The human body normally contains approx. 5000-10000 ug of vitamin B12, equally distributed in the liver and the nervous system. Due to the presence of the cobalt atom (trace element), vitamin B12 is also called cobalamin.

Anaemia

Vitamin B12 deficiencies have been mainly related to blood deficiency diseases, such as macrocytos and pernicious aneamia. First described in 1855, the latter was usually lethal. The connection with cobalamin was not established until after vitamin B12 was first isolated in 1948. (As early as 1926, however, it was found that raw liver, which later proved to be rich in vitamin B12, could effectively cure anaemia).

Causes and Symptoms

Deficiencies can be caused by low intestinal B12 uptake (intestinal disorders), low intrinsic factor (a substance essential for its transport to the blood) in the stomach, deficiency of hydrochloric acid in the gastric juices (increasing with old age), regular use of laxatives or medicines like Losec (for treatment of peptic ulcer), low uptake in the central nervous system (CNS) or excessive B12 degradation. Lack of calcium in the food can also reduce the uptake and so can heavy metals.

Vitamin B12 deficiencies are followed by neurological and psychological disorders, such as 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, psychological deviances.

Non-anaemic deficiencies

Lately it has been discovered that anaemia is not always present in neurogical and psychological disturbances associated with B12 deficiencies. In diseases such as Alzheimer's and suspected amalgam-related disorders, hidden B12 deficiencies in the CNS (without low blood values) have been found.

The transport of vitamin B12 to the brain can be disturbed or interrupted by heavy metals such as inorganic mercury, which affects the blood-brain barrier by causing leakage and hampering the active transport of nutrients. Exposure to laughing gas (N2O), commonly given to women in labour, causes similar B12 deficiencies in the brain of the infant, and sometimes in mothers with low B12 levels (and the anaesthetist). When used as a sedative in connection with an operation, the gas can cause irreparable damage in an individual with B12 deficiency.

Non-anaemic vitamin B12 deficiencies also play a role in diseases like Multiple Sclerosis, Fibromyalgia, Diabetes and Chronic Fatigue Syndrome. Schizophrenia, a psychotic condition, has been successfully treated with B12 injections in combination with other supplements. There also seems to be a connection between B12 deficiencies and cardiovascular diseases

In the 1950's, it was common practice to treat a patient with the first signs of herpes zoster with a vitamin B12 injection which effectively reversed the symptoms. This knowledge has fallen into oblivion. Ongoing research will most probably further increase the area of use of vitamin B12.

Test methods

Rarely detectable through normal testing procedures, such as blood serum or methyl malonic acid, B12 deficiencies in the brain and CNS can be determined by checking "increased homocystein in LIQUOR", (liquor cerebrospinalis)*, the most appropriate test method.

*) In rare cases, mainly very young patients, side-effects such as headaches may occur. It is therefore recommended to drink water and rest immediately after the spinal test.

The LIQUOR-test method is rather complicated. Ordinary equipment can be used, but at the Uddevalla Hospital in Sweden, the method of analysis has been especially designed for the purpose. According to Dr. Bo Nilsson, Chief Physician, it is important to measure with an exactness of 1 pmol/L**. The secret is to extract the minute quantity of B12 available without changing the molecule.

**) One thousand of a millionth of a millionth mol per litre, which makes one millionth of a millionth of a gram/litre.

High doses

It has been suggested that in the presence of heavy metals the cobalt atom is oxidized from CO2+ to CO3+ (denaturation) at the same time as the heavy metal is reduced. The properties of the cobalamin are hypothetically changed and B12 has lost its biological properties. Due to its molecular size, B12 normally has difficulties in crossing the blood-brain barrier and it is possible that denaturation make this even more difficult. This process is analogous to the behaviour of laughing gas.

One of the advocates of this hypothesis is Dr. Britt Ahlrot-Westerlund in Stockholm. The reason why high doses are recommended is that, in the presence of heavy metals in the blood-brain-barrier (more specifically in the plexus chorioideus), most of the vitamin B12 seems to be consumed (for reasons we don't know) and, depending on the level of heavy metal exposure, part of the supplemented B12 will most probably also be consumed in this way until the surplus can be used in the brain where it is needed.

Hg seems to change valency and binding site in the body, and this causes increased free radical formation. It is possible that the Hg change in valency in prooxidative direction oxidizes the cobalt atom. There is, according to Dr. Westerlund, reason to believe that the process of Hg oxidation of the cobalt atom is analogous to the way in which Fe2+ in haemoglobulin is oxidized to Fe3+ in methaemoglobulin (incapable of releasing oxygen) by exogene toxic substances.

