 There is substantial evidence that direct folic supplementation increases blood serum levels of bioavailable folate even though at least one study have shown slow and variable activity of dihydrofolate reductase in human liver.A diet rich in natural folate (350 μg/d) can show as much increase in plasma folate as taking low levels of folic acid (250 μg/d) in individuals However a comparison of general population outcomes across many countries with different approaches to increasing folate consumption has found that only general food fortification with folic acid reduces neural tube defects.While there have been concerns about folic acid supplementation being linked to an increased risk for cancer, a systematic review in 2012 shows there is no evidence except in the case of prostate cancer which indicates a modest reduction in risk.