Parenteral Cobalamin Supplementation Research Articles

Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

The Intestinal Microbiome in Dogs with Chronic Enteropathies and Cobalamin Deficiency or Normocobalaminemia-A Comparative Study.

Cobalamin deficiency is a common sequela of chronic enteropathies (CE) in dogs. Studies comparing the intestinal microbiome of CE dogs with cobalamin deficiency to those that are normocobalaminemic are lacking. Therefore, our aim was to describe the fecal microbiome in a prospective, comparative study evaluating 29 dogs with CE and cobalamin deficiency, 18 dogs with CE and normocobalaminemia, and 10 healthy control dogs. Dogs with cobalamin deficiency were also analyzed after oral or parenteral cobalamin supplementation. Overall microbiome composition (beta diversity) at baseline was significantly different in CE dogs with cobalamin deficiency when compared to those with normocobalaminemia (p = 0.001, R = 0.257) and to healthy controls (p = 0.001, R = 0.363). Abundances of Firmicutes and Actinobacteria were significantly increased (q = 0.010 and 0.049), while those of Bacteroidetes and Fusobacteria were significantly decreased (q = 0.002 and 0.014) in CE dogs with cobalamin deficiency when compared to healthy controls. Overall microbiome composition in follow-up samples remained significantly different after 3 months in both dogs receiving parenteral (R = 0.420, p = 0.013) or oral cobalamin supplementation (R = 0.251, p = 0.007). Because cobalamin supplementation, in combination with appropriate therapy, failed to restore the microbiome composition in the dogs in our study, cobalamin is unlikely to be the cause of those microbiome changes but rather an indicator of differences in underlying pathophysiology that do not influence clinical severity but result in a significant aggravation of dysbiosis.

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.

Cobalamin deficiency in dogs and cats

Cobalamin is a member of the B-group of vitamins and a cofactor for metabolic processes like nucleic acid synthesis, amino acid synthesis, and the citric acid cycle. Mammals are unable to synthesize cobalamin and therefore rely on adequate food intake. Cobalamin absorption is a complex process in the stomach, duodenum, and ileum, requiring a functional exocrine pancreas. Thus, a great number of gastrointestinal diseases like chronic enteropathies, intestinal lymphoma, or exocrine pancreatic insufficiency can lead to hypocobalaminemia. Furthermore, some dog breeds (Giant Schnauzer, Border Collie, Australian Sheperd Dog, and Beagle) can have a primary, hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome). Clinical signs of cobalamin deficiency comprise anorexia, vomiting, diarrhoea, failure to thrive, and neuropathies. Laboratory findings like non-regenerative anemia, leukopenia, hypoglycemia, and hyperammonaemia have also been described. When hypocobalaminemia is suspected usually in dogs and cats, the cobalamin concentration is usually measured by immunoassay. Because the concentrations of cobalamin in blood and cells can differ the sole measurement of the vitamin concentration is of limited informative value. Treatment depends on the underlying disease aiming at eliminating the cause of hypocobalaminemia. However, successful therapy of gastrointestinal diseases often requires an additional oral or parenteral cobalamin supplementation. In patients with Imerslund-Gräsbeck syndrome, a regular and lifelong cobalamin supplementation is essential.

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.

Effects of 6Weeks of Parenteral Cobalamin Supplementation on Clinical and Biochemical Variables in Cats with Gastrointestinal Disease.

BackgroundEffects and duration of commonly used protocols for cobalamin (Cbl) supplementation on cellular Cbl deficiency have not been determined in hypocobalaminemic cats.Hypothesis/ObjectivesTo evaluate effect of Cbl supplementation on clinical signs, serum and urine methylmalonic acid (MMA) concentrations over 16 weeks.AnimalsTwenty client‐owned hypocobalaminemic cats with enteropathy.MethodsProspective study. Serum Cbl and serum and urine MMA concentrations were determined prospectively in cats at enrollment (t0), immediately before (t6), and 4 (t10) and 10 weeks (t16) after 6th Cbl injection (250 μg, IM q 7 days). Clinical signs severity (activity, appetite, vomiting, diarrhea, body weight) graded at each time point and expressed as clinical disease activity score.ResultsClinical disease activity score decreased during supplementation and increased after treatment discontinuation. Median serum Cbl concentration increased significantly from t0 (111 pmol/L, range 111–212) to t6 (2,332.5 pmol/L, range 123–22,730) (P < 0.01). Values at t10 were 610.5 pmol/L (range, 111–2,527) and 180.5 pmol/L (range, 111–2,262) at t16 (P < 0.01). Median baseline serum MMA concentration (372 μmol/L, range 0.39–147,000) decreased significantly to 1.62 μmol/L (range, 0.18–806) at t6 (P < 0.01) and gradually increased to 5.34 μmol/L (range, 0.13–1,730) at t10 and 189 μmol/L (range, 0.4–983) at t16. Similar, nonsignificant, pattern observed for urine MMA concentration. Serum and urine MMA concentrations had not normalized in 12 and 6 cats, respectively, at t6.Conclusion and Clinical ImportanceThe Cbl supplementation protocol used here did not lead to complete normalization of cellular Cbl deficiency in all examined cats, and biochemical improvements were transient.

