October 25, 2016

Vitamin B12

Vitamins are essential nutrients which we must have daily for normal growth and development. Vitamins are categorized into two groups i.e. water soluble (vitamins B and C) and fat soluble (vitamins A, D, E and K). There is a keen interest among health professionals to use vitamins not only to support treatment but also as preventive therapy for some diseases. Vitamins are required daily in small quantities to work optimally to boost the immune system and promote optimal tissue and organ function. There is insufficient evidence from clinical research to demonstrate the effectiveness of mega doses of vitamins as therapy. Some vitamins if use above the recommended daily dose can result in toxicity.

What is Vitamin B12?

B-complex vitamins include Vitamins B1, B2, B3, B6, B9 and B12. Vitamin B12 is a water-soluble vitamin which plays a key role with the formation of red blood cells. It is also essential for the proper functioning of nerve cells and by extension, the nervous system and the brain. Vitamin B12 is needed for metabolism at the cellular level to synthesize DNA, amino acid and fatty acids. The structure of Vitamin12 is comprised of vitamers and cobalt.  We are not able to synthesize Vitamin B12 but it is produced by certain bacteria. We in turn get our source of Vitamin B12 from the food we eat.

Synthetic Vitamin B12 is produced commercially in large quantities. This is done by chemically modifying bacterial hydroxocobalamin. This synthetic Vitamin B12 is an important ingredient for the pharmaceutical and food industries. The food industry uses it to fortify foods especially cereals and health drinks. Dietary supplement of all kinds include Vitamin B12 in the formula for multivitamins but is also available as a single vitamin.

Why is Vitamin B12 necessary?

The association of Vitamin B12 with an autoimmune illness called pernicious anemia underscored for health professionals and researchers, the importance of this vitamin. Vitamin B12 is required for proper red blood cell formation. Researchers have also demonstrated the integral requirement for Vitamin B12 to prevent other neurological disorders.  Vitamin B12 deficiency can cause severe damage, to the brain and nervous system. Symptoms as mild as fatigue, depression, and poor memory could be as a result of Vitamin B12 deficiency. More severe symptoms are psychosis and mania.

What are the signs of Vitamin B 12 Deficiency?

Vitamin B12 (cobalamin) deficiency is a common disorder with potential irreversible hematological and neurological consequences. The main causes of vitamin B12 deficiency include vitamin B12 malabsorption from food, pernicious anemia, postsurgical malabsorption, and dietary deficiency However, in many cases, the cause of vitamin B12 deficiency is unknown. The following groups are among those most likely to be vitamin B12 deficient.

Elderly persons: Individuals with atrophic gastritis are unable to absorb the vitamin B12 that is naturally present in food.  Atrophic gastritis is a condition which affects 10%–30% of older population. In this type of gastritis there is a decrease in the secretion of hydrochloric acid in the stomach. This in turn results in decreased absorption of vitamin B12. In addition to this, decreased hydrochloric acid levels might also increase the growth of normal intestinal bacteria that use vitamin B12.

Synthetic vitamin B12 added to fortified foods and dietary supplements is fairly well tolerated with good absorption by the intestinal tract. The IOM recommends vitamin B12 supplements and fortified foods for adults 50 years and older. Elderly patients with atrophic gastritis require higher doses to prevent vitamin B12 deficiency.

Individuals with pernicious anemia: Pernicious anemia, a condition that affects 1%–2% of older adults is characterized by a lack of intrinsic factor. Individuals with pernicious anemia cannot properly absorb vitamin B12 in the gastrointestinal tract Pernicious anemia is usually treated with intramuscular vitamin B12. However, approximately 1% of oral vitamin B12 can be absorbed passively in the absence of intrinsic factor suggesting that high oral doses of vitamin B12 might also be an effective treatment.

Individuals with gastrointestinal disorders: Individuals with stomach and small intestine disorders, such as celiac disease and Crohn’s disease, may be unable to absorb enough vitamin B12 from food to maintain healthy body stores. Subtly reduced cognitive function resulting from early vitamin B12 deficiency might be the only initial symptom of these intestinal disorders, followed by megaloblastic anemia and dementia.

