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. More...

Now that the tanning industry has had its nosed bloodied by the Federal Trade Commission, maybe it’s time for the Food and Drug Administration to step up to the plate.

That’s the question that is looming large for many interested in the issue of tanning bed risk, and the upcoming FDA meeting on March 25 where further restrictions on tanning beds are going to be considered.

From my point of view, and based on my personal/family experience, action can't come soon enough.

This is clearly not a new topic.

Several years ago, the World Health Organization published a detailed, comprehensive report on the risks of tanning beds.  They concluded they were bad for your health, and recommended that youth under the age of 18 should be banned from using them.

Fast forward to this past July, and you have the International Agency for Research in Cancer—better known as IARC—issuing a statement that tanning beds are in fact a Class I carcinogen, on the same page and same line as tobacco.

In other words, just like tobacco, here is a product that when used as intended has a considerable chance of causing you harm.  And, at the same time, it is unclear except in the most limited of circumstances how tanning beds can possibly offer any benefit that can’t be achieved using approaches that are much less risky at substantially less cost.

In very condensed terms, what happened this past Tuesday was that the FTC charged the Indoor Tanning Association (ITA)—a trade industry that is supported by the tanning industry—of “making false health and safety claims about indoor tanning.”  According to the FTC press release, the association simultaneously “agreed to a settlement that bars it from any further deception.”

So what did they “decept” you might ask?

In a March 2008 advertising campaign—one that raised great concern among those aware of the risks of indoor tanning—the Association claimed:

·        Indoor tanning is approved by the government

·        Indoor tanning is safer than tanning outdoors because the amount of ultraviolet light received when tanning indoors is monitored and controlled

·        Research shows that vitamin D supplements may harm the body’s ability to fight disease, and

·        A national Academy of Sciences study determined that “the risks of not getting enough ultraviolet light far outweigh the hypothetical risk of skin cancer.”

As part of the settlement, the industry has to let people know that they don’t have to become tan to get vitamin D and that doing so “may increase the likelihood of developing skin cancer and can cause serious eye injury.”

When you look at a more detailed report of the FTC investigation, you find that the industry actually claimed—according to the FTC—that indoor tanning does not increase the risk of skin cancer.  The FTC countered that “tanning, including indoor tanning, increases the risk of skin cancer, including squamous cell and melanoma skin cancers.”

I distinctly remember the advertisements in question. 

Some of us were so concerned that—through the National Council on Skin Cancer Prevention—we actually wrote a letter to the ombudsman of a major national newspaper that ran the ads, taking them to task for running an advertisement that was clearly full of dangerous misinformation.  To the best of my knowledge, we never received a response.

And then there was the article that appeared in the New England Journal of Medicine that provided an excellent review of vitamin D but also included tanning beds as a means of supplementing vitamin D.  We complained about that as well, but the editor declined to run our letter.

Shortly thereafter, there were published reports  and an article on this blog discussing the fact that the researcher who wrote the article indicated that his research was supported by the Ultraviolet Foundation, which is a “foundation” wholly supported by the ITA.

So the battle goes on an on.

This past November, I had the privilege of testifying on behalf of the American Cancer Society at a hearing in Howard County MD that resulted in a county-wide ban on the use of tanning beds by minors under the age of 18.  This was an outright ban, not one of those “if your parents give you permission it’s OK” types of restrictions.

The room was filled with people in favor and opposed to the ban, and to be certain there were a number of tanning salon owners there who said they don’t want to harm children, and feel that tanning is safe (there were also a number of people there who had a strange looking tan, but that’s not a topic for this blog.  They just looked really out of place.)

There were also experts there who testified on behalf of the tanning salon owners.  One of those was a recently retired FDA official who just happened to be intimately involved with tanning bed regulation at the FDA prior to his retirement.

We are going to have a replay of that hearing on March 25^th at an FDA advisory committee meeting just outside of Washington DC, when the FDA is going to consider whether they should reclassify tanning lamps from their “essentially safe” list to one that has a bit more teeth. 

That, at least, would reflect current thinking on the question that these lamps are not safe when used as intended, and in fact can cause serious harm.

Like many things in life, this all comes down to one’s personal experiences.  And my family has had one of those experiences.

When my daughter was in high school, she succumbed to the lure of the tanning industry and wanted to get tan for her prom.

As you might imagine, she never told me or consulted with me about this.  After all, dear old Dad may have some knowledge about these things, but what does he really know?

Well, Dad may not know anything but my daughter soon discovered the problem with tanning beds.

You see, she has what is called “type I” skin.  That means she is very fair, and can’t tan.  She burns.

And that’s how I found out that my daughter was going to the “tanning” salon.  She returned home one Saturday, red as a lobster from head to toe, burned by one of those salons that allegedly always follows the rules.  And now she is at a lifetime increased risk of skin cancer and melanoma as a direct result of her sessions under the “safe” UV light in a local tanning salon.

I guess I shouldn’t be surprised.

Researchers have documented the dangers of tanning devices.  They have also documented the lack of controls on the tanning industry.

So I ask you, why?  Why continue this charade?  Why let this go on? 

Tanning isn’t something we need.  It’s something we want—for all the wrong reasons. It can even be addicting like cigarettes.  And, like cigarettes, when used as intended it does bad things—even causing cancer that can result in death—and doesn’t do anything good that can’t be done otherwise more safely, more effectively and less expensively.

