Methylcobalamin Vs. Cyanocobalamin: Which B12 Is Best For You?

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Medically reviewed by Dr. Saad Ansar

Key Information

Methylcobalamin is the natural form of B12

Methylcobalamin is the form of B12 that is found in animal-based foods and is readily absorbed by the body.

Cyanocobalamin is the synthetic form of B12

Cyanocobalamin is the form of B12 that is commonly used in supplements and contains a cyanide molecule that needs to be removed.

Methylcobalamin is more active and beneficial than Cyanocobalamin

Methylcobalamin is the most bio-available and effective form of B12 for energy production, red blood cell formation, DNA synthesis, and nerve function.

Methylcobalamin can help with various health conditions

Methylcobalamin can help with Alzheimer’s disease, diabetic neuropathy, visual impairment, circadian rhythm, pain states, and rheumatoid arthritis.

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Vitamin B12 is an essential nutrient and has many functions in the body.

It is a water-soluble vitamin crucial for the proper functioning and developing of the brain, red blood cells, and the nervous system.

It acts as a potent cofactor for many enzymatic and primary functions of the body.

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Methylcobalamin vs Cyanocobalamin

There are various coenzyme forms of vitamin b12, such as Methylcobalamin, Cyanocobalamin, and Hydroxycobalamin. Those deficient in vitamin b12 suffer many downstream physical and mental health problems.

While b12 is rich in many foods, you can also supplement to ensure you’re getting an adequate daily allowance of the nutrient.

The two most commonly supplemented forms of b12 are Methylcobalamin and Cyanocobalamin.

The following post takes a deep dive to compare each form and break down which one may be best for you.

How does Vitamin B12 Enter my Body?

A series of steps must occur for your body to absorb vitamin B12 from animal-based foods. The HCl in your stomach removes vitamin B12 from the food.

After that, vitamin B12 combines with intrinsic factors. Intrinsic factor is a protein produced by your stomach that mediates the absorption of vitamin B12. The digestive tract will then be able to absorb Vitamin B12 and use it in various body functions.1Alex Ankar; Anil Kumar.Vitamin B12 DeficiencyStatPearls Publishing; 2022

Some people have pernicious anemia. This means their stomach does not produce intrinsic factors. As a result, their bodies cannot absorb vitamin B12, resulting in a vitamin B12 deficiency.

What Vitamin b12 Does In The Body

Vitamin B12 has several vital functions it performs in our bodies. Some include:

Vitamin b12 Is Beneficial For The Nervous System.

Vitamin B12 is an important nutrient as it acts as a coenzyme in synthesizing myelin. It also promotes DNA and RNA synthesis in myelin-producing oligodendrocytes.

It modulates the synthesis and resynthesis of myelin, thus repairing nerve injury. This makes it essential in helping the nerve and brain cells to function properly.2Carlos Alberto Calderón‐Ospina 1 and Mauricio Orlando Nava‐Mesa, B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalaminCNS Neurosci Ther. 2020

Vitamin b12 Is Important for Methionine Synthesis.

Vitamin b12 is involved in the production of methionine. It does this in its metabolically active coenzyme forms. One such coenzyme form is Methylcobalamin.

Cobalamin facilitates the action of the enzyme methionine synthase. Methionine then participates in a variety of protein synthesis functions.

This shows Methylcobalamin’s importance. The coenzyme forms convert homocysteine to methionine3Lindsay H Allen, Vitamin B-12Adv Nutr. 2012, reducing the potential for damage.

The reaction forms the body’s main antioxidant, glutathione. Glutathione promotes nervous system health by preventing destruction and demyelination by free radicals.4Erik E van de Lagemaat , Lisette C P G M de Groot , Ellen G H M van den Heuvel, Vitamin B 12 in Relation to Oxidative Stress: A Systematic ReviewNutrients. 2019

Vitamin b12 Is Important in Red Blood Cell Formation.

Erythrocytes need folate and vitamin B12 for their proliferation and differentiation. This makes vitamin b12 an essential nutrient for red blood cells. Cobalamin deficiency inhibits purine and thymidylate synthesis.5Annu Rev Nutr. 2004, New insights into erythropoiesis: the roles of folate, vitamin B12, and ironMark J Koury , Prem Ponka

The deficiency impairs DNA synthesis and reduces red blood cell production, resulting in anemia. The anemia is termed Vitamin b12 deficiency anemia.

Vitamin b12 Prevents Major Birth Defects.

A healthy pregnancy requires adequate vitamin B12 levels. According to research, a fetus’s brain and nervous system need acceptable B12 levels from the mother to develop correctly.6Ram K Chandyo et al, The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled TrialBMJ Open. 2017

A lack of vitamin B12 in the early stages of pregnancy may increase the risk of congenital disabilities such as neural tube defects. 7Ram K Chandyo et al, The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled TrialBMJ Open. 2017

Furthermore, the mother’s lack of vitamin B12 may contribute to premature birth or miscarriage.

