Which Form of Vitamin B12 is Best?

Even if you eat a healthy diet, you may not absorb enough vitamin B12 to meet your daily needs. Luckily, vitamin B12 supplementation is an effective strategy for improving and maintaining vitamin B12 status, which translates to improved energy levels, mood, nervous system regulation, and more. 

With so many supplements available, how do you know the best form of vitamin B12? What’s the difference between cyanocobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin? 

Keep reading to learn the answers to these supplement questions and more. I’ll cover: 

• Vitamin B12 and why you need it
• Vitamin B12 dietary requirements and absorption issues
• Vitamin B12 deficiency
• The four forms of vitamin B12 supplements, along with the best form in terms of effectiveness and bioavailability 
• The benefits of sublingual delivery 

Let’s dive in! 

What is Vitamin B12, and Why Do You Need it?

Vitamin B12, called cobalamin, is a water-soluble essential nutrient naturally bound to protein in animal foods. Food sources include: 

• Meat, fish, eggs, dairy products, and other animal products
• Fortified foods such as bread, cereals, and breakfast bars (Source 1)

In the body, vitamin B12 is an essential cofactor for two key enzymes, methionine synthase and l-methyl malonyl-CoA mutase, inside every cell of the body. First, as a cofactor to methionine synthase, vitamin B12 is involved in the methylation cycle that recycles homocysteine back to the amino acid methionine and produces methyl donors involved in hundreds of body processes. Read about the methylation cycle here. (Source 1)

Second, as the cofactor for l-methyl malonyl-CoA mutase, vitamin B12 is required for the production of succinyl CoA, an intermediate in the citric acid cycle that turns calories into cellular energy (ATP) and produces the short-chain fatty acid propionate. Read more about micronutrients and the citric acid cycle here. (Source 1)

If all this sounds like too much science, here’s what it means for your health: vitamin B12 is critical for: 

• Healthy red blood cells
• Cardiovascular function (protects against heart diseases)
• DNA synthesis 
• Brain and nervous system function (myelin sheath formation that protects nerve cells)
• Energy production 
• Growth and development (Source 1)

Vitamin B12 Requirements and Absorption

Adults need at least 2.4 micrograms (mcg) of daily vitamin B12. The highest requirements are during pregnancy (2.6 mcg daily) and lactation (2.8 mcg daily). (Source 1)

In addition to adequate daily intake, vitamin B12 digestion and absorption must work properly for the nutrient to make its way inside the body and into cells. Here’s what’s required:

• Stomach acid and digestive enzymes help release vitamin B12 bound in protein. 
• Intrinsic factor, a transport protein made in the stomach, binds to vitamin B12. 
• Vitamin B12 bound to intrinsic factor is absorbed in the small intestine and enters the bloodstream. (Source 1)

Vitamin B12 Deficiency

Vitamin B12 deficiency, defined as B12 levels below 148 pmol/l, is common worldwide. In the United States, deficiency affects at least:

• 3% of adults aged 20-30
• 4% of adults aged 40-59
• 6% of adults over age 60 (Source 2)

If you include marginal depletion, serum B12 levels of 148-221 pmol/l, the numbers affect even more, including 15% of adults and over 20% of adults over 60! (Source 2) 

With such high deficiency rates, something needs to be fixed with intake and vitamin B12 absorption. When vitamin B12 deficiency progresses, it may result in neurological and hematological abnormalities and a host of symptoms such as neuropathy and cognitive impairment. (Source 2)

Therefore, diagnosing this nutrient deficiency early and addressing the underlying cause is critical. Some reasons for low vitamin B12 include low intake, poor absorption, and increased requirements.

• Inadequate intake – Not eating enough vitamin B12-rich foods can lead to deficiency. Vegetarians, vegans, and others restricting animal foods are at higher risk. (Source 3)

• Poor B12 absorption – Malabsorption is the most common cause of vitamin B12 deficiency. Some reasons for poor B12 absorption include pernicious anemia, age, and weight loss surgery. (Source 2)

Pernicious anemia is an autoimmune condition resulting in less intrinsic factor, decreasing the amount of vitamin B12 absorption. (Source 4)

Another risk factor for poor B12 absorption is advanced age because of reduced stomach acid and intrinsic factor levels. (Source 2)

In addition, people who have undergone bariatric surgery (weight loss surgery) are at greater risk for vitamin B12 and other micronutrient deficiencies. (Source 5)

• Increased vitamin B12 requirements – Those with genetic variants (SNPs) in genes related to B12 absorption and metabolism may have increased needs for this nutrient outside what is easily obtainable through food alone. 

Another reason behind the need for greater B12 intake is medication use. Some medications, including metformin, birth control pills, and acid-lowering medications, deplete vitamin B12. Supplementation may be required to maintain adequate levels. (Source 6, 7, 8)

If you fall into any category for increased vitamin B12 deficiency risk or are experiencing symptoms, please work with your healthcare provider for personalized testing and medical advice. 

