Serum Cobalamin Concentrations Research Articles

Effect of withholding food on serum concentrations of cobalamin, folate, trypsin-like immunoreactivity, and pancreatic lipase immunoreactivity in healthy dogs.

To evaluate the effects of withholding food on the results for measurements of serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) in healthy dogs. 11 healthy employee- or student-owned dogs. Food was withheld from the dogs for 12 hours, baseline blood samples were collected, then dogs were fed. Postprandial blood samples collected 1, 2, 4, and 8 hours later were assessed. A mixed-effects ANOVA model with fasting duration (time) as a fixed factor and dog as a random effect was fit for each analyte variable. Additionally, a mixed-effects ANOVA model controlling for the variable of time was fit to assess whether lipemia affected serum concentrations of the analytes. The median serum cobalamin concentration was lower at 4 hours (428 ng/L) and 8 hours (429 ng/L) postprandially, compared with baseline (479 ng/L), but this difference was not clinically meaningful. Although there were no substantial differences in serum concentrations of folate, cPLI, or cTLI, postprandial changes in serum concentrations of cTLI or folate could potentially affect diagnoses in some dogs. Although results indicated that feedings rarely resulted in clinically important differences in the median serum concentrations of cobalamin, folate, cPLI, or cTLI in healthy dogs, given the further processing required for lipemic samples, withholding food for at least 8 hours is an appropriate recommendation when measuring these analytes. Similar research is needed in dogs with gastrointestinal disease to determine whether the withholding of food is necessary when measuring these analytes in affected dogs.

Effects of oral cobalamin supplementation on serum cobalamin concentrations in dogs with exocrine pancreatic insufficiency: A pilot study

The objective of this retrospective study was to evaluate serum cobalamin concentrations before and after oral cobalamin supplementation in dogs with low serum cobalamin concentrations and exocrine pancreatic insufficiency (EPI). Eighteen dogs with serum trypsin-like immunoreactivities between <1.0−2.7 μg/L (reference interval, 5.2−35 μg/L) and serum cobalamin concentrations ≤350 ng/L (reference interval, 244–959 ng/L) were enrolled. All dogs were treated with oral cyanocobalamin according to a previously described protocol (0.25–1.0 mg daily, depending on bodyweight). Median (range) serum cobalamin concentrations at inclusion was 188 ng/L (<111−350 ng/L), which increased significantly to 1000 ng/L (794−2385 ng/L; P < 0.001) after cobalamin supplementation for 19−199 days (median, 41 days). Oral cobalamin supplementation is a potential alternative to parenteral supplementation in dogs with EPI.

Anemia, iron deficiency, and cobalamin deficiency in cats with chronic gastrointestinal disease.

BackgroundIron deficiency and cobalamin deficiency, as sequelae to chronic gastrointestinal (GI) disease, could result in anemia and increased morbidity in cats with chronic enteropathies.ObjectiveTo evaluate iron deficiency in cats with chronic GI disease and its relationship with hypocobalaminemia, anemia, and disease severity.AnimalsTwenty client‐owned cats with primary GI disease.MethodsProspective, cross‐sectional study. Cats were enrolled at the time of evaluation for chronic GI disease, after exclusion of comorbidities. CBC with reticulocyte indices, iron metabolism (serum iron and ferritin concentrations, total iron binding capacity [TIBC]), serum methylmalonic acid (MMA), cobalamin, and folate concentrations, pancreatic lipase and trypsin‐like immunoreactivity, and disease severity were evaluated.ResultsAnemia (hematocrit <30%), iron deficiency, and cobalamin deficiency were diagnosed in 4/20, 7/20, and 8/20 cats, respectively. Hematocrit (r s = −.45; P < .05) and body condition score (r s = −.60; P < .01) negatively correlated with MMA. Median TIBC was lower in cats with increased vs normal MMA (218 μg/mL; range, 120‐466 μg/mL vs 288 μg/mL; range, 195‐369 μg/mL; P = .02). Hematocrit (r s = .51; P = .02), reticulocyte MCV (r s = .52; P = .02), reticulocyte hemoglobin content (r s = .71; P < .001), and percent transferrin saturation (r s = .79; P < .0001) positively correlated with serum iron concentration.Conclusions and Clinical ImportanceFunctional iron deficiency was common in cats with chronic GI disease. Associations between hypocobalaminemia, iron parameters, and hematologic parameters warrant further investigation on the impact of iron deficiency on chronic GI disease morbidity in cats.