I say it’s time for the FDA to follow the lead of the FTC and get on with the job that has to be done.

And, as reflected in a number of bills and proposed regulations currently pending in state and local legislative and regulatory bodies around the country, it’s time to ban the tan—especially for those under the age of 18.

Finally, we have the results of a large scale randomized, placebo-controlled clinical trial to tell us whether or not vitamin D can reduce the risk of breast cancer.

The study, reported in today’s issue of the Journal of the National Cancer Institute, concludes that there is no evidence that vitamin D decreases breast cancer incidence in post-menopausal women.

But I will bet you dollars-to-doughnuts (well, maybe not doughnuts—they are fattening) that this study isn’t going to provide closure to the hotly-debated question of whether or not vitamin D reduces breast cancer risk.

The study was part of the larger Women’s Health Initiative which was designed to look at the impact of hormone therapy on the health of post-menopausal women.  As part of that study, close to 18000 post-menopausal women were randomly assigned to take 1000 mg of calcium and 400 IU (international units—the recommended daily allowance for vitamin D) daily.  The other 18,000 women took placebos.

The problem is that both groups of women were allowed to take extra vitamin D and calcium, and a good number of them did just that—although the number of women who did so was basically the same in both groups. By year 6 of the trial, about half of the women in both groups were taking extra vitamin D.

The end result was that over the seven years of this study, there was no difference in the frequency of breast cancer between the two groups.  The vitamin D did not make a difference in how often women developed breast cancer.

An editorial that accompanied the report pointed out some of the problems with the study, and which I would also consider important:

• There were large number of women took vitamin D and calcium on their own, even if they were selected as part of the vitamin D treatment group or as part of the placebo group.  

• Breast cancer takes a long time to develop in most women.  Seven years may simply not be enough time to detect a benefit that may have been seen if the study was longer. 

• It is possible based on the results of other studies that vitamin D would be more effective if given to pre-menopausal women as opposed to post-menopausal women as was the case in this study. 

• Some experts recommend a fairly high dose of vitamin D to prevent cancer which is much greater than that studied here (however, if women were taking vitamin D on their own, it is quite possible that they were taking doses greater than 1000 units a day).

In the same editorial, the authors wrote:

“Because preclinical, epidemiological, and clinical trial results of vitamin D supplementation are conflicting, additional studies will be needed to determine whether vitamin D plus calcium will prevent breast cancer…Future clinical trials should address the above questions to help determine whether higher does of vitamin D supplements will be cancer preventive.  The potential health benefits of vitamin D and calcium may yet have a bright future.”

Another interesting finding pointed out by the authors of the research report was that vitamin D blood levels measured at the beginning of the study didn’t necessarily relate that closely to the amount of vitamin D that the women had been taking in the past.  High vitamin D intake did not necessarily mean high vitamin D levels in the blood.  That raises the question of how much vitamin D our bodies absorb when we take supplements.  Those amounts may be different in different people, and may be controlled by other factors such as our genetic makeup.

The authors concluded:

“Such results suggest that factors other than dietary and supplement intake of vitamin D likely influence (blood levels of vitamin D)…Before future clinical trials of high-dose vitamin D regimens to reduce breast cancer risk are implemented, it will be important to demonstrate that the selected vitamin D dose can definitively increase (blood vitamin D) levels to the projected target level.  Definitive assessment of factors that influence the relationship between vitamin D supplement use and subsequent changes in circulating (vitamin) D levels are therefore a research priority.”

The bottom line?

When it comes to vitamin D there are a lot of questions and not many answers.

For now, we would be hard-pressed to conclude that vitamin D reduces the risk of breast cancer in post-menopausal women.

There is still a lot we don't know:  we don't know how much vitamin D is healthy in our bodies, and if in fact there are risks associated with too much vitamin D (see prior blog).  We don't know whether or not we should be routinely measuring vitamin D in our bodies with blood tests.  We don't know how much vitamin D we should be taking every day, and whether each person responds the same way to the same dose of vitamin D.  We don't know whether vitamin D reduces cancer risk or influences outcome after cancer is diagnosed and for which cancers, if any.

Unfortunately, when it comes to vitamin D, confusion reigns supreme.  We deserve better.

Are we looking for cancer prevention clues in all the wrong places?  That is the question I am asking myself as another vitamin theory bites the dust.

A report in this week’s Journal of the American Medical Association (and supported in part by research funding from the American Cancer Society) examined the relationship between folic acid, vitamin B6 and vitamin B12 and breast cancer.

The bad news? A combination vitamin pill did not reduce the risk of breast cancer. 

The good news? A combination vitamin pill did not increase the risk of breast cancer, or any other cancer.

In the study, the researchers examined the effect of giving a daily dose of the three vitamins in a single pill to a group of women who were at high risk of heart disease.  Half the participants received the vitamins, and the other half took a placebo (or dummy pill) that did not contain the vitamins.

After a little over 7 years of treatment, there was no difference between the two groups of women with respect to the incidence of breast cancer or any other cancer.  There was also no difference in the frequency of cancer deaths between the two groups

The theory behind this research was that these particular vitamins play an important role in orderly cell growth, and therefore may prevent cancer. 

