The Importance of Methyl B12

The Importance of Methyl B12

Man with glasses

Good health depends on a steady supply of vitamins. They’re necessary to your body’s normal functions and often to life itself. Since your body cannot manufacture essential vitamins, they must be obtained from food.   

All vitamins are important. However, vitamin B12, a water-soluble micronutrient, is not easily stored and must be consumed regularly. Only 1-5 mg are stored regularly in your body, so vitamin B12 deficiency may take years to manifest.i Only a small amount is needed to maintain a healthy level, however, much can go wrong. Do you feel tired all the time? Have muscle weakness? Experience tingling, itching or prickling in your hands and feet? Are you depressed or confused? These could be signs of vitamin B12 deficiencies. More serious signs are a sore and red tongue and mouth ulcers.i  

Naturally present in meat, fish, eggs, and dairy products, with the latter containing three times more than other food sources, vitamin B12 is readily available in a varied diet. However, it’s not found in vegetables and fruits,ii except perhaps in nori, a Japanese sea vegetable used in sushi, though even nori is an unreliable source.iii Some food products such as nutritional yeast and cereal products are synthetically fortified with vitamin B12.i 

Vitamin B12 comes in four natural forms: cyanocobalamin and hydroxocobalamin, and two metabolically active forms: methylcobalamin and 5-deoxyadenosylcobalamin.i, ii  The cyanocobalamin and methylcobalamin forms are prevalent in supplements.  

As a vitamin, B12 is essential for the development and function of the central nervous system, red blood cell formation and DNA production.ii, iii It also works with folic acid (vitamin B9) as a cofactor with two enzymes that convert homocysteine, an inflammatory byproduct of protein metabolism into methionine, an important amino acid that is required to produce S-adenosylmethionine (SAMe), a universal methyl donor necessary for almost 100 metabolic actions involved in forming DNA, RNA, and other substances needed for the function and maintenance of a healthy body.i, iv 

While vitamin B12 is readily available in animal protein, for the body to absorb and use it, a complex process needs to occur, which may encounter stumbling blocks to its absorption if there are digestive issues or other health conditions present.  

B12 in food is bound to complex proteins. Digestion starts by mixing food with saliva, releasing some of the B12 in free form in the mouth. In the stomach, hydrochloric acid and the protease enzyme release more of it from the digesting food mass. Once it exits into the duodenum, the upper part of the small intestine, it combines with intrinsic factor, a protein that helps your intestines absorb vitamin B12, so that it can then go through the walls of the intestine and be transported via the circulation system throughout the body.i, iii  

Miss any of these steps and vitamin B12 from food may be unusable leading to B12 deficiency. Although normal healthy people can successfully get their B12 this way, deficiencies are reported to affect many people globally for a variety of reasons.ii 10-30% of people over the age of 50 with a lack of stomach acid are estimated to have difficulties absorbing B12 from food. Fortified food and B-12 supplements as cyanocobalamin and methylcobalamin on the other hand, are already in free form and therefore more readily absorbable if the intrinsic factor is available.i They are estimated to be 50% more available than B12 from food.i  

Although estimates differ, the National Institute of Health estimates that approximately 15% of the general American population is deficient in B12. A lack of intrinsic factor is responsible for deficiencies and insufficiencies of dietary vitamin B-12 that occur through the digestive process, especially in older populations who may also suffer from lack of hydrochloric acidi, v or who may be on diabetic or acid reflux (GERD) medications.v Certain population groups have the MTHFR gene, a mutation that may interfere with the body’s ability to absorb certain vitamins, such as B12 and prevent detoxification of homocysteine. Pernicious anemia is also a sign of B12 deficiency. People who have digestive conditions such as low stomach acid, Crohn’s, and Celiac diseases, who have a bacteria H. pylori infestation, those who have had stomach or intestinal surgeries, or who take certain medications that help reduce stomach acid may be at risk of having low levels of B12. People with reduced kidney function may also have lower than normal levels of B12.i, ii 

Individuals with normal digestion could also be at risk, such as pregnant women who may need more in gestation, or vegetarians and vegans who do not eat meat products. Vegan women with undiagnosed B12 deficiencies may experience fatigue, developmental delays, and other neurological damage, as well as anemia in their infants. Another at-risk group are individuals who have a restricted or a nutritionally poor diet, and those who live in poor socioeconomic situations.i 

The cyanocobalamin B12 is the most common form of the vitamin supplement. However, this form may not be adequate for others with digestive or underlying health issues.  Methyl B12 might be the answer for those with underlying health issues because methylcobalamin is the most bioavailable B12 form.ii Methyl groups are needed for the body’s production of DNA, protein and phosphatidylcholine, a necessary component of all cell membranes. A methyl deficient diet has been reported to disturb energy metabolism and muscle disorders.v 

Chronic B12 deficiency appears to also increase with age, especially for those with decreased stomach acid and intrinsic factor.i, vi Seniors over the age of 60 with health conditions such as blood disorders or diabetes, with tingling in the feet and hands, and loss of sensation in the nerves which are a sign of peripheral neuropathy may suggest a B12 deficiency.vii Nerves are like electric wires that need a protective coating to guard them as they send their electrical impulses in the central and peripheral nervous systems. B12 deficiency erodes this protective cover called the myelin sheath.ii, vi 

Methylcobalamin is necessary for the development of the myelin sheath, which requires methyl groups. It is the only form of B12 that can cross the blood brain barrier and it accounts for 90% of the B12 levels in the cerebrospinal fluid.vii Studies have reported that it has the potential to regenerate nerve cells, suggesting this might be the most appropriate form to supplement with, rather than other forms.vii In a double-blind clinical trial studying the effects of methylcobalamin on patients with diabetic neuropathy, statistical improvements on symptoms of neuropathy were observed.vii 

Even at high doses, vitamin B-12 supplements are considered to have a low potential for toxicity because the body does not store it. There are no upper level (UL) established for vitamin B-12.i, iii 



i Vitamin B12: Fact Sheet for Health Professionals: National Institutes of Health; 2022 [updated March 9, 2022. Available from: 

ii Cooper J. The causes of B12 deficiency and how it’s related to MTHFR 2020 [Available from: 

iii Vitamin B12: Harvar T.H. Chan School of Public Health; 2022 [Available from: 

iv Browne R. MTHFR & Vitamin B12: MTHFR Genehealth; 2022 [Available from: 

v Obeid R. 2013. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients; 5(9), pp. 3481-3495. 

vi Sil A, et al. 2018. A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy. The Korean Journal of Pain; 31(3), pp. 183-190. 

vii Yaqub BA, et al. 1992. Effects of methylcobalamin on diabetic neuropathy. Clinical neurology and neurosurgery; 94(2), pp. 105-111.