Vitamin B12 Deficiency: What are the consequences?

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Treatment of Vitamin B12 Deficiency 

By far the best method of treating Vitamin B12 deficiency with all its undesirable consequences, is to avoid becoming deficient in the first place. Whilst generally this can be achieved through adequate dietary uptake in many instances the genetic make-up of an individual, infections, or the use of various drugs may lead either to reduced uptake of vitamin B12 from the gut, or may lead to excessive use or depletion of vitamin B12 stores in the liver, brain and other tissues. Once this has occurred the individual must make every effort to restore and maintain adequate vitamin B12 levels in the serum, liver and in particular the central nervous system including the brain.

Measurement of vitamin B12

Measurement of vitamin B12 is normally performed by analysis of circulating vitamin B12 levels in the blood. The standard test, however, measures not only the active forms of vitamin B12 (methylcobalamin and adenosylcobalamin) but also inactive forms of vitamin B12, such as CN-cobalamin and nitrosylcobalamin. This can lead to spuriously high levels of vitamin B12 being measured, despite the patient showing overt signs of clinical insufficiency. Compounding this is the insistence of Pathology labs around the world to quote vitamin B12 in reference to the range of data that they measure, and hence to determine levels as being "normal" if they fit within their standard "range" of measurement. As such the quoted levels include many individuals who have sub-clinical deficiency. Thus, in the USA and Australia, normal levels of vitamin B12 have been determined by Pathology Labs to be in the range 180-750 pmol/L (244-1017 pg/ml), withnormally much lower at around 110 pmol/L, being regarded as deficient. Recently, many studies looking at biological markers of vitamin B12 deficiency (MMA and Hcy) as well as neurological markers of deficiency, have suggested that deficiency may start at 300 pmol/L (406 pg/ml). When this level of vitamin B12 is used to define the lower level of normal, it is estimated that functional vitamin B12 deficiency may be as high as 14-40% of the population even in omnivorous populations, and even higher in communities which are predominantly of vegetarian or vegan persuasion(see PDF),.

Prevention of Vitamin B12 Deficiency

Vitamin B12 insufficiency can be prevented either by adherence to a diet that is sufficient in vitamin B12 (see link), by the use of supplements, by injection of vitamin B12 or via topical administration of vitamin B12. Persons who are deficient due to poor absorption, or through conditions affecting absorption require regular vitamin B12 supplementation either via vitamin B12 injections or  by regular application of topical vitamin B12.

Overcoming Vitamin B12 Deficiency

Unfortunately it is almost impossible to to overcome deficiency once it occurs, through either a change in diet or by the use of standard supplements. The normal uptake system in the gut for vitamin B12 is not sufficient to deliver enough vitamin B12 to overcome deficiency, a situation made even worse in those who have compromised intestinal uptake, are on various drugs or take metformin. Prompt treatment of B12 deficient patients is required to prevent progressive, irreversible neurological and cognitive impairment.

Vitamin B12 in Supplements

The use of vitamin B12 in supplements for treatment of deficiency is controversial with many studies showing no benefit being obtained from standard supplements as the amount of vitamin B12 that is absorbed from the standard supplements is too low, even in high dose supplements. In addition many supplements contain cyanocobalamin (a synthetic pro-vitamin) rather than adenosylcobalamin or methylcobalamin, the two natural forms of the vitamin. Furthermore, studies with high dose oral supplements with cyanocobalamin were not effective in restoring normal levels of homocysteine or methylmalonic acid, in reversing clinical signs of deficiency, or in maintaining normal levels of serum vitamin B12 once supplements were ceased. In addition, high dose oral supplements have NOT been shown to be able to increase the concentration of vitamin B12 in the cerebral spinal fluid, or the brain. Furthermore, in inflammatory conditions where there increased production of nitric oxide,  vitamin B12 introduced by supplements is quickly inactivated to form nitrosylvitamin B12.

Vitamin B12 Injections

Vitamin B12 injections can be administered in cases of insufficiency, however these are generally expensive, must be given by a medical practitioner, are painful and like oral supplements, invariably contain cyanocobalamin (a synthetic pro-vitamin) rather than adenosylcobalamin or methylcobalamin, the two natural forms of the vitamin. In some countries such as Europe and South America both the methyl and adenosyl-vitamin B12 forms of the vitamin are available for injection. Injections must be given every 4 to 6 weeks, as they do not seem to overcome deficiency, but merely provide a temporarily boost in circulating levels of the injected form of vitamin B12, often with little change from provitamin forms (OHCbl or CNCbl) to the active forms (MeCbl and AdoCbl). Evidence suggests that persons with mutations in the methionine synthase reductase enzyme (MTRR) have trouble converting CN-Cbl and OH-Cbl to adenosyl and methylcobalamin. This mutation is relatively common and may explain why many individuals who have symptoms of vitamin B12 deficiency do not respond to treatment with either CN-Cbl or OH-Cbl. It may also explain why many supplementation trials using CN-Cbl have not been effective in treating conditions that are apparently linked to vitamin B12 deficiency (ie, dementia, AD, PD, MS).

Topical Vitamin B12

A topical form of vitamin B12 has recently been developed. This preparation is easy to administer, contains the natural forms of the vitamin (adenosyl and methylcobalamin), is able to deliver therapeutic amount of vitamin B12 and has the added advantage of providing a prolonged release of the vitamin over several hours.  This prolonged release potentially allows for continuous loading of the various organs including the liver and more importantly the CNS and brain. Moreover, the high dose of vitamin B12 that is deliverable by this method is sufficient to act as a powerful antioxxidant and also to neutralize circulating levels of homocysteine, thus reducing the incidence and severity of conditions associated with hyperhomcysteinemia. This is not possible with the much lower dose of vitamin B12 that is delivered via supplements See   .

Therapeutic use of Vitamin B12 

Vitamin B12 has been used in therapy for many conditions including AIDS/HIV support, anaemia, anaemia of pregnancy, pernicious anaemia, asthma, atherosclerosis, allergies, atopic dermatitis, contact dermatitis, psoriasis, seborrheic dermatitis, bursitis, sciatica, canker sores, chronic fatigue syndrome, Alzheimer’s disease, dementia, depression, Crohn’s disease, diabetes mellitus, diabetic neuropathies, neuralgias, post-herpetic neuralgia, diabetic retinopathy, fatigue, herpes zoster, high cholesterol, high blood  homocysteine levels, insomnia, male infertility,   tinnitus, viral hepatitis, and vitiligo. Recent studies have shown that high dose vitamin B12 treatment can slow or prevent brain shrinkage and loss of cognitive impairment. High dose formulations have also been shown to reverse bowel and bladder incontinence. Continued high dose injection of methylcobalamin has been shown to reverse the clinical signs of dementia.


Further Information on Vitamin B12 and its uses

Further information on vitamin B12 and deficiency states, as well as potential use of vitamin B12 can found by following the links. NIHPDF PDF :

Pacholok, S.M. and Stuart, J. J. Could it be B12? An epidemic of misdiagnosis.