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Abstracts

Life Extension Magazine January 2009
Abstracts

B12

Treatment of vitamin b(12)-deficiency anemia: oral versus parenteral therapy.

OBJECTIVE: To evaluate the use of oral cyanocobalamin therapy in the treatment of cobalamin (vitamin B(12))-deficient anemia. DATA SOURCES: Primary and review articles were identified by MEDLINE search (1966-May 2000) and through secondary sources. DATA SYNTHESIS: Cobalamin-deficient anemia is among the most common diagnoses in older populations. Cobalamin-deficient anemia may be diagnosed as pernicious anemia, resulting from the lack of intrinsic factor required for cobalamin absorption or as protein malabsorption from the inability to displace cobalamin from protein food sources. Several studies provide evidence that daily oral cyanocobalamin as opposed to monthly parenteral formulations may adequately treat both types of cobalamin-deficient anemias. CONCLUSIONS: Daily oral cyanocobalamin at doses of 1000-2000 microg can be used for treatment in most cobalamin-deficient patients who can tolerate oral supplementation. There are inadequate data at the present time to support the use of oral cyanocobalamin replacement in patients with severe neurologic involvement.

Ann Pharmacother. 2002 Jul-Aug;36(7-8):1268-72

Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients.

OBJECTIVES: The aim of this trial was to demonstrate the efficacy of one month of oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin deficiency related to food-cobalamin malabsorption (FCM). PATIENTS AND METHOD: Twenty elderly patients (mean age: 78+/-17 years) with established cobalamin deficiency related to FCM were included in an open-label, non-randomized, non-placebo trial. They were treated with a maximum of 1,000 microgram per day of oral crystalline cyanocobalamin for at least 1 month. Serum cobalamin levels (primary endpoint), blood count abnormalities and reticulocytes count (secondary endpoints) were determined at baseline and during the first month of treatment. RESULTS: 85% of the patients normalized their serum cobalamin levels with a mean increase of+167 pg/ml (p<0.001 compared with baseline). 100% of the patients corrected their initial macrocytosis and 25% their anemia; 100% of the patients had medullar regeneration with a mean increase of reticulocytes count of 32+/-11.3 x 106/l (p=0.03 compared with baseline). CONCLUSIONS: Our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM.

J Nutr Health Aging. 2006 Jan-Feb;10(1):3-6

Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial.

BACKGROUND: Supplement-ation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B(12) deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain. METHODS: We conducted a randomized, parallel-group, double-blind, dose-finding trial to determine the lowest oral dose of cyanocobalamin required to normalize biochemical markers of vitamin B(12) deficiency in older people with mild vitamin B(12) deficiency, defined as a serum vitamin B(12) level of 100 to 300 pmol/L (135-406 pg/mL) and a methylmalonic acid level of 0.26 mumol/L or greater. We assessed the effects of daily oral doses of 2.5, 100, 250, 500, and 1000 mug of cyanocobalamin administered for 16 weeks on biochemical markers of vitamin B(12) deficiency in 120 people. The main outcome measure was the dose of oral cyanocobalamin that produced 80% to 90% of the estimated maximal reduction in the plasma methylmalonic acid concentration. RESULTS: Supplementation with cyanocobalamin in daily oral doses of 2.5, 100, 250, 500, and 1000 mug was associated with mean reductions in plasma methylmalonic acid concentrations of 16%, 16%, 23%, 33%, and 33%, respectively. Daily doses of 647 to 1032 mug of cyanocobalamin were associated with 80% to 90% of the estimated maximum reduction in the plasma methylmalonic acid concentration. CONCLUSION: The lowest dose of oral cyanocobalamin required to normalize mild vitamin B(12) deficiency is more than 200 times greater than the recommended dietary allowance, which is approximately 3 mug daily.

Arch Intern Med. 2005 May 23;165(10):1167-72

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency is common and rises with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular vitamin B12 which is a considerable source of work for health care professionals. Several case control and case series studies have reported equal efficacy of oral administration of vitamin B12 but it is rarely prescribed in this form, other than in Sweden and Canada. Doctors may not be prescribing oral formulations because they are unaware of this option or have concerns regarding effectiveness. OBJECTIVES: To assess the effectiveness of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH STRATEGY: Searches were undertaken of The Cochrane Library, MEDLINE, EMBASE and Lilacs in early 2005. The bibliographies of all relevant papers identified using this strategy were searched. In addition we contacted authors of relevant identified studies and Vitamin B12 research and pharmaceutical companies to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) examining the use of oral or intramuscular vitamin B12 to treat vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: All abstracts or titles identified by the electronic searches were independently scrutinised by two reviewers. When a difference between reviewers arose, we obtained and reviewed a hard copy of the papers and made decisions by consensus. We obtained a copy of all pre-selected papers and two researchers independently extracted the data from these studies using piloted data extraction forms. The whole group checked whether inclusion and exclusion criteria were met, and disagreement was decided by consensus. The methodological quality of the included studies was independently assessed by two researchers and disagreements were brought back to the whole group and resolved by consensus. MAIN RESULTS: Two RCT’s comparing oral with intramuscular administration of vitamin B12 met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to four months. High oral doses of B12 (1000 mcg and 2000 mcg) were as effective as intramuscular administration in achieving haematological and neurological responses. AUTHORS’ CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 mcg doses of oral vitamin B12 daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients.

Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004655

Vitamin B12 injections versus oral supplements. How much money could be saved by switching from injections to pills?

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.

Can Fam Physician. 2001 Jan;47:79-86

Vitamin B12 status and rate of brain volume loss in community-dwelling elderly.

OBJECTIVES: To investigate the relationship between markers of vitamin B(12) status and brain volume loss per year over a 5-year period in an elderly population. METHODS: A prospective study of 107 community-dwelling volunteers aged 61 to 87 years without cognitive impairment at enrollment. Volunteers were assessed yearly by clinical examination, MRI scans, and cognitive tests. Blood was collected at baseline for measurement of plasma vitamin B(12), transcobalamin (TC), holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), and serum folate. RESULTS: The decrease in brain volume was greater among those with lower vitamin B(12) and holoTC levels and higher plasma tHcy and MMA levels at baseline. Linear regression analysis showed that associations with vitamin B(12) and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, ApoE epsilon4 status, tHcy, and folate. Using the upper (for the vitamins) or lower tertile (for the metabolites) as reference in logistic regression analysis and adjusting for the above covariates, vitamin B(12) in the bottom tertile (<308 pmol/L) was associated with increased rate of brain volume loss (odds ratio 6.17, 95% CI 1.25-30.47). The association was similar for low levels of holoTC (<54 pmol/L) (odds ratio 5.99, 95% CI 1.21-29.81) and for low TC saturation. High levels of MMA or tHcy or low levels of folate were not associated with brain volume loss. CONCLUSION: Low vitamin B(12) status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly.

Neurology. 2008 Sep 9;71(11):826-32

Vitamin B12 deficiency neurological syndromes: correlation of clinical, MRI and cognitive evoked potential.

OBJECTIVE : To evaluate cognitive function in B12 deficiency neurological syndromes and response to B12 therapy. METHODS : Patients were diagnosed on the basis of low serum B12 or megaloblastic bone marrow or both. Detailed neurological examination was performed and mental status was evaluated by the Mini Mental State Examination (MMSE). Hemoglobin, RBC indices, blood counts, serum chemistry, HIV, thyroid profile, antiparietal cell antibody and craniospinal MRI were done. Cognitive evoked potential was carried out using the odd ball auditory paradigm and recording was achieved from Fz, Cz and Pz referred to mastoid. P3 latency and amplitude were measured and compared with 33 age and sex matched controls. Three months following B12 therapy, clinical and P3 values were reevaluated and compared with the baseline values. RESULTS : 36 patients, aged 16-80 years were included; 32 patients were above 40 years of age. Their median education level was 14 years. The presenting syndrome was myeloneurocognitive in 9, myeloneuropathy in 10, myelocognitive in 8,myelopathy in 8 and only cognitive in 1 patient.MMSE was abnormal in 17; between 28-19 in 14 and 18-11 in 3 patients. Cranial MRI carried out in 14 patients revealed multiple white matter hyperintensity in T2 in 3 and cortical atrophy in 1. P3 was unrecordable in 7 and latency was prolonged in 8 out of 33 patients. P3 latency was significantly prolonged in patients compared to controls and both MMSE and P3 latency improved significantly at the 3-month follow-up. CONCLUSION : MMSE was abnormal in 47 % and P3 in 45.5% of patients with B12 deficiency neurological syndromes which improved following treatment. SIGNIFICANCE : There is high incidence of reversible cognitive impairment and P3 abnormalities in B12 deficiency neurological syndromes.

J Neurol. 2008 Mar;255(3):353-9

Cobalamin: a critical vitamin in the elderly.

