Cobalamin Values Research Articles

Evaluation of trypsin-like immunoreactivity, pancreatic lipase immunoreactivity, cobalamin, and folate in zoo-housed African painted dogs (Lycaon pictus) at a North American zoological facility.

Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI), canine pancreatic lipase immunoreactivity (cPLI), cobalamin, and folate at one North American facility. 15 healthy African painted dogs held at one institution were sampled during routine health examinations. Blood was collected at routine health examinations, and serum was separated and stored until testing. Serum was analyzed for cTLI, cPLI, cobalamin, and folate. The results were evaluated for correlation to sex, age, and storage time of samples. All individuals had cTLI and folate levels below normal reference ranges for domestic dogs (< 5.0 µg/L and < 7.7 µg/L, respectively). Cobalamin values were within or above reported domestic dog ranges, and cPLI values were within range as well. No analytes were significantly influenced by sex or time in storage, while cTLI was positively correlated with age. cTLI and folate did not fall within normal domestic canid reference ranges in this population of healthy African painted dogs. Clinical interpretation of these values based on domestic canid recommendations would indicate clinical disease, which was not apparent in this population. Analytes for pancreatic function and malabsorption or gastrointestinal indicators, including cTLI, cPLI, and folate, in African painted dogs should be interpreted with caution when using domestic dog references ranges.

Prospective Randomized Controlled Clinical Trial of the Long-Term Effects of Omeprazole on Healthy Dogs.

The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T0), 30 days after the start of treatment (T1), and at 60 days (T2). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T0, 481.4 (±170.21) at T1, and 513.2 (±174.50) at T2. In the omeprazole group, the values were 424.62 (±161.57) at T0, 454.5 (±160.96) at T1, and 414.87 (±127.90) at T2. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17-218.75] at T0, 76.06 [30.67-199.87] at T1, and 63.02 [35.81-176.06] at T2. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T0, 191.77 [75.31-1901.77] at T1, and 128.16 [43.62-1066.46] at T2. Statistically significant differences were detected (p = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.

RELATIVE COMPARISON OF STABILITY AND DEGRADATION OF METHYLCOBALAMIN TABLETS OF DIFFERENT BRANDS AT DIFFERENT STORAGE SETTINGS

Objective: To assess relative comparison of stability and degradation of Methylcobalamin tablets of different brands at various storage circumstances.&#x0D; Methods: The comparative in vitro study of Methycobal (innovator brand) with its other 5 different brands Cobalamin, Neuromet, Incobal, Qbal and Mecobal was organized for evaluation of physicochemical features of hardness, thickness, friability, weight variation, disintegration time and accelerated stability at 3 temperatures, 25 °C, 30 °C±65 % and 40 °C±75 % respectively for 3 mo. Later all brands were passed through HPLC for checking the extent of degradation of drug products.&#x0D; Results: All tablet brands were within the weight variation specified limits except Mecobal with a relative standard deviation of 6.83%. The weight variation values of Methycobal, Cobalamin, Neuromet, Incobal, Qbal and Mecobal were 0.29%, 0.11%, 0.09%, 0.13%, 0.09% and 0.14% after friability test respectively as per standard limits. The average thickness of Cobalamin, Incobal and Mecobal were not within specified limits. The average hardness of all trades was within limits except Cobalamin and Mecobal exceeding 6kp. The disintegration time of all companies was as per specifications.&#x0D; Conclusion: Qbal was found economical and cost-effective. However, study facts unveiled no noteworthy variety in the Q. C assessments of Methylcobalamin brands.

Identification of Patients with Cobalamin Deficiency Crucially Depends on the Diagnostic Strategy.

