March 14, 2009
Folic Acid Prostate Cancer Risk?

Whether you get your folic acid in foods or supplement pills might determine whether you get a net benefit or net harm from it.

A study led by researchers at the University of Southern California (USC) found that men who took a daily folic acid supplement of 1 mg daily had more than twice the risk of prostate cancer compared with men who took a placebo.

The finding came from a secondary analysis of the Aspirin/Folate Polyp Prevention Study (AFPP), a placebo-controlled randomized trial to determine the impact of aspirin and folic acid on colon polyps in men and women who were at high risk for the disease. The results appear in the March 10 online issue of the Journal of the National Cancer Institute.

Folic acid (folate) is a B vitamin found in many vegetables, beans, fruits and whole grains. While evidence of its ability to reduce neural tube defects in infants while taken by the mother before or during pregnancy has been well documented, its effects on other conditions are unclear.

Folate delivers many benefits. But that doesn't mean all its effects are beneficial.

We know that adequate folate levels are important in the prevention of several cancer types, cardiovascular and neurological diseases,” says lead author Jane Figueiredo, Ph.D., assistant professor of preventive medicine at the Keck School of Medicine of USC. “However, little has been known about its role in prostate cancer. Our objective was to investigate the relationship between folic acid supplements and dietary folate and risk of prostate cancer.”

Supplementary folic acid appears to boost risk of advanced polyps in the colon. Not good. So far studies have found conflicting results of folic acid supplements on prostate cancer risk.

The AFPP study was conducted between 1994 and 2006 and found that aspirin reduced the risk of colon polyps while folic acid had a negative effect and increased the risk of advanced and multiple polyps. The first analysis did not address the impact of folic acid supplements on prostate cancer risk. Previous observational studies have been inconsistent. Some studies suggest that increased folate in the diet or in supplements might actually lower the risk of prostate cancer, and others have suggested no effect or even a potential harmful effect.

So we do not know the answer from one study. But there's a prudent response: eat foods (beans, green leafy vegetables) that are higher in folate rather than pills. Those foods are beneficial for other reasons.

The difference between placebo and folic acid supplements was large. But even the 3.3% rate of prostate cancer in the placebo group is too high. We need cures for cancer.

In the secondary analysis, researchers looked at prostate cancer incidence among 643 men who were randomly assigned to 1 mg daily folic acid supplements or placebo in the AFPP study and who enrolled in an extended follow-up study. The estimated prostate cancer risk was 9.7 percent at 10 years in men assigned to folate, compared with 3.3 percent in men assigned to placebo.

They found a benefit from folate in foods.

By contrast, dietary folate intake and plasma folate showed a trend toward reduced risk of prostate cancer, although the difference did not reach statistical significance. It remains unclear why dietary and circulating folate among non-multivitamin users may be inversely associated with risk, Figueiredo says.

The synthetic form is more bioavailable. But this isn't just a matter of total dose. The pill form is going to absorb into the bloodstream more rapidly, especially if taken on an empty stomach. The problem might come from a spike in blood folate levels where the extra folate drives, for example, methylation of DNA and causes gene regulatory changes.

“The synthetic form of folate, folic acid, found in supplements, is more bioavailable compared to folate from dietary sources and we know the amount of folate available is critical,” she says. “Adequate levels of folate may be beneficial, but too much folate is unlikely to be beneficial.”

A larger study is needed to confirm or dismiss these results. What I'd like to see in a larger study: 3 groups. The first group would get placebo, the second group folic acid, the third group folic acid in a time release form. The time release form would tell us if the problem is due to a spike in levels. Maybe a fourth group is needed to get a different form of folate.

Alternatively, these results may be due to chance, and replication by other studies is needed, she notes.

Eat better food. That's your best bet.

Share |      Randall Parker, 2009 March 14 09:43 AM  Aging Diet Cancer Studies

Bob Badour said at March 14, 2009 10:02 AM:
Eat better food. That's your best bet.

Eat better food, and get more and better sleep.

Michael G.R. said at March 14, 2009 11:29 AM:

I'm male and I've been taking a folic acid supplement daily for a few months. Now considering stopping it. Hmm..

David Govett said at March 15, 2009 10:24 AM:

The coming Singularity will allow us humans to understand ourselves as a unique, wondrous, and fantastically complex hierarchy of biological systems. That understanding will allow us to tailor our dietary and other behavior to optimize our heath. Unfortunately, the spendthrifts in the White House and Congress will tax away from potential investors much of the money necessary to drive biotechnological and nanotechnological innovation. Worry not, however, because even if U.S. innovation lags, we will be able to buy from the hard-charging Chinese the products necessary to extend healthy life, assuming, of course, we Americans will be able to afford them.

Kudzu Bob said at March 15, 2009 5:38 PM:

Mark Twain once advised us to be careful of what we read in health books, since we might die of a misprint. Even that old cynic, however, might be angered by the bad science and outright disinformation that we are spoon-fed today.

Consider the recent scientific report touted by the media that allegedly showed no disease-fighting benefits from taking a daily multivitamin. What didn't get mentioned in the many stories about this so-called finding was that multivitamins having nutrient levels above the RDA were specifically excluded from use in the study.

This matters a great deal. Most claims involving nutrient-based prevention of such health problems as heart disease and cancer typically involve higher vitamin levels than the knife-and-fork amounts of the RDA. The only problems that a Centrum-type multi will prevent are disease of overt malnutrition, such as beriberi and scurvy, conditions that First Worlders seldom get unless they are unlucky enough to find themselves in Asian POW camps.

A noted Yale tocopherol researcher once explained to me that similar sleight-of-hand took place several years back with a well-publicized meta-analysis that purported to show that users of vitamin E had higher mortality rates than non-users. In that particular instance the researchers discarded all previous work in which few or none of the subjects died, which the scientist I spoke with believed seriously skewed their results. He was far too cautious a man to say that he believed this to be deliberate on their part, but I found his tone of voice quite eloquent.

This latest folic acid study brings to mind tales of wary and skeptical Soviet-era Pravda readers, who, when they came across the latest front-page claim of record wheat harvests, knew to stock up on food. Myself, I will continue to take a wide variety of high-potency supplements each day, as well as to eat plenty of veggies, to fasten my seat belt, and to regard media health stories with considerable skepticism, since I am—so far, at any rate—quite pleased with the results. Ask this self-selected guinea pig in another fifty years whether he wasted his money.

As for Mr. Govett’s talk of the coming Singularity, well, I don’t know if his eschatological hopes are warranted, but I find it telling that even in his optimistic scenario we will still need money. That doesn't sound very Singular to me.

M-K said at March 16, 2009 9:16 AM:

All the B vitamins work synergetically with each other and with various minerals (magnesium being especially important). Excesses of one B vitamin can cause shortages of others, and probably of associated minerals. Taking a large amount of Folic Acid (and 1 mg is large for this vitamin) over a protracted period of time, without complimentary amounts of other B vitamins and associated nutrients (and nobody knows exactly what proportions any given individual requires) can be expected to cause problems.

Shannon Love said at March 16, 2009 1:38 PM:

It does raise ethical questions about the government mandated fortification of foods such a flour. Does the state have the right to increase the health of some at the risk to others?

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