Folic Acid, B12 May Increase Cancer Risk

Study Shows Slight Increase in Cancer Risk From Large Doses of Supplements

By Salynn Boyles
WebMD Health News

Reviewed By Louise Chang, MD

Nov. 17, 2009 -- There is new evidence that folic acid, taken in large doses, may promote some cancers.

Heart patients in Norway who took folic acid and vitamin B12 supplements were found to have a slightly increased risk for cancer and death from all causes, compared to heart patients who did not take the supplements in a study published in The Journal of the American Medical Association.

Unlike the U.S., Norway does not fortify flour and grain food products with folic acid, which is the synthetic form of the B vitamin folate.

Because of this, Norwegians tend to have much lower blood folate levels than Americans, making the population a good one for studying the impact of folic acid supplementation on cancer risk, study researcher Marta Ebbing, MD, of Norway's Haukeland University Hospital tells WebMD.

Folic Acid, B12, and Lung Cancer

Ebbing and colleagues analyzed data from two studies that included almost 7,000 heart patients treated with B vitamin supplements or placebo for an average of three and one-half years between 1998 and 2005.

The original intent of the studies was to determine if taking vitamin B supplements improved cardiovascular outcomes, which it didn't do.

During treatment, blood folate levels among patients who took 0.8 milligrams a day of folic acid plus 0.4 milligrams a day of vitamin B12 increased more than sixfold.

The patients were followed for an average of three years after supplementation ended, during which time 341 patients who took folic acid and B12 (10%) and 288 patients who did not (8.4%) were diagnosed with cancer.

Folic acid and B12 supplementation was associated with a 21% increased risk for cancer, a 38% increased risk for dying from the disease, and an 18% increase in deaths from all causes.

This finding was mainly driven by an increase in lung cancer incidence among the folic acid and B12-treated patients.

Seventy-five (32%) of the 236 cancer-related deaths among the study participants were due to lung cancer, and the cancer incidence among the study group was 25% higher than in the population of Norway as a whole.

Roughly 70% of all the patients in the study were either current or former smokers, including more than 90% of those who developed lung cancer.

Other Views

In a statement issued in response to the study, a spokesman for the supplement-industry trade association Council for Responsible Nutrition (CRN) noted that the lung cancer finding has not been seen in other studies.

"The real headline of this study should be that smoking increases the risk of lung cancer -- the study found that a total of 94% of the subjects who developed lung cancer were either current or former smokers," CRN Vice President for Scientific and Regulatory Affairs Andrew Shao, PhD, says in a news release.

In the U.S., mandatory folic acid fortification of flour and grains has been in effect for just over a decade, and fortification has succeeded in dramatically lowering the incidence of neural tube birth defects.

Shao says the fact that lung cancer rates have also dropped during this time in both men and women suggest folic acid and B12 do not promote lung cancer.

Bettina F. Drake, PhD, of Washington University in St. Louis School of Medicine, says it is not likely that fortification has led to an increase in cancers in the U.S. In fact, several studies suggest just the opposite.

"We would expect to see an excess in cancers within a few years after folic acid fortification began, and we have not seen that," she tells WebMD.

Drake says it is possible that folic acid protects against cancer at certain points in life and promotes the growth of cancers at other times. It may also be true that too little folate in the blood or too much of the B vitamin are both associated with an increased risk for cancer.

In an editorial published with the study, Drake and Graham A. Colditz, MD, write that it may take decades to fully understand how folic acid fortification affects health.


Skin Cancer Symptoms, Types, Images See Slideshow

Ebbing, M. The Journal of the American Medical Association, Nov. 18, 2009; vol 302: pp 2119-2126.

Marta Ebbing, MD, department of heart disease, Haukeland University Hospital, Bergen, Norway.

Bettina F. Drake, PhD, MPH, assistant professor, Washington University, St. Louis School of Medicine, St. Louis.

News release, The Journal of the American Medical Association.

News release, Council for Responsible Nutrition.

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