Lower brain levels of vitamin B12 in schizophrenia, Supplementation May be Needed

Recent findings indicated vitamin B12 levels in the brain decrease with aging and are lower in individuals with autism or schizophrenia, compared with age-matched healthy controls.

To our knowledge, this is the first report of pathologically reduced levels of active B12 in autistic and schizophrenic brain. Although the number of brain samples analyzed was limited, our findings highlight a possible role for vitamin B12-dependent methylation reactions in brain function and in the etiology of neurological disorders.

“These are particularly significant findings because the differences we found in brain B12 with aging, autism and schizophrenia are not seen in the blood, which is where B12 levels are usually measured.” Richard C. Deth, PhD, of Northeastern University, Boston, said in a press release. “The large deficits of brain B12 from individuals with autism and schizophrenia could help explain why patients suffering from these disorders experience neurological and neuropsychiatric symptoms.”

Our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

While provision of supplemental vitamin B12 may be helpful in treating the aforementioned brain disorders, several issues must be considered.

The required dosage may significantly exceed the Recommended Dietary Allowance (RDA) of 2.4 μg/day. (2.4 micrograms/day).

Note: only about 10 mcg of a 500 mcg oral supplement is actually absorbed in healthy people (source NIH)

Thus supplementation with higher dose levels of the active Vitamin B12 variations (i.e. MeCbl and AdoCbl) may be required to address an oxidative stress-related functional deficiency.

Both autism and schizophrenia are associated with oxidative stress, which also plays an important role in aging, and oxidative stress may underlie the decreased brain B12 levels observed in this study. The findings suggest the need for further research to determine if the use of supplemental methyl B12 and antioxidants like glutathione could help prevent oxidative stress and be useful in treating these conditions.

NOTE: After seeing this research we contacted one of the researchers to get more information. Below is the result:

Short Interview with Richard Carlton Deth, Ph.D., He is a neuropharmacologist, a professor of pharmacology at Nova Southeastern University and Lead Author on this recent research.

Can you please tell me what your researchers believe might be the level of supplemental Vitamin B12 that could be required to address the deficit.

Response by Professor Richard Deth:

I’m a molecular scientist, not a clinician, so I can’t give medical advice. However, methylB12 supplements with 1-5 mg are commonly available, including sublingual forms.

Common sense would suggest a cautious gradual approach starting with a lower dose (e.g. 1 mg every other day). The important thing is that methylB12 (methylcobalamin) is likely to be more effective that standard B12 (cyanocobalamin).

Schizophrenia.com: What is the evidence for this lower level of B12 in schizophrenia being causative vs. correlational?

Response by Professor Richard Deth:

My view:
MethylB12 exerts control over methylation reactions and there is extensive evidence of impaired methylation in schizophrenia, dating way back to early studies in the 60’s and 70’s which gave rise to the single-carbon theory of schizophrenia. This theory and the subsequent dopamine theory are embodied in the unique phospholipid methylation activity of the D4 dopamine receptor, which is now recognized as being capable of modulating NMDA (i.e. glutamate) receptor activity. These are related to the molecular mechanism of attention, which appears to be dysfunctional in schizophrenia (i.e. gamma frequency synchronization of neural networks).

I wrote a short book about this, (Molecular Origins of Human Attention: The Dopamine-Folate Connection, available on Amazon). You might find it interesting, especially the schizophrenia chapter (please forgive the feeble fictional attempt to personalize the problem).

These days the role of methylation-dependent epigenetic regulation of gene expression (i.e. DNA methylation) is a big deal, so it is not hard to think that a problem with methylation could translate into a problem with gene expression. Changes in DNA methylation leading to changes in gene expression appears to be a mechanism of memory formation. Thus if there is problem with methylB12 it could be manifested as a problem with attention and a problem with memory. In several studies we’ve shown dramatic naturally occurring age-dependent decreases in methylB12 and expression of its methylation-regulating enzyme methionine synthase. Thus the age-dependent onset of schizophrenia might be a consequence of this age-dependent decrease adversely affecting a vulnerable subpopulation.

Schizophrenia.com: Are you aware of any research that would suggest there are potential preventative dosing / prophylactic applications of Methyl-B12 for people at high risk of schizophrenia or autism given family history?

Response by Professor Richard Deth:

The concept of prophylactic dosing is interesting, but I’m not aware of any research on it. Our findings are new so perhaps there will be trials in the future.

Just my thoughts!

Best regards,


Thank you Dr. Richard, We appreciate the information and knowledge you’ve shared.

Sources of Methyl-B12

Since Professor Deth suggested that Methyl-B12 is the type of Vitamin B12 that is likely to be most effective - we’'ve provided a link to Google Shopping search engine of possible sources - click on the link below to see the information:

Google Shopping Search on Methyl-B12 Supplements


Full Research Paper Here:

More about Methyl-B12 and Vitamin B12:

Vitamin B12 Dietary Supplement Fact Sheet


I take a weak b complex, and it chills me out for a few hours. B vitamins work best together, rather than just taking one.

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Thank you for the news updates SzAdmin. Coincidentially, I began treatment again and vitamin B12 was prescribed along with the medication. Your updates remind me there are still people working day in day out to help.


I dont take b vitamins but i eat a lot of meat and ive recovered i realised that meat has b vitamins in it

I take methyl b12 10,000mg. I like it

I think B-12 deficiency in Sz is often coupled with Folate deficiency. I’m about to talk to pdoc about this.

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Found had significant deficiency of B12. Taking B12 relieved some sz symptoms. Increased B12 to relieve sz symptoms and decreased when taking more made symptoms worse. SZ symptoms better when balanced on B12 and taking regular B12 supplements.

I might revisit b12

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After 37 years of sz, B12 deficiency was significant to say the least. Here’s the graph showing what it took to remove the deficiency. Of course this went WAY over RDA, but B12 was immediately lowered when the body adjusted and decided it was too much. Now there is no B12 deficiency and close to RDA is fine.

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Yup, it’s important to take sublingual b-12. It absorbs much more effectively. I get mine at a local grocer for $7 for 120 pills.

Also synthetic folate (folinic acid) doesn’t cross absorb as well compared to methylated folate. Besides eating lots of greens, metafolin by Merck is calcium based salt instead of a glucosamine based salt. It has the advantage of crossing the blood brain barrier.

I was a vegetarian for a long while. I even started to flirt with veganism and used less and less dairy products, eggs, etc. I also mostly forgot to take B12 supplements.

Re-introduced meat, fish, eggs and dairy again 1.5 month ago and seem to feel better. I seem to be more stable and happy and less psychotic. Others notice this too. I’m ethically very much of a supporter of vegetarian or even vegan diets, but they don’t seem to work for me. Might have to do with this B12-thing. Or it’s something else - coincidence, something else that changed?

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