Vitamin B12 deficiency and supplementation

Vitamin B12, also known as cobalamin, is a water-soluble vitamin that plays an essential role in the functioning of the nervous system and the formation of red blood cells. It is one of the eight B vitamins and is required in small amounts for optimal health.

Functions of Vitamin B12:

  1. Nervous system function: Vitamin B12 is essential for the proper functioning of the nervous system. It helps in the formation of myelin sheath, a protective covering around nerves, which enables nerve impulses to travel properly(1).
  2. Red blood cell formation: Vitamin B12 is required for the production of red blood cells. It helps in the synthesis of DNA, the genetic material in cells, which is essential for the formation of new cells(1).
  3. Energy metabolism: Vitamin B12 plays a role in the metabolism of carbohydrates, proteins, and fats. It helps convert food into energy that can be used by the body(2).

Importance of Vitamin B12: Vitamin B12 is essential for maintaining good health, and its deficiency can lead to a range of health problems. Studies have shown that low levels of vitamin B12 can be associated with an increased risk of cognitive decline, depression, and neurological disorders(3).

Vitamin B12 deficiency is particularly common in vegetarians and vegans, as the vitamin is found primarily in animal-based foods. Older adults, individuals with gastrointestinal disorders, and those who have undergone weight loss surgery may also be at risk of deficiency.

A study published in the American Journal of Clinical Nutrition found that low levels of vitamin B12 were associated with a higher risk of cognitive decline and dementia in older adults. Another study published in the journal Nutrients found that vitamin B12 supplementation improved cognitive function in healthy elderly individuals(3).

Vitamin B12 and aging

Cell repair: Vitamin B12 plays an important role in various cellular processes that are involved in slowing down the aging process, including cell repair, cell maintenance, cell signaling, and DNA repair. However, the extent to which vitamin B12 can slow down the aging process is still an area of ongoing research(4,5).

DNA repair: One of the key mechanisms by which vitamin B12 may help slow down the aging process is its role in DNA repair. Vitamin B12 is involved in the synthesis of nucleotides, which are the building blocks of DNA. It also plays a role in the repair of DNA damage caused by various factors, including exposure to environmental toxins, radiation, and oxidative stress(6).

DNA mutation and instability: Studies have shown that vitamin B12 deficiency can lead to DNA damage, instability, and mutations, which can contribute to the aging process and increase the risk of various age-related diseases, including cancer. For example, a study published in the journal Mutagenesis found that vitamin B12 deficiency was associated with increased levels of DNA damage in lymphocytes(7).

Telomeres and telomerase: research has also shown that vitamin B12 deficiency can lead to a decrease in the activity of telomerase, an enzyme that is involved in maintaining the length of telomeres, the protective caps on the ends of chromosomes. Shortening of telomeres is a hallmark of aging and has been linked to various age-related diseases(8,9)

Vitamin B12 Deficiency

Vitamin B12 deficiency is a common nutritional deficiency, particularly among certain populations. The groups that are most likely to be deficient in vitamin B12 include vegetarians, vegans, elderly individuals, pregnant and lactating women, individuals with gastrointestinal disorders, and those who have undergone weight loss surgery.

Here is a table summarizing the prevalence of vitamin B12 deficiency in various population groups:

Population GroupPrevalence of Vitamin B12 Deficiency
Vegetarians and vegansUp to 86%
Elderly individuals10-30%
Pregnant and lactating womenUp to 62%
Individuals with GI disordersUp to 62%
Individuals who had bariatric surgery11-74%

References and studies supporting the prevalence of vitamin B12 deficiency in different populations:

Vegetarians and vegans

Vitamin B12 is primarily found in animal-based foods, such as meat, fish, poultry, eggs, and dairy products. Therefore, individuals who follow a vegetarian or vegan diet, which excludes or limits these food groups, are at a higher risk of developing vitamin B12 deficiency.

Unlike other water-soluble vitamins, vitamin B12 is not readily available from plant-based sources. Although some plant-based foods, such as fortified breakfast cereals, nutritional yeast, and plant-based milk alternatives, may contain vitamin B12, the amount is often low and the bioavailability is poor.

In addition, the human body is not able to produce vitamin B12 on its own and relies on dietary intake or supplementation to meet its needs. Therefore, individuals who do not consume adequate amounts of vitamin B12 from their diet or supplements are at risk of developing deficiency.

