11.2 Vitamin B12

Vitamin B12

Vitamin B₁₂ is unique among vitamins in that it contains an element (cobalt) and is found almost exclusively in animal products. Vitamin B₁₂‘s scientific name is cobalamin, which is a reference to that fact that it contains cobalt. Neither plants nor animals can synthesize vitamin B₁₂.

Instead, vitamin B₁₂ in animal products is produced by microorganisms within the animal itself. Animals consume the microorganisms in soil while eating and grazing. Additionally, bacteria in

the stomachs of ruminant animals, like cows and sheep, can produce vitamin B 1. Some plant

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products, such as fermented soy products (tempeh, miso) and the sea algae supplement, spirulina, are advertised as being good sources of B₁₂. However, fermented soy products are not a reliable vitamin B₁₂ source,2 and spirulina contains a pseudovitamin B₁₂ compound that is not bioavailable3. For vegans, supplements, nutritional yeast, and fortified products like fortified soy milk can help them meet their vitamin B₁₂ needs4.

The uptake, absorption, and transport of vitamin B₁₂ is a complex process. The following descriptions explain, and figures illustrate, this process.

Vitamin B₁₂ is normally bound to protein in food. Salivary glands in the mouth produce haptocorrin (formerly known as R protein), which travels with the food into the stomach. In the stomach, acid converts pepsinogen into pepsin, which breaks the B₁₂ free from its protein. In addition, vitamin B₁₂ intrinsic factor is released from the parietal cells1,7. Vitamin B₁₂ intrinsic factor (sometimes referred to simply as intrinsic factor) is a protein-like compound that will aid in B₁₂ absorption as will see in a moment.

Figure 11.22 Vitamin B₁₂ in the stomach part 17,8

As pepsin frees B₁₂ from protein, haptocorrin binds to the newly freed vitamin B₁₂ (haptocorrin

+ B₁₂). Intrinsic factor escapes digestion and, along with haptocorrin + B₁₂, exits the stomach and enters the duodenum1,7.

Figure 11.23 Vitamin B₁₂ in the stomach part 27,8

In the duodenum, pancreatic proteases break down haptocorrin, and again vitamin B₁₂ is freed. Intrinsic factor then binds vitamin B₁₂ (intrinsic factor + B₁₂); intrinsic factor + B₁₂ continues into the ileum to prepare for absorption1,7.

Figure 11.24 Vitamin B₁₂ in the duodenum7,8

In the ileum, intrinsic factor + B₁₂ is believed to be endocytosed into the enterocyte. Intrinsic factor is broken down in the enterocyte, freeing vitamin B₁₂. The free vitamin B₁₂ is then bound to transcobalamin II (TC II + B₁₂); TC II + B₁₂ moves into circulation7.

Figure 11.25 Vitamin B₁₂ absorption8,9

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The liver is the primary storage site for vitamin B₁₂. Unlike most other water-soluble vitamins, the liver is able to maintain significant stores of vitamin B₁₂. Uptake into the liver occurs through the binding of TC II + B₁₂ to the TC II Receptor and the endocytosis of both the compound and the receptor8. Vitamin B₁₂ is once again freed after degradation of TC II. Vitamin B₁₂ is primarily stored in the liver as adenosylcobalamin5,7.

Figure 11.26 Hepatic uptake and storage of vitamin B 8

The overall bioavailability of vitamin B₁₂ is believed to be approximately 50%3. Sublingual supplements of vitamin B₁₂ have been found to be equally efficacious as oral supplements6. Excretion occurs mostly through bile, with little loss in urine5.

The Required Web Link below provides more information on vitamin B₁₂.

Required Web LinkVitamin B12 Fact Sheet

Subsections:

• 11.21 Vitamin B₁₂ Functions
• 11.22 Vitamin B₁₂ Deficiency & Toxicity

References & Links

• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s Perspectives in Nutrition. New York, NY: McGraw-Hill.
• Craig W, Mangels A. (2009) Position of the American Dietetic Association: Vegetarian Diets. J Am Diet Assoc 109(7): 1266-1282.

