This week’s research review focuses on a recent study that showed folic acid supplementation (made by Wyeth Home Pharmaceuticals) increased the risk of prostate cancer. The study was published in the Journal of the National Cancer Institute.
Of particular interest are quotes from the article. (Figueiredo 2009)
Baseline dietary folate intake and plasma folate in non-multivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses.
Those randomly assigned to folic acid supplementation had statistically signiﬁcantly lower baseline plasma vitamin B12 (placebo = 348.1 pmol/L; folic acid = 317.0 pmol/L, difference = 31.1 pmol/L, 95% CI = 1.8 to 60.4 pmol/L, P = .04).
Folate supplementation in the trial was in the form of folic acid, a fully oxidized, monoglutamyl form of folate that may differ in its effects from the natural reduced and methylated forms (mostly 5-methyl tetrahydrofolate). Folic acid is more bioavailable than natural sources; natural folates exist as polyglutamates that are hydrolyzed to monoglutamates in the small intestine and then polyglutamated in peripheral cells
These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid-containing supplements vs natural sources of folate.
A review article published in the same issue brings up other relevant issues. (Kristal 2009)
Figueiredo et al. have conducted a secondary analysis from a trial that reported previously that folate (1 mg/d) increased the risk of recurrence of an advanced colorectal adenoma by 67%. They have found that folate increased the risk of prostate cancer by 163%.
In the trial reported by Figueiredo et al., for example, high serum folate at baseline was associated with reduced prostate cancer risk; this association likely was with foods high in folate or with a dietary pattern containing high-folate foods and not with folate itself since folate supplementation increased the risks of prostate cancer.
Again, using the folate supplementation trial as an example, it is not unreasonable to assume that optimal levels of folate are associated with more ﬁdelity in DNA replication and thus a lower risk of spontaneous mutations, but high folate may also support more rapid cell growth and promote carcinogenesis in previously initiated cells.
It is safe to conclude that cancer prevention is not going to be as simple as recommending high-dose micronutrient supplements for middle-aged and older adults.
Folic acid and risk of prostate cancer: results from a randomized clinical trial
(Figueiredo, Grau et al. 2009) Download
Data regarding the association between folate status and risk of prostate cancer are sparse and conflicting. We studied prostate cancer occurrence in the Aspirin/Folate Polyp Prevention Study, a placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between July 6, 1994, and December 31, 2006. Participants were followed for up to 10.8 (median = 7.0, interquartile range = 6.0-7.8) years and asked periodically to report all illnesses and hospitalizations. Aspirin alone had no statistically significant effect on prostate cancer incidence, but there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval [CI] = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). In contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid-containing supplements vs natural sources of folate.
Nutritional prevention of cancer: new directions for an increasingly complex challenge
(Kristal and Lippman 2009) Download
Figueiredo, J. C., M. V. Grau, et al. (2009). "Folic acid and risk of prostate cancer: results from a randomized clinical trial." J Natl Cancer Inst 101(6): 432-5.
Kristal, A. R. and S. M. Lippman (2009). "Nutritional prevention of cancer: new directions for an increasingly complex challenge." J Natl Cancer Inst 101(6): 363-5.