Produced by the Royal College of Physicians of Edinburgh and Royal College of Physicians and Surgeons of Glasgow

Folic acid and breast cancer

  • Dr IH Kunkler, Consultant and part-time Senior Lecturer in Clinical Oncology, Western General Hospital, University of Edinburgh, Edinburgh, Scotland


In this BTMH user-requested article Dr Ian Kunkler aims to answer concerns about the safety of folic acid following the publication of a study which suggested an increased risk of breast cancer for women taking oral folic acid Supplements. How safe is folic acid, what link is there with breast cancer and should women continue to take folic acid?

Key Points

  • It is well established that folic acid supplementation reduces the risk of neural tube defects.
  • Most of the evidence suggests that folic acid contributes to preventing breast cancer rather than causing it.
  • The apparent association between taking high doses of folic acid and increased risk of dying from breast cancer may be a chance finding. Further studies are needed.
  • Women contemplating pregnancy should take folic acid supplements to reduce the risk of neural tube defects in the developing child.
  • More studies are needed.

Declaration of interests: No conflict of interests declared

Folic acid and health

Folic acid is a B vitamin which plays an important role in cell synthesis and repair. Leafy vegetables, fruits and animal protein are all rich sources of folic acid, but folic acid is easily destroyed by prolonged cooking. Total body stores of folate are quite small and deficiency can occur within weeks leading mainly to megaloblastic anaemia. Folate stores in the body are best reflected in the folate concentrations in red blood cells. Folate can also be measured in the plasma, but plasma concentrations can change rapidly and do not accurately reflect body stores. Natural folates in foods lose their activity relatively rapidly over a period of days or weeks because of their chemical instability. In contrast, synthetic folic acid is virtually completely stable for months or years. This means that synthetic folate provides a much more reliable source of dietary intake than naturally occurring folates.

Folic acid plays an important role in preventing birth defects

There is good evidence that dietary supplementation with folate before conception and during the first trimester reduces the risk of NTDs. It is between the seventeenth and thirtieth day after conception or four to six weeks after the first day of the last menstrual period that the neural tube forms in the embryo and then closes. Neural tube defects occur when the neural tube fails to close properly leaving the brain and spinal cord exposed to amniotic fluid. Anencephaly and spina bifida are the commonest NTDs. Current advice is that women should receive 400 mcg (0·4 mg) of folic acid per day before they become pregnant.

Folic acid preventing or causing breast cancer?

Most of the published evidence shows that plasma folate concentrations are inversely associated with the risk of developing breast cancer. Folate deficiency may lead to DNA damage. An example is the misincorporation of uracil into DNA and the development of single and double-strand chromosomal breaks in DNA.1 These defects may result in a reduced DNA repair capacity. Three large prospective epidemiological studies, the Nurses’ Health Study,2 the Iowa Women’s Health Study,3 and the Canadian National Breast Screening Study4 have demonstrated that low dietary folate carries an increased risk of breast cancer. In the Nurses’ Health Study,2 of 121,700 female re