error] and 60.3 ± 7.9, respectively, p < 0.02), and urinary thiocyanate excretion (an index of the exogenous cyanide load) was inversely associated with serum B₁₂. Similarly, in a study of pregnant women, the distribution of values of serum B₁₂ was slightly lower for smokers than for nonsmokers. However, in a cross-sectional study, differences in B₁₂ concentrations of smokers and nonsmokers were not significant in multivariate analyses. The effect of smoking on the B₁₂ requirement thus appears to be negligible.

In a cross-sectional study of 77 young men and 82 young women (Fernandes-Costa et al., 1985), the women were found to have significantly higher serum B₁₂ values and unsaturated cobalamin binding capacity than did the men (p < 0.001 and 0.05, respectively). Subjects were excluded if they were taking vitamin supplements, oral contraceptive agents, or other medications other than patent analgesics. Mean serum B₁₂ values were 477 and 604 pmol/L (647 and 819 pg/mL) for men and women, respectively—well above the cutoff of adequacy. Other investigators have reported similar findings (Low-Beer et al., 1968; Metz et al., 1971). Studies that have found no difference in mean B₁₂ values were smaller and less well-controlled for other factors that could influence B₁₂ values (Rosner and Schreiber, 1972; Scott et al., 1974). Taken together, these studies do not provide sufficient evidence on which to quantitate a difference in B₁₂ requirements by gender.

Although adequate or high folate intake may mitigate the effects of a B₁₂ deficiency on normal blood formation, there is no evidence that folate intake or status changes the requirement for B₁₂.

Low serum B₁₂ values reported in persons receiving megadoses of vitamin C are likely to be artifacts of the effect of ascorbate on the radioisotope assay for B₁₂ (Herbert et al., 1978) —and thus not a true nutrient-nutrient interaction.