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Vitamin B9 (folic acid) and vitamin B12 supplements linked with higher risks of cancer

November 19, 2009

Patients with heart disease have an associated increased risk of cancer and death from any cause if treated with vitamin B9 (folic acid) and vitamin B12, a new study criticized by experts suggest.

The study combined data from two randomized, placebo-controlled clinical trials, which included 6,837 patients with ischemic heart disease who were treated with B vitamins or placebo between 1998 and 2005 (1). Patients were randomized to receive oral treatment with folic acid (0.8 mg/d), plus vitamin B12 (0.4 mg/d), plus vitamin B6 (40 mg/d); folic acid (0.8 mg/d) plus vitamin B12 (0.4 mg/d); vitamin B6 alone (40 mg/d); or placebo. After a median 39 months of treatment and an additional 38 months of post-trial observational follow-up, 8.4 percent of the participants who did not receive folic acid plus vitamin B12 vs. 10.0 percent of participants who received such treatment were diagnosed with cancer (mainly lung cancer), a 21 percent increased risk. A total of 2.9 percent of patients who did not receive folic acid plus vitamin B12 vs. 4.0 percent who received such treatment died from cancer, a 38 percent increased risk. A total of 16.1 percent of patients who received folic acid plus vitamin B12 vs. 13.8 percent who did not receive such treatment died from any cause.

No adverse effects have been associated with the consumption of folate from foods to date. The authors speculate that folate deficiency from food may promote initial stages of cancer development, whereas high doses of folic acid in supplements may enhance the growth of cancer cells. However, they give no explanation for the observation that a good intake of folate reduces the risk of developing (lung) cancer, notwithstanding the phenomenon that the cancer risk increases when folic acid is given.

Experts commented that it is indisputable that folic acid and folate have a recognized preventive effect with regard to the reduction of neural tube defects in newborns and that good folate levels can reduce not only the risk of developing cancer but also the risk of strokes and neurodegenerative diseases. Since 1998, many countries, including the United States, have implemented mandatory folic acid fortification of flour and grain products to reduce the risk of neural-tube birth defects. Current evidence shows that higher average folic acid intake in adults is related to lower cancer incidence and a 50% reduction in mortality risk from colorectal cancer, experts say.

In addition, the intervention (800 micrograms folic acid/day) used in the study is 4-6 times higher than the average dose delivered through mandatory fortification of flour, researchers criticized. Moreover, the authors found a non-statistically significant association between folate treatment and cancer incidence and mortality at those high folate acid supplementation levels.

In an accompanying editorial in the same journal, experts wrote, “Preventive interventions require long-term evaluation. While the report by Ebbing et al. provides important short-term data, the findings do not nullify the potential long-term benefits that folic acid fortification may have on population health. The time frame for the benefits of some preventive interventions may span decades, although smoking cessation may be unique among lifestyle changes that produce a rapid reduction in cancer risk” (2).

References

  1. Ebbing M et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009; 302(19): 2119–2126.
  2. Drake BF and Colditz GA. Assessing cancer prevention studies – A matter of time. JAMA. 2009; 302(19): 2152–2153.