Guest guest Posted April 14, 2005 Report Share Posted April 14, 2005 http://www.autisme-montreal.com/congres/2003/Neubrander.html " Cobalamin/ " B12 " deficiency leads to three problems. First, when adenosylcobalamin coenzyme is deficient, the substrate methylmalonic acid cannot be converted into succinic acid. Therefore levels of methylmalonic acid with continue to increase and spill over into the urine, a phenomenon known as methylmalonic aciduria. Second, when the methylcobalamin coenzyme is deficient, the substrate homocysteine cannot be converted to methionine. Therefore levels of homocysteine will continue to increase and may be seen in the blood or urine resulting in homocystinemia and homocystinuria respectively. Third, a phenomenon known as " folate trapping " occurs when hydroxycobalamin is deficient in the presence of adequate methyl-tetrahydrofolate. When this situation occurs, the methyl group on methyl-tetrahydrofolate is trapped because " it wants to leave (to become tetrahydrofolate) but can’t get away " B12 - rationale for using vitamin B12 5th November 2003 Over the last 22 years of treating over 3,000 patients with chronic fatigue syndrome, I have developed a programme of treatment which I believe all patients must do as the foundation before proceeding to other treatments. Vitamin B12 by injection I see as an integral part of this programme and it is effective for many, regardless of the cause of their chronic fatigue syndrome. Those patients who respond to B12 are not obviously deficient in B12, indeed blood tests usually show normal levels. The " normal " levels of B12 have been set at those levels necessary to prevent pernicious anaemia - this may not be the same as those levels for optimal biochemical function. B12 has a great many other functions as well as the prevention of pernicious anaemia. However, what is interesting is how B12 is beneficial in so many patients with fatigue, regardless of the cause of their CFS, and suggests that there is a common mechanism of chronic fatigue which B12 is effective at alleviating. General mechanism by which B12 relieves the symptoms of CFS Professor Pall has looked at the biochemical abnormalities in CFS and shown that sufferers have high levels of nitric oxide and its oxidant product peroxynitrite. These substances may be directly responsible for many of the symptoms of CFS and are released in response to stress, whether that is infectious stress, chemical stress or whatever. B12 is important because it is the most powerful scavenger of nitric oxide and will therefore reduce the symptoms of CFS regardless of the cause.(1, 2, 3, 4, 5, 6) Nitric oxide is known to have a detrimental effect on brain function and pain sensitivity. Levels are greatly increased by exposure to chemicals such as organophosphates and organic solvents(7). When sensitive tests of B12 were applied (serum methylmalonic acid and homocysteine) before and after B12 therapy, the following symptoms were noted to be caused by subclinical B12 deficiency: parasthesia, ataxia, muscle weakness, hallucinations, personality and mood changes, fatigue, sore tongue and diarrhoea.(8) B12 in fatigue syndromes The " foggy brain " with difficulty thinking clearly, poor short term memory and multitasking are often much improved by B12.(9, 10, 11). Mood and personality changes, so often a feature of patients with chemical poisoning, can be improved by B12(12). The physical fatigue and well being are often both improved. A study Twenty eight subjects suffering from non-specific fatigue were evaluated in a double-blind crossover trial of 5 mg of hydroxocobalamin twice weekly for 2 weeks, followed by a 2-week rest period, and then a similar treatment with a matching placebo. The placebo group in the first 2 weeks had a favourable response to the hydroxocobalamin during the second 2 week period with respect to enhanced general well being. Subjects who received hydroxocobalamin in the first 2-week period showed no difference between responses to the active and placebo treatments, which suggests that the effect of vitamin B12 lasted for over 4 weeks. It is noted there was no direct correlation between serum vitamin B12 concentrations and improvement. Whatever the mechanism, the improvement after hydroxocobalamin may be sustained for 4 weeks after stopping the medication. " A Pilot Study of Vitamin B12 in the Treatment of Tiredness, " Ellis, F.R., and Nasser, S., British Journal of Nutrition, 1973;30:277-283. Practical Details Vitamin B12 has no known toxicity and B12 surplus to requirement is simply passed out in the urine (which may discolour pink). It is theoretically possible to be allergic to B12, but in the thousands of injections that I have sanctioned this has only ever occurred after several injections and causes local itching, redness and swelling (although the commonest cause of redness and swelling is poor injection technique). It does not seem to matter whether hydroxocobalamin or cyanocobalamin is used. I usually start with 2mgs weekly by i.m. injection, then adjust the frequency according to response - some patients will respond straight away, some need several doses before they see improvement. I would do at least 10 injections before giving up. Many of my patients learn to inject themselves - this means they can be independent of their doctors. The cost is & #65443;1.60 per injection (2ml B12 plus syringe and needle). (1) Pall ML. Elevated, sustained peroxynitrite level as the cause of chronic fatigue syndrome. Medical Hypotheses 2000;54:115-125. Pall ML. Elevated peroxynitrite as the cause of chronic fatigue syndrome: Other inducers and mechanisms of symptom generation. Journal of Chronic Fatigue Syndrome 2000;7(4):45-58. (2) Pall ML. Cobalamin used in chronic fatigue syndrome therapy is a nitric oxide scavenger. Journal of Chronic Fatigue Syndrome, 2001;8 (2):39-44. (3) Pall ML, Satterlee JD. Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome and posttraumatic stress disorder. ls of the New York Academy of Science 2001;933:323-329. (4) Pall ML. Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite, Medical Hypotheses, 2001; 57:139-145. (5) Pall ML. Levels of the nitric oxide synthase product citrulline are elevated in sera of chronic fatigue syndrome patients. J Chronic Fatigue Syndrome 2002; 10 (3/4):37-41 (6) Pall ML. Chronic fatigue syndrome/myalgic encephalitis. Br J Gen Pract 2002;52:762. Smirnova IV, Pall ML. Elevated levels of protein carbonyls in sera of chronic fatigue syndrome patients. Mol Cell Biochem, in press. (7) Pall ML. NMDA sensitisation and stimulation by peroxynitrite, nitric oxide and organic solvents mechanism of chemical sensitivity in multiple chemical sensitivity. FASEB J 2002;16:1407-1417. (8) Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anaemia or macrocytosis J Lindenbaum et al New Engl J Med 1988; 318: 1720-1728. (9) Mac Holmes J. Cerebral manifestations of vitamin B12 deficiency. Br Med J 1956; 2: 1394-1398. (10) Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973; 30: 277-283 (11) Langdon FW. Nervous and mental manifestations of pre-pernicious anaemia. J Amer Med Assoc 1905; 45: 1635-1638 (12) Strachan RW, JG. Psychiatric syndromes due to avitamiosis B12 with normal blood and marrow. Ouart J Med New Series XXXIV 1965: 303-317 Novel chronic fatigue syndrome (CFS) theory finally produces detailed explanations for many CFS observations: Help Support this Reseach A novel theory of the cause of CFS has been published which is supported by diverse biochemical and physiological observations of CFS, while providing explanations for five of most difficult puzzles about this medical condition. The