Feline comorbidities: What do we really know about feline triaditis?

Feline triaditis describes concurrent pancreatitis, cholangitis and inflammatory bowel disease (IBD). The reported prevalence is 17-39% in ill referral patients. While the aetiology is poorly understood, it is known to include infectious, autoimmune and physical components. What is not known is whether different organs are affected by different diseases, or the same process; indeed, triaditis may be part of a multiorgan inflammatory disease. Feline gastrointestinal tract anatomy plays its role too. Specifically, the short small intestine, high bacterial load and anatomic feature whereby the pancreatic duct joins the common bile duct before entering the duodenal papilla all increase the risk of bacterial reflux and parenchymal inflammation. Inflammation may also be a sequela of bowel bacterial translocation and systemic bacteraemia. Cholangitis, pancreatitis and IBD manifest with overlapping, vague and non-specific clinical signs. Cholangitis may be accompanied by increased serum liver enzymes, total bilirubin and bile acid concentrations, and variable ultrasonographic changes. A presumptive diagnosis of pancreatitis is based on increased serum pancreatic lipase immunoreactivity or feline pancreas-specific lipase, and/or abnormal pancreatic changes on ultrasonography, though these tests have low sensitivity. Diagnosis of IBD is challenging without histopathology; ultrasound findings vary from normal to mucosal thickening or loss of layering. Triaditis may cause decreased serum folate or cobalamin (B12) concentrations due to intestinal disease and/or pancreatitis. Triaditis can only be confirmed with histopathology; hence, it remains a presumptive diagnosis in most cases. The literature on feline triaditis, pancreatitis, cholangitis and IBD is reviewed, focusing on histopathology, clinical significance and diagnostic challenges. Current management recommendations are provided. Further studies are needed to understand the complex pathophysiology, and in turn improve diagnosis and treatment.

Prevalence and clinical relevance of hypercobalaminaemia in dogs and cats

Hypocobalaminaemia is common in dogs and cats with exocrine pancreatic insufficiency and/or chronic enteropathy. While hypocobalaminaemia has been extensively studied, naturally-occurring serum hypercobalaminaemia (i.e. without supplementation) might be an underestimated finding in small animal medicine. Studies in human medicine have associated hypercobalaminaemia with neoplastic, hepatic and renal disease. Medical records of all dogs and cats with serum cobalamin concentration measurements (2007–2019) were retrospectively analysed; any that had received supplemental cobalamin were excluded from the analysis. Of 654 dogs, 3% (n = 21) were hypercobalaminaemic (median serum cobalamin concentration, 1307 ng/L [965 pmol/L]; range, 914–3561 ng/L [675–2628 pmol/L]). Chronic gastrointestinal signs were common in hypercobalaminaemic dogs (48%). Two of the 21 hypercobalaminaemic dogs were diagnosed with hypoadrenocorticism. Of 323 cats, 11% (n = 34) were hypercobalaminaemic (median serum cobalamin concentration, 1713 ng/L [1264 pmol/L]; range, 1370–3107 ng/L [1011–2293 pmol/L]). The following comorbidities were diagnosed in hypercobalaminaemic cats: chronic enteropathy, 65% (n = 22); acute or chronic pancreatitis, 24% (n = 8); cholangiohepatopathy, 18% (n = 6); gastric lymphoma, 6% (n = 2); and 3% hyperthyroidism (n = 1). Naturally-occurring increased serum cobalamin concentrations occurred infrequently in cats and even less often in dogs. Since hypercobalaminaemia can occur in dogs and cats with severe inflammatory, immune-mediated, and neoplastic conditions, it should not be ignored.

