vitamin B₁₂ deficiency. First, numerous human case reports show onset or progression of neurological complications in vitamin B₁₂-deficient individuals receiving supplemental folate (Table 8-12). Second, studies in monkeys (Agamanolis et al., 1976) and fruit bats (van der Westhuyzen and Metz, 1983; van der Westhuyzen et al., 1982) show that vitamin B₁₂-deficient animals receiving supplemental folate develop signs of neuropathology earlier than do controls. The monkey studies used dietary methods to induce vitamin B₁₂ deficiency whereas the fruit bat studies used a well-described method involving nitrous oxide (Metz and van der Westhuyzen, 1987). Third, a metabolic interaction between folate and vitamin B₁₂ is well documented (Chanarin et al., 1989). Although the association between folate treatment and neurological damage observed in human case reports does not provide proof of causality, the hazard associated with excess supplemental folate cannot be ruled out. The hazard remains plausible given the findings from animal studies and the demonstrated biochemical interaction of the two nutrients. The resulting neurological damage may be serious, irreversible, and crippling.

For many years, it has been recognized that excessive intake of folate supplements may obscure or mask and potentially delay the diagnosis of vitamin B₁₂ deficiency. Delayed diagnosis can result in an increased risk of progressive, unrecognized neurological damage. Evidence from animal as well as in vitro tissue and cell culture studies (Baxter et al., 1973; Hommes and Obbens, 1972; Kehl et al.,