Low Cobalamin Concentrations Research Articles

Breastfeeding and biomarkers of folate and cobalamin status in Norwegian infants: a cross-sectional study

Abstract Folate and vitamin B12 (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B12 status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0–12 months (n = 125) were recruited through public health clinics. We registered breastfeeding status and measured serum concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). The associations between infant age, breastfeeding, and biomarker concentrations were estimated in regression models. The mean (SD) age was 24 (16) weeks, and 42% were exclusively breastfed, 38% were partially breastfed, and 21% were weaned. Overall, median (IQR) folate, cobalamin, tHcy, and MMA concentrations were 47 (35–66) nmol/L, 250 (178–368) pmol/L, 6.99 (5.69–9.27) µmol/L, and 0.35 (0.24–0.83) µmol/L, respectively. None of the infants were folate deficient, 15% were vitamin B12 deficient (< 148 pmol/L), and 23% had low vitamin B12 status (148–221 pmol/L). Elevated tHcy (> 6.5 μmol/L) and MMA (> 0.26 μmol/L) were found in 62% and 69% of the infants, respectively. Compared to weaned, exclusively or partially breastfed infants were younger and had 46% higher tHcy concentrations (P < 0.001), in addition to 47% and 39% lower cobalamin concentrations (P < 0.001), respectively. However, the observed biomarker concentrations appeared to be independent of infant age. In conclusion, low vitamin B12 status was prevalent and appeared to be more common in the younger exclusively breastfed compared to older weaned infants. The implications of low vitamin B12 status in infancy are unknown and require further investigation.

Effects of oral versus parenteral cobalamin supplementation on methylmalonic acid and homocysteine concentrations in dogs with chronic enteropathies and low cobalamin concentrations

The objective of this study was to compare the effects of parenteral (PE) versus oral (PO) cobalamin supplementation on serum methylmalonic acid (MMA) and homocysteine (HCY) concentrations in dogs with hypocobalaminaemia. Thirty-six dogs with serum cobalamin concentrations below 285ng/L (reference interval (RI): 244–959ng/L) were treated with PO (0.25–1.0mg daily) or PE cobalamin (0.25–1.2mg/injection) using a block-randomized schedule. Serum MMA and HCY concentrations were analysed at day 0, 28 and 90 after start of supplementation.There was no significant difference between the PO and PE group regarding serum MMA or HCY concentrations at any time point. Median (range, P comparing baseline and 28 days, P comparing 28days and 90 days) serum MMA concentrations (nmol/L; RI 415–1193) were 932 (566–2468) in the PO and 943 (508–1900) in the PE group at baseline, respectively, 705 (386–1465, P<0.0001) and 696 (377–932, P<0.0001) after 28 days, and 739 (450–1221, P=0.58) and 690 (349–1145, P=0.76) after 90 days. Serum HCY concentrations (median (range), P comparing baseline and 28 days, P comparing 28days and 90 days, μmol/L; RI 5.9–31.9) in the PO and PE groups were 12.2 (3.3–62.2) and 8.4 (3.7–34.8) at baseline, 12.5 (5.0–45.0, P=0.61) and 8.0 (3.8–18.3, P=0.28) after 28 days, and 17.7 (7.3–60.0 P=0.07) and 12.4 (6.3–33.1, P=0.0007) after 90 days, respectively. Oral and parenteral cobalamin supplementation had the same effect on serum MMA concentrations in this group of dogs.