Individuals who have had gastrointestinal surgery: Surgical procedures in the gastrointestinal tract, such as weight loss surgery or surgery to remove all or part of the stomach, often result in a loss of cells that secrete hydrochloric acid and intrinsic factor. This reduces the amount of vitamin B12, particularly food-bound vitamin B12 that the body releases and absorbs. Surgical removal of the distal ileum also can result in the inability to absorb vitamin B12. Individuals undergoing these surgical procedures should be monitored preoperatively and postoperatively for several nutrient deficiencies, including vitamin B12 deficiency.

Vegetarians: Strict vegetarians and vegans are at greater risk than lacto-ovo vegetarians and non-vegetarians of developing vitamin B12 deficiency because natural food sources of vitamin B12 are limited to animal foods. Fortified breakfast cereals are one of the few sources of vitamin B12 from plants and can be used as a dietary source of vitamin B12 for strict vegetarians and vegans.

Pregnant and lactating women who follow strict vegetarian diets and their infants

Vitamin B12 crosses the placenta during pregnancy and is present in breast milk. Exclusively breastfed infants of women who consume no animal products may have very limited reserves of vitamin B12 and can develop vitamin B12 deficiency within months of birth. Undetected and untreated vitamin B12 deficiency in infants can result in severe and permanent neurological damage.

The American Dietetic Association recommends supplemental vitamin B12 for vegans and lacto-ovo vegetarians during both pregnancy and lactation to ensure that enough vitamin B12 is transferred to the fetus and infant. Pregnant and lactating women who follow strict vegetarian or vegan diets should consult with a pediatrician regarding vitamin B12 supplements for their infants and children.

How much and what kind does an adult need?

Intake recommendations for vitamin B12 and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine (IOM) of the National Academies (formerly National Academy of Sciences) DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender include:

  • Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals.
  • Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
  • Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.

Table 1 lists the current RDAs for vitamin B12 in micrograms (mcg) For infants aged 0 to 12 months, the FNB established an AI for vitamin B12 that is equivalent to the mean intake of vitamin B12 in healthy, breastfed infants.

Table 1: Recommended Dietary Allowances (RDAs) for Vitamin B12  
Age Male Female Pregnancy
0–6 months* 0.4 mcg 0.4 mcg  
7–12 months* 0.5 mcg 0.5 mcg  
1–3 years 0.9 mcg 0.9 mcg  
4–8 years 1.2 mcg 1.2 mcg  
9–13 years 1.8 mcg 1.8 mcg  
14+ years 2.4 mcg 2.4 mcg 2.6 mcg

 

How do you get enough Vitamin B 12 from Food?

Food

Vitamin B12 is naturally found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B12 is generally not present in plant foods, but fortified breakfast cereals are a readily available source of vitamin B12 with high bioavailability for vegetarians]. Some nutritional yeast products also contain vitamin B12. Fortified foods vary in formulation, so it is important to read product labels to determine which added nutrients they contain.

Animal sources

Vitamin B12 is found in most animal-derived foods, including fish and shellfish, meat (especially liver), poultry, eggs, milk, and milk products.] The bioavailability from eggs is less than 9%, compared to 40% to 60% from fish, fowl and meat.[26] An NIH fact sheet lists a variety of animal food sources of B12.

Non-animal sources

Besides certain fermented foods, there are few known vegan food sources of biologically active B12 and none of these have been subjected to human trials.

Chlorella, a fresh-water single-cell green alga, may be a source of biologically-active vitamin B12 for use by humans.  The B12 in Chlorella has been identified as methylcobalamin.  Algae are thought to acquire B12 through a symbiotic relationship with heterotrophic bacteria, in which the bacteria supply B12 in exchange for fixed carbon. Spirulina and dried Asakusa-nori (Porphyra tenera) have been found to contain mostly pseudovitamin-B12 (see Controversial sources in algae section) instead of biologically active B12. While Asakusa-nori (Porphyra tenera) contains mostly pseudovitamin-B12 in the dry state, it has been reported to contain mostly biologically active B12 in the fresh state, but even its fresh state vitamin activity has not been verified by animal enzyme assay. One group of researchers has reported that the purple laver seaweed known as Susabi-nori (Pyropia yezoensis) in its fresh state contains B12 activity in the rat model, which implies that source would be active in humans. However, a study showed that in humans both dried and raw nori reduced the vitamin B12 status. Unconventional natural sources of B12 also exist, but their utility as food sources of B12 is doubtful. For example, plants pulled from the ground and not washed may contain remnants of B12 from the bacteria present in the surrounding soil.

