Vitamin B12, known as cobalamin, plays a crucial role as a water-soluble Vitamin, participating in processes such as red and white blood cell formation, neurological and brain function, energy production, as well as DNA synthesis.
A deficiency of this essential Vitamin is very common today and leads to serious health problems, including nerve and DNA damage, fatigue, depression, memory impairment, and compromised immunity.
There are two types of anaemia caused by B12 deficiency. The first one is known as megaloblastic. In this form of anaemia, red blood cells are fewer and enlarged. The second type is pernicious anaemia. It is the most common cause of B12 deficiency in the UK. In this anaemia, our own immune system attacks and destroys the cells in the stomach that produce the intrinsic factor which is required for the absorption of Vitamin B12. As a result, the body is unable to absorb cobalamin leading to anaemia.
Cyanocobalamin vs Methylcobalamin
Typically, Vitamin B12 supplements are sourced from two primary forms: cyanocobalamin and methylcobalamin.
Methylcobalamin is natural whereas Cyanocobalamin is artificially produced synthetic form. However, the human body can convert synthetic cyanocobalamin into bioavailable methylcobalamin.
Both forms carry the same cobalamin (Vitamin B12). What makes them different is the molecule attached to the cobalamin. In methylcobalamin, a methyl group is combined with cobalamin, whereas in cyanocobalamin, a cyanide molecule is attached to cobalamin.
Cyanocobalamin, being synthetic and more cost-effective than methylcobalamin, is more commonly used in supplements. It is also the more stable form because the cyanide molecule has a greater attraction to the cobalamin. For this reason, it protects it better against degradation caused by light, high temperatures, and other environmental factors.
Some studies suggest that cyanocobalamin might be absorbed slightly more efficiently by the body than methylcobalamin. For example, one study observed that the body absorbed approximately 49% of a 1-microgram dose of cyanocobalamin, compared to 44% of the same dose of methylcobalamin (1).
However, a different study found that about three times as much cyanocobalamin was excreted in urine, indicating that methylcobalamin is better retained in the body (2).
Methylcobalamin is less stable and more prone to degradation when exposed to light. Consequently, higher doses of methylcobalamin may be necessary in certain cases. For instance, individuals with kidney failure might require daily doses of one to two thousand micrograms, in contrast to the 50 micrograms of cyanocobalamin recommended for individuals with normal kidney function. Remarkably, in one experiment, even doses as high as 2,000 micrograms a day of methylcobalamin failed to correct B12 deficiency in one out of three vegans tested (14).
One study showed that treating seven individuals with a Vitamin B12 deficiency using oral methylcobalamin resulted in normalized Vitamin B12 levels in their blood within just two months (3). Another study demonstrated that taking cyanocobalamin for three months increased Vitamin B12 levels in ten people with pernicious anemia (4).
A review of seven studies found that both methylcobalamin and a B-complex containing cyanocobalamin were effective in reducing symptoms of diabetic neuropathy, a complication of diabetes that causes nerve damage (5). Furthermore, several animal studies have suggested that each form of Vitamin B12 might have neuroprotective effects and could be beneficial in treating conditions that affect the nervous system (6).
The proponents of methylcobalamin argue that cyanocobalamin requires a methyl group to detoxify itself from cyanide before it is converted to methylcobalamin. Although the amount of cyanide is considered toxicologically insignificant, our body still has to remove the small amount of cyanide using glutathione thus depleting this most important antioxidant.
Methylation is one of the main ways through which our body detoxifies itself. It requires methyl donors, in which we are often deficient due to the high levels of toxins. For this reason, methylcobalamin is very beneficial because it is an important methyl donor. Cyanocobalamin, on the other hand, steals methyl molecules as it needs them for its own detoxification. This is why individuals with methylation issues (like autistic children) can get worse on cyanocobalamin while improving on methylcobalamin (8, 9).
Some experts also claim that when taken orally, cyanocobalamin absorption is significantly reduced in people with insufficient gastric acid production (a common problem today).
According to the information from Nutrition Journal, methylcobalamin can slow the growth of tumors and improve the apoptosis (death) of cancer cells (15, 16, 17). According to the same source, cyanocobalamin was not able to produce this effect. Methylcobalamin has also shown promise in increasing the survival time of mice with leukaemia, whereas cyanocobalamin had no effect under the same conditions (18).
Regular administration of methyl B12 has been found to protect cultured retinal neurons from the damaging effects of glutamate neurotoxicity (19).
Methylcobalamin is the best choice for addressing Vitamin B12 deficiency in chronic smokers and individuals with renal (kidney) or hepatic (liver) conditions (20).
According to one trial, participants who took methylcobalamin demonstrated significantly better cognitive performance than those who took cyanocobalamin supplements (11). It is especially beneficial in individuals with degenerative neurological problems and peripheral neuropathies.
However, not all research has consistently demonstrated the superiority of methylcobalamin over cyanocobalamin (12).
Methylcobalamin plays the most vital role in lowering homocysteine levels (21). Sublingual methylcobalamin has become very popular because it is easily absorbed and because it increases the available amount of S-adenosyl methionine (SAMe), which serves as our primary methyl donor and acts as a mood enhancer (22, 23).
High doses of methylcobalamin have been very beneficial in the management of conditions such as amyotrophic lateral sclerosis and Parkinson's disease (24, 25). Additionally, it demonstrates substantial benefits in improving visual and auditory issues in multiple sclerosis, and in enhancing memory and cognitive function in Alzheimer's disease (26).
It has the potential to significantly enhance facial nerve recovery in Bell's palsy patients when administered in high doses (27). Furthermore, at elevated levels, it may promote neuronal function, facilitate nerve regeneration, and protect cortical neurons from neurotoxicity. In cases of diabetic neuropathy, methylcobalamin was able to alleviate burning sensations and numbness (28).
A case study featured a 48-year-old woman with classic B12 deficiency symptoms, including motor weakness, dementia, sensory disturbances, and coarse hair. Treatment with methyl B12 shots (500mcg every other day) led to the resolution of her unusual sensations, reduced dementia symptoms, improved hand grip strength, normalized hair texture, and restored her ability to walk on tiptoe (29, 30).
Studies have reported significant improvements in sperm count and quality as a result of supplementing with methylcobalamin.
A study comparing the effects of methyl and cyano B12 on sleep quality (circadian rhythms), well-being, alertness, and concentration, found that the methylcobalamin group experienced reduced sleep time, improved sleep quality, enhanced focus, and a refreshed feeling. The authors concluded that only methylcobalamin exhibited a positive psychotropic effect (31).
Unfortunately, due to the lack of a sufficient amount of research and controversial study results, healthcare professionals find it difficult to choose between cyanocobalamin and methylcobalamin.
There are doctors who continue recommending cyanocobalamin due to its lower cost and available more extensive research. They also point to a 2021 experiment with 42 healthy vegans that seemed to prove the superiority of cyanocobalamin over methylcobalamin (7).
Others argue in favour of methylcobalamin because unlike cyanocobalamin it is an important methyl group doner and due to its higher bioavailability, better retention rate, and many additional health benefits.
Some experts recommend taking both forms at the same time. For instance, 1000 mcg of oral cyanocobalamin every other day and at the same time 1000-2000 mcg of sublingual methylcobalamin every day after breakfast.
Sublingual methylcobalamin (1000-3000mcg daily after breakfast) seems to be a better and safer option for individuals with insufficient gastric acid production, elevated homocysteine levels, cancer, autism, IBD (inflammatory bowel disease), low sperm count, liver problems, renal failure, neuropathies, or those who smoke as their bodies may struggle to effectively clear cyanide.
According to one research article, “Cyanocobalamin, a cyanide-containing form of vitamin B-12, may be inappropriate where the body burden of cyanide is already high, e.g. smokers and those exposed to environmental pollutants” (13).
I personally recommend taking sublingual methylcobalamin (1000-3000 mcg daily after breakfast, depending on age, health status, diet, and lifestyle).
- The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis - PMC (nih.gov)
- Dangour AD, et al. (2012) B-vitamins and fatty acids in the prevention of cognitive decline and dementia. Proceedings of the Nutrition Society. 2012; 71(1): 62-8.
- Hoover EL, Strickland KM (2020) Methylcobalamin versus cyanocobalamin: are there any differences between their effects on cognition? a systematic review. International Journal of Neuroscience, 130(5), 471–481
- Michael Greger M.D. Vitamin B12 Deficiency: Symptoms & Treatment. FACLM. September 10, 2021
- Michael Greger M.D. The Best Type of Vitamin B12: Cyanocobalamin or Methylcobalamin? FACLM, November 4, 2020 · Volume 51
- Metz J, Kelly A, Swett VC, Waxman S, Herbert V. Deranged DNA synthesis by bone marrow from vitamin B-12-deficient humans. Br J Haematol. 1968; 14: 575-592.
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