Vitamin B12 Supplement Forms

Because of the prevalence of vitamin B12 deficiency and the need to address underlying causes, many people benefit from dietary supplements. Remember that vitamin B12 is a water-soluble vitamin. Therefore, side effects are unlikely as the body clears excess vitamin B12 from high doses. 

Vitamin B12 supplementation is available in many forms, including: 

• Oral supplements: Options are a multivitamin, B complex, vitamin B12 with folate, or different forms of vitamin B12. 

• Intramuscular: Vitamin B12 injections may be offered by your healthcare provider to bypass the GI system and deliver vitamin B12 directly into the bloodstream. In many cases, oral therapy is effective for treating vitamin B12 deficiency, and injections may not be needed. Further, injections may be costly or inaccessible. (Source 2, 9)

• Sublingual: Sublingual lozenges or chewable tablets are another option for vitamin B12 delivery that bypasses the gut and the need for intrinsic factor. Dissolving a tablet in the mouth allows for direct absorption into the bloodstream and is a good choice for older adults and others with B12 malabsorption issues. 

In addition to choosing the best type of dietary supplement, choosing the optimal form of vitamin B12 is imperative. Let’s look at the four supplemental forms. 

Cyanocobalamin

Cyanocobalamin is inexpensive and the most common form of vitamin B12 in supplements. You’ll also find this form in vitamin-fortified foods. 

Cyanocobalamin is a synthetic form of vitamin B12 supplement where vitamin B12 is attached to a cyanide molecule, which may present toxicity issues. Cyanocobalamin is the form of vitamin B12 with the least bioavailability because it’s not directly usable by the body. The body must release the cyanide molecule and attach it to a methyl or adenosyl group for activation. (Source 10)

Methylcobalamin

Methylcobalamin, or methyl B12, is one of the two active forms of vitamin B12 and is directly usable by cells in the methylation cycle. Research suggests that the nature-identical forms of vitamin B12, including methyl B12, are preferred over cyanocobalamin because of superior bioavailability and safety. (Source 10) 

When well tolerated, methylcobalamin is one of the preferred forms of vitamin B12. Many functional medicine doctors recommend methyl B12 to their patients to support various goals, including fertility, brain health, heart health, and more. 

Adenosylcobalamin 

Adenosylcobalamin, adenosyl B12, is the other active form of vitamin B12 and is highly bioavailable as a supplement. Cells directly use adenosyl B12 in the citric acid cycle. Combining methyl B12 and adenosyl B12 in a supplement provides both active forms and a beneficial approach for treating vitamin B12 deficiency. (Source 9)

Hydroxocobalamin

Hydroxocobalamin is a precursor to the active forms of B12 and is still nature-identical and highly bioavailable. Because of genetic variants or other reasons, a small percentage of people may tolerate hydroxocobalamin (or adenosylcobalamin) better than methylcobalamin. (Source 10)

Core Med Science Active Methyl B12 Folate Tablets

Core Med Science understands vitamin B12 deficiency and the need for affordable yet effective supplements in the correct form and delivery. Core Med Science Active Methyl B12 Folate Tablets combine active vitamin B12 (not cyanocobalamin) and active folate (not synthetic folic acid) to support cellular health, energy, methylation, and overall body function. 

One tablet provides 800 mcg dietary folate equivalents (DFE) of methylfolate and 1000 mcg of vitamin B12, with 80% from methyl B12 and 20% from adenosyl B12. 

Along with the preferred forms of these vitamins and an effective dosage, you’ll find a preferred delivery system. A chewable tablet improves the digestion and absorption of the supplement and offers an option for those who don’t like or can’t take pills, children, older adults, and other populations. You don’t want to miss this physician-formulated, high-quality option!

When it comes to which B12 is best, the best option is the one that works for your body, provides effective results, and is easy for you to take consistently. Skip cyanocobalamin in favor of the nature-identical forms, especially active methylcobalamin and adenosylcobalamin, which you’ll find in Core Med Science’s tablets. 

References

1. National Institutes of Health. Vitamin B12: Fact Sheet for Health Professionals. Accessed 7/19/23 at https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/ 
2. Shipton, M. J., & Thachil, J. (2015). Vitamin B12 deficiency - A 21st century perspective. Clinical medicine (London, England), 15(2), 145–150. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4953733/ 
3. Rizzo, G., Laganà, A. S., Rapisarda, A. M., La Ferrera, G. M., Buscema, M., Rossetti, P., Nigro, A., Muscia, V., Valenti, G., Sapia, F., Sarpietro, G., Zigarelli, M., & Vitale, S. G. (2016). Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients, 8(12), 767. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5188422/ 
4. 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/ 
5. Majumder, S., Soriano, J., Louie Cruz, A., & Dasanu, C. A. (2013). Vitamin B12 deficiency in patients undergoing bariatric surgery: preventive strategies and key recommendations. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery, 9(6), 1013–1019. Abstract: https://pubmed.ncbi.nlm.nih.gov/24091055/ 
6. 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/ 
7. 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 
8. 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/ 
9. Thakkar, K., & Billa, G. (2015). Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. European journal of clinical nutrition, 69(1), 1–2. Abstract: https://pubmed.ncbi.nlm.nih.gov/25117994/