addition to food folate. Therefore, the recommendation for women capable of becoming pregnant is to take 400 µg/day of folate from fortified foods and/or a supplement as well as food folate from a varied diet. It is not known whether the same level of protection could be achieved by using food that is naturally rich in folate. Neither is it known whether lower intakes would be protective or whether there is a threshold below which no protection occurs.

Elevated homocysteine values have been associated with increased risk of vascular disease, and intakes of folate and vitamins B₆ and B₁₂ have been inversely related to homocysteine values. However, conflicting evidence exists and it is premature to conclude that increasing the intake of these B vitamins could reduce the risk of vascular disease and thrombosis. Randomized trials among high-risk, healthy individuals and among patients with vascular disease are expected to provide evidence useful in resolving this matter.

Many studies have investigated relationships between folate status and carcinogenesis. The data suggesting an inverse relationship between folate status and the occurrence of colorectal cancer are stronger than for other forms of cancer (e.g., cancer of the cervix, esophagus, stomach, and lung) but are not conclusive.

Although available information suggests that a link may exist between folate deficiency and abnormal mental function, more than three decades of research have not produced a definitive connection. Other than for relatively rare inborn errors of metabolism, it is not known whether low folate or vitamin B₆ status increases the risk of neuropsychiatric disorders or results from them. Neither is it known definitively how vitamin B₁₂ status above that usually presumed to be adequate relates to psychiatric disturbances.

A risk assessment model is used to derive the Tolerable Upper Intake Levels (ULs). The model consists of a systematic series of