In the mid- to late 1990s folate (also known as vitamin B9) supplementation of white flour was mandated in the US to prevent neural tube birth defects such as spina bifida. It worked admirably for this purpose but unfortunately there is a downside.
In what follows I will let the researchers do the talking:
[T]he pivotal role of folate in nucleotide synthesis, including its role as a cofactor in a rate-limiting step for DNA synthesis, also makes it a potential growth factor for neoplastic cells. The potential for folate to serve as a growth factor for neoplastic cells is further amplified by the tendency of most cancer cells to up-regulate the membrane receptors that mediate their uptake of folate, as well as some of the critical folate-dependent enzymes necessary for DNA synthesis. Moreover, this is not just a theoretical concern: two groups of clinical investigators inadvertently provided us with explicit proof of this in the 1940s when they gave large doses of folic acid to individuals with acute leukemia and observed what Sidney Farber politely termed ‘‘the acceleration phenomenon’’ whereby the rate of expansion of the leukemic clone increased tremendously (this, incidentally, prompted Farber and others to try antifolates for the treatment of childhood leukemia, and it was this latter step that is generally considered to be the beginning of the modern era of cancer chemotherapy).
Controlled studies in a variety of animal models of colon cancer have provided similar findings: in settings where there is a particularly strong underlying predisposition to colon cancer or in a setting where neoplastic tumors are already established, supplemental folic acid is protective only before neoplastic foci appear in the intestine. Once such foci are established, the more folic acid that is given, the faster microscopic foci and macroscopic tumors arise. Also consistent with this concern are contemporary human data. In a large multicenter trial 1,021 individuals with recently resected colorectal adenomas were randomized to receive either 1 mg of folic acid or a placebo over a period of 3 to 5 years. Analysis of the final follow- up colonoscopy did not reveal a protective effect of folic acid supplementation; rather, there was a small but significant increased risk in the multiplicity of recurrent adenomas with supplementation as well as a marginally significant increase in ‘high-risk’ adenomas.
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However, a remarkable departure from this decline [in colorectal cancer] is noted for each country in the mid-1990s: in the United States beginning in 1996 and continuing through 1998, and in Canada beginning in 1997 and extending through 2000. Neither parametric nor nonparametric curve fitting procedures could adequately capture the apparent sharp bends [upward] in the data associated with the implementation of folic acid fortification [Click on heading link to see chart in pdf document]. These abrupt changes in the prefortification trends are underscored by the fact that it is not possible to draw a straight line through the shaded area from end to end, indicating that the bends in the curves starting at 1996 (United States) and 1997 (Canada) are not the result of random variability about a straight line. In each instance, the sudden increase in CRC incidence represents a highly statistically significant deviation from the pre-1996/1997 trend, resulting in an excess of f 4 to 6 additional cases per 100,000 individuals.
Results During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B12. Vitamin B6 treatment was not associated with any significant effects.
Conclusion Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.
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.
What to do about this? Folate supplementation is common. The typical multivitamin supplement contains .8 mg of folic acid. For that reason I have dropped my multivitamin supplement. My B complex supplement contained .5 mg of 5-methyltetrahydrofolic acid (Methyl folate). Methyl folate is directly usable by the body as opposed to folic acid which has to be turned into methyl folate first. Circulating folic acid is not a good thing because it can take the place of methyl folate in folate receptors, but is inactive. So that is an improvement, but based on the foregoing research I have concluded that any folate supplementation is a bad idea. There is a B complex without folate, “B Minus” which I am now taking. I have also added an inexpensive trace mineral supplement which contains the trace minerals that were in the multivitamin, plus other vitamins separately.