Our goal was to determine vitamin B12 (cobalamin) deficiency with different diagnostic strategies, to propose the best possible laboratory strategy, and to synthesize the relevance of biomarkers in the diagnosis of a cobalamin deficiency. We performed a secondary data analysis. The testing strategies were (i) vitamin B12 solely, (ii) holotranscobolamin solely, (iii) vitamin B12 and holotranscobolamin, and (iv) reflex testing of holotranscobalamin in samples with vitamin B12 < 300 pmol. A set of 3,044 laboratory samples with vitamin B12 and holotranscobalamin serum values from unselected in- and outpatients from a secondary care hospital. A sample was classified as cobalamin deficient when low values of vitamin B12 < 137 pmol/L or holotranscobalamin ≤ 37 pmol/L were measured. Low cobalamin values were identified in 591 (19.4%) samples either according to low vitamin B12 values (305; 10.0%) or low holotranscobalamin values (436; 14.3%). For 2,404 values with vitamin B12 < 300 pmol/L, the additional measurement of holotranscobalamin (reflex-testing) enabled the detection of an additional 278 (9.1%) deficiencies. When the grey zone was decreased to 138 - 219 pmol/L, the reflex testing of an additional 1,240 samples identified a total of 511 (16.8%) samples as cobalamin deficient. The identification of cobalamin deficiency or sufficiency highly depends on the diagnostic strategy. A reflex testing with a grey zone for vitamin B12 < 220 pmol/L identifies cobalamin deficiency cost efficiently in 86.5% cases (511 out of 591). Physicians should apply a uniform strategy on how to address the diagnosis of cobalamin deficiency and indication for treatment. In-hospital guidelines, which describe methodology and sensitivity of the locally used assays for vitamin B12 and holotranscobalamin could guide them.

Predictors of serum cobalamin and its association with homocysteine in community-dwelling older adults

Background/objectivesThis study investigates the predictors of serum cobalamin concentrations in community-dwelling older adults and the relationship between serum cobalamin and plasma homocysteine.Subjects/methodsSerum cobalamin and plasma homocysteine were measured by SimulTRAC-SNB radio assay and HPLC, respectively. Linear multiple regression analyses were performed with cross-sectional data of 352 participants aged 60–90 years to examine (1) the predictors of serum cobalamin and (2) the association between cobalamin and homocysteine status. Age, sex, body composition, diet, supplement use, smoking, serum folate, serum pyridoxal 5´-phosphate, serum creatinine, and selected diseases were considered as potential predicting/confounding factors.ResultsMedian values of serum cobalamin, plasma homocysteine, and dietary cobalamin intake were 256 pmol/L, 9.7 µmol/L, and 5.7 µg/day, respectively. In multiple regression analysis, cobalamin intake, sex, body composition, serum creatinine and smoking did not predict serum cobalamin (all P > 0.05). In contrast, age (β = 0.111, P = 0.031), serum folate (β = 0.410, P < 0.001) and diagnosis of chronic inflammatory bowel disease (IBD) (β = 0.101, P = 0.037) were positively and cancer diagnosis (β = −0.142, P = 0.003) was negatively associated with serum cobalamin. The model explained 23% of the variability of serum cobalamin. After exclusion of subjects with IBD/cancer diagnosis and/or vitamin B/multi-vitamin supplementation, only serum folate remained as positive predictor of serum cobalamin (β = 0.407, P < 0.001). Serum cobalamin was positively associated with inverse-transformed plasma homocysteine before (β = 0.298, P < 0.001) and after (β = 0.199, P < 0.001) multiple adjustments.ConclusionsSerum folate but not cobalamin intake or age proves to be a main predictor of cobalamin status. Nevertheless, independent of serum folate and other potential confounders, serum cobalamin is inversely associated with plasma homocysteine.

Effects of storage conditions and duration on cobalamin concentration in serum samples from cats and dogs.

OBJECTIVE To evaluate the effects of storage conditions and duration on cobalamin concentration in serum samples from dogs and cats. DESIGN Experiment. SAMPLE Serum samples from 9 client-owned cats and 9 client-owned dogs. PROCEDURES Serum harvested from freshly obtained blood samples was separated into 11 aliquots/animal. One aliquot (baseline sample) was routinely transported in light-protected tubes to the laboratory for cobalamin assay; each of the remaining aliquots was stored in a refrigerator (6°C; n = 5) or at room temperature (20°C) with exposure to daylight (5) for 24, 48, 72, 96, or 120 hours. Aliquots were subsequently wrapped in aluminum foil, frozen (-20°C), and then transported to the laboratory for measurement of cobalamin concentration, all in the same run. Percentage decrease in cobalamin concentration from baseline was analyzed by means of linear mixed modeling. RESULTS No differences in cobalamin values were identified between cats and dogs; therefore, data for both species were analyzed together. Median baseline serum cobalamin concentration was 424 ng/L (range, 178 to 1,880 ng/L). Values for serum samples stored with daylight exposure at room temperature were significantly lower over time than were values for refrigerated samples. Although values for refrigerated samples did not decrease significantly from baseline values over time, values for the other storage condition did; however, the mean percentage decrease for serum samples stored at room temperature was small (0.14%/h; 95% confidence interval, 0.07% to 0.21%/h). CONCLUSIONS AND CLINICAL RELEVANCE Overall, serum cobalamin concentration appeared stable for 5 days when feline and canine serum samples were refrigerated at 6°C. The effect of light and room temperature on serum cobalamin concentration, although significant, was quite small for samples stored with these exposures for the same 5-day period.

