Normalization of Low Vitamin B ₁₂ Serum Levels in Older People by Oral Treatment

To the Editor: Low serum vitamin B12 levels unrelated to pernicious anemia are found frequently in older people. Prevalence varies from 1 to 31.5%; the causes and the clinical significance remain unclear. It has been suggested that in some older people, a malabsorption for food-bound or protein-bound cobalamin exists despite a normal intrinsic factor mechanism1,2 and normal absorption of free vitamin B12. The occurrence of atrophic gastritis resulting in hypochlorhydria increases with age and could play a role in decreased vitamin B12 absorption.3,5 As the pH in the stomach rises, the vitamin B12 has more difficulty detaching from the proteins in the food. As a result, less vitamin B12 binds to the R-protein and to the intrinsic factor, and ileal absorption could become insufficient. Serum gastrin levels are found to be higher in patients with protein-bound vitamin B12 malabsorption, a finding that supports the hypothesis of hypochlorhydria as an important pathophysiological mechanism.3 The absorption of food-bound vitamin B12 decreases throughout the normal aging process.3,6 Malabsorption of protein-bound vitamin B12 not detected by the Schillingtest may cause a vitamin B12 deficiency of clinical importance. The absorption of unbound vitamin B12 does not change, as indicated by the normal Schillingtest in most older patients with low vitamin B12 serum levels.2,3 Therefore, oral administration of vitamin B12 will not be effective. Only occasional observations of orally administered vitamin B12 have been described in the literature.6,7 We studied the effect of oral substitution therapy with free vitamin B12 in older people with low vitamin B12 serum levels. In a prospective open study on two geriatric wards, we screened all consecutively hospitalized patients older than 70 years for vitamin B12 serum concentration of less than 220 ng/L. The determination of vitamin B12 serum levels was done using the Becton Dickinson Simultrac technique. For this method, normal serum levels are between 220 and 940 ng/L. The patients were treated with 0.1 mg oral vitamin B12 a day (10 mL of a solution containing 1 mg vitamin B12 in 100 mL water). Vitamin B12 serum levels were evaluated before therapy, after 10 days, and after 1 month of therapy. A Schillingtest was performed at the completion of this follow-up. We excluded from the study all patients with diarrhea and vomiting. Patients with pernicious anemia on the basis of a pathological Schillingtest and/or those having positive anti-intrinsic factor or anti-parietal cell antibodies, or an elevated gastrin serum level (more than double of normal values) were also excluded. The change of the serum vitamin B12 level was analyzed by one-way ANOVA. A total of 94 patients for whom at least two determinations were obtained (mean age of 84.4 years, SD = 6.4; 69 women and 25 men) were included in the study. Follow-up data were available for 88 patients after 10 days and for 44 patients after 1 month. Missing patients had left the hospital and had either stopped the treatment or were not prepared to return for a further follow-up. The mean vitamin B12 serum level increased from 146.5 ng/L (SD = 35.6) on Day 0 to 271.5 ng/L (SD = 95.5) after 10 days; a further increase to 371.2 ng/L (SD = 285.4) was seen after 30 days of treatment (P < .001). The normalization of vitamin B12. serum levels occurred rapidly: after 10 days, 69% of patients and after 1 month 88% of patients had normal serum levels (Figure 1) Other studies have also indicated that oral substitution might be effective. Some studies revealed that in patients with pernicious anemia, a small but constant proportion of an oral dose of cyanocobalamin was absorbed even without intrinsic factor, so that by sufficiently increasing the dose, adequate absorption could be attained.8,9 Several groups reported clinical and hematological remissions and normalization of serum levels by treating pernicious anemia with doses of 300 to 1000 μg daily.10–12 For a systematic treatment of older patients with low vitamin B12 serum levels unrelated to pernicious anemia, oral substitution appears to be effective and has to be preferred above intramuscular administration. The administration of injections is often difficult for older people who live alone and expensive if given by medical personnel.7,13 From our study we conclude that oral substitution with 100 μ daily is efficient in most older people with vitamin B12 deficiency.