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Taking folate in pregnancy and risk of maternal breast cancer

BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.329.7479.1375 (Published 09 December 2004) Cite this as: BMJ 2004;329:1375

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Folic Acid

Re BMJ Article showing an increase in breast cancer among women who had taken folic acid during pregnancy

A minority of those of us who have worked in the field (I am now retired from active participation but researched pteridine biochemistry for almost forty years) have been concerned about food supplementation with folic acid as an alternative to elective medication. When I was drawing attention to possible dangers ten years ago it was not a popular standpoint. My principal argument at that time was that it could precipitate neurological disease in those, particularly the elderly, with vitamin B12 deficiency but above that I believe we should be conservative about medication through the food change. The article in The British Medical Journal puts a different slant on the issue.

The report that high doses of folic acid are associated with neoplasia should not come as a complete surprise. Folic acid, pteroyl-L-monoglutamic acid, is a product of the pharmaceutical industry which rarely occurs in nature. Folic acid is a substrate for dihydrofolate reductase, first being reduced to dihydrofolate and then tetrahydrofolate. If large enough doses of folic acid are given then some will enter cells unchanged be polyglutamated and retained as are all folates and some antifolates eg methotrexate.

To my knowledge there are a very few situations where folic acid administration can be immediately harmful and they are exceedingly rare, one is dihydropteridine reductase deficiency, a failure in the salvage of quinonoid dihydrobiopterin to tetrahydrobiopterin. The effects of folate administration in that particular disorder serve to underline the complexities of folate interactions with other pteridines and the minor pathways or back-up mechanisms in one carbon transfers. Iatrogenic disturbance of folate metabolism will at least alter purine and pyrimidine synthesis with all that that entails. In view of the role of folates in cellular replication throughout the body, if there was to be an increase in the number of malignancies then one would expect that to manifest itself in the commonest, which in women is breast cancer.

There are benefits as well as side effects to all medication. These have to be weighed carefully against each other but the individuals who suffer have more right to complain when food is medicated unasked than when they swallow tablets they have accepted.

The increase in breast cancer among those taking high doses of folic acid during pregnancy coincides with reports of increasing malignancies among children. This might not be a coincidence, The downside of vitamin medication is an important fundamental issue of which I am sure everyone is aware.

Competing interests: None declared

Competing interests: No competing interests

15 December 2004
Robert LEEMING
Hon Senior Clinical Fellow
Clin Chem Childrens Hospital Birmingham B4 6NH