Relationship Between the Levels of Holotranscobalamin and Vitamin B12 in Children

The purpose of this study was to evaluate the relationship between the plasma holoTC and serum vitamin B12 in children and to identify a cutoff cobalamin values according to holoTC. One hundred and fifty-five children were enrolled into the study. All children were evaluated for hemoglobin, vitamin B12, folate, ferritin and holoTC levels. Children were grouped as with low vitamin B12 level (≤200pg/mL, group I) and normal vitamin B12 (>200pg/mL, group II). Serum vitamin B12, and holoTC levels were performed in each patient in the study. In 101 patients with low vitamin B12 (group I) the mean holoTC was 21.74±1.14pmol/L. In 54 children with normal vitamin B12 (group II) mean holoTC was 44.0±2.7pmol/L (p<0.01). A ROC curve analysis was performed to delineate the optimum cut-off point for vitamin B12 level and it was found to be 165pg/mL with a sensitivity of 70% and specificity of 74%; the area under curve was 0.783 (p<0.01). Our study displayed a positive correlation between vitamin B12 and holoTC, and defined an optimum cutoff value for vitamin B12 as 165pg/mL. Further studies using the markers both MMA, tHcy and holoTC to confirm the findings are needed.

Low Cobalamin Levels as Predictors of Cobalamin Deficiency: Importance of Comorbidities Associated with Increased Oxidative Stress

BackgroundCobalamin (B12) deficiency can lead to irreversible neurocognitive changes if unrecognized. Screening involves measurement of serum cobalamin levels, but the sensitive metabolic indicators of cobalamin deficiency, methylmalonic acid (MMA) and homocysteine (HCys), may be normal when cobalamin values are low and elevated when cobalamin values are normal. Because cobalamin is inactivated by oxidation, the relationship between these metabolites and comorbidities associated with increased oxidative stress (oxidant risks) in subjects with low and low-normal cobalamin levels was studied. MethodsA retrospective record-review was conducted of community-dwelling adults evaluated for cobalamin deficiency during a 12-year period with serum cobalamin values in the low (≤ 200 pg/mL; n = 49) or low-normal (201-300 pg/mL; n = 187) range and concurrent measurement of MMA. ResultsWhen “No” oxidant risk was present, elevated MMA (>250 nmol/L) and HCys (>12.1 μmol/L) values occurred in 50% and 30% of subjects, respectively (P <.01). In contrast, when “Three or More” oxidant risks were present, mean MMA and HCys values were significantly higher, and elevated MMA and HCys values occurred in 84% and 78% of these subjects, respectively (P ≤.012). Pharmacologic doses of cyanocobalamin significantly decreased metabolite values in ≥ 94% of treated subjects. ConclusionIn subjects with low or low-normal cobalamin values, metabolic evidence of cobalamin deficiency is more frequent when 3 or more oxidant risks are present. Thus, defining a low serum cobalamin level to screen for cobalamin deficiency may be a “moving target” due to the variable presence and severity of often subtle, confounding clinical conditions in individual subjects.

Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid

Background: Diagnosing cobalamin deficiency is critical, given the high prevalence of cobalamin deficiency particularly in developing countries. Measuring serum cobalamin levels is of limited diagnostic sensitivity, in other words its specificity and sensitivity are low. The present study investigated the changes in the levels of metabolic markers – plasma homocysteine, plasma methylmalonic acid (MMA) and urinary MMA – of cobalamin metabolism.Methods: Plasma cobalamin and serum folic acid were studied in 206 pregnant women over the last four prenatal weeks. Plasma cobalamin, folic acid, homocysteine, MMA from umbilical cord blood and urinary MMA in newborns were studied.Results: Plasma cobalamin values were low in 66% of the mothers. There was a positive correlation between maternal and neonatal plasma cobalamin values (r = 0.72, p < 0.001). B12 was strongly inversely associated with plasma MMA, urine MMA and plasma homocysteine. To predict cobalamin deficiency, sensitivities of plasma MMA, urinary MMA and homocysteine were 96.4%, 95.6% and 88.2%, respectively. And positive predictive values (PPV) were 96.2%, 96.9% and 86% for plasma MMA, urinary MMA and plasma homocysteine levels, respectively.Conclusion: Plasma MMA and urinary MMA B12 are the most robust markers of cobalamin deficiency. As a non-invasive method, urinary MMA is a sensitive method in demonstrating cobalamin deficiency in the newborn.

