Vitamin B12 Abstracts 10

©

Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin
            (Bauman et al., 2000)  Download
OBJECTIVE: Of patients who are prescribed metformin, 10-30% have evidence of reduced vitamin B12 absorption. B12-intrinsic factor complex uptake by ileal cell surface receptors is known to be a process dependent on calcium availability Metformin affects calcium-dependent membrane action. The objective of this study was to determine the magnitude and mechanism of the reduction in serum vitamin B12 after metformin administration. RESEARCH DESIGN AND METHODS: A comparative study design was employed using 2 groups (metformin and control). A total of 21 patients with type 2 diabetes received sulfonylurea therapy; 14 of these 21 patients were switched to metformin. Monthly serum total vitamin B12 measurements and holotranscobalamin (holoTCII) (B12-TCII) were performed. After 3 months of metformin therapy, oral calcium supplementation was administered. RESULTS: Serial serum vitamin B12 determinations revealed a similar decline in vitamin B12 and holoTCII. Oral calcium supplementation reversed the metformin-induced serum holoTCII depression. CONCLUSIONS: Patients receiving metformin have diminished B12 absorption and low serum total vitamin B12 and TCII-B12 levels because of a calcium-dependent ileal membrane antagonism, an effect reversed with supplemental calcium.

Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gastritis.
            (Carmel et al., 2001)  Download
OBJECTIVES:  Food-cobalamin malabsorption is common in patients with low cobalamin levels. However, characterization of affected subjects has been limited. The aim of this study was to analyze demographic and gastric data in a large study population. METHODS:  Data were collected prospectively in 202 subjects (43 volunteers and 159 patients) who underwent the egg yolk-cobalamin absorption test (EYCAT). H. pylori status was determined in 167 of the subjects, serum gastrin and antiparietal cell antibody in 158 and pepsinogen (PG) I and PG II levels in 133. RESULTS:  Latin American and black patients had lower EYCAT results than did white or Asian-American ones (p = 0.0001) and had severe food-cobalamin malabsorption (EYCAT < 1%) more often (p = 0.0001). Age correlated inversely with EYCAT results (p = 0.02). H. pylori infection was associated with food-cobalamin malabsorption (p = 0.0001), especially with severe malabsorption where 29/37 subjects (78.4%) were infected. Malabsorption was also associated with higher gastrin levels (p = 0.0001) and lower PG I levels (p = 0.01) and PG I:PG II ratios (p = 0.0001). Multivariate analysis showed that ethnic origin, gastrin levels, H. pylori infection and, to a lesser extent, age were independently associated with the EYCAT results. CONCLUSIONS:  Latin American and black patients have food-cobalamin malabsorption more often than do white and Asian-American patients. This association is independent of the malabsorption's association with H. pylori infection, markers of gastritis, such as gastrin, and older age. The patterns of gastric tests suggest that malabsorption may be due to diverse mechanisms, not just atrophic gastritis. The possible role of H. pylori infection in many cases of severe food-cobalamin malabsorption also suggests avenues of treatment and prevention.

Vitamin B12 deficiency in untreated celiac disease.
            (Dahele and Ghosh, 2001)  Download
OBJECTIVES:  Iron and folate malabsorption are common in untreated celiac disease as the proximal small intestine is predominantly affected. Vitamin B12 deficiency is thought to be uncommon, as the terminal ileum is relatively spared. This study aims to investigate the prevalence of vitamin B12, deficiency in patients with untreated celiac disease. METHODS:  Prospective study of 39 consecutive biopsy-proven celiac disease patients (32 women, seven men; median age 48 yr, range 22-77 yr) between September 1997 and February 1999. The full blood count, serum vitamin B12, red blood cell folate, and celiac autoantibodies (IgA antigliadin and IgA antiendomysium antibodies) were measured before and after a median of 4 months (range 2-13 months) of treatment with a gluten-free diet. In vitamin B12-deficient patients, intrinsic factor antibodies and a Schilling test, part 1, were performed. RESULTS:  A total of 16 (41%) patients were vitamin B12 deficient (<220 ng/L) and 16 (41%) patients (11 women and live men) were anemic. Concomitant folate deficiency was present in only 5/16 (31%) of the vitamin B12 patients. The Schilling test, performed in 10 of the vitamin B12-deficient patients, showed five low and five normal results. Although only five patients received parenteral vitamin B12, at follow-up the vitamin B12 results had normalized in all patients. Acral paraesthesia at presentation in three vitamin B12-deficient patients resolved after vitamin B12 replacement. CONCLUSIONS:  Vitamin B12 deficiency is common in untreated celiac disease, and concentrations should be measured routinely before hematinic replacement. Vitamin B12 concentrations normalize on a gluten-free diet alone, but symptomatic patients may require supplementation.