The reason the theory is so attractive is the same as it is for every vitamin claim: vitamins are easy to take, inexpensive, and thought to be harmless.  For many of us, they are a part of our daily routine.  What could be easier than popping a vitamin pill in the morning to prevent cancer and a host of other diseases?

The problem is—as it has been for many years—that when the vitamin claims are subjected to the magnifying glass of a well-done clinical trial, the claims simply don’t hold up.

Trust me, I know.  Years ago, vitamin C and vitamin E were the rage.  I took them until the research didn’t support the claims that they reduced the risk of cancer and heart disease, respectively. 

Then there was folate, which many of us take that as part of our daily multivitamin tablets.

First folate was reported to reduce the risk of colorectal cancer.  More recently, some research suggests that folate may promote polyp growth for people who already have colon polyps possibly resulting in an increased risk of colon cancer.

To be honest, the research on the risks and benefits of folate in colorectal cancer is conflicting and confusing to medical experts, let alone people who are trying to make the right decisions about their health.

This is important, since beginning in 1998 folate was added to our food in an effort to reduce the incidence of a certain birth defect in the spinal cord.  The food fortification program has been successful, and blood levels of folate in our bodies have increased over the past decade.

But now there is concern—in part because of the research results noted above—that too much folate may actually cause harm, and increase the risk of some cancers.

That’s why this study’s negative outcome is so important: folate did not increase the incidence of colorectal cancer or any other cancer.

Do you find yourself asking the question how something so simple—and so “natural”--as a vitamin can hurt people? 

If we hadn’t done the research, we would all be taking large doses of vitamin C to prevent cancer (it doesn’t).  We would never have found out that beta carotene leads to an increased risk of lung cancer in heavy smokers.  We wouldn’t know that vitamin E and selenium—alone or in combination—did nothing to reduce prostate cancer in men.

Next on my list is vitamin D.  But we won’t have definitive answers to questions about the cancer-related benefits and risks of the “sunshine vitamin” for years.

Maybe we are looking for cancer prevention in all the wrong places, and maybe not. 

It would be great if something as simple as a vitamin pill would ward off the risk of cancer.  Right now, however, the vitamins aren’t scoring any home runs in the cancer prevention arena.    

For now, we are just going to have to do things the old fashioned way: eat your five fruits and vegetables a day, maintain a healthy weight, eat a balanced diet, and exercise, exercise, exercise.

I know.  That’s much more complicated than taking a vitamin pill once a day.  But at least we know those are strategies that work for reducing your risk of cancer.

Broccoli, anyone?

.

Just because it’s “natural” and looks like it might work to prevent cancer doesn’t mean it will work to prevent cancer.

That’s the message of today’s announcement from the National Cancer Institute and the Southwest Oncology Group (which is a national research group that does clinical trials in cancer) that they are telling the over 35,000 men participating in a prostate cancer prevention trial to stop taking their pills.

The study, called “SELECT” and which was started in 2001, was based on two earlier trials that found pretty much by accident that it appeared selenium and vitamin E decreased the incidence of prostate cancer. 

Both of those studies were designed to primarily look at cancers other than prostate cancer. One, in Finland, was done to see if vitamin E reduced lung cancer incidence and the other examined the impact of selenium on the incidence of skin cancer.  In both of the studies, there was tempting data that selenium or vitamin E unexpectedly reduced the risk of prostate cancer.

But those “accidental findings” didn’t hold up in a well-designed clinical trial.  Life is not always simple in medical research.

After 7 years, the results are in: An independent review board which monitored the SELECT trial found selenium and vitamin E—either alone or in combination—did not reduce the risk of developing prostate cancer.  In fact, there was a small but not significant increase in the incidence of prostate cancer in the men taking only vitamin E and diabetes in the men taking only selenium.

The result: men are being instructed to stop their pills, but will continue to be monitored for several years.

The theories that vitamin E or selenium can reduce the risk of prostate cancer have been around for awhile.   There were many men who already believed that vitamin E and selenium could reduce the risk of prostate cancer.  But, once subjected to critical study through a randomized clinical trial—the gold standard of medical research—we find the evidence didn’t support the theories.

We have been here before with various vitamins and minerals.  And, there are those out there who have been suggesting that other vitamins and minerals can reduce cancer risk.

This blog is no stranger to evidence based medicine.  No matter how tempting the reports of success may be, until the right trial is done you simply can’t authoritatively support an unproven theory that a vitamin or anything else can prevent cancer.

Let’s always keep that principle in mind before we start advocating that “this thing” or “that thing” prevents cancer.

Until the evidence is in, the evidence isn’t in.

A study in the current issue of the Archives of Internal Medicine addresses a question that has interested me for some time: does vitamin D really reduce the risk of death for the general population?

The study, from Johns Hopkins in Baltimore and the Albert Einstein College of Medicine in New York, examined data from a national health survey performed in the United States from 1988 through 1994.

The studies did back up the claim that vitamin D deficiency is associated with an increased risk of death in the general population, but did not show that it reduced deaths from all types of cancer. 

Perhaps even more important to me was an observation in the report that suggested there may indeed be an increase in death rates for women who have higher levels of vitamin D in their blood.

The authors noted that approximately 41% of men and 53% of women in the United States are deficient in vitamin D based on prior studies.

