B₁₂-deficient individuals who are at risk for Leber’s optic atrophy should not be given cyanocobalamin to treat the B₁₂ deficiency. Leber’s optic atrophy is a genetic disorder caused by chronic cyanide intoxication (present in tobacco smoke, alcohol, and some plants). Reduced serum B₁₂ concentrations have been associated with a reduced ability to detoxify the cyanide in exposed individuals (Foulds, 1968, 1969a, b, 1970; Wilson and Matthews, 1966). Cyanocobalamin may increase the risk of irreversible neurological damage (from the optic atrophy). Hydroxocobalamin is a cyanide antagonist and therefore not associated with adverse effects when given to these individuals.

The data on adverse effects of B₁₂ intake were considered not sufficient for a dose-response assessment and derivation of a UL.

In 1986 approximately 26 percent of adults in the United States took a supplement containing B₁₂ (Moss et al., 1989). Although no UL can be set for B₁₂, an exposure assessment is provided here for possible future use. Based on data from the Third National Health and Nutrition Examination Survey (see Appendix H), the highest median intake of B₁₂ from diet and supplements for any life stage and gender group was for males aged 31 through 50 years: 17 µg/ day. The highest reported intake at the ninety-fifth percentile was 37 µg/day for pregnant females aged 14 through 55 years.

On the basis of the review of data involving high-dose intakes of B₁₂, there appear to be essentially no risks of adverse effects to the general population even at the current ninety-fifth percentile of intake noted above. Furthermore, there appear to be no risks associated with intakes of supplemental B₁₂ that are more than two orders of magnitude higher than the ninety-fifth percentile of intake. Although there are extensive data showing no adverse effects associated with high intakes of supplemental B₁₂, the studies in which such intakes were reported were not designed to assess adverse effects.