An Introduction To Cobalamin Metabolism-

I am not a health and nutrition expert, nor am I an expert at biochemistry. But to the best of my knowledge the information here is correct, being derived from well informed sources, but given some of my own interpretations and deductions. Some information is based on reading and knowledge gained from sources not mentioned in the references, such as the well known food chain effect in concentrating toxins up the food chain.

Introduction

I hope to encourage people to read about, examine and challenge popular nutritional and health issues, because my experience has tought me that only learning the issues for yourself frees one from the many misleading schools of thought that surround dietary practices. Perhaps most people will be satisfied just to know that they get enough B12, but this text is for those who want to understand what the real health issues are.

I suggest that rather than focusing always on B12 intake, a far more health giving practice is to ensure that the B12 in your body is used effectively. The human body can only absorb about 8 µg of B12 from any one oral dose. If one lives a conventional "toxic" lifestyle it would seem sensible to take a modest B12 supplement if you are a vegan. I have yet to see any strong evidence that this is necessary or what levels of intake may be required depending on lifestyle factors.

Lifestyle risks other than your heavy metal load

• meat or other animal products and refined carbohydrates (sugars) when used generously may more than double B12 needs
• persons who use drugs (eg Losec), chemicals, or beverages which destroy or remove B12 (e.g., tobacco*, alcohol, caffeine, laxatives, etc.)
• egg albumin and egg yolk decrease B12 absorption
• heavy metals present in food decrease dietary uptake
• a lack of calcium in food may decrease dietary uptake
• intestinal disorders or surgery affecting the intestines
• washing, cooking and light exposure of food containing B12

The primary loss of B12 in the human body seems to be through bile excretion, which is a greater factor amongst meat eaters. Also failure of intrinsic factor or poor production of stomach acid (usually due to aging) can contribute to B12 deficiency.

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.

Myelin is the insulating layer which, along with fatty acids*, surrounds nerve fibres. This protects nerves just like the insulation arround electrical cables. In B12 deficiency, toxic 15-17 coal atom fatty acids have a demyelinating effect on nerves, and electrical impulse transmission is disturbed. Large doses of B12 supplements may help to repair damage to the myelin given time, but once a nerve cell is destroyed it will not "grow back". Essential fatty acids and antioxidants will also assist with protection and regeneration of myelin.

*Myelin is made up of; cholesterol, polyunsaturated fats (PUFA), and phosphatidyl choline complex with lipid call sphingosine. (L. Mervyn)

What Is Cobalamin and What Does It Do?

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.

Detailed structure of cobalamin showing the corrin ring (in black), cobalt (in red) and 5,6-di-methylbenzimidazole ribonucleotide (in blue). The corrin ring coordinates the metal cobalt and the benzimidazole ribonucleotide is coordinated with the cobalt of the corrin ring and also via the phosphoester linkage to a side chain of the corrin ring system

Vitamin B12 is converted to 2 coenzyme forms of cobalamin (methyl and adenosyl) by enzyme catalysis to catalyse reactions in the human body. The vitamin is therefore a precursor, and not the active substance. Cobalamin coenzymes are part of the prosthetic group, that is the tightly bound group of coenzymes. This refelects the strength of interactions with their apoenzymes (proteins), which are inactive without the cobalamin cofactors, but convert to active holoenzymes when bound (The coenzymes bind to help form the active sites of their apoenzymes thus making an active enzyme). So, if methylcobalamin is inhibited, then the building and repair of nervous tissues is inhibited due to enzyme inactivity. Read literally, we get a "nervous breakdown"!

Symptoms would 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.

What May Cause Non-Anaemic Deficiency?

The transport of vitamin B12 into the brain can be disturbed or prevented by heavy metals such as inorganic mercury or lead. These affect the blood-brain barrier by causing leakage and restricting the active transport of nutrients. Also exposure to nitrous oxide (N2O), often called laughing gas, can cause cobalamin deficiencies in the brain. This may occur to women given the gas in labour or otherwise during use of this anaesthetic, and may result in permanant brain damage to someone with B12 deficiency. It is also worth bearing in mind that since metals can cause deficiency, then anyone exposed to sufficient quantity of metals may suffer permanent brain damage, even when ingesting RDA levels of the vitamin.

Heavy metals such as mercury, lead and cadmium can be detoxified by high doses of vitamin C (3000mg/day) plus supplementary essential minerals. (L. Mervyn)

The stock method of measuring vitamin B12 levels is not going to reveal deficiencies of the coenzymes required for healthy neurological functioning since it measures blood levels of vitamin B12 and not the CNS levels. These are not necessarily related to blood levels of B12. Deficiencies in the brain and CNS can be measured by checking "increased homocystein in LIQUOR", (liquor cerebrospinalis). However it would be expected that lower B12 levels in serum would indicate lower levels in the CNS.

