Vitamin B12

Names: Vitamin B12, cobalamin, cyanocobalamin, methylcobalamin
Wikipedia entry:

Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins. It is normally involved in the metabolism of every cell of the human body, especially affecting DNA synthesis and regulation, but also fatty acid synthesis and energy production. As the largest and most structurally complicated vitamin, it can be produced industrially only through bacterial fermentation-synthesis.

Vitamin B12 consists of a class of chemically-related compounds (vitamers), all of which have vitamin activity. It contains the biochemically rare element cobalt. Biosynthesis of the basic structure of the vitamin in nature is only accomplished by simple organisms such as some bacteria and algae, but conversion between different forms of the vitamin can be accomplished in the human body. A common synthetic form of the vitamin, cyanocobalamin, does not occur in nature, but is used in many pharmaceuticals and supplements, and as a food additive, because of its stability and lower cost. In the body it is converted to the physiological forms, methylcobalamin and adenosylcobalamin, leaving behind the cyanide, albeit in minimal concentration. More recently, hydroxocobalamin (a form produced by bacteria), methylcobalamin, and adenosylcobalamin can also be found in more expensive pharmacological products and food supplements. The utility of these is presently debated...
http://en.wikipedia.org/wiki/Vitamin_b12

Dr. Ray Shahelien entry:

Vitamin B12 May Reduce Risk of Alzheimer's Disease

ScienceDaily (Oct. 18, 2010) — A new study shows that vitamin B12 may protect against Alzheimer's disease, adding more evidence to the scientific debate about whether the vitamin is effective in reducing the risk of memory loss... The study found that for each micromolar increase in the concentration of homocysteine, the risk of Alzheimer's disease increased by 16 percent, whereas each picomolar increase in concentration of the active form of vitamin B12 reduced risk by two percent. The results stayed the same after taking into account other factors, such as age, gender, education, smoking status, blood pressure and body mass index. The addition of folate did not appear to raise or lower the risk of Alzheimer's disease...
http://www.sciencedaily.com/releases/2010/10/101018162922.htm

B-Vitamin Deficiency May Cause Vascular Cognitive Impairment

ScienceDaily (Sep. 2, 2008) — A deficiency of B-vitamins may cause vascular cognitive impairment, according to a new study. Researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University used an experimental model to examine the metabolic, cognitive, and microvascular effects of dietary B-vitamin deficiency. "Metabolic impairments induced by a diet deficient in three B-vitamins -folate, B12 and B6- caused cognitive dysfunction and reductions in brain capillary length and density in our mouse model," says Aron Troen, PhD, the study's lead author. "The vascular changes occurred in the absence of neurotoxic or degenerative changes."...
http://www.sciencedaily.com/releases/2008/09/080902095110.htm

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice
Aron M. Troen*, Melissa Shea-Budgell, Barbara Shukitt-Hale, Donald E. Smith, Jacob Selhub, and Irwin H. Rosenberg
Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111-1524
Communicated by Leon E. Rosenberg, Princeton University, Princeton, NJ, June 5, 2008 (received for review July 20, 2007)

Abstract

In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease, and Alzheimer's disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic, or vascular processes. We report here that feeding male C57BL6/J mice a B-vitamin-deficient diet for 10 weeks induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies (r = −0.757, P < 0.001), and with plasma total homocysteine (r = −0.631, P = 0.007). Feeding mice a methionine-rich diet produced similar but less pronounced effects. Our findings suggest that cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration. Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline...
http://www.pnas.org/content/105/34/12474

"Could It Be B12?: An Epidemic of Misdiagnoses"
by Sally M. Pacholok RN and Jeffrey J. Stuart DO

I am an MD, a nutritional physician, and a psychiatrist (Canadian-board-certified) who has been studying vitamin B12 extensively since 1976, and applying that knowledge in my private nutritional, metabolic and psychiatric practice in Tucson AZ since 1994 (and Portsmouth VA before that).

This book is an outstanding compilation of anecdotes, references and experiences on the "underground devastator" of our society. The reason why this is not common knowledge in the medical profession in the US is because the laboratory "normal range" is way too low. In Japan the range is 2.5 times higher at its low end - and Japan has very little "Alzheimer's Dementia", and less depression and bipolar disorders, than we do in the US.

