Today's Los Angeles Times has an article on the failure of several recent randomized clinical trials to show benefits of taking vitamin supplements for disease prevention. The article provides some good explanation for the layperson on the differences between experimental (i.e., RCT) and observational (i.e., correlational) studies for being able to make causal inferences, in my view. It also discusses some problems, specific to vitamin research, that complicate the interpretation of experimental/RCT studies, even though they're designed to hold extraneous factors constant.
First, here are some examples of the article's discussion of experimental vs. observational research:
Randomized clinical trials are designed to test one factor at a time, but vitamins and minerals consumed as part of a healthy diet work in concert with each other.
"You don't eat a food that just has beta carotene in it," said Dr. Mary L. Hardy, medical director of the Simms/Mann UCLA Center for Integrative Oncology...
"The observational studies that originally linked vitamins to better health may have been biased because people who take supplements are often healthier overall than people who don't.
"They tend to be more physically active, better educated, eat better diets, and tend not to be smokers," [the NIH's Paul] Coates said. "So you can't say for certain it's your item of interest that causes" the health benefit.
The issue that's specific to vitamin studies is as follows, focusing on the need for a "placebo" or "control" group that does not receive the treatment being tested:
For several reasons, researchers say, vitamins don't lend themselves to randomized controlled trials. Chief among them is that there is no true placebo group when it comes to vitamins and minerals, because everyone gets some in their diet."
For drugs, someone either has [the anti-impotence drug] Cialis in their system or he doesn't have Cialis," said Paul Coates, director of the NIH Office of Dietary Supplements in Bethesda, Md. But with vitamins, "there's a baseline exposure that needs to be taken into account. It makes the challenge of seeing an improvement more difficult."
My (Alan's) initial reaction to this statement was that extraneous exposure to vitamins from food consumption should not necessarily compromise researchers' ability to make a causal inference about the vitamin supplements. The experimental group would be ingesting vitamin pills plus vitamins in food, whereas the control group would be ingesting placebo (sugar) pills plus vitamins in food. Assuming the food intake to be similar in the experimental and control groups -- which is what random assignment to groups is supposed to buy us -- then the only difference between the groups should be the vitamin vs. placebo pills.
However, there's yet another complication:
A vitamin's benefit may become apparent only if people aren't getting enough of it. That could explain why vitamin D has been linked to reduced rates of heart disease, cancer and diabetes.
"Most people are vitamin-D-deficient, and that's not true for vitamin E," [the USDA's Jeffrey] Blumberg said.