Oral Cobalamin Supplementation Research Articles

Vitamin B12 in Cats: Nutrition, Metabolism, and Disease.

Cobalamin is a water-soluble molecule that has an important role in cellular metabolism, especially in DNA synthesis, methylation, and mitochondrial metabolism. Cobalamin is bound by intrinsic factor (IF) and absorbed in the ileal tract. The IF in cats is synthesized exclusively by pancreatic tissue. About 75% of the total plasma cobalamin in cats is associated with transcobalamin II, while in this species, transcobalamin I is not present. In cats, the half-life of cobalamin is 11-14 days. Diagnostic biomarkers for B12 status in cats include decreased levels of circulating total cobalamin and increased levels of methylmalonic acid. The reference interval for serum cobalamin concentrations in cats is 290-1500 ng/L, and for the serum methylmalonic acid concentration, it is 139-897 nmol/L. Therapy for hypocobalaminemia mainly depends on the underlying disease. In some cases, subcutaneous or intramuscular injection of 250 μg/cat is empirically administered. In recent years, it has been demonstrated that oral cobalamin supplementation can also be used successfully in dogs and cats as a less invasive alternative to parental administration. This review describes the current knowledge regarding B12 requirements and highlights improvements in diagnostic methods as well as the role of hypocobalaminemia in its associated diseases.

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 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.

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.

Oral cobalamin supplementation in cats with hypocobalaminaemia: a retrospective study.

Objectives The objective of the study was to evaluate whether oral cobalamin supplementation can restore normocobal-aminaemia in cats with hypocobalaminaemia and clinical signs of gastrointestinal disease. Methods This was a retrospective study based on a computerised database search for client-owned cats treated at Evidensia Specialist Animal Hospital, Helsingborg, Sweden, during the period December 2013 to August 2016. Inclusion criteria were cats with clinical signs of chronic enteropathy, an initial serum cobalamin concentration ⩽250 pmol/l (reference interval 214-738 pmol/l) and oral treatment with cobalamin tablets. Results Twenty-five cats met the inclusion criteria. The cats were treated with 0.25 mg cyanocobalamin tablets once daily. Serum cobalamin concentration was rechecked 27-94 days after continuous oral cobalamin supplementation. All cats had serum cobalamin concentrations above the reference interval after oral cobalamin supplementation. Median (range) serum cobalamin concentration was 128 pmol/l (111-250 pmol/l) prior to treatment and 2701 pmol/l (738-16,359 pmol/l) after supplementation. This difference was statistically significant ( P <0.0001). Conclusions and relevance Our results suggest that oral cobalamin supplementation is effective in increasing serum cobalamin to supranormal concentrations in cats with hypocobalaminaemia. Thus, oral cobalamin supplementation is a promising alternative to parenteral administration. Prospective comparative studies in cats being treated with parenteral vs oral cobalamin supplementation in a larger number of patients are warranted before oral supplementation can be recommended for routine use.

Oral Cobalamin Supplementation in Dogs with Chronic Enteropathies and Hypocobalaminemia

BackgroundCobalamin deficiency is commonly associated with chronic enteropathies (CE) in dogs and current treatment protocols recommend parenteral supplementation. In humans, several studies have reported equal efficacy of oral and parenteral cobalamin administration of cobalamin.ObjectivesTo retrospectively evaluate whether oral cobalamin supplementation can restore normocobalaminemia in dogs with CE and hypocobalaminemia.AnimalsFifty‐one client‐owned dogs with various signs of CE and hypocobalaminemia.Material and MethodsRetrospective study based on a computerized database search for dogs treated at Evidensia Specialist Animal Hospital, Helsingborg, Sweden during January 2012–March 2014. Inclusion criteria were dogs with signs of CE, an initial serum cobalamin ≤270 ng/L (reference interval: 234–811 ng/L) and oral treatment with cobalamin tablets. Serum cobalamin for follow‐up was analyzed 20–202 days after continuous oral cobalamin supplementation started.ResultsAll dogs became normocobalaminemic with oral cobalamin supplementation. The mean increase in serum cobalamin concentration after treatment was 794 ± 462 ng/L. Serum cobalamin concentrations were significantly higher after supplementation (mean 1017 ± 460 ng/L; P < .0001) than at baseline (mean 223 ± 33 ng/L).Conclusion and Clinical ImportanceOur results suggest that oral cobalamin supplementation is effective in normalizing serum cobalamin concentrations in dogs with CE. Prospective studies comparing cellular cobalamin status in dogs being treated with parenteral versus oral cobalamin supplementation are warranted before oral supplementation can be recommended for routine supplementation.

Cobalamin deficiency in the elderly: aetiology and management: a study of 125 patients in a geriatric hospital.

Cobalamin deficiency is frequent in elderly patients and the main aetiologies are food-cobalamin malabsorption and pernicious anaemia. The aim of our retrospective study was to identify the causes and methods of management of cobalamin deficiency at Nice geriatric university hospital. A retrospective monocentric study was conducted over 14 months at Nice geriatric hospital, which included patients with cobalamin deficiency having received supplementation. The clinical and paraclinical data, etiological diagnosis, treatment and follow-up modalities were analyzed retrospectively. We studied 125 elderly patients whose median age was 85.5 ± 7 years. The etiological diagnosis was food-cobalamin malabsorption for 72 patients (57.6 %), nutritional cobalamin deficiency for 15 patients (12 %), pernicious anaemia for 12 patients (9.6 %) and there was no etiological diagnosis for 26 patients (20.8 %). Concerning cobalamin therapy, 111 patients (88.8 %) received oral therapy and 14 (11.2 %) intramuscular therapy. Vitamin B12 levels increased significantly after supplementation (p<0.001) but cobalamin administration varied according to the diagnoses (p<0.001) and was less effective in patients with dementia (p=0.04) and food-cobalamin malabsorption. Our study showed the importance of food-cobalamin malabsorption in etiological diagnosis in accordance with the literature, but also the non-negligible share of nutritional cobalamin deficiency. Mainly oral cobalamin supplementation was used in our study with a significant increase in vitamin B12 levels. An oral cobalamin regimen is proposed for elderly patients with cobalamin deficiency but with no severe neurological signs.

Schizophrenia-like psychotic episode precipitated by cobalamin deficiency

Although cobalamin deficiency is widely known and usually presents with hematologic and neuropsychiatric manifestations, the psychiatric symptoms are not usually the predominant manifestation. We describe a young single male vegetarian who developed a cobalamin-induced psychotic episode without preceding neurologic manifestations and without any hematologic symptoms. He recovered after a short course of antipsychotics and oral cobalamin supplementation and remained asymptomatic and functionally independent at 1 year of follow-up.

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.