Efficacy of a 28-Day Oral Cyanocobalamin Supplementation on Vitamin B Status in Spanish Institutionalized Elderly

Cobalamin deficiency is a common problem in the elderly. There is no consensus about adequate doses for supplementation. We performed an intervention study in order to establish the efficacy of a supplement providing 500 µg cyanocobalamin for four weeks in sixty-four institutionalized elderly residents, over 60 years of age, in Madrid (Spain). Before and after treatment, concentrations of serum cobalamin, serum holotranscobalamin, serum total homocysteine, and serum and red blood cell folate were analyzed. Clusters were built according to the initial cobalamin status and differences in the effect of supplementation were checked using a general linear model for repeated measures. Cobalamin and holotranscobalamin increased highly significantly from 308 to 558 pmol/L and from 54 to 96 pmol/L (p < 0.001) in the whole study group as well as in each subgroup (clustered by initial cobalamin levels, all p < 0.01), with the highest relative change in the subgroup with the lowest initial cobalamin values. Total homocysteine decreased from 15 to 13 µmol/l, p < 0.001). Only the change of cobalamin (F = 4.61, p < 0.01), but not of holotranscobalamin nor total homocysteine, depended on the initial serum cobalamin status. A supplementation with an oral supplement solution of 500 µg cyanocobalamin daily for only four weeks, a shorter period than that found in former studies, may be considered suitable in institutionalized elderly.

Functional vitamin B12 deficiency in alcoholics: An intriguing finding in a retrospective study of megaloblastic anemic patients

Background Measurement of serum cobalamin levels is the standard investigation for assessing Vitamin B12 deficiency. However some patients with clinical evidence of cobalamin deficiency may have serum levels within the normal range. Since falsely increased values of cobalamin can be caused by alcoholic liver disease, we evaluated the impact of this disease on the diagnosis of cobalamin and folic acid deficiency. Methods We reviewed data of 101 adult patients with megaloblastic anemia assessed by measuring in parallel serum cobalamin, serum folate and red blood cell folate levels. Further tests were performed in order to find the cause of megaloblastosis. All patients were treated with cobalamin and/or folic acid therapy. Results Vitamin B12, folate and both deficiency were found in 86, 5 and 6 cases respectively. Normal cobalamin serum levels, normal serum and erythrocyte folate levels were found only in 3 patients, all alcohol-dependent, while in another alcoholic borderline vitamin B12 serum levels were found. All the four patients responded to cobalamin treatment. Conclusion Some alcohol-dependent patients with megaloblastic anemia may respond to vitamin B12 treatment despite normal cobalamin serum levels; therefore in alcoholics caution is urged in the interpretation of these vitamin assays, because of possible functional vitamin B12 deficiency.

Prevalence of low serum cobalamin in infertile couples

A high prevalence of low levels of cobalamin had been found in a survey of multi-ethnic normal individuals in Israel. The purpose of this study was to investigate the incidence of cobalamin deficiency among Israeli couples suffering from infertility. All couples seen at the in vitro fertilization clinic at an urban hospital (Shaare Zedek Medical Center) in Jerusalem for a 6-month period were invited. Mean cobalamin levels were 259.2 pg ml(-1) in males and 275.1 pg ml(-1) in females (normal >200 pg ml(-1)), 35.5% of 172 men and 23.3% of 223 females had cobalamin deficiency (P = 0.01). There were 171 couples with complete demographic questionnaires and cobalamin values for each partner. In 74 couples (43.3%), one partner was cobalamin deficient, with no significant difference between those with unexplained infertility versus those with explained infertility; and in 13 couples, both partners were cobalamin deficient. Thirty-nine per cent of all men with an abnormal semen analysis had cobalamin deficiency, a finding that requires further investigation. This study questions whether higher rates of male infertility in Israel are partially ascribable to cobalamin deficiency. Recommendation for supplementation in both males and females to achieve high-normal levels of cobalamin would be prudent.

