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. Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms Oral cobalamin remains medicine's best kept secret. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial Performance of the Serum Cobalamin Assay for Diagnosis of Cobalamin Deficiency Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. Cobalamin dose regimen for maximum homocysteine reduction in end-stage renal disease. Clinical effect of computer generated physician reminders in health screening in primary health care - a controlled clinical trial of preventive services among the elderly Plasma Homocysteine Is a Sensitive Marker for Tissue Deficiency of Both Cobalamines and Folates in a Psychogeriatric Population Nasal absorption of hydroxocobalamin in healthy elderly adults. Total serum homocysteine in senile dementia of Alzheimer type. Long-term effects of nitrous oxide anaesthesia on laboratory and clinical parameters in elderly Omani patients: a randomized double-blind study. Comparative effects of hydroxocobalamin and cyanocobalamin on plasma homocysteine concentrations in end-stage renal disease.
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 Abstract Early diagnosis of cobalamin deficiency is crucial , owing to the latent nature of this disorder and the result ing possible irreversible neurological damage . A normal serum cobalamin concentration does not reliably rule out a functional cobalamin deficiency and there does not at present seem to be any single diagnostic approach to achieve this diagnosis . A new marker for cobalamin status is the serum concentration of cobalamin bound to transcobalamin II ( holoTC ) . Because methods suitable for routine use have been unavailable until recently , the clinical value of lowholoTC is still uncertain . Furthermore , there is at the moment no gold st and ard or true reference method to diagnose subtle cobalamin deficiency , which makes evaluation of the clinical usefulness of holoTC and the estimation of sensitivity and specificity problematic . In this study , we aim ed to assess whether low holoTC concentrations are congruent with other biochemical signs of cobalamin deficiency in a group of psychogeriatric patients . The findings in the present study showthat holoTC is strongly related to serum cobalamin ( 0.68 ; p<0.001 in both patients and controls ) . Distribution of the different markers for cobalamin/folate status in the 33 patients with low levels of serum holoTC ( below40 pmol/l ) showed that 17 patients had normal levels of the other markers for cobalamin status . This may indicate poor specificity of lowholoTC for cobalamin deficiency . In 23 out of 176 patients with normal levels of holoTC  we observed pathological levels of other markers for cobalamin deficiency . The use of  holoTC  in the present study group did not give significant additional information other than that given by serum cobalamin and therefore can not be recommended in this clinical setting 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 OBJECTIVES To investigate the effect of cobalamin/folate supplementation on cognitive function in elderly patients with dementia . METHOD The cobalamin/folate status of the patients was evaluated by measuring plasma homocysteine , serum methylmalonic acid , serum cobalamin and blood folate .  Thirty-three patients were studied and repeatedly assessed with the  Mini-Mental State Examination ( MMSE )  and  ' A short cognitive performance test for assessing memory and attention ' ( SKT )  during vitamin substitution . RESULTS Patients with mild-moderate dementia and elevated plasma homocysteine levels improved clinical ly with increased test scores after vitamin substitution , while severely demented patients and patients with normal plasma homocysteine levels did not improve clinical ly . CONCLUSIONS Plasma homocysteine may be the best marker for detecting treatable cobalamin/folate deficiency in patients with dementia Background Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants . Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights ( 2000 - 3000 g ) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function ( total homocysteine ( tHcy ) > 6.5 μmol/L ) at 6 months . Methods Levels of cobalamin , folate , riboflavin and pyridoxal 5´-phosphate , and the metabolic markers tHcy and methylmalonic acid ( MMA ) , were determined at 6 weeks , 4 and 6 months ( n = 80/68/66 ) . Neurodevelopment was assessed with the Alberta Infants Motor Scale ( AIMS ) and the parental question naire Ages and Stages ( ASQ ) at 6 months . At 6 months , 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind r and omized controlled trial to receive 400 μg hydroxycobalamin intramuscularly ( n = 16 ) or sham injection ( n = 16 ) . Biochemical status and neurodevelopment were evaluated after one month . Results Except for folate , infants who were exclusively breastfed for > 1 month had lower B vitamin levels at all assessment s and higher tHcy and MMA levels at 4 and 6 months . At 6 months , these infants had lower AIMS scores ( p = 0.03 ) and ASQ gross motor scores ( p = 0.01).Compared to the placebo group , cobalamin treatment result ed in a decrease in plasma tHcy ( p < 0.001 ) and MMA ( p = 0.001 ) levels and a larger increase in AIMS ( p = 0.02 ) and ASQ gross motor scores ( p = 0.03 ) . Conclusions The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants , and that this may have a negative effect on early gross motor development . In infants with mild cobalamin deficiency at 6 months , cobalamin treatment significantly improvement cobalamin status and motor function , suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding , may be due to cobalamin deficiency . Clinical trial registration Clinical Trials.gov , number The authors ' objective , with this study , was to determine the use in routine clinical practice of the cobalamin serum assay in evaluating patients suspected of having cobalamin