Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients. Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Cobalamin absorption and serum homocysteine and methylmalonic acid in elderly subjects with low serum cobalamin. Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons. Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. High prevalence of cobalamin deficiency in elderly outpatients. Effective treatment of cobalamin deficiency with oral cobalamin.
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 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 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 We prospect ively studied 41 consecutive elderly patients with serum cobalamin ( vitamin B12 ) levels lower than 125 pmol/l . The protein-bound cobalamin absorption test ( PBAT ) was performed in 34 of them and in 27 selected elderly control patients . The lower decision limit was 0.18 % and an abnormal test was detected in only 9 ( 26 % ) of the 34 patients with low serum cobalamin level . When the PBAT was compared to the Schilling ( Dicopac method ) test , a concordant result was found in 80 % . Serum methylmalonic acid and /or total homocysteine concentrations were elevated in 75 % ( 26/35 ) of the patients with low serum cobalamin levels but also in 30 % ( 5/17 ) of the control patients . Of the 12 and 9 cobalamin-deficient patients with elevated serum levels of methylmalonic acid and homocysteine , normalization after cobalamin therapy was obtained in 11 and 5 respectively . In conclusion , determination of serum metabolites and their response to cobalamin therapy are a sensitive index of significant cobalamin deficiency and a useful means of distinguishing between cobalamin and folate deficiency . The PBAT offers little advantage over the Schilling test in diagnosing cobalamin malabsorption in elderly patients BACKGROUND A high prevalence of cobalamin deficiency occurs in the elderly population , which may be treated orally or with injections . Little is known about the relative bioavailability of crystalline cobalamin added to food products . OBJECTIVE The objective was to assess the effect of supplementation with 1000 microg crystalline cobalamin , carried either by a milk product or a capsule , on cobalamin status in mildly cobalamin-deficient elderly Dutch persons . DESIGN Two double-blind r and omized controlled intervention studies , each covering a 12-wk supplementation period , were carried out in parallel . Mildly cobalamin-deficient elderly persons ( n = 112 ) were separately recruited for the milk and capsule trials . Mild cobalamin deficiency was defined as a cobalamin concentration between 100 and 300 pmol/L and a plasma methylmalonic acid ( MMA ) concentration > or = 0.30 micromol/L. Allocation to the placebo or cobalamin carrier was carried out independently in both trials . RESULTS In the fortified-milk group , the mean ( + /-SD ) increase in serum cobalamin was 250 + /- 96 pmol/L , the median ( 5th and 95th percentiles ) decrease in plasma MMA was 0.19 ( -0.76 , -0.04 ) micromol/L , and the median decrease in plasma homocysteine was 4.0 ( -7.3 , 3.0 ) micromol/L. All changes were significantly different from those in the placebo milk group ( P < 0.01 ) . Likewise , in the cobalamin-capsule group , the mean increase in serum cobalamin was 281 + /- 136 pmol/L , the median decrease in plasma MMA was 0.18 ( -2.95 , 0.14 ) micromol/L , and the median decrease in plasma homocysteine was 1.8 ( -10.6 , 2.4 ) micromol/L ; all changes were significantly different from those in the placebo capsule group ( P < 0.01 ) . No significant differences were observed between the fortified-milk and capsule groups ( P > 0.40 ) . CONCLUSION Crystalline cobalamin added to milk is an effective alternative to cobalamin capsules for improving cobalamin status 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 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 OBJECTIVE To measure the prevalence of cobalamin ( vitamin B12 ) deficiency in geriatric out patients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment . DESIGN Prospect i ve study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays . In patients with serum cobalamin levels < or = 300 pg/mL , the response to cobalamin treatment in the group with levels of methylmalonic acid and /or homocysteine > 3 st and ard deviations ( SD ) above the mean for normals was compared with that of those without such elevations . SETTING Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center , Denver , CO . PATIENTS One-hundred and fifty-two consecutive out patients , ages 65 to 99 , were screened . Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospect ively evaluated and treated with cobalamin . MAIN OUTCOME MEASURES Cobalamin , methylmalonic acid , homocysteine , complete blood counts , neurologic examination , and neuropsychological testing . RESULTS The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and /or homocysteine elevated to > 3 SD was 14.5 % of the screened out patients . A similar proportion of patients with low normal serum cobalamin levels ( between 201 and 300 pg/mL ) demonstrated elevated metabolites > 3 SD ( 56 % ) compared with patients with low serum cobalamin levels ( < or = 200 pg/mL ) ( 62 % ) . Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospect ively . Results for complete blood count , lactate dehydrogenase , bilirubin , baseline neurologic score , and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites . The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment . One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment . CONCLUSION There was a high ( 14.5 % ) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly out patients . The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201 - 300 pg/mL compared with patients with low cobalamin levels ( < or = 200 pg/mL ) had markedly elevated metabolites which fell with cobalamin treatment . Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects 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
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
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 .