Useful Facts About Cobalamin (vitamin B12)

Cobalamin (vitamin B12) is the largest B vitamin and was the last one to be isolated in 1948 by Dr E. Lester Smith in the UK from liver. It is a red crystalline substance. It had been known as early as 1926, that something in raw liver was a treatment for anaemia. There are various forms of the cobalamin (so called due to the presence of cobalt) molecule, some of these are; methyl-, cyano, adnosyl- and hydroxocobalamin (B12b). There are also nitrit (B12c), sulphito and aquacobalamins. The human body can normally convert from one to the other. The human body typically contains 5000-10000 ?g of B12 distributed about equally between the liver, kidneys and nervous system. Indeed the liver can store enough B12 for many years of supply, so that daily ingestion of B12 is not required. Most of the B12 present in animal tissues is in one of the two coenzyme forms, adnosylcobalamin or methylcobalamin, and not actual vitamin B12 (cobalamin), which may be present due to diffusion from gut bacteria or active transport using intrinsic factor. Vitamin B12 is also water soluble and therefore easily lost, whereas cobalamin coenzymes will remain in the liver and nerve cells, and can be effectively recycled. B12 is now obtained by deep fermentation. According to Leonard Mervyn, B.Sc., PH.D., C.Chem F.R.S.C, in Thorsons Complete Guide to Vitamins & Minerals, pp42, 8 ?g of B12 can be absorbed at any one time by the intrinsic factor and calcium mechanism, only 1% being absorbed by simple diffusion following oral dose. According to Mervyn, pig's liver contains 25.0?g/100g of B12, therefore 100g of pigs liver will result in 8.017?g of B12 absorbed, assuming digestion is healthy.

Vitamin B12 is produced exclusively by microorganisms, but is also found in animal flesh due to ingestion, or presence of the micro organisms in the gut. However, since grazing "meat animals" tend to accumulate heavy metals from the environment, it might be suggested that animal sources of B12 are not as "good" a source as might be supposed. Poultry, especially chickens, are routinely fed fishmeal, which may contain significant amounts of mercury and other heavy metals. Bottom feeding rather than deep sea fish contain the most mercury. Vegans, by avoiding eating higher on the food chain, will therefore accumulate less heavy metals (via diet) and may require far less B12 as a result of that risk factor. We may therefore expect to find a lower incidence of dementia, caused by heavy metal intoxication, amongst amalgam free vegans.

B12 is a vitamin required for blood formation and rapidly growing tissues. Methylcobalamin production requires cobalamin and is the cobalamin found in the central nervous system (CNS) and brain where it transports methyl groups (-CH3) to proteins in the myelin. It is for these reasons that B12 deficiency leads to anaemia (blood disorders include macrocytos and pernicious anaemia) and neurological disorders (Alzheimer's disease and suspected amalgam related disorders). There are, as with many diseases, usually more than one factor which may be involved with causation. Given that the former disorders are rare, even in vegans who have low B12 intakes, what I am more concerned about is the potential for neurological disorders that may be subclinical. This occurs because it is possible to have a deficiency of B12 in the CNS even when blood levels of B12 are "normal", or what is called non-anaemic deficiencies. These occur for meat eaters with huge B12 intakes as well as for vegans. So laying the blame for neurological problems on veganism or indeed any alleged B12 intake deficiency is not always accurate, since increased B12 dietary intake will evidently, not always work. In these serious cases B12 is usually injected since dietary availability of B12 can be as low as 1% of the total ingested for mega B12 doses, and some patients do not convert dietary B12 to the methylcobalamin required for normal neurological activity so well.

Symptoms could include: disturbed sense of co-ordination, paraesthesiae, loss of memory, abnormal reflexes, weakness, loss of muscle strength, exhaustion, confusion, low self-confidence, spacticity, incontinence, impaired vision, abnormal gait, frequent need to pass water and psychological deviances. Non-anaemic deficiencies play a role in diseases such as Multiple Sclerosis, Fibromyalgia, Diabetes and Chronic Fatigue Syndrome. Schizophrenia has also been successfully treated with B12 plus other supplements, and cardiovascular disease is linked to B12 deficiency while herpes zoster used to be treated with B12 injections back in the 1950s.