In the 26 years that I have been investigating B12, memory disorders and depressive/ bipolar illnesses, NO patient who came to me with a memory problem (early Alzheimer's) has gone on to Alzheimer's dementia, and I have a near-perfect track record in helping people overcome depression and bipolar disorders. These outcomes are largely due to my permanent optimization of every patient's serum B12 level.

Congratulations to Ms Sally Pacholok RN on an outstanding recording of most of the important facts and treatments for this serious condition. I believe it to be the best book out there for a combination of both medical and lay readers on this condition.

[To anyone reading this review: Please do not simply go and buy B12 tablets or lozenges and start taking them, before getting an accurate serum level measured.]

John V Dommisse MD, MBChB, FRCP(C)
Tucson, AZ, USA

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Protective effects of a vitamin B12 analogue, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons
Akaike A Tamura Y Sato Y Yokota T,
Eur J Pharmacol (1993 Sep 7) 241(1):1-6

The effects of methylcobalamin, a vitamin B12 analogue, on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Cell viability was markedly reduced by a brief exposure to glutamate followed by incubation with glutamate-free medium for 1 h. Glutamate cytotoxicity was prevented when the cultures were maintained in methylcobalamin-containing medium. Glutamate cytotoxicity was also prevented by chronic exposure to S-adenosylmethionine, which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and S- adenosylmethionine also inhibited the cytotoxicity induced by methyl-D-aspartate or sodium nitroprusside that releases nitric oxide. In cultures maintained in a standard medium, glutamate cytotoxicity was not affected by adding methylcobalamin to the glutamate-containing medium. In contrast, acute exposure to MK-801, a NMDA receptor antagonist, prevented glutamate cytotoxicity. These results indicate that chronic exposure to methylcobalamin protects cortical neurons against NMDA receptor-mediated glutamate cytotoxicity.

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Methylcobalamin and Diabetic Neuropathy

Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy
Ide H Fujiya S Asanuma Y Tsuji M Sakai H Agishi Y, Clin Ther (1987) 9(2):183-92

Seven men and four women with symptomatic diabetic neuropathy were treated with methylcobalamin (2,500 micrograms in 10 ml of saline) injected intrathecally. Treatment was begun when patients had good metabolic control, as determined by measurements of plasma glucose and hemoglobin, and was repeated several times with a one-month interval between injections. Three patients were re-treated one year after the last intrathecal injection. Symptoms in the legs, such as paresthesia, burning pains, and heaviness, dramatically improved. The effect appeared within a few hours to one week and lasted from several months to four years. The mean peroneal motor-nerve conduction velocity did not change significantly. The mean (+/- SD) concentration of methylcobalamin in spinal fluid was 114 +/- 32 pg/ml before intrathecal injection (n = 5) and 4,752 +/- 2,504 pg/ml one month after intrathecal methylcobalamin treatment (n = 11). Methylcobalamin caused no side effects with respect to subjective symptoms or characteristics of spinal fluid. These findings suggest that a high concentration of methylcobalamin in spinal fluid is highly effective and safe for treating the symptoms of diabetic neuropathy.

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Nerve Regeneration with Methylcobalamin

Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy.
Watanabe T Kaji R Oka N Bara W Kimura J, J Neurol Sci (1994 Apr) 122(2):140-3

Despite intensive searches for therapeutic agents, few substances have been convincingly shown to enhance nerve regeneration in patients with peripheral neuropathies. Recent biochemical evidence suggests that an ultra-high dose of methylcobalamin (methyl-B12) may up-regulate gene transcription and thereby protein synthesis. We examined the effects of ultra-high dose of methyl-B12 on the rate of nerve regeneration in rats with acrylamide neuropathy, using the amplitudes of compound muscle action potentials (CMAPs) after tibial nerve stimulation as an index of the number of regenerating motor fibers. After intoxication with acrylamide, all the rats showed equally decreased CMAP amplitudes. The animals were then divided into 3 groups; rats treated with ultra-high (500 micrograms/kg body weight, intraperitoneally) and low (50 micrograms/kg) doses of methyl- B12, and saline-treated control rats. Those treated with ultra-high dose showed significantly faster CMAP recovery than saline-treated control rats, whereas the low-dose group showed no difference from the control. Morphometric analysis revealed a similar difference in fiber density between these groups. Ultra-high doses of methyl-B12 may be of clinical use for patients with peripheral neuropathies.

