doses of pyridoxine to treat carpal tunnel and premenstrual syndromes (Schaumburg et al., 1983, as cited in IOM, 1998). With the neuropathy related to high-dose treatments of pyridoxine, there was sufficient scientific documentation for the panel to identify a NOAEL and a LOAEL to derive a UL for adults and to address specific issues based on limited data related to the life stage groups of those under 19 years of age, pregnancy, and lactation (IOM, 1998). Because pyridoxine had been used as a single-treatment modality at high doses, the relationship could be identified. With other nutrients, more often the case was that the data were too limited to clearly demonstrate a relationship between the biological endpoint and the dose or duration of treatment. With pyridoxine, a dose-response relationship and the development of neuropathology had been well described in animal studies prior to the first reports in humans (Phillips et al., 1978, as cited in IOM, 1998). While the LOAEL and NOAEL for pyridoxine were identified based on human studies, the animal data served to confirm the dose cut-points.

The ability to set a UL for a nutrient is particularly important for discretionary fortification. For most nutrients there is limited indication that the UL could be reached through the intake of nutrients from conventional food marketed for the general population 4 years of age and older. The risk may be greater for food marketed to specific life stage and gender groups and through the prolonged use of high doses of dietary supplements either as part of the overall diet or for treatment purposes. The committee recommends that support for research on adverse effects become a high priority for those nutrients for which no UL could be established and for which initial data indicate that the general population or particular life stage and gender groups may be at risk from high intakes.

In addition, the committee recommends that the Food and Drug Administration and Health Canada expand their educational efforts to help consumers and health care professionals clearly understand the breadth of possible adverse effects, the information needed to identify a relationship between a food or dietary supplement and an adverse effect, and the best process for accurately reporting this information.


There is an urgent need for empirical research to determine the impact of discretionary fortification practices on the distribution of usual nutrient intakes and on the prevalence of nutrient inadequacy

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