A number of cases with iron deficiency anemia (IDA) are associated with low vitamin B12 (LB12). However, LB12 is not synonymous with B12 deficiency. An increase in homocysteine (Hcy) or methylmalonic acid can differentiate cases with a real deficiency from those with apparently innocuous LB12. Our aim was to study LB12 and low red cell folate (LRCF) prevalence in IDA cases and to determine the existence of B12/folate deficiency. A prospective case-control study was carried out in patients with anemia consecutively admitted to our Hospital. The case group included 506 IDA patients (Hb <115g/l, MCV <98fl, serum ferritin <20microg/l or soluble transferrin receptor >5mg/l). The control group was made up of 117 patients with anemia of chronic disorders (ACD) (Hb <115g/l, MCV 80-98fl, iron <10micromol/l, total iron binding capacity <40micromol/l, serum ferritin >100microg/l and soluble transferrin receptor <4mg/l). Serum B12 and RCF were evaluated in all cases and controls. Serum homocysteine was determined in those with B12 and/or RCF below percentile 10 (B12 <200pmol/l, RCF <590nmol/l). HyperHcy was considered when Hcy exceeded >17micromol/l. Several variables were included in a multiple regression analysis to build a predictive model for IDA with LB12 and hyperHcy. LB12 was observed in 17.8% of IDA cases (87 cases), including 8.2% with B12<150pmol/l (percentile 2.5). Interestingly, 60% of patients with B12 <150pmol/l had hyperHcy and 48% of those with B12 between 150 and 200pmol/l. Low RCF was found in 6.3% (13 cases). All cases with RCF <500nmol/l (percentile 2.5) showed hyperHcy and 50% of cases with RCF between 500 and 590nmol/l. LB12 was observed in 7 patients in the control group (5.4%) and LRCF in 10%. LB12 was more frequent in IDA than in ACD (p<0.0001). The best predictive variable for IDA and LB12 with hyperHcy was age and the cut-off was 60 years (sensitivity: 91%). In summary, in our study 18% of cases with IDA showed LB12, and a high percentage had a real vitamin deficiency. Age was the main predictive factor. Thus, serum B12 should be determined in IDA patients over 60 years

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