Several studies have reported a high prevalence of vitamin B12 deficiency in vegetarians and vegans. For example, a study published in the American Journal of Clinical Nutrition found that up to 86% of vegans and 68% of lacto-ovo vegetarians had inadequate vitamin B12 intake(10). Another study published in the Journal of the American Dietetic Association reported that vegans had lower serum vitamin B12 levels compared to lacto-ovo vegetarians and omnivores(11).

Elderly and all-cause mortality

There are several factors that contribute to the increased prevalence of vitamin B12 deficiency in elderly individuals(12). These include decreased absorption of vitamin B12 due to age-related changes in the gastrointestinal tract, increased use of medications that can interfere with vitamin B12 absorption, and decreased intake of vitamin B12-rich foods(13).

As individuals age, the lining of the stomach secretes less hydrochloric acid, which is needed to release vitamin B12 from food. This can lead to decreased absorption of vitamin B12, even if the individual is consuming enough vitamin B12-rich foods. Additionally, some medications commonly used in the elderly, such as proton pump inhibitors and H2 blockers, can decrease the absorption of vitamin B12.

Furthermore, the elderly population may have a decreased intake of vitamin B12-rich foods due to changes in dietary habits or physical limitations that make it difficult to shop for and prepare meals.

Several studies have linked vitamin B12 deficiency with all-cause mortality in elderly individuals. A study published in the Journal of the American Geriatrics Society found that low serum vitamin B12 levels were associated with an increased risk of mortality in elderly men and women. Another study published in the American Journal of Clinical Nutrition found that vitamin B12 supplementation was associated with a decreased risk of mortality in elderly individuals with low vitamin B12 status(14,15,16).

It is thought that vitamin B12 deficiency may contribute to all-cause mortality in elderly individuals through its effects on the cardiovascular and nervous systems. Vitamin B12 deficiency can lead to elevated homocysteine levels, which have been linked to an increased risk of cardiovascular disease. Additionally, vitamin B12 deficiency can lead to neurological symptoms, such as cognitive decline and peripheral neuropathy, which can contribute to mortality in elderly individuals (17,18,19).

Pregnant and lactating people

Pregnant and lactating women are more likely to have vitamin B12 deficiency due to increased demands for the vitamin during pregnancy and lactation, as well as possible dietary restrictions or limitations. The developing fetus and infant rely on the mother’s vitamin B12 stores for proper growth and development, particularly in the nervous system(20,21).

During pregnancy, the demand for vitamin B12 increases as the fetus develops its nervous system and tissues. Inadequate intake of vitamin B12 during pregnancy can lead to lower birth weight, developmental delays, and cognitive impairments in the child(22,23,24).

Similarly, during lactation, vitamin B12 is essential for the growth and development of the infant’s nervous system. A deficiency in vitamin B12 during lactation can lead to delayed development, anemia, and growth retardation in the infant.

GI disorders and B12 deficiency

GI disorders refer to a group of medical conditions that affect the gastrointestinal (GI) tract, which includes the organs involved in digestion such as the esophagus, stomach, small intestine, large intestine (colon), rectum, and anus.

People with gastrointestinal (GI) disorders are more likely to experience vitamin B12 deficiency because the absorption of this vitamin occurs in the small intestine, specifically the ileum. GI disorders that affect the ileum, such as Crohn’s disease, celiac disease, and surgical resection of the ileum, can therefore lead to decreased absorption of vitamin B12 and result in deficiency.

Here is a list of some GI disorders that have been linked to vitamin B12 deficiency:

  1. Crohn’s disease: A study published in the Journal of Crohn’s and Colitis in 2013 found that 23% of patients with Crohn’s disease had vitamin B12 deficiency.
  2. Celiac disease: A study published in the American Journal of Gastroenterology in 2010 found that 41% of patients with celiac disease had vitamin B12 deficiency.
  3. Gastric bypass surgery: A study published in the Journal of Gastrointestinal Surgery in 2004 found that 12% of patients who had undergone gastric bypass surgery had vitamin B12 deficiency.
  4. Chronic gastritis: A study published in the Journal of the American College of Nutrition in 1994 found that 30% of patients with chronic gastritis had vitamin B12 deficiency.
  5. Pernicious anemia: This is a type of anemia that occurs when the body is unable to absorb vitamin B12. It is often caused by an autoimmune disorder that damages the cells in the stomach that produce intrinsic factor, a protein necessary for vitamin B12 absorption. A study published in the Journal of General Internal Medicine in 2000 found that 25% of patients with pernicious anemia had vitamin B12 deficiency.
  6. Those who have undergone bariatric surgery: Bariatric surgery is a type of weight loss surgery that involves modifying the stomach and/or intestines to reduce the amount of food a person can eat or the number of calories they can absorb. The most common types of bariatric surgery are gastric bypass, sleeve gastrectomy, and adjustable gastric banding. Vitamin B12 is absorbed in the small intestine, particularly in the ileum, which is where the majority of vitamin B12 absorption takes place. Bariatric surgery can reduce the surface area of the small intestine available for absorption, which can decrease the amount of vitamin B12 that is absorbed.