The researchers examined data from a nationwide health survey that was performed in the United States from 1988 through 1994.  They evaluated health-related surveys, physical examinations and blood samples that were obtained from 13,331 people representative of the United States population who were 20 years or older.  They then examined the causes of death in this group through December 31, 2000.

In this study, the profile of people who had the lowest levels of vitamin D was older age, female, and non-Hispanic black.  People with low vitamin D levels in this study also tended to include those with higher blood pressures, higher body mass index or BMI (reflecting a greater incidence of overweight and obesity), diabetes, lower socioeconomic status and less physical activity when compared to people with higher levels of vitamin D.

When the researchers looked carefully at the rates of death from any cause, the 20% of the people studied with the lowest level of vitamin D in their blood had a 26% increased chance of death.  Many of the people in this group also were smokers and had other medical illnesses, but the authors were able to discount those factors as contributing to the increased death rate they observed

Unlike heart disease, the investigators found no evidence that vitamin D levels had any influence on the risk of dying from cancers of all types. 

When looking only at death rates for cancers which had previously been associated with vitamin D—including colorectal, breast and prostate cancer—there was no association seen in those who were most vitamin D deficient.  There was a suggestion of lower death rates for those specific cancers at a slightly higher vitamin level—which was still deficient, but not the most seriously deficient group. 

And then there was the graph I came across when looking at the paper.

You may recall back in June I reported on a study presented at ASCO which demonstrated that higher vitamin D levels in post-menopausal women diagnosed with breast cancer were associated with a better prognosis.

In the same study—reported at the meeting but not included in the abstract—there was a slide showing death rates from all causes in women who participated in the study.

In that study, as expected based on the conclusions of the research, the slide showed that women who presented with primary breast cancer and were deficient in vitamin D had a higher death rate compared to women with the middle range of vitamin D levels.

But it was the other end of the curve that gave me cause for concern, namely that the researchers in that study also observed an increased death rate from “other causes” at the higher vitamin D levels found in some of the women.  Those deaths were not from breast cancer, and the research did not point to any specific reason.

The researcher who presented the paper noted the finding, but also indicated that it had to be confirmed by other studies.

That was the first time that I had heard that people from an otherwise “normal” population (except for their breast cancer, of course) had an increased risk of death related to higher—but still acceptable--vitamin D levels.

We must always bear in mind that there may be many explanations for that observation, since the study wasn’t designed to measure that specific outcome.  It could be related to some other factor, or may have occurred just by chance.

Then there was the graph in the current study, and that graph showed a similar curve.  I can’t explain all the statistical considerations, but the graph showed that the women in this study who had higher levels of vitamin D in their blood also had what appears to be either a significant or a borderline significantly increased risk of death from all causes.

They really didn’t say much about the increased mortality rates seen in the 20% of the women in the study with the highest levels of vitamin D in their blood.

“This is the first study, to our knowledge, to explore the association between (vitamin D) levels and mortality in the general population…

“As shown, in women, having both low (<20 ng/ml) and high (>50 ng/ml) (vitamin levels) was associated with an increased rate of mortality. (Emphasis mine)

“Several authors have commented that the optimal levels of (vitamin D) should be greater than 30 ng/ml.  In our observational study, we found that there was a lower risk of mortality at levels of 30-49 ng/ml, but that at levels greater than 50 ng/ml, there was again a higher risk of mortality in women. (Emphasis mine) This is similar to findings about antioxidant vitamins and vitamin E, which show that too much may be harmful.”

I have to say that seeing this information in two separate studies certainly raises a concern as to whether or not this observation is real.  When you start to see a pattern like this in studies of this size, then one’s instinct is to start to pay attention to the finding.

If it is real, then the statement that there is no risk to having high levels of vitamin D—or trying to raise vitamin D levels beyond a “normal” or “middle” range—may not be correct.  Seeing two independent studies point in the same direction is suggestive that this is something worthy of further investigation.  It is not conclusive of evidence of harm.

As I have written previously, there is much yet that we need to learn about this vitamin and its role in health.  But before we can start making recommendations that people take large quantities of vitamin D, we need to know whether there in fact may be a serious mortality risk involved, especially for women.

Vitamin D deficiency is a cause for real concern in this country.  There is no doubt that many people in this country are vitamin D deficient, and that deficiency impacts their bone health, and may impact their overall health as well.

What we need to do now is look at a total strategy regarding vitamin D, beginning with a review of dietary guidelines and how all of this information plays into the everyday practice of medicine.  We need better understanding of the precise role of vitamin D in relationship to health and to cancer specifically.  We need to know if there is benefit from routinely measuring vitamin D levels as part of our general medical care, and what the best advice is regarding replacement and follow-up measurement.  We need to educate the public and the profession alike about vitamin D, but at the same time we need to understand the limitations of our knowledge.

This study did suggest that vitamin D deficiency is associated with an increased death rate from all causes, and supported in some cancers that there may be a relationship between vitamin D levels and the risk of cancer death.

But we also need to know if there is a downside, and the magnitude of risk from that downside.

As the authors clearly pointed out, we have been down this path before. 

Vitamins are assumed to be “safe” because they are “natural.”  But when studied carefully in some situations where there were claims of health benefits, they have been shown not only to not have a health benefit, but have actually caused harm.

