B12 - Maintaining a Healthy Status

What you need to know about maintaining healthy B12 status

Beth Ellen DiLuglio, MS, RDN, LDN

Vitamin B12, technically known as “cobalamin,” is a popular subject throughout the population, but what do we really need to know about B12?

• Although the RDA is set at 2.4 ug/day (adults, not pregnant or lactating), higher levels may be needed for optimal B12 status.
• May need at least 4-7 ug B12/day to positively impact plasma methylmalonic acid, homocysteine, cobalamin, transcobalamin, and holo-transcobalamin.[1]
• May need at least 7 ug/day to support DNA replication and genomic stability.[2]
• At least 17.6 ug/day reflects average B12 intake over evolutionary periods.[3]
• B12 is recycled and stored in the body and utilized by two enzymes (methylmalonyl-CoA mutase and methionine synthase).

 Sources of B12

• Animal-based foods are the best source of B12, including fish, shellfish, liver, and dairy because B12 is stored in their muscle, organs, liver, milk, meat, and eggs.
• Dairy foods appear to promote the greatest increase in serum B12, followed by fortified cereals, meat, fish, and poultry.[4]
• B12 analogues or “imposters” can be produced by plants or fermented foods but they are not considered bioactive forms, therefore vegans can be at risk of deficiency.[5]

*DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for vitamin B12 on the new Nutrition Facts and Supplement Facts labels and used for the values in Table 2 is 2.4 mcg for adults and children age 4 years and older [17]. FDA required manufacturers to use these new labels starting in January 2020, but companies with annual sales of less than $10 million may continue to use the old labels that list a vitamin B12 DV of 6.0 mcg until January 2021 [16,18]. FDA does not require food labels to list vitamin B12 content unless vitamin B12 has been added to the food. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet. [6]

Route and type of B12 supplementation

Supplemental B12 is available in the natural bioidentical forms of methylcobalamin, adenosylcobalamin, and hydroxocobalamin, as well as the synthetic form cyanocobalamin.

• High-dose oral B12 (1-2 mg/day) may be equivalent to IM injections taken for pernicious anemia.
• Lower doses of 500-1000 ug/day may be used in the absence of pernicious anemia for those with a low-normal B12 level.[7] Doses above 50 ug can be absorbed without intrinsic factor.[8]
• Cyanocobalamin has inferior bioavailability due to less efficient uptake and decreased metabolic activation. Researchers don’t recommend cyano- form due to potential cyanide buildup.
• B12 absorption decreases as dose increases: 50% for a dose less than 0.5 ug and 0.01-0.012% for a 1000 ug dose.[9]
• No adverse reactions have been observed at high doses and there is no upper limit for B12.
• Supplemental forms, methylcobalamin, adenosylcobalamin, and hydroxocobalamin, are reduced to cobalamin and then reassembled in the cell. Methyl- is a readily available, inexpensive form.

The main functions of vitamin B12 should be kept in mind during clinical evaluations:

• RBC synthesis and prevention of megaloblastic anemia [and white blood cell formation]
• Neurologic function including prevention of neuropathy and demyelination
• Support of cognitive function and prevention of dementia
• Prevention of hyperhomocysteinemia
• Support of DNA synthesis

Assessing B12 status

• Vitamin B12 deficiency may be asymptomatic and may progress despite levels of serum B12 being within normal standard range.
• Laboratory diagnosis of B12 deficiency should include at least two biomarkers, ideally holotranscobalamin and serum MMA
• Early screening can be based on homocysteine of greater than 9 umol/L. Testing for elevated MMA can help distinguish between B12 and folate deficiency in hyperhomocysteinemia.

What's Next? Read the "ODX B12 Deficiency Series" in our Research Blog

REFERENCES

[1] Bor, Mustafa Vakur et al. “Daily intake of 4 to 7 microg dietary vitamin B-12 is associated with steady concentrations of vitamin B-12-related biomarkers in a healthy young population.” The American journal of clinical nutrition vol. 91,3 (2010): 571-7. doi:10.3945/ajcn.2009.28082

[2] Fenech, M. “The role of folic acid and Vitamin B12 in genomic stability of human cells.” Mutation research vol. 475,1-2 (2001): 57-67. doi:10.1016/s0027-5107(01)00079-3

[3] Cordain, Loren. "The nutritional characteristics of a contemporary diet based upon Paleolithic food groups." J Am Neutraceutical Assoc 5.3 (2002): 15-24.

[4] Allen, Lindsay H et al. “Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review.” The Journal of nutrition vol. 148,suppl_4 (2018): 1995S-2027S. doi:10.1093/jn/nxy201

[5] Paul, Cristiana, and David M Brady. “Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms.” Integrative medicine (Encinitas, Calif.) vol. 16,1 (2017): 42-49.

[6] NIH. ODS. Vitamin B12 Fact Sheet for Health Professionals.

[7] Smith, A David et al. “Vitamin B12.” Advances in food and nutrition research vol. 83 (2018): 215-279. doi:10.1016/bs.afnr.2017.11.005

[8] Allen, Lindsay H et al. “Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review.” The Journal of nutrition vol. 148,suppl_4 (2018): 1995S-2027S. doi:10.1093/jn/nxy201

[9] Paul, Cristiana, and David M Brady. “Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms.” Integrative medicine (Encinitas, Calif.) vol. 16,1 (2017): 42-49.