# 8.5 Vitamin B12

Vitamin B12 is a water soluble vitamin also known as Cobalamin. Water soluble vitamins are hydrophilic and are absorbed directly into the blood where they travel freely in water filled compartments through out the body. The water soluble vitamins are less likely to create toxicity in the body due to the daily excretion of excess vitamins in urine. B12 helps with the synthesis of new cells, is a coenzyme to folate, and helps to break down fatty acids and amino acids in the daily diet (Whitney, 2002).

## 8.5.1 Sources

Vitamin B12 is only found it animal products including: meat, fish, poultry, milk cheese and eggs. Since B12 is not naturally occurring in grains, it can be fortified into different cereals and breads (Whitney, 2002). The vitamin is also produced in the colon of humans by bacteria, but not enough is absorbed to be considered a good source. In ruminants B12 is synthesized using bacteria and cobalt, it is carried to the blood and enterocytes on the carrier Transcobalamin (Albert, 1980).
The greatest source of vitamin B12 is milk and fish. It is primarily found in animal products (Whitney, 2002). The reason that vegans have difficult consuming enough vitamin B12 is that finding sources that are not animal products is difficult. A couple of options include fortified soymilk or vitamin B12 supplements (Whitney, 2002).
The bioavailability of vitamin B12 in humans from fish meat averages 42 percent, sheep meat 56-89 percent, and chicken 61-66 percent (Watanabe, 2007). Compared to other animal products, B12 in eggs is not as well absorbed. Absorption is less than nine percent while typically 50 percent of B12 consumed will be absorbed (Watanabe, 2007).
While vitamin B12 is often reported as a nutrient in plants, the amounts could be inaccurate because the vitamin is in a form that cannot be absorbed and used by the body (Roman, 2013).

## 8.5.2 Functions

B12 creates the coenzyme to help activate folate, and helps to maintain nerve cells by protecting and synthesis of the myelin sheath. Another important function is the synthesis of new cells, specifically red blood cells with the production of hemoglobin and the synthesis of the coenzyme methylcobalamin. Some methylcobalamin is converted into homocysteine, which can result in cardiovascular disease at high concentrations (“Coenzyme Functions”).
Vitamin B12 is required for healthy neurological development, biological methylation and DNA synthesis. Another function it participates in is the mitochondrial catabolism of odd-chain fatty acids and some amino acids (Troen). Limited evidence has also been found suggesting there is an association between vitamin B12 and neurological function in older adults (Miles, 2015). There is still little research as to what roles vitamin B12 plays in memory, but as more information is discovered, more correlations between memory and B12 are found.
Another function vitamin B12 plays is in maternal development. Vitamin B12 is involved in one-carbon metabolism along with folate and docosahexaenoic acid (DHA) and plays a major role during pregnancy in developing the fetus and is an important determinant of epigenesist (Dhobale, 2012). Low-weight babies have a higher risk for developing brain disorders such as cognitive dysfunction and psychiatric disorders because of this (Dhobale, 2012).
Vitamin B12 depends on folate for activation and folate depends on vitamin B12. Vitamin B12 removes a methyl group to active folate which in tern activates vitamin B12 when folate gives up the methyl group (Whitney, 2002k). The regeneration of methionine and the synthesis of DNA and RNA need both folate and vitamin B12 (Whitney, 2002).

## 8.5.3 Requirements

Vitamin B-12 requirements vary by age. Recommended daily amounts (RDAs) are shown below (National Institutes of Health). According to two cross-sectional studies done comparing men to women, B-12 requirements do not very by gender (Rosner and Schreiber, 1972; Scott et al., 1974). Vitamin B-12 requirements do, however, increase for pregnant and lactating women because the mother transfers some to the infant via the placenta and through breast milk (Kaiser, 2008). No UL has been set for vitamin B-12 (Whitney and Rolfes, 2014).
The Recommended Dietary Allowance (RDA) set in 1998 for adults is 2.4 µg/day.
People over the age of 50 need higher amounts due to a decrease in absorption (Whitney, 2002).

## 8.5.4 Deficiency

People who follow a vegetarian or vegan diet have a higher chance of developing a deficiency (Pawlak, 2013, 110). To avoid such deficiencies having an adequate intake of animal products such as eggs and milk for vegetarians or consuming foods that are enriched with B12 for individuals who follow a vegan diet. Supplements can also be taken to decrease the likelihood of a deficiency. Megaloblastic Anemia (large cell type) is due to a deficiency in B12 or folate; a high folate level can mask the deficiency of B12 and correct the anima, but not the damage to the heme (“Vitamin B12 Deficiency And Paralysis”).
Pernicious Anemia is caused by the lack of red blood cells due to a deficiency in B12, caused primarily by a lack of intrinsic factor. Intrinsic factor is the protein secreted by the stomach to help the intestines absorb vitamin B12. A lack in intrinsic factor can be a result of old age or Atrophic Gastritis which is the inflammation of the stomach epithelium which results in loss of the stomach mucosa cells which secrete the intrinsic factor and other digestive enzymes (Zayouna).
Muscle Weakness and Paralysis- B12 deficiency can result in skeletal muscle weakness due to decreased nerve cell function, in more serious cases where the B12 stores are completely depleted paralysis can occur (Morris, 2012, p. 1457).
Memory Loss- With a deficiency fewer red blood cells are synthesized resulting in anemia, with less than usual red blood cell count a decreased amount of essential nutrients are delivered to the brain. Some people with a severe deficiency could be misdiagnosed with Alzheimer’s disease due to the similar symptoms (“Vitamin B12 Deficiency And Paralysis”).
Other deficiency symptoms include fatigue and dizziness, which are side effects of anemia
Vitamin B-12 deficiency can lead to decreased neurological function, prevent DNA and RNA synthesis, impair liver and pancreatic function, and damage the intestinal tract including loss of villi and decreased nutrient absorption (Riordan, 2012). It is important in the production of red blood cells, and can help to prevent or correct pernicious anemia (Frazier). Because vitamin B-12 is only found in meat products, most deficiency occurs in vegans, infants breast fed by vegans, and the elderly. Vegans do not consume any animal products. This means that they need another reliable source of the vitamin, usually in the form of an oral supplement or a fortified plant-based milk. Infants breast fed by vegans can develop deficiency only a few months following birth (National Institutes of Health). To prevent this, B-12 should be supplemented during both pregnancy and lactation to transfer enough to the fetus and infant to avoid developmental delays (Kaiser, 2008).
Elderly are at risk of becoming B-12 deficient because as they age their stomach produces decreased amounts of HCl which is necessary to break down protein efficiently enough to unbind B-12. This phenomenon, called atrophic gastritis, is characterized by thinned stomach lining resulting in insufficient vitamin absorption regardless of availability (Dunkin, 2013). For this reason, a vitamin B-12 supplement is recommended in older adults (Von Castel-Roberts, 2015). Those suffering from dietary vitamin B-12 deficiency can recover by adding B-12 into their diets either through meat, fortified foods, or a supplement (Dunkin, 2013). However, prolonged deficiency may lead to irreversible damage.
Pernicious anemia is decreased red blood cell production by lack of vitamin B-12. An intrinsic factor, a glycoprotein secreted by the stomach that binds with B-12, is necessary for intestinal absorption. Those who lack the intrinsic factor necessary to absorb B-12 (by either a genetic defect or an injured stomach) will develop pernicious anemia, as they are not able to absorb B-12 in the small intestine no matter how much of the vitamin they get from food (Institute of Medicine, 1998). Individuals lacking the intrinsic factor require medical treatment. Data from over one hundred patients with pernicious anemia revealed that liver and stomach therapy increased red blood cell production (Raphael, 1938). Also, a B-12 injection would provide enough of the vitamin while bypassing intestinal absorption (Whitney and Rolfes, 2014).

## 8.5.5 Toxicity

There is no reported vitamin B-12 toxicity to date. Being a water-soluble vitamin, B-12 is difficult to overdose or build up in toxic amounts since the body excretes excess amounts in the urine instead of storing it (Frazier). Many B-12 vitamins are combined with other B vitamins, including riboflavin. If you have ever noticed that your urine is bright yellow after taking a B-complex vitamin, it is the result of extra riboflavin being excreted in the urine.

## 8.5.6 Absorption

The absorption of vitamin B12 in the body is a multistep process that requires many other compounds before entering the bloodstream. Absorption of B12 is essential for it to be able to perform its vital functions in the body. If it is consumed in animal products, the vitamin is attached to proteins (“Vitamin B12”). When this complex enters the stomach, chief cells and parietal cells from pits in the lining of the stomach secrete pepsin and hydrochloric acid, respectively. These compounds break vitamin B12 off from the proteins (Marieb, 2011). Also in the stomach, B12 binds to an R-protein that comes from the salivary glands. This complex enters the small intestine where B12 separates from the protein by pancreatic enzymes. Vitamin B12 then binds with intrinsic factor, which is synthesized in the stomach, and travels to the last section of the small intestine, the ileum. Here, the intrinsic factor binds to a receptor site at the lining of the small intestine so vitamin B12 can be absorbed by crossing the intestinal cell membrane. Vitamin B12 then attached to a protein called transcobalamin II so it can enter the bloodstream via the portal vein. Once Vitamin B12 enters the bloodstream it gets to the bone marrow and red blood cells which allows for it to carry out its main functions in maintaining healthy red blood cells, maintaining healthy nervous tissue, and being utilized in DNA synthesis. Since there are so many steps and other compounds in these absorption processes, not having one of the proteins or enough intrinsic factor could actually lead to a B12 deficiency independent of how much the vitamin is consumed in the diet (Whitney, 2002).

