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

Dr. Perlmutter's Brain Health Program in Grain Brain includes a Grain Free, GAPS Style Diet

I don't know anyone who doesn't want to age in good 

health and avoid Alzheimer's. 

We get a lot of information about how to do this, but does this information have to be updated from the 30's and 40's when most of these principles were established? There is a large movement to update classical teachings and Dr. Perlmutter, a neurologist in practice has put up-to-date research and recommendations into a book called "Grain Brain". 

Dr. David Perlmutter says in this interview: the first step is to stop gluten! (My bold):

Research suggests gluten can play a damaging role by the changes it imparts on your microbiome, the bacteria in your gut. But gluten can also wreak havoc with your neurological health via the inflammation it causes. Non-celiac gluten sensitivity may involve 30 to 40 percent of the population and according to work done at Harvard by Dr. Alessio Fasano, it may even affect every single human being.

The reason for this is because gluten, a protein found in wheat, barley, and rye, has significant effects on your gut cells, which leads to the production of a chemical called zonulin. Zonulin enhances inflammation and tends to make your gut porous and leaky (i.e. leaky gut syndrome). But that's not all. Dr. Fasano discovered that it can also make your blood-brain barrier leaky, allowing foreign proteins to migrate into your brain, where they clearly do not belong.

Listen to the full interview to pick up some brain saving tips.

Let's talk about those foreign proteins mentioned above. These proteins that migrate into the brain are recognized as "foreign invaders" mimicking a life threatening microorganism invasion, like "swine flu" or encephalitis, which then triggers a life saving reaction by the immune system. The reaction however, can go wrong with the confusion of the system when it thinks our own tissues look like gliadin proteins. Dr. Fraser Scott showed that celiac subjects had tissues that look like gliadin back in 2002, but other researchers have shown the same thing in other organs' connective tissues!!! 

This starts a reaction to one's own tissues with the production of anti deamidated gliadin, anti gliadin,  and  anti tissue transglutaminase antibodies (Tg2,3,and 6), especially worrisome is Tg6 but also Tg2, which attack the brain tissues and the tissues around the blood vessels blocking the "blood brain barrier".  Tg6's attack on the brain causes dozens of neurological disorders especially cerebellar ataxia, cerebral calcifications, peripheral neuropathy, epilepsy, migraines and possibly MS. 

Dr. Hadjivassiliou has written an extensive article  "Gluten Sensitivity; From Gut to Brain" on these neurological diseases and the good news is he has shown these conditions improve on a gluten free diet. If you want to see what the blood brain barrier thickened up with Tg6 looks like, go to page nine, and look at the picture labelled "A". The circle in the middle is the lumen of a blood vessel and around it is a cuff of thickness imbedded with Tg6 antibodies. This is very abnormal as the area around the blood vessel is rarely bigger than 1/5th of the diameter of the blood vessel. With one look at the diseased brain tissue's blood vessel you can tell there is something horribly wrong.

This abnormal attack on our own tissues also leads to psychiatric conditions. Here is a case of severe psychiatric symptoms, at one point requiring hospital admission, who improved with GAPS diet and B12 shots.

If your aim is good brain health, the first step is to stop eating gluten. 
You will want to get rid of all grains, though, because of the cross reactive and toxic proteins in them that promote leaky gut and inflammation just like gluten, which is the mechanism for the damage to the brain. 

There is more to do, of course, like remove chemical exposure especially to pesticides, proper dental care by a biological dentist, keeping your vitamin D levels good, keeping your blood sugar levels low and stable, keep your uric acid levels low by limiting your ingestion of fructose to 25 grams a day or less, monitor your B12 levels with a Homocysteine test, supplement with lots of folate (not folic acid, the chemical) probiotics and zinc, exercise moderately and keep your stress levels manageable.

To Your "Brain" Health

Dr. Barbara