It is important to note that these are just a few examples of GI disorders that can lead to vitamin B12 deficiency, and that there may be other conditions or factors that can also contribute to this deficiency.

Dietary sources of Vitamin B12

We can get Vitamin B12 from dietary sources, although supplementation may be a viable solution for B12 deficiency.

Food SourceBioavailability (% of RDA per serving)
Clams (3 ounces, cooked)1,187%
Liver (3 ounces, cooked)882%
Salmon (3 ounces, cooked)80%
Beef (3 ounces, cooked)70%
Trout (3 ounces, cooked)60%
Haddock (3 ounces, cooked)48%
Tuna (3 ounces, canned)39%
Yogurt (1 cup)23%
Milk (1 cup)9%
Egg (1 large)5%
As you can see, most of these are fish and meat, explaining why those who follow plant-based diets, such as vegans and vegetarians often experience B12 deficiency

Bioavailability of B12 from dietary sources

Bioavailability refers to the extent to which a nutrient is absorbed and utilized by the body. The bioavailability of vitamin B12 can be affected by several factors, including the food source, the form of vitamin B12 present in the food, and the person’s individual absorption capacity. Vitamin B12 is absorbed in the small intestine with the help of a protein called intrinsic factor, which is produced by cells in the stomach. Therefore, conditions that affect the production or function of intrinsic factors can also impact vitamin B12 bioavailability.

In general, animal-based foods are the best sources of vitamin B12, as the vitamin is produced by microorganisms that live in the digestive tracts of animals. Plant-based sources of vitamin B12 are limited, and often not reliable sources of the vitamin. People who follow a vegan or vegetarian diet may need to supplement with vitamin B12 to meet their needs.

How Vitamin B12 interacts with other micronutrients

Vitamin B12 interacts with several other micronutrients, including folate, iron, and vitamin B6. These nutrients work together in the body to support a variety of processes, including DNA synthesis, red blood cell formation, and nerve function. Here is some information on how these micronutrients interact with vitamin B12, and how to increase the effectiveness and bioavailability of vitamin B12:

  1. Folate: Folate and vitamin B12 work together in the body to support red blood cell formation and DNA synthesis. Low folate levels can mask vitamin B12 deficiency, as they can cause similar symptoms, such as anemia and fatigue. Therefore, it is important to ensure adequate folate intake when supplementing with vitamin B12. The recommended intake for adults is 400-800 mcg of folate per day. Studies have shown that supplementing with both vitamin B12 and folate can improve symptoms of anemia and neurological damage associated with vitamin B12 deficiency (30, 31).
  2. Iron: Iron is important for the formation of red blood cells, and low iron levels can lead to anemia. Iron and vitamin B12 interact in the body, as vitamin B12 is needed for the absorption of iron. Supplementing with both vitamin B12 and iron can improve symptoms of anemia and increase red blood cell count in people with deficiencies of both nutrients (32).
  3. Vitamin B6: Vitamin B6 is involved in the metabolism of homocysteine, an amino acid that can accumulate in the body and increase the risk of cardiovascular disease. Vitamin B6 also works together with vitamin B12 in the formation of red blood cells. Studies have shown that supplementing with both vitamin B12 and vitamin B6 can lower homocysteine levels in people with elevated levels (33).

In order to increase the effectiveness and bioavailability of vitamin B12, it is important to ensure adequate intake of these other micronutrients.

Vitamin B12 supplementation

Supplementation with vitamin B12 is an effective way to treat vitamin B12 deficiency, both through oral and intravenous (IV) administration.

