Vitamin B12 Abstracts 11

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Cobalamin level is related to self-reported and clinically rated mood and to syndromal depression in bereaved HIV-1(+) and HIV-1(-) homosexual men.
            (Baldewicz et al., 2000)  Download
OBJECTIVE:  An examination of the relationship of plasma cobalamin (vitamin B(12)) level to overall psychological distress, specific mood states, and major depressive disorder was conducted in 159 bereaved men (90 HIV-1(+) and 69 HIV-1(-)). METHODS:  The relationship of a continuous measure of cobalamin level to psychological distress was examined, while controlling for HIV-1 serostatus, life stressors, social support, and coping styles. RESULTS:  Of this sample, 23.9% were either overtly or marginally cobalamin deficient; however, the deficiency rate was not significantly different by HIV-1 serostatus. Cobalamin level was inversely related to self-reported overall distress level and specifically to depression, anxiety, and confusion subscale scores, as well as to clinically rated depressed and anxious mood. Lower plasma cobalamin levels also were associated with the presence of symptoms consistent with major depressive disorder. CONCLUSION:  These findings suggest that cobalamin level may be physiologically related to depressed and anxious mood level, as well as to syndromal depression.

Shaky-leg syndrome and vitamin B12 deficiency.
            (Benito-León and Porta-Etessam, 2000) Download
A 68-year-old man presented with a three- year history of trembling of the legs. The tremor began immediately after he stood and subsided when he began walking. Results of laboratory tests were remarkable only for a serum vitamin B12 level of 132 ng per liter (normal range, 222 to 753). A Schilling test demonstrated malabsorption of vitamin B12.  Clonazepam (1 mg per day) and cyanoco- balamin (injections of 1000 mg given daily for two weeks, then weekly for two months, and once a month thereafter) provided complete relief of the tremor. Follow-up after one year showed no abnormalities. Treatment with clonazepam was then discontinued without recurrence of the tremor. We think that shaky-leg syndrome was the result of disturbances in the cerebellum or related pontine structures as a result of vitamin B12 deficiency. In fact, there is evidence that these structures may be affected by vitamin B12 deficiency. (Katsaros 1998 - MRI of spinal cord and brain lesions in subacute combined degeneration)


Omeprazole and vitamin B12 deficiency.
            (Bradford and Taylor, 1999) Download
The mainstay for cobalamin deficiency is correction of the underlying disorder and replacement therapy. Because the defect is often one of absorption, parenteral or intranasal routes are recommended. In most cases, replacement therapy is all that is needed. The vitamin preparation most commonly used is cyanocobalamin (also called vitamin B12), which has no known physiologic role but instead is converted to a biologically active form before it can be used by tissues. The studies reviewed in this article clearly show that omeprazole therapy will decrease the absorption of vitamin B12 by preventing its cleavage from dietary proteins. However, these data are insufficient to infer that clinically significant deficiency will occur over time. In fact, some of the studies suggest that the simple addition of juices or other acidic drinks into the diet may dramatically increase cobalamin absorption. Clearly, well-designed clinical trials are needed to evaluate this theory over an extended follow-up period to determine the clinical significance of omeprazole-associated vitamin B12 deficiency and possibly identify patients at risk for deficiency. In conclusion, the possibility of dietary vitamin B12 malabsorption should be considered in patients receiving chronic omeprazole treatment and presenting with signs and symptoms of deficiency. All healthcare workers should be made aware of the potential clinical complications of omeprazole-associated vitamin B12 deficiency since it may go unrecognized and is easily corrected. This is particularly relevant for elderly patients with poor dietary intake of vitamin B12, impaired vitamin B12 stores, and certain gastrointestinal disorders.

Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia.
            (Chao et al., 1999)  Download
This study showed that short-term vitamin administration effectively reduced post-methionine load homocysteine levels and thereby ameliorated endothelium-dependent flow-mediated vasodilation in 16 healthy adults. Post-methionine load homocysteine levels decreased from 22.7+/-3.8 to 17.0+/-2.1 micromol/L (p <0.001), and flow-mediated vasodilation after methionine load increased from 8.6+/-3.6% to 13.8+/-2.9% (p <0.001) after vitamin administration.


