by Dr. Kelly Brogan
One of the most remarkable papers I have read in the psychiatric literature was about a 57 year old woman who was treated with months of both antipsychotic and antidepressant medications and given two rounds of electroconvulsive treatment before anyone bothered to check her vitamin B12 level.
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Her symptoms were years in the making including tearfulness, anxiety, movement abnormalities, constipation, lethargy, and eventually perceptual disturbances (hearing her name called) and the ultimate in severe psychiatric pathology: catatonia. Despite her inpatient treatment, she remained suicidal, depressed, and lethargic.
Within two months of identifying her deficiency, and subsequent B12 treatment, she reverted to her baseline of 14 years previous, and remained stable with no additional treatment.
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:
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.
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.
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.
How Do We Test?
There are few empirical treatments, meaning treatments that apply to everyone, in functional medicine, but I believe B12 to be one of them, particularly in light of the fact that some 2/5ths of the population present with severe deficiency. Testing is available, and most data on deficiency has relied on blood levels, with deficiency defined as being below 150-200 pg/ml. It turns out that testing for deficiency by blood level is not always a reliable indicator of what is going on in the brain, or functionally, in the body.
An important study in women identified markers of B12 deficiency in 27% of depressed patients by using methylmalonic acid instead of B12 levels. Relatedly, an excellent review of clinical improvement with B12 treatment speaks to ten studies which demonstrated “normal” B12 levels, often finding mean levels in the 3-400pg/ml range (but never above 600) in patients with fatigue, sleep disorders, depression, and dementia.