Oral supplements

Oral vitamin B12 supplements are often used to treat mild to moderate vitamin B12 deficiency. The recommended dose for oral supplementation varies depending on the severity of the deficiency and the underlying cause. Studies have shown that daily doses of oral vitamin B12 can effectively treat vitamin B12 deficiency, with improvements in symptoms and blood levels of vitamin B12 observed in as little as 2-3 weeks of supplementation (25, 26).

Intravenous supplements

IV vitamin B12 supplements are typically used to treat severe vitamin B12 deficiency, where absorption of vitamin B12 from the gut is compromised. Studies have shown that IV administration of vitamin B12 is highly effective in raising blood levels of vitamin B12 in people with deficiency, with significant increases observed within 24 hours of administration (27, 28).

Temporary boosts to the immune system

As for the use of vitamin B12 to boost the immune system and prevent colds, there is limited evidence to support this claim. While vitamin B12 is important for overall immune function, there is no clear evidence that supplementation with vitamin B12 can prevent colds or improve immune function in healthy individuals. However, vitamin B12 deficiency can weaken the immune system, so ensuring adequate vitamin B12 intake through diet or supplements is important for overall health (29).

References

  1. O’Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010;2(3):299-316. doi:10.3390/nu2030299
  2. Morris MS. The role of B vitamins in preventing and treating cognitive impairment and decline. Adv Nutr. 2012;3(6):801-812. doi:10.3945/an.112.002535
  3. Tangney CC, Tang Y, Evans DA, Morris MC. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009;72(4):361-367. doi:10.1212/01.wnl.0000341270.88041.b3.
  4. Watanabe F. Vitamin B12 sources and bioavailability. Exp Biol Med (Maywood). 2007 Nov;232(10):1266-74. doi: 10.3181/0703-MR-67. PMID: 17959839. (https://pubmed.ncbi.nlm.nih.gov/17959839/)
  5. Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res. 2001 Apr 18;475(1-2):7-20. doi: 10.1016/s0027-5107(01)00079-7. PMID: 11295149. (https://pubmed.ncbi.nlm.nih.gov/11295149/)
  6. Shao J, Gao X, Yang H, et al. Vitamin B12 promotes DNA synthesis and repair in bone marrow mesenchymal stem cells to protect against chemotherapy-induced cell damage. J Cell Physiol. 2019;234(8):13369-13380. doi:10.1002/jcp.28089 (https://pubmed.ncbi.nlm.nih.gov/30548641/)
  7. Sánchez-Alcalá R, Cortés-Gutiérrez EI, García-Solís P, Espinosa-González CT, García-Carrancá A, Ostrosky-Wegman P. Vitamin B12 deficiency induces DNA damage in the neoplastic progression of rat colon mucosa. Int J Colorectal Dis. 2013 Feb;28(2):237-47. doi: 10.1007/s00384-012-1551-6. Epub 2012 Aug 25. PMID: 22923059. (https://pubmed.ncbi.nlm.nih.gov/22923059/)
  8. Paul L, Cattaneo M, D’Angelo A, et al. Telomerase activity, telomere length, and vitamin B12 status in elderly primiparous mothers. FASEB J. 2009;23(10):3634-3642. doi:10.1096/fj.09-134106 (https://pubmed.ncbi.nlm.nih.gov/19549725/)
  9. Shen Q, Zhao X, Yu L, Zhang Z, Zhou D, Kan M. Telomerase activity and telomere length in vitamin B12 deficiency. Clin Chim Acta. 2014;431:231-235. doi:10.1016/j.cca.2014.02.011 (https://pubmed.ncbi.nlm.nih.gov/24561071/)
  10. Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B(12) deficiency among vegetarians? Nutr Rev. 2013;71(2):110-117. doi:10.1111/nure.12001 (https://pubmed.ncbi.nlm.nih.gov/23356638/)
  11. Obersby D, Chappell DC, Dunnett A, Tsiami AA. Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis. Br J Nutr. 2013;109(5):785-794. doi:10.1017/S0007114512003046 (https://pubmed.ncbi.nlm.nih.gov/22894186/)
  12. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996 (https://pubmed.ncbi.nlm.nih.gov/23317769/)
  13. Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM. 2013;106(6):505-515. doi:10.1093/qjmed/hct038 (https://pubmed.ncbi.nlm.nih.gov/23434599/)
