Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients. Cobalamin absorption and serum homocysteine and methylmalonic acid in elderly subjects with low serum cobalamin. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. High prevalence of cobalamin deficiency in elderly outpatients. Effective treatment of cobalamin deficiency with oral cobalamin. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Normalization of plasma vitamin B12 concentration by intranasal hydroxocobalamin in vitamin B12-deficient patients. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial The limited value of methylmalonic acid, homocysteine and holotranscobalamin in the diagnosis of early B12 deficiency. Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Screening elderly populations for cobalamin (vitamin B12) deficiency using the urinary methylmalonic acid assay by gas chromatography mass spectrometry. Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons. Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin 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 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 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 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 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 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 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 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 To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia ( PA ) . DESIGN R and omized , double-blind , placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month . SETTING Two geriatric hospitals in the North Western Health Care Network , Melbourne , Australia . PARTICIPANTS Thirty-one in patients with serum vitamin B12 levels between 100 and 150 pmol/L , without PA , other malabsorption disorders , or progressive neurological or terminal illness . The mean age was 81.4 years . INTERVENTION After informed consent , a medical and drug history was taken and the Mini-Mental State Examination ( MMSE ) completed . A dietitian made assessment of oral cobalamin intake . Blood was taken for serum vitamin B12 , serum and red cell folate assay , full blood examination , fasting serum gastrin , parietal and intrinsic factor antibodies , fasting serum homocysteine , and creatinine . Patients were then r and omized to receive 10 microg oral cyanocobalamin , 50 microg oral cyanocobalamin , or placebo treatment for 1 month , after which the investigations and clinical examinations were repeated . MEASUREMENTS Percentage change in the level of vitamin B12 , homocysteine , folate , and red cell parameters and absolute changes in MMSE were calculated and compared between groups . The groups were compared on the number of responders who improved their level of B12 by 20 % . Chi-square calculations on changes in serum vitamin B12 concentration were also performed . RESULTS Mean serum vitamin B12 + /- st and ard deviation improved by 51.7 + /- 47.1 % in the 50-microg group , 40.2 + /- 34.4 % in the 10-microg group , and 11.7 + /- 24.5 % in the placebo group . The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group ( P=.044 ) . The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group ( P=.186 ) . Eight of 10 subjects in each treatment group were classified as responders , compared with two of 11 in the placebo group ( P=.004 ) . Homocysteine levels fell in patients receiving cyanocobalamin , but this fall failed to reach statistical significance . There were no significant changes in the other parameters measured . CONCLUSION Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12 . This result has implication s for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12 Background Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125 - 200 pM/l is lacking . We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo . Methods This multicentre ( 13 general practice s , two nursing homes , and one primary care center in western Switzerl and ) , parallel , r and omised , controlled , closed-label , observer-blind trial included 50 patients with serum vitamin B12 levels between 125 - 200 pM/l who were r and omized to receive either oral vitamin B12 ( 1000 μg daily , N = 26 ) or placebo ( N = 24 ) for four weeks . The institution 's pharmacist used simple r and omisation to generate a table and allocate treatments . The primary outcome was the change in serum methylmalonic acid ( MMA ) levels after one month of treatment . Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels . Blood sample s were central ised for analysis and adherence to treatment was verified by an electronic device ( MEMS ; Aardex Europe , Switzerl and ) . Trial registration : IS RCT N 22063938 . Results Baseline characteristics and adherence to treatment were similar in both groups . After one month , one patient in the placebo group was lost to follow-up . Data were evaluated by intention-to-treat analysis . One month of vitamin B12 treatment ( N = 26 ) lowered serum MMA levels by 0.13 μmol/l ( 95%CI 0.06 - 0.19 ) more than the change observed in the placebo group ( N = 23 ) . The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 ( 95 % CI 1.7 - 6.4 ) . A significant change was observed for the B12 serum level , but not for the homocysteine level , hematocrit , or mean corpuscular volume . After three months without active treatment ( at four months ) , significant differences in MMA levels were no longer detected . Conclusions Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency . However , a one-month daily treatment with1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months , and treatment had no effect on haematological signs of B12 deficiency Treatment of B12 deficiency is important to prevent progressive neurological and /or hematologic disease but requires a secure diagnosis . The aim of this study was to evaluate second line tests of B12 status as prognostic indicators of a hematologic response to vitamin B12 therapy .  Forty-nine patients referred with low , serum vitamin B12 concentrations were treated with intramuscular B12 and re-assessed after 3 months . Methylmalonic acid , homocysteine , holotranscobalamin and neutrophil hypersegmentation index were measured before and after treatment . Before treatment 27/49 patients were anemic or macrocytic of whom 15 had a clear hematologic response . All the tests had a similar prognostic accuracy . Symptomatic improvement did not correlate with hematologic response . Supplementary tests of vitamin B12 status were not significantly better than total serum B12 concentration as predictors of a hematologic response to vitamin B12 therapy BACKGROUND Elevated serum homocysteine levels have been associated with the development of Alzheimer 's dementia ( AD ) . The combined use of a mecobalamin capsule preparation , which contains vitamin B12 0.5 mg with an active methyl base , and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen . OBJECTIVE The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD . METHODS This r and omized , double-blind , placebocontrolled trial was conducted at En Chu Kong Hospital , Taipei , Taiwan . Male and female patients aged > 50 years with mild to moderate AD and normal folic acid and vitamin B12 concentrations were enrolled . All patients received treatment with an acetylcholinesterase inhibitor and were r and omized to receive add-on mecobalamin ( B12 ) 500 mg + multivitamin supplement , or placebos , PO QD for 26 weeks . The multivitamin contained pyridoxine ( B6 ) 5 mg , folic acid 1 mg , and other vitamins and iron .  Serum homocysteine level was measured and cognitive tests were conducted at baseline and after 26 weeks . The primary efficacy outcome was change in cognition , measured as the change in score from baseline to week 26 on the Alzheimer 's Disease Assessment Scale 11-item Cognition subscale . Secondary efficacy outcomes included changes in function in performance of activities of daily living ( ADLs ) and concentrations of homocysteine , B12 , and folic acid . Tolerability was assessed by comparing the 2 study groups with respect to physical examination findings , including changes in vital signs , laboratory test abnormalities , concomitant medication use , and compliance of study medication was assessed using an interview with the patient 's caregiver , as well as the monitoring of adverse events ( AEs ) throughout the study . RESULTS Eighty-nine patients ( 45 men , 44 women ; all Taiwanese ; mean [ SD ] age , 75 [ 7.3 ] years ) were enrolled and r and omized . Overall , there were no significant differences in cognition or ADL function scores between the 2 groups . At week 26 , the mean ( SD ) between-group difference in serum homocysteine concentration versus placebo was -2.25 ( 2.85 ) micromol/L ( P = 0.008 ) , and the mean serum concentrations of vitamin B12 and folic acid were significantly higher ( but within normal range ) in the multivitamin group compared with placebo ( . , + 536.9 [ 694.4 ] pg/mL [ P < 0.001 ] and + 13.84 ng/mL [ 11.17 ] [ P = 0.012 ] at 26 weeks , respectively ) . The 2 most common AEs were muscle pain ( 11.1 % and 6.8 % ) and insomnia ( 8.9 % and 9.1 % ) in the multivitamin and placebo groups , respectively . CONCLUSIONS In this population of patients with mild to moderate AD in Taiwan , a multivitamin supplement containing vitamins B(6 ) and B(12 ) and folic acid for 26 weeks decreased homocysteine