Fortified food

Foods fortified with B12 are also dietary sources of the vitamin. Foods for which B12-fortified versions are widely available include breakfast cereals, soy products, energy bars, and nutritional yeast. The UK Vegan Society, the Vegetarian Resource Group, and the Physicians Committee for Responsible Medicine, among others, recommend that every vegan who is not consuming adequate B12 from fortified foods takes supplements. Reputable manufacturers of fortified foods and dietary supplements include an overage (excess) in their formulas so that the products still contain the labeled amounts at the end of shelf life.

Several food sources of vitamin B12 are listed in Table 2.

Table 2: Selected Food Sources of Vitamin B12

Food Micrograms (mcg)
per serving
Percent DV*
Clams, cooked, 3 ounces 84.1 1,402
Liver, beef, cooked, 3 ounces 70.7 1,178
Breakfast cereals, fortified with 100% of the DV for vitamin B12, 1 serving 6.0 100
Trout, rainbow, wild, cooked, 3 ounces 5.4 90
Salmon, sockeye, cooked, 3 ounces 4.8 80
Trout, rainbow, farmed, cooked, 3 ounces 3.5 58
Tuna fish, light, canned in water, 3 ounces 2.5 42
Cheeseburger, double patty and bun, 1 sandwich 2.1 35
Haddock, cooked, 3 ounces 1.8 30
Breakfast cereals, fortified with 25% of the DV for vitamin B12, 1 serving 1.5 25
Beef, top sirloin, broiled, 3 ounces 1.4 23
Milk, low-fat, 1 cup 1.2 18
Yogurt, fruit, low-fat, 8 ounces 1.1 18
Cheese, Swiss, 1 ounce 0.9 15
Beef taco, 1 soft taco 0.9 15
Ham, cured, roasted, 3 ounces 0.6 10
Egg, whole, hard boiled, 1 large 0.6 10
Chicken, breast meat, roasted, 3 ounces 0.3 5

*DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers determine the level of various nutrients in a standard serving of food in relation to their approximate requirement for it. The DV for vitamin B12 is 6.0 mcg. However, the FDA does not require food labels to list vitamin B12 content unless a food has been fortified with this nutrient. 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. The U.S. Department of Agriculture’s (USDA’s) Nutrient Database Web site lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin B12 arranged by nutrient content and by food name.

Dietary supplements

In dietary supplements, vitamin B12 is usually present as cyanocobalamin, a form that the body readily converts to the active forms methylcobalamin and 5-deoxyadenosylcobalamin. Dietary supplements can also contain methylcobalamin and other forms of vitamin B12.

Existing evidence does not suggest any differences among forms with respect to absorption or bioavailability. However the body’s ability to absorb vitamin B12 from dietary supplements is largely limited by the capacity of intrinsic factor. For example, only about 10 mcg of a 500 mcg oral supplement is actually absorbed in healthy people.

In addition to oral dietary supplements, vitamin B12 is available in sublingual preparations as tablets or lozenges. These preparations are frequently marketed as having superior bioavailability, although evidence suggests no difference in efficacy between oral and sublingual forms.

 

Treatment with Prescription medications

Vitamin B12 deficiency is treated usually treated with vitamin B12 injections. This is especially beneficial for persons who are having malabsorption issues. Oral high doses of vitamin B12 may also be effective. The clinician must determine the patient’s ability to absorb vitamin B12 in order to make a decision on whether vitamin B12 should be administered orally or via an intramuscular injection.

There is a gel formulation of Vitamin B12 available as a prescription medication. It is applied intra-nasally and may appeal to persons who are averse to injections.

Are there any risks associated with too much Vitamin B 12?