 

Clinical and laboratory features and sequelae of deficiency of folic acid (folate) and vitamin B12 (cobalamin) in pregnancy and gynecology.
            (Frenkel and Yardley, 2000)   Download
Classically, deficiency of folic acid (folate) or vitamin B12 (cobalamin) was recognized by the presence of a macrocytic anemia resulting from megaloblastic changes in the bone marrow. A markedly changing paradigm has identified both new mechanisms for altered folate and cobalamin status and new sequelae and clinical interrelationships that include altered mechanisms of absorption, a changing pattern of neurologic deficits, an increased risk of vascular occlusive lesions, and an important relationship with the mechanisms of neoplastic transformation. Several of these newer characterizations relate to issues of neoplasia in the nonpregnant woman and to issues in pregnancy, such as the potential for developmental abnormalities of the fetal nervous system.

Sleep-wake schedule disorders.
            (Kastner et al., 1995)   Download
Comment on Sadeh 1995 Case study: sleep and aggressive behavior in a blind, retarded adolescent. A concomitant schedule disorder? [J Am Acad Child Adolesc Psychiatry. 1995] PMID: 7608057. We disagree with the diagnosis of concomitant schedule disorder. Based upon our review of the data contained within article, we feel that the patient more likely suffers from an affective illness (presumably rapid-cycling bipolar disorder) and would respond well to appropriate treatment.

 [Clinical efficacy of mecobalamin in the treatment of oligozoospermia--results of double-blind comparative clinical study].
            (Kumamoto et al., 1988)  Download
The clinical efficacy of mecobalamin in the treatment of male infertility was investigated by means of a multicenter collaborative study with 25 participating institutions. The study was carried out as a double-blind, comparative trial using three administration groups: 6,000 micrograms of mecobalamin per day, 1,500 micrograms of mecobalamin per day and a placebo group for 12 wk. The following results were obtained. 1. The total number of evaluated subjects was 375, consisting of 125 in the 6,000 micrograms/day mecobalamin group, 124 in the 1,500 micrograms/day mecobalamin group and 126 in the placebo group. There were no significant differences among the three administration groups in terms of the patient's background factors. 2. When all of the patients were analyzed, there were no statistically significant differences among the three administration groups in terms of the efficacy in relation to the sperm count or the motility rate. 3. However, it was decided to perform a more detailed analysis of the therapeutic efficacy in patients whose pretreatment sperm counts were 20 x 10(6)/ml or less. The reasons for this decision were two-fold: 1) There was a large degree of fluctuation in patients whose pretreatment sperm counts showed a mean value of more than 20 x 10(6)/ml for two or more determinations, and it was surmised that this fluctuation might have masked any therapeutic effect in those cases. 2) The WHO definition of oligozoospermia was recently decided as a sperm count of 20 x 10(6)/ml or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis.
            (Lindenbaum et al., 1988)  Download
Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; longstanding neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.

Vitamin B12 absorption in cystic fibrosis.
            (Lindemans et al., 1984)  Download
Vitamin B12 absorption was measured in 30 patients with cystic fibrosis by means of the urinary excretion method and found to be impaired, i.e. less than 10%, in 25. The mean urinary excretion amounted to 4.7 +/- 0.8%. In all patients vitamin B12 absorption improved by the addition of trypsin (18.9 +/- 2.1%). Addition of the vitamin B12 analogue cobinamide, which prevents vitamin B12-binding by R-binders, raised the vitamin B12 absorption to 15.0 +/- 2.2%. A further improvement was obtained by the simultaneous addition of cobinamide and trypsin, 18.2 +/- 2.6%, the same value as with trypsin alone. Assuming that cobinamide addition was effective in suppressing all R-binder activity, the additional effect of trypsin suggests a second, stimulatory function of trypsin on vitamin B12 absorption, separate from R-binder-inactivation. In 5 patients only marginal improvement of vitamin B12 absorption was gained by the addition of either trypsin or cobinamide. The deficient serum vitamin B12 (110 pmol/l) in one of them indicates that the normal pancreas-substitution therapy not always implies sufficient restoration of vitamin B12 absorption.

Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis.
            (Lindenbaum et al., 1988) Download
Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; longstanding neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.