Dynamics and interactions of cobalamin and folate status during advanced aging \u2013 a longitudinal study in a community-dwelling cohort with multiple follow-ups

BackgroundOlder people are reported to be prone to imbalances between cobalamin and folate status with possible adverse effects on health. This longitudinal study investigates dynamics and interactions of cobalamin and folate status in a cohort of community-dwelling older adults by considering possible influencing factors.MethodsIn total, 332 subjects ≥ 60 years were investigated over a mean observation period of 12 years. Data collection included serum cobalamin, folate and creatinine, dietary intakes of cobalamin, folate and alcohol, use of supplements, body composition, smoking behavior, and diseases. Linear mixed-effects models with repeated measurements were used to investigate the influence of variables on serum cobalamin and folate.ResultsAt baseline, median cobalamin intake exceeded the dietary reference value (DRV), while median folate intake was considerably below DRV. In most subjects, serum concentrations of both vitamins were within reference ranges. For serum cobalamin, apart from supplement use (Parameter estimate [95% confidence interval]: 130.17 [53.32, 207.01]), the main positive predictor was serum folate (4.63 [2.64, 6.62]). For serum folate, serum creatinine (10.85 [4.85, 16.86]), use of supplements (7.86 [5.05, 10.67]), serum cobalamin (0.01 [< 0.01, 0.01]), and dietary folate intake (0.02 [0.01, 0.03]) were positive predictors. No main effects of age, sex, body composition, alcohol intake or smoking were found after adjusting for simultaneous inference.ConclusionsAdvancing age, per se, is no risk factor for a decline in serum concentrations of cobalamin or folate in subjects ≥ 60 years. Suboptimal folate intake may limit the function of folate regarding the supply of methyl groups for methylation of cobalamin and subsequent creatine biosynthesis. The positive association of serum creatinine with folate deserves further exploration with regard to its possible relevance for maintaining energy dependent functional integrity in the course of ageing.

Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults.

Background and objectives: Lower vitamin status has been linked to cognitive deficits, pending mechanistic elucidation. Serum 25-hydroxyvitamin D [25(OH)D], folate and cobalamin were explored against brain volumes and white matter integrity (WMI).Methods: Two prospective waves from Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study were primarily used [Baltimore, City, MD, 2004–2015, N = 183–240 urban adults (Agev1: 30–64 years)]. Serum vitamin 25-hydroxyvitamin D [25(OH)D], folate and cobalamin concentrations were measured at visits 1 (v1: 2004–2009), while structural and diffusion Magnetic Resonance Imaging (sMRI/dMRI) outcomes were measured at vscan: 2011–2015. Top 10 ranked adjusted associations were corrected for multiple testing using familywise Bonferroni (FWER < 0.05) and false discovery rates (FDR, q-value < 0.10).Results: We found statistically significant (FWER < 0.05; β±SE) direct associations of 25(OH)D(v1) with WM volumes [overall: +910 ± 336/males: +2,054 ± 599], occipital WM; [overall: +140 ± 40, males: +261 ± 67 and Agev1 > 50 years: +205 ± 54]; parietal WM; [overall: +251 ± 77, males: +486 ± 129 and Agev1 > 50 years: +393 ± 108] and left occipital pole volume [overall: +15.70 ± 3.83 and above poverty: 19.0 ± 4.3]. Only trends were detected for cobalamin exposures (q < 0.10), while serum folate (v1) was associated with lower mean diffusivity (MD) in the Anterior Limb of the Internal Capsule (ALIC), reflecting greater WMI, overall, while regional FA (e.g., cingulum gyrus) was associated with greater 25(OH)D concentration.Conclusions: Among urban adults, serum 25(OH)D status was consistently linked to larger occipital and parietal WM volumes and greater region-specific WMI. Pending longitudinal replication of our findings, randomized controlled trials of vitamin D supplementation should be conducted against brain marker outcomes.

