Printer Friendly Email a Friend PDF RSS Feed

Dynamic Chiropractic – May 6, 2009, Vol. 27, Issue 10

B Vitamins Disappoint in Large Randomized Controlled Trials

By G. Douglas Andersen, DC, DACBSP, CCN

The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS) was a branch of the Women's Antioxidant Cardiovascular Study (WACS). More than 8,100 female health care professionals were enrolled in a randomized controlled trial (RCT) on antioxidants. Of these, 5,442 participants in the study agreed to a second leg, which ran concurrently.1

All subjects were ages 42 and older, and had either pre-existing cardiovascular disease (CVD) or multiple risk factors. These women took one of three regimens: 2,500 mcg of folic acid, 50 mg of vitamin B6 and 1,000 mcg of vitamin B12, or a placebo daily. The trial lasted 7.3 years; results are shown in Table 1. A secondary analysis on the participants in the WAFACS trial was done to determine how the B complex influenced cancer.2 These results are shown in Table 2.

Table 1: B Vitamins and Cardiovascular Disease in Adult Women at Risk
B Vitamin Group Placebo Group
Number of subjects 2,721 2,721
Cardiovascular disease 406 390
Cardiovascular mortality 96 94

In the WAFACS study, homocysteine was only tested in a sample of 300 women (150 from each treatment group). Members of the intervention group did have lower homocysteine levels in their blood, but this did not impact either cardiovascular or cancer incidence. The lingering questions were: How representative was the sample, and would an effect have been seen if all subjects had been tested?

Table 2: B Vitamins and Cancer in Adult Women at Risk for CVD
B Vitamin Group Placebo Group
Number of subjects 2,721 2,721
Breast cancer 70 84
Other cancers 117 108
Cancer mortality 47 57

I located a third RCT that did test all 3,096 participants for homocysteine while they took various combinations of 40 mg of B6, 400 mcg B12, 800 mcg folic acid or placebo for four years following coronary angiography.3 In groups that took either folic acid and vitamin B12, or folic acid, B12 and B6, homocysteine was reduced 30 percent after one year and remained at that level for the next three years. Unfortunately, a corresponding mortality reduction was not observed. The results are shown in Table 3.

Table 3: B Vitamins and Mortality Post-Angiography
Intervention Subjects Mortality
Folic acid, B12, B6 771 35
Folic Acid, B12 769 38
B6 771 28
Placebo 779 30

The results of these large RCTs were surprising and disappointing. Clearly the homocysteine question has yet to be fully resolved.


  1. Albert CM, Cook NR, Gaziano JM, et al. The effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA, 2008;299(17):2027-36.
  2. Zhang SM, Cook NR, Albert CM, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA, 2008;300(17):2012-21.
  3. Ebbing M, Bleie O, Ueland PM, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA, 2008;300(7):795-804.

Dr. Andersen's previous column (April 9 issue) discussed disappointing results from RCTs involving selenium and vitamins C and E. Read the full article online at

Click here for previous articles by G. Douglas Andersen, DC, DACBSP, CCN.

To report inappropriate ads, click here.