Vitamin B(12) deficiency is a common problem in elderly subjects. If a serum cobalamin level of about 150 pmol/L (200 pg/mL) is considered normal, 10-15% of the elderly are deficient. Today, however, a threshold of 220-258 pmol/L (300-350 pg/mL) is recognized as desirable in the elderly, or else sensitive markers like the blood concentration of homocysteine or methylmalonic acid (MMA) are used. Then the prevalence of cobalamin deficiency rises to up to 43%. In the elderly, this high prevalence of poor cobalamin status is predominantly caused by atrophic gastritis type B. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal absorption of the cobalamin protein complexes from food. About 20-50% of the elderly are affected. Furthermore, the reduced acid secretion leads to an alkalinization of the small intestine, which may result in bacterial overgrowth and thus to a further decrease of the bioavailability of the vitamin. In addition, some drugs such as proton pump inhibitors or H2 receptor antagonists inhibit the intestinal absorption of vitamin B(12). An already moderately reduced vitamin B(12) level is associated with vascular disease and neurocognitive disorders such as depression and impaired cognitive performance. Furthermore, a poor vitamin B(12) status is assumed to be involved in the development and progression of dementia (e.g., Alzheimer’s dementia). This is especially observable if the folic acid status is reduced as well. Due to the insecure supply, the cobalamin status of elderly persons (>/=60 years) should be regularly controlled and a general supplementation with vitamin B(12) (>50 microg/day) should be considered.

Prev Med. 2004 Dec;39(6):1256-66

Vitamin B12 deficiency in the aged: a population-based study.

BACKGROUND: vitamin B12 deficiency is common in the aged, but it is controversial whether only some risk groups should be investigated instead of screening the entire aged population. OBJECTIVES: to describe the prevalence of vitamin B12 deficiency in the Finnish aged, and to find out if the subjects especially prone to vitamin B12 deficiency could be identified by the risk factors or clinical correlates. DESIGN: a cross-sectional, population-based study of 1048 aged subjects (age 65-100 years) was carried out. Data on lifestyle factors and clinical conditions were collected, physical examinations were conducted and laboratory variables related to vitamin B12 were measured. RESULTS: vitamin B12 deficiency had been previously diagnosed in 27 (2.6%) subjects, and a laboratory diagnosis (total vitamin B12 <150 pmol/l, or total vitamin B12 150-250 pmol/l and holotranscobalamin < or =37 pmol/l and homocysteine > or =15 micromol/l) was made for 97 (9.5%) subjects. Low serum total vitamin B12 (<150 pmol/l) was observed in 6.1% and borderline total vitamin B12 (150-250 pmol/l) in 32% of the subjects. Male gender (OR 1.9, 95% CI 1.2-2.9), age > or =75 (OR 2.2, 95% CI 1.4-3.4) and refraining from milk products (OR 2.3, 95% CI 1.2-4.4) increased the probability for vitamin B12 deficiency. Anaemia (OR 1.3, 95% CI 0.7-2.3) or macrocytosis (OR 1.2, 95% CI 0.6-2.7) did not predict vitamin B12 deficiency. CONCLUSION: undiagnosed vitamin B12 deficiency is remarkably common in the aged, but no specific risk group for screening can be identified. Thus, biochemical screening of unselected aged population is justified. General practitioners play a key role in diagnosing early vitamin B12 deficiency.

Age Ageing. 2007 Mar;36(2):177-83

Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn’s disease.

BACKGROUND: Crohn’s disease (CD) can commonly involve the terminal ileum, which is the site of B(12) absorption. The aim of this study was to define the prevalence of vitamin B(12) abnormalities in a population with CD and to identify risk factors associated with B(12) abnormalities in CD. METHODS: The medical records of 201 patients with CD evaluated at a tertiary care center were retrospectively reviewed to determine the prevalence of B(12) deficiency and to evaluate factors associated with B(12) deficiency. The prevalence of B(12) deficiency in a control population of 40 patients with ulcerative colitis was also assessed. RESULTS: The prevalence of an abnormal serum B(12) concentration in patients with CD was 18.4% (95% confidence interval [CI] 13.1-23.8%) compared with 5% (95% CI, 0-11.8%) (P = 0.035) in ulcerative colitis controls. Risk factors for B(12) deficiency in patients with CD included prior ileal (odds ratio [OR], 7.22; 95% CI, 1.97-26.51) or ileocolonic (OR, 5.81; 95% CI, 2.09-16.12) resection and the need for ongoing medical therapy (OR, 2.59; 95% CI, 1.03-6.47). Neither disease location nor duration was independently associated with the risk of B(12) deficiency. CONCLUSIONS: Vitamin B(12) abnormalities are common in patients with CD and patients with a prior ileal or ileocolonic resection are at particular risk. Routine screening for B(12) deficiency in patients with CD is warranted.

Inflamm Bowel Dis. 2008 Feb;14(2):217-23

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