Erythrocyte alterations in older lacto-ovo-vegetarians with serum vitamin B12 within the laboratory reference interval: a cross-sectional study

Introduction Serum vitamin B12 is widely used to assess cobalamin status, but concentrations within the laboratory reference interval do not establish adequate tissue status. We examined erythrocyte indices in older long-term lacto-ovo-vegetarians with serum vitamin B12 within the reference interval, without treating these indices as diagnostic evidence of functional vitamin B12 deficiency. Methods This exploratory cross-sectional study included 81 adults aged ≥65 years: 28 with serum vitamin B12 < 190 pg/mL (Group A), 29 long-term lacto-ovo-vegetarians with serum vitamin B12 ≥ 190 pg/mL (Group B), and 24 omnivorous participants with serum vitamin B12 ≥ 190 pg/mL (Group C). The primary comparison was Group B versus Group C. Serum vitamin B12, homocysteine (Hcy), folate, ferritin, and complete blood count indices were assessed. Between-group estimates included 95% confidence intervals (CIs), with Holm correction for six primary outcomes; other analyses were exploratory. Results Compared with Group C, Group B had lower red blood cell (RBC) count (mean difference, −0.63 × 10 12 /L; 95% CI, −0.79 to −0.46), hematocrit (−3.63 percentage points; 95% CI, −5.53 to −1.72), and hemoglobin (−14.23 g/L; 95% CI, −18.74 to −9.72), and higher mean corpuscular volume (MCV; +4.04 fL; 95% CI, 1.71 to 6.37) and red cell distribution width-coefficient of variation (RDW-CV; +2.01 percentage points; 95% CI, 1.68 to 2.35); all Holm-adjusted p ≤ 0.0024. The Hcy difference (+1.73 μmol/L; 95% CI, −0.01 to 3.46) did not meet the adjusted significance threshold ( p = 0.051). In adjusted analysis, vegetarian status remained associated with higher MCV (β = 4.09 fL; 95% CI, 1.59 to 6.58; p = 0.002), whereas Hcy models were less robust. Anemia occurred in 11/29 (37.9%) Group B participants and 0/24 Group C participants; macrocytosis occurred in 7/29 (24.1%) and 3/24 (12.5%), respectively. Conclusion Older long-term lacto-ovo-vegetarians with serum vitamin B12 within the laboratory reference interval had lower RBC count, hematocrit, and hemoglobin and higher MCV and RDW-CV than omnivorous controls. These findings support interpreting serum B12 alongside the complete blood count and considering functional B12 markers and broader nutritional assessment when abnormalities are present. The data do not establish functional B12 deficiency, screening performance, or causality.