Benefits Your Brain by Preventing Neuron Loss

Memory loss has been linked to vitamin B12 deficiency, particularly in older adults.

The vitamin may help to prevent brain shrinkage, which is the loss of nerve cells and is frequently associated with loss of memory or dementia.8Health Quality Ontario, Vitamin B12 and cognitive function: an evidence-based analysisOnt Health Technol Assess Ser. 2013

What Is The Difference Between Methylcobalamin vs Cyanocobalamin

Methylcobalamin and Cyanocobalamin are the two forms of vitamin B12 most studied.

The two forms have different origins.

Methylcobalamin is the naturally occurring form of vitamin b12.

Cyanocobalamin is the synthetic form of vitamin B12 not found in nature. It’s used more frequently in supplements as it’s more stable and cost-effective than other vitamin B12 forms.

Methylcobalamin can be obtained as supplements as well from animal-based foods. The methyl compound is required by the human body to function properly.

The difference between the two forms is that Methylcobalamin contains only carbon and hydrogen. On the other hand, Cyanocobalamin contains a cyanide molecule. The amount of cyanide in B12 supplements is insignificant. Still, your body will need to eliminate and remove it because cyanide can have a toxic effect. The cyano compound has no use in the body. Therefore the body will convert any cyanocobalamin into Methylcobalamin as quickly as possible.

In the structure of the cobalamin molecule, a cobalt ion lies at the center of the corrin ring. The cobalt ion surrounded by all corrin rings is attached through different molecules. The sixth coordination site is the active biological center of vitamin B12 and is variable.

Depending on the type, either methyl, adenosyl, cyano, or hydroxy group are attached at this site. Cyanocobalamin and Hydroxycobalamin are converted into Adenosylcabolamin or Methylcobalamin in vivo. They lose the cyanide or hydroxide moiety and add adenosyl or a methyl group.

Which Is The More Active Form of Vitamin B12?

Comparing the two forms shows that Methylcobalamin is more active than Cyanocobalamin. Cyanocobalamin is the most commonly supplemented form. It is now, however, getting replaced by Methylcobalamin.

The body must first process Cyanocobalamin into the active form to use it. The rapidly gaining popularity of Methylcobalamin is due to it being the most bio-available form. Because of its immediate activity, Methylcobalamin is the preferred form for oral administration.

Cyanocobalamin And The Cyanide Molecule

The body can absorb Cyanocobalamin to a significant extent. Still, synthetic Cyanocobalamin isn’t the best source of vitamin B12. The body must remove cyanide from cobalamin before it can perform its biological functions in the body.

People who have a higher toxic body burden or cyanide exposure are less likely to be able to detoxify toxins properly. This includes the extra toxins they consume through supplements, such as cyanide. This could be dangerous because the body’s toxic burden will eventually reach a point where it cannot handle more toxins.9Jessica Morales-Gutierrez, Sebastián Díaz-Cortés , María A Montoya-Giraldo, Andres F Zuluaga, Toxicity induced by multiple high doses of vitamin B 12 during pernicious anemia treatment: a case reportClin Toxicol (Phila). 2020

How Many Active Forms Of Vitamin B12 Are There?

Though vitamin B12 is isolated in the form of Cyanocobalamin, it is only in three states that it is biologically active: adenosylcobalamin (AdoCbl), hydroxocobalamin (HOCbl), and Methylcobalamin (MeCbl)

Of the four forms of vitamin b12, the most active form of vitamin B12 is the one containing the methyl group, Methylcobalamin. It is also the most bio-available form.10Cristiana Paul, MS and David M. Brady, ND, DC, CCN, DACBN Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic PolymorphismsIntegr Med (Encinitas). 2017

What type of B12 is best absorbed?

Methylcobalamin is the most bio-available and readily absorbable form of Vitamin B12.

Is methylcobalamin B12 better than Cyanocobalamin?

Methylcobalamin is the superior form of B12 because it stays in your body for an extended period. When you use Methylcobalamin, your body gets more vitamin B12 than when you use the Cyanocobalamin form.

What does methylated B12 do for the body?

Methylated B12 is rapidly gaining popularity because it can benefit the body in many ways. Some common diseases it is beneficial in treating include:

Alzheimer’s Disease:

Subcellular organelles of neurons effectively take Methylcobalamin up. This accounts for better treatment of nervous disorders using this supplement. There is neuroinflammation in Alzheimer’s indicated by high free homocysteine levels. This can be lowered using the Methylcobalamin form of vitamin B 12. Methylcobalamin can convert homocysteine into other formats.11Andrew McCaddon, Peter R Hudson, L-methylfolate, methylcobalamin, and N-acetylcysteine in the treatment of Alzheimer’s disease-related cognitive declineAndrew McCaddon, Peter R Hudson

Methylcobalamin can improve memory, emotional functions, and communication in Alzheimer’s patients. It does this by protecting injured nerves and promoting axonal regeneration.

