Which Form of B12 is Right for You?

vitaminB12

Vitamin B12 deficiency is a common occurrence in the general population as well as in ME/CFS and fibromyalgia patients. Vitamin B12 is nearly exclusively found in animal products, so vegans and vegetarians are most at risk of deficiency. It is also commonly depleted in those with gastrointestinal disorders—GERD, SIBO, or other forms of dysbiosis—due to inadequate absorption.

Since B12 is involved in many aspects of physiology, deficiency can lead to anemias, peripheral nerve disorders, muscle weakness, nonspecific gastrointestinal symptoms, brain fog, etc.

Recent interest has emerged as to which form of this crucial vitamin to supplement. Here are your 4 choices…

Methylcobalamin (MetCbl)

The active, methylcobalamin form of B12 is the most abundant form in blood and body fluids. It plays a vital role in the methylation cycle. It is the necessary cofactor for converting homocysteine to methionine, which later becomes S-adenosylmethionine (SAMe)—the primary methyl- donor in the body (1).

Methylcobalamin is now widely available in supplement preparations and may be very beneficial to those ME/CFS or fibromyalgia patients that are undermethylated. This may be determined by measuring blood homocysteine or genetic testing for MTHFR genetic mutations.

Hydroxycobalamin (HCbl)

This less known form of B12 is sometimes used as an antidote to cyanide exposure as it readily binds to the toxic molecule making it inert. This form of B12 binds to 2 important molecules implicated in ME/CFS and fibromyalgia.

HCbl readily binds with nitric oxide—a powerful inhibitor of the methylation cycle and pro-oxidant implicated in ME/CFS pathology. HCbl also binds the highly toxic hydrogen sulfide (H2S)—a small molecule that can cross the blood-brain barrier. In dysbiosis, unwanted species of microbes release small amounts of H2S, which may perpetuate cognitive symptoms or muscle pain in ME/CFS and fibro (2).

This form of B12 may be a powerful intervention for those with severe gut problems or severe oxidative stress.

Adenosylcobalamin (AdCbl)

Adenosylcobalamin is the active B12 form stored in the mitochondria of the cell. Here it acts like a B12 depot, drawn on to participate in chemical reactions that create cellular energy: ATP. With AdCbl deficiency, metabolism is hindered leading to disruptions in the breakdown of fats, carbohydrates, and proteins; the latter also disrupting how ammonia is handled (1).

The AbCbl form may be of important use for ME/CFS to improve mitochondrial function. Taken in combination with one of the other forms mentioned above, the beneficial effects may be synergistic.

Cyanocobalamin (CCbl)

Cyanocobalamin is an active form of B12 required for red blood cell formation and proper nerve cell function. Breakdown of this form produces a molecule of cyanide which must be excreted properly. This form is not recommended in smokers or those exposed to secondhand smoke since cyanide derivatives are high in the inhaled smoke. It is also worth discussion the possibility that this form is contraindicated in subsets ME/CFS patients who have decreased detoxification due to chronic oxidative stress (1).

While cyanocobalamin is most commonly used due to its inexpensive, it may be contraindicated in more severe ME/CFS cases. Minimal amounts utilized in conjunction with the other 3 forms likely pose little threat to milder forms of the illness.


Thakkar K, Billa G. (2014) Treatment of vitamin B12 deficiency-Methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. Eur J Clin Nutr. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/25117994

Vasquez, A. (2014) Mitochondrial Nutrition and Mitochondrial Medicine for Primary Care Conditions: Text and Presentation Slides. CreateSpace Independent Publishing Platform.