As has been said, those that forget the past are condemned to repeat it. On the other hand, for the sake of our physical well-being, we also need evidence-based answers for the questions related to the relationship between vitamin D and our health.

A couple of weeks ago, I wrote a blog about vitamin D deficiency and its impact on breast cancer recurrence.  The information was based on an abstract that had been released in advance of the American Society of Clinical Oncology’s annual meeting, currently underway in Chicago.

In that blog, I reported on the conclusions of the researchers from the University of Toronto, Canada, that outcomes for women with breast cancer were worse if they were vitamin D deficient at the time of diagnosis, compared to women who had sufficient amounts of vitamin D in their blood.

Yesterday, the researchers presented their paper at the ASCO meeting.  And that presentation emphasized the fact that what appears in an abstract is not always the whole story.

The basic results reported at the meeting were essentially the same as those in the abstract.  Adequate levels of vitamin D in the blood of newly diagnosed breast cancer patients were associated with a less aggressive cancer and a better prognosis.

But there were two important points that were made that were in fact different from what was in the abstract or weren’t in the abstract at all.

First, during her presentation, Dr. P.J. Goodwin, who was the lead author on the study, commented that unlike what was printed in the abstract about the vitamin D relationship only pertaining to women with hormonally sensitive (estrogen receptor (ER) positive) breast cancers, in fact the study data showed that higher vitamin D levels were associated with an improved prognosis of all women with breast cancer—whether or not their cancers were hormonally sensitive.

That is an important point, since ER negative breast cancers—although representing a minority of breast cancers—are known to be more aggressive.  If vitamin D levels didn’t influence their prognosis, then that would represent one more negative differentiating factor for women diagnosed with these tumors.

Another interesting corollary—although not addressed specifically in this abstract presentation—is the fact that recent research has shown that African American women have a greater proportion of ER negative breast cancers. They also have more aggressive disease, with presentation at younger ages and with higher mortality compared to white women.  (It remains unclear how much of this difference is related to biology vs. lack of access to affordable, adequate health care.)

African Americans are also known to have a greater prevalence and degree of vitamin D deficiency.

If that is the case, then there is an intriguing question of whether or not there is a link here.  If we addressed vitamin D deficiency in African American women, could we reduce their risk of developing ER negative breast cancers, and improve their prognosis once diagnosed?

The second point that was presented in yesterday’s session was not addressed in the printed abstract.  Yet, in my opinion, it is possibly one of the most important observations regarding vitamin D being used to decrease the risk of cancer.  It is critical to assessing  the claims of many researchers and others that vitamin D supplementation is not toxic, and that we should be routinely recommending large doses of vitamin D through supplements or UV exposure to prevent cancer.

Dr. Goodwin showed a slide which looked at mortality in the women who participated in this study, based solely on their measured vitamin D levels.  (Unfortunately, I have not been able to get hold of a copy of this slide.)

The finding as reported, from my point of view, was unexpected and certainly should provide us with a sense of caution as we pursue to question of vitamin D as a cancer prevention agent.

The slide showed death rates over time as a function of vitamin D levels in these women with newly diagnosed breast cancer.

As would be expected, increased deaths were seen with low levels of vitamin D.  That in large part was due to increased deaths from breast cancer.

As vitamin D levels in the blood at the time of diagnosis increased, there was a fall-off in deaths, again probably due to fewer deaths from breast cancer.

But then there was the unexpected finding that as vitamin D levels increased, death rates increased as well.  That should not have happened from breast cancer, since the data was clear that higher levels of vitamin D were associated with better prognosis.  So something else was leading to more deaths than expected.  (For the scientists among you, this is what we call a “U” shaped mortality curve—increased deaths at the upper and lower limits of the measured variable, with a low level in the middle.)

What Dr. Goodwin reported was that there essentially was a “sweet spot” for blood levels of vitamin D that maximized its benefit with respect to breast cancer, while minimizing harm.  But the data also suggests that increased levels of vitamin D were in fact potentially harmful.

Dr. Goodwin mentioned that she did not know why this happened, and that it merits further research as to the cause as well as careful evaluation in upcoming studies.  She cited prior research that has suggested higher blood vitamin D levels may be associated with an increased number of cardiac events.

In any event, this is the first time I have heard of a potentially harmful relationship of this type, implying that we should be cautious before we recommend megadoses of vitamin D for women for the prevention of breast cancer, or as part of their treatment.

So what are the lessons?

First, what we see in print in an abstract is frequently never the whole story, and we don’t have the “final word” until a study is actually published in a peer review journal.  Even then, research studies are always subject to further discussion and scrutiny.

In this situation, the abstract said the benefits of higher vitamin D levels were limited to women with ER positive cancers.  In the presentation yesterday, we heard that women with both ER positive and ER negative breast cancers who had higher levels of vitamin D in their blood had better prognoses.

Second, there may be harm with having too much vitamin D in the blood.  This is very much a preliminary observation, and clearly needs more study to help us understand if this is a consistent, real finding. 

As I have noted before, we must always approach new ideas with caution.  We need to do the appropriate research to demonstrate both the benefits and the risks of vitamin D before we make recommendations for millions of people.

Only then can we have the confidence that the recommendations we are making are backed by the strongest and best scientific studies, and won’t result in more harm than good.