Serum vitamin B12 and folate status among patients with chemotherapy treatment for advanced colorectal cancer

Background. There are conflicting results on the role of cobalamin and folate for epidemiology and carcinogenesis in colorectal cancer patients and the need of supplementation for prevention of chemotherapy toxicity.Patients and methods. Serum cobalamin, folate, and homocysteine were analysed before and during the treatment of 93 patients with advanced colorectal cancer (ACRC) with first-line chemotherapy treatment. This cohort was compared with a healthy control group of 224 individuals.Results. Patients with ACRC had similar cobalamin, folate, and homocysteine values as the healthy control group. There were no correlations between serum cobalamin, folate, and homocysteine values and objective response. There were no correlations to anaemia or other severe toxicity for cobalamin and homocysteine. A total of 12 patients had folate deficiency, and 10 of those suffered from severe toxicity (grade 3 or more). All patients had markedly increased folate values after 2 months of treatment. Folate and homocysteine did not predict patient outcome; however, patients with subclinically low cobalamin values (<300 pmol/L) had significant better overall survival and time to progression than patients with normal or high cobalamin values.Conclusion. Patients with ACRC seem to have fairly adequate cobalamin and folate status before and during chemotherapy treatment. This study indicates that ACRC patients receiving chemotherapy do not need supplementation with vitamin B12 and folate. A minor portion of the patients had folate deficiency, and most of those patients had severe toxicity. Patients with subclinically low cobalamin values had surprisingly better survival.

Elevated Methylmalonic Acid (MMA) and Homocysteine (Hcys) Levels in Patients with Normal Serum Cobalamin (Cbl) Values: Diabetes Mellitus (DM) and Age as a Possible Causes of Cbl Resistance.

Survey studies consistently show that 7–30% of older subjects with normal serum Cbl values have elevated levels of the Cbl-dependent metabolites, MMA and HCys, even when renal function is normal. Although this finding may reflect insensitivity of the measurement of total serum Cbl to early Cbl depletion, the possibility of Cbl “resistance” with “functional” Cbl deficiency should also be considered. I recently reported that Cbl, MMA and HCys levels are not predictive of clinical responses to Cbl therapy (Blood2005;105, 2005). Interestingly, 8 of the 30 neurologic responders had DM and 5 of these DM pts had elevated MMA values despite normal serum Cbl levels. DM is common in the elderly and produces neurologic changes similar to those of Cbl deficiency. Thus, a retrospective review of Cbl, MMA and HCys levels in patients evaluated for Cbl deficiency during a 10 year period at a staff model HMO was performed with particular attention to the presence of DM. Since both MMA and HCys increase in renal disease, men with serum creatinine &gt;1.5 mg/dl and women with serum creatinine &gt;1.3 mg/dl were excluded from analysis. MMA was measured in 406 subjects, including 49 pts with DM and 357 non-diabetic pts (Non-DM). HCys levels were considered evaluable in 223 non-alcoholic pts (30 DM pts and 193 Non-DM pts) all of whom had normal serum or red cell folate values and normal thyroid function. When serum Cbl levels were ≤ 300 pg/ml, high MMA values (&gt;250 nmol/l) occurred with similar frequency in DM pts (7 of 16; 44%) and in Non-DM pts (93 of 153; 61%)(χ 2=0.305; NS). In contrast, when Cbl values were &gt;300 pg/ml, MMA was significantly more likely to be increased in DM pts (20 of 33; 61%) than in Non-DM pts (70 of 204; 34%)(χ 2=7.238; p&lt;0.01). Indeed, even when serum Cbl levels were &gt;600 pg/ml, MMA values were increased in 6 of 8 DM pts (75%) and in only 10 of 41 Non-DM pts (24%)(χ2=5.813;p&lt;0.02). Moreover, of the 70 Non-DM pts with normal Cbl and increased MMA values, 43 had fasting blood glucose studies performed within 6 months of evaluation and 15 of them had increased values (≥ 100 mg/dl). Thus, DM or impaired fasting glucose was present in at least 35 of the 90 pts (39%) with normal Cbl and increased MMA values. Hgb A1C was measured within 4 mo of evaluation in 38 of the 49 DM pts. MMA was increased in 15 of the 21 DM pts with A1C values &gt;7.0% (71%) and in only 7 of 17 pts with A1C values ≤ 7.0% (41%)(χ2=3.936; p&lt;0.05), suggesting that poorly controlled DM pts were more likely to have high MMA levels. Although metformin use in DM can impair Cbl absorption, only 6 of the 27 DM pts with high MMA values were on metformin therapy (22%). In Non-DM pts with normal Cbl levels, MMA was increased in 31 of 108 pts ≤ 60 years old (29%) and in 29 of 57 patient &gt;70 years old (53%)(χ 2=7.395; p&lt;0.01). This difference remained significant when only those Non-DM pts with serum creatinine ≤ 1.1 mg/dl were considered. High HCys values (&gt;12.1 μmol/l) were also more frequent in DM pts (9 of 22; 40%) than in Non-DM pts (29 of 115; 25%) when serum Cbl was &gt;300 pg/ml, but this difference was not statistically significant (χ2= 2.452; p=0.12). It is concluded that 1) DM is associated with “functional” Cbl deficiency and a role for pharmacologic doses of Cbl in the therapy of diabetic neuropathy should be further explored; and 2) age is also a determinant of MMA in Non-DM pts with normal serum Cbl levels and normal renal function suggesting that other age-related disorders can impair Cbl utilization.