Vitamin B12 and hepatitis C: molecular biology and human pathology.
            (Lott et al., 2001)  Download
Cobalamins are stored in high concentrations in the human liver and thus are available to participate in the regulation of hepatotropic virus functions. We show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent manner without significantly affecting the cap-dependent mechanism. Vitamin B12 failed to inhibit translation by IRES elements from encephalomyocarditis virus (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship between the total cobalamin concentration in human sera and HCV viral load (a measure of viral replication in the host). The mean viral load was two orders of magnitude greater when the serum cobalamin concentration was above 200 pM (P < 0.003), suggesting that the total cobalamin concentration in an HCV-infected liver is biologically significant in HCV replication.

The association between antiulcer medication and initiation of cobalamin replacement in older persons.
            (Mitchell and Rockwood, 2001)  Download
As chronic use of antiulcer medications might predispose older persons to cobalamin deficiency, we studied participants (> 65 years) in the clinical examination of the Canadian Study of Health and Aging to test the association between the use of an antiulcer medication (histamine-2 blocker or proton pump inhibitor) at baseline with initiation of cobalamin replacement during the 5 year follow-up period. Of 1054 eligible subjects, 125 (11.7%) were taking an antiulcer medication at baseline. At follow-up, 49 (4.6%) had started cobalamin replacement. Antiulcer medication use at baseline was significantly associated with the initiation of cobalamin therapy (odds ratio 2.56, 95% confidence interval 1.30-5.05), even after adjusting for age, gender and institutional residence (odds ratio 2.61, 95% confidence interval 1.31-5.23). There is an independent association between the use of antiulcer medication and initiation of cobalamin therapy. While the relationship is not unambiguously causal, this finding underscores the need for judicious prescribing of antiulcer medications for older persons.

Treatment of cobalamin deficiency in dementia, evaluated clinically and with cerebral blood flow measurements.
            (Nilsson et al., 2000)  Download
We investigated the relation between cobalamin deficiency, clinical changes and brain function in dementia patients. On admittance to the clinic, 24 patients had cobalamin deficiency, and dementia with additional symptoms of delirium. During cobalamin supplementation, the patients underwent repeated regional cerebral blood flow (rCBF) studies, psychiatric evaluations, and in some cases assessment with MMSE and the Organic Brain Syndrome scale. Fifteen patients who showed mild to moderate dementia improved clinically, and also showed a concomitant increase in their general CBF after treatment. In contrast, 9 patients who were severely demented showed no obvious clinical improvement, and no general blood flow change, although some regional flow increases were seen in sensory motor areas. We conclude that symptoms which probably indicated superimposed delirium such as clouding of consciousness, disorientation and clinical fluctuation, responded to the vitamin B12 supplementation, while the underlying dementia condition remained basically unchanged. The clinical improvement was also mirrored in general and focal rCBF changes.


Vitamin B12 treatment for sleep-wake rhythm disorders.
            (Okawa et al., 1990)  Download
Vitamin B12 (VB12) was administered to two patients suffering for many years from different sleep-wake rhythm disorders. One patient was a 15-year-old blind girl suffering from a free-running sleep-wake rhythm (hypernychthemeral syndrome) with a period of about 25 h. In spite of repeated trials to entrain her sleep-wake cycle to the environmental 24-h rhythm, her free-running rhythm persisted for about 13 years. When she was 14 years old, administration of VB12 per os was started at the daily dose of 1.5 mg t.i.d. Shortly thereafter, her sleep-wake rhythm was entrained to the environmental 24-h rhythm, and her 24-h sleep-wake rhythm was maintained while she was on the medication. Within 2 months of the withholding of VB12, her free-running sleep-wake rhythm reappeared. The VB12 level in the serum was within the normal range both before and after treatment. The other patient was a 55-year-old man suffering from delayed sleep phase syndrome since 18 years of age. After administration of VB12 at the daily doses of 1.5 mg, his sleep-wake rhythm disorder was improved. The good therapeutic effect lasted for more than 6 months while he was on the medication.