theory has been published by Dr. L. Pall (Professor of Biochemistry and Basic Medical Sciences, Washington State University) in several publications (1-4,9). The theory starts with the observation that infections that precede and may therefore induce CFS and related conditions act to induce excessive production of inflammatory cytokines that induce, in turn, the inducible nitric oxide synthase (iNOS). This enzyme, in turn, synthesizes excessive amounts of nitric oxide which reacts with another compound (superoxide) to produce the potent oxidant peroxynitrite (see Fig. 1). Peroxynitrite acts via six known biochemical mechanisms to increase the levels of both nitric oxide and superoxide which react to produce more peroxynitrite (Fig. 1). In this way, once peroxynitrite levels are elevated, they may act to continue the elevation, thus producing a self-sustaining vicious cycle (ref.1). It is this cycle, according to the theory, that maintains the chronic symptoms of CFS and it is this cycle, therefore, that must be interrupted to effectively treat this condition. Twelve different observations on chronic fatigue syndrome and its symptoms provide support for this theory: 1. The levels of neopterin, a marker for the induction of the inducible nitric oxide synthase are reported to be elevated in CFS (1). 2. Mitochondria are reported to be dysfunctional in CFS and mitochondria are known to be attacked by peroxynitrite and also by nitric oxide (1). 3. Both cis-aconitate and succinate levels are reported to be elevated in CFS and the enzymes that metabolize these two compounds are known to be inactivated by peroxynitrite (1). 4. The four inflammatory cytokines implicated have been reported to been reported to be elevated in 10 different studies of CFS (1,2). 5. These same inflammatory cytokines have been reported to induce fatigue when injected into humans (1). 6. An animal (mouse) model of CFS has " fatigue " induced by a bacterial extract that can induce both the inflammatory cytokines and also the inducible nitric oxide synthase. 7. Polyunsaturated fatty acid pools are reported to be depleted in CFS and such polyunsaturated fatty acids are known to be oxidized by oxidants such as peroxynitrite. 8. Anecdotal evidence has suggested that antioxidants such as coenzyme Q-10, flavonoids and glutathione precursors may be useful in CFS treatment, consistent with a role for an oxidant such as peroxynitrite. 9. Women are reported to produce more nitric oxide than men, possibly explaining the gender bias seen in CFS. A similar gender bias is seen in autoimmune diseases characterized by excessive peroxynitrite (i.e. lupus, rheumatoid arthritis). 10. Cases of CFS are associated with high levels of deleted mitochondria DNA, suggesting but not proving that mitochondrial dysfunction can produce the symptoms of CFS (1). 11. Biochemical similarities †" depletion of glutamine and cystine pools †" have been reported in CFS and several diseases characterized by elevated peroxynitrite levels, suggesting a similar biochemical basis for all of these conditions (1). 12. Because peroxynitrite is a potent oxidant, this theory predicts that oxidative stress will be elevated in CFS. There was no direct evidence for this when the theory was published but three subsequent papers have reported substantial evidence for such oxidative stress in CFS (5-7A). These results, may therefore, be considered to confirm important predictions of the theory, although the authors were unaware of this theory when they initiated these studies. CFS puzzles explained by the elevated nitric oxide/peroxynitrite theory: There are five different puzzles of CFS that are explained by this theory. The first of these, the chronic nature of CFS, is explained by the self-sustaining vicious cycle that is central to this theory. The second is how infection and other stress which often precede CFS may produce CFS. This theory predicts that each of these can lead into this mechanism by inducing excessive nitric oxide. Infection is not the only stress that may be involved in this way †" both physical trauma and severe psychological trauma can produce excessive nitric oxide synthesis (2). In addition, tissue hypoxia may induce this cycle by increasing levels of superoxide (the other precursor of peroxynitrite) (2). A third puzzle about CFS is how it leads to the many biochemical/physiological correlates reported to occur in CFS. This is discussed with the list of 12 such correlates described above. A fourth puzzle about CFS is how the diverse symptoms of this condition may be generated. It turns out that a variety of factors, including nitric oxide, superoxide, oxidative stress and mitochondrial/energy metabolism dysfunction may have important roles (2). For example, nitric oxide is known to stimulate the nociceptors that initiate the perception of pain, and therefore excessive nitric oxide may cause the multi-organ pain associated with CFS (2). Nitric oxide has a central role in learning and memory and so its elevation may also provide a partial explanation for the cognitive dysfunction characteristic of CFS (2). Other symptoms explained by this theory include orthostatic intolerance, immune dysfunction, fatigue and post- exertional malaise (2). The immune dysfunction reported in CFS, may allow for opportunistic infections to develop, such as mycoplasma or HHV6 infections, which may exacerbate the basic CFS mechanism by increasing inflammatory cytokine synthesis. What about multiple chemical sensitivity, posttraumatic stress disorder and fibromylagia? A fifth puzzle regarding CFS is its variable symptoms and, most importantly, its association with three other conditions of equally puzzling etiology, multiple chemical sensitivity (MCS), posttraumatic stress disorder (PTSD) and fibromylagia (FM). The theory explains the variable symptoms, from one case to another, in part, by a somewhat variable tissue distribution of the elevated nitric oxide/peroxynitrite. A common etiology (cause) for CFS with MCS, PTSD and FM has been suggested by others (discussed in refs 4,9). A common causal mechanism for these four conditions is suggested not only by the association among these different conditions (many people are afflicted by more than one) but also by the overlapping symptoms typically found in these four conditions (see refs. 4 and 9 for discussion). These overlaps raise the question about whether MCS, FM and PTSD may be caused by excessive nitric oxide and peroxynitrite. Each of these four conditions is reported to be often preceded by and possibly induced by exposure to a relatively short-term stress that can induce excessive nitric oxide synthesis. Pall and Satterlee (4) present a substantial case for an excessive nitric oxide/peroxynitrite cause for multiple chemical sensitivity (MCS), including the following: Organic solvents and pesticides whose exposure is reported to precede and presumably induce multiple chemical sensitivity, are also reported to induce excessive nitric oxide synthesis. Such chemicals are also reported to induce increased synthesis of inflammatory cytokines which induce, in turn, the inducible nitric oxide synthase (leading to increased synthesis of nitric oxide). Neopterin, a marker of induction of the inducible nitric oxide synthase, is reported to be elevated in MCS. Markers of oxidative stress are reported to be elevated in MCS, as predicted if excessive peroxynitrite is involved. In animal models of MCS, there is convincing evidence for an essential role for both excessive NMDA activity (where such activity is known to induce excessive nitric oxide) and for excessive nitric oxide synthesis itself. If one blocks the excessive nitric oxide synthesis in these animal models, the characteristic biological response is also blocked. This and other evidence shows the nitric oxide has an essential role (4). Somewhat similar evidence is available suggesting an elevated nitric oxide/peroxynitrite mechanism for both PTSD and FM (9). PTSD is thought to be induced by excessive NMDA stimulation, which, as discussed above, is known to produce excessive nitric oxide and peroxynitrite (9). Two inflammatory cytokines known to induce increased synthesis of nitric oxide have been reported to be elevated in PTSD. PTSD animal model studies have reported an essential role for both excessive NMDA stimulation and nitric oxide synthesis in producing the characteristic biological response. Interestingly, a recent study of FM implicates elevated nitric oxide and also elevated NMDA stimulation (8), and such NMDA stimulation is known to increase nitric oxide synthesis. As in the other conditions discussed here, there is a pattern of evidence from studies of FM patients, consistent with the proposed nitric oxide/peroxynitrite mechanism (9). The theory that elevated nitric oxide/peroxynitrite is responsible for the etiology of CFS, MCS, PTSD and FM appears to be the only mechanism to be proposed that explains the multiple overlaps among these four conditions. While the pattern of evidence supporting it cannot be considered definitive, the many types of evidence providing support for this view must be considered highly suggestive. What does this proposed mechanism suggest about CFS treatment? As discussed in ref 1, there are a number of agents that may be useful in the treatment of CFS, based primarily on anecdotal evidence, that are expected to lower the consequences of the proposed nitric oxide/peroxynitrite mechanism. Possibly the most intriguing such mechanism relates to the widespread use of vitamin B12 injections in treatment of CFS (3). Two forms of vitamin B12 are being used here, hydroxocobalamin, which is a nitric oxide scavenger and cyanocobalamin, which is converted to hydroxocobalamin by Pall human cells (3). These observations suggest that the nitric oxide/peroxynitrite proposed mechanism for CFS makes useful predictions for effective treatment. It is hoped that this proposed mechanism may allow us to optimize the use of these and other agents for treatment of CFS and related conditions. Other sites with thoughtful presentations that you may wish to access are as follows: http://www.cfsresearch.org/cfs/ http://www.square-sun.co.uk/cfs-nim/ http://www3.sympatico.ca/me-fm.action/ References: 1. Pall ML. Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Medical Hypotheses 2000;54:115-125. (link) 2. Pall ML. Elevated peroxynitrite as the cause of chronic fatigue syndrome: Other inducers and mechanisms of symptom generation. Journal of Chronic Fatigue Syndrome, 2000;7:45-58. 3. Pall ML. Cobalamin used in chronic fatigue syndrome therapy is a nitric oxide scavenger. Journal of Chronic Fatigue Syndrome, 2001;8:39-44. 4. Pall ML, Satterlee JD. Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome and posttraumatic stress disorder. ls of the New York Academy of Science, 2001;933:323-329. 5. s RS, TK, Mathers MB, RH, McGregor NR, Butt HL. Investigation of erythrocyte oxidative damage in rheumatoid arthritis and chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome 2000;6:37-46. 6. s RS, TK, McGregor NR, RH, Butt HL. Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep 2000;5:35-41. (link) 7. Fulle S, Mecocci P, Fano G, Vecchiet I, Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF. Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radicals in Biology and Medicine 2000;15:1252-1259. (link) 7A. Keenoy BM, Moorkens G, Vertommen J, DeLeeuw I. Antioxidant strotus and lipoprotein oxidation in chronic fatigue syndrom. Life Sciences 2001;68:2037-2049. 8. Larson AA, Giovengo SL, IJ, Michalek JE. Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. Pain 2000;87:201-211. (link) 9. Pall ML. Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite, Medical Hypotheses, 2001;57:139-145.  Pernicious Anemia is a rare blood disorder characterized by the inability of the body to properly utilize vitamin B12 (a cobalamin), which is essential for the development of red blood cells.           The symptoms of Pernicious Anemia may include weakness, fatigue, an upset stomach, an abnormally rapid heartbeat (tachycardia), and/or chest pains.           Recurring episodes of anemia (megaloblastic) and an abnormal yellow coloration of the skin (jaundice) are also common.           Pernicious Anemia is thought to be an autoimmune disorder, and certain people may have a genetic predisposition to this disorder.           The three recognized forms of Pernicious Anemia include: Congenital Pernicious Anemia, Juvenile Pernicious Anemia, and Adult Onset Pernicious Anemia. The subdivisions are based on the age at onset and the precise nature of the defect causing impaired B12 utilization (e.g., absence of intrinsic factor). Hypokalemia and sudden death may occur when severe megaloblastic anemia is treated intensively. Lack of therapeutic response may be due to infection. Before administering vitamin B12, an intradermal test dose is recommended for patients known to be sensitive to cobalamines. Excessive alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B12. Doses of vitamin B12 exceeding 10 µg daily may produce a hematologic response in patients who have a folate deficiency. Indiscriminate administration of vitamin B12 may mask the true diagnosis of pernicious anemia. A dietary deficiency of only vitamin B12 is rare. Multiple vitamin deficiency is expected in any dietary deficiency. In patients with ian (pernicious) anemia, parenteral therapy with vitamin B12 is the recommended method of treatment and will be required for the remainder of the patient's life. Oral therapy is not dependable. Serum potassium must be watched closely the first 48 hours; and potassium should be replaced if necessary. Reticulocyte plasma count, vitamin B12 and folic acid levels must be obtained prior to treatment and between the fifth and seventh day of therapy. There is some evidence that pernicious anemia may be genetic although its mode of inheritance is poorly documented. There is a congenital form of pernicious anemia due to defect of intrinsic factor at birth that is clearly inherited as an autosomal recessive trait with the affected child having received two copies of the gene, one from each parent. The intrinsic factor gene itself has been localized to human chromosome 11. Pernicious anemia probably is an autoimmune disorder with a genetic predisposition. Pernicious anemia is more common than is expected in families of patients with pernicious anemia, and the disease is associated with human leucocyte antigen (HLA) types A2, A3, and B7 and type A blood group. Patients may report either constipation or having several semisolid bowel movements daily. This has been attributed to megaloblastic changes of the cells of the intestinal mucosa. Mortality/Morbidity: The disease is called pernicious anemia because it was fatal prior to the discovery that it was a nutritional disorder. The megaloblastic appearance of cells led many to speculate that it was a neoplastic disease. The response of patients to liver therapy suggested that a nutritional deficiency was responsible for the disorder. This became obvious in clinical trials once vitamin B-12 was isolated. Presently, patients on appropriate treatment have a normal lifespan. • Nervous system: Neurological symptoms can be elicited in most patients with pernicious anemia, and the most common symptoms are paresthesias, weakness, clumsiness, and an unsteady gait. The 2 latter symptoms become worse in a dark room because they reflect the loss of proprioception in a patient who is unable to rely upon vision for compensation. These neurological symptoms are due to myelin degeneration and loss of nerve fibers in the dorsal and lateral columns of the spinal cord and cerebral cortex. â—¦ Neurological symptoms and findings may be present in the absence of anemia; this is more common in patients taking folic acid or on a high-folate diet. â—¦ Patients who are older may present with symptoms suggesting senile dementia or Alzheimer disease; memory loss, irritability, and personality changes are commonplace. Megaloblastic madness is less common and can be manifested by delusions, hallucinations, outbursts, and paranoid schizophrenic ideation. Identifying the cause is important because significant reversal of these symptoms and findings can occur with vitamin B-12 administration • Abnormal mentation and deterioration of vision and hearing may be observed. â—¦ Central nervous system: Suspect pernicious anemia in all patients with recent loss of mental capacities. Somnolence, dementia, psychotic depression, and frank psychosis may be observed, which can be reversed or improved by treatment with Cbl. Perversion of taste and smell and visual disturbances, which can progress to optic atrophy, can likewise result from central nervous system Cbl deficiency. â—¦ Combined system disease: A history of either paresthesias in the fingers and toes or difficulty with gait and balance should prompt a careful neurological examination. Loss of position sense in the second toe and loss of vibratory sense for a 256-Hz but not a 128-Hz tuning fork are the earliest signs of posterolateral column disease. If untreated, this can progress to spastic ataxia from demyelinization of the dorsal and lateral columns of the spinal cord. Causes: An increased incidence of pernicious anemia in families suggests a hereditary component to the disease. Patients with pernicious anemia have an increased incidence of autoimmune disorders and thyroid disease, suggesting that an immunological component to the disease exists. Children who develop Cbl deficiency usually have a hereditary disorder, and the etiology of their Cbl deficiency is different from the etiology observed in classic pernicious anemia. Homocysteine is used in many of the important steps your body uses to break down methionine into non-essential proteins. At the end of the cycle, homocysteine is used to recombine the “leftovers†from this process back into a little methionine. This entire process takes a lot of energy. Your body gets this energy from vitamins and other nutrients. If you don’t have enough nutrition, especially if you are B-12 deficient—either because you are not getting B vitamins from the foods you eat or because your body is not able to adequately absorb them (which happens as we age)—the methionine is not recombined and homocysteine escapes into your bloodstream. If it does, the homocysteine will eventually become toxic and will damage your arteries and brain cells. Homocysteine is formed by the body as a naturally synthesized byproduct of methionine ( a very important amino acid in your body) metabolism. Like cholesterol, homocysteine performs a necessary function in the body, after which, if the right cofactors are present, it will eventually convert to cysteine (and this is one of the amino acids needed to produce glutathione, which is very critical in your detoxifications pathways.) and other beneficial compounds such as ATP, (the energy molecule of the body) and S-adenosylmethionine (SAM). When left intact, it enters the bloodstream and begins attacking blood vessel walls, laying the foundation for heart disease, stroke and other cardiovascular diseases. The clear message from new scientific findings is that there is no safe " normal range " for homocysteine. While commercial laboratories state that normal homocysteine can range from 5 to 15 micromoles per liter of blood, epidemiological data reveal that homocysteine levels above 6.3 cause a steep, progressive risk of heart attack (the American Heart Association's journal Circulation, Nov. 15, 1995, 2825-30). One study found each 3-unit increase in homocysteine equals a 35% increase in myocardial-infarction (heart-attack) risk (American Journal of Epidemiology, 1996, 143[9]:845-59). Many enzymes, or catalysts are involved in the complete metabolism of homocysteine. If any of these enzymes is defective or functions inefficiently, the body is less able to successfully process homocysteine. Although this enzyme dysfunction may be due to a mutated or defective gene, ( identified by Dr. Rima Rozen at McGill University in Montreal), more often this breakdown in metabolism is due to deficiencies of certain nutrients. . .particularly B-6, B-12 and folic acid. When this function is disordered, whether due to genetic defect or nutrient deficiency, homocysteine accumulates and enters the bloodstream where it promotes oxidation of lipids, causes platelets to stick together, enhances the binding of lipoprotein (a) to fibrin and promotes free radical damage to the inside of arteries. Some have suggested that the obvious solution to reducing homocysteine would be to restrict methionine intake by restricting foods such as meats that are rich in methionine. Then the supermarket shelves would be lined with low methionine and methionine-free foods. That makes about as much sense as switching cabins on the Titanic. Methionine is a sulfur-containing amino acid that is involved in the synthesis of protein, important in the maintenance of cartilage, and needed for the formation of other important amino acids such as taurine and carnitine. Methionine is not at fault. The problem is when homocysteine cannot be converted. Reducing Homocysteine Levels The good news is...elevated homocysteine levels, whether due to nutrient deficiencies or defective genes, can easily be normalized in virtually all cases, simply and inexpensively, using a combination of nutritional supplements. The most effective defense against homocysteine buildup is a combination of vitamins B-6 and B-12, folio acid and trimethylglycine (TMG). So you have a way to naturally lower cholesterol. There are three biochemical pathways used by the body to reduce homocysteine. In one pathway TMG donates a methyl group which detoxifies homocysteine. In this reaction, TMG is reduced to DMG (dimethylglycine), that familiar-product sold as a supplement for its energizing effects. In the other routes, folic acid, B12 and B6 convert homocysteine into nontoxic substances. Some people can't utilize one or another of these pathways. That is why a combination of all these nutrients is most effective for lowering homocysteine. In some people vitamin B may not be efficiently converted to its active co-enzyme form, pyridoxyl-5-phosphate. In that case supplementing with pyridoxyl-5-phosphate would be necessary. There we go again..good health depends on nutrition and yet many medical types insist nutrition has nothing to do with overall health  Trimethylglycine Trimethylglycine (aka TMG) is the biochemical term for betaine. TMG is able to donate methyl groups (a methyl group is one carbon molecule and three hydrogens..very, very important to our chemistries) to biochemical events and in the case of homocysteine this leads to the increased production of S-adenosyl-methionine (SAM or sometimes it is written SAMe) which is the bioactive form of the amino acid methionine…also a methyl donor. SAM has been used successfully to treat problems such as cirrhosis of the liver, depression, osteoarthritis and Fibromyalgia. Methyl groups are thought to protect cellular DNA from mutation, a process which is also helped by good antioxidants. As people age, they often do not have enough available methyl groups to safeguard DNA. Abnormal methylation patterns are found in many people with cancer. Eating foods that contain methyl groups such as beets, green leafy vegetables and legumes is helpful, but these must be eaten in relatively large quantities several times a week. Therefore, dietary supplements such as TMG may often be necessary to provide the body with sufficient protective methyl groups. Betaine comes from beet sugar and is extracted through a very complex process. Don’t think the betaine HCL you see in digestive supports is the same thing..it isn’t. It has not been shown that betaine HCL is a methyl donator..although it may be..it is very acidic and for long term use, would not be a good plan. There are essentially two ways to lower homocysteine levels. One, the most common, would be to add methyl groups to it to convert it to methionine or SAMe. This is accomplished, as mentioned, through TMG (which as its name suggests, has three methyl groups on each glycine molecule – glycine is another amino acid. They are transferred to homocysteine, but need the help of folic acid, vitamin B12, and zinc. Another methyl donor of importance is choline and this remethylation of homocysteine does NOT need co-factors. One hitch, though, is that this process is only active in the liver and kidneys..so to protect the whole body, in particular the brain one should be sure to take a complex with all factors present. The second pathway to lower homocysteine involves converting it into cysteine (an very important amino acid), which then through a cascade of chemistry becomes glutathione. This pathway is dependent on vitamin B6 and the exact amount needed to lower homocysteine from person to person can vary greatly. It is only the amino acid methionine which can create homocysteine and the amount of that in someone’s diet, really depends on the individual’s diet. One higher in red meat and chicken would be higher in methionine and so this person would need more B6 (and the other co-factors for that matter) to ensure the clearing of homocysteine. Elevated homocysteine can also be caused by a genetic defect that blocks the trans-sulfuration pathway (the path which ultimately changes it to glutathione) by inducing a deficiency of the vitamin B6-dependent enzyme cystathionine-B-synthase. In this case, high doses of vitamin B6 are required to suppress excessive homocysteine accumulation. Since one would not want to take excessive doses of vitamin B6 (greater than 300 to 500 mg a day for a long time period), a homocysteine blood test can help determine whether you are taking enough vitamin B6 to keep homocysteine levels in a safe range. There are some people who lack an enzyme to convert vitamin B6 into its biologically active form, pyridoxal-5-phosphate. In this case, if low-cost vitamin B6 supplements do not sufficiently lower homocysteine levels, then a high-cost pyridoxal-5-phosphate supplement may be required. I generally suggest to my patients to take the bio-active form without thinking about the cheaper brands. For many people, the daily intake of 500 mg of TMG, 800 mcg of folic acid, 1000 mcg of vitamin B12, 250 mg of choline, 250 mg of inositol, 30 mg of zinc, and 100 mg of vitamin B6 will keep homocysteine levels in a safe range. But the only way to really know is to have your blood tested to make sure your homocysteine levels are under 7. If homocysteine levels are too high, then up to 6 grams of TMG may be needed along with higher amounts of other remethylation cofactors. Some people with cystathione-B synthase deficiencies will require 500 mg a day or more of vitamin B6 to reduce homocysteine to a safe level. For the prevention of cardiovascular disease, you would want your homocysteine blood level to be under 7. For the prevention of aging, some people have suggested that an even lower level is desirable, but more research needs to be done before any scientific conclusions can be reached. A Life Extension article (July, 1997), sites these cases of people with problems in these pathways. “People with these disorders frequently die of cardiovascular disease before reaching adulthood. In one case history report, a 16-year-old Japanese girl was unable to walk with or without support, and had severe peripheral neuropathy, muscle weakness and convulsions. Her vascular system was on the verge of collapse. B6 or B12 didn't help. Folic acid lowered homocysteine, but didn't improve her symptoms. Two months after adding TMG to the regimen, her homocysteine level dropped and she was able to walk with support. Seventeen months later, she was free from convulsions and able to walk normally again. This case history demonstrates the seesaw relationship between homocysteine and SAM. The girls SAM levels went from undetectable to near normal after the first two months of treatment while her homocysteine levels fell dramatically. If these nutrients can overcome a genetic disorder, consider how powerful they can be in reducing the risks associated with elevated homocysteine in the general population. Some people who have been taking this homocysteine lowering nutrient combination for more than a decade reported many benefits including fewer colds, more energy, increased endurance and lower blood sugar levels.†Methylation/Homocysteine and Other Disease I cannot speak enough of the importance of the process of methylation to our health and functions. For one, it is essential to DNA repair, which if not repaired will result in breaks and mutation. This in turn leads to accelerated aging because of larger amounts of “half-baked†or even dangerous proteins being produced. In fact, in a journal Medical Hypothesis (1998, 51[3]:179-221), it was suggested that aging, period, could be a result of cellular demethylation, or in other words, a slowing of “re-methylation†needed to maintain and repair DNA.  Methylation is a key process in the liver with respect to its ability to detoxify our bodies. It is needed for the growth of new cells, nerve sheath production (myelination) and a whole host of other critical processes.   Homocysteine is a “biggy†for interfering with the whole methylation pathway. High homocysteine speaks to us of poor methylation in a patient. Homocysteine may also be causing damage through oxidative stress (free radical formation). This is the reason I use a good antioxidant with most protocols such as Metagenic’s Oxygenics or Naturpharm’s Super A/O. Many studies have been done on the relationship between homocysteine levels and dementia, and while research does not conclusively prove the relationship, it strongly suggests that homocysteine directly promotes the development of dementia and Alzheimer’s disease. Vitamin B12: Surprising New Findings by: Terri Page 1 of 4 For years, vitamin B12 languished as the vitamin that cures anemia. Hardly any research was done into what this vitamin could do for non-anemic people. It turns out that it may do a lot. New studies show that the right amount of B12 can protect against dementia, boost immune function, maintain nerves, regenerate cells and more. B12 is in the news because it lowers homocysteine and protects against atherosclerosis. It’s also vital for maintaining methylation reactions that repair DNA and prevent cancer. One of the crucial areas for B12 is the brain. It’s not surprising that people with B12 deficiency develop mental disorders. The vitamin is crucial