Cobalamin and Your Blood.

  Popularly referred to as Vitamin B12, cobalamin is the most complex of all proteins, it's complex structures comes as no surprise as regards it's vast biological functions.
  Cobalamin is essential in erthropoesis and also in the functioning of the nervous system, it is also vital in cell metabolism of amino acids and fatty acids, it is also essential in DNA synthesis.
  This wide area of function of cobalamin makes it a very essential vitamin as it's deficiency spans many biological processes in the human body.

           Discovery And Structure
Vitamin B 12 was discovered as a result of its relationship to the disease pernicious anemia , an autoimmune disease in which parietal cells of the stomach responsible for secreting intrinsic factor are destroyed.
Vitamin B 12 consists of a class of chemically related compounds ( vitamers), all of which show pharmacological activity. It contains the biochemically rare element cobalt (chemical symbol Co ) positioned in the center of a planar tetra- pyrrole ring called a corrin ring. The vitamer is produced by bacteria as hydroxocobalamin , but conversion between different forms of the vitamin occurs in the body after consumption. It is stored in the liver.
[Wikipedia]
               SOURCES
Food
Animal sources with a significant content of vitamin B 12 (range among top 20 sources of 50 to 99 µg per 100 grams) include clams, organ meats (especially liver ) from lamb , veal , beef, and turkey , fish eggs, mackerel, and crab meat .
Plant sources containing significant amounts of B 12 include fermented beans and vegetables (up to 8 µg per 100 grams), seaweed (particularly for purple laver up to 134 µg per 100 grams, when dried), and mushrooms (up to 3 µg per 100 grams).

Bacteria
B 12 is produced in nature only by prokaryotes in the form of certain bacteria and archaea ; it is not made by any multicellular or single-celled eukaryotes . It is synthesized by some gut bacteria in humans and other animals, but humans cannot absorb the B 12 made in their guts, as it is made in the colon which is too far from the small intestine , where absorption of B12 occurs. Ruminants , such as cows and sheep, absorb B 12 produced by bacteria in their guts. [27] For gut bacteria of ruminants to produce B 12 the animal must consume sufficient amounts of cobalt . Grazing animals pick up B 12 and bacteria that produce it from the soil at the roots of the plants they eat.

