Oh, vitamin D, where have ye gone? We miss ya!!
That might be the refrain of many who have labored so long to promote awareness of vitamin D as a possible cancer prevention agent for the past number of years.
Not that the advocates have lost their faith-a recent article from Dr. Cedric Garland, who is an expert on vitamin D as a case in point-but a report from the Institute of Medicine (IOM) has thrown a bit of a damper on the unbridled enthusiasm that vitamin D was the answer to cancer prevention that many have been seeking for some time.
No, the IOM did not endorse vitamin D as a cancer prevention agent. And based on what they could say from the literature, the panel did endorse the concept that vitamin D is important for bone health, while blood tests that reportedly showed substantial deficiencies throughout the United States were in fact not being appropriately interpreted.
Now, in a "Perspective" piece in this week's New England Journal of Medicine, three of the IOM panel members share their thoughts with the public as to why the panel did not reach the conclusion that vitamin D decreases cancer risk. And, while they support that conclusion, they also don't lose sight of the possibility that there may just be some truth behind the claims-bit it hasn't been proven just yet.
First, the authors-all highly regarded-make the general observation that "the prevalence of vitamin D inadequacy in North America has been overestimated. Most North Americans have serum 25-hydroxyvitamin D concentrations above 20 ng per milliliter, which is adequate for bone health in at least 97.5% of the population."
That statement is important, because bone health is the one area that the panelists agree the evidence is adequate that vitamin D does something valuable in our bodies.
But when it comes to cancer, the authors paint a less complete picture about the evidence surrounding the benefits of vitamin D as a cancer prevention agent.
According to the authors, the committee's review of the evidence surrounding vitamin D and cancer "revealed that the research is inconsistent and doesn't establish a cause-effect relationship."
One of the real sticking points is the absence of forward-looking, randomized trials where vitamin D was the sole variant and cancer incidence was the endpoint. Too many of the trials look at different information that was collected in a variety of ways to assess the impact of vitamin D on cancer outcomes. There are simply too many factors that could and did interfere with the interpretation of that data, and they cited circumstances where data analysis which appeared to show a benefit of vitamin D on a particular cancer in fact didn't pan out when the data was analyzed a different way, taking into account some of those "interfering factors" (which we call "confounders").
What are some of those factors?
As the authors note, some that are associated with a higher cancer risk include obesity (which harbors vitamin D in fatty tissue), the absence of outdoor activity (not being active is associated with all sorts of health problems, including cancer), dark skin pigment (reducing the amount of vitamin D made in the skin because of less production), diet, and whether or not a person takes vitamin D supplements.
So, just because something appears to be the case doesn't mean that it is the case.
If you went to the Eastern shore of Maryland and didn't know anything about life, and you saw a lot of sunburned people drinking beer and eating crabs at night, you might think that beer and crabs caused sunburn. That is an example of "true-true-but-not-related." The same thing may be happening in a lot of the research reported on the association of vitamin D and cancer. That's why properly done clinical trials-which admittedly take a long time to do-are what we need to definitively answer the question up or down as to whether or not vitamin D decreases cancer risk, and for which cancers.
This is not a new problem by any stretch of the imagination.
Very competent and committed scientists have drawn similar conclusions about different vitamins and minerals in the past, based on data seen in various clinical studies. Selenium, beta-carotene and vitamins C and E are but a few examples that have been suggested as cancer preventive agents previously.
But when the appropriate trials were done, the associations did not hold up. In fact, in one classic and frequently cited study, the beta-carotene actually had the opposite effect, by leading to the deaths of more smokers that occurred on the control arm of the trial, where they did not receive the vitamin in question.
It is important to note, however, that the authors of the current paper in the Journal do not close the door on the possible activity of vitamin D on preventing cancer:
"The theory that vitamin D can help prevent cancer is biologically plausible. The vitamin D receptor is expressed in most tissues. Studies in cell culture and experimental models suggest that calcitriol promotes cell differentiation, inhibits cancer-cell proliferation, and exhibits anti-inflammatory, proapoptotic (cancer cell death mechanisms0 and antiangiogenic (slows growth of tumor-related blood vessels) properties. Such findings suggest, but don't prove, that vitamin D has a role in preventing the development of cancer or slowing its progression."
I wouldn't call that a "death knell" statement regarding the possible relationship between vitamin D and cancer prevention. Just a bit of a hazard warning while moving on to a better scientific place where the ground is firmer and the sky a little less cloudy.
The authors go on to site data regarding some specific cancers and previous claims that vitamin D reduced the risk of getting those cancers. They include breast cancer, colorectal and prostate cancers. In each situation, they point out the conflicting and/or inconclusive evidence regarding the possible association. They also comment that for less common cancers, the evidence is equally conflicting or not adequate to draw firm conclusions. Of interest was their observation that in one study of pancreatic cancer, higher levels of vitamin D were actually associated with a significantly increased risk of getting that usually fatal illness. Similar increased risk has also been reported for esophageal cancers.
Their final statement in their report was pretty blunt:
"Despite biologic plausibility and widespread enthusiasm, the IOM committee found that the evidence that vitamin D reduces cancer incidence and related mortality was inconsistent and inconclusive as to causality. New trials assessing moderate-to-higher dose vitamin D supplementation for cancer prevention are in progress and should provide additional information within 5 to 6 years. Although future research may demonstrate clear benefits of vitamin D related to cancer and other nonskeletal health outcomes, and possibly support higher intake requirements, the existing evidence falls short."
I guess that statement is pretty conclusive, isn't it? And if we have waited this long to find out what we don't know for certain, maybe waiting another couple of years to get better answers may not be a bad idea.
Just don't get burned in the sunshine getting your vitamin D while you are waiting for the results of the research. At least we know for certain that sunburn is not good for your health.