Recently we were advised to take lots of folic acid to help prevent Alzheimer's. (Of course, that study, when scrutinized, showed itself to be highly flawed.) Now, we are supposed to avoid folic acid like the plague because it will cause cancer:

High doses of folic acid do not prevent precancerous colon polyps in people prone to them and may actually increase the risk of developing the growths, a new study finds.

This study (Cole et al., 2007. Folic acid for the prevention of colorectal adenomas: A randomized clinical trial. JAMA. 297:2351-2359) actually finds a lot of non-statistical differences between groups of about 500, one taking folic acid supplements for several years, and one not. The only probable real difference in the groups (considering the large number of comparisons they made) was in those people with 3 or more adenomas (pre-cancerous growths) found 6-8 years after the study began.

One issue muddying the water in the study, which was not the fault of the authors, was the addition of folic acid supplements to quite a lot of the American food supply by the FDA, starting in 1998, two years after the study began. This presumably helped to obscure potential differences between the treatment and control groups because all were essentially taking folic acid supplements, with the treatment groups taking more. Additionally, the supplemented amounts were more than double (1 milligram) the "recommended daily value" of 400 micrograms - and that is ignoring the folate they were getting from whatever plants they were eating, and piles of folic acid they started getting in their diet after the FDA's intervention. Six years is a long time to be pounding your body with a huge excess of any one nutrient.

The mainstream media love a more sensational representation of the latest medical news, however:

Cancer patients should discuss taking vitamins with their doctors, and anyone over 50 who takes vitamins should have a colorectal screening test, said Cornelia Ulrich of Seattle's Fred Hutchinson Cancer Research Center, who co-wrote an accompanying editorial.

Apparently, suddenly all our doctors are going to have all this knowledge about what supplements their patients should take, because of this one paper telling us that infusing our systems with one particular compound for six years is probably a bad idea. (And cancer doctors aren't exactly who I would pinpoint to be nutrition fairies - most of the cancer patients I have known would have been better off without being poisoned slowly by doctors using the euphamism "chemotherapy.") Shouldn't everyone (who can afford it) over 50 get a colorectal screening test? Colorectal cancer is one of the easiest cancers to prevent by snipping off the adenomas within the colon. Who cares about vitamins?

Our obsession with supplements has gotten entirely out of control. Instead of taking policy steps that would help people consume good foods to obtain the nutrients our bodies need at levels to which they are adapted, our government and media imply there is always an easy fix by taking some supplement or other in absurd dosages. Certainly they give lip service to eating a balanced diet, but government policies actually subsidize, and thus promote, the production of cheap processed foods that are little but empty calories. On the NIH page linked to above explaining the folic acid food supplementation, it is actually stated, after a list of the easily obtained, unprocessed plant foods that contain natural folate (as opposed to the synthetic folic acid):

The March of Dimes Birth Defects Foundation warns women not to rely on these foods for enough folic acid to prevent serious birth defects in their future babies (March of Dimes 1997).

We know the March of Dimes is focused solely on preventing every possible birth defect, but doesn't this seem a bit extreme? Certainly it is possible, and in some societies routine - to give birth to a healthy baby without taking a lot of supplements; yet we are issued a "warning" to take supplements, implying an "or else."

Fortunately, a subset of Americans is taking back control over their diet, by creating more farmer's markets, and supporting organic, and more important, local food production so more of us can eat better without resorting to cheap junk. Unfortunately, the medical community is still all about fixing us after there's something wrong. That's why even when considering prevention, they think in terms of medication, rather than the inculcation of lifestyle changes which are known to keep us healthy in the first place. Certainly in this world today the former way of thinking is much easier to promote. This has led to a plethora of studies on drugs and supplements, giving people substances our bodies are not adapted to, or abnormal amounts of substances our bodies do normally encounter, with results that have really not been very helpful in the long term. As one doctor says:

"Right now it would not be appropriate to blindly go forth and further increase the levels of folic acid without better understanding the potential risks," Mason said. "And whether we continue folic acid fortification should be an open debate over the next few years."

Amen to that. How about instead we spend some money finding a way to make it a lot easier for people to eat what they are designed to eat?