deficiency . The design was a prospect i ve observational study of a diagnostic test compared with a criterion gold st and ard . The setting was the Veterans Affairs hospital inpatient wards and outpatient clinics . The authors prospect ively identified all patients who had serum cobalamin measured and enrolled all those with cobalamin < 133 pmol/L ( 180 pg/mL ) and a r and om sample of patients with cobalamin greater than or equal to 133 pmol/L ( N = 168 ) . There were no interventions .To identify cobalamin deficiency , subjects underwent blinded clinical and laboratory examinations , Schilling test , and urinary methylmalonic acid assay , with a trial of cobalamin replacement , if needed . Of 1,599 patients assayed , 84 ( 5.2 % ) had low cobalamin levels . After evaluation , 16 of those with low cobalamin levels , but none of those with normal cobalamin levels , were confirmed as deficient . Positive predictive value of a low cobalamin level in this population was 22.2 % ( 95 % confidence interval , 12.6–31.8 % ) . After correcting for sampling procedure , the calculated sensitivity rate was 100 % ( 95 % confidence interval , 20.6–100 % ) , and specificity rate was 95.8 % ( 95 % confidence interval , 95.2–100 % ) . The authors conclude that in routine use , the positive predictive value of the cobalamin assay is low . Low cobalamin levels should not be used alone to justify a lifetime of parenteral therapy or to rule out other conditions that mimic cobalamin deficiency 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 Plasma total homocysteine ( tHcy ) concentrations are markedly increased in end-stage renal disease and only partially corrected by folic acid supplementation . We and others have reported that cobalamin , administered parenterally , reduces plasma tHcy substantially below the lowest concentrations attainable with folic acid . We have now carried out a r and omized controlled clinical trial to compare the plasma Hcy-lowering effect of 3 intravenous cyanocobalamin dose regimens in maintenance hemodialysis patients : 1 mg postdialysis every 28 , 14 , and 7 days in addition to routine oral vitamin B supplementation .  All patients in the hemodialysis unit where the study was carried out routinely received 1 mg intravenous cyanocobalamin every month , so participants who were r and omized to receive the vitamin every 28 days simply continued with their existing treatment program . Serum cobalamin and plasma tHcy concentrations in the control group did not change over the course of the study . As measured after 8 weeks of therapy , intravenous cyanocobalamin every 14 days increased serum cobalamin approximately 2.5-fold and reduced plasma tHcy by 11.5 % ( P = .035 ) below the concentration previously attained with monthly administration , whereas treatment every 7 days increased serum cobalamin concentrations approximately 5-fold and reduced plasma tHcy by 11.0 % ( P = .013 ) . These results show that intravenous cyanocobalamin at 7- or 14-day intervals reduces plasma tHcy concentrations of hemodialysis patients below the levels brought about by prior long-term administration every 4 weeks and confirms that plasma tHcy lowering with parenteral cobalamin is a true pharmacological effect and not merely correction of a latent deficiency state OBJECTIVES To apply and evaluate the effects of a program for computer generated physician reminders , integrated with an electronic patient record ( EPR ) system , for opportunistic health screening in elderly patients . DESIGN A pilot study design ed as a 20-month clinical trial with a control group and a 20-month non-intervention follow-up using a computer reminder program that selects patients for screening in five intervention areas ( diabetes , hypertension , cobalamin deficiency , hypothyroidism and anaemia ) . SETTING Four primary health care ( PHC ) centres in suburban Stockholm . SUBJECTS The intervention was design ed for patients 70 years or older from one health care centre who visited a general practitioner ( GP ) during the first 20-month period . Patients from the three remaining centres served as controls . MAIN OUTCOME MEASURES The number of patients who underwent the tests , who had pathological test results , new diagnoses and new pharmacological treatments in both patient groups . RESULTS In total , 602 patients underwent screening and 1989 were controls . There was a statistically significant , moderate or marked increase ( 13 - 75 % ) in the number of patients who were tested in all five intervention areas . An increase in pathological test results ( 1 - 8 % ) was found in two areas : hypertension and cobalamin deficiency . There was an increase in the number of patients with the diagnosis of cobalamin deficiency during the study . At follow-up a decrease in new diagnoses for anaemia was found . CONCLUSION The system seems to be associated with a moderate to large increase in laboratory and manual screening tests for both established and new screening areas . The effect on clinical outcomes was found mainly in a not-yet-established screening area ( cobalamin deficiency ) , indicating that the system may be clinical ly useful when introducing new screening services The concentration of blood folates was decreased and the concentration of plasma homocysteine was increased in a psychogeriatric population , whereas the concentrations of methylmalonic acid or serum cobalamins were not changed compared with healthy subjects . The highest frequency of abnormal values was shown by plasma homocysteine concentration , which was increased in 88 of 168 patients . In 29 of these 88 patients increased concentration of plasma homocysteine could possibly be attributed to tissue cobalamin deficiency . One patient had only a lowered concentration of blood folate . Thirteen patients had elevated concentrations of serum creatinine which could explain increased plasma homocysteine concentration . Even if the remaining