 

Vitamin B12 deficiency in dementia and cognitive impairment: the effects of treatment on neuropsychological function.
            (Eastley et al., 2000)  Download
BACKGROUND:  Vitamin B12 assay is part of the routine investigation of dementia, although few studies have investigated the effects of treatment on cognition. We examined the effects of B12 treatment on neuropsychological function and disease progression in patients presenting with dementia or cognitive impairment. METHODS:  From 1432 patients who were assessed at the Bristol Memory Disorders Clinic, 125 patients with low serum B12 were identified. Sixty-six patients presenting with dementia, and 22 with cognitive impairment were seen for a second assessment after treatment. Changes in neuropsychological test scores were compared with those of patients with normal serum B12, matched by age and diagnosis. RESULTS:  The majority of patients with low serum B12 had normal Hb and MCV values. We found no cases of reversible B12 deficiency dementia. The B12 treatment patients who presented with dementia showed no significant improvement, and no less deterioration, in their neuropsychological function than their matched group. However, a treatment effect was demonstrated among the patients presenting with cognitive impairment. These improved significantly compared to matched patients on the verbal fluency test (p<0.01). CONCLUSION:  All patients with cognitive impairment should be investigated for B12 deficiency. Vitamin B12 treatment may improve frontal lobe and language function in patients with cognitive impairment, but rarely reverses dementia.

Methylcobalamin treatment of Bell's palsy.
            (Jalaludin, 1995)  Download
Sixty patients with Bell's palsy were included in an open randomized trial. 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 ( p < 0.001) in the methylcobalamin (mean of 1.95 +/- 0.51 weeks) and methylcobalamin plus steroid groups (mean of 2.05 +/- 1.23 weeks) than in the steroid group (mean of 9.60 +/- 7.79 weeks). 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.


 

Helicobacter pylori--is it a novel causative agent in Vitamin B12 deficiency
            (Kaptan et al., 2000)  Download
BACKGROUND:  Evidence for vitamin B12 deficiency usually involves combinations of low serum vitamin B12 levels, clinical and metabolic abnormalities, and therapeutic response. Identification of the underlying cause is important in the diagnosis of vitamin B12 deficiency that is usually attributed to malabsorption. Helicobacter pylori is one of the most common causes of peptic ulcer disease worldwide and a major cause of chronic superficial gastritis leading to atrophy of gastric glands. It is suggested that there may be a casual relationship between H. pylori and food-cobalamin malabsorption. OBJECTIVES:  To evaluate the H. pylori incidence in patients with vitamin B12 deficiency prospectively and to assess whether treatment for H pylori infection could correct this deficiency over time. PATIENTS AND METHODS:  We performed a prospective cohort study involving 138 patients who had anemia and vitamin B12 deficiency. An upper gastrointestinal endoscopy was performed to assess the severity of atrophic gastritis and biopsy specimens for Campylobacter-like organisms tests and histological examination for H pylori were obtained at the time of diagnosis. The diagnosis of H. pylori prompted a combination treatment. RESULTS:  Helicobacter pylori was detected in 77 (56%) of 138 patients with vitamin B12 deficiency and eradication of H pylori infection successfully improved anemia and serum vitamin B12 levels in 31 (40 %) of 77 infected patients. CONCLUSIONS:  Helicobacter pylori seems to be a causative agent in the development of adult vitamin B12 deficiency. Eradication of H. pylori infection alone may correct vitamin B12 levels and improve anemia in this subgroup of patients.

MRI of spinal cord and brain lesions in subacute combined degeneration.
            (Katsaros et al., 1998) Download
Subacute combined degeneration is a rare cause of demyelination of the dorsal and lateral columns of the spinal cord and even more rarely of the pyramidal and spinocerebellar tracts and cerebellum. We present the initial and follow-up MRI appearances in a patient with subacute combined degeneration of the spinal cord, brain stem and cerebellum, due to vitamin B12 deficiency. The lesions in these structures were demonstrated clearly as pathologically high-signal areas on T2-weighted images. These lesions, except those of the brain stem and cerebellum, disappeared 4 months after therapy. MRI 14 months after the patient's discharge on vitamin B12 therapy showed the same picture.


 

Serum levels of folic acid and vitamin B12 in Korean patients with vitiligo.
            (Kim et al., 1999) Download
The association of vitiligo and pernicious anemia has been previously documented. The low levels of folic acid and vitamin B12 were thought to be related to vitiligo. To date, there have been very few reports about the serum levels of folic acid and vitamin B12 in patients with vitiligo. Using radioimmunoassay, we measured the serum levels of folic acid and vitamin B12 in 100 Korean patients with vitiligo. The mean serum levels of folic acid and vitamin B12 were 6.31 +/- 2.82 ng/ml and 630.25 +/- 230.94 pg/ml, respectively, in patients with vitiligo. These levels showed no significant difference compared to the normal control group, suggesting that folic acid and vitamin B12 do not appear to play a role in the pathogenesis of vitiligo.