Relationship between methylmalonic acid and cobalamin in uremia

Relationship between methylmalonic acid and cobalamin in uremia. To evaluate the requirement for routine supplementation with vitamin B12 and to study the effect of a change from injection to oral B12 supplementation, we examined the relationship between cobalamin and methylmalonic acid in plasma from 67 patients on chronic hemodialysis, all in regular therapy with intramuscular cobalamin injections (1 mg) every third month. Starting just before one cobalamin injection, blood samples were collected once a month during a nine-month withdrawal from regular cobalamin substitution to a final three-month period with cyanocobalamin tablets (1 mg) administered once daily. Plasma cobalamin was above the lower reference limit in all subjects, and from a peak value one month after the regular injection, the cobalamin concentration during the withdrawal period decreased to a level below the point of origin, followed by a significant rise after cyanocobalamin tablets. The methylmalonic acid concentrations were above the reference interval. In the withdrawal period, the concentrations significantly increased further, followed by a significant decrease after oral cyanocobalamin substitution. We demonstrated a within-patient inverse relationship between the concentrations of methylmalonic acid and cobalamin in plasma from these uremic patients. Despite the fact that only two of the patients developed subnormal plasma cobalamin values, we demonstrated a B12 depletion during the withdrawal period. Treatment with cyanocobalamin tablets once daily was found efficient, but the oral doses should possibly be increased.

Vitamin status of elderly people in Germany.

In the last decade several attempts (Nationale Verzehrsstudie, NVS; Verbundstudie Ernährungserhebung und Risikofaktoren-Analytik, VERA: Bethanien-Ernährungsstudie, BEST) have been made to assess the nutritional status of the elderly in Germany. A careful evaluation of those data describing the vitamin status clearly indicate that healthy older people are not at higher risk for vitamin deficiency compared to younger adults. The results of the NVS showed that, except for folic acid, mean intake of all vitamins exceeded 80% of the current recommendations. Only 5% of blood vitamin concentrations analyzed in a subpopulation (VERA-Study) were founded to be below the physiological range. Only the incidence of low cobalamin values increased with age, presumably due to gastrointestinal problems (atrophic gastritis). In contrast, geriatric patients showed markedly lower vitamin blood concentrations compared to healthy subjects of the same age (BEST-Study). This might be explained by physical and mental deterioration, handicaps, chronic diseases and multiple chronic drug use. Underrepresentation of very old people, lack of reliable reference values for biomarkers and uncertainties in data collection may have contributed to misinterpretations. Representative studies are needed to objectively assess the nutritional status of the elderly population in Germany.

Schilling and protein-bound cobalamin absorption tests are poor instruments for diagnosing cobalamin malabsorption.

