Abstract
The importance of folic acid supplementation in reducing the risk of neural tube defects is well established. However, the effects of folic acid on other diseases, including cancer, are less well understood and have been the subject of several clinical trials. Folate vitamers are chemically similar substances derived from the parent compound pteroyl monoglutamic acid. Several placebo-controlled clinical trials have assessed the impact of folate vitamer supplements on cancer incidence and mortality with differing results. Meta-analyses have found an association between folate supplements and cancer outcomes with different estimates of certainty. However, we believe that differentiating between the different vitamer forms will account for much of the heterogeneity seen in the data. This protocol aims to define the methods for a systematic review and meta-analysis to assess if individual folate vitamers modify the risk of cancer incidence and cancer-associated mortality.