title: Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Nasal absorption of hydroxocobalamin in healthy elderly adults. Effective treatment of cobalamin deficiency with oral cobalamin. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Oral cobalamin remains medicine's best kept secret. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients. Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients. Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients.
abstract: BACKGROUND The st and ard treatment for cobalamin ( vitamin B(12 ) ) deficiency involves regular intramuscular cobalamin injection . It has been suggested that oral cobalamin therapy may be effective for treating patients who have food-cobalamin malabsorption . SUBJECTS AND METHODS We prospect ively studied 10 patients with cobalamin deficiency and well-established food-cobalamin malabsorption who received 3000 microg or 5000 microg of oral crystalline cyanocobalamin once a week for at least 3 months .  Complete blood counts and serum cobalamin , homocysteine , and folate levels were determined at baseline and after 3 months of treatment . Patients were reexamined after 6 months . RESULTS After 3 months of treatment , all patients had increased hemoglobin levels ( mean increase , 1.9 g/dL ; 95 % confidence interval : 0.9 to 3.9 g/dL;P < 0.01 compared with baseline ) and decreased erythrocyte cell volume ( mean decrease , 7.8 fL ; 95 % confidence interval : 0.9 to 16.5 fL;P<0.001 ) . However , 2 patients had only minor , if any , responses . Serum cobalamin levels were increased in all 8 patients in whom it was measured . CONCLUSION Our findings suggest that moderate doses of crystalline cyanocobalamin given orally may be an effective treatment for food-cobalamin malabsorption AIMS To investigate the nasal absorption of hydroxocobalamin in 10 healthy elderly adults . METHODS In a cross-over study , blood sample s were collected before administration of the drug and after 10 , 20 , 30 , 40 , 60 , 120 , 180 and 240 min . The plasma cobalamin concentration was determined by competitive radioisotope binding technique . RESULTS The maximal plasma cobalamin concentration ( Cmax ) after nasal administration of 750 microg hydroxocobalamin was 1900 + /- 900 pmol l(-1 ) ( mean + /- s.d . ) . The maximal plasma cobalamin concentration was reached in 35 + /- 13 min ( t[max ] ) . The Cmax after nasal administration of 1500 microg hydroxocobalamin was 3500 + /- 2500 pmol l(-1 ) with a t(max ) of 28 + /- 16 min . Both the AUC(0,240 min ) and AUC(0,00 ) increased significantly with an increase of the dose from 750 microg to 1500 microg ( P = 0.037 and P = 0.028 , respectively ) . The nasal spray was well tolerated . No signs of irritation or local sensitivity were noted . CONCLUSIONS The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid , high and well tolerated Because cobalamin deficiency is routinely treated with parenteral cobalamin , we investigated the efficacy of oral therapy . We r and omly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1 , 3 , 7 , 10 , 14 , 21 , 30 , 60 , and 90 or 2 mg orally on a daily basis for 120 days . Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin ( normal , 200 to 900 pg/mL ) methylmalonic acid ( normal , 73 to 271 nmol/L ) , and homocysteine ( normal , 5.1 to 13.9 micromol/L ) . Five patients were subsequently found to have folate deficiency , which left 18 evaluable patients in the oral group and 15 in the parenteral group . Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups . The mean pretreatment values for serum cobalamin , methylmalonic acid , and homocysteine were , respectively , 93 pg/mL , 3,850 nmol/L , and 37 . 2 micromol/L in the oral group and 95 pg/mL , 3,630 nmol/L , and 40.0 micromol/L in the parenteral therapy group . After 4 months of therapy , the respective mean values were 1,005 pg/mL , 169 nmol/L , and 10.6 micromol/L in the oral group and 325 pg/mL , 265 nmol/L , and 12.2 micromol/L in the parenteral group . The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant , with P < .0005 and P < .05 , respectively . In cobalamin deficiency , 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior BACKGROUND Cobalamin ( vitamin B12 ) deficiency , the most common cause of megaloblastic anemia , is treated with intramuscular ( IM ) cobalamin . It has been suggested by some investigators that oral ( p.o . ) cobalamin treatment may be as effective in the treatment of this condition , with the advantages of ease of administration and lower cost . OBJECTIVE This study assessed the effects and cost of p.o . versus i.m . cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency . METHODS This was a 90-day , prospect i ve , r and omized , open-label study conducted at the Division of Hematology , Department of Internal Medicine , Adnan Menderes University Research and Practice Hospital ( Aydin , Turkey ) . Patients aged > or = 16 years with megaloblastic anemia due to cobalamin deficiency were r and omized to receive 1000-microg cobalamin p.o . once daily for 10 days ( p.o . group ) or 1000-microg cobalamin i.m . once daily for 10 days ( i.m . group ) . After 10 days , both treatments were administered once a week for 4 weeks , and after that , once a month for life . Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected . Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0 , 10 , 30 , and 90 and serum vitamin B12 concentration on days 0 and 90 . The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing . Neurologic sensory assessment , including soft-touch and pinprick examinations , was used to identify neuropathy at baseline and study end . Tolerability was assessed using laboratory tests and patient interview . Cost was assessed using the cost of the study drug and of the injection . RESULTS Sixty patients completed the study 26 in the p.o . group ( 16 men , 10 women ; mean [ SD ] age , 60 [ 15 ] years ) and 34 in the i.m . group ( 17 men , 17 women ; mean [ SD ] age , 64 [ 10 ] years ) .  