patients ( n = 45 ) had normal vitamin levels in circulation , the increased plasma homocysteine concentration in most cases must be attributed to tissue deficiency of cobalamins and /or folates . Thus , many patients with increased plasma homocysteine concentrations need further vitamin supplementation despite their normal vitamin levels in serum and blood 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 OBJECTIVE The main hypothesis was that subtle vitamin B12 deficiencies occur more commonly in senile dementia of Alzheimer type ( SDAT ) that in healthy elderly individuals , and may be revealed by elevated total serum homocysteine ( tHcy ) . A subsidiary hypothesis was that such deficiencies would be nutritionally independent as determined by retinol binding protein ( RBP ) . DESIGN A prospect i ve case-controlled survey . SETTING A Welsh urban psychogeriatric assessment centre and local general practice . PATIENTS Thirty patients , aged 65 or over , seen consecutively in 1994 with features compatible with DSM-III-R criteria for primary degenerative dementia of Alzheimer type and 30 cognitively intact age-matched control subjects . MEASURES Diagnosis was assessed using the CAMDEX . Cognitive scores were evaluated with the CAMCOG scale for patients and MMSE scores for control subjects . THcy was measured using high performance liquid chromatography ( HPLC ) , and RBP assayed by a radial immunodiffusion method . RESULTS Patients had a highly significant elevation of tHcy compared with control ( p < 0.0001 ) . Multiple regression highlighted the interrelated effects of tHcy and total serum cobalamin on cognitive scores . RBP did not differ between groups . Macrocytosis was absent , and neutrophil hypersegmentation uncommon , in hyperhomocysteinaemic patients . CONCLUSIONS SDAT patients have significantly elevated tHcy . This is independent of RBP determined nutritional status . ' Classical ' haematological changes of cobalamin or folate deficiency are poor predictors of tHcy in these patients . Aberrant cobalamin tissue delivery appears to contribute to SDAT cognitive decline . Relative contributions of other tHcy determinants require further investigation AIMS This study examined the long-term effects of nitrous oxide anaesthesia on serum levels of cobalamin and folate , red cell folate levels and haematological parameters , and neurological status in elderly Omani patients . METHODS Sixty-nine consecutive patients undergoing ophthalmic surgery were r and omly and double-blind assigned to nitrous oxide or propofol anaesthesia .  They met the following entry criteria : age 55 years or above , no major organ failure , no clinical signs or symptoms of cobalamin or folate deficiency , mean cell volume ( MCV ) < /= 96 fl , haematocrit ( Hct ) higher than 0.3 and no cobalamin and /or folate substitution therapy during the preceding months .  Serum levels of cobalamin and folate , red cell folate levels , and haematological parameters were measured prior to anaesthesia and 3 - 5 weeks later . At that time , the patients also underwent thorough neurological examination . RESULTS Data of 51 patients were complete and considered for analysis . In both nitrous oxide and propofol group , the range of exposure time was comparable ( + /-1 h ) . In the nitrous oxide group , a slight but significant decrease in haemoglobin , Hct , and red blood cell count ( RBC ) ( P < 0.001 ) was observed , whereas there was a mild increase in mean cell haemoglobin ( MCH ) and mean cell volume ( P < 0.05 ) . In addition , there was a significant decrease in serum folate levels ( P < 0.05 ) . Hct and RBC decreased slightly in the propofol group ( P < 0 . 05 ) , whereas there was a small increase in MCH . There was no difference between the two anaesthetics with regard to serum cobalamin and red cell folate levels , but there was a significant decrease in serum folate levels in the nitrous oxide group compared to those in the propofol group . Three patients with pre-existing low red cell folate levels , who were r and omized to nitrous oxide anaesthesia , developed clinical symptoms of folate deficiency . CONCLUSION This study showed that short-term ( 40 - 80 min ) nitrous oxide anaesthesia did not affect cobalamin levels but reduced serum folate levels in this elderly population . Although this reduction was clinical ly irrelevant , some patients with pre-existing asymptomatic folate deficiency developed nitrous oxide-induced folate deficiency End-stage renal disease ( ESRD ) is associated with marked hyperhomocysteinemia which is only partially corrected by folic acid and pyridoxine supplementation . We and others have reported that various forms of parenteral cobalamin reduce plasma total homocysteine ( tHcy ) concentrations of patients with ESRD substantially below the lowest levels attainable with folic acid . We here report a 16-week r and omized controlled crossover trial which directly compared the Hcy-lowering effect of intravenous hydroxocobalamin ( HC ) with that of cyanocobalamin ( CC ) .  Folic acid- and vitamin B12-replete maintenance hemodialysis patients were r and omly assigned to receive either 1 mg intravenous HC weekly for 8 weeks followed by CC for a further 8 weeks , or CC for 8 weeks followed by HC for 8 weeks . Hydroxocobalamin  increased serum cobalamin concentrations 40-fold , whereas CC increased them only 10-fold , but both treatments reduced plasma tHcy concentrations similarly by 33 % ( P < .001 ) . Crossover to the alternate form of the vitamin greatly affected the serum cobalamin concentration but was without further effect on the plasma tHcy concentration . These results confirm that weekly cobalamin injections lower plasma tHcy concentrations of hemodialysis patients well below the level attainable with folic acid . Hydroxocobalamin and CC are equipotent despite producing very different serum cobalamin concentrations
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 .