Comparison of efficacy of oral and parenteral cobalamin supplementation in normalising low cobalamin concentrations in dogs: A randomised controlled study

The aim of this study was to compare the efficacies of parenteral and oral cobalamin supplementation protocols in dogs with chronic enteropathies and low cobalamin concentrations. It was hypothesised that both treatments would increase serum cobalamin concentrations significantly. Fifty-three dogs with chronic enteropathies and serum cobalamin concentrations<285ng/L (reference interval 244–959ng/L) were enrolled. Dogs were randomised to treatment with either daily oral cobalamin tablets (0.25–1.0mg cyanocobalamin daily according to body weight) or parenteral cobalamin (0.4–1.2mg hydroxycobalamin according to body weight). Serum cobalamin concentrations were analysed 28±5days and 90±15days after initiation of supplementation. After 28 days, all dogs had serum cobalamin concentrations within the reference interval or above. In the parenteral group (n=26), median (range) cobalamin concentrations were 228 (150–285) ng/L at inclusion, 2107 (725–10,009) ng/L after 28days and 877 (188–1267) ng/L after 90 days. In the oral group (n=27), median (range) serum cobalamin concentrations were 245 (150–285) ng/L at inclusion, 975 (564–2385) ng/L after 28days and 1244 (738–4999) ng/L after 90 days. In both groups, there were significant differences in serum cobalamin concentrations between baseline and 28 days, and between 28days and 90days (P<0.001). In conclusion, both parenteral and oral cobalamin supplementation effectively increase serum cobalamin concentrations in dogs with chronic enteropathies and low cobalamin concentrations.

MTRR rs326119 polymorphism is associated with plasma concentrations of homocysteine and cobalamin, but not with congenital heart disease or coronary atherosclerosis in Brazilian patients

BackgroundDifferences in the distribution of the MTRR rs326119 polymorphism (c.56+781 A>C) between patients with congenital heart disease (CHD) and controls have been described in Chinese individuals. The association is thought to be due to deregulation of homocysteine-cobalamin pathways. This has not been replicated in other populations. The primary objective of this study was to assess the influence of the MTRR rs326119 polymorphism on biochemical parameters of vitamin B12 metabolism, coronary lesions, and congenital heart disease in Brazilian subjects. MethodsWe selected 722 patients with CHD, 1432 patients who underwent coronary angiography, and 156 blood donors. Genotyping for the MTRR polymorphism was evaluated by high-resolution melting analysis, and biochemical tests of vitamin B12 metabolism were measured. ResultsSubjects carrying the AC or CC genotypes had higher homocysteine concentrations (9.7±0.4μmol/L and 10.1±0.6μmol/L) and lower cobalamin concentrations (260.5±13.3pmol/L and 275.6±19.9pmol/L) compared with the subjects carrying the AA genotype (8.7±0.5μmol/L and 304.8±14.7pmol/L), respectively. A multiple linear regression model also identified a significant association between the number of C variant alleles with the concentrations of homocysteine and cobalamin. Nonetheless, the allelic and genotypic distributions for MTRR rs326119 were not associated with CHD or coronary atherosclerosis in the studied samples. ConclusionOur findings indicate that the MTRR rs326119 variant might be a genetic marker associated with homocysteine and cobalamin concentrations, but not a strong risk factor for CHD or coronary atherosclerosis in the Brazilian population.

Influence of duration and dose of metformin on cobalamin deficiency in type 2 diabetes patients using metformin

Metformin use is associated with cobalamin (vitamin B12) deficiency. However, the influence of both duration and dose of metformin is unclear. Studies using holotranscobalamin, a marker for cellular cobalamin deficiency, are scarce. We therefore investigated the prevalence of cobalamin deficiency in type 2 diabetes patients using both markers, and its relation with duration and dose of metformin use. This cross-sectional study among 550 type 2 diabetes patients using metformin (mean daily dose 1,306 mg; mean duration 64 months) was conducted in four primary care centers in Utrecht, the Netherlands. Cobalamin and holotranscobalamin concentrations were measured at the annual diabetes check. Detailed information on metformin use and confounding variables was collected from medical records. The prevalence of a cobalamin deficiency was 28.1 %, while a holotranscobalamin deficiency occurred in 3.9 % of the patients. Adjusting for multiple confounders, a 1 mg/day increase in daily metformin dose was associated (p < 0.001) with 0.042 (95 % CI -0.060, -0.023) decrease in cobalamin concentrations. Similarly, a 10 g increase of cumulative metformin dose was associated (p = 0.006) with -0.070 (-0.12, -0.021) lower cobalamin concentrations after adjustment for confounders. Duration of metformin use was not associated with cobalamin concentrations after multivariable adjustment. Similar results were observed for holotranscobalamin. Cobalamin deficiency occurs frequently among diabetes patients using metformin. A higher daily and cumulative doses of metformin were strongly associated with lower cobalamin and holotranscobalamin concentrations, while duration was not. It is thus important to account for metformin dose in recommendations for screening for cobalamin deficiency.

