Vitamin B12 treatment for sleep-wake rhythm disorders

Vitamin B12 (VB12) was administered to two patients suffering for many years from different sleep-wake rhythm disorders. One patient was a 15-year-old blind girl suffering from a free-running sleep-wake rhythm (hypernychthemeral syndrome) with a period of about 25 h. In spite of repeated trials to entrain her sleep-wake cycle to the environmental 24-h rhythm, her free-running rhythm persisted for about 13 years. When she was 14 years old, administration of VB12 per os was started at the daily dose of 1.5 mg t.i.d. Shortly thereafter, her sleep-wake rhythm was entrained to the environmental 24-h rhythm, and her 24-h sleep-wake rhythm was maintained while she was on the medication. Within 2 months of the withholding of VB12, her free-running sleep-wake rhythm reappeared. The VB12 level in the serum was within the normal range both before and after treatment. The other patient was a 55-year-old man suffering from delayed sleep phase syndrome since 18 years of age. After administration of VB12 at the daily doses of 1.5 mg, his sleep-wake rhythm disorder was improved. The good therapeutic effect lasted for more than 6 months while he was on the medication.     

Anaphylaxis to riboflavin (vitamin B2).

BACKGROUND: Vitamin supplements are used more commonly in normal healthy subjects than in patients with vitamin deficiency. Thiamine (vitamin B,) is the vitamin that most frequently induces allergic reactions. To the best of our knowledge, no case of anaphylaxis to riboflavin (vitamin B2) has thus far been reported in the literature. OBJECTIVE: We describe a previously healthy 15-year-old boy in whom anaphylaxis developed several times after he drank one soft drink or took a single multivitamin tablet. This study was done to determine which of the many components found in the soft drink and vitamin tablet caused the anaphylactic reaction. METHODS: In an outpatient clinic with the availability of complete resuscitative procedures, we performed single-blind prick skin tests and intradermal skin tests on the patient with various pure vitamin components of the soft drink and the multivitamin tablet. Physiologic saline and histamine were used for negative and positive controls, respectively. RESULTS: Riboflavin, a component of both the soft drink and the vitamin tablet, produced positive reactions on intradermal skin tests in the patient. Positive reactions were not present in the normal control subjects. CONCLUSIONS: Riboflavin is a previously unreported cause of anaphylaxis. Free-form riboflavin may potentially be associated with an anaphylactic reaction. It is a vitamin widely used in many patients with chronic disease and in healthy subjects. Vitamin B2 must be considered as a cause of anaphylaxis.     

Selective malabsorption of vitamin B12 and vitamin B12-intrinsic factor with megaloblastic anemia in an adult

The first case of megaloblastic anemia due to selective malabsorption of vitamin B₁₂ and vitamin B₁₂-intrinsic factor is described in an otherwise normal female adult, in whom pernicious anemia had previously been diagnosed.     

Experiences with dual protein bound aqueous vitamin B12 absorption test in subjects with low serum vitamin B12 concentrations.

A dual isotope vitamin B12 absorption test in which vitamin B12 is given both in aqueous solution and bound to protein (chicken serum), was evaluated in 26 controls and 68 patients with subnormal serum vitamin B12 concentrations (19 with pernicious anaemia, 13 with iron deficiency, seven after partial gastrectomy, seven with malabsorptive states, five with folate deficiency, four with chronic alcoholism and 13 in whom no cause was apparent). In control patients protein bound absorption decreased with age; isotope excretion was 1.0% or over in those aged under 60 and 0.5% or over in those aged 60 and above. Malabsorption of protein bound vitamin B12 with normal aqueous absorption occurred in five patients with iron deficiency, three with alcoholism, two after partial gastrectomy, two with folate deficiency and in one with a malabsorptive state. In alcoholics abstinence produced an improvement in protein bound absorption. All patients in the group for whom no cause could be found for the subnormal serum vitamin B12 concentration had normal aqueous absorption but four had malabsorption of protein bound vitamin. Although the dual isotope test gave reproducible results and was consistent with the standard Schilling test some anomalies were detected; nine patients had reduced aqueous absorption with normal protein bound absorption. Despite this the dual test may prove useful in determining the importance of a subnormal vitamin B12 concentration where the cause is not clinically apparent. Further development is needed before it can be considered for routine use.     

Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency

A male infant with methyl-B12 deficiency (cblE) presented at age 6 weeks with lethargy, staring spells, and vomiting. He later became hypotonic and unresponsive to stimuli and required intubation and ventilation. He had homocystinuria and hypomethioninemia with megaloblastic anemia but normal serum folate and vitamin B12 concentrations. No methylmalonic aciduria was detected. Fibroblasts, cultured from the patient, were unable to grow in medium in which homocysteine replaced methionine and incorporated abnormally small amounts of [14C]-methyl-tetrahydrofolate but normal amounts of [14C]-propionate into protein. Methyl-B12 content of fibroblasts was low, while the adenosyl-B12 content was normal. Methionine synthase activity was decreased when the assay was performed under both optimal and suboptimal reducing conditions, suggesting heterogeneity in the cblE disease. The patient responded dramatically to hydroxocobalamin treatment. Homocystinuria disappeared after 10 days of therapy, and methionine was normalized after 3 weeks. Psychometric testing at age 15 months showed a developmental age of 9 months.     

Vitamin B12 absorption studies: effect of parenteral non-radioactive vitamin B12 on serum level of 57Co vitamin B12

The intestinal absorption of (57)Co vitamin B(12) has been measured by counting the radioactivity in the serum, and the effect of the parenteral administration of 1 mg. non-radioactive vitamin B(12) two hours after the oral dose has been studied. When parenteral vitamin B(12) was not given, the mean radioactivity in the serum was lower in both patients with pernicious anaemia and in control subjects, and the results in the patients with pernicious anaemia were more definitive. There was no significant difference between the results obtained with an Ekco scaler and those with an I.D.L. scaler.This is the simplest and most convenient method of measuring vitamin B(12) absorption. It is suggested that the test be standardized by giving 0.5 mug. (57)Co vitamin B(12) with a maximal histamine stimulation of intrinsic factor secretion, but without a parenteral dose of non-radioactive vitamin B(12). The results are expressed most usefully as a percentage of the administered dose per litre of serum or plasma.     

Serum vitamin B12 in renal failure

The serum vitamin B₁₂ level was abnormally high in 14 out of 32 cases of renal failure. This was probably due to impaired excretion of the vitamin, but the results of measurements of the rate of excretion of radioactive vitamin B₁₂ did not provide unequivocal evidence on this point; other possible explanations are discussed. Renal failure must be added to the causes of high serum B₁₂ levels.