Diet and lifestyle characteristics associated with dietary supplement use in women.
            (Kirk et al., 1999) Download
OBJECTIVES:  To describe the characteristics of dietary supplement users in a large cohort of women and test the hypothesis that supplement users would be more likely to have a healthier lifestyle than non-users. DESIGN:  Comparison of nutrient intakes from food frequency questionnaire (FFQ) data for 8409 supplement users and 5413 non-users. Use of logistic regression modelling to determine predictors of supplement use in this cohort. SUBJECTS:  13,822 subjects from the UK Women's Cohort Study (UKWCS) for whom data on supplement use was available. RESULTS:  Significant differences in nutrient intakes from FFQ were seen between the two groups, with supplement users having higher intakes of all nutrients, except for fat and vitamin B12. Use of dietary supplements was associated with being vegetarian, vegan or fish-eating, consuming more fruit and vegetables, being more physically active and having a lower alcohol intake. Supplement use was less likely in those with a body mass index above 25 and those who reported smoking regularly. CONCLUSIONS:  The findings are consistent with the hypothesis that supplement use is associated with a healthier lifestyle profile and an adequate nutritional intake, suggesting that supplement users do not need to take supplements to meet a nutrient deficiency.

Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors.
            (Laine et al., 2000)  Download
This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long-term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins. Prolonged proton pump inhibitor use may lead to enterochromaffin-like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long-term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long-term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger-Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high-dose proton pump inhibitors for many years. Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow-up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long-term acid suppression.

Homocystinuria and psychiatric disorder: a case report.
            (Li and Stewart, 1999) Download
Deficiency of cystathionine beta-synthase (CBS) is the commonest cause of primary homocystinuria. Homocysteine metabolism is intimately linked with the metabolism of folate, vitamin B12 (cobalamin) and pyridoxine. It is hypothesised that the pathogenesis of neuropsychiatric manifestations in homocystinuria, folate and cobalamin deficiencies are related to imbalance neurotransmitters in the CNS through disturbances in the pathways linking the metabolism of homocysteine and these vitamins. Although neuropsychiatric disorders are relatively common among patients with homocystinuria, it is not well recognised as the causative factor among patients presenting with neuropsychiatric disorders. A 31 year old woman presented with a three week history of delirium and inappropriate and labile affect. There was no history suggestive of drug or alcohol abuse, nutritional deficiency or organic disorders. EEG, cerebral CT, MRI and microbiological investigations did not reveal any organic causes. Because of a diagnosis of pyridoxine-responsive homocystinuria seven years previously, the possibility of homocystinuria was considered and investigated. Laboratory tests revealed macrocytosis and a high concentration of urinary total homocystine. Commencement of pyridoxine at 400 mg/day resulted in disappearance of homocystine in urine within four days with remarkable clinical improvement. Homocystinuria should be considered in the differential diagnosis of unexplained neuropsychiatric disorders in patients who have past or family history of homocystinuria, mental retardation, thromboembolic episodes, vascular diseases or clinical and laboratory features resembling folate and/or vitamin B12 deficiencies. Homocystinuria-associated neuropsychiatric disturbances can easily be treated with pyridoxine in 50% of cases.

Vitamin B12 deficiency may cause benign familial infantile convulsions: a case report.
            (Lundgren and Blennow, 1999)  Download
Vitamin B12 is essential for DNA synthesis and hematopoesis and deficiency of vitamin B12 is not uncommon in man, especially in the elderly. Nutritional vitamin B12 deficiency has also been reported in infants, most often with vegetarian mothers (5–8), causing megaloblastic anemia, cerebral atrophy with symptoms of lethargy, or cerebral involvement with hyperirritability. A recent report (9) included convulsions among other severe neurological symptoms caused by B12 deficiency during the first year of life. The entity, now named benign familial infantile convulsions (BFIC), has recently been mapped to chromosome 19 by linkage analysis. We hypothesize that transient vitamin B12 deficiency is involved in BFIC.

Atrophic gastritis during long-term omeprazole therapy affects serum vitamin B12 levels.
            (Schenk et al., 1999)  Download
BACKGROUND:  Omeprazole maintenance therapy for gastro-oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori-infected patients and with a decreased absorption of protein-bound, but not of unbound cobalamin. AIM:  : To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy. METHODS:  Forty-nine H. pylori-positive GERD patients were treated with omeprazole for a mean (+/- s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow-up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow-up for histopathological scoring according to the updated Sydney classification. RESULTS:  At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow-up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow-up. During follow-up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136-716) vs. (T1) 341 (136-839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156-716) at latest follow-up (P < 0.01). CONCLUSIONS:  The development of atrophic gastritis during omeprazole treatment in H. pylori-positive GERD patients is associated with a decrease of serum vitamin B12 levels.