To confirm this, an in vitro investigation using electron spin resonance is planned at Stockholm University, Department of Biophysics.

Many different forms

The active vitamin comes in many different forms, i.e. methyl-, cyano-, adnosyl- and hydroxocobalamin, freely transformed into each other in the body. However, vitamin B12 in the brain and CNS is only present as methylcobalamin, which effectively transports methyl groups (-CH3) to proteins in the myelin, the insulating layer which together with fatty acids surrounds the nerve fibers, protecting them just like insulation on electric cables.

In cases of B12 deficiency, toxic fatty acids with 15-17 carbon atoms with a demyelinating effect on the myelin are formed, and the transmission of electrical impulses is disturbed. If enough B12 is supplied, the myelin might be repaired in the course of time.

Methylcobalamin

The uptake from oral B12 supplementation is usually very low, approx. 1 %. Vitamin B12 is therefore often given intramuscularly.

Although vitamin B12 can be supplemented in any of its forms, it is given as hydroxo- or sometimes as cyanocobalamin in many countries. In the south of Europe, however, methylcobalamin is generally used to treat disorders such as neuritis and polyneuropathia. Highly recommended by the Swedish Association of Dental Mercury Patients, it is usually the drug of choice for the treatment of patients with amalgam-induced disorders.

In the experience of Dr. Ahlrot-Westerlund among others, B12 in its active form, methylcobalamin, gives a much better result than other forms which have to be transformed into methylcobalamin. It is possible that the process of transformation itself is inefficient in many patients.

It has been suspected that the supplementation of methylcobalamin in the presence of mercury could lead to the formation of methyl mercury. Inorganic mercury steals methyl groups from methylcobalamin, and methyl mercury is formed. However, methyl mercury is not more toxic than inorganic in mercury and the positive effects of B12 supplementation in this form seem to outweigh the possible disadvantages.

Preservatives

Methylcobalamin should be obtained with dry substance and liquid packed separately to increase the shelf life. The preparation should be kept in the dark stored at a temperature below 25 degees C and used within a year. (Premixed preparations, on the other hand, should be kept in a refrigerator).

Many of the vitamin B12 preparations on the market contain preservatives which can cause problems in sensitive patients. However, the methylcobalamin available under the product names "Algobaz" from Portugal or "Cobamet" produced by a French company (Roussel) also in Portugal do not.

The corresponding Japanese preparation, Esai's Mecobal, contains only 0.5 mg B12. According to Dr. Bo Nilsson, it is probable that, given daily, the transport between the blood-brain barrier is saturated even by such a small dose. In Dr. Ahlrot-Westerlund's opinion, however, methylcobalamin for patients with metal-induced disorders should be given daily intramuscularly* in doses of 10 mg with 8 x 5 mg oral folic acid and 300 mg vitamin B6 for 6 days a week until a positive effect is achieved and then continued until no further peak is achieved. This can take as long as 1/2-1 year or perhaps even longer. The dose should then be gradually diminished (given every other day for example).

*) given subcutaneously, the B12 treatment is, according to Dr. Westerlund, not as effective.

Multiple deficiencies

In many cases it can be assumed that multiple deficiencies, not always easily separable, are present. For example, lack of folic acid can also cause anaemia and its supplementation can mask a B12 deficiency. Therefore it is important that both vitamins are supplied, and to some extent also the other vitamins in the B-complex. Some of the symptoms of B12 deficiency are also present in B1 deficiency** and both deficiencies can be present at the same time.

**) diagnosed by testing thiamin pyrimydine phosphate in serum (expensive)

Some addresses and prices: Methylcobalamin: The two recommended preparations are of equal quality. Both can be ordered from a pharmacy in Lisbon, phone number: +351 1 342 3821. Ask for the head pharmacist, Maria Augusta. Since the preparation is prescription free, it can also easily be obtained during a trip to Portugal. However it should be ordered at least one week ahead.

B12 testing: Uddevalla Hospital in Sweden fax No: +46 522 93101
Test facilities available at the cost of SEK 130:- for B12, 200:- for homocystein and 200:- for methylmalonic acid (MMA). 1 USD is approx. 7 SEK.

According to the Charing Cross & Westminster Medical School, B12 Unit, Dr. Bhatt, there are "a handful" of laboratories worldwide, specialized in vitamin B12 testing. For further information: Tel: +44 (0)181 746 8625, Fax No.:+44 (0)181 746 8860

Monica Kauppi (with thanks to Dr. Westerlund for her kind assistance)

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