Translations:Folate/44/en

Reviews of clinical trials that called for long-term consumption of folic acid in amounts exceeding the UL have raised concerns. Excessive amounts derived from supplements are more of a concern than that derived from natural food sources and the relative proportion to vitamin B₁₂ may be a significant factor in adverse effects. One theory is that consumption of large amounts of folic acid leads to detectable amounts of unmetabolized folic acid circulating in blood because the enzyme dihydrofolate reductase that converts folic acid to the biologically active forms is rate limiting. Evidence of a negative health effect of folic acid in blood is not consistent, and folic acid has no known cofactor function that would increase the likelihood of a causal role for free folic acid in disease development. However, low vitamin B₁₂ status in combination with high folic acid intake, in addition to the previously mentioned neuropathy risk, appeared to increase the risk of cognitive impairment in the elderly. Long-term use of folic acid dietary supplements in excess of 1,000 μg/day has been linked to an increase in prostate cancer risk.