Intrinsic Factor Blocking Antibody Interference Is Not Detected in Five Automated Cobalamin Immunoassays

To systematically assess five automated cobalamin assays for intrinsic factor binding antibody (IFBA)-induced interference using pooled serum. Six pools created from IFBA-negative and IFBA-positive serum representing low, normal, and high cobalamin concentrations were analyzed before and after polyethylene glycol (PEG) precipitation of immunoglobulins on five cobalamin assays: the Centaur XP (Siemens Healthcare Diagnostics, Tarrytown, NY), IMMULITE 2000 (Siemens Healthcare Diagnostics), ARCHITECT i2000SR (Abbott Diagnostics, Abbott Park, IL), UniCel Dxl 800 (Beckman Coulter, Chaska, MN), and Modular E170 (Roche Diagnostics, Indianapolis, IN). Cobalamin concentrations before and after PEG treatment were similar, almost all within a 30% total allowable error, with no difference in pattern between the IFBA-negative and IFBA-positive pools regardless of the cobalamin concentration. Our results suggest that, under optimal conditions, the five automated cobalamin assays assessed are not susceptible to IFBA-mediated interference.

Serum autoimmune gastritis markers, pepsinogen I and parietal cell antibodies, in patients with Type 1 diabetes mellitus: A 5-year prospective study

To determine the temporal evolution of serum markers of autoimmune gastritis, mainly pepsinogen I (PI) and parietal cell antibodies (PCA), in patients with Type 1 diabetes mellitus (DM1). A 5-yr prospective follow-up study of 168 DM1 patients (87 men, aged 31 ± 9.3 yr) attending the endocrinology outpatient clinic of a university hospital evaluated in 2001 and 2006. Serum PI, gastrin, hemoglobin, cobalamin concentrations, PCA and antibodies to intrinsic factor were measured. In 2001, 11 patients had low PI concentrations and positive PCA (group I), 11 had only low PI concentrations (group II), and 33 had only positive PCA (group III). After 5 yr, PI remained low and PCA positive in all patients from group I. In group II, PI remained low in 4 and normalized in 7. In group III, 4 patients presented low PI concentrations after 5 yr, which remained normal in the other 29 subjects. PCA became negative in 17 patients from group III. In 2001, 3 of the 11 patients of group I had low cobalamin concentrations. In 2006, 2 additional patients from this group presented low cobalamin concentrations. These results show the importance of determining PI together with PCA, since the presence of abnormal results in both tests, that is low PI and positive PCA, is the association that best identifies patients with a higher risk to decrease cobalamin concentrations during follow-up.

Cobalamin and folate status in infants and young children in a low-to-middle income community in India

Background: Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking.Objective: The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6–30 mo residing in a low-to-middle income community in North India.Design: Children aged 6–30 mo (n = 2482) were identified through a community survey in a low-to-middle socioeconomic area in New Delhi, India. Non-fasting venous blood samples were collected before enrollment in another trial.Results: The median (interquartile range; IQR) cobalamin concentration in 6–11-mo-old children was substantially lower in breastfed (183; 120–263 pmol/L) than in nonbreastfed (334; 235–463 pmol/L) children. Cobalamin concentrations decreased progressively with increasing age in the nonbreastfed children. Median (IQR) plasma folate concentrations in the 6–11-mo-old group were higher in breastfed (20.3; 11.7–34.4 nmol/L) than in nonbreastfed (5.3; 3.4–7.7 nmol/L) children (P < 0.001). Folate concentrations decreased with increasing age in the breastfed children. In the nonbreastfed children, folate concentrations increased with increasing age. Low concentrations of plasma cobalamin (<150 pmol/L) were detected in 36% of breastfed and 9% of nonbreastfed children (P < 0.001). The proportions of children with plasma folate concentrations <5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P < 0.001).Conclusions: In north Indian preschool children, cobalamin and folate concentrations were commonly low and were associated with elevated total homocysteine and methylmalonic acid concentrations. Because low cobalamin and folate concentrations have functional consequences, population-based measures for improving cobalamin and folate concentrations need to be seriously considered.

Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns

Pregnant women with low cobalamin concentrations are unable to provide the necessary amount of cobalamin to their fetuses. The effect of low maternal cobalamin concentrations on transmethylation metabolism in pregnant women and their newborns is unknown. We investigated the relation between maternal and neonatal cobalamin concentrations and changes in total homocysteine (tHcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). Hematologic data and concentrations of cobalamin, red blood cell folate, serum folate, tHcy, methylmalonic acid, SAM, SAH, and other metabolites were measured in 119 serum specimens from pregnant Brazilian women (gestational age: 37-42 wk) and their newborns' placental veins at the time of delivery. The tHcy concentrations were higher in placental vein serum from newborns whose mothers had low cobalamin. Serum SAH concentrations were elevated and serum SAM and methionine concentrations were decreased in pregnant women with lower cobalamin concentrations. SAM:SAH was significantly decreased in both cobalamin-deficient pregnant women and their newborns. Lower maternal cobalamin concentrations are associated with higher tHcy and lower SAM:SAH in newborns. Because SAM:SAH is closely linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation could be impaired in cobalamin-deficient pregnant women and their newborns.

Mild transcobalamin I (haptocorrin) deficiency and low serum cobalamin concentrations.

Low cobalamin concentrations are common, but their causes are often unknown. Transcobalamin I/haptocorrin (TC I/HC) deficiency, viewed as a rare cause, has not been examined systematically in patients with unexplained low serum cobalamin. Total TC I/HC was measured by RIA in three subgroups of 367, 160, and 38 patients with different categories of low cobalamin concentrations and three comparison subgroups of 112, 281, and 119 individuals with cobalamin concentrations within the reference interval. Additional studies, including family studies, were done in selected patients found to have low TC I/HC concentrations. Low TC I/HC concentrations suggestive of mild TC I/HC deficiency occurred in 54 of 367 (15%) patients with low cobalamin identified by clinical laboratories and 24 of 160 (15%) patients whose low cobalamin was unexplained after absorption and metabolic evaluation, but in only 2 of 38 patients with malabsorptive causes of low cobalamin concentrations (5%). The prevalence was only 3% (8 of 281 plasma samples) to 5% (6 of 112 sera) in patients with cobalamin concentrations within the reference interval and 3% (4 of 119) in healthy volunteers. Three patients with low cobalamin (0.6%) had severe TC I/HC deficiency with undetectable TC I/HC. Presumptive heterozygotes for severe TC I/HC deficiency in two families had the findings of mild TC I/HC deficiency; mild deficiency was also found in at least three of seven studied families of patients with mild TC I/HC deficiency. Mild TC I/HC deficiency is frequently associated with low cobalamin, is often familial, and its biochemical phenotype appears identical to the heterozygous state of severe TC I/HC deficiency. Severe TC I/HC deficiency also appears to be more common than suspected. Both diagnoses should be considered in all patients with unexplained low serum cobalamin.