Labels: brain, health, humans, vitamins

An excellent article by Michael Pollan in this week's Times magazine has relevance to the subject I had already picked for my next post: how bad science and standard journalism practices contribute to a raft of contradictory, misleading, and often worse-than-useless nutritional and medical advice. He explains how another important facet of the problem is purely political, but touches more briefly on the issues to do with bad science. I will leave the politics to him and focus on the science. The media's role should be fairly obvious already.

What is the bad science? For an example I will use a paper whose topic has been publicized recently by the media: Corrada, et al. 2005. Reduced risk of Alzheimer's disease with high folate intake: the Baltimore longitudinal study of aging. Alzheimer's & Dementia 1:11-18.

This paper is first a perfect example of the reductionist approach to nutrition that Pollan discusses in his article. How do the authors identify folate as a nutrient associated with Alzheimer's? They first use self-reported diet and supplement data, which is notoriously bad in the first place (I can't help but add, probably even worse in a study which assumes a certain proportion of the participants will be having dementia during the study). Then, one author estimates the level of each of 6 nutrients of interest (vitamins C,E,B6,B12, folate and carotenoids). For some reason I can't yet figure out, they then decide whether each person took more or less than the U.S. R.D.A. for each nutrient. The relative risk for Alzheimer's is then calculated with a particular type of regression that I have not used, but let's assume that part's fine.

This procedure provides the following summary of results: the calculated relative risk (RR) for folate is .41, supposedly meaning that if you imbibe more than the RDA of folate over a number of years, your risk for Alzheimer's is only 41% of that of someone who takes less than the RDA.

Both vitamins E and B6 showed a tendency to reduce risk as well, so the authors reran the data in a test using these nutrients only, designed to confirm the importance of these vitamins and find out if RR was correlated among these three. They found some correlations but decided it didn't matter, and determined that folate was the nutrient they were looking for.

There are (at least) two major statistical problems with the paper. The first is common to a lot of scientific papers, especially medical ones, which doesn't make it any more wrong: using the wrong significance level. The scientific standard is to find two different groups of data different if there the chance they came from the same population is less than 5%. This is a completely arbitrary standard, but considered conservative enough to be accepted by the scientific community. Trouble is, every time you run a statistical test, there is a 5% chance that data that look different really aren't. Simply, this means that if you run 20 statistical tests as part of your analysis, then on average one of them is a false positive. This is why I do not panic when I do a free blood workup every other year offered by our insurance, and it always says that one of the things it is testing for (cholesterol, iron, etc.) is out of the "normal" range - if you test over 20 things and use 95% confidence intervals for where they should be, then that's what happens.

The paper does 6 initial analyses so at a minimum, the significance level should be set to 5%/6 = .833%. By this standard only folate shows any activity in the orginal test. But then they do a whole lot of other comparisons - they take each vitamin and break it into smaller groups and compare different levels of each to see what levels are associated with Alzheimer's. In the first table alone, there are a total of 18 statistical comparisons. Bottom line: if you fish for enough stuff for a long time, you're bound to catch something. (This also explains why all these "breakthrough" studies are so ridiculously contradictory when you put them all together - which the authors of this paper themselves admit in their discussion - and why all these nutrition fads come and go with such rapidity.)

The next statistical problem is that when they find 3 nutrients of interest, they reuse the same data set to confirm the suggestion that one or more of these are actually having an effect. This breaks a cardinal rule of statistics. If a data set gives you the idea that there is a certain effect, using the same data set to confirm the effect is basically self-confiming prophecy. How do you deal with this problem when the data are from a long-term study? You don't want to have to wait 20 years to confirm your suspicions. Fortunately, you don't have to. Before the study begins, you arbitrarily break your group into two. Then when doing the analysis, you use one group to hunt for any nutrients that might be doing something, and you use the second group to test your (now formulated) hypothesis that a particular nutrient is significant.

And by the way - the actual numbers of the study show that those taking more than the RDA of folate had a 7% chance of getting Alzheimer's, while those taking less had an 11% chance. Not exactly earth-shattering.

None of this touches on the idiotic notion that single nutrients are somehow acting in a vacuum to prevent or cause disease. But the media is just as in love with this idea as "nutritionists" are. Read Pollan's article. It will be obvious how this all fits together to create a multibillion-dollar supplements industry for stuff we feel we need because we are eating so much crap produced by the multibillion-dollar processed food industry.

These studies are a waste of time and money.

Labels: brain, health, humans, statistics, vitamins