Bacterial fecal microbiota is only minimally affected by a standardized weight loss plan in obese cats

BackgroundResearch in humans and mice suggests that obesity influences the abundance and diversity of gastrointestinal (GI) microbiota, and that an “obese microbiome” influences energy metabolism and fat storage in the host. Microbiota membership and composition have been previously assessed in healthy cats. However, research investigating the effects of obesity and weight loss on the cat’s fecal microbiota is limited. Therefore, this study’s objective was to evaluate differences in fecal microbial abundance and biodiversity, as well as serum cobalamin and folate concentrations in obese cats, before and after weight loss, and compare to lean cats.Fourteen lean and 17 obese healthy client-owned cats were fed a veterinary therapeutic weight loss food at maintenance energy requirement for 4 weeks. At the end of week 4, lean cats finished the study, whereas obese cats continued with a 10-week weight loss period on the same food, fed at individually-tailored weight loss energy requirements. Body weight and body condition score were recorded every 2 weeks throughout the study. At the end of each period, a fecal sample and food-consumption records were obtained from the owners, and serum cobalamin and folate concentrations were analysed. DNA was extracted from fecal samples, polymerase chain reaction (PCR) was performed, and products were sequenced using next-generation sequencing (Illumina MiSeq).ResultsNo significant differences in the relative abundance of taxa and in biodiversity indices were observed between cats in either group (P > 0.05 for all tests). Nevertheless, some significantly enriched taxa, mainly belonging to Firmicutes, were noted in linear discriminant analysis effect size test in obese cats before weight loss compared to lean cats. Serum cobalamin concentrations were significantly higher in lean compared to obese cats both before and after weight loss. Serum folate concentrations were higher in obese cats before weight loss compared to after.ConclusionsThe association between feline obesity and the fecal bacterial microbiota was demonstrated in enriched taxa in obese cats compared to lean cats, which may be related to enhanced efficiency of energy-harvesting. However, in obese cats, the fecal microbial abundance and biodiversity were only minimally affected during the early phase of a standardized weight loss plan.

Assessment of folate and cobalamin concentrations in relation to their dependent intracellular metabolites in serum of pigs between 6 and 26 weeks of age

Folate (vitamin B9) and cobalamin (vitamin B12) play an important role in amino acid metabolism, nucleic acid synthesis, and methyl group transfer. Two intracellular enzymes, methionine synthase and methylmalonyl-CoA mutase, are folate and/or cobalamin-dependent, respectively. At the cellular level, a lack of folate and cobalamin leads to accumulation of serum homocysteine (HCY) and a lack of cobalamin leads to increased methylmalonic acid (MMA) concentrations. Altered serum HCY and MMA concentrations can influence amino acid metabolism and nucleic acid synthesis in pigs. Therefore, we aimed to evaluate serum folate, cobalamin, HCY, and MMA concentrations in postweaning pigs between 6 and 26 weeks of age. Serum samples from 12 pigs collected at week 6, 7, 8, 9, 10, 14, 18, 22, and 26 as part of an unrelated study were analyzed. Serum folate (p < .0001), cobalamin (p = .0001), HCY (p < .0001), and MMA (p < .0001) concentrations differed significantly during the postweaning period between 6 and 26 weeks of age; with significantly higher serum HCY (at weeks 6 and 7 compared to weeks 9, 14, 18, 22, and 26) and MMA concentrations (at weeks 6, 7, and 8 compared to weeks 14, 18, 22, and 26) and an overall decrease of serum MMA concentrations from week 6 to week 14 in the pigs studied. This study suggests age-dependent changes in intracellular folate- and cobalamin-dependent metabolites (i.e., HCY and MMA) in pigs between 6 and 26 weeks of age, possibly reflecting decreased availability of intracellular folate and/or cobalamin for amino acid metabolism, nucleic acid synthesis, and methyl group transfer.

Longitudinal age-related changes in cobalamin and folate status in community-dwelling older adults

