Vitamin B12 is a naturally occurring water-soluble compound. It is essential for generating new red blood cells, maintaining neurological function, and synthesizing DNA. Note that there are several forms of vitamin B12. The primary form used in most nutritional supplements is cyanocobalamin.
Overview of Cognitive Effects
Vitamin B12 has been shown to have beneficial effects on cognitive function as well as general health of neurons. The functional forms of B12, methylcobalamin and hydroxocobalamin, have been shown to improve memory, as well as neurogenesis, maintenance of neuronal structure and axon growth.
Methylcobalamin is an active form of vitamin B12. It has been shown to have a variety of positive effects, in particular on memory and general neuronal health.
Cyanocobalamin is the most common form of vitamin B12 in supplements. Cyanocobalamin needs to be converted into its active forms, methylcobalamin and hydroxocobalamin, in order to exert its effects on the human body.
Is it safe? Are there side effects?
Vitamin B12, and specifically methylcobalamin and cyanocobalamin, are approved as a dietary supplement component under provisions of the Dietary Supplement Health and Education Act of 1994.
There are no major side effects if taken in safe quantities. Mild side effects include diarrhea and swelling. Serious side effects include shortness of breath, headache, exhaustion, flushed skin, and irregular heartbeats. However, serious side effects are rare in healthy individuals.
Effects on Cognition
Mental Status in Older Adults
Generally, levels of vitamin B12 are lower in older people. A recent systematic review showed that there may be some correlations between vitamin B12 status and neurological function, although the evidence is inconclusive. Several studies did not find major associations of low B12 status with electrophysiological measures of nerve function. One of these studies showed that although there were no major changes in nerve function, heart rate variability improved in the elderly subjects.
There was one study that showed that low B12 status correlated with some electrophysiological measures of nerve function. In particular, this study found that low B12 status was correlated with lower sensitivity to light touch and lower nerve conduction amplitude and velocity.
A study of 113 community dwelling subjects between 50-75 years old without dementia, showed that administration of an antioxidant blend consisting of 720 mcg methylcobalamin (along with 33 other antioxidants) given daily for 4 months, resulted in improved memory. Memory was assessed by a 50 part paired association test and a 20-word immediate recall test. Furthermore, there was a significant decrease in serum homocysteine (a high level of homocysteine increases risk for endothelial cell injury, which can lead to cardiovascular diseases) levels over the 4 months as a result of the treatment.
Figure 2. Supplementation with methylcobalamin contributes to improvements in working memory as measured by the Names-Learning paired association test (NLT). A score improvement is seen 4 months into the intervention.
Figure 3. Supplementation with methylcobalamin contributes to improvements in working memory as measured by the Names-Learning paired association test (WRT). A score improvement is seen 4 months into the intervention.
There are various studies that have measured the effect of B12 and folate combination on cognitive function in healthy people. A meta-analysis showed that supplementation with B12 and folate did not have a significant effect on memory in healthy elderly people.
A meta-analysis showed that there was no significant effect of methylcobalamin on mood.
Effects on Medical Conditions
Mild Cognitive Impairment
Mild cognitive impairment is a condition characterized by mild dementia, and can be seen as a less severe form of Alzheimer’s disease. Vitamin B12 deficiency has been linked to dementia, and is one of the only few reversible causes.
Some studies have found a positive effect of vitamin B12 in reversing some of the symptoms of dementia. A case report in an 83-year old woman found that methylcobalamin ingestion led to a rapid decrease in symptoms in the patient, over a period of two months in which the patient ingested 3,000 micrograms methylcobalamin daily, along with 1,200 micrograms of folic acid.
In a study involving 10 patients with Alzheimer’s disease, methylcoblamin was found to improve various intellectual functions such as memory, emotional control, and interactions with other people.
Some evidence suggests that methylcobalamin can be useful for lowering homocysteine, a biomarker for neuroinflammation that is found in cases of Alzheimer’s disease.
Studies have shown that dietary supplementation of B vitamins including vitamin B12 are associated with lower levels of inflammatory biomarkers for vascular dementia such as thromboxane, homocysteine, and isoprostane (See Figure 1).
Figure 1. Supplementation with vitamin B6 and B12 is associated with decreases in levels of inflammatory biomarkers for vascular dementia such as homocysteine, thromboxane and isoprostane.
A study of 113 50-75 year olds without dementia showed a significant decrease in serum homocysteine levels over 4 months as a result of 720 micrograms of B12 given daily. A high level of homocysteine increases risk for endothelial cell injury, which can lead to cardiovascular diseases. This suggests that B12 may have a vacscular protective effect.
A recent meta-analysis of 1221 peripheral neuropathy patients found that combining prostaglandin E1 and methylcobalamin along with lipoic acid resulted in drastic improvements in peroneal nerve conduction velocity compared with taking just prostaglandin E1 and methylcobalamin alone. This research suggests that there may be a synergistic effect of lipoic acid along with methylcobalamin, and should motivate future studies on the topic.
One study found that methylcobalamin combined with prostaglandin E1 was effective for the treatment of diabetic peripheral neuropathy, which was assessed by median sensory nerve conduction velocity, median motor nerve conduction velocity, peroneal motor nerve conduction velocity, and peroneal sensory nerve conduction velocity.
A study in 14 patients with peripheral neuropathy found that intravenous delivery of 25 mg/day of of methylcobalamin for 10 days followed by monthly 25 mg for 5 months, was efficacious and safe for treating peripheral neuropathy.
A study involving 98 patients with herpetic neuralgia (pain related to the infection with herpes zoster virus), showed that taking injections of methylcobalamin reduced pain significantly. The pain was measured in several ways, including total pain, continuous spontaneous pain, paroxysmal pain, and allodynia.
Animal studies of nerve regeneration
A study in rats found that methylcobalamin facilitates axon growth after end-to-end neurorrhaphy (suturing of a divided or severed nerve). Studies like this should motivate future work on the usage of methylcobalamin on recovery from nerve damage. In addition, this implicates that methylcobalamin can be useful for neurogenesis in normal humans, which may help to enhance cognitive function.
Structure & Synthesis
Vitamin B12 is obtained from many animal-derived foods including fish, red and white meat, poultry and milk products. The B12 from animals is usually derived produced by bacteria in the gut.
In addition to natural sources, foods that are fortified with B12 can also be great sources. These include energy bars, protein bars, juices, and breakfast cereal. In most B12-fortified foods, B12 is added in the form of cyanocobalamin. B12 is also commonly used in energy drinks.
Methylcobalamin has been isolated from E. coli and Streptomyces rimosus.
Mechanisms of Action
Most nutritional supplements contain vitamin B12 in the form of cyanocobalamin. Usually cyanocobalamin is broken down into the active form of hydroxocobalamin and then methylcobalamin and adenosylcobalamin.
Regardless of which form of vitamin B12 is ingested, it needs to be absorbed into the body.17Intrinsic factor from the intestinal barrier binds to the cobalamin (in whichever form), which allows for absorption into the bloodstream. Next, the cobalamin is internalized into the cell, and eventually converted into the active forms of hydroxycobalamin and methylcobalamin. See figure below for details.
Figure 4. Process of cobalamin internalization into cells and subsequent conversion to the active form of hydroxycobalamin and methylcobalamin.