Interactions between drugs and vitamins at advanced age.
            (Schümann, 1999) Download
Drug consumption increases at advanced age due to increased morbidity. At the same time the state of repletion is reduced for several vitamins. Physiological and kinetic alterations in the elderly are reviewed in order to analyse possible interrelations between these two phenomena. At high age the status of all vitamins is compromised by reduced food intake. Decreased active intestinal transport and an increased propensity for atrophic gastritis may reduce the absorption of vitamins A, B1, folate and B12. Decreased exposure to sunlight and reduced cutaneous synthesis impair the vitamin D status. Studies on the state of vitamin repletion in hospital patients indicate a specific response of vitamins A, B1, B6 and C to drug administration at advanced age. Reduced food intake in the elderly is further compromised by drugs that impair appetite and absorption. Anticonvulsives and other drugs that induce hepatic microsomal enzymes accelerate vitamin D metabolism and aggravate post-menopausal osteoporosis. Acid inhibiting agents increase achlorhydria and reduce vitamin B12 absorption. Renal clearance of acidic drugs such as acetylsalicylic acid and barbituric acid, which is impaired at high age, is further reduced by high doses of vitamin C. Vitamin B6 reduces the therapeutic effect of L-dopa. When recognised, the negative effects of drug-vitamin interactions can be compensated by adequate vitamin supplementation and by adaptation of drug dosing.

Autonomic dysfunction and orthostatic hypotention caused by vitamin B12 deficiency.
            (Toru et al., 1999) Download
Orthostatic   hypotension sometimes is a reversible neurological complication of vitamin B12 deficiency. Daily intramuscularly administered 1 mg vitamin B12 for a week then 1 mg once amonth increased its serum concentration rapidly to normal,  resulting in the gradualamelioration of orthostatic dizziness, and his neurological  symptoms except for erectile failure, after a month. The abnormalities seen in the autonomic nervous system tests also disappeared whenvitamin B12 was given for 6 months. Vitamin  B12  is  related  to  the  methylationreaction regulated by S-adenosylhomocystineand   S-adenosylmethionine. This reaction has a crucial role in the myelin  formation associated with neurological deficits in patients with vitamin B12 deficiency. Dysfunction in unmyelinated  sympathetic neurons, however, has not been shown. Our findings suggest that vitamin B12 is required for thephysiological  function of  sympathetic post-ganglionic fibres.


 

Treatment of hyperhomocysteinemia with folic acid and vitamins B12 and B6 attenuates thrombin generation.
            (Undas et al., 1999) Download
The effect of homocysteine-lowering treatment on thrombin generation was investigated in 17 subjects with hyperhomocysteinemia (aged 22-60 years), 11 of whom had symptomatic atherosclerotic vascular disease. All subjects had fasting total homocysteine levels above 16 micromol/L. The formation of thrombin was assessed by measuring thrombin-antithrombin III complexes and prothrombin fragment 1+2 in peripheral venous blood and in the bleeding time blood collected at 30-second intervals from skin incisions on a forearm. All the tests were performed before and after an 8-week treatment with folic acid p.o. 5 mg/day, vitamin B6 p.o. 300 mg/day, and vitamin B12 i.m. 1000 microg given on a weekly basis. Following the 8-week therapy, the median plasma homocysteine concentration became significantly reduced from 20 to 10 micromol/L, while plasma levels of fibrinogen, prothrombin, and antithrombin III as well as activity of protein C, S, and factor VII showed no changes. Vitamin treatment was associated with a significant fall in thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds. At sites of hemostatic plug formation, plasma concentrations of both thrombin markers significantly decreased. Compared with pretreatment values, significantly less thrombin was produced during the first 3 minutes of bleeding after homocysteine-lowering therapy. In subjects with hyperhomocysteinemia a reduction of plasma fasting homocysteine concentration by folic acid and vitamins B12 and B6 administration is associated with attenuation of thrombin generation both in peripheral blood and at sites of hemostatic plug formation.