Just as mercury may cause cobalamin deficiency in the nervous system, so alcohol can cause deficiency in tissues. Even worse, alcohol seems to raise serum levels of vitamin B12, so that the deficiency is masked and the subject may look like they have higher than normal B12 levels! Whether these effects correlate to alcohol intake, or are only found in "alcoholics" is not clear.

The Recommended Daily Allowances (RDAs) are (?g/day): 0.3 at age 0-6 months, 0.5 for 6-12 months, 0.7 for 1-3 years, 1.0 for 4-6 years, 1.4 for 7-10 years, 2.0 for adolescents and adults, 2.2 in pregnancy and 2.6 in lactation. Usual intakes are about 4-8 ?g/d. Pregnant, lactating, and long-term strict vegetarians should take supplements providing the RDA.

The stomach secretes intrinsic factor that binds B-12 and mediates its absorption at receptor sites in the ileum. Inadequate intrinsic factor secretion occurs in pernicious anemia, an autoimmune disease. In the elderly, atrophic gastritis is commonly associated with B-12 malabsorption and deficiency. Because the absorbed vitamin is secreted in bile and subsequently reabsorbed, deficiency symptoms can take 20 years to develop from low intakes, e.g., in strict vegetarians. However, in malabsorption, deficiency occurs in months or a few years because absorption from both the diet and enterohepatic circulation is impaired.

The application of sensitive metabolic tests, such as the deoxyuridine suppression test and measurement of homocysteine and methylmalonic acid, to cobalamin status has identified the entity of mild, preclinical cobalamin deficiency. This state, common in the elderly, responds to cobalamin therapy. Preclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect cobalamin deficiency. Interpretation of metabolic results still requires caution, as do proposals to raise the cut-off point for low cobalamin levels to capture some normal levels that are associated with metabolic abnormality. The recognition of mild, preclinical deficiency has opened up many important issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Although malabsorptive disorders, especially food-cobalamin malabsorption, underlie about half of all cases of preclinical deficiency, no cause can be found in the remainder of these cases; poor dietary intake appears to be uncommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly deficient mothers. All of these have broadened and complicated the picture of cobalamin deficiency while providing greater opportunities for prevention.

Vitamin B12 deficiency associated neuropathy, originally called subacute combined degeneration, is particularly common in the elderly. The potential danger today is that with supplementation with folic acid of dietary staples such as flour, that the incidenceof this disease could rise as folic acid, as opposed to natural folate (N5CH3HFGlu1), enters the cell and the metabolic cycle by a cobalamin independent pathway. This chapter briefly describes the clinical presentation of the disease, which unless treated will induce permanent CNS damage. The biochemical basis of the interrelationship between folate and cobalamin is the maintenance of two functions, nucleic acid synthesis and the methylation reactions. The latter is particularly important in the brain and relies especially on maintaining the concentration of S-adenosylmethionine (SAM) which, in turn, maintains the methylation reactions whose inhibition is considered to cause cobalamin deficiency associated neuropathy. SAM mediated methylation reactions are inhibited by its product S-adenosylhomocysteine (SAH). This occurs when cobalamin is deficient and, as a result, methionine synthase is inhibited causing a rise of both homocysteine and SAH. Other potential pathogenic processes related to the toxic effects of homocysteine are direct damage to the vascular endothelium and inhibition of N-methyl-D-aspartate receptors.

Mild cobalamin deficiency is most common in elderly white men and least common in black and Asian American women. Hyperhomocysteinemia, which is most strongly associated with low cobalamin concentrations, is also most common in elderly whites, whereas that associated with renal insufficiency is more common in blacks and Asian Americans. Ethnic differences in cobalamin deficiency and the homocysteine patterns associated with it or with renal insufficiency warrant consideration in supplementation strategies.

  • John Coleman. An Introduction To Cobalamin Metabolism-cobalamins: form, function, inhibitors, a vegan perspective
  • Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med 2000;51:357-75
  • Weir DG, Scott JM. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull 1999;55(3):669-82
  • Ralph Carmel, Ralph Green, Et al. Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities. merican Journal of Clinical Nutrition, Vol. 70, No. 5, 904-910, November 1999
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