Reticulocytosis was observed in all patients . In the p.o . group , at days 30 and 90 , all hematologic parameters changed significantly versus day 0 ( mean hemoglobin levels increased [ both P<0.001 ] ; mean corpuscular volume decreased [ both P<0.001 ] ; mean white blood cell count increased [ day 30 , P<0.01 ; day 90 , P<0.001 ] ; and mean platelet count increased [ both P<0.001 ] ) . The mean serum vitamin B12 concentration increased significantly from day 0 to 90 ( P<0.001 ) . These hematologic parameters and the recovery patterns were similar between the 2 groups . Neurologic findings included sensitive peripheral neuropathy in 9 patients ( 15.0 % ) , alteration of cognitive function ( loss of memory , impaired concentration ) in 7 patients ( 11.7 % ) , and loss of sense of vibration in 5 patients ( 8.3 % ) . Neurologic improvement was detected in 7 of 9 patients ( 77.8 % ) in the p.o . group and 9 of 12 patients ( 75.0 % ) in the i.m . group at day 30 . CONCLUSIONS In this study of patients with megaloblastic anemia due to cobalamin deficiency , p.o . cobalamin treatment was as effective as i.m . cobalamin treatment . P.o . treatment also was better tolerated and less expensive compared with IM treatment . However , because of the small sample size and the short term of this study , further long-term studies are needed to determine the efficacy of p.o . cobalamin treatment A cross-sectional survey was conducted in order to describe the use of oral cobalamin among geriatricians , hematologists , and general practitioners , and to explore factors related to its use . The study population consisted of all geriatricians ( n = 138 ) and hematologists ( n = 317 ) listed in the Canadian Medical Directory plus a r and om sample of 307 general practitioners . The overall response rate was 40 % . Intramuscular and oral cobalamin was prescribed by 76 and 32 % of the respondents , respectively . Twenty seven percent reported using both  oral and intramuscular cobalamin  and 6 % reported using only oral cobalamin . Only 25 % of respondents indicated they were aware of a RCT demonstrating the efficacy of oral cobalamin prior to reading a synopsis of the study in the survey . After multivariate adjustment , only the belief that oral cobalamin was effective and certainty about who carried oral preparations remained independently associated with oral cobalamin use . Oral cobalamin has been shown to be an efficacious , cost efficient and safe method of treating cobalamin deficiency . Nonetheless , it is not used by the majority of physicians treating this condition . Strategies to promote the use of oral cobalamin should be directed at educating physicians of its efficacy and providing them with prescribing information on where it can be purchased BACKGROUND Supplementation 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 r and omized , 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 BACKGROUND It has been suggested that oral cobalamin ( vitamin ( B12 ) ) therapy may be an effective therapy for treating cobalamin deficiencies related to food-cobalamin malabsorption . However , the duration of this treatment was not determined . PATIENTS AND METHOD In an open-label , nonplacebo study , we studied 30 patients with established cobalamin deficiency related to food-cobalamin malabsorption , who received between 250 and 1000 microg of oral crystalline cyanocobalamin per day for at least 1 month .  ENDPOINTS Blood counts , serum cobalamin and homocysteine levels were determined at baseline and during the first month of treatment . RESULTS During the first month of treatment , 87 % of the patients normalized their serum cobalamin levels ; 100 % increased their serum cobalamin levels ( mean increase , + 167 pg/dl ; P < 0.001 compared with baseline ) ; 100 % had evidence of medullary regeneration ; 100 % corrected their initial macrocytosis ; and 54 % corrected their anemia . All patients had increased hemoglobin levels ( mean increase , + 0.6 g/dl ) and reticulocyte counts ( mean increase , + 35 x 10(6)/l ) and decreased erythrocyte cell volume ( mean decrease , 3 fl ; all P < 0.05 ) . CONCLUSION Our findings suggest that crystalline cyanocobalamin , 250 - 1000 microg/day , given orally for 1 month , may be an effective treatment for cobalamin deficiencies not related to pernicious anemia BACKGROUND & AIMS Patients with previous stomach and terminal ileum resections are often treated with intramuscular vitamin B12 injections . Disadvantages are , on a worldwide scale , the frequent need for medical personnel to administer injections and the sometimes painful way of application . This study was design ed to investigate the feasibility of intranasal hydroxocobalamin suppletion in cobalamin-deficient patients and to assess whether intranasal hydroxocobalamin application could be an alternative for intramuscular injection . METHODS Six patients with plasma cobalamin concentrations of < 200 ng/L were recruited . A dose of 1500 micrograms hydroxocobalamin was applied intranasally at days 0 , 14 , and 21 . Plasma cobalamin concentrations were determined 1 hour after hydroxocobalamin application and on days 0 , 7 , 21 , 28 , and 35 . RESULTS All patients showed substantial increase of cobalamin concentrations 1 hour after intranasal application . In these 6 patients , there was an eightfold increase of mean baseline cobalamin concentrations . All patients showed a sustained increase of baseline cobalamin concentrations 1 week after prior intranasal application of hydroxocobalamin . No side effects were noted . CONCLUSIONS Intranasal application of hydroxocobalamin in cobalamin-deficient patients results in fast nasal absorption and leads to sustained increase of baseline cobalamin concentrations 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-r and omized , 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
target: The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters , for example hemoglobin level , mean erythrocyte cell volume and reticulocyte count .
  Oral cobalamin treatment avoids the discomfort , inconvenience and cost of monthly injections .
  TAKE HOME MESSAGE Our experience and the present analysis support the use of oral cobalamin therapy in clinical practice
background: IMPORTANCE OF THE FIELD Cobalamin ( vitamin B12 ) deficiency is particularly common in the elderly ( > 15 % ) .
  Management of cobalamin deficiency with cobalamin injections is well codified at present , but new routes of cobalamin administration ( oral and nasal ) are being studied , especially oral cobalamin therapy for food-cobalamin malabsorption .
  AREAS COVERED IN THIS REVIEW The objective of this review is to evaluate the efficacy of oral cobalamin treatment in elderly patients .