AbstractAdvancing age is regarded as a risk factor for an insufficient cobalamin and folate status. However, longitudinal data are lacking and little is known on the impact of age in subjects ≥ 60 years after considering potential confounding factors. Therefore, the present study investigates age-related changes in cobalamin and folate status in older adults by using longitudinal data of 332 German subjects aged ≥ 60 years, who participated in the longitudinal study on nutrition and health status of senior citizens in Giessen (GISELA study). All subjects had complete data records on at least three follow-ups between 1997 and 2014. The mean follow-up time was 12 years. Fasting serum concentrations of cobalamin and folate were determined with SimulTRAC-SNB radio assay kit. In each follow-up, body composition (bioelectrical impedance analysis), dietary cobalamin and folate intakes (3-day estimated dietary record), supplement use and lifestyle factors (questionnaires) were assessed. Linear mixed models were used to analyze age-related changes in serum concentrations of cobalamin and folate by considering sex, absolute fat-free mass, supplement use, dietary intakes and smoking behavior as potential confounding variables. Furthermore, due to the metabolic interaction of cobalamin and folate, linear mixed models implemented a mutual adjustment of serum cobalamin and serum folate. At baseline, 11.4 % and 7.8 % of the subjects had cobalamin concentrations &lt; 148 pmol/L and folate concentrations &lt; 10 nmol/L, respectively. In contrast, dietary cobalamin intakes &lt; 4 μg/d and folate intakes &lt; 300 μg/d were found in 24.4 % and 76.5 % of the subjects, respectively. Without adjustments, a positive influence of age on serum cobalamin [parameter estimate (95 % CI) = 4.57 (1.67, 7.46)] and serum folate [0.29 (0.18, 0.40)] was found. After multiple adjustments, age was still a positive predictor of serum folate [0.25 (0.14, 0.36)], whereas no significant influence on serum cobalamin was found [2.73 (-0.23, 5.69)]. Similar results were noticed when the analyses were restricted to non-users of B-vitamin/multi-vitamin supplements. In conclusion, the present study in community-dwelling subjects does not confirm age-related declines in serum concentrations of cobalamin and folate between the ages of 60 and 90 years. Although a significant proportion of the subjects showed dietary intake levels below the current European references values, serum concentrations of cobalamin and folate were predominantly in reference ranges. Longitudinal investigations on other biomarkers of cobalamin and folate status are warranted.

Review of cobalamin status and disorders of cobalamin metabolism in dogs.

Disorders of cobalamin (vitamin B12) metabolism are increasingly recognized in small animal medicine and have a variety of causes ranging from chronic gastrointestinal disease to hereditary defects in cobalamin metabolism. Measurement of serum cobalamin concentration, often in combination with serum folate concentration, is routinely performed as a diagnostic test in clinical practice. While the detection of hypocobalaminemia has therapeutic implications, interpretation of cobalamin status in dogs can be challenging. The aim of this review is to define hypocobalaminemia and cobalamin deficiency, normocobalaminemia, and hypercobalaminemia in dogs, describe known cobalamin deficiency states, breed predispositions in dogs, discuss the different biomarkers of importance for evaluating cobalamin status in dogs, and discuss the management of dogs with hypocobalaminemia.

Diagnostic features, treatment, and outcome of dogs with inflammatory protein-losing enteropathy.

BackgroundProtein‐losing enteropathy (PLE) because of chronic inflammatory enteropathy (CIE) in dogs is often treated with a combination of glucocorticoids and second‐line immunosuppressant (SLI). This combined approach might not be necessary in all dogs.Hypothesis/objectivesTo describe diagnostic features and outcomes of dogs with PLE treated with glucocorticoids alone (group P) or with glucocorticoids and SLI (group S).AnimalsThirty‐one dogs with PLE.Material and methodsRetrospective analysis of signalment data from diagnostic procedures, treatment, and outcome of dogs with CIE/PLE (from 2015 to 2017), using the hospital's digital case database. Dogs with hypoalbuminemia and CIE were included. Because of a stepwise treatment algorithm, dogs were allocated to group P or S. Time to serum albumin concentrations ≥20 g/L and survival data were collected. Dogs were additionally categorized by their albumin and cobalamin serum concentrations. Multivariate and univariate analysis as well as Pearson's correlation and Kaplan‐Maier survival analysis were performed.ResultsSeventeen dogs were included in group P and 14 in group S. World Small Animal Veterinary Association score of the duodenum was different between groups (P = .05), but none of the other examined data. Median time until serum albumin reached >20 g/L was 13 days. Median survival time after start of treatment was 85 days (range, 13‐463 days) in group P and 166 days (range, 8‐390 days) in group S.Conclusion and Clinical ImportanceNo routine diagnostic test was predictive of clinical response, treatment group, or outcome. Glucocorticoid treatment alone can be appropriate in dogs with PLE.

Time course of serum cobalamin, folate, and total iron binding capacity concentrations in pregnant bitches and association with hematological variables and survival.