Vitamin B12 Deficiency in Resistant Schizophrenia in Tropics

Vitamin B12 deficiency and hyperhomocysteinemia are common in tropical developing countries. In prevalence study, among Indian population by Yajnik and colleagues, 67% of men had low vitamin B12 concentration and 58% had hyperhomocysteinemia [1]. Here, we report two patients with vitamin B12 deficiency presented with symptoms of schizophrenia and required very high doses of antipsychotic medication surprisingly without any anticipated extra pyramidal side effects. The initial requirement of high dose of antipsychotic medication significantly came down after adding parenteral cobalamin supplementation.

Congenital cobalamin malabsorption (Imerslund-Gräsbeck syndrome) in two Beagles in the UK

Two immature Beagles, one nine months old and one six months old, presented with a variety of clinical signs, including pyrexia, lethargy, weight loss and intermittent vomiting and diarrhoea in...

Clinical and Laboratory Findings in Border Collies with Presumed Hereditary Juvenile Cobalamin Deficiency

Juvenile cobalamin deficiency is a rare disease in border collies and its diagnosis requires a high level of clinical suspicion. The goal of this study was to increase awareness of this disease by describing the clinical and laboratory findings in four young border collies with inherited cobalamin deficiency. The median age of the dogs was 11.5 mo (range, 8-42 mo), and two of the four dogs were full siblings. Clinical signs included intermittent lethargy (n = 4), poor body condition (n = 4), odynophagia (n = 2), glossitis (n = 1), and bradyarrhythmia (n = 1). Pertinent laboratory abnormalities were mild to moderate normocytic nonregenerative anemia (n = 3), increased aspartate aminotransferase (AST) activity (n = 3), and mild proteinuria (n = 3). All of the dogs had serum cobalamin levels below the detection limit of the assay, marked methylmalonic aciduria, and hyperhomocysteinemia. Full clinical recovery was achieved in all dogs with regular parenteral cobalamin supplementation, and laboratory abnormalities resolved, except the proteinuria and elevated AST activity persisted. This case series demonstrates the diverse clinical picture of primary cobalamin deficiency in border collies. Young border collies presenting with ambiguous clinical signs should be screened for cobalamin deficiency.

Prognostic Factors in Canine Exocrine Pancreatic Insufficiency: Prolonged Survival is Likely if Clinical Remission is Achieved

Background: Response to therapy in canine exocrine pancreatic insufficiency (EPI) varies considerably, making it difficult to determine prognosis for individual patients.Hypothesis: Response to initial treatment (RIT) and survival are affected by signalment, clinical variables, and therapeutic regimen employed.Animals: Client‐owned dogs diagnosed with EPI between 1990 and 2002 were included in this study.Methods: The study comprised a retrospective, questionnaire‐based review.Results: One hundred seventy‐eight completed questionnaires were returned. RIT was good in 60% of treated dogs, partial in 17%, and poor in 23%. On univariate analysis, dogs that received antibiotics (P= .037) or had high serum folate concentration (P= .037) had a poorer RIT. On multivariate analysis, there were no strong predictors of good RIT. Nineteen percent of treated dogs were euthanized within 1 year, but overall median survival time for treated dogs was 1919 days. No clear benefit of changing to a fat‐restricted diet could be demonstrated, but marked hypocobalaminemia (&lt; 100 ng/L) was associated with shorter survival (P= .012). Use of uncoated pancreatic enzyme supplements, antibacterials, or H2 antagonists was not associated with longer survival. Breed, sex, age at diagnosis (≥4 years or &gt; 4 years), and clinical signs at diagnosis also made no difference.Conclusions and Clinical Importance: Long‐term prognosis in canine EPI is favorable for dogs that survive the initial treatment period. Although there are few predictors of good RIT or long‐term survival, severe cobalamin deficiency is associated with shorter survival. Therefore, parenteral cobalamin supplementation should be considered when hypocobalaminemia is documented.