Bioavailability of dried asakusanori (porphyra tenera) as a source of Cobalamin (Vitamin B12).
            (Yamada et al., 1999)  Download
We have already reported that raw nori (Porphyra tenera) contains cobalamin (Cbl) but not Cbl analogues (J. Nutr. Sci. Vitaminol., 42, 497, 1996). It seems, therefore, that it is an excellent natural vegetable source of Cbl. On the other hand, it has been reported that the Cbl nutritional status of vegetarian children deteriorated as estimated by the hematological index, mean corpuscular volume (MCV), after they had dried nori as a source of Cbl. Such a discrepancy between raw and dried nori as a source of Cbl led us to investigate whether Cbl in dried nori had different properties from that in raw nori. We found that contents of Cbl homologues determined by a bioassay method in both raw and dried nori were similar. The urinary methylmalonic acid excretion increased when human female volunteers were given 40 g of dried nori daily during the test period. On the other hand, the urinary methylmalonic acid excretion did not change when volunteers were daily given 320 g of raw nori, which was equivalent to 40 g of the dried one on the basis of dehydrated weight, during the test period. By paper chromatography, 65% of the Cbl homologues were found to be comprised of Cbl analogues in dried nori, while 73% of the Cbl homologues in the raw nori were genuine Cbl. These results were confirmed by the finding that the bioassay method gave higher values for Cbl homologues than those obtained by a competitive binding assay method using an intrinsic factor as a Cbl-binding protein. Our present data demonstrated that Cbl in raw nori can be changed into harmful Cbl analogues by the drying process.

 


References

Baldewicz, TT, et al. (2000), ‘Cobalamin level is related to self-reported and clinically rated mood and to syndromal depression in bereaved HIV-1(+) and HIV-1(-) homosexual men.’, J Psychosom Res, 48 (2), 177-85. PubMed: 10719135
Benito-León, J and J Porta-Etessam (2000), ‘Shaky-leg syndrome and vitamin B12 deficiency.’, N Engl J Med, 342 (13), 981. PubMed: 10744502
Bradford, GS and CT Taylor (1999), ‘Omeprazole and vitamin B12 deficiency.’, Ann Pharmacother, 33 (5), 641-43. PubMed: 10369631
Chao, CL, KL Chien, and YT Lee (1999), ‘Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia.’, Am J Cardiol, 84 (11), 1359-61, A8. PubMed: 10614808
Eastley, R, GK Wilcock, and RS Bucks (2000), ‘Vitamin B12 deficiency in dementia and cognitive impairment: the effects of treatment on neuropsychological function.’, Int J Geriatr Psychiatry, 15 (3), 226-33. PubMed: 10713580
Jalaludin, MA (1995), ‘Methylcobalamin treatment of Bell’s palsy.’, Methods Find Exp Clin Pharmacol, 17 (8), 539-44. PubMed: 8749227
Kaptan, K, et al. (2000), ‘Helicobacter pylori--is it a novel causative agent in Vitamin B12 deficiency’, Arch Intern Med, 160 (9), 1349-53. PubMed: 10809040
Katsaros, VK, et al. (1998), ‘MRI of spinal cord and brain lesions in subacute combined degeneration.’, Neuroradiology, 40 (11), 716-19. PubMed: 9860120
Kim, SM, YK Kim, and SK Hann (1999), ‘Serum levels of folic acid and vitamin B12 in Korean patients with vitiligo.’, Yonsei Med J, 40 (3), 195-98. PubMed: 10412328
Kirk, SF, et al. (1999), ‘Diet and lifestyle characteristics associated with dietary supplement use in women.’, Public Health Nutr, 2 (1), 69-73. PubMed: 10452734
Laine, L, et al. (2000), ‘Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors.’, Aliment Pharmacol Ther, 14 (6), 651-68. PubMed: 10848649
Li, SC and PM Stewart (1999), ‘Homocystinuria and psychiatric disorder: a case report.’, Pathology, 31 (3), 221-24. PubMed: 10503267
Lundgren, J and G Blennow (1999), ‘Vitamin B12 deficiency may cause benign familial infantile convulsions: a case report.’, Acta Paediatr, 88 (10), 1158-60. PubMed: 10565467
Schenk, BE, et al. (1999), ‘Atrophic gastritis during long-term omeprazole therapy affects serum vitamin B12 levels.’, Aliment Pharmacol Ther, 13 (10), 1343-46. PubMed: 10540050
Schümann, K (1999), ‘Interactions between drugs and vitamins at advanced age.’, Int J Vitam Nutr Res, 69 (3), 173-78. PubMed: 10389024
Toru, S, et al. (1999), ‘Autonomic dysfunction and orthostatic hypotention caused by vitamin B12 deficiency.’, J Neurol Neurosurg Psychiatry, 66 (6), 804-5. PubMed: 10400513
Undas, A, et al. (1999), ‘Treatment of hyperhomocysteinemia with folic acid and vitamins B12 and B6 attenuates thrombin generation.’, Thromb Res, 95 (6), 281-88. PubMed: 10527405
Yamada, K, et al. (1999), ‘Bioavailability of dried asakusanori (porphyra tenera) as a source of Cobalamin (Vitamin B12).’, Int J Vitam Nutr Res, 69 (6), 412-18. PubMed: 10642899