At a glance......
- 1 Vitamin B12
- 1.1 Causes
- 1.2 Symptoms of vitamin B12 deficiency
- 1.3 A B12 deficiency can go undiagnosed for years, but this is how you know it’s time to take notice.
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Vitamin B12also called cobalamin is a water-soluble vitamin that has a key role in the normal functioning of the brain and nervous system, and the formation of red blood cells. It is one of eight B vitamins. It is involved in the metabolism of every cell of the human body, especially affecting DNA synthesis, fatty acid and amino acid metabolism. No fungi, plants, or animals (including humans) are capable of producing vitamin B12. Only bacteria and archaea have the enzymes needed for its synthesis. Some substantial sources of B12 include animal products (shellfish, meat), fortified food products, and dietary supplements.B12 is the largest and most structurally complicated vitamin and can be produced industrially only through bacterial fermentation synthesis, typically used to manufacture B12 for fortified foods and supplements.
Structurally vitamin B12 are a large mollecules & in this reason it inter in the body by converting into cyanocobalamone.Booster dose such as injection form are the best for patient benefit.
- Inadequate dietary intake of vitamin B12. Vitamin B12 occurs in animal products (eggs, meat, milk) and in some edible alge. B12 isolated from bacterial cultures is also added to many fortified foods, and available as a dietary supplement. Vegans, and to a lesser degree vegetarians, may also be at risk for B12 deficiency due to inadequate dietary intake of B12, if they do not supplement. Children are at a higher risk for B12 deficiency due to inadequate dietary intake, as they have fewer vitamin stores and a relatively larger vitamin need per calorie of food intake.
- Selective impaired absorption of vitamin B12 due to intrinsic factor deficiency. This may be caused by the loss of gastric parietal cells in chronic atrophic gastritis (in which case, the resulting megaloblastic anemia takes the name of “pernicious anemia”), or may result from wide surgical resection of stomach (for any reason), or from rare hereditary causes of impaired synthesis of intrinsic factor. B12 deficiency is more common in the elderly because gastric intrinsic factor, necessary for absorption of the vitamin, is deficient, due to atrophic gastritis.
- Impaired absorption of vitamin B12 in the setting of a more generalized malabsorption or maldigestion syndrome. This includes any form due to structural damage or wide surgical resection of the terminal ileum (the principal site of vitamin B12 absorption).
- Forms of achlorhydria (including that artificially induced by drugs such as proton pump inhibitors and histamine 2 receptor antagonists) can cause B12 malabsorption from foods, since acid is needed to split B12 from food proteins and salivary binding proteins. This process is thought to be the most common cause of low B12 in the elderly, who often have some degree of achlorhydria without being formally low in intrinsic factor. This process does not affect absorption of small amounts of B12 in supplements such as multivitamins, since it is not bound to proteins, as is the B12 in foods.
- Surgical removal of the small bowel (for example in Crohn’s disease) such that the patient presents with short bowel syndrome and is unable to absorb vitamin B12. This can be treated with regular injections of vitamin B12.
- Long-term use of ranitidine hydrochloride may contribute to deficiency of vitamin B12.
- Untreated celiac disease may also cause impaired absorption of this vitamin, probably due to damage to the small bowel mucosa. In some people, vitamin B12 deficiency may persist despite treatment with a gluten-free diet and require supplementation.
- Some bariatric surgical procedures, especially those that involve removal of part of the stomach, such as Roux-en-Y gastric bypass surgery. (Procedures such as the adjustable gastric band type do not appear to affect B12 metabolism significantly).
- Bacterial overgrowth within portions of the small intestine, such as may occur in blind loop syndrome, (a condition due to a loop forming in the intestine) may result in increased consumption of intestinal vitamin B12 by these bacteria.
- The diabetes medication metformin may interfere with B12 dietary absorption.
- A genetic disorder, transcobalamin II deficiency can be a cause.
- Alcoholism – if a “diet” of excessive alcohol intake is substituted for a diet adequate in sources of B12.
- Nitrous oxide exposure, and recreational use.
- Infection with the Diphyllobothrium latum tapeworm
Symptoms of vitamin B12 deficiency
Anaemia and anaemia caused by a lack of vitamin B12 can result in symptoms which include:
- Extreme tiredness or fatigue
- A lack of energy or lethargy
- Being out of breath
- Feeling faint
- Ringing in the ears (tinnitus)
- Lack of appetite
More specific symptoms linked to a lack of vitamin B12 include:
- Yellowing of the skin
- Sore, red tongue
- Mouth ulcers
- Changes or loss of some sense of touch
- Feeling less pain
- Walking problems
- Vision problems
- Mood changes, irritability, depression or psychosis
- Symptoms of dementia
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.
|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||2.8 mcg|
* Adequate Intake
Selected Food Sources of Vitamin B12
|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
A B12 deficiency can go undiagnosed for years, but this is how you know it’s time to take notice.