## 8.5.7 Role in DNA Synthesis

Vitamin B12 plays an important role in the synthesis of DNA. It is a cofactor for the enzyme methionine synthase. This enzyme catalyzes the reaction that converts homocysteine to the methionine protein. S-adenosylmethionine, made from methionine, donates a methyl for DNA (“Vitamin B12”).

## 8.5.8 B12 and Folate

As with all B vitamins, vitamin B12 plays an active role in human metabolism (Ehrlich). B12 converts THF, a form of folate, to its active form by removing a methyl group. This process allows folate to enter the TCA cycle. Thus, B12 is used in the formation of new cells (“Vitamin B12”).

## References

Albert, M. (1980, February 21). Vitamin B12 synthesis by human small intestinal bacteria. Retrieved November 10, 2015.
Coenzyme Functions. (n.d.). Retrieved November 10, 2015.
Dhobale, M., & Joshi, S. (2012, April). Altered maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids through oxidative stress may reduce neurotrophic factors in preterm pregnancy. Journal of Maternal-Fetal & Neonatal Medicine, 25(4), 317-323. doi: 10.3109/14767058.2011.579209
Dunkin, M. (2011). Vitamin B12 Deficiency. Web. 24 Oct. 2015.
Ehrlich, S. (2015, October 19). Vitamin B12 (Cobalamin). Retrieved November 26, 2015, from http://umm.edu/health/medical/altmed/supplement/vitamin-b12-cobalamin
Frazier, K. (n.d.). Side Effects of Too Much Vitamin B12. Web. 25 Oct, 2015.
Institute of Medicine US (1998). Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Washington (DC): National Academies Press (US).
Kaiser L, Allen LH. (2008). Position of the American Dietetic Association: nutrition and lifestyle for a healthy pregnancy outcome. J Am Diet Association; 108:553-61
Marieb, E. (2011). The Digestive System. In Applied Human Anatomy (2nd ed., p. 695). Pearson Custom Publishing.
Miles, L. M. (2015). Is there an association of vitamin B12 status with neurological function in older people? A systematic review. British Journal of Nutrition Br J Nutr, 114(04), 503-508. doi:10.1017/S0007114515002226
Morris, M. (2012). American Geriatrics Society. Vitamin B-12 and Folate Status in Relation to Decline in Scores on the Mini-Mental State Examination in the Framingham Heart Study, 60, 1457–1464-1457–1464.
National Institutes of Health. (2011). Vitamin B-12 fact sheet for consumers. U.S. Department of Health and Human Services, 24 June 2011. Web. 12 Oct. 2015.
Riordan HD, Mikirova N, Taylor PR, Feldkamp CA, Casciari JJ. (2012). The Effects of a Primary Nutritional Deficiency (Vitamin B Study). Food and Nutrition Sciences, Vol. 3 No. 9, pp. 1238–1244
Rosner F, Schreiber ZA. (1972). Serum vitamin B12 and vitamin B12 binding capacity in chronic myelogenous leukemia and other disorders. Am J Med Sci. ; 263:473–480.
Scott JM, Bloomfield FJ, Stebbins R, Herbert V. (1974). Studies on derivation of transcobalamin 3 from granulocytes. Enhancement by lithium and elimination by fluoride of in vitro increments in vitamin B12-binding capacity. J Clin Invest. ; 53:228–239.
Pawlak, R. (2013). How prevalent is vitamin B 12 deficiency among vegetarians? In Nutrition Reviews (Vol. 71, pp. 110–117).
Powlak, R. (2013, January). Understanding vitamin B12 [Electronic version]. American College of Lifestyle Medicine, 7(1), 60-65. doi:10.1177/1559827612450688
Troen, A. M. Folate and vitamin B12: Function and importance in cognitive development. Meeting Micronutrient Requirements for Health and Development Nestlé Nutrition Institute Workshop Series, 70, 161-171. Retrieved from CINAHL.
Vitamin B12. (2011, June 24). Retrieved November 14, 2015, from https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional
Vitamin B12 Deficiency And Paralysis | Vitamin B12 Patch. (2010, August 11). Retrieved November 10, 2015.
Von Castel-Roberts, Kristina. (2015) Water-soluble Vitamins. University of Florida. McCarty Hall C Auditorium, Gainesville, Fl. Lecture.
Watanabe, F. (2007, November). Vitamin B12 sources and bioavailability. Experimental Biology and Medicine, 232(10), 1274-1622. doi:10.3181/0703-MR-67
Whitney, E., & Rolfes, S. (2002). The Water Soluble Vitamins: B Vitamins and C Vitamins. In Understanding nutrition (9th ed.). Belmont, CA: Wadsworth.
Zayouna, N. (n.d.). Atrophic Gastritis. Retrieved November 10, 2015.