What is the difference between cyanocobalamin and methylcobalamin - absorption, bioavailability, toxicity

The true differences between B12 Cyanocobalamin and B12 Methylcobalamin

Cyanocobalamin and methylcobalamin are two forms of Vitamin B12 available as supplements. So what is the difference between them?

Vitamin B12, also known as cobalamin, is an essential nutrient in human metabolism. It is a molecule with mineral cobalt ion in the centre. It is vital for several important functions:

  • Synthesis of the human body’s genetic material, DNA and RNA
  • Brain and nervous system function
  • Red blood cell formation
  • Vitamin B12 is also essential for heart health as it aids in the breakdown of homocysteine, an amino acid associated with cardiovascular disease.

You will find Vitamin B12 in animal products, including fish, meat, poultry, eggs, milk, and milk products. Because vitamin B12 is not present in plant-based foods, persons on plant-based diets need to get it via supplementation to avoid deficiency.

Four forms of B12 that become one, and then two

Depending on the ligand (bonded molecule) bonded to the central cobalt ion, there are four types of cobalamin:

  • Hydroxylcobalamin (with bound water H2O)
  • Methylcobalamin (with bound methyl group CH3)
  • Adenosylcobalamin (with bound 5’-deoxyadenosyl)
  • Cyanocobalamin (with bound cyanide).

Hydroxylcobalamin and adenosylcobalamin are very unstable in supplemental forms. For that reason, methylcobalamin and cyanocobalamin are most often used for oral supplementation.

Both of these forms, and despite the marketing claims of some companies, are inactive forms of cobalamin. When absorbed, both methylcobalamin and cyanocobalamin have to remove the ligand to convert it to active cobalamin. This is then converted to the intracellular active forms: methylcobalamin and adenosylcobalamin.

Difference in absorption of methylcobalamin and cyanocobalamin B12 supplements via oral route

It makes no difference for synthesis of active cobalamin whether you first ingest it as Cyanocobalamin or Methylcobalamin. The active form of Methylcobalamin is synthetized with the use of methyl groups donated from folate or SAMe, not from ingested Methylcobalamin.

The differences in absorption of methylcobalamin and cyanocobalamin – are there any?

Methylcobalamin is often marketed as more bio-available and more readily absorbed than Cyanocobalamin. When used intravenously that might be the case. Yet, when it comes to taking it orally, the evidence does not suggest any significant difference in absorption. The same is true between the sublingual and oral route.

B12 Methylcobalamin and Cyanocobalamin material source

Cyanocobalamin is synthethised in the laboratories. For that reason it is often referred to as a synthetic form of B12.

There are three ways to obtain Methylcobalamin:

  1. By methylation of cyanocobalamin – this is the non-GMO and vegan form
  2. By extracting it from animal material
  3. Or getting it from genetically modified micro-organisms (GMM).

It is often referred to as being a more natural product. Yet, as you can see, if it is non-GMO and vegan, its manufacturing process is in fact similar to that of cyanocobalamin.

Cyanocobalamin safety

The medical profession has used cyanocobalamin for years now – both in supplement and injection form.

There are many studies confirming its safety and effectiveness. Yes, it contains cyanide molecule which separates from the cobalamin and is excreted in your urine. Note though that each 1000mcg cyanocobalamin tablet contains only 20 micrograms of cyanide. This is far less than you consume in almonds, millet sprouts, lima beans, soy, spinach, bamboo shoots, or tapioca. Should you accidentally chewed one apple pip you’ll swallow roughly 490 milligrams of cyanide. That’s almost twenty-five times more than one 1000mcg cyanocobalamin tablet.

The verdict

Currently, there is not enough evidence to suggest that the benefits of using methylcobalamin override that of using cyanocobalamin. This is in terms of bioavailability, biochemical effects, or clinical efficacy. Yet, if you have kidney issues (which can affect cyanide elimination) methylcobalamin may be a better choice for you. In all other cases cyanocobalamin will work as well.