• Watanabe F. (2007) Vitamin B12 sources and bioavailability. Exp Biol Med 232(10): 1266- 1274.
• http://www.vrg.org/nutrition/b12.php
• Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.
• https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
• Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. (2006) Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins.
• http://commons.wikimedia.org/wiki/File:Illu_small_intestine_catal%C3%A0.png

Links

Vitamin B12 Fact Sheet – https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

Vitamin B12 Functions

Vitamin B₁₂ is a cofactor for 2 enzymes:

• Methionine synthase
• Methylmalonyl mutase

Methionine Synthase

Methionine synthase is an important enzyme in 1-carbon metabolism that uses methyl- cobalamin as its cofactor and converts homocysteine to methionine by adding a methyl group. Methionine then is converted to other compounds that serve as methyl donors, as shown below1.

Figure 11.211 1-carbon metabolism

Methymalonyl Mutase

Methymalonyl mutase is important in the breakdown of odd chain fatty acids (one containing 5, 7, 9 carbons, etc.). Odd chain fatty acids are less common than even chain fatty acids, but this enzyme is required to properly handle these less common fatty acids1.

Demyelination

In addition to its role as a cofactor for enzymes, vitamin B₁₂ is also important for preventing degradation of the myelin sheath that surrounds neurons, as shown below.

Figure 11.212 Vitamin B₁₂ is needed to maintain the myelin sheath that surrounds neurons2 The mechanism through which vitamin B₁₂ prevents demyelination is not known3.

References & Links

• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s Perspectives in Nutrition. New York, NY: McGraw-Hill.
• https://en.wikipedia.org/wiki/Myelin#/media/File:Neuron_Hand-tuned.svg
• http://lpi.oregonstate.edu/infocenter/vitamins/vitaminB12/

Vitamin B12 Deficiency & Toxicity

There are 2 primary symptoms of vitamin B₁₂ deficiency:

• Megaloblastic (Macrocytic) Anemia
• Neurological Abnormalities

Megaloblastic (Macrocytic) Anemia

This is the same type of anemia that occurs in folate deficiency, and is also characterized by fewer, enlarged, immature red blood cells. In vitamin B₁₂ deficiency, this occurs because there is not enough cobalamin to generate THF (illustrated in Figure 11.211). Thus, THF is not available for normal DNA synthesis and the red blood cells do not divide correctly.

Neurological Abnormalities

Vitamin B₁₂ deficiency also results in nerve degeneration and abnormalities that can often precede the development of anemia. These include a decline in mental function, and burning, tingling, and numbness of legs. These symptoms can continue to worsen and deficiency can be fatal1.

The most common cause of vitamin B₁₂ deficiency is pernicious anemia, a condition of inadequate intrinsic factor production that causes poor vitamin B₁₂ absorption. This condition is common in people over the age of 50 because they have the condition atrophic gastritis2.

Atrophic gastritis is a chronic inflammatory condition that leads to the loss of gastric glands in the stomach, as shown in the figure in the following Required Web Link.

Required Web LinkAtrophic Gastritis

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The loss of gastric glands leads to decreased intrinsic factor production. It is estimated that ~6% of individuals age 60 and over are vitamin B₁₂ deficient, with 20% having marginal status3. In addition to the elderly, vegans are also at risk for vitamin B₁₂ deficiency because they do not consume animal products. However, the deficiency may take years to develop in adults because of stores and recycling of vitamin B 2. Deficiency has the potential to occur much quicker in infants or young children on vegan diets because they do not have adequate B₁₂ stores like adults4.

Folate/Folic Acid masking vitamin B12 deficiency

As mentioned above, folate and vitamin B₁₂ lead to the same megaloblastic (macrocytic) anemia. If high levels of folate or folic acid (most of the concern is with folic acid since it is fortified in foods and commonly taken in supplements) is given during vitamin B₁₂ deficiency, it can correct this anemia. This is referred to as masking because it does not rectify the deficiency, but it “cures” this symptom. This is problematic because it does not correct the more serious neurological problems that can result from vitamin B₁₂ deficiency. There are some people who are concerned about the fortification of cereals and grains with folic acid because people who are B₁₂ deficient might not develop megaloblastic anemia, which makes a vitamin B₁₂ deficiency harder to diagnose2.

No toxicity of vitamin B₁₂ has been reported.

References & Links

• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s Perspectives in Nutrition. New York, NY: McGraw-Hill.
• Whitney E, Rolfes SR. (2008) Understanding Nutrition. Belmont, CA: Thomson Wadsworth.
• Allen L. (2009) How common is vitamin B-12 deficiency? Am J Clin Nutr 89(2): 693S-696S.
• Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.

Links

Atrophic Gastritis – http://catalog.nucleusinc.com/enlargeexhibit.php?ID=3754