Localized folate and vitamin B-12 deficiency in squamous cell lung cancer is associated with global DNA hypomethylation.
            (Piyathilake et al., 2000)  Download
We measured the concentrations of folate and vitamin B-12 in paired tissue samples of squamous cell cancer (SCC) and adjacent grossly normal-appearing uninvolved bronchial mucosa (from which SCC developed and also "at risk" of developing SCC) of the lung in 12 subjects to determine the involvement of these vitamins in 1) lung carcinogenesis and 2) global DNA methylation. The folate concentrations were significantly lower in SCCs than in uninvolved tissues (p = 0.03). The vitamin B-12 concentrations were also significantly lower in SCCs than in uninvolved tissues (p = 0.02). The radiolabeled methyl incorporation (inversely related to the degree of in vivo DNA methylation) was significantly higher in SCCs than in uninvolved tissues (p < 0.0001). The correlation between folate and radiolabeled methyl incorporation was inverse and statistically significant in SCCs (p = 0.03). The correlation between vitamin B-12 and radiolabeled methyl incorporation also was inverse and statistically significant in SCCs (p = 0.009). The relationship between tissue vitamin B-12 and DNA methylation was minimal in uninvolved tissues. The relationship between folate and DNA methylation, however, was inverse in uninvolved tissues. In the multiple regression models that included both vitamins, only folate was inversely associated with radiolabeled methyl incorporation in uninvolved and cancerous tissues. These results suggested that folate might be the limiting vitamin for proper DNA methylation in SCC as well as in tissues at risk of developing SCC. Several possible mechanisms of folate deficiency, including inactivation of the vitamin by exposure to carcinogens of cigarette smoke and underexpression or absence of folate receptor in SCCs and associated premalignant lesions, are discussed in light of these findings.

Investigation and treatment of facial paralysis.
            (Riordan, 2001)  Download
In summary, patients presenting with acute lower motor neurone facial paralysis require a thorough physical examnation. Full neurological examination, otoscopy, and blood pressure measurement are mandatory. In the absence of any abnormal symptoms or signs, further investigation is unnecessary. To date there is no clear evidence that any form of treatment improves outcome of idiopathic facial palsy in children. Ninety five per cent of children will recover full function, most within the first three weeks of the illness. Protection of the cornea, with artificial tears and overnight patching, is normally all that is required. Follow up is advisable. Neurophysiological assessment is helpful in patients with weakness persisting beyond three weeks. In an open, randomised trial, patients treated with vitamin B12, alone or in combination with steroids, recovered faster than those treated with steroids alone. Jalaludin MA. Methylcobalamin treatment of Bell’s palsy.

Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss.
            (Shemesh et al., 1993) Download
INTRODUCTION:  This study examines the incidence of vitamin B12 deficiency in three groups of noise-exposed subjects: patients with chronic tinnitus and noise-induced hearing loss (NIHL), patients with NIHL only, and subjects demonstrating normal hearing. MATERIALS AND METHODS:  A group of 113 army personnel exposed to military noise was studied. The mean age was 39 years. Chronic tinnitus and NIHL existed in 57 subjects. NIHL alone was observed in 29 subjects, and 27 subjects had normal audiograms. All subjects were queried about noise exposure and dietary habits. Vitamin B12 serum levels were measured. RESULTS:  Patients with tinnitus and NIHL exhibited vitamin B12 deficiency in 47% of cases (blood levels < or = 250 pg/mL). This was significantly more (P < .023) compared with NIHL and normal subjects who exhibited vitamin B12 deficiency in 27% and 19%, respectively. CONCLUSION:  These observations suggest a relationship between vitamin B12 deficiency and dysfunction of the auditory pathway. Some improvement in tinnitus and associated complaints were observed in 12 patients following vitamin B12 replacement therapy. The authors recommend that routine vitamin B12 serum levels be determined when evaluating patients for chronic tinnitus.


 

Vitamin B12 therapy in allergy and chronic dermatoses.
            (Simon, 1951)  Download
Vitamin B12 therapy using 1,000 pg. doses intramuscularly at weekly inter- vals was tried on 20 patients with asthma and 28 patients with chronic dermatoses. The number of patients treated with each type of chronic dermatitis is too small to draw any definite conclusions. However, it is felt that further trial of this therapy in chronic contact dermatitis and chronic urticaria is indicated. The response to B12 by the patients with asthma was equivocal and in no case was spectacular.

Cyanocobalamin (B12) Comparison Of Aqueous And Repository Preparations In Urticaria; Possible Mode Of Action
            (Simon, 1964)  Download
A previous study with cyanocobalamin, vitamin Biz, showed that this com- pound produces prompt and often complete clearing of acute and chronic urticaria (1). More than 100 patients have been treated subsequently, and relief obtained in the majority. The present study was instigated through the need for a logical explanation of the action of vitamin BIZin a syndrome unrelated to pernicious anemia. Repository Bl2 is more effective than the aqueous preparation when higher and more sustained serum levels are desired. Though B12 (cyanocobalamin) in either vehicle provides prompt, striking, and a t times permanent relief of urticaria1 lesions, there is apparently a better chance for prolonged or permanent relief with use of the repository form. Various dosages, combinations and administration periods of Bl2 have been tried, but no definite regimen can be advocated as superior at this time.

