Methyl B12 vs B12

Every cell in your body depends on vitamin B12 for energy production, DNA expression and communication. Vitamin B12 is essential for healthy red blood cells that deliver oxygen throughout the body. Yet, many of us may be deficient in this micronutrient and not even know it. 

What’s more, we may be already supplementing with vitamin B12, but not reaping the full benefits that supplementation has to offer. Why? The form of the nutrient in the supplement matters. 

In this article, I will walk you through all the details about vitamin B12 that you need to know. I’ll answer these questions: 

• What is vitamin B12?
• What foods contain vitamin B12 and how much do I need?
• Who is at risk for vitamin B12 deficiency and what are the symptoms? 
• What should I look for in a vitamin B12 supplement? 

Let’s get started! 

What is Vitamin B12? 

Vitamin B12 is an essential water-soluble vitamin that we must obtain from the diet. It is also known as cobalamin because it contains the mineral cobalt. 

Vitamin B12, in an active form, is a cofactor for two critically important enzymes in the body. 

The first is the enzyme methionine synthase, which catalyzes the conversion of homocysteine to methionine (an amino acid) as part of the methylation cycle. 

This cycle produces SAMe, the body’s main methyl group donor required for DNA expression, cell division, detoxification, neurotransmitter production and other methylation roles. 

Read more about the importance of vitamin B12 in the methylation cycle in my article: The Methylation Cycle and Active Methyl B12 and Methyl Folate. 

The second enzyme vitamin B12 is the required cofactor for is called l-methylmalonyl-CoA mutase. This enzyme produces succinyl CoA, which is involved in energy metabolism and short chain fatty acid production. (Source 1, 2)

Because vitamin B12 is a helper, or cofactor, for these enzymes, it becomes necessary for important body functions including:

• The synthesis of red blood cells
• The production of the myelin sheath, a fatty coating that protects nerve cells
• DNA synthesis and expression
• Cellular energy production
• Central nervous system function
• Growth and development (Source 1, 2, 3)

Vitamin B12 Food Sources and Daily Requirements 

Vitamin B12 is bound to protein in all animal products, including meat, dairy products, fish, shellfish, eggs, poultry and organ meats. It is also found in fortified foods such as cereals, protein bars and nutritional yeast. (Source 1)

Interestingly, dairy products tend to have a higher bioavailability than meat, meaning that vitamin B12 is better absorbed and increases blood levels of the nutrient. (Source 4) Vitamin B12 supplements have a higher bioavailability than food. (Source 5) I will discuss supplements in detail below. 

Although plant foods have many benefits as part of the diet, they do not naturally contain vitamin B12. 

Digestion and absorption of vitamin B12 require good stomach acid and digestive enzyme levels. It also requires a transport protein made in the stomach, called intrinsic factor, that binds to vitamin B12 allowing for absorption. (Source 1) 

The recommended dietary allowance, or RDA, for vitamin B12 is 2.4 micrograms (mcg) per day for adults. The requirement increases to 2.6 mcg per day in pregnancy and 2.8 mcg per day during lactation. (Source 1, 2)

Despite the relatively small amount of vitamin B12 required to meet daily needs, vitamin B12 deficiency is still quite common, especially in certain populations. 

Vitamin B12 Deficiency

Vitamin B12 deficiency is defined as blood levels of cobalamins less than 200pg/mL. This number tells us what is in the blood but doesn’t show what is in cells. (Source 2)

The most sensitive marker for vitamin B12 deficiency is a B12 metabolite called methylmalonic acid, or MMA for short. High homocysteine levels are also a clue for vitamin B12 (or folate) deficiency. (Source 2, 6)

Vitamin B12 deficiency classically presents as macrocytic anemia, where red blood cells appear large. This can also result from a folate deficiency as both B vitamins are required for methylation. (Source 7)