BackgroundHypocobalaminemia, hypofolatemia and iron deficiency are associated with pregnancy‐related anemia (PRA) and neonatal survival (NS) in women. Similar associations have not been investigated in pregnant bitches.ObjectivesTo investigate time course and associations of serum cobalamin, folate and iron status indicators with hematological variables and NS in pregnant bitches.AnimalsForty‐eight pregnant bitches.MethodsA prospective cohort study. Pregnancy was confirmed by abdominal ultrasonography twice during mid‐ and late pregnancy, concurrently with blood sampling. Associations among pregnancy stage, NS and laboratory variables were assessed by generalized estimating equations.ResultsCompared with midpregnancy, serum cobalamin (adjusted mean [95% confidence interval, CI]) decreased at late pregnancy (430 pg/mL [394‐466] versus 330 pg/mL [303‐357], respectively; P < .001), whereas serum folate did not. Every increment of 1 in parity number or litter size corresponded to 28.6 pg/mL (95% CI, 5.6‐51.6; P = .02) and 20.3 pg/mL (95% CI, 10.9‐29.7; P < .001) decrease in serum cobalamin concentration. Compared with midpregnancy, serum iron (P < .001) and transferrin saturation (P = .01) increased at late pregnancy. The decrease in red blood cell count (P < .001) at late pregnancy was significantly, albeit weakly, correlated with decreasing serum folate concentration (r = 0.33; P = .02). None of the measures was associated with NS.Conclusions and Clinical SignificancePregnancy‐related anemia was common at late pregnancy. Unlike in women, in pregnant bitches, serum iron and transferrin saturation were increased at late pregnancy. Future studies are warranted to investigate the clinical ramifications of hypocobalaminemia in pregnant bitches and the utility of prophylactic folate administration in mitigating PRA.

Serum Cobalamin and Folate Concentrations in Common Marmosets (Callithrix jacchus) with Chronic Lymphocytic Enteritis.

Serum cobalamin and folate concentrations can serve as surrogate markers of gastrointestinal disease in dogs and cats, where they can have diagnostic, therapeutic, and prognostic implications. Chronic disease of the gastrointestinal tract, particularly chronic lymphocytic enteritis (CLE), occurs frequently in captive common marmosets. The aims of this study were to validate a commercially available assay for measuring serum cobalamin and folate concentrations in common marmosets, to establish reference intervals for these analytes in healthy marmosets, and to measure serum concentrations in common marmosets with CLE. The commercial assay was linear, accurate, precise, and reproducible for the measurement of serum cobalamin and folate concentrations in common marmosets. In healthy marmosets, the serum cobalamin concentration ranged from 322 to 2642 pg/mL (n = 35) and serum folate concentration from 54.8 to 786.4 ng/mL (n = 37). Low serum folate concentrations were moderately sensitive (greater than 70%) for CLE, and low serum cobalamin concentrations were moderately (greater than 70%) specific for CLE. Both serum cobalamin and folate concentrations were relatively unchanged in marmosets during 120 to 220 d. Serum cobalamin and folate concentrations were stable for approximately 7 y when samples were stored at -80 °C. Additional studies are warranted to further study the clinical implications of low serum cobalamin and folate concentrations in common marmosets.

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.

Relationship between cobalamin and folate deficiencies and anemia in dogs.