Glutamate Neurotoxicity

Glutamate neurotoxicity can be prevented by chronic exposure to Methylcobalamin and S-adenosylmethionine (SAM). 12M Kikuchi , S Kashii, Y Honda, Y Tamura, K Kaneda, A Akaike, Protective effects of methylcobalamin, a vitamin B12 analog, against glutamate-induced neurotoxicity in retinal cell cultureInvest Ophthalmol Vis Sci. 1997

Diabetic Neuropathy

Patients with diabetic neuropathy have impaired nerve conduction. Methylcobalamin has neuronal regeneration ability. This makes it useful in improving the nerve conduction in these diabetic patients.13Devathasan, G.; Teo, W.L.; Thai, A.C.; Mylvaganam, A.; Chin, J.H., Methylcobalamin methycobal in chronic diabetic neuropathy a double blind clinical and electrophysiological studyClinical Trials Journal.1986

Visual Impairment

Nerves from both divisions of the autonomic nervous system supply the accommodation system of the eye. The methylated form of vitamin b12 can improve visual acuity and accommodation. It does this by maintaining nerve health. Thus, Methylcobalamin can improve visual function and light sensitivity. 14T Iwasaki, S Kurimoto, Effect of methylcobalamin in accommodative dysfunction of eye by visual loadJ UOEH. 1987

Disturbed Circadian rhythm

Melatonin secretion in the pineal gland influences the circadian rhythm. The exact mechanism of this is still under study. Research is being done to see how Methyl-b12 can modulate melatonin secretion.15K Takahashi, M Okawa, M Matsumoto, K Mishima, H Yamadera, M Sasaki, Y Ishizuka, K Yamada, T Higuchi, N Okamoto, H Furuta, H Nakagawa, T Ohta, K Kuroda, Y Sugita, Y Inoue, N Uchimura, H Nagayama, T Miike, K Kamei, Double-blind test on the efficacy of methylcobalamin on sleep-wake rhythm disordersPsychiatry Clin Neurosci. 1999

Research suggests that methyl-B12 amplifies the melatonin-induced phase of the sleep-wake cycle. It can modulate melatonin secretion during the early night and also increase it. Thus, supplementation with methyl-b12 improves sleep quality and enhances light sensitivity.

The individuals often need slightly less sleep and feel refreshed early morning. Methylcobalamin is effective when the 24-hour clock of the changing sleep-wake cycle is disturbed.

Pain states

MeCbl improves nerve conduction velocity, promotes injured nerve regeneration, and inhibits the spontaneous discharges from peripheral primary sensory neurons in neuropathic pain states. This makes it effective as an analgesic in various painful conditions like back pains. 16Ming Zhang , Wenjuan Han, Sanjue Hu , Hui Xu, Methylcobalamin: a potential vitamin of pain killerNeural Plast. 2013

Rheumatoid Arthritis

Methyl B12 suppresses cytokine production by T lymphocytes. Such immunosuppressive effects can benefit patients with rheumatoid arthritis, especially at articulation lesion sites.

How is Methylcobalamin made?

In a laboratory, reducing Cyanocobalamin with sodium borohydride yields Methylcobalamin. An alkaline solution is used. It is then followed by adding methyl iodide to yield the end product.

This important nutrient has an intricate biosynthesis process. Only certain members of the prokaryotic kingdom can synthesize it. Microbial fermentation is used for the large-scale industrial manufacturing of vitamin B12. Primarily industry uses Pseudomonas denitrificans and other such bacteria for this purpose. 17M Yamashiki, A Nishimura, Y Kosaka, Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blood mononuclear cellsJ Clin Lab Immunol. 1992


So, what is the verdict? Is Methylcobalamin better than Cyanocobalamin? The answer is a resounding yes. Methylcobalamin is the more active form of vitamin B12, and it is also better absorbed by the body. On the other hand, Cyanocobalamin contains cyanide, which can be harmful in high doses. The benefits of Methylcobalamin are manifold- it helps with energy production, red blood cell formation, DNA synthesis, and nerve function. So if you’re looking for a quality vitamin B12 supplement, look for Methylcobalamin on the label.


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Erik Abramowitz is a certified Nutritional Therapy Practitioner (NTP), Naturopathic Doctoral student, health coach, and father. He is the primary content creator for and the host of the Holistic Nootropics Podcast.

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