Can Folate Help Lower Cancer Risk in BRCA Carriers?
What the Guidelines Say
Major health organizations such as the Centers for Disease Control and Prevention (CDC) and the American College of Medical Genetics (ACMG) are clear on two points:
Folic acid supplementation (400 µg/day) is recommended for people who could become pregnant to reduce the risk of neural tube defects.
MTHFR gene variants (like C677T and A1298C) are known to affect folic acid metabolism. People with these variants can still process folic acid and benefit from supplementation. These variants are common in the population and routine testing for these variants is currently not recommended. The presence of these variants do not currently change clinical recommendations for folic acid supplementation.
These recommendations are based on decades of strong evidence from population-level studies with a primary focus on preventing neural tube defects in newborns.
Why Folate Might Matter in Cancer Research
Folate (vitamin B9) is vital for DNA repair. Because BRCA1 and 2 carriers already face challenges in DNA repair, researchers have asked whether folate status could play a role in modifying cancer risk.
Some studies suggest a U-shaped curve of benefit/risk:
Low folate levels may contribute to DNA instability, which could raise cancer risk.
Very high folate levels may, in certain contexts, support the growth of abnormal cells.
Moderate folate levels may be most protective.
It is important to note that this research is early, inconsistent, and not yet strong enough to change clinical recommendations.
What Research Has Found So Far for Women at High Risk
Study 1: Plasma Folate and Breast Cancer Risk in BRCA1 Carriers (Poland)
A 2011 Polish case–control study measured plasma folic acid levels in 155 BRCA1 carriers with breast cancer and 155 matched BRCA1 carriers without cancer.
Findings: Women with moderate plasma folate levels tended to have lower odds of breast cancer than those with very low or very high levels.
Genotype effects: Variants in the MTHFR gene appeared to modify these associations, but the sample size in the study was small, and there was a wide range of responses found in the results.
Takeaway: This study suggests a possible “sweet spot” for folate levels.
Study 2: Folic Acid Supplement Use in BRCA Carriers (Canada)
A Canadian study also looked at supplement use in BRCA1 and BRCA2 carriers.
Findings: Moderate use of folic acid–containing supplements was associated with a reduced risk of breast cancer, especially in BRCA1 carriers.
Takeaway: This points toward a potential benefit of supplementation, but the study design type cannot prove cause and effect.
Emerging Science on MTHFR Variants
MTHFR is an enzyme involved in folate metabolism. Variants can modestly reduce enzyme activity, which may influence how efficiently folate moves from the bloodstream into cells. Some research shows this affects red blood cell folate, which indicates how much folate is present and being effectively used by the body’s cells, even when blood (serum/plasma) folate looks normal, which only indicates the amount of folate consumed recently.
Researchers have also explored whether 5-MTHF, also known as methylated folate or the active form of folate, might help bypass this step. Small trials suggest 5-MTHF is as effective as folic acid in improving folate status and may reduce potentially harmful unmetabolized folic acid in the blood for some people. However:
There is currently no evidence that 5-MTHF lowers cancer risk in BRCA carriers.
There is currently no evidence that it prevents neural tube defects.
At this point, however, there have been no studies able to definitively show that 5-MTHF provides any additional health benefit over folic acid.
For these reasons, public health guidance continues to recommend folic acid as the standard form of supplementation.
Our Role at BRCAinBC
BRCAinBC is not a public health authority. Our mission is to support people at high genetic risk of cancer. This sometimes means discussing emerging science that is not yet conclusive. We share this information to help our community stay informed and to encourage meaningful conversations with healthcare providers.
Key Takeaways
Follow the guidelines: Folic acid remains the recommended supplement for general health and neural tube defect prevention in people who may become pregant, regardless of MTHFR status.
Research is ongoing: Two small studies in BRCA carriers suggest serum folate levels may influence cancer risk, but the evidence is preliminary and not practice-changing.
Stay curious, but cautious: If you are interested to learn more about your folate levels or in using different forms of folate, discuss it with your healthcare team.