BackgroundMegaloblastic, nonregenerative anemia is a well‐known consequence of cobalamin or folate deficiencies in humans but is not recognized in hypocobalaminemic or hypofolatemic dogs. Establishment of relationships between hypocobalaminemia or hypofolatemia and hematologic disease would encourage vitamin B testing, and potentially supplementation, in anemic dogs.ObjectivesTo determine the prevalence of anemia in hypocobalaminemic or hypofolatemic dogs and to report the prevalence of hypocobalaminemia and hypofolatemia and nonregenerative anemia, macrocytosis, and anisocytosis in anemic dogs.AnimalsOne hundred and fourteen client‐owned dogs with known serum cobalamin and folate concentrations and CBCs and 42 client‐owned anemic dogs.MethodsRetrospective comparison of anemia prevalence in hypocobalaminemic or hypofolatemic and normocobalaminemic or normofolatemic dogs was performed. Prospective measurement of erythrocyte variables and cobalamin and folate concentrations in anemic dogs was carried out; relationships among hypocobalaminemia and regenerative status, mean corpuscular volume, and red cell distribution width were evaluated.ResultsSignificant differences in prevalence of anemia between hypocobalaminemic (36%) and normocobalaminemic dogs (26%; P = .23) or between hypofolatemic (31%) and normofolatemic dogs (30%; P = .99) were not detected. Between hypocobalaminemic and normocobalaminemic dogs, no significant differences in prevalence of nonregenerative anemia (69% vs 63%; P = .65), macrocytosis (17% vs 0%; P = .53), or anisocytosis (28% vs 0%; P = .14) were detected. Anemic dogs had high prevalence of vitamin B deficiencies (nonregenerative: 64% hypocobalaminemic, 18% hypofolatemic; regenerative: 57% hypocobalaminemic, 21% hypofolatemic).Conclusions and Clinical ImportanceThe association between cobalamin and folate deficiencies and macrocytic, nonregenerative anemia established in humans is not routinely present in dogs.

Serum cobalamin and folate as prognostic factors in canine exocrine pancreatic insufficiency: An observational cohort study of 299 dogs

Exocrine pancreatic insufficiency (EPI) in dogs is a gastrointestinal condition leading to a severe impairment of nutrient absorption. The disease is frequently associated with vitamin disturbances especially regarding cobalamin and folate. Dogs with EPI need daily expensive supportive treatment. The aim of the present study was to identify prognostic factors for EPI in dogs, through a long-term survival study of 299 dogs, taking into account epidemiological, clinical, biological and therapeutic data, with particular emphasis on serum cobalamin and folate concentration.The prevalence of low serum cobalamin (cobalamin<350ng/L) and high serum folate (folate>12μg/L) concentrations were 67% (200/299) and 55% (164/299), respectively. Dogs with hypocobalaminemia at diagnosis were significantly older than those with serum cobalamin concentration within the reference interval (P<0.001). Hypocobalaminemia at diagnosis (P=0.04), male sex (P=0.01), decreased appetite at diagnosis (P=0.008) and not receiving enzyme replacement therapy (P=0.003) were significant and independent risk factors for decreased survival in EPI. In contrast, hyperfolatemia was associated with improved prognosis (P=0.02). These results confirm the importance of measuring serum cobalamin and folate concentrations at the time EPI is diagnosed, as hypocobalaminemia is negatively associated with prognosis, particularly in the absence of a high serum folate concentration.

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.

SERUM COBALAMIN AND FOLATE CONCENTRATIONS AS INDICATORS OF GASTROINTESTINAL DISEASE IN KILLER WHALES ( ORCINUS ORCA).

Cobalamin and folate are water-soluble vitamins that are useful indicators of chronic gastrointestinal (GI) function in humans and some animal species. Serum cobalamin and folate concentrations in an ex situ population of killer whales ( Orcinus orca) were measured and factors that may affect their serum concentrations were identified. Serum samples ( n = 104) were analyzed from killer whales ( n = 10) both while clinically healthy and during periods of clinical GI disease as defined by clinical signs and fecal cytology. To characterize serum cobalamin and folate concentrations in clinically healthy animals, a mixed-model regression was used, with cobalamin and folate both significantly affected by weight (cobalamin: P < 0.0001, folate: P = 0.006) and season (cobalamin: P < 0.0001, folate: P < 0.0001). The marginal mean concentrations for cobalamin and folate across weight and season were 742 ± 53.6 ng/L and 30.2 ± 2.6 μg/L, respectively. The predicted 95% confidence intervals (CI) for these analytes were then compared with samples collected during periods of GI disease. Across individuals, 22% (2/9) of the folate and 80% (8/10) of the cobalamin samples from the animals with GI disease fell outside the 95% CI for the population. When comparing samples within an individual, a similar pattern presented, with 100% of cobalamin of the observed abnormal samples reduced compared to healthy animal concentration variability. The same was not true for folate. These results suggest that serum concentrations of cobalamin and folate may be useful minimally invasive markers to identify GI disease in killer whales, especially when values are compared within an individual.

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.