Methyl B12—A Generous Donor Essential to Health - News and Education Blog

Methyl B12—A Generous Donor Essential to Health

         Vitamin B12 is a highly versatile, water-soluble nutrient that plays a critical role in mood, energy, memory, cognition, cardiovascular function, neurological function, digestion, and hormonal balance. It is vital to a well-functioning and healthy body, and is necessary for DNA synthesis and red blood cell production.1 B12 is so precious to the body that, according to Northeastern University professor of pharmacology Richard Deth, “If you eat a piece of rib eye steak, the B12 released from the proteins is instantly bound right there in the GI tract and chaperoned as if in a football handoff to be carried to cells, transported inside and then processed into the two active forms of the vitamin.”

         And yet vitamin B12 deficiency is a global problem.3 The National Institute of Health’s (NIH) Dietary Office estimates that up to 15 percent of people in the U.S. are deficient in vitamin B12.4 Other studies put the number even higher—suggesting that as much as 39 percent of the population may suffer from a vitamin B12 deficiency.5 In addition, some researchers contend that the current norms for vitamin B12 levels are too low.6

             Vegans and vegetarians are at risk of vitamin B12 deficiency because animal protein, including dairy products, eggs, meat, fish, poultry and organ meats, offers the most absorbable form of vitamin B12. Plant foods do not naturally contain vitamin B12 unless they are synthetically fortified. The elderly are also at risk, because as we age we often have more difficulty absorbing B12 and other nutrients from food due to hypochlorhydria and diminished pancreatic enzyme secretion.7,8,9 Smokers are at risk (since nicotine can block absorption), as are alcoholics, and individuals with digestive disorders like celiac or Crohn’s disease.10,11,12 In addition, those of us with genetic variations that inhibit our ability to transform vitamin B12 into its highly active form, methylcobalamin, can be functionally deficient.13

It is that active form, methylcobalamin (or methyl B12), that supports one of the most fundamental biological processes in our body-- methylation. Methylation seems incredibly simple—in essence, it means that a ‘methyl group’, formed by a single carbon with three hydrogen atoms, has been added to a substance. Methyl B12 is one substance which is able to provide these crucial methyl groups. But in the simplicity of methylation lies its profundity, for nature talks to itself through methylation, and many biochemical pathways are critically dependent on recycling and activating substances via the process of methylation. The simple act of methylation regulates gene expression,14 protein function, and even RNA metabolism.15 It is important for the processes of detoxification, as the methylation of a fat-soluble toxin helps change it to a water-soluble form that can be more easily processed and excreted.16

There are 150-200 enzymes involved in the processes of methylation in the body, and each enzyme can methylate multiple targets. 17 You might picture methylation as an intricate spider web within each cell, a web that has many critical joints and attachments giving it structural integrity, with connections in every direction. The process of methylation is like this – critical for the function of our cellular biochemistry at many points along the pathway, each somehow connected. If a path or a joint is disrupted, there often are alternate routes, but they are less efficient in getting things done.

Methyl B12 in part works its magic by donating an all-important methyl group to a molecule called homocysteine, which then turns into methionine, an essential amino acid. When your levels of methyl B12 are too low, homocysteine can build up. High homocysteine levels have been linked to an increased risk of cardiovascular disease, as well as Alzheimer’s disease. And low levels of methyl B12 have been linked to everything from peripheral neuropathy to autism and mercury toxicity.18,19,20

Enhancing the body’s level of B12 can be achieved by a liposomal delivery system, which improves the bioavailability of vitamin B12, provided as methylcobalamin. Small liposomal vesicles are absorbed intraorally, circumventing issues with gastrointestinal absorption that may exist for other oral, including sublingual, B12 supplements. Studies have shown no significant difference between absorption of oral or sublingual B12, however the absorption of liposomal B12 has been demonstrated to have faster absorption and lead to higher plasma levels (see figure).21 The phospholipids that form the liposomes delivering methyl B12 nourish the membranes of the cells, ensuring proper function for the absorption of nutrients, the excretion of cellular waste products and toxins, and cellular communication.


1 Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017 May 11;129(19):2603-2611. View Abstract.

2 Personal interview, August, 2011.

3 Stabler SP, Allen RH Vitamin B12 deficiency as a worldwide problem. Rev Nutr. 2004;24:299-326. View Abstract

4Vitamin B12 Fact Sheet for Consumers. June 24 2011 (cited 17 July 2017). Available from:

5 Tucker KL, Rich S, Rosenberg I et al. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000 Feb;71(2):514-22. View Abstract

6 Goodman M, Chen XH, Darwish D. Are U.S. lower normal B 12 limits too low? J Am Geriatr Soc. 1996 Oct;44(10):1274-5. PMID: 8856015

7 Green R, Allen LH2, Bjørke-Monsen AL Vitamin B12 deficiency. Nat Rev Dis Primers. 2017 Jun 29;3:17040. View Abstract

8 Nilsson-Ehle H. Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy.

Drugs Aging. 1998 Apr;12(4):277-92. View Abstract.

9 Rothenbacher D, et al. Prevalence and determinants of exocrine pancreatic insufficiency among older adults: results of a population-based study. Scand J Gastroenterol. 2005 Jun;40(6):697-704. View Abstract

10 Linnell JC. Effects of Smoking on Metabolism and Excretion of Vitamin B12 J. Br Med J. 1968 Apr 27;2(5599):215-6. View Full Paper

11 Pott JW. Detection of vitamin B12 deficiency in alcohol abuse. Acta Ophthalmol. 2014 Feb;92(1):e76-7. View Full Paper

12 Pan Y et al. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis. Nutrients. 2017 Apr 13;9(4). View Full Paper

13 Paul C, Brady DM. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med (Encinitas). 2017 Feb;16(1):42-49. Review. View Abstract

14 Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003 Mar;33 Suppl:245-54. View Full Paper

15 Riddihough G. RNA Methylation and Metabolism Science 2013 Feb; 339: 490-491. View Abstract

16 Wilson, L Methylation. The Center for Development. July 2016. (cited July 17, 2017). Available from:

17 Katz, JE, Dlakic M, Clarke S 2003 July. Automated identification of putative methyltransferases from genomic open reading frames. Molecular & Cellular Proteomics. 2: 525–40 View Abstract

18 Li S, Chen X, Li Q, Du J et al. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial.J Diabetes Investig. 2016 Sep;7(5):777-85. View Full Paper

19 Zhang Y, Hodgson NW, Trivedi MS et al. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. PLoS One. 2016 Jan 22;11(1):e0146797. View Full Paper

20 T Kasuya M. The effect of methylcobalamin on the toxicity of methylmercury and mercuric chloride on nervous tissue in culture. Toxicol Lett. 1980 Nov;7(1):87-93. View Abstract

21 Sharabi A, Cohen E, Sulkes J. Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. Br J Clin Pharmacol. 2003 Dec;56(6):635-8. View Full Paper

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