This week we had another report from the Women’s Health Initiative (WHI), a federally sponsored long term study which has looked at a number of issues, such as hormones, diet and cancer prevention. 

This report, appearing in the New England Journal of Medicine, studied the value of calcium and vitamin D in the prevention of colorectal cancer. 

Last week, I was less than enthusiastic about their research report on the value of a low fat diet in reducing the risk of breast and colorectal cancer.

This week, different scenario, but the same conclusion.  

Once again, we will not have the answer to the specific question about whether or not calcium and vitamin D reduce the risk of colorectal cancer.  And this is after many, many years of study, in a research program that one of my colleagues called "the Rolls Royce of studies”.

I don’t mean to sound critical.  These are very well designed studies, by leading investigators who have contributed a heck of a lot more than their time to this effort for the past 15+ years.  These researchers are highly regarded, and are very knowledgeable. 

Sometimes, though, in science as in life, for whatever reason, situations change, knowledge changes, and new ideas need to be investigated.  When you have a study of this size and complexity you cannot change your plans or your design in mid-stream.  You have to deal with the hand you are dealt, in other words.

These women were part of a large cohort of women who were in fact able to participate in several studies at once: the value of hormone replacement therapy, the ability of a low fat diet to reduce the risks of breast and colorectal cancer, and whether taking calcium and vitamin D would reduce the risks of colorectal cancer, among other areas of medical interest. 

You have possibly heard the results of this portion of the study by now: postmenopausal women who took 1000 mg of calcium and 400 IU of vitamin D (or perhaps we should say were assigned to take those doses) did not have fewer cases of colorectal cancer than those who were given placebos, or sugar pills.

As noted in an editorial in the same issue of the New England Journal of Medicine that accompanied the research article, reducing the risk or preventing colorectal cancer is an important goal, in no small part because this cancer is the second leading cause of cancer deaths in this country. 

That translates into a lot of interest in finding a medicine, vitamin, mineral, herb or whatever (hopefully something that is simple and well tolerated with few short term and no long term side effects) that will reduce the risk of getting colorectal cancer and/or dying from it.  (Of course, this ignores the fact that if we did early detection tests that we currently have available and know work, we could reduce the number of deaths from this cancer by half.  Yes, that is correct: by half!!!!  But that is a topic for a different day.)

But as the editorial also noted, the fact that this study was “sliced and diced” (my words) into so many compartments may have in fact diminished its ability to answer the question it was designed to ask.  And, the doses of vitamin D and calcium may have been insufficient to have the desired effect, as these recommended doses (especially for vitamin D) have increased over the years.

The same basic criticism applies here as I mentioned in my blog last week on the low fat study: would you expect any intervention short of a miraculous one to reduce the risk of colorectal cancer in a group of older post-menopausal women who were followed for 7 years on average?  After all, these women were entering the prime age to develop a disease whose beginnings probably started many, many years previously.

In this paper, unlike the last one, the researchers were a bit more forthcoming in this regard.  They wrote, “If the benefit of calcium with vitamin D supplementation is to prevent or slow the progression of colorectal cancer in its early stages and if colorectal cancer has a latency of 10 to 20 years, the average intervention and follow-up of 7 years in our study may have been insufficient to demonstrate an effect.” 

In my opinion, that is a true statement.  And it was not offered in the low fat study, where the same criticism was valid. 

In contrast, there were numerous media interviews by experts who proclaimed the low fat diet was of no benefit in reducing the risk of colorectal or breast cancer based on that research report.  That may in fact be a true statement—but based on prior research, not the results of the study that was reported last week. 

As I have written previously, my colleagues tell me the evidence has been reasonably well established that a low fat diet on its own was proven years ago not to be effective in lowering the risk of colorectal and breast cancer.  In other words, to those in the scientific community, this new research report was not news.

There was an important subtext to this research that cannot be overlooked and that is the issue of vitamin D alone and colorectal cancer prevention. (See a related blog entry from early January for a more detailed discussion of this topic.)

The researchers measured the blood levels of vitamin D in participants at the start of the trial.  What they found was that women who had higher vitamin D levels in their blood test at the beginning of the trial had a significantly reduced risk of developing colorectal cancer during the course of the trial.  They also found that it didn’t make any difference which group the women were assigned to during the trial (remember, some of the women received vitamin D and calcium, and the others received sugar pills or placebos).  So, there was something about their initial vitamin D levels that was important in decreasing the chances that a particular woman would develop the disease.

Maybe the next trial should look at vitamin D as a colorectal cancer prevention strategy.  But my hunch is now that the “gold standard” trial was completed at great expense with less than clear findings, there won’t be much incentive to repeat the effort and invest the substantial cost.

So for now we will continue our confusing messages to the public about the role of calcium, vitamin D, aspirin, non-steroidal anti-inflammatory drugs, and whatever in reducing the risk of colorectal cancer.  My confession here is that even I am confused on what the evidence shows, and this study certainly did provide me any help.

As the doctors who wrote the editorial commenting on the study concluded, “Thus, the conclusion of Wactawski-Wende et al. about the role of calcium plus vitamin D supplementation in the prevention of colorectal cancer needs to be interpreted in the light of the complexities of the WHI study and the probability that the doses of these substances may have been too low to achieve the desired effect.”

I couldn’t have said it better myself.