for the synthesis or utilization of important neuro-factors including monoamines, melatonin and serotonin. In addition, B12 is absolutely critical for the function and maintenance of nerves themselves. B12 is needed for methylation reactions that maintain these cells, and enable them to function. For this reason, the methylated form of B12, methylcobalamin, may be superior to other forms of the vitamin. Methylcobalamin is considered “bioactiveâ€, which means that it doesn’t have to undergo any chemical reactions in the body before it starts working. B12 contributes to brain function by lowering homocysteine. Homocysteine is a toxic by-product of methionine metabolism that can damage neurons. Importantly, homocysteine interferes with the methylation reactions critical for brain function. Studies show that people with elevated homocysteine can’t think. I can’t remember B12-deficiency can cause a dementia that looks exactly like Alzheimer’s disease. And Alzheimer’s disease itself is characterized by brain deficiencies of both vitamin B12 and the methylating factor, S-adenosylmethionine (SAMe). A new study from Germany correlates B12 deficiency in Alzheimer’s patients with two personality changes—irritability and disturbed behavior. The connection between B12 deficiency and mental illness has been documented repeatedly. According to the latest research, as much as 30% of hospitalized mental patients may be deficient in the vitamin. And what’s disturbing is that studies repeatedly show that the deficiency is frequently missed by standard blood tests. For example, a recent study from Germany shows that out of 67 hemodialysis patients who were B12-deficient by the measurement of methylmalonic acid (it goes up when B12 goes down), only two of them were deficient by a standard blood test. Looking at the data, one can’t help but wonder how many people with B12 deficiency get treated for mental illness when what they should get is a vitamin! B12 and folate Folate deficiency can also produce mental symptoms, although it is less common. Folate and vitamin B12 are both required for biochemical reactions that occur in the brain. One won’t work without the other: a deficiency in one produces a deficiency in the other. Should a folate deficiency be suspected, both folate and vitamin B12 should be taken. This is because the deficiencies look so similar. If the deficiency is, in fact, B12 instead of folate, folate will appear to correct it in blood cells (where deficiencies are measured). But folate will not correct a B12 deficiency in the brain. Permanent brain damage can result if B12 deficiency is treated with folate. For years, this problem has caused the government to resist supplementing the food supply with significant amounts of folate. Be aware, also, that high amounts of folate in the absence of adequate B12 can provoke or worsen neurological conditions. It’s important to get adequate amounts of both of these vitamins simultaneously. Aging Many studies have been done on the issue of whether B12 deficiency relates to age-related cognitive decline in normal people. Results have been mixed. One of the problems is getting an accurate reading on B12 levels. Blood levels don’t necessarily reflect tissue levels. Another problem is that folate deficiency can complicate the picture. A study in people 65+ found that folate levels significantly correlate with cognitive function, but B12 did not. Another study published at the same time (but using a different kind of evaluation) found that supplemental B12 improves cognition, notably, a person’s ability to remember words. Protect your nerves Methylcobalamin is terrific for protecting neurons. It saves the brain from the damaging effects of glutamate, nitric oxide, low blood sugar and low oxygen. Low oxygen occurs during stroke or heart attack. Low blood sugar is a chronic problem in diabetes. Glutamate and nitric oxide toxicity are features of Alzheimer’s and Parkinson’s diseases. Taking methylcobalamin everyday may provide immediate protection should a person be suddenly injured or have a stroke. Researchers in Japan demonstrated that chronic application of methylcobalamin to neurons protects them, but in order for the vitamin to work, it has to be ready and available before the injury occurs. The supplement-of-choice Vitamin B12 is the only vitamin that is part mineral. The scientific name for B12 is cobalamin. Cobalamin contains cobalt, a mineral that stimulates the production of red blood cells. The most common forms of supplemental B12 are cyanocobalamin or hydroxycobalamin. The natural form of B12 found in food is methylcobalamin (or a similar form, adenosylocobalamin). The structure of B12 is very complex, with numerous methyl groups attached. Methyl groups (CH3) are used in beneficial methylation reactions, such as those that reduce homocysteine. Methylcobalamin is the supplement-of-choice in Japan where it’s approved to treat anemia. This form may have advantages over the cyano form. In a study on sleep patterns, methylcobalamin seemed to work better than cyanocobalamin. And this form is the B12 used in neuron protection studies. Myelin sheath, the “insulation†around nerve cells, is critical for nerve conduction. Degeneration of this protein causes serious neurological diseases. Myelin is created and maintained by methylation reactions that depend on vitamin B12. Recently, researchers in France succeeded in creating for the first time a model of vitamin B12 deficiency in oligodendrocytes, the cells that produce myelin sheath. This will enable the in-depth study of the effects of vitamin B12 on the synthesis of myelin for the first time. Data from this new model could lead to new insight into muscular dystrophy, amyotrophic lateral sclerosis, subacute combined degeneration of the spinal cord, multiple sclerosis and other neuro-degenerative diseases. Methylcobalamin has been used in animal studies on neurodegenerative diseases. The methyl form of vitamin B12 clearly promotes nerve regeneration and slows the progression of neurodegenerative diseases. Neuropathies are strange and sometimes painful sensations caused by degeneration of nerves. Methylcobalamin is effective for this condition. In a study on diabetic rats, methylcobalamin reduced demyelination. In a study on humans undergoing hemodialysis, 500 micrograms of methylcobalamin by injection three times a week, lessened neuropathies. Heart attack and stroke Vitamin B12 has an important role in reducing levels of homocysteine to prevent heart attack and stroke. Homocysteine is a by-product of methionine metabolism that can damage blood vessels. B12 and folate are critical for the production of the tongue-twisting enzyme, methylenetetrahydrofolatereductase, which helps convert homocysteine to methionine. Dozens of studies show that the most common cause of elevated homocysteine is inadequate folate or vitamin B12. Supplementation with these vitamins lowers homocysteine levels, but vitamin B6 and trimethylglycine (TMG) are usually also required to lower homocysteine to a healthy range. Vitamin B12 deficiency has another effect on the heart as well. Turkish researchers recently reported that people with megalobastic anemia have abnormal electrical conductivity of the heart. The problem originates in the nerves that control heart rate. When the anemic volunteers took supplemental B12, heart rate returned to normal. Cancer Methylcobalamin (B12) and Bell's Palsy Bell’s palsy is a temporary paralysis of the facial nerve. A person with Bell’s palsy may not be able to open their eye or close one side of their mouth. Since this condition involves nerves, and vitamin B12 is critical for nerves, the vitamin was tested as a treatment for this nerve condition. Sixty people with Bell’s palsy were divided into three groups. The first group was given standard steroid therapy. The second group was given methylcobalamin plus steroid. The third group was given methylcobalamin alone. It took 2-9 weeks for the drug group to recover. The groups given methylcobalamin recovered much quicker, some within days. The group given methylcobalamin alone recovered the quickest. MA Jalaludin. 