Prognostic Factors in Canine Exocrine Pancreatic Insufficiency: Prolonged Survival is Likely if Clinical Remission is Achieved

Response to therapy in canine exocrine pancreatic insufficiency (EPI) varies considerably, making it difficult to determine prognosis for individual patients. Response to initial treatment (RIT) and survival are affected by signalment, clinical variables, and therapeutic regimen employed. Client-owned dogs diagnosed with EPI between 1990 and 2002 were included in this study. The study comprised a retrospective, questionnaire-based review. One hundred seventy-eight completed questionnaires were returned. RIT was good in 60% of treated dogs, partial in 17%, and poor in 23%. On univariate analysis, dogs that received antibiotics (P = .037) or had high serum folate concentration (P = .037) had a poorer RIT. On multivariate analysis, there were no strong predictors of good RIT. Nineteen percent of treated dogs were euthanized within 1 year, but overall median survival time for treated dogs was 1919 days. No clear benefit of changing to a fat-restricted diet could be demonstrated, but marked hypocobalaminemia (< 100 ng/L) was associated with shorter survival (P = .012). Use of uncoated pancreatic enzyme supplements, antibacterials, or H2 antagonists was not associated with longer survival. Breed, sex, age at diagnosis ( < or = 4 years or > 4 years), and clinical signs at diagnosis also made no difference. Long-term prognosis in canine EPI is favorable for dogs that survive the initial treatment period. Although there are few predictors of good RIT or long-term survival, severe cobalamin deficiency is associated with shorter survival. Therefore, parenteral cobalamin supplementation should be considered when hypocobalaminemia is documented.

Révélation neurologique aiguë d’une avitaminose B12 par l’administration d’acide folique

A paradigmatic case of acute combined spinal cord degeneration and delirium due to inappropriate administration of folic acid in the context of chronic cobalamin deficiency is described. Rapid improvement was obtained with immediate cessation of folate administration and parenteral cobalamin supplementation. Folic acid and cobalamin prescription rules are recalled. Pathophysiological hypotheses tentatively explaining the neurotoxicity of folic acid in case of vitamin B12 deficiency are summarized.

Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation

Effectiveness of sublingual cobalamin-replacement therapy was studied in 18 people with cobalamin deficiency. Administration was efficacious and convenient, and compliance was high.

Feline Exocrine Pancreatic Disorders

Despite the uncommon clinical diagnosis, cats frequently suffer from disorders of the exocrine pancreas. Pancreatitis is the most common feline exocrine pancreatic disorder. Pancreatitis can be acute or chronic and mild or severe. The etiology of most cases of feline pancreatitis is idiopathic. Some cases have been associated with severe abdominal trauma, infectious diseases, cholangiohepatitis, and organophosphate and other drug intoxication. The clinical presentation of cats with pancreatitis is nonspecific. Vomiting and signs of abdominal pain, which are the clinical signs most commonly observed in humans and dogs with pancreatitis, are only uncommonly observed in cats with pancreatitis. Routine laboratory findings are also nonspecific. Abdominal ultrasonography is a valuable diagnostic tool in feline patients with pancreatitis. Serum activities of lipase and amylase are rarely increased in cats with pancreatitis; however, these cats often have elevated serum fTLI concentrations. The goals of management are removal of the inciting cause, provision of supportive and symptomatic therapy, and careful monitoring for and aggressive treatment of systemic complications. Exocrine pancreatic insufficiency is a syndrome caused by insufficient synthesis of pancreatic digestive enzymes by the exocrine portion of the pancrease. The clinical signs most commonly reported are weight loss, loose and voluminous stools, and greasy soiling of the hair coat. Serum fTLI is subnormal in affected cats. Treatment of cats with EPI consists of enzyme supplementation with powdered pancreatic extracts or raw beef pancreas. Many cats with EPI have concurrent small intestinal disease. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require parenteral cobalamin supplementation. Pancreatic adenocarcinoma is the most common neoplastic condition of the exocrine pancreas in the cat. At the time of diagnosis, the tumor has already metastasized in most cases, and the prognosis is poor. Pancreatic pseudocyst, pancreatic abscess, pancreatic parasites, pancreatic bladder, and nodular hyperplasia are other exocrine pancreatic disorders, that are less commonly seen in cats.