To assess the advantage of a protein-bound cobalamin absorption test (PBAT) over the Schilling test in patients with suspected cobalamin (vitamin B12) malabsorption. Clinical study of consecutive patients referred from primary care units, medical and neurological clinics. The catchment area of Sahlgrenska University Hospital, Göteborg. Referred patients (n = 155) with suspected cobalamin deficiency and at least one serum cobalamin value < 200 pmol L-1. All patients were investigated with upper gastrointestinal endoscopy with biopsies taken from the gastric body and duodenal mucosa. Serum methylmalonic acid (MMA) and homocysteine (Hcy) were determined in all 109 patients not on cobalamin substitution. A dual isotope cobalamin absorption test was then performed with the concomitant administration of crystalline (Schilling) and protein-bound cobalamin (PBAT). Number of patients with gastric body atrophy diagnosed with each absorption test and the relation between these results and functional cobalamin deficiency defined as elevated MMA and Hcy, that normalized after cobalamin substitution treatment. The majority of patients with abnormal absorption tests had already developed elevated MMA and/or Hcy. PBAT was more sensitive than the Schilling test in identifying patients with gastric body atrophy but the sensitivity was too low for clinical use. About 1/3 of the patients with gastric body atrophy and normal absorption tests had elevated MMA and/or Hcy, indicating cobalamin deficiency. PBAT may be somewhat more sensitive than the Schilling test but neither test is sensitive enough for diagnosing cobalamin malabsorption at an early stage.

Cobalaminopenia in a postindustrial society: minimal incidence, age distribution, and differences by sex

The aim of this study was to obtain a conservative estimate of the current incidence of low serum cobalamin levels (cobalaminopenia) in a modern, postindustrial region in Sweden. All serum cobalamin determinations made during 1993 in one health care area (Umeå) with 131,393 inhabitants were analyzed. These analyses were all performed in a single laboratory; data were available for 6451 serum samples from 5225 patients. Serum cobalamin levels <145 pmol/L (corresponding to the lowest decile determined in previous years) were identified in 582 samples from 473 patients. Data from these samples were further investigated to determine distributions of cobalaminopenia based on age and sex. The overall minimal incidence of low serum cobalamin levels (<145 pmol/L) was 0.36%; the incidence increased with age. Low serum cobalamin levels occurred significantly more frequently in women aged 15 to 44 years than in men in the same age group. In contrast, men older than 70 years of age were more prone to cobalaminopenia than women of the same age. The current minimal incidence of low serum cobalamin values suggests adequate functioning of social and health care networks, with an overall minimal incidence of cobalaminopenia of 0.36% and a projected incidence of cobalaminopenia in the Umeå health care area of approximately 1%.

12 Cobalamin and folate deficiency in the elderly

Elderly persons are more likely to have low values for serum and erythrocyte folate, and for serum cobalamin. Many of those with low vitamin levels have biochemical abnormalities consistent with true deficiency, including increased formiminoglutamic acid excretion, abnormal marrow deoxyuridine suppression, and raised serum levels of methylmalonic acid and homocysteine. Therapy with the appropriate vitamin reverses the biochemical defect. Despite this, the clinical consequences for most elderly persons are remarkably few. True megaloblastic anaemia is rare, and the small number of therapeutic trials to date have not improved the levels of haemoglobin in the treated subjects, although the mean corpuscular volume has decreased significantly. There has been recent concern that these low blood vitamin levels might be important causes of nervous system damage, but studies specifically of the elderly have not demonstrated overall improvements in neurological function following therapy. Vascular damage from high blood homocysteine levels secondary to cobalamin or folate deficiency remains a potential hazard. Dietary insufficiency, malabsorption of protein-bound vitamin B12 secondary to atrophic gastritis, and defective absorption of folyl polyglutamates seem the likeliest possible causes. Pernicious anaemia, although a common cause of severe megaloblastic anaemia in the elderly, is an infrequent cause for the low cobalamin levels in population studies. Although the benefits are uncertain, the balance of the evidence suggests that one should treat elderly persons with low values of cobalamin or folate. Crystalline vitamin B12 and folic acid are absorbed normally and are therefore suitable for replacement therapy, provided that pernicious anaemia is excluded.

Trypsin inhibition: A potential cause of cobalamin deficiency common to the pathogenesis of Alzheimer-type dementia and AIDS dementia complex?

There is increasing evidence for an association between Alzheimer-type dementia (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and histopathological confirmation of AD neuropathology. The cobalamin deficiency could be either a consequence or cause of amyloidogenesis. Cobalamin deficiency is also associated with the acquired immunodeficiency syndrome (AIDS). A common pathogenic mechanism may exist for AIDS dementia complex (ADC) and AD, but there is no explanation at present for these associations. This paper presents the hypothesis that protease inhibition is a common factor in AD and ADC resulting in protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.