1995. Methylcobalamin treatment of Bell’s palsy. Methods Find Exp Clin Pharmacol 17:539-44. Elevated homocysteine is rightfully considered a risk factor for cancer. High levels of homocysteine are consistently linked with DNA damage. The connection was shown recently in a study from Australia where the micro-nucleus index (a measure of DNA damage) increased as levels of homocysteine increased. This held true for both younger (18-32) and older (50-70) people. Fifty-six percent of the men in the older bracket either tested below par for B12 or folate, or abnormally high for homocysteine. Men with homocysteine levels greater than 10 micromoles per liter had significantly more DNA damage than those with lower homocysteine, even if they had normal levels of B12 and folate. Despite no folate deficiency, supplementation with 3.5 times the recommended allowance of folate and B12 still significantly reduced the micronucleus index in people where it was initially elevated above the 50th percentile. (Note: in this study, taking 10 times the recommended amount of folate and B12 did not have any added benefit). One of the implications of this study is that “normal†levels of these vitamins—standard blood levels—are probably not adequate to prevent DNA damage. It also indicates that high homocysteine levels are a red flag that DNA damage is occurring whether or not homocysteine-lowering vitamins are adequate by blood measurements. Men with low, but still “normalâ€, levels of B12 had significantly more damage. According to Dr. Fenech, author of the study, “the accepted standard for vitamin B12 sufficiency (i.e., plasma concentration <150 pmol/L) may not be adequate to minimize chromosome damage rates.†H. Pylori and vitamin B12 deficiency Researchers have discovered a connection between anemia, B12 deficiency, and infection with H. Pylori, the organism that causes stomach ulcers. The study enrolled 138 people with B12 deficiency and anemia. Fifty-six percent of them tested positive for H. Pylori. Many had no symptoms; others had “heartburn†or other stomach problems. When the bacteria were eradicated with antibiotics, vitamin B12 levels returned to normal without supplementation. It took a month for this to occur, and three to six months more for full improvement. In people where the antibiotic treatment didn’t work, anemia and B12 levels didn’t improve. The difference in B12 levels before and after treatment is striking: after treatment, levels were approximately four times higher. H. Pylori may partly explain mysterious studies showing that elderly people are taking in enough B12, but turning up deficient anyway. Older people are prone to atrophic gastritis, a condition where there is not enough acid and pepsin in the stomach to properly digest food. This creates a friendly climate for unfriendly bacteria such as H. Pylori. It also impairs the stomach’s ability to acquire vitamin B12 from food. People with stomach pain or “heartburn†often take antacids, including drugs such as Prolisec or Prevacid. While these types of drugs temporarily ease the pain, they further suppress acid necessary to maintain B12 levels and proper stomach bacteria. If the stomach is infected with H. Pylori or other pathogenic bacteria (overgrowth of bacteria in the small intestine can cause similar symptoms), the answer is to kill the bug, allow the ulcers to heal, then augment (not suppress) stomach acid with supplements designed to maintain acidity and discourage bacterial growth. Oral B12 works Despite what it says on the package insert of injectable B12, oral B12 works. For example, gastrointestinal surgery usually causes B12 depletion and anemia. Japanese researchers used 500-1500 mcg/day of oral B12 to treat B12 deficiency after total gastrectomy. This amount reversed the deficiency quickly and efficiently. B12 blood levels of patients receiving 750+mcg were comparable to patients receiving 500 mcg by injection every two months. Japan has long recognized the benefits of using the methylated form of B12, methylcobalamin. Despite strong evidence that oral B12 is effective, physicians are slow to recommend this form to their patients. A study published in 1998 reports that 71% of the internists surveyed don’t believe that oral B12 works as well as injections. Widespread deficiency A new study from Tufts University reports that B12 supplements are the most important source of vitamin B12 for Americans. Those taking supplements or eating cereal supplemented with B12, are half as likely to be B12 deficient than those who don’t. Meat, the primary source of B12 for Americans, is not as good a source. This is probably due to problems in digestion and prescription drugs that interfere with the absorption of B12 when it’s attached to proteins such as meat. Cooking may also affect the vitamin B12 content of meat. B12 deficiency has gotten so bad in America that the RDA has been increased from 2.0 micrograms a day to 2.4. It’s not only older people who are deficient these days. The Tufts study looked at the children of people who took part in the original Framingham heart study. They were stunned to see that in one generation, B12 deficiency in kids had caught up to the generation before. Pizza, one of the foods evaluated, is apparently not a good source of vitamin B12. Although the body needs minute amounts of vitamin B12, Americans are not getting enough for general health, let alone optimal DNA and heart protection. H. Pylori infection, drugs, over-cooking meat, increased demand and other factors may be robbing us of this highly crucial vitamin. The mistaken belief that B12 has to be given by injection may be keeping people from getting the extra B12 they need. High amounts of the vitamin are not toxic; and may in fact be more beneficial than we currently know. Evidence is stacking up that amounts of vitamin B12 above and beyond the current recommended daily allowance may help protect nerves and protect us from cancer, infections and a host of other adverse conditions. Methylcobalamin (B12) and immunity Methylcobalamin enhances the activity of natural killer and T-cells. These immune cells are important for killing cancer and viruses. Japanese researchers have discovered that ratio of T-helper cells to T-suppressor cells is abnormal in people with anemia. Methylcobalamin corrects this defect. Vegans with B12 deficiency have lowered numbers of immune cells. People infected with HIV are more likely to get AIDS if their B12 levels are low, irrespective of whether they take antiviral drugs. Methylcobalamin is required for both the synthesis and function of immune cells. In a study on people with low tissue levels of B12, methionine synthetase activity was very low, indicating that very few immune cells were being synthesized. Treatment with methylcobalamin restored immunity almost immediately. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted April 14, 2005 Report Share Posted April 14, 2005 I have known about excessive Nitric Oxide theory for some time however my Doc #2 who deals exclucively with FMS says that it is a lack of NO that causes FMS. This puzzles me. Why such a completely opposite approach to the same illness. One thing I finally figured out is that I cannot take the Teitlebaum's formula for fatigue. It is a powder with umpteen supplements.. My understanding is that the formula is designed in part to increase Nitric Oxide ( that is what I understood him to say). For a long time I have had overwhelming fatigue in the after noon. I arise and begin taking meds and supplements late in the day. Mid afternoon I would get shakey, sweaty and utterly exhausted which would lead to my resting for most of the rest of the day. I would have 3-4 hours of activity-max. Finally I made the connection that it might be the supplement. I stopped taking it and now I don't have this spell - felt like adrenal fatigue. I don't know if it is the whey ( I am allergic to dairy) or now I am wondering if it was the increased NO. B 12 definitely gives me a boost as well. Marie --- Colourbleu <colourbleu@...> wrote: > http://www.autisme-montreal.com/congres/2003/Neubrander.html > > " > Cobalamin/ " B12 " deficiency leads to three problems. > First, when > adenosylcobalamin coenzyme is deficient, the > substrate methylmalonic > acid cannot be converted into succinic acid. > Therefore levels of > methylmalonic acid with continue to increase and > spill over into the > urine, a phenomenon known as methylmalonic aciduria. > Second, when the > methylcobalamin coenzyme is deficient, the substrate > homocysteine > cannot be converted to methionine. Therefore levels > of homocysteine > will continue to increase and may be seen in the > blood or urine > resulting in homocystinemia and homocystinuria > respectively. Third, a > phenomenon known as " folate trapping " occurs when > hydroxycobalamin is > deficient in the presence of adequate > methyl-tetrahydrofolate. When > this situation occurs, the methyl group on > methyl-tetrahydrofolate is > trapped because " it wants to leave (to become > tetrahydrofolate) but > can’t get away " > > B12 - rationale for using vitamin B12 > > > 5th November 2003 > > Over the last 22 years of treating over 3,000 > patients with chronic > fatigue syndrome, I have developed a programme of > treatment which I > believe all patients must do as the foundation > before proceeding to > other treatments. Vitamin B12 by injection I see > as an integral part > of this programme and it is effective for many, > regardless of the > cause of their chronic fatigue syndrome. > > Those patients who respond to B12 are not > obviously deficient in B12, > indeed blood tests usually show normal levels. The > " normal " levels of > B12 have been set at those levels necessary to > prevent pernicious > anaemia - this may not be the same as those levels > for optimal > biochemical function. B12 has a great many other > functions as well as > the prevention of pernicious anaemia. However, > what is interesting is > how B12 is beneficial in so many patients with > fatigue, regardless of > the cause of their CFS, and suggests that there is > a common mechanism > of chronic fatigue which B12 is effective at > alleviating. > > General mechanism by which B12 relieves the > symptoms of CFS > Professor Pall has looked at the > biochemical abnormalities in > CFS and shown that sufferers have high levels of > nitric oxide and its > oxidant product peroxynitrite. These substances > may be directly > responsible for many of the symptoms of CFS and > are released in > response to stress, whether that is infectious > stress, chemical > stress or whatever. B12 is important because it is > the most powerful > scavenger of nitric oxide and will therefore > reduce the symptoms of > CFS regardless of the cause.(1, 2, 3, 4, 5, 6) > > Nitric oxide is known to have a detrimental effect > on brain function > and pain sensitivity. Levels are greatly increased > by exposure to > chemicals such as organophosphates and organic > solvents(7). When > sensitive tests of B12 were applied (serum > methylmalonic acid and > homocysteine) before and after B12 therapy, the > following symptoms > were noted to be caused by subclinical B12 > deficiency: parasthesia, > ataxia, muscle weakness, hallucinations, > personality and mood > changes, fatigue, sore tongue and diarrhoea.(8) > > B12 in fatigue syndromes > The " foggy brain " with difficulty thinking > clearly, poor short term > memory and multitasking are often much improved by > B12.(9, 10, 11). > Mood and personality changes, so often a feature > of patients with > chemical poisoning, can be improved by B12(12). > The physical fatigue > and well being are often both improved. > > A study > Twenty eight subjects suffering from non-specific > fatigue were > evaluated in a double-blind crossover trial of 5 > mg of > hydroxocobalamin twice weekly for 2 weeks, > followed by a 2-week rest > period, and then a similar treatment with a > matching placebo. The > placebo group in the first 2 weeks had a > favourable response to the > hydroxocobalamin during the second 2 week period > with respect to > enhanced general well being. Subjects who received > hydroxocobalamin > in the first 2-week period showed no difference > between responses to > the active and placebo treatments, which suggests > that the effect of > vitamin B12 lasted for over 4 weeks. It is noted > there was no direct > correlation between serum vitamin B12 > concentrations and improvement. > Whatever the mechanism, the improvement after > hydroxocobalamin may be > sustained for 4 weeks after stopping the > medication. " A Pilot Study > of Vitamin B12 in the Treatment of Tiredness, " > Ellis, F.R., and > Nasser, S., British Journal of Nutrition, > 1973;30:277-283. > > Practical Details > Vitamin B12 has no known toxicity and B12 surplus > to requirement is > simply passed out in the urine (which may > discolour pink). It is > theoretically possible to be allergic to B12, but > in the thousands of > injections that I have sanctioned this has only > ever occurred after > several injections and causes local itching, > redness and swelling > (although the commonest cause of redness and > swelling is poor > injection technique). It does not seem to matter > whether > hydroxocobalamin or cyanocobalamin is used. I > usually start with 2mgs > weekly by i.m. injection, then adjust the > frequency according to > response - some patients will respond straight > away, some need > several doses before they see improvement. I would > do at least 10 > injections before giving up. Many of my patients > learn to inject > themselves - this means they can be independent of > their doctors. The > cost is & #65443;1.60 per injection (2ml B12 plus > syringe and needle). > > (1) Pall ML. Elevated, sustained peroxynitrite > level as the cause of > chronic fatigue syndrome. Medical Hypotheses > 2000;54:115-125. Pall > ML. Elevated peroxynitrite as the cause of chronic > fatigue syndrome: > Other inducers and mechanisms of symptom > generation. Journal of > Chronic Fatigue Syndrome 2000;7(4):45-58. > > (2) Pall ML. Cobalamin used in chronic fatigue > syndrome therapy is a > nitric oxide scavenger. Journal of Chronic Fatigue > Syndrome, 2001;8 > (2):39-44. > > (3) Pall ML, Satterlee JD. Elevated nitric > oxide/peroxynitrite > mechanism for the common etiology of multiple > chemical sensitivity, > chronic fatigue syndrome and posttraumatic stress > disorder. ls of > the New York Academy of Science 2001;933:323-329. > > (4) Pall ML. Common etiology of posttraumatic > stress disorder, > fibromyalgia, chronic fatigue syndrome and > multiple === message truncated === __________________________________________________ Quote Link to comment Share on other sites More sharing options...
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