The precise mechanism of brain B12 deficiency causation is theorised to be the oxidation of cobalt from CO2+ to CO3+ due to heavy metal action. The denatured and thus enlarged cobalt molecule will therefore not pass through the blood-brain barrier, the molecules size being already large. Meanwhile the heavy metal molecule will have been reduced. The result is a biologically inactive B12, and a modified heavy metal.

Dr. Britt Ahlrot-Westerlund from Stockholm is an advocate of this hypothesis. She recommends high doses of B12 for those suffering from heavy metal exposure, such as from dental amalgam, since in the presence of metals in the blood-brain barrier (plexus chorioideus), most of the vitamin B12 is consumed depending on the level of metal, such that regular B12 intake will not be sufficient.

Mercury (Hg) seems to change valency and binding site in the body, and therefore causes increased formation of free radicals. Maybe Hg valency change in pro-oxidative direction oxidizes cobalt atoms. To confirm this theory, electron spin resonance investigation was planned at Stockholm University's Department of Biophysics.

With dental amalgam now banned in Sweden and Germany, we can only wonder at the fate of populations who are continually exposed to this major mercury source in other nations. It would be sensible for people with amalgam fillings to have them replaced by a non-metal material. Vegans should also be careful to avoid alocohol, refined sugar, smoking and the other risk factors listed above. It would also be advisable to filter tap water. Dietary fibre helps to remove heavy metals from the body as does sweating. Unfortunately the half life of Hg in the brain/CNS is 25 years, thus steady accumulation, leading to neurological disorders is virtually guaranteed.

Alcohol May Cause Tissue Cobalamin Deficiency

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.

Serum, erythrocyte, and liver levels of total corrinoids, cobalamin (vitamin B12), and cobalamin analogues were determined by differential radioassay in 27 patients with alcoholism. Compared with normal subjects, liver content of total corrinoids and cobalamin in alcoholics was low. Conversely, serum total corrinoids and cobalamin were high. Compared with normal, levels of erythrocyte cobalamin analogue in alcoholics were elevated, but levels of cobalamin were not. Analogues in liver represented a similar percentage of total corrinoids in alcoholics as in normals. The data confirm prior work suggesting that, in alcoholism and in liver disease, cobalamin depletion in tissues may be masked by normal to high serum cobalamin and analogue levels. The failure of damaged liver to take up from the serum cobalamin and analogues, compounded by release of these compounds and their binders from damaged liver into the serum, can account for these findings.

Mercury Sources

More alarming than these WHO figures is the conclusion of Prof. Aposhian and his colleagues at the University of Arizona who demonstrated that two-thirds of the body load of mercury with those with dental amalgam, comes from mercury vapour released from the amalgam.
[Aposhian HV; Bruce DC; Alter W; Dart RC; Hurlbut KM; and Aposhian MM.
Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid:
correlation with dental amalgam score. FASEB J. 6:2472-2476,1 1992]

A similar study in Germany by Zander et al, provides data to show that release of mercury from amalgam fillings represents the main source of mercury exposure in subjects with amalgam fillings.
[Zander D; Ewers U; Freier I; Brockhaus. Studies on human exposure to mercury. 3.
DMPS induced mobilization of mercuy in subjects with and without amalgam fillings.
Zentralblatt fur Hygiene und Umwelmedizin 192(5):447-454, Feb 1992.]

Most of the scientific evidence used by the pro-amalgam "experts" to justify the continued use of amalgam represent gross underestimates of mercury exposure because they only measure exposure during dental visits, and do not include the exposure due to vapour found otherwise!

Psychological and Neurological symptoms Related To Amalgam

Conclusion

Meat, fish and dairy products may be "good" sources of vitamin B12, but expect them to also be good sources of heavy metals that will accumulate in tissues over time. Winding up in a hospital dribbling and with dimentia is perhaps the worst way to go out. Going vegan is a good way to significantly reduce your heavy metal intake.

High dietary intakes of vitamin B12 do not always guarantee safety from neurological disorders, as metal patients with "normal" B12 serum levels exist. In contrast, vegans with "low" serum levels of B12 do not always display medical problems associated with B12 deficiency.

Many factors inhibit cobalamin bioavailability and function. These have been highlighted and should be eliminated or heavily restricted for a healthy mind and body. How much B12 we each need will vary widely depending on your lifestyle. We can only absorb small quantities of B12 via digestion, so it is safest to reduce the B12 expendature. Consider the risk factors indicated, and if you fit any of the groups, then supplementation may be required. If you have mercury "amalgam" fillings your B12 requirements may be drastically increased to the point that only injected B12 will help you. Some nutritional supplement providers suggest that hydroxocobalamin rather than cyanocobalamin is preferable.

