Physician's management of suspected vitamin B12 deficiency.

A retrospective study was undertaken to audit physician''s management of patients with a low serum level of vitamin B12 who were admitted to a university-affiliated teaching hospital during 1 year. Among the 34 patients 13 were proved to have pernicious anemia or vitamin B12 malabsorption, but for 12 of them there were unnecessary delays (several days or weeks) before initiation of investigation and therapy. An additional six patients, who had low serum levels of vitamin B12 and macrocytosis, most likely had true vitamin B12 deficiency, but proper investigation was not done and they did not receive any vitamin B12 or folic acid therapy. In another nine cases unexplained low serum levels of vitamin B12 were not properly investigated, and the patients either did not receive any vitamin B12 therapy or received it without proper documentation of a deficiency. Suggestions for facilitating early detection, investigation and treatment of megaloblastic anemia or vitamin B12 deficiency are given.     

The effect of nitrous oxide-induced vitamin B12 deficiency on in vivo folate metabolism

The effect of N₂O-induced vitamin B₁₂ deficiency on $\text{in}\text{vivo}$ folate metabolism was studied in an animal model previously developed for studies of the folate enterohepatic cycle, and in rats with localized, subcutaneous tumor nodules. While N₂O inhibited liver folate polyglutamate formation, it did not affect the absorption of (³H)PteGlu₁ from the gut, its reduction, methylation, and transport to the liver, or the subsequent secretion of CH₃H₄(³H)PteGlu₁ into bile—the folate enterohepatic cyle. In addition, N₂O did not impair folate polyglutamate formation in the fibrosarcoma tumor nodule suggesting that tumor tissue can either demethylate CH₃H₄PteGlu₁ by an alternate pathway or can utilize it as a substrate for polyglutamate formation without demethylation.     

The diagnosis of vitamin B 12 deficiency]

In 5 normal persons, 1 patient with pernicious anemia, 5 patients with renal insufficiency in the state of compensation, and in one patient with chronic hemodialysis Schilling tests, activity of 57Co and vitamin B12 serum levels were measured. It was obvicous that activity of 57Co in serum 8 hours after oral application of 0.5 muCi 57Co-vitamin B12 showed reliable results to clear the problem of vitamin B12 malresorption. This method is easier than the Schilling test because the collection of 24-hour-urine is not necessary and an insufficiency of renal function does not influence the result.     

Relationships between biotin and vitamin B12. Effects of biotin and vitamin B12 on folic acid metabolism

1. The effects of dietary biotin compared with vitamin B₁₂ on the total content and on the distribution of the various folate derivatives in the liver of rats given a biotin-free diet have been studied. The effect of both vitamins on the conversion in vitro of folic acid into citrovorum factor in the same experimental conditions was also examined. 2. In biotin-treated rats as well as in vitamin B₁₂-treated rats the total content of folic acid-active substances measured microbiologically by Pediococcus cerevisiae, Streptococcus faecalis and Lactobacillus casei is significantly higher than that in biotin-deficient rats. The liver distribution of various folate derivatives in the three groups of animals is also markedly modified. 3. The amount of citrovorum factor formed in systems with liver homogenate of rats receiving biotin or vitamin B₁₂ is higher than that with liver homogenates of deficient rats. 4. The results obtained demonstrate the influence of biotin in the metabolism of folic acid, and the similar actions at this level of both biotin and vitamin B₁₂. These results are discussed in relation to the participation of the two vitamins in the metabolism of C₁ units, as a biochemical interpretation of the relationships between vitamin B₁₂ and biotin.     

