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Information from the Boston Nutritional Status Survey on folate supplement use by a free-living elderly population from 1981 to 1984 is given in Appendix F. Both the fiftieth percentile and seventy-fifth percentiles of folate intake from supplements were 400 µg for supplement users. Largely because of supplement use, the median folate intake by pregnant women in NHANES III in 1988 to 1994 was nearly 1,000 µg/day (Appendix H). Supplements containing 1,000 µg or more of folate are available only by prescription in the United States and Canada. Smaller doses, usually 400 (g, are available over the counter.

TOLERABLE UPPER INTAKE LEVELS

Hazard Identification

This section reviews the potential hazards associated with high intake of folate as one of the primary steps in developing a Tolerable Upper Intake Level (UL). In reviewing potential hazards, careful consideration was given to the metabolic interrelationships between folate and vitamin B12, which include shared participation of the two vitamins in an enzymatic reaction; identical hematological complications resulting from deficiency of either nutrient; amelioration by folate administration of the hematological complications caused by either folate or vitamin B12 deficiency; and in vitamin B12 deficiency, the occurrence of neurological complications that do not respond to folate administration.

Adverse Effects

No adverse effects have been associated with the consumption of the amounts of folate normally found in fortified foods (Butterworth and Tamura, 1989). Therefore, this review is limited to evidence concerning intake of supplemented folate. The experimental data in animal studies and in vitro tissue and cell culture studies were considered briefly to determine whether they supported the limited human data.

Neurological Effects. The risk of neurological effects described in this section applies to individuals with vitamin B12 deficiency. Vitamin B12 deficiency is often undiagnosed but may affect a substantial percentage of the population, especially older adults (see Chapter 9). Three types of evidence suggest that excess supplemental folate intake may precipitate or exacerbate the neurological damage of



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