Why Cancer Is The Question
Folic acid forms the building blocks of DNA and drives cell division. Early embryos have cells dividing at enormous speed and they need a ready supply. Anything that helps cell division presents a hypothetical risk for people with cancer and also for the initiation of cancer in healthy people. Consequently, studies have been carried out to try and measure where that hypothetical concern is present in reality.
Measuring the Harm
The strongest test for harm is a randomised controlled trial, in which people are assigned by the toss of a coin to receive either the treatment or a placebo and are then followed up to see what happens. In 2013, researchers pooled every large folic acid trial, involving around fifty thousand people, into one analysis in The Lancet. They reported no significant effect on cancer. That result became the basis of the official safety verdict.
A year earlier, a separate, more careful review split the same trials by dose given. It found an increase in cancer in the trials using lower doses, close to the amount fortification delivers, but none in the trials using much higher doses.
That headline, a six per cent increase reported as no significant effect, is an average across every dose the trials used. Split the trials into three dose groups, on both the published figures and the patient-level data behind the 2013 analysis, and the average comes apart.
The increase is seen at the exact range that fortifying flour will deliver. That is the reverse of how a drug normally behaves, since a larger dose would usually carry more risk, not less. The result below 1 milligram is the same even if the single polyp-prevention trial that critics single out is excluded and it is seen in ordinary adults rather than just in high-risk groups.
Prostate cancer in particular is a concern. In one trial, men given 1 milligram of folic acid a day were diagnosed with prostate cancer at 2.6 times the rate of those on a placebo, a ten-year risk of 9.7 per cent against 3.3 per cent. The trial had been designed to study bowel polyps rather than the prostate. Sixteen years later, there have still been no further trials to measure this properly. Instead, researchers re-examined the data from the other folic acid trials already run. Pooled together, six trials covering around 25,000 men showed a 24 per cent increase in prostate cancer among the men given folic acid (relative risk 1.24, 95 per cent confidence interval 1.03 to 1.49). A reanalysis at a case level claimed there was no signal but they specifically excluded dosages within the fortification range. Folate obtained from food carried no such risk, which points to the synthetic form rather than the vitamin as it occurs in the diet.
Hellbound and Down 