Bottom line: B12 deficiency can be devastating, and it’s easily avoidable. Supplementing is quick and incredibly safe; because B12 is a water-soluble vitamin, your body uses what you need and your kidneys simply flush away the rest, without any side effects.
The most effective way to take a B12 supplement is sublingually or as a shot. Since most people don’t like the idea of injections, a sublingual supplement is the simple answer. (“Sublingual” just means using drops or a lozenge that melts in your mouth. It’s especially useful for people who don’t absorb B12 well in their stomachs because of medication use or other digestive issues.)
Health Risks from Excessive Vitamin B12
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) .
Interactions with Medications
Vitamin B12 has the potential to interact with certain medications. In addition, several types of medications might adversely affect vitamin B12 levels. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin B12 status with their healthcare providers.
Chloramphenicol (Chloromycetin®) is a bacteriostatic antibiotic. Limited evidence from case reports indicates that chloramphenicol can interfere with the red blood cell response to supplemental vitamin B12 in some patients .
Proton pump inhibitors
Proton pump inhibitors, such as omeprazole (Prilosec®) and lansoprazole (Prevacid®), are used to treat gastroesophageal reflux disease and peptic ulcer disease. These drugs can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach . However, the evidence is conflicting on whether proton pump inhibitor use affects vitamin B12 status . As a precaution, health care providers should monitor vitamin B12 status in patients taking proton pump inhibitors for prolonged periods .
H2 receptor antagonists
Histamine H2 receptor antagonists, used to treat peptic ulcer disease, include cimetidine (Tagamet®), famotidine (Pepcid®), and ranitidine (Zantac®). These medications can interfere with the absorption of vitamin B12 from food by slowing the release of hydrochloric acid into the stomach. Although H2 receptor antagonists have the potential to cause vitamin B12 deficiency , no evidence indicates that they promote vitamin B12 deficiency, even after long-term use . Clinically significant effects may be more likely in patients with inadequate vitamin B12 stores, especially those using H2 receptor antagonists continuously for more than 2 years .
Metformin, a hypoglycemic agent used to treat diabetes, might reduce the absorption of vitamin B12 , possibly through alterations in intestinal mobility, increased bacterial overgrowth, or alterations in the calcium-dependent uptake by ileal cells of the vitamin B12-intrinsic factor complex . Small studies and case reports suggest that 10%–30% of patients who take metformin have reduced vitamin B12 absorption . In a randomized, placebo controlled trial in patients with type 2 diabetes, metformin treatment for 4.3 years significantly decreased vitamin B12 levels by 19% and raised the risk of vitamin B12 deficiency by 7.2% compared with placebo . Some studies suggest that supplemental calcium might help improve the vitamin B12 malabsorption caused by metformin, but not all researchers agree .
Vitamin B12 and Healthful Diets
The federal government’s 2015-2020 Dietary Guidelines for Americans notes that “Nutritional needs should be met primarily from foods. … Foods in nutrient-dense forms contain essential vitamins and minerals and also dietary fiber and other naturally occurring substances that may have positive health effects. In some cases, fortified foods and dietary supplements may be useful in providing one or more nutrients that otherwise may be consumed in less-than-recommended amounts.”
The Dietary Guidelines for Americans describes a healthy eating pattern as one that
- Fish and red meat are excellent sources of vitamin B12. Poultry and eggs also contain vitamin B12.
- Includes a variety of vegetables, fruits, whole grains, fat-free or low-fat milk and milk products, and oils.Milk and milk products are good sources of vitamin B12. Many ready-to-eat breakfast cereals are fortified with vitamin B12.
- Includes a variety of protein foods, including seafood, lean meats and poultry, eggs, legumes (beans and peas), nuts, seeds, and soy products.
- Limits saturated and trans fats, added sugars, and sodium.
- Stays within your daily calorie needs.
- L. R. McDowell. Vitamins in animal and human nutrition. Booksgoogle.com. Retrieved 28 January 2018.
- EISAI SUBMITS NEW DRUG APPLICATION FOR MECOBALAMIN ULTRA-HIGH DOSE PREPARATION AS TREATMENT FOR AMYOTROPHIC LATERAL SCLEROSIS IN JAPAN” (PDF). Eisai.com. Retrieved 28 January 2018.
- A Human Vitamin B12 Trafficking Protein Uses Glutathione Transferase Activity for Processing Alkylcobalamins”. Journal of Biological Chemistry. 284: 33418–33424. doi:10.1074/jbc.M109.057877. PMC .
- “Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product”. Molecular Genetics and Metabolism. 97: 260–266. doi:10.1016/j.ymgme.2009.04.005. PMC .
- “Genetic disorders of vitamin B12 metabolism: eight complementation groups – eight genes”. Expert Reviews in Molecular Medicine. 12. doi:10.1017/S1462399410001651. PMC .
- enon Schneider, Andrzej Stroiński, Comprehensive B12: Chemistry, Biochemistry, Nutrition, Ecology, Medicine