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Methylcobalamin, Bell's Palsy

Methylcobalamin treatment of Bell's Palsy
Jalaludin MA, Methods Find Exp Clin Pharmacol (1995 Oct) 17(8):539-44

Bell's palsy patients were assigned into three treatment groups: steroid (group 1), methylcobalamin (group 2) and methylcobalamin + steroid (group 3). Comparison between the three groups was based on the number of days needed to attain full recovery, facial nerve scores, and improvement of concomitant symptoms. The time required for complete recovery of facial nerve function was significantly shorter in the methylcobalamin and methylcobalamin plus steroid groups than in the steroid group. The facial nerve score after 1-3 weeks of treatment was significantly more severe (p < 0.001) in the steroid group compared to the methylcobalamin and methylcobalamin plus steroid groups. The improvement of concomitant symptoms was better in the methylcobalamin treated groups than the group treated with steroid alone.

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Nerve Terminal Regeneration

Methylcobalamin (methyl-B12) promotes regeneration of motor nerve terminals degenerating in anterior gracile muscle of gracile axonal dystrophy (GAD) mutant mouse.
Yamazaki K Oda K Endo C Kikuchi T Wakabayashi T, Neurosci Lett (1994 Mar 28) 170(1):195-7

We examined the effects of methylcobalamin (methyl-B12, mecobalamin) on degeneration of motor nerve terminals in the anterior gracile muscle of gracile axonal dystrophy (GAD) mutant mice. GAD mice received orally methyl-B12 (1 mg/kg body wt/day) from the 40th day after birth for 25 days. In the distal endplate zone of the muscle, although most terminals were degenerated in both the untreated and methyl-B12-treated GAD mice, sprouts were more frequently observed in the latter. In the proximal endplate zone, where few degenerated terminals were seen in both groups of the mice, the perimeter of the terminals was increased and the area of the terminals was decreased significantly in the methyl-B12-treated GAD mice. These findings indicate that methyl-B12 promotes regeneration of degenerating nerve terminals in GAD mice.

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Fighting Neurotoxicity

Protective effects of methylcobalamin, a vitamin B12 analogue, against glutamate-induced neurotoxicity in retinal cell culture.
Kikuchi M Kashii S Honda Y Tamura Y Kaneda K Akaike, Invest Ophthalmol Vis
Sci (1997 Apr) 38(5):848-54

Purpose: To examine the effects of methylcobalamin on glutamate- induced neurotoxicity in the cultured retinal neurons. Methods: Primary cultures obtained from the fetal rat retina (gestation days 16 to 19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method. Results: Glutamate neurotoxicity was prevented by chronic exposure to methylcobalamin and S-adenosylmethionine (SAMe), which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and SAMe also inhibited the neurotoxicity induced by sodium nitroprusside that release nitric oxide. By contrast, acute exposure to methylcobalamin did not protect retinal neurons against glutamate neurotoxicity. Conclusions: Chronic administration of methylcobalamin protects cultured retinal neurons against N-methyl-D- aspartate-receptor-mediated glutamate neurotoxicity, probably by altering the membrane properties through SAMe-mediated methylation.

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Methyl Donor Effects

Effect of cobalamin derivatives on in vitro enzymatic DNA methylation: methylcobalamin can act as a methyl donor.
Leszkowicz A Keith G Dirheimer G, Biochemistry (1991 Aug 13) 30(32):8045-51

Methylcytosine synthesis in DNA involves the transfer of methyl groups from S-adenosylmethionine to the 5'-position of cytosine through the action of DNA (cytosine-5)-methyltransferase. The rate of this reaction has been found to be enhanced by cobalt ions. We therefore analyzed the influence of vitamin B12 and related compounds containing cobalt on DNA methylation. Vitamin B12, methylcobalamin, and coenzyme B12 (methylcobalamin) were found to enhance significantly the de novo DNA methylation in the presence of S-adenosylmethionine for concentrations up to 1 microM, but at higher concentrations these compounds were found to inhibit DNA methylation. Methylcobalamin behaves as a competitive inhibitor of the enzymatic methylation reaction (Ki = 15 microM), the Km for S-adenosylmethionine being 8 microM. In addition, the use of radioactive methylcobalamin shows that it can be used as a methyl donor in the de novo and maintenance DNA methylation reactions. Thus, two DNA methylation pathways could exist: one involving methylation from S-adenosylmethionine and a second one involving methylation from methylcobalamin.