Effect of high levels of dietary folic acid on folate metabolism in vitamin B12 deficiency

The effect of administering high levels of folic acid to vitamin B12-deficient animals was studied. In B12 deficiency histidine oxidation is decreased. This is the result of both decreased liver folate levels and increases in the proportion of methyltetrahydrofolates. The purpose of this study was to determine if the addition of very high levels of folic acid to B12-deficient diets could increase liver folates and thereby restore histidine oxidation. Rats were fed a soy protein B12-deficient diet containing 10% pectin which has been shown previously to accelerate B12 depletion. When this diet was supplemented with B12 and folic acid, histidine oxidation was 5.4% in 2 h and the livers contained 3.49 micrograms of folate/g. In the absence of B12, the histidine oxidation rate was 0.34% and the liver folate level was 1.33 micrograms/g. When 200 mg/kg of folic acid was added to the B12-deficient diet there was no increase in histidine oxidation (0.35%) but the liver folates were increased to 3.68 micrograms which is about the same as that with B12 supplementation. The percentage tetrahydrofolate of the total liver folates was the same with and without a high level of dietary folic acid. Thus there was an increase in the absolute level of tetrahydrofolate without any increase in folate function as measured by histidine oxidation. Red cell folate levels were the same with and without B12, which is in contrast to the markedly lower liver folate levels in B12 deficiency. These data suggest a difference between B12 regulation of folate metabolism in the liver and in the bone marrow.     

Factors affecting formiminoglutamic acid excretion in vitamin B12 deficiency

1. Formiminoglutamic acid, a product of the catabolism of histidine, is excreted in abnormally large amounts in the urines of vitamin B(12)-deficient rats and of vitamin B(12)-deficient sheep; the excretion is reduced to negligible amounts after administration of vitamin B(12). 2. After administration of certain methyl donors to vitamin B(12)-deficient rats or sheep urinary excretion of formiminoglutamic acid is temporarily decreased. 3. Irrespective of the pteroylglutamic acid status of the animals neither vitamin B(12)-deficient rats nor vitamin B(12)-deficient sheep have the ability to deal efficiently with histidine. 4. In sheep, urinary excretion of formiminoglutamic acid is increased after administration of aminopterin; treatment with pteroylglutamic acid restores the ability of the animal to deal with the catabolic products of histidine. 5. The possible functions of vitamin B(12) and methionine in relieving a virtual deficiency of pteroylglutamic acid are discussed.     

Sequential changes in propionate metabolism during the development of cobalt/vitamin B12 deficiency in sheep

The changes in propionate metabolism that accompany cobalt deficiency in sheep are described. Two groups of sheep, fed either a cobalt sufficient or deficient diet, were given an iv propionate load at intervals during a 14 w experiment. There was a tendency towards increased propionate half-life as the animals became cobalt deficient. However, significant changes in the area under the plasma methylmalonic acid-time curve occurred very early, indicating significant impairment of propionate metabolism. Despite this, the area under the plasma glucose-time curve was unaffected by cobalt deficiency, suggesting that the impairment of propionate metabolism, although significant, is not extensive.     

The effect of vitamin B12 and biotin on the metabolism of vitamin B12 in biotin-deficient rats

1. The effect of the administration of vitamin B₁₂ and biotin on the metabolic pattern of vitamin B₁₂ in biotin-deficient rats was studied. 2. No significant changes in the absorption and excretion of orally administered [⁵⁸Co]vitamin B₁₂ were noted either in vitamin B₁₂-treated and or in biotin-fed rats. A significant decrease of the uptake of orally given [⁵⁸Co]vitamin B₁₂ was observed in the liver and kidneys of biotin-treated rats, whereas an increase of uptake in the kidneys of vitamin B₁₂-treated rats was noted as compared with biotin-deficient animals. 3. No significant difference in the excretion of radioactivity was noted between biotin deficient and biotin-fed rats when [⁵⁸Co]vitamin B₁₂ was administered by injection. A small decrease was observed in vitamin B₁₂-treated rats. The retention of injected [⁵⁸Co]vitamin B₁₂ by major organs of biotin-treated rats was lower than that of biotin-deficient rats. A lower content of [⁵⁸Co]vitamin B₁₂ was also detected in the organs, with the exception of the kidneys, of vitamin B₁₂-treated rats. 4. These results are discussed in terms of an interrelationship between biotin and vitamin B₁₂.