B VITAMINS DISSAPPOINT IN LARGE RANDOMIZED CONTROLLED TRIALS

The Women’s Antioxidant and Folic Acid Cardiovascular Study 1 (WAFACS) was a branch of the Women’s Antioxidant Cardiovascular Study (WACS).  Over 8,100 female healthcare professionals were enrolled in a randomized controlled trial (RCT) on antioxidants.  5,442 participants in the study agreed to a second leg which ran concurrently. They were no younger than 42 and had either pre-existing cardiovascular disease or multiple risk factors for it. These women took either 2500 mcg of folic acid, 50 mg of vitamin B6 and 1000 mcg of vitamin B12 or placebo daily.  The length of the trial was 7.3 years.  The results were as follows:  See Table 1.

 

Table 1

 B Vitamins and Cardiovascular Disease in Adult Women at Risk

 

B Vitamins

Placebo

 Number of Subjects

2721

2721

 Cardiovascular Disease

406

390

 Cardiovascular Mortality

96

94

                                     

 

A secondary analysis on the participants in the WAFACS trial was done to determine how the B complex influenced cancer.2

The results were as follows:  See Table 2.

 

 

Table 2

B Vitamins and Cancer in Adult Women at Risk for Cardiovascular Disease

 

B Vitamins

Placebo

 Number of Subjects

2721

2721

 Breast Cancer

70

84

 Other Cancers

117

108

 Cancer Mortality

47

57

 

 

                                                     

 

 

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

 

I located a third recent RCT that did test all 3096 participants for homocysteine while they took various combinations of 40 mg of B6, 400 mcg B12, 800 mcg folic acid or placebo following coronary angiography for 4 years.3  In groups who took either folic acid and vitamin B12 or folic acid, B12 and B6, homocysteine was reduced 30% after one year and remained at that level for the next 3 years..  Unfortunately, a corresponding mortality reduction was not observed.

See Table 3

 

 

Table 3

B Vitamins and Mortality Post Angiography 3

 Intervention

Subjects

Mortality

 Folic acid, B12, B 6

771

35

Folic Acid, B12 

769

38

 B6

771

28

Placebo

779

30

                                                          

COMMENT

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

 

 

 

REFERENCES

 

  1. Albert, C.M., Cook, N.R., Gaziano, J. M., 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): 2027-2036

 

 

  1. Zhang, S. M., Cook, N.R., Albert, C.M., et al.  Effect of Combined Folic Acid, Vitamin B6, and Vitamin B12 on Cancer Risk in Women:  A Randomized Trial.  JAMA 2008; 300(17):  2012-2021

 

 

Ebbing, M., Bleie, O., Ueland, P.M., 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.