High prevalence of cobalamin deficiency in Guatemalan schoolchildren: associations with low plasma holotranscobalamin II and elevated serum methylmalonic acid and plasma homocysteine concentrations

Studies conducted in Guatemala, Mexico, and Venezuela have found high prevalences of low plasma cobalamin (vitamin B-12) concentrations in infants and children. It is not known whether these low cobalamin concentrations are accompanied by altered metabolic functions. We sought to assess the prevalence of cobalamin deficiency in Guatemalan children by using sensitive and specific markers of deficiency. Children (n = 553) were screened for low plasma cobalamin. Those with low plasma cobalamin (< 162 pmol/L) were matched by age, grade, and sex to those with marginal (162-221 pmol/L) and adequate (> 221 pmol/L) concentrations. In this matched subset (n = 180), additional biochemical indicators of cobalamin deficiency were measured. Of the 553 children screened, 11% had low plasma cobalamin and an additional 22% had marginal concentrations. The prevalences of elevated serum methylmalonic acid (MMA), plasma homocysteine, or both were significantly higher in children with low and marginal plasma cobalamin than in children with adequate plasma cobalamin. Mean serum MMA was high in all groups compared with values reported in other populations. Mean plasma holotranscobalamin II concentrations were significantly lower in children with low rather than marginal or adequate plasma cobalamin. However, holotranscobalamin II was a less sensitive indicator of cobalamin depletion than was MMA. Biochemical markers of cobalamin deficiency confirmed that the cobalamin status of children with low and marginal plasma cobalamin is inadequate to support normal metabolic function.

Measuring and Interpreting Holo-Transcobalamin (Holo-Transcobalamin II)

At one time, diagnosing cobalamin deficiency was fairly simple, usually involving a patient with clinical problems, and was usually settled by determining whether the serum cobalamin concentration was low or not. As reviewed elsewhere (1), things began to change after sensitive metabolic tests were introduced and as attention extended to the cobalamin status of asymptomatic persons. Metabolic studies confirmed that most low cobalamin concentrations in asymptomatic patients and seemingly healthy persons represented subclinical cobalamin insufficiency, but ∼30–40% of these cobalamin concentrations did not represent insufficiency and thus could be considered “falsely low”. The diagnostic reliability of serum cobalamin was further challenged by metabolic demonstrations of “falsely normal” cobalamin concentrations; these too occurred most often, but not exclusively, in asymptomatic persons. The search continues for the optimal test to diagnose deficiency because the metabolic tests also have disadvantages. Increased plasma total homocysteine is too nonspecific; methylmalonic acid determination, although posing fewer problems of specificity, is complex and expensive; and the deoxyuridine suppression test is too unwieldy for practical use. Interest has been drawn to the possible benefit of measuring only the cobalamin attached to transcobalamin (TC; also called TC II; the TC-cobalamin complex is called holo-TC or holo-TC II) rather than the total cobalamin content of plasma. The concept, suggested by Lindemans et al. in 1983 (2), is simple and attractive: holo-TC contains the biologically available cobalamin because only TC promotes specific uptake of its cobalamin by all cells. The much larger fraction of serum cobalamin carried by haptocorrin (HC; also called TC I, R binder, or sometimes cobalophilin) is considered metabolically inert because no cellular receptors exist for holo-HC (also called holo-TC I). However, the physiologic cycle of holo-TC is quite complex: ( a ) ileal holo-TC enters the portal circulation, carrying cobalamin absorbed from the gut (3); ( b ) some of the …

Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities

Low cobalamin concentrations and mild hyperhomocysteinemia are common in the elderly but ethnic differences have not been defined. Our objective was to determine the demographic characteristics of cobalamin deficiency in the elderly and its role in their hyperhomocysteinemia. We measured serum cobalamin, total homocysteine (Hcys), and methylmalonic acid (MMA) concentrations in 725 subjects >60 y old, and folate concentrations in 520 subjects. After exclusion of subjects taking cobalamin supplements or with renal insufficiency, high prevalences of low cobalamin (11.8%), high MMA (16.6%), and high Hcys (26.1%) concentrations were seen. Most cobalamin concentrations <140 pmol/L appeared to reflect deficiency because 78. 3% of them were accompanied by abnormal metabolites. Subjects with cobalamin concentrations of 140-258 pmol/L had significantly fewer metabolic abnormalities. A low cobalamin concentration and renal insufficiency were the strongest predictors of abnormal Hcys concentrations. Elderly men had higher Hcys concentrations than did women (P = 0.0001). Whites and Latin Americans had lower cobalamin concentrations than did blacks and Asian Americans (P < 0.005). Whites also had higher Hcys concentrations than all the other groups (P < 0.05). When included in the analysis, renal insufficiency in subjects was associated with 23.8% of all high Hcys and 25.5% of all high MMA concentrations; most with renal insufficiency were Asian American and black men. Mild cobalamin deficiency is most common in elderly white men and least common in black and Asian American women. Hyperhomocysteinemia, which is most strongly associated with low cobalamin concentrations, is also most common in elderly whites, whereas that associated with renal insufficiency is more common in blacks and Asian Americans. Ethnic differences in cobalamin deficiency and the Hcys patterns associated with it or with renal insufficiency warrant consideration in supplementation strategies. Extending suspicion of deficiency to persons with cobalamin concentrations of 140-258 pmol/L appears to provide more disadvantages than advantages.

Hormone replacement therapy and cobalamin status in elderly women

Serum cobalamin concentrations are frequently low in the elderly but the cause is often not apparent. Because oral contraceptives have been associated with low cobalamin concentrations in young women, we compared hormone use with cobalamin status in elderly women to determine whether it could account for their unexplained low cobalamin concentrations. Thirty-eight of the 111 women had abnormal cobalamin status (defined by low cobalamin, elevated methylmalonic acid, and/or elevated homocysteine concentrations) and 73 had normal status. There was no difference in hormone use between the two groups: 7 (18.4%) of the 38 cobalamin-deficient subjects used estrogens compared with 20 (27.4%) of the 73 control subjects. No differences in hormone use were apparent either when analysis was confined to abnormal serum cobalamin concentrations alone. Similarly, the 27 women taking hormones and the 84 women not taking hormones did not have significantly different serum cobalamin or serum total homocysteine concentrations. Indeed, hormone users had slightly, though not significantly, higher cobalamin concentrations and lower homocysteine concentrations than nonusers; furthermore, hormone users also had significantly lower serum methylmalonic acid concentrations. Thus, neither cobalamin concentrations nor cobalamin metabolic status were significantly worse in elderly women taking estrogen than in those not taking it (and, if anything, may have been slightly better). Hormone use does not appear to be a significant contributor to the low cobalamin concentrations or the mild metabolic evidence of cobalamin deficiency so often seen in the elderly.

Anti-intrinsic factor antibodies in systemic lupus erythematosus.

As the co-existence of pernicious anaemia (PA) and systemic lupus erythematosus (SLE) has been repeatedly reported, we have investigated the presence of anti-intrinsic factor antibodies (IFAb), the immunological hallmark of PA, in patients diagnosed with SLE. Serum cobalamin levels and IFAb were determined in 30 women diagnosed with SLE as well as in 45 controls. Cobalamin levels were low in 7/30 patients. IFAb were detected in 3/30 sera from patients but in none of the control sera. The presence of IFAb was associated with a low cobalamin concentration, anaemia and macrocytosis in only one patient. There was no evident relationship between the presence of IFAb and serological markers of SLE. We conclude that IFAb may appear in SLE patients, although the cobalamin deficiency described in SLE seems to be due to the presence of IFAb in only a minority of cases.

Studies on methylmalonic acid in humans. II. Relationship between concentrations in serum and urinary excretion, and the correlation between serum cobalamin and accumulation of methylmalonic acid.