As I write this, my mind is on my exit for the weekend, and thoughts of being with my family, friends, and the dogs (two very active golden retrievers, but more about them another day) in the north Georgia mountains.  (Yes, there are mountains in north Georgia. Not too high, but they are mountains.)  

I am thinking of taking walks, doing some cooking, maybe fishing, and basically taking 72 hours to relax a bit (If  that is possible with the dogs.  They don’t get much attention normally, so this is their time for vacation, too.).

But it is also that time of year when we need to be thinking about not only the good things associated with being out of doors, but how we have to take care of ourselves and our health when we are out in the sun.

May is Skin Cancer Prevention Month.  

The timing is obviously not coincidental. Many of you—like me—dramatically increase our time outside during the summer months.  For those of you who live in sunnier climates, it’s a time of the year when the intensity of the sun becomes greater as do the risks of damage from the sun.

So it is never a bad idea to remember that being out of doors is a good thing.  But you should always make certain you are adequately protected.

The American Cancer Society suggests you remember the phrase “Slip, Slop, Slap!”  when you are enjoying yourself in the sun.

What does “Slip, Slop, Slap” mean?

Slip! - Slip on a shirt. Wear protective clothing when out in the sun. Choose clothes made of tightly woven fabrics that you can’t see through.

Slop! - Slop on sunscreen. Wear sunscreen with a sun protection factor (SPF) of 15 or higher on any exposed skin. Apply sunscreen 15-20 minutes before going outdoors, and be sure to reapply as necessary, especially after swimming, sweating or toweling off.

Slap! – Slap on a hat. Wear a wide-brimmed hat that shades the face, neck and ears.

And, while you’re at it, don’t forget to wear sunglasses that block 99-100% of the UV rays that can damage the skin and the eyes.

Sunscreen is probably one of the most misunderstood products we use.  Some people confuse high SPF values with all day protection.  It doesn’t mean that a higher SPF lasts longer.  It just means that it is stronger in blocking the sun’s rays.

So remember to use lots of sunscreen (about a palmful) and reapply it regularly—like it says above--especially after swimming, sweating (after a tough game of beach volleyball would be a good example), or drying off after coming out of the pool or ocean.  

My message about sunscreen: use it or pay the price!!!!!  Sunburns are bad for you, and what’s more, they HURT!!!!  But I suspect you already know that, probably from personal experience.  So why do you keep going back for another one?

You should also cover up as much as possible, and stay under the shade.  My wife and I have learned that reading, relaxing, and enjoying a beverage while under a beach umbrella or one of those beach huts works just as well if not better than baking and wrinkling your skin in the blazing sun.

Be especially careful during peak sun hours, which usually run from 10-4.

You can actually check on the projected degree of risk from the sun by looking up the “UV Index” online on the EPA Sunwise website.The EPA website will give you all the information you need to understand the UV index and what it means for your day in the sun.

The bottom line message that I try to give people about sun exposure is to enjoy it and use the sun wisely.  I don’t recommend seeking the sun to replenish vitamin D.  There are supplements that do that much more safely than the sun.

You can’t ignore the fact that we enjoy being outdoors, just like I am going to enjoy my weekend with my family.  Being outdoors is part of a healthy life style.

By taking a couple of sensible sun-safe precautions, it can also be part of a long and healthy life, free of skin cancers that sometimes can kill.

So, ENJOY!!!!

Have a safe and happy holiday weekend, and on Monday take a moment to remember those who have given their lives to make ours better.

We are getting into the “season” when there is a plethora of cancer news, primarily due to forthcoming annual meeting of the American Society of Clinical Oncology meeting, which is scheduled to begin in two weeks in Chicago.

Unlike years past, when the abstracts were embargoed until the scientific studies had been presented at the meeting, this year ASCO released almost all of the abstracts last evening.  Only a handful of the most significant abstracts have been withheld from the public release.

One of the abstracts highlighted by ASCO had to do with vitamin D levels of women diagnosed with breast cancer.  The results of that study are certainly thought provoking, and will undoubtedly add to the discussion on the role of vitamin D in health and its influence on cancer incidence and prognosis.

We need to bear in mind that all we have so far is an abstract of the research, which essentially represents the most preliminary form of reporting scientific results.  The actual public presentation of the data won’t happen until the ASCO meeting.  That’s when other researchers have a chance to listen to the information, get clarification of the data, and ask questions of the researchers.

Based on what I do have available to review at this time, this study certainly appears to be well done and will likely raise as many or more questions than it answers.

According to the abstract, the researchers at 3 University of Toronto (Canada) hospitals took blood samples from 512 women who were diagnosed with breast cancer.  The women studied were all diagnosed between 1989 and 1995, and the course of their disease was followed until 2006.

What the researchers found was very interesting.

37.5 % of the women had low vitamin D levels which were considered deficient.  38.5 % had intermediate levels, or what the researchers called “insufficient.”  The remaining women—24% of those studied—had adequate levels of vitamin D at the time of their diagnoses.

The researchers found that there was a seasonal variation associated with vitamin D levels, as would be anticipated, with higher levels when the blood was drawn in the summer, and lower levels when the diagnoses and blood drawing occurred in the winter.

There were some other factors that were associated with vitamin D levels, including lower vitamin D levels in women who drank less alcohol, or consumed lower amounts of vitamin E, grains and retinol in their diets.