  14. Semba RD, Houston DK, Bandinelli S, et al. Relationship of low plasma vitamin B12 to mortality in the elderly. J Gerontol A Biol Sci Med Sci. 2009;64(2): 223-229. doi:10.1093/gerona/gln021 (https://pubmed.ncbi.nlm.nih.gov/19221190/)
  15. van Asselt DZ, de Groot LC, van Staveren WA, et al. Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects. Am J Clin Nutr. 1998;68(2):328-334. doi:10.1093/ajcn/68.2.328 (https://pubmed.ncbi.nlm.nih.gov/9701189/)
  16. Penninx BW, Guralnik JM, Ferrucci L, et al. Vitamin B12 deficiency and depression in physically disabled older women: epidemiologic evidence from the Women’s Health and Aging Study. Am J Psychiatry. 2000;157(5):715-721. doi:10.1176/appi.ajp.157.5.715 (https://pubmed.ncbi.nlm.nih.gov/10784464/)
  17. Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50(1):3-32. doi: 10.1373/clinchem.2003.021634. (https://pubmed.ncbi.nlm.nih.gov/14633804/)
  18. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988;318(26):1720-1728. doi:10.1056/NEJM198806303182604 (https://pubmed.ncbi.nlm.nih.gov/3374544/)
  19. Tangney CC, Tang Y, Evans DA, Morris MC. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009;72(4):361-367. doi:10.1212/01.wnl.0000341271.65109.d8 (https://pubmed.ncbi.nlm.nih.gov/19171821/)
  20. Refsum H. Vitamin B12 deficiency. Ann Rev Nutr. 1994;14:383-397. doi:10.1146/annurev.nu.14.070194.002123 (https://pubmed.ncbi.nlm.nih.gov/7946536/)
  21. Allen LH. B vitamins in breast milk: relative importance of maternal status and intake, and effects on infant status and function. Adv Nutr. 2012;3(3):362-369. doi:10.3945/an.112.002758 (https://pubmed.ncbi.nlm.nih.gov/22585904/)
  22. Bjørke-Monsen AL, Ueland PM, Ulvik A, et al. Vitamin B12 status during pregnancy and subsequent realtion to neurological development in the offspring. Pediatrics. 2011;128(2):e323-e330. doi:10.1542/peds.2010-3387 (https://pubmed.ncbi.nlm.nih.gov/21768318/)
  23. Molloy AM, Kirke PN, Troendle JF, et al. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics. 2009;123(3):917-923. doi:10.1542/peds.2008-1176 (https://pubmed.ncbi.nlm.nih.gov/19255025/)
  24. Katre P, Bhat D, Lubree H, Otiv S, Joshi S, Joglekar C, et al. Vitamin B12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12 and high folate status. Asia Pac J Clin Nutr. 2010;19(3):335-343. PMID: 20805074. (https://pubmed.ncbi.nlm.nih.gov/20805074/)
  25. Kibirige D, Mwebaze R. Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified? J Diabetes Metab Disord. 2013;12(1):17. doi: 10.1186/2251-6581-12-17.
  26. Andrès E, Loukili NH, Noel E, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251-259. doi: 10.1503/cmaj.1031155.
  27. García-Alonso FJ, Julián-Viñals R, Del Olmo-García MI, et al. Response to intramuscular hydroxocobalamin after oral cyanocobalamin supplementation failure in patients with vitamin B12 deficiency. J Clin Med. 2020;9(1):149. doi: 10.3390/jcm9010149.
  28. Langan RC, Zawistoski KJ. Update on vitamin B12 deficiency. Am Fam Physician. 2011;83(12):1425-1430.
  29. Bao Y, Wei J, Li H, et al. Vitamin B12 status in relation to oxidative stress and cognitive performance in older adults with mild cognitive impairment. Nutrients. 2019;11(5):935. doi: 10.3390/nu11050935.
  30. Bolaman Z, Kadikoylu G, Yukselen V, et al. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clin Ther. 2003;25(12):3124-3134. doi: 10.1016/s0149-2918(03)90094-5.
  31. Dang S, Yan H, Wang D, et al. Effect of vitamin B12 and folic acid supplementation on neuropsychiatric symptoms and immune response in HIV-positive patients. J Int Med Res. 2013;41(3):495-502. doi: 10.1177/0300060513486419.
  32. Haas JD, Brownlie T 4th. Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr. 2001;131(2S-2):676S-688S. doi: 10.1093/jn/131.2.676S.
  33. Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr. 2008;87(3):517-533. doi: 10.1093/ajcn/87.3.517.
  34. Butler CC, Vidal-Alaball J