Methylmalonic acid (MMA) concentrations are increased in cobalamin (vitamin B12) deficiency, but the relative diagnostic usefulness of determination of MMA in serum vs urine has not yet been assessed. We obtained urine collections and matched serum samples from 28 healthy volunteers and from 20 consecutive patients admitted for clinical and hematological evaluation because of low cobalamin concentrations in serum. Increased concentrations of MMA in serum were found in 12 patients, in all of whom a clinical diagnosis of cobalamin deficiency was established. By contrast, cobalamin deficiency was excluded in seven of the eight remaining patients, who all had normal MMA concentrations. Here we report that linear relationships exist between MMA concentrations in serum (investigated range: 0.05-34.2 mumol/L) and MMA concentrations in urine (r = 0.74), concentrations relative to creatinine (r = 0.98), and MMA excretion rates (r = 0.97) (P less than 0.001 in each instance). Our data are consistent with glomerular filtration and passive reabsorption of MMA by the tubules. We demonstrate, for the first time, a negative correlation between concentrations of cobalamin and MMA in serum in clinical cobalamin deficiency (r = -0.69; P less than 0.01; n = 12); when the values for MMA were log transformed, the correlation with cobalamin was much better (r = -0.84; P less than 0.0005).

Haematological Abnormalities and Reference Intervals in the Elderly

We compared three representative population samples aged 70 (n = 312), 75 (n = 486) and 81 (n = 404) years. Anaemia defined either as blood haemoglobin concentration below the corresponding health-related lower reference limits or according to WHO was, in the total study groups, more common at age 81. Anaemia of unknown cause was rare, but somewhat more common at age 81. Mean blood haemoglobin concentrations in subsamples without definable disorders were significantly lower at age 81 than at ages 70 and 75, whereas the lower health-related reference limits did not differ significantly. White blood cell counts tended to be lower and iron deficiency was somewhat more common at age 81. No significant differences were found in platelet counts or in the prevalence of low plasma cobalamin concentrations. These results indicate a fall in blood haemoglobin with advancing age. The arbitrary WHO criteria for anaemia are clinically applicable at age 70-81.

Measuring low cobalamin concentrations in the presence of excess (greater than 20-100-fold) cobalamin analog, cobinamide: a survey.

Journal Article Measuring low cobalamin concentrations in the presence of excess (greater than 20-100-fold) cobalamin analog, cobinamide: a survey. Get access R K Jhangiani, R K Jhangiani Search for other works by this author on: Oxford Academic Google Scholar A C Bello, A C Bello Search for other works by this author on: Oxford Academic Google Scholar W Johnson, W Johnson Search for other works by this author on: Oxford Academic Google Scholar R Stauffenberg R Stauffenberg Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 32, Issue 8, 1 August 1986, Pages 1597–1598, https://doi.org/10.1093/clinchem/32.8.1597 Published: 01 August 1986

The effect of cyanide on serum cobalamin and on cobalamin analogues when measured by radioassay using R-protein and intrinsic factor.

Concentrations of cobalamin measured in human serum by radioassay differ when R-protein or intrinsic factor is used as the binding determinant. Experiments were carried out to determine whether the concentration of cyanide used to extract the serum cobalamin could account for this difference. When either R-protein or intrinsic factor was used, the cobalamin measured in serum extracted in the absence of cyanide was low. As the concentration of cyanide was raised in the extraction mixture, the cobalamin concentration that was measured increased when either protein binder was used, but the absolute increase was greater with R-protein. R-protein or intrinsic-factor-reactive cobalamin could be recovered from serum proteins precipitated in the absence of cyanide and reextracted in the presence of cyanide. There was low recovery of hydroxo, methyl, or adenosyl cobalamins added to serum when the serum was extracted in the absence of cyanide, but recovery was quantitative when using either protein binder with cyanide in the extraction step. With 0.25 microgram of potassium cyanide/ml of extraction mixture and R-protein as the binding determinant in the radioassay, sera with normal, moderately low, and very low cobalamin concentrations could by separated. These experiments indicate that the concentration of cyanide used to extract cobalamin from the serum may account for some but not all of the differences observed when R-protein and intrinsic factor are used in the radioassay. The range of normal and low serum cobalamin are method-dependent and must be established by each laboratory for the radioassay procedure used.