An Introduction To Cobalamin Metabolism-
cobalamins: form, function, inhibitors, a vegan perspective
John Coleman
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
Most vegans, sooner or later, will discover the Vitamin B12 (cobalamin) requirement stories that circulate and often form the basis for demonstrating the alleged dangers of veganism. For more information on vitamin B12 and the vegan diet, click here. This text aims to demonstrate that it is not just a lack of B12 that causes ill health, but that it is also the modern western lifestyle that may generate excess requirements of this micronutrient. In particular this text will look at the little known issue of mercury, and how it could interfere with normal cobalamin metabolism.
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.
I suggest that rather than just focusing always on B12 intake, an additional good 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.
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 [adapted from; Thrash & Thrash, "NUTRITION FOR VEGETARIANS", 1982, "Heavy Metal Bulletin" Vol 2, Iss 3, Dec 1995 and Thorsons "Complete Guide To Vitamins and Minerals"]*B12 detoxifies cyanide in food and also tobacco smoke 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?
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 µg 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 µg 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 25.0µg/100g of B12, therefore 100g of pigs liver will result in 8.017µg 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.
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"!
Methylcobalamin participates in the transfer of methyl groups as in the regeneration of methionine from homocysteine in mammals, as shown here. The methyl group of 5-methyltetrahydrofolate is passed to a reactive reduced form of cobalamin to form methylcobalamin, which transfers the methyl group to the thiol side chain of homocystein
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.
The late Dr. Britt Ahlrot-Westerlund from Stockholm was an advocate of this hypothesis. She recommended 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. (Christina Bolander-Gouaille, author of Focus on Homocysteine and the Vitamins Involved in its Metabolism, has also spoken on this topic. You can click here to find out more.
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, we can only wonder at the fate of populations who are continually exposed to this major mercury source in other nations. It would seem to 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, perhaps leading to neurological disorders is a distinct risk.
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.
Kanazawa S; Herbert V,Total corrinoid, cobalamin (vitamin B12), and cobalamin analogue levels may be normal in serum despite cobalamin in liver depletion in patients with alcoholism, Lab Invest, 53:1, 1985 Jul, 108-10
Upon investigating Victor Herberts research I found useful background information at the Journal of Optimum Nutrition (JON) web site. Also the book Dirty Medicine by Martin J Walker contains some critique of Herberts research methods and his political actions against the alternative health movement. Elaborating upon the quality of his studies is beyond the scope of this article and is covered by the JON.
Mercury Sources
Table 2 on page 36 of the WHO Health Criteria 118 has the following table: Estimated average daily intake and retention (ug/day) of total mercury and mercury compounds in the general population exposed to mercury Exposure Elemental mercury vapour Inorganic Mercury vapour Methylmercury
Air 0.030(0.024) 0.002(0.001) 0.008(0.0064)
Diet/Fish 0 0.600(0.042) 2.4(2.3)
Diet/Non-Fish 0 3.6(0.25) 0
Drinking Water 0 0.050(0.0035) 0
Dental Amalgam 3.8-21(3-17) 0 0
TOTAL 3.9-21(3.1-17) 4.3(0.3) 2.41(2.31)
From: Environmental Health Criteria 101: Methylmercury (WHO 1990)
Values given are the estimated average daily intake; the figures in parentheses
represent the estimated amount retained in the body of an adult.
Values are quoted to 2 s.fs.
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
Psychological Neurological/Neuromuscular
Irritability Numbness
Nervousness Sensitivity to EMF
Sleeping Difficulties Tingling Sensation
Anxiety Headaches
Sudden Anger Dizziness
Rapid mood swings Chronic fatigue
Forgetfulness Tremor
Impaired shortterm memory Speech problems
Suicidal tendancies Restless legs
Concentraion difficulties Cramps
Hallucinations Stiffness
Lack of self-control Feeling of pressure in the body
Depression Fainting
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 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 useful to reduce the likelihood of B12 being poorly absorbed or utilised.
Links
The links below will fill you in on many other environmental hazards, and what you can do to help yourself avoid them.
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://vest.gu.se/~bosse/MercuryPage.html (Mercury page)
http://203.23.131.20/wholmed/lphs18.htm (Amalgam in your teeth)
http://netvoyage.net/~daveq/amalgam.htm (Amalgam and MS?)
Bibliography
Much of this text was adapted from an article Vitamin B12- metals disturb transport by Monica Kauppi, assisted by Dr. Ahlrot-Westerlund, which appeared in "Heavy Metal Bulletin" dec 1995 vol 2, 3:8-10.
HMB is available from Lilla Aspuddsv. 10, S-12649 STOCKHOLM, SWEDEN, tel/fax: +46 8 184086.
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.
The original references for this article are:
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 article also goes in to some detail on explaining how B12 levels are assessed and the use of methylcobalamin to treat metal patients, and the problems associated with non methylcobalamin treatment. Details on B12 testing and supply of methylcobalamin were also given. Multiple deficiencies/excesses can also obscure diagnosis of B12 deficiency, ie. folic acid and B1 and other B vitamins.
Dr. Ahlrot-Westerlund also presents some case studies of successful methylcobalamin treatments.
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)
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