Vitamin B12 as an anti-anaphylactic.
            (Traina, 1950)  Download
Following the pure hypothesis that macrocytic anæmias could be due to an anaphylactic blockage of the bone marrow, especially as regards erythropoiesis, it was supposed that folic acid, the action of which in these anæmias has been of some help, might have an anti-anaphylactic action. Experiments were therefore performed which showed folic acid to possess a protective action on the anaphylaxis of the guinea pigs1. I thought it would be interesting to see whether such an anti-anaphylactic action might be shown also by vitamin B12, which has turned out to be very effective, even in a very small dosage, in the treatment of pernicious and some other macrocytic anæmias2–4.


 

Vitamin B12 injections versus oral supplements. How much money could be saved by switching from injections to pills
            (van Walraven et al., 2001) Download
OBJECTIVE:  To estimate savings, using a third-party payer perspective, if all elderly patients currently receiving vitamin B12 (cobalamin) injections were switched to high-dose oral therapy. DESIGN:  We modeled high-dose oral B12 supplement costs to include drugs, pharmacists' fees, and one-time conversion costs consisting of two physician visits and laboratory monitoring. The number of vitamin-injection visits avoided by switching to oral therapy was predicted using a multivariate model that considered covariates for overall patient illness. SETTING:  Ontario family physicians' and internists' practices. PARTICIPANTS:  Population-based administrative databases for Ontario were used to identify all people between 65 and 100 years who received parenteral vitamin B12 during 1995 and 1996. MAIN OUTCOME MEASURES:  The cost of parenteral vitamin B12 for each patient, including drugs, injections, pharmacists' fees, and injection-associated physician visits, was measured directly from the databases. RESULTS:  The annual cost of parenteral vitamin B12 therapy averaged $145.88 per person and totaled a maximum $25 million over 5 years. Converting all patients to high-dose oral B12 and treating them for 5 years would cost $7.4 million. Depending on how many vitamin-injection visits are avoided by switching to oral therapy, between $2.9 million and $17.6 million would be saved. Switching to oral B12 administration saved costs as long as 16.3% of injection-associated visits were avoided. CONCLUSION:  Switching all patients from B12 injections to oral cobalamin therapy could result in substantial savings.

The return of the Scarlet Pimpernel: cobalamin in inflammation II - cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS.
            (Wheatley, 2007)  Download
The up-regulation of transcobalamins [hitherto posited as indicating a central need for cobalamin (Cbl) in inflammation], whose expression, like inducible nitric oxide synthase (iNOS), is Sp1- and interferondependent, together with increased intracellular formation of glutathionylcobalamin (GSCbl), adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), may be essential for the timely promotion and later selective inhibition of iNOS and concordant regulation of endothelial and neuronal NOS (eNOS/nNOS.) Cbl may ensure controlled high output of nitric oxide (NO) and its safe deployment, because: (1) Cbl is ultimately responsible for the synthesis or availability of the NOS substrates and cofactors heme, arginine, BH(4) flavin adenine dinucleotide/flavin mononucleotide (FAD/FMN) and NADPH, via the far-reaching effects of the two Cbl coenzymes, methionine synthase (MS) and methylmalonyl CoA mutase (MCoAM) in, or on, the folate, glutathione, tricarboxylic acid (TCA) and urea cycles, oxidative phosphorylation, glycolysis and the pentose phosphate pathway. Deficiency of any of theNOS substrates and cofactors results in 'uncoupled' NOS reactions, decreasedNO production and increased or excessive O(2) (-), H(2)O(2), ONOO(-) and other reactive oxygen species (ROS), reactive nitric oxide species (RNIS) leading to pathology. (2) Cbl is also the overlooked ultimate determinant of positive glutathione status, which favours the formation of more benign NO species, s-nitrosothiols, the predominant form in which NO is safely deployed. Cbl status may consequently act as a 'back-up disc' that ensures the active status of antioxidant systems, as well as reversing and modulating the effects of nitrosylation in cell signal transduction.New evidence shows that GSCbl can significantly promote iNOS/ eNOS NO synthesis in the early stages of inflammation, thus lowering high levels of tumour necrosis factor-a that normally result in pathology, while existing evidence shows that in extreme nitrosative and oxidative stress, GSCbl can regenerate the activity of enzymes important for eventual resolution, such as glucose 6 phosphate dehydrogenase, which ensures NADPH supply, lactate dehydrogenase, and more; with human clinical case studies of OHCbl for cyanide poisoning, suggesting Cbl may regenerate aconitase and cytochrome c oxidase in the TCA cycle and oxidative phosphorylation. Thus, Cbl may simultaneously promote a strong inflammatory response and the means to resolve it.