Premenopausal women and those with higher body mass indexes—a measure of overweight and obesity—also had lower vitamin D levels.

But here is the part of the research that is so interesting:

The time to recurrence of breast cancer was significantly lower in women with insufficient vitamin D levels, compared to women with adequate vitamin D levels in their blood samples.  Overall survival was also significantly better in women with adequate vitamin D as compared to those who were deficient.

For women with estrogen receptor negative breast cancer—which is known to be a more aggressive form of breast cancer—their survival was not related to their vitamin D status.

As noted in a press release that accompanied the abstract, “after 10 years of follow-up, 83 percent of women with adequate levels remained free of metastases and 85 percent were still alive, compared with only 69 percent and 74 percent, respectively, of women with vitamin D deficiency. Most of these deaths were attributed to breast cancer.”

The conclusion of the researchers was simple and straightforward in the abstract: “Vitamin D deficiency is common at breast cancer diagnosis and is associated with poor prognosis.”

In the same press release, the researchers clearly pointed out that these results need to be confirmed by a second trial, which is already underway.  If that research supports these findings, then, as noted by the lead researcher on the team, they “recommend(s) a new randomized clinical trial examining the effects of raising blood levels of vitamin D on outcomes in women with breast cancer.”

As I mentioned, this is certainly a provocative study. 

There are certain things we look for in studies of this type, including the fact that the women were not selected at random, but represented all the women who presented for treatment of their breast cancer who met certain criteria.  The blood levels were obtained at the same equivalent time, namely when the cancer was diagnosed.

There has been a lot of research published on vitamin D and its relationship to cancer, some of which has supported a possible role of vitamin D in reducing the incidence of various cancers, other research suggesting that higher vitamin D levels at the time of diagnosis of certain cancers may be associated with an improved prognosis, and other research claiming the role of vitamin D in cancer incidence is limited.

We struggle with what to tell people to do when it comes to vitamin D and their health.

Clearly, the evidence indicates that vitamin D benefits bone and muscle health.  It may also influence cancer and other diseases such as autoimmune diseases and multiple sclerosis.

Yet when it comes to understanding vitamin D levels of people in the United States and elsewhere, we have much to learn.  We know many people—especially those with darker complexions and the elderly—have vitamin D deficiency. 

We don’t routinely measure vitamin D levels as part of a routine physical, yet maybe it’s time for us to consider doing that. 

Many experts believe that the current dietary guidelines for daily vitamin D intake are too low.  Some advocate daily sun exposure to maintain vitamin D levels, while the American Cancer Society and others say that you should not “seek the sun” for vitamin D replacement.  That’s because there are risks to daily sun exposure, and there are safer alternatives in over-the-counter vitamin D3 supplements which avoid skin wrinkling and increased risk of skin cancer over time.

With all of these questions and all of these controversies, it is time to move forward and get the answers.

I applaud the caution of the Canadian researchers in tempering the expectations that will inevitably follow the release of their report. 

They emphasize that we need to confirm their results, and if that confirmation does occur, then we need to do a clinical trial to determine whether vitamin D supplementation can influence the incidence of breast cancer.

We also need to focus our resources in bringing together knowledgeable experts to guide us on the appropriate daily vitamin D dietary recommendations.  We need to do the studies that will answer the question whether or not vitamin D does reduce cancer risk, and for which cancers.

As I have said before and will continue to say, there is enough research that has been published which suggests there is a relationship between vitamin D intake, vitamin D blood levels and cancer risk and incidence. 

But the type of studies that have to be done to provide us with the best evidence have not yet been done.  Those studies will require a significant commitment of researchers, money and willing participants.  They will take years to complete.

The problem I have is that in the past we have had suggestions that various vitamins reduced the risk of cancer.  When properly studied however, those claims didn’t hold up.  Not only did they not hold up, in some cases they were actually associated with an increased risk of harm. 

The conclusion: just because it’s a vitamin doesn’t mean it doesn’t have risks.

I am looking forward to hearing this presentation in Chicago in two weeks. 

I suspect I will come out of that meeting with the same thoughts I have going in, namely that we need to find out whether vitamin D is really the miracle vitamin that some claim, or is just another example of a failed hope that didn’t survive the careful scrutiny afforded by a well-designed clinical trial.

Millions of people are awaiting the answer.

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I will post links on this story at a later time.

If you want to understand why some of us are concerned about conflicts of interest, you need go no further than an article that appeared in last Friday’s edition of the Cancer Letter.

The article, written by Paul Goldberg, goes into great detail to explain why a scientific review on vitamin D, sun exposure and tanning booths which appeared in the New England Journal of Medicine last July may have been influenced by tanning industry funding.

The fallout from this conflict, in my opinion, may have substantial negative impact on how we are able to regulate tanning bed use, especially among young women who are putting their health at risk from the adverse effects of articial tanning.

The story is not new to regular readers of this blog.  I covered it in July 2007 when the review article first appeared in the New England Journal.

Essentially, the article was a review article on vitamin D and its potential role in health and disease.  As I noted at that time and on many occasions subsequently, I admired the depth of the science in the report regarding vitamin D and how it relates to human health.