Animal sources
Animals store vitamin B 12 in liver and muscle and some pass the vitamin into their eggs and milk; meat, liver, eggs and milk are therefore sources of the vitamin for other animals, including people. For humans, the bioavailability from eggs is less than 9%, compared to 40% to 60% from fish, fowl and meat. Insects are a source of B 12 for animals (including other insects and humans).
Feces is a rich source of vitamin B12 and many species, including rabbits,dogs, and cats eat feces.
Fortified foods
Foods fortified with B 12 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 take supplements.
Supplements
Hydroxocobalamin injection USP (1000 µg/mL) is a
transparent red liquid solution of hydroxocobalamin which
is available in a 30 mL brown glass multidose vial
packaged in a paper box. Shown is 500 µg B 12 (as
1/2 cc) drawn up in a 1/2 cc U-100 27 gauge x
1/2" insulin syringe, as prepared for subcutaneous
injection.
Vitamin B 12 is an ingredient in multi-vitamin pills and in some countries used to enrich grain-based foods such as bread and pasta. In the U.S. non-prescription products can be purchased providing up to 5000 µg/serving, and it is a common ingredient in energy drinks and energy shots , usually at many times the recommended dietary allowance of B 12 . The vitamin can also be a prescription product via injection or other means.
The sublingual route, in which B 12 is presumably or supposedly taken in more directly under the tongue, has not proven to be necessary or helpful, even though a number of lozenges, pills, and even a lollipop designed for sublingual absorption are being marketed. A 2003 study found no significant difference in absorption for serum levels from oral versus sublingual delivery of 0.5 mg of cobalamin. Sublingual methods of replacement are effective only because of the typically high doses (0.5 mg), which are swallowed, not because ofbplacement of the tablet. As noted below, such very high doses of oral B 12 may be effective as treatments, even if gastro-intestinal tract absorption is impaired by gastric atrophy (pernicious anemia).
Injection and patches are sometimes used if digestive absorption is impaired, but there is evidence that this course of action may not be necessary with modern high-potency oral supplements (such as 0.5–1 mg or more). Even pernicious anemia can be treated entirely by the oral route.  These supplements carry such large doses of the vitamin that 1% to 5% of high oral doses of free crystalline B12 is absorbed along the entire intestine by passive diffusion.
If the person has inborn errors in the methyltransfer pathway (cobalamin C disease, combined methylmalonic aciduria and homocystinuria), treatment with intravenous, intramuscular hydroxocobalamin or transdermal B 12 is needed.
The UK Vegan Society , the Vegetarian Resource Group, and the Physicians Committee for Responsible Medicine , among others, recommend that vegans either consistently eat B12 -fortified foods or take a daily or weekly B 12 supplement to meet the recommended intake. Non-cyanide forms as supplements.
Recently sublingual methylcobalamin has become available in 5 mg tablets. The metabolic fate and biological distribution of methylcobalamin are expected to be similar to that of other sources of vitamin B 12 in the diet. No cyanide is released with methylcobalamin, and the amount of cyanide (20 µg) in a 1,000 µg cyanocobalamin tablet is less than daily consumption from food.
Safety of all forms of the vitamin is well established.
Untested Sources
Besides certain fermented foods, there are few known plant, fungus or algae sources of biologically active B 12 and none of these have been subjected to human trials. Vitamin B12 deficiencies are therefore common in strict vegetarians and in the elderly. Many algae are rich in vitamin B12, with some species, such as Porphyra yezoensis , containing as much cobalamin as liver. There have been no significant human trials of sufficient size to demonstrate enzymatic activity of B 12 from nonbacterial sources, such as Chlorella and edible sea algae (seaweeds, such as lavers), although chemically some of these sources have been reported to contain B 12 that seems chemically similar to the active vitamin.
Pseudovitamin-B 12
Pseudovitamin-B 12 refers to B12 -like analogues that are biologically inactive in humans and yet found to be present alongside B 12 in humans, many food sources (including animals), and possibly supplements and fortified foods. Most cyanobacteria, including Spirulina, and some algae, such as dried Asakusa-nori ( Porphyra tenera ), pseudovitamin-B 12 have been found to contain mostly pseudovitamin-B 12 instead of biologically active B 12.
[Wikipedia]
           Relevance in Hematology
The most important function of cobalamin is to act as co-enzyme for reducing ribonucleotides and deoxyribonucleotides, this step is necessary in gene replication. Cobalamin also acts as a hydrogen accept or co-enzyme. This accounts for it's haematologic functions which includes promotion of the formation, growth and maturation of blood cells.
              DEFICIENCY
Cobalamin deficiency has adverse effects on blood production and normal nervous function.
   Symptoms of cobalamin deficiency includes.
*Extreme Tiredness due to a lack of energy
*Paraesthesia
*Sore and red tongue
*Mouth ulcers
*Muscle weakness
*Disturbed vision
*Psychological problems, which may include depression and confusion.
*Problems with memory, understanding and judgement
Some of these problems can also occur if you have a deficiency in vitamin B12 or folate, but don't have anaemia.
      Effect of Cobalamin Deficiency
           Magaloblastic Anaemia
Deficiency of Cobalamin causes a delay in cell division and nuclear maturation of erythrocytes [and other blood cells], thus a reduction in number of red blood cell, blast cells in the bone marrow are enlarged but the haemoglobin content of the blood remains normal [macrocytic(MCV>91fl) and normochromic]. There is also an increased destruction of the red blood cells resulting in Anaemia.
This condition can also result from pernicious anemia which occurs mostly as a result of atrophy of the stomach.
  Cobalamin deficiency has similar effect on white blood cells. There is a fall in neutrophil content with hypersegmentation of the nuclear lobes of the neutrophil. There is also a reported reduction in platelet count.
   As stated before, not only the blood sufferers the deficiency of cobalamin, there is in addition, a neurological disorder known as Posterolateral Sclerosis which is  characterized by a demyelination of nerve fibers columns in the posterior and lateral regions of peripheral nerves and spinal cord. This is due to the inability of the body to metabolize certain fatty acids as cobalamin is required for the metabolism of such fatty acids.
      Coping With Cobalamin Deficiency
Most cases of vitamin B12 and folate deficiency can be easily treated with injections or tablets to replace the missing vitamins.
Vitamin B12 supplements are usually given by injection at first. Then, depending on whether your B12 deficiency is related to your diet, you'll either require B12 tablets between meals or regular injections. These treatments may be needed for the rest of your life.
Folic acid tablets are used to restore folate levels. These usually need to be taken for four months.
In some cases, improving your diet can help treat the condition and prevent it recurring. Vitamin B12 is found in meat, fish, eggs, dairy products, yeast extract (such as Marmite) and specially fortified foods.
The best sources of folate include green vegetables such as broccoli, Brussels sprouts and peas.

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