Vitamin B12 deficiency frequently results in neurological symptoms including peripheral neuropathy, numbness and tingling in the extremities. Cognitive impairment including memory loss, decreased concentration, disorientation, dementia and mood changes are also seen. Neurological complications are seen in 75 to 90 percent of deficiency cases, whether anemia is also observed or not. (Source 2)

Factors accounting for an increased risk for vitamin B12 deficiency include: 

• Age – Older adults have lower levels of stomach acid and intrinsic factor production, affecting vitamin B12 absorption. Older adults may also be more prone to having a poor diet, certain health conditions and be using medication. (Source 1)

• Pernicious anemia – Pernicious anemia is an autoimmune disease that affects the production of intrinsic factor, leading to poor B12 absorption and vitamin B12 deficiency. (Source 8)

• Gastrointestinal disorders or surgery – Those with celiac disease, inflammatory bowel disease and other GI conditions may be at greater risk for developing vitamin B12 and other nutrient deficiencies. People who have undergone bariatric surgery or other GI surgeries may require vitamin B12 supplementation. (Source 1)

• Vegetarian and vegan diet – Since animal foods are the only natural source of vitamin B12 in the diet, when these foods are limited or eliminated from the diet supplementation may be required. (Source 1)

• Infants – Vitamin B12 is passed from mother to child through breastfeeding. If the mother is deficient in vitamin B12, the infant is at increased risk for deficiency. (Source 1)

• Genetic variants – Single nucleotide polymorphisms, or SNPs, in the genetic code for certain enzymes involving vitamin B12, such as MTHFR, methionine synthase or vitamin B12 transport proteins, may create an increased vitamin B12 requirement for certain people. 

• Medication use – Certain medications including proton pump inhibitors, metformin and birth control pills may lead to the side effect of vitamin B12 deficiency. (Source 9, 10, 11) 

Having optimal vitamin B12 status is protective against depression, heart disease, Alzheimer’s disease, neural tube defects and more. (Source 3, 12)

Vitamin B12 Supplements: Cyanocobalamin Vs. Methylcobalamin

The use of dietary supplements is a safe and effective way to improve vitamin B12 status and reverse a deficiency. But not all B12 is created equal. The form of vitamin B12 matters!

Vitamin B12 is found in multivitamins, B-complex combination products as well as on its own. 

There are four forms of vitamin B12 (cobalamins) you may find in supplements:

1. Cyanocobalamin – This is the most common form of vitamin B12 found in supplements and fortified foods. It is so widely used because it is inexpensive. This form is synthetic and not found in nature. It’s called “cyano” cobalamin because cobalamin is bound to a cyanide molecule. This form of vitamin B12 is inactive; the body needs to convert cyanocobalamin into an active form to utilize it. (Source 13)

2. Hydroxycobalamin – This form of vitamin B12, sometimes also referred to as hydroxocobalamin, is a naturally occurring or “nature bioidentical” form. However, it isn’t an active form of vitamin B12 and does need to be converted by the body before it can be used as a cofactor. (Source 13)

3. Adenosylcobalamin – Adenosylcobalamin is one of the two coenzyme forms, or active forms, of vitamin B12. This is the form used by the body in the l-methylmalonyl-CoA mutase reaction. As a supplement, it is bioidentical and well absorbed. (Source 13)

4. Methylcobalamin – Methylcobalamin, or methyl B12, is the second active coenzyme form of vitamin B12 and is bioidentical as a supplement. This is the form used in the methylation cycle and may be the most beneficial form for methylation support, especially for those with genetic SNPs, including MTHFR, in the methylation pathway. (Source 13)

Just as we want to choose bioidentical folate over synthetic folic acid, the bioidentical forms of vitamin B12 are also superior. (Source 13)

Vitamin B12 supplements can be taken orally, as a sublingual or as vitamin B12 injections. B12 shots may be recommended to get high doses while bypassing the GI tract. 

Supplemental dosages of vitamin B12 are often much higher than the RDA, typically around 1000 mcg or more. Since it is water-soluble, excess amounts are excreted via the urine. 

