Reactions 1280 - 28 Nov 2009

Folic acid could kill you –or this study could be flawed

A retrospective analysis published in JAMA suggeststhat folic acid, in combination with cyanocobalamin[vitamin B12], is associated with an increased incidenceof cancer and increased all-cause mortality in patientswith ischaemic heart disease.1

Data were combined from two randomised controlledtrials (RCTs) conducted in Norway: NORVIT* andWENBIT** .

Overall, cancer was diagnosed in 10.0% of patientstreated with folic acid + cyanocobalamin comparedwith 8.4% of controls (hazard ratio 1.21 [95% CI; 1.03,1.41]; p < 0.05). The rate of cancer-related mortalitywas 4.0% versus 2.9% (1.38 [1.07, 1.79]; p = 0.01), andthe rate of all-cause mortality was 16.1% versus 13.8%(1.18 [1.04, 1.33]; p = 0.01).

Hazard ratios were significantly higher in patientswith higher serum folate levels, but there was norelationship between hazard ratios and serumcobalamin levels. The researchers suggest that theseresults "underline the call for safety monitoring followingwidespread consumption of folic acid from dietarysupplements and fortified foods".

However, in an accompanying editorial, Drs BettinaDrake and Graham Colditz point out that the dosages offolic acid consumed in fortified foods are generally lowerthan the 0.8 mg/day used in these two studies.2 Theeditors also identify observational evidence suggestingan inverse relationship between folic acid intake andcancer incidence in the US. They suggest that RCTs areperhaps too short to identify the benefits of long-termexposure to folic acid.

Daniel Fabricant, vice president of scientific andregulatory affairs for the Natural Products Association(NPA), further criticises the Norwegian analysis, sayingthat NORVIT was inadequately powered to isolate theeffects of folate, and the WENBIT trial was terminatedearly.3 He suggests that, "[in this analysis] two flawedstudies are combined to yield one larger flawed study".Fabricant also notes that the use of concomitantmedications, such as β-blockers, statins and ACEinhibitors, is not adjusted for. He states that "this doesnot seem to be in the best interest of medical science orpublic health."* Norwegian Vitamin Trial** Western Norway B Vitamin Intervention Trial

1. Ebbing M, et al. Cancer incidence and mortality after treatment with folic acidand vitamin B12. JAMA: the Journal of the American Medical Association 302:2119-2126, No. 19, 18 Nov 2009.

2. Drake BF, et al. Assessing cancer prevention studies - a matter of time. JAMA:the Journal of the American Medical Association 302: 2152-2153, No. 19, 18Nov 2009.

3. Natural Products Association. Spokesperson Alert: Natural Products AssociationSpokesperson Challenges Findings of JAMA Study on Health Risks Associatedwith Folic Acid and B12 Treatment. Media Release : 17 Nov 2009. Availablefrom: URL: http://www.naturalproductsassoc.org.

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Reactions 28 Nov 2009 No. 12800114-9954/10/1280-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved