Complete Remission of Psychiatric Symptoms with Vitamin B12 -Case Study in Literature; It's What's In The Brain That Counts

I felt this article was well worth repeating, with some minor editing. 

Many neurological and psychiatric conditions are related to B12 deficiency. 

The rates of B12 deficiency in people with gluten sensitivity is very high. Easy to misdiagnose if you only use a serum B12 level. And it is how much B12 is in the brain that counts. 

I list a number of mechanisms for low B12:

-low stomach acid ( achlorhydria) from an autoimmune process (Gluten sensitive people have 12 times the rate of autoimmune disorders) or from drugs like metformin and proton pump inhibitors

-antibodies to the intrinsic factor producing parietal cell, lowering the amount of the protein that carries B12 from the GI system into the bloodstream- autoimmune atrophic gastritis

- dietary restrictions

- higher B12 needs because of methylation gene abnormalities called MTHFR

- and brain fluid called cerebrospinal fluid (CSF) may have a much lower level of B12 because of an impaired blood brain barrier (described by Dr. Hadjivassiliou in Lancet 2010 and caused by antibodies called Tg6) and so the brain function may be impaired.


All these factors also make it tricky to take oral B12 and expect it to increase the amount of B12 in the brain, where you want it.The blood level does not accurately reflect the level of B12 in the CSF. ( van Tiggelen CJM, Peperkamp JPC, Tertoolen JFW. Vitamin B12 levels of cerebrospinal fluid in patients with organic mental disorders. J Orthomolec Psych. 1983;12:305–311.)

I would like to report the case of a man in his early thirties who came into my practice a few months after he was admitted to a psychiatric facility for 6 weeks. After a few days of treatment, he had refused all medication, and being assess as a person with schizoaffective disorder he was discharged in much the same condition. I placed him on a gluten free diet while testing proceeded, but this was easy as he was living with his parents and his mother was on a gluten free diet already. It was difficult to get testing done but when it was done it was clear he was vitamin B12 deficient. And he had two genes for celiac disease.

He had suffered for years with mood swings, lethargy, and intermittent perceptual disturbances and had been prescribed psychotropic drugs on and off. He was never suicidal although this symptom is common in gluten sensitive individuals. (gluten sensitive teens have a 40% increased risk of dying of suicide by the age of 20, a horrible statistic.)

On the gluten free diet, he was having less negative symptoms, but there was a noticeable improvement when he self administered B12 shots. He has had periods of going off B12 shots, but his family members notice and remind him to give himself a shot. When taking shots regularly, he is alert, oriented, and has a stable romantic relationship. He is looking for work in his field.

In the literature we find a severe case where B12 was the only additional treatment. I frequently find B12 deficiency in patients with mental symptoms and neurological symptoms. For testing I use homocysteine and urinary methylmalonic acid measurements as I find serum B12 measurements unreliable and it can miss methylation polymorphisms ( which has an prevalence in my practice of 76% for at least one SNP of c677T or a1298c). I will also do a trial of IM or Subcutaneous B12, and see what happens. If people feel better after the B12 the next step is to find the frequency. Some people need a shot a day but this is unusual.( this indicates multiple methylation polymorphisms, and/or heavy metal intoxication and/or active autoimmune disorders blocking B12 from going easily through the blood brain barrier, leading to low brain levels of B12.And needing more help). I recommend folate with B12 shots to avoid folate deficiency, in the form of a good B complex, with or without NAC.

Here is what Dr. Kelly Brogan, a psychiatrist has to say about B12 and mental health:

If this is not a wake up call to the average psychiatric prescriber, I’m not sure what is. Much of what we attribute to serotonin and dopamine “deficiencies” melts away under the investigative eye of a more personalized style of medicine that seeks to identify hormonal, nutritional, and immune imbalances that can “look” psychiatric in nature.

How can B12 impact brain health?
B12 supports myelin (which allows nerve impulses to conduct) and when this vitamin is deficient, has been suspected to drive symptoms such as dementia, multiple sclerosis, impaired gait, and sensation. Clinically, B12 may be best-known for its role in red blood cell production. Deficiency states may result in pernicious anemia. But what about B12’s role in psychiatric symptoms such as depression, anxiety, fatigue, and even psychosis?


The one-carbon cycle refers to the body’s use of B vitamins as “methylators” in DNA synthesis and the management of gene expression. There are three concepts that relate to B12’s role in chronic, long-latency neuropsychiatric syndromes: 

1. Methylation
This process of marking genes for expression, like little “read me!” signs, is also critical for detox and elimination of chemicals and hormones (estrogen), building and metabolizing neurotransmitters, and producing energy and cell membranes.

2. Homocysteine recycling

B12 is a primary player in the one-carbon cycle and a co-factor for the methylation, by activated folate, of homocysteine, to recycle it back to methionine. From there, SAMe is produced, the body’s busiest methyl donor. 

3. Genetic override
Sufficient supply of an activated/bioavailable form of a vitamin (ie methylfolate vs folic acid) is even more necessary in the setting of gene variants such as transcobalamin II, MTHFR, and MTRR which may function less optimally in certain individuals and result in pathology under stress. An example of this is a report of death in a B12-deficient patient with genetic variants who underwent anesthesia with nitrous (which causes stress to the system). Notably the B12 blood level was normal, so this fatal case was attributed to functional deficiency, suggesting that access to B vitamins may not always guarantee proper utilization. For this reason, supplementing with activated forms of B vitamins enhances their likelihood of effectively supporting cellular processes.

Read her take on testing and causes of vitamin B12 deficiencies.


If you are interested in the scientific studies, see Dr. Prousky's award winning article on the rational of using B12 therapeutically for psychiatric conditions, even in the absence of "classical" deficiency.

In conclusion: if you are not feeling 100%, mentally or physically or neurologically, it could be B12.


To Your Health
Dr. Barbara