Vitamin B12 supplementation has a low risk for toxicity and side effects; however, please note that depending on genetic factors some people may tolerate certain forms better than others. Please work with your healthcare provider for personalized medical advice regarding supplements. 

Here at CoreMed Science we take great pride in providing you high-quality, active nutrients in delivery modes that enhance absorption and bioavailability. 

Core Med Science Active B12 + Active Folate is a sublingual lozenge that dissolves in the mouth, allowing for the absorption of B12 without intrinsic factor. This product contains a combination of the coenzyme forms methylcobalamin and adenosylcobalamin, along with methylfolate. 

Core Med Science Liposomal B12 Folate TMG offers superior methylation support in a liquid liposomal supplement that is easy to titrate the dosages to your needs. This option contains vitamin B12 as methylcobalamin only, along with folate and betaine. Liposomal delivery mimics the body’s cell membranes enhancing absorption into the bloodstream and cells themselves. 

If you fall into a high-risk group for vitamin B12 deficiency, or it’s hard to meet your daily needs by diet alone, have your vitamin B12 levels checked. Supplementation is an effective way to increase and maintain vitamin B12 levels for optimal wellness.  

References

1. National Institutes of Health. Vitamin B12: Fact Sheet for Health Professionals. Accessed 2/7/22 at https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/ 
2. Institute of Medicine, Food and Nutrition Board. (1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press. Excerpt: https://www.ncbi.nlm.nih.gov/books/NBK114310/ 
3. O'Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. Nutrients, 2(3), 299–316. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257642/ 
4. Vogiatzoglou, A., Smith, A. D., Nurk, E., Berstad, P., Drevon, C. A., Ueland, P. M., Vollset, S. E., Tell, G. S., & Refsum, H. (2009). Dietary sources of vitamin B-12 and their association with plasma vitamin B-12 concentrations in the general population: the Hordaland Homocysteine Study. The American journal of clinical nutrition, 89(4), 1078–1087. Abstract: https://pubmed.ncbi.nlm.nih.gov/19190073/ 
5. Tucker, K. L., Rich, S., Rosenberg, I., Jacques, P., Dallal, G., Wilson, P. W., & Selhub, J. (2000). Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. The American journal of clinical nutrition, 71(2), 514–522. Abstract: https://pubmed.ncbi.nlm.nih.gov/10648266/ 
6. Langan, R. C., & Goodbred, A. J. (2017). Vitamin B12 Deficiency: Recognition and Management. American family physician, 96(6), 384–389. Full text: https://www.aafp.org/afp/2017/0915/p384.html 
7. Kaferle, J., & Strzoda, C. E. (2009). Evaluation of macrocytosis. American family physician, 79(3), 203–208. Full text: https://www.aafp.org/afp/2009/0201/p203.html 
8. Andres, E., & Serraj, K. (2012). Optimal management of pernicious anemia. Journal of blood medicine, 3, 97–103. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441227/
9. Jung, S. B., Nagaraja, V., Kapur, A., & Eslick, G. D. (2015). Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis. Internal medicine journal, 45(4), 409–416. Abstract: https://pubmed.ncbi.nlm.nih.gov/25583062/ 
10. Miller J. W. (2018). Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Advances in nutrition (Bethesda, Md.), 9(4), 511S–518S. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054240/ 
11. Palmery, M., Saraceno, A., Vaiarelli, A., & Carlomagno, G. (2013). Oral contraceptives and changes in nutritional requirements. European review for medical and pharmacological sciences, 17(13), 1804–1813. Full text: https://www.europeanreview.org/article/4579 
12. Tiemeier, H., van Tuijl, H. R., Hofman, A., Meijer, J., Kiliaan, A. J., & Breteler, M. M. (2002). Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. The American journal of psychiatry, 159(12), 2099–2101. Abstract: https://pubmed.ncbi.nlm.nih.gov/12450964/ 
13. Paul, C., & Brady, D. M. (2017). Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integrative medicine (Encinitas, Calif.), 16(1), 42–49. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312744/