The IOM did not establish a UL for vitamin B12 because of its low potential for toxicity. In Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, the IOM states that “no adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals”

Findings from intervention trials support these conclusions. In the NORVIT and HOPE 2 trials, vitamin B12 supplementation (in combination with folic acid and vitamin B6) did not cause any serious adverse events when administered at doses of 0.4 mg for 40 months (NORVIT trial) and 1.0 mg for 5 years (HOPE 2 trial)

Drug Interactions

Persons taking Vitamin B12 should disclose this to their healthcare providers as this vitamin has the potential to interact with some medications. In addition, several types of medications might adversely affect vitamin B12 levels. Here are a few examples:

  • Hormonal contraception: The studies are split on this. Some studies have found reduced serum levels in oral contraceptive users, but others have found no effect despite use of oral contraceptives for up to 6 months.
  • Chloramphenicol: It has been suggested that chloramphenicol can interfere with the reticulocyte. Blood counts should be monitored closely.
  • Aminosalicylic acid: Megaloblastic changes and cases of symptomatic anemia have been reported.
  • Cobalt irradiation: Cobalt irradiation of the small bowel can decrease gastrointestinal (GI) absorption of vitamin B12.
  • Colchicine: Colchicine can disrupt normal intestinal mucosal function, leading to malabsorption of several nutrients, including vitamin B12. Vitamin B12 levels should be monitored in people taking large doses of colchicine for prolonged periods.
  • Colestipol: The resins could decrease the absorption of vitamin B12. Patients could require Vitamin B12 supplements.
  • Folic acid: Large doses of folic acid have been shown to mask vitamin B12 deficiency by completely correcting hematological abnormalities.
  • H2-receptor antagonists: Reduced secretion of gastric acid and pepsin produced by H2 blockers can reduce absorption of dietary protein-bound vitamin B12, but not of supplemental vitamin B12. H2-receptor antagonists include Tagamet (cimetidine), Pepcid (famotidine) and Zantac (ranitidine).
  • Proton pump inhibitors: Proton pump inhibitors, such as omeprazole and lansoprazole, can interfere with vitamin B12 absorption from food.
  • Metformin (Glucophage): Metformin may reduce serum folic acid and vitamin B12 Long-term use of metformin substantially increases the risk of B12 deficiency.
  • Neomycin: Large doses of neomycin could interfere with the absorption of Vitamin B12 and induce pernicious anemia.
  • Nicotine: Nicotine can reduce serum vitamin B12 The question whether smokers should take Vitamin B12 has not been clinically established.
  • Nitrous oxide: Nitrous oxide inactivates the cobalamin form of vitamin B12 by oxidation. Chronic nitrous oxide B12 poisoning (usually from use of nitrous oxide as a recreational drug) may result in B12 functional deficiency even with normal measured blood levels of B12.[60]
  • Dilantin (Phenytoin), phenobarbital: These anticonvulsants have been associated with reduced vitamin B12 This may contribute to the megaloblastic anemia, primarily caused by folate deficiency, associated with these drugs.
  • Potassium: In some individuals potassium supplements can reduce absorption of vitamin B12.
  • Zidovudine (AZT): Reduced serum vitamin B12 levels may occur when zidovudine therapy is started.

 

Special considerations

It is important to be aware that adverse reactions to Vitamin B12 could occur in a few individuals. The adverse reactions are not at all commonly experienced.

  • Hematologic:

Peripheral vascular thrombosis has been reported. Treatment of vitamin B12 deficiency can unmask polycythemia vera, which is characterized by an increase in blood volume and the number of red blood cells. The correction of megaloblastic anemia with vitamin B12 can result in fatal hypokalemia and gout in susceptible individuals, and it can obscure folate deficiency in megaloblastic anemia.

Vitamin B12 in the form of cyanocobalamin is contraindicated in early Leber’s disease, which is hereditary optic nerve atrophy. Known carriers of this genetic defect should be counseled to have an adequate dietary intake of vitamin B12.

  • Allergies

Direct allergy to a vitamin or nutrient is extremely rare, and if reported, other causes should be sought. Vitamin B12 supplements in theory should be avoided in people sensitive or allergic to cobalamin, cobalt, or any other product ingredients.

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