Where I had a problem was that the author, who is widely known to be supported by and supportive of the indoor tanning industry, failed to make any comment in the article about the potential harms and risks of his recommendation that we should get regular sun exposure to get adequate amounts of vitamin D.  He also recommended tanning salons as an effective and safe means of getting vitamin D.

What he didn’t do was comment on the fact that there are many well-qualified experts in this field who disagree with his recommendations.  These experts don’t dispute the need to better understand vitamin D as it applies to our population, or that there is a role for vitamin D as part of being healthy.  The evidence is strong that vitamin D plays a role in muscle and bone health.  There is evidence that suggests vitamin D may play a role in cancer prevention. 

These experts feel that the recommendations for sun exposure and using tanning salons to increase vitamin D levels in our bodies do not take into account the risks of skin cancer that would result.  Nor do these recommendations take into consideration the realities that we are all different in where we live, the color of our skin, and our individual sensitivity to sun.  All of these factors and others influence our sensitivity to sun and how much vitamin D we produce in our bodies from sun exposure.

These experts feel that there is a safe alternative to get vitamin D into our bodies, either through our diets (which admittedly is difficult to accomplish) or through inexpensive, safe dietary supplements which are available at virtually every supermarket, drug stores and many other retail outlets throughout the country.

The Cancer Letter article makes the same points I did in my blog last July, and expands in greater detail to show how a conflict that is not recognized or declared can influence a host of subsequent events.

Basically, what happened in the New England Journal article was that the author acknowledged his research was supported by the Ultraviolet Foundation.

Google the Ultraviolet Foundation and its tax filings and you find out that it is funded by the Indoor Tanning Association. 

And that is not a conflict that should be considered in editing or publishing an article on vitamin D and health?

The Cancer Letter notes that the amount of support in question is small when viewed as a totality of the research support for the author.  But it was significant enough in this circumstance to be noted as a source of funding for the research that led to the publication of the article.

One needs to take a look at what I call “second level effects” of such events.

Maybe the author and the New England Journal consider the conflict of interest to be immaterial.   The potential fallout and damage is not.

Here is a possible scenario of how these things play out, and what in fact is happening right now:

The New England Journal of Medicine is one of—if not the—finest and most highly regarded medical journals in the world.  It is viewed as an authoritative source of medical information, and its influence in scientific, medical and legislative arenas is without peer.

As a result, having research published in the New England Journal provides a widely accepted “stamp of approval” on the research reported, or the information provided in a review article.

Since the editors and reviewers of the article did not see any reason for the author to address the concerns of many experts regarding the risks of tanning and sun exposure—even a sentence or two would have been sufficient—the article stands alone as a firm recommendation on the value of sun exposure and tanning beds as a means of getting vitamin D into our bodies.  (I should note that supplements were also offered as an option.  I am concentrating here on the absence of comment by the author on the risks of tanning beds and sun exposure.)

There are a number of states that are considering or have implemented legislation and regulation of tanning bed use, particularly by young women who represent a population at risk that use these services.

If you have watched legislation and public policy being formulated and debated, you know it is not always a pretty process.  It is usually not very deliberative—legislators always have many items on their agendas, and too little time to do much independent research or investigation.

That’s where this article comes in.  

An article in a prestigious medical journal which makes positive comments about tanning booths is invaluable when lobbying legislators. What could be more authoritative in making the case that effective regulation of this potentially life-threatening device is unnecessary? 

Now maybe you can appreciate why I am so concerned about this particular conflict of interest.

This scenario is not so far fetched. 

The Indoor Tanning Association has embarked on a nationwide advertising campaign to influence people--including state legislators--that tanning is safe, and actually healthy for you. 

Unfortunately, I can’t link to a copy of an ad which recently appeared in the New York Times.  What you see, in large print, is the statement, “Tanning Causes Melanoma.”  Superimposed over that is a “stamp” that says, in bold letters, “HYPE.”  At the bottom of the ad is a link to a website called “SunlightScam.com.”

Although I can’t find much in the way of true scientifically valid supportive evidence on the website, I can’t help but think somewhere someone is using the New England Journal article to support the claims of “hype” and “scam.”

Maybe I am moving with the wrong crowd on this one. 

My problem is that the experts I rely on don’t think that the claims of increased risk of skin cancer and melanoma are a hype or scam.  They do acknowledge that not all melanoma is caused by sun exposure, but they do note that sunburns in youth are a major risk factor for melanoma later in life.  And ultraviolet light—definitely UVB and quite possibly UVA—are the major risk factor for skin cancer.  Skin cancer is not always “benign”.  It can be fatal (melanoma) or very disfiguring when treated (squamous cell and basal cell carcinomas).

Perhaps you can now appreciate why understanding conflicts of interest are important, and that they are not trivial.  Many of us involved in medical science and medical leadership have conflicts.  They are almost unavoidable.

It’s not the conflicts that are always the problem (although in an increasing number of circumstances, they are in fact problematic).  It’s the recognition of the conflict, the declaration of the conflict, and the mitigation of the conflict that offer us the best hope to enable us to continue to maintain our trust in our most valued institutions, researchers, and leaders in medicine.

As I have said recently in another blog, it is up to the professions to deal with conflicts of interest issues and give them the visibility they deserve. 

Only through awareness, discussion and full disclosure will we be able to move forward and maintain the trust that the public has vested in us as physicians and medical scientists.