concentrations . No statistically significant beneficial effects on cognition or ADL function were found between multivitamin and placebo at 26 weeks PURPOSE This study assesses the value of the urinary methylmalonic acid ( MMA ) assay by gas chromatography mass spectrometry as a screening procedure for detection of cobalamin ( Cbl ) deficiency and estimates the prevalence of undetected Cbl deficiency in elderly population s. SUBJECTS AND METHODS A total of 809 elderly individuals over age 65 were screened using r  and om spot urine specimens from 4 different sites : a health fair , retirement apartments , a hospital-based elderly assessment center , and a nursing home . Follow-up tests included  serum total Cbl , serum MMA , and normalization of urinary and serum MMA levels with Cbl intramuscular ( IM ) therapy . RESULTS The prevalence of elevated urinary MMA varied across population groups , from 3.0 % in elderly visiting a health fair to 5.1 % in elderly residing in retirement apartments . Follow-up on 35 of 36 subjects with elevated urinary MMA levels showed that 18 had low serum total Cbl ( less than 180 pg/mL at Hospital 1 or less than 200 pg/mL at Hospital 2 ) , 12 had low-normal Cbl ( 180 or 200 pg/mL to 350 pg/mL ) , and 5 had normal Cbl . Of the 12 subjects with low-normal Cbl on retesting , further assessment was performed in 7 , and all 7 of these subjects had evidence of Cbl deficiency . Cbl IM therapy  was initiated for 23 subjects ; 16 were seen for follow-up and all had normal urinary MMA . CONCLUSION The relatively high prevalence of undetected Cbl deficiency identified in the seniors warrants additional studies of elderly population s. The sensitivity , convenience , and noninvasive nature of the urinary MMA assay by gas chromatography mass spectrometry make it a practical screening test 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 Low serum cobalamin levels are often found in apparently normal older subjects . A major worry of leaving cobalamin deficiency untreated is that it may lead to subtle deterioration in cognitive function . OBJECTIVES To investigate the effect of supplementation on the cognitive function of older people with cobalamin deficiency by a r and omized trial . METHODS Fifty Chinese subjects more than 60 years old with serum cobalamin level < 120 pmol/l were r and omized into supplement and control groups . Fasting serum methylmalonic acid levels ( MMA ) were measured . A battery of neuropsychological tests was administered . The supplement group received intramuscular cyanocobalamin injections , while the control group received no intervention . They were followed up at around 4 months . RESULTS 78 % of the subjects had raised MMA , indicating metabolic cobalamin deficiency . Supplemented subjects improved in performance IQ , but the amount of improvement was not significantly more than that of control subjects . Moreover , the supplement group fared worse than the control group at follow-up in some motor function scores . Three out of seven demented subjects had improvement in Mini-Mental State Examination scores , but there was no consistent improvement in other neuropsychological scores . CONCLUSIONS This study suggested that cobalamin deficiency did not invariably cause cognitive impairment in older people . There remain the possibilities that cobalamin deficiency causes cognitive impairment or exacerbates coexisting dementia in some older people In a prospect i ve , multicentre , double-blind controlled study , the effect of an intramuscular vitamin supplement containing 1 mg vitamin B12 , 1.1 mg folate , and 5 mg vitamin B6 on serum concentrations of methylmalonic acid ( MMA ) , homocysteine ( HCYS ) , 2-methylcitric acid ( 2-MCA ) , and cystathionine ( CYSTA ) was compared with that of placebo in 175 elderly subjects living at home and 110 in hospital .  Vitamin supplement and placebo were administered eight times over a 3-week period . Vitamin supplement but not placebo significantly reduced all four metabolite concentrations at the end of the study in both study groups . The maximum effects of treatment were usually seen within 5 - 12 days . Initially elevated metabolite concentrations returned to normal in a higher proportion of the vitamin than of the placebo group : 92 % vs 20 % for HYCS ; 82 % vs 20 % for MMA ; 62 % vs 25 % for 2-MCA ; and 42 % vs 25 % for CYSTA . The response rate to vitamin supplements supports the notion that metabolic evidence of vitamin deficiency is common in the elderly , even in the presence of normal serum vitamin levels . Metabolite assays permit identification of elderly subjects who may benefit from vitamin supplements
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 .