 


References

Bauman, W. A., et al. (2000), ‘Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin’, Diabetes Care, 23 (9), 1227-31. PubMed: 10977010
Carmel, R, I Aurangzeb, and D Qian (2001), ‘Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gastritis.’, Am J Gastroenterol, 96 (1), 63-70. PubMed: 11197289
Dahele, A and S Ghosh (2001), ‘Vitamin B12 deficiency in untreated celiac disease.’, Am J Gastroenterol, 96 (3), 745-50. PubMed: 11280545
Frenkel, EP and DA Yardley (2000), ‘Clinical and laboratory features and sequelae of deficiency of folic acid (folate) and vitamin B12 (cobalamin) in pregnancy and gynecology.’, Hematol Oncol Clin North Am, 14 (5), 1079-100, viii. PubMed: 11005035
Kastner, T, et al. (1995), ‘Sleep-wake schedule disorders.’, J Am Acad Child Adolesc Psychiatry, 34 (12), 1557-58. PubMed: 8543524
Kumamoto, Y, et al. (1988), ‘[Clinical efficacy of mecobalamin in the treatment of oligozoospermia--results of double-blind comparative clinical study].’, Hinyokika Kiyo, 34 (6), 1109-32. PubMed: 3223457
Lindemans, J, et al. (1984), ‘Vitamin B12 absorption in cystic fibrosis.’, Acta Paediatr Scand, 73 (4), 537-40. PubMed: 6464742
Lindenbaum, J, et al. (1988), ‘Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis.’, N Engl J Med, 318 (26), 1720-28. PubMed: 3374544
Lott, WB, et al. (2001), ‘Vitamin B12 and hepatitis C: molecular biology and human pathology.’, Proc Natl Acad Sci U S A, 98 (9), 4916-21. PubMed: 11296247
Mitchell, SL and K Rockwood (2001), ‘The association between antiulcer medication and initiation of cobalamin replacement in older persons.’, J Clin Epidemiol, 54 (5), 531-34. PubMed: 11337218
Nilsson, K, et al. (2000), ‘Treatment of cobalamin deficiency in dementia, evaluated clinically and with cerebral blood flow measurements.’, Aging (Milano), 12 (3), 199-207. PubMed: 10965378
Okawa, M, et al. (1990), ‘Vitamin B12 treatment for sleep-wake rhythm disorders.’, Sleep, 13 (1), 15-23. PubMed: 2305167
Piyathilake, CJ, et al. (2000), ‘Localized folate and vitamin B-12 deficiency in squamous cell lung cancer is associated with global DNA hypomethylation.’, Nutr Cancer, 37 (1), 99-107. PubMed: 10965526
Riordan, M (2001), ‘Investigation and treatment of facial paralysis.’, Arch Dis Child, 84 (4), 286-88. PubMed: 11259220
Shemesh, Z, et al. (1993), ‘Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss.’, Am J Otolaryngol, 14 (2), 94-99. PubMed: 8484483
Simon, SW (1951), ‘Vitamin B12 therapy in allergy and chronic dermatoses.’, J Allergy, 22 (2), 183-85. PubMed: 14823832
——— (1964), ‘Cyanocobalamin (B12) Comparison Of Aqueous And Repository Preparations In Urticaria; Possible Mode Of Action’, J Am Geriatr Soc, 12 79-85. PubMed: 14106281
Traina, V (1950), ‘Vitamin B12 as an anti-anaphylactic.’, Nature, 166 (4210), 78-79. PubMed: 15439146
van Walraven, C, P Austin, and CD Naylor (2001), ‘Vitamin B12 injections versus oral supplements. How much money could be saved by switching from injections to pills’, Can Fam Physician, 47 79-86. PubMed: 11212437
Wheatley, C (2007), ‘The return of the Scarlet Pimpernel: cobalamin in inflammation II - cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS.’, J Nutr Environ Med, 16 (3-4), 181-211. PubMed: 18836533