Since the various state, medical and nutritional bodies are evidently aware of the problems, but do not inform the public of the dangers, one can only conclude that there is a conspiracy of silence to protect economic interests and credability to the public. This comes at the expense to the publics health and wealth, and the future viability of the affected populations.

Links

• Aluminum: Human Neurophysiology, Behavior, Alzheimers
• Chemical Control of the Human Population
• Leading Edge Research Group: Biological Effect of Mercury Amalgam
• http://www.algonet.se/~leif/AmFAQigr.html (A good FAQ on the subject)
• http://emporium.turnpike.net/P/PDHA/health.htm ( IAOMT's web page)
• http://home.sol.no/reiersol/amalgam.htm (Recent amalgam research)
• http://203.23.131.20/wholmed/lphs18.htm (Amalgam in your teeth)
• http://netvoyage.net/~daveq/amalgam.htm (Amalgam and MS?)

Bibliography

• Dr. Ahlrot-Westerlund was the first physician in Sweden to identify the need for Selenium supplementation due to very low soil levels in Sweden. In the 70's she suspected that there might be a connection with heavy metals and Multiple Sclerosis. In 1978 she was invited by the Norwegian Scientific Acadamy to speak about selenium and vitamin E deficiency, as she had found that these were involved in the lipid peroxidation of cells in MS patients. Free radicals and dental amalgam are, according to her, an important part in explaining the MS syndrome. From 1980 she worked at the Institute for Neurochemistry and Neurotoxicology. She has been studying the effects of B12 mainly in heavy metal patients since 1987. In 1990 she was associated to the Karolinska Institutes Department of Applied Biochemistry.

• Cees J.H./van Tiggelen. Alzheimers Disease/Alcohol Dementia: Association with Zinc Deficiency and Cerebral vitamin B12 Deficiency. J. of Orthomolecular Psychiatry, 1983, vol 12, No. 2, 97-104.
• Eriksson S/Svensson.A, Catalytic effects by thiotransferase on the transfer of methylmercury and p-mercury-benzoate from macromolecules to low molecule weight thiol compounds. Toxicology 10, 1978, 115-122.
• Gran B. B12 i hög dos vid neuropsykiatriska symtom hos misstäktamalgamsjuka patienter. Swedish Medical Journal, 1994
• Hanson M. Vitamin B12, TF-bladet, 4, 1992
• Ideda T. et al. Vitamin B12 levels in serum and cerebrospinal fluid of people with Alzheimer's disease. Acta-Psychatr. Scand 1990, 82:337-329
• Lind/Friberg/Nylander. Demethylation of mercury in brain, National Institute of Environmental Medicine and Dept. of Environmental Hygiene, Presented at the First Meeting of the International Society for Trace Element Research in humans, Palm Springs, Dec.8-12., 1986.
• Lindenbaum J. et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anaemia of macrocytos. The new England Journal of Medicine, June 30, 1988.
• Metz J. Cobalamin Defciciency and the pathogensis of Nervous System Disease. Ann Ren Nub., 1992, 12:59-79.
• Mottet K. et al. Effects of Methylmercury Exposure in Primates, Presented at the First Meeting of the International Meeting of the International Society for Trace Element Research in humans, Palm Springs, Dec. 8-12, 1986.
• Mörnstad H/Norberg B. Paradigmskifte för bedömning och behandling av vitamin B12-brist, Swedish Dental Journal, nr 1 1994.
• Patridge W. Inorganic mercury; selective effects on blood-brain barrier transport systems. J. of Neurochemistry, 1976, No. 27:333-335.
• Reynalds E.H. Multiple Sclerosis and vitamin B12 metabolism. J, of Neuroimmunol. 40 (1992):225-230.
• Rochelle et al. Interactions between Hydroxocobalamin and Nitric Oxide (NO): Evidence of Redox Reaction between NO and Reduced Cobalamin and Reversible NO Binding to Oxidized Cobalamin, 1995, Journal of Pharm. and Exp. Terapheutics, vol 275, 1995, No. 1:48-52.

The following publications were also used:

• Sam Ziff, Michael F. Ziff, DDS Dentistry Without Mercury, Bio-Probe, Inc. Available from Bio-Probe web site.
• Horton/Moran/Ochs/Rawn/Scrimgeour Principles of Biochemistry 2nd Ed., Prentice-Hall International, Inc. Available from Prentice-Halls web site.
• Leonard Mervyn, B.Sc., PH.D., C.Chem F.R.S.CThorsons Complete Guide to Vitamins & Minerals, Published by Thorsons available via HarperCollins web site.
• Brian Leibovitz, Ph.D. Journal of Optimal Nutrition Editorials, Journal of Optimal Nutrition (contains useful critique of Victor Herbert)