Folic acid is most commonly known as a supplement to reduce neural tube defects during pregnancy.
Some countries, including the United States, forficate grain products for this health effect.
However, issues have been raised about possible deleterious effects of high folic acid intake.
A recent study from the Yale School of Public Health gives some new insights.
Folic acid is the synthetic form of the water soluble b-vitamin folate. It is included in many food items and supplements because it has increased bioavailability and bioactivity compared to folate.
Folate plays a role in the formation of nucleotides, the building blocks for DNA synthesis and repair. Therefore, folate is required for genomic stability and low folate levels are associated with increased cancer risk.
However, high levels of folate provide a high availability of nucleotides for fast dividing tissues like (pre-)cancerous lesions.
Indeed, some recent studies suggest that folic acid supplementation may increase cancer risk in some individuals (i.e. those with undiagnosed precancerous lesions). It has been suggested that the relationship between folic acid intake and cancer risk has a reverse U-shape, as seen in the figure below.
Therefore, mandatory folic acid fortification of grain products in the United States may have unintended negative consequences.
The study had a cohort design, meaning that data on the subjects was collected over time, but that the subjects lived their normal lives and did not undergo any interventional treatment.
The first data was collected before fortification, while later data was from the postfortification period.
The researchers found that increased total folic acid intake was associated with decreased colorectal cancer risk. Higher intakes of folic acid from either the diet or supplements were also protective.
These associations where found in both the pre- and postfortification period and were similar. These results suggest that high doses of folic acid have a protective, rather than a negative effect on colorectal cancer risk and the source of folic acid intake does not appear to influence the results.
However, the researchers are careful with their conclusions.
They mention that the postfortification period of 8.5 years may have been too short to identify possible effects of folic acid on colorectal cancer development, which may take 10+ years to become evident.
They also comment that high folic acid intake could have different effects in high risk subgroups, i.e people with existing undiagnosed precancerous lesions.
In light of the emerging public belief that ‘natural = good, synthetic = bad’, it is interesting to mention that the intake of synthetic folic acid had a stronger inverse relation with colorectal cancer risk than the intake of natural folates.
Trying to eat natural might still be a good approach, but predicting results based on a single concept rarely pans out.