.1017/S1461145713001569. Epub 2013 Dec 17.
Decreased global methylation in patients with bipolar disorder who respond to lithium.
Huzayyin et al PMID: 24345589 DOI: 10.1017/S1461145713001569
[v] Free Radic Biol Med. Author manuscript; available in PMC 2012 Aug 15. Published in final edited form as: Free Radic Biol Med. 2011 Aug 15; 51(4): 876–883. Published online 2011 Jun 2. doi:  10.1016/j.freeradbiomed.2011.05.034 PMCID: PMC3163124 NIHMSID: NIHMS309867 PMID: 21672628 Vitamin B12 protects against superoxide-induced cell injury in human aortic endothelial cells.
Edward S. Moreira,1,2,3 Nicola E. Brasch,2,3 and June Yun1,3,*
[vi] Br J Pharmacol. 2001 Oct; 134(3): 521–528. doi:  10.1038/sj.bjp.0704287 PMCID: PMC1572981 PMID: 11588105 Effects of agents that inactivate free radical NO (NO•) on nitroxyl anion-mediated relaxations, and on the detection of NO• released from the nitroxyl anion donor Angeli's salt Anthie Ellis, et.al.
Please help and support this site. 

Hi my name is Peter Smith I specialise in treating and coaching people how to live well with mental health problems, digestive health problems/IBS, sleep problems and type II diabetes using natural therapies.
I used these techniques to overcome and live well with my own bipolar disorder and IBS. I've been in practice as a natural medicine practitioner since 1988.

What I Treat

  • Brain Chemistry and Mental Health problems (depression, anxiety, bipolar disorder, addiction, OCD)
  • Digestive Health: IBS, bloating, SIBO (which can be the cause of  60% of IBS) and parasites (with external lab testing)
  • Mercury and Heavy Metal Detoxification (with external lab testing)
  • Addiction (by balancingbrainchemistry, supporting healthy dopamine levels etc.)
  • Meditation and Relaxation brain-training for mental health problems, and adrenal exhaustion (individual and small classes)
  • Cognitive hypnotherapy and NLP
  • Drug-Free better Sleep
  • Insulin resistance, pre- and early type II diabetes
If you’d like treatment for any of the issues discussed in this article I specialise in treating and coaching people how to obtain better mental health with natural remedies and self-help techniques. If you would like me to look into your individual case and develop a tailor-made programme of natural remedies, dietary advice and brain training exercises I’m available for private consultations and I’m available for private consultations at my London clinic and online for people that live too far away.
I also run regular meditation classes in London and online.
I’m passionate about treating mental health and I’d be very happy to work with you.
Click on the
bookings tab to make an appointment.
To Book an Appointment
At my London clinic please call the Hale clinic reception:
020 7631 0156
(online bookings will be made available soon on the Hale Clinic website**)

For a Skype coaching session email me letting me know where you are located/what time zone you are in:

For enquiries/further information:
Mobile: 07941 331 329
Email: hello@PeterSmithUK.com

(please keep your email brief)

As a general rule improvements are seen within 2-3 appointments so you can quickly know if the treatments are helping you and you are making a good investment.
For a more information about me and what the conditions I treat click here: About About Peter Smith
Please help and support this site.  
I’m giving you the information first instead of selling the information as an e-book and then asking you to make a donation if you feel that the information has helped you and would have been happy if you had bought it as an e-book you could buy me a couple of coffees or more :) using the PayPal Donate below Button below
Another way you could contribute to this site by helping me with the proofreading. People regularly point out that there’s a large number of errors on my site which I find quite embarrassing, but I’m quite dyslexic and I don’t notice them myself.
If you find spelling and grammatical errors in the text please email the page and paragraph of the error, I really appreciate the help.
©Peter Smith. Please feel free to download or print my work for personal use, I wrote it to help people. You can copy and distribute my work on your web pages and in literature but please give me credit for the fruits of my labour and don’t turn yourself into a plagiarist. When you copy my work please indicate where you got the information from (e.g. from or according to the website balancingbrainchemistry “…”) and include a reference/link to my name and the website or book you used. [#22]