Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2008 Nov 5;300(17):2012-21.
doi: 10.1001/jama.2008.555.

Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial

Shumin M Zhang  1 , Nancy R Cook, Christine M Albert, J Michael Gaziano, Julie E Buring, Joann E Manson
Affiliations
Randomized Controlled Trial

Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial

Shumin M Zhang et al. JAMA. .

Abstract

Context: Folate, vitamin B(6), and vitamin B(12) are thought to play an important role in cancer prevention.

Objective: To evaluate the effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on cancer risk in women at high risk for cardiovascular disease.

Design, setting, and participants: In the Women's Antioxidant and Folic Acid Cardiovascular Study, 5442 US female health professionals aged 42 years or older, with preexisting cardiovascular disease or 3 or more coronary risk factors, were randomly assigned to receive either a daily combination of folic acid, vitamin B(6), and vitamin B(12) or a matching placebo. They were treated for 7.3 years from April 1998 through July 31, 2005.

Intervention: Daily supplementation of a combination of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) (n = 2721) or placebo (n = 2721).

Main outcome measures: Confirmed newly diagnosed total invasive cancer or breast cancer.

Results: A total of 379 women developed invasive cancer (187 in the active treatment group and 192 in the placebo group). Compared with placebo, women receiving the active treatment had similar risk of developing total invasive cancer (101.1/10,000 person-years for the active treatment group vs 104.3/10,000 person-years for placebo group; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.79-1.18; P = .75), breast cancer (37.8/10,000 person-years vs 45.6/10,000 person-years, respectively; HR, 0.83; 95% CI, 0.60-1.14; P = .24), or any cancer death (24.6/10,000 person-years vs 30.1/10,000 person-years, respectively; HR, 0.82; 95% CI, 0.56-1.21; P = .32).

Conclusion: Combined folic acid, vitamin B(6), and vitamin B(12) treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era.

Trial registration: clinicaltrials.gov Identifier: NCT00000541.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Flow Diagram of the Folic Acid, Vitamin B6, and Vitamin B12 Component of WAFACS Trial
Abbreviations: WACS: Women’s Antioxidant Cardiovascular Study; WAFACS: Women’s Antioxidant and Folic Acid Cardiovascular Study. a Mortality and morbidity information was complete for 98.9% and 98.0% of person-years of follow-up, respectively.
Figure 2
Figure 2
Cumulative Incidence Estimates of total invasive cancer (panel A) and breast cancer (panel B) (adjusted for age and randomized vitamin E, vitamin C, and beta-carotene assignments)
Figure 2
Figure 2
Cumulative Incidence Estimates of total invasive cancer (panel A) and breast cancer (panel B) (adjusted for age and randomized vitamin E, vitamin C, and beta-carotene assignments)
See this image and copyright information in PMC

Comment in

References

    1. Mason JB, Levesque T. Folate: effects on carcinogenesis and the potential for cancer chemoprevention. Oncology (Williston Park) 1996;10(11):1727–1736. 1742–1743. discussion 1743–1744. - PubMed
    1. Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res. 2001;475(1–2):7–20. - PubMed
    1. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340(19):1449–1454. - PubMed
    1. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999–2000. Am J Epidemiol. 2004;160(4):339–349. - PubMed
    1. Giovannucci E. Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr. 2002;132(8 Suppl):2350S–2355S. - PubMed

Publication types

Associated data