
Read too many headlines and you might think that everything under the sun causes cancer. And, of course, the sun itself can increase your risk of the disease, because the ultraviolet radiation it puts out is the major cause of skin cancer.
But recently, some researchers have suggested that sunlight could also protect us from cancer – you’ve probably seen stories about it in the media. When sunlight shines onto our skin, we produce vitamin D and indeed, sun exposure is our main source of this chemical. We need vitamin D for strong, healthy bones but some studies suggest that it can also reduce the risk of many types of cancer.
Understandably, this is a fairly controversial issue – how do you balance the need for some sun exposure in order to make enough vitamin D with the need to stay safe in the sun and reduce your risk of skin cancer? And is it true that vitamin D can reduce the risk of cancer at all?
This month, the authoritative International Agency for Research into Cancer (IARC) have weighed in on the issue. By gathering a group of expert scientists, they have looked at all the available evidence and published a detailed report on vitamin D and cancer. The massive tome weighs in at 465 pages, but we’ll take a look at the key points in the first of two posts looking at the vitamin D debate.
Does vitamin D reduce the risk of cancer?
Possibly, according to IARC, although to a lesser extent than is commonly suggested. You’ll often see claims that vitamin D protects against a wide range of different cancers including very common types such as breast, bowel and prostate cancer. But the IARC report paints a different picture.
Much of the evidence that vitamin D could protect against cancer comes from studies looking at how rates of different cancers change depending on where in the world you live. These studies are called “ecological studies” and they have mostly found that the further north from the equator you go, the more likely people are to develop, or die from, many types of cancer.
The big idea is that the sun’s rays are weaker at higher latitudes, so people living in northerly places make less vitamin D. And it’s this that, in theory, accounts for their higher rates of cancer.
But the IARC report heavily criticises this type of research for several reasons:
- These studies are based on a faulty assumption – that people have less vitamin D the further north they live. In fact, studies in Europe show the opposite trend; people living further north often have higher levels of vitamin D. And in North America, the link between latitude and vitamin D is a weak one.
- These studies often don’t adjust for other things that vary with latitude and could also explain differences in cancer rates, such a what people eat, how active they are or how wealthy they are.
- These studies don’t account for differences in the way people behave, such as their desire for a tan, whether they work indoors or whether they go on holidays in sunny places. These things have a much greater effect on a person’s vitamin D levels than simple geography does.
So ecological studies tell us very little about vitamin D and cancer – they are like looking at the issue through a fogged-up pair of glasses. For a clearer view, some studies have looked at individual people, actually measuring the vitamin D in their blood and comparing it to their risk of cancer.
These studies have found that people with higher levels of vitamin D in their blood are indeed less likely to get bowel cancer. So an association does exist. However, the evidence for breast cancer is “limited” – lots of studies have looked into a possible link and their results are so inconsistent that any protective effect could well be a fluke. And “there is no evidence” that vitamin D could reduce the risk of prostate cancer.
What does vitamin D actually do?
So all in all, there is growing evidence that vitamin D is linked to a reduced risk of bowel cancer in some way, but the jury’s very much out for other types. Even then, the IARC report says “The key question is to understand whether low vitamin D status causes an increased risk of cancer… or is simply a consequence of poor health status”. Is vitamin D directly influencing the biology of cells in our bodies, or are vitamin D levels a ‘proxy’ for something else?
There are certainly signs that a person’s levels of vitamin D could reflect their health in general. Many things that increase the risk of conditions like cancer and heart disease are also linked to low levels of vitamin D. These include old age, a high body weight, being inactive, smoking or an unhealthy diet. In at least one large study, the researchers adjusted their results to account for these other factors. They found that this weakened the link between vitamin D and cancer or heart disease.
On the other hand, studies using animals or cells in a laboratory have found that vitamin D could well have direct biological effects. The chemical is good at multi-tasking – it does a large number of jobs in our cells. And according to laboratory experiments, many of these – from stopping cells from growing to causing damaged ones to commit suicide – could help to prevent cancer.
But again, the IARC report advises us to interpret these experiment with care. What happens in laboratory cells may not apply to humans and all too often, researchers have been led down dead-ends by these types of experiments.
Other nutrients, such as beta-carotene or vitamin E, have shown similar anti-cancer abilities in a lab, but failed to deliver on this early promise when supplements were tested in humans. Indeed, in some clinical trials, people who received high-dose vitamin supplements actually had higher risks of cancer. It just goes to show that we have to be very careful when making assumptions about what happens in real people based on what happens in small samples of cells.
So…
So what does this mean for us? Should people be actively seeking out vitamin D supplements, or treating them with caution until more research is done? And should we still bother staying safe in the sun? We’ll see how the new report answers these questions in Part Two.
Ed
Comments
Narek March 23, 2009
Why are doctors more worried about Rickets making a comeback than the very real epidemic of Skin Cancer, especially Melanoma? Most of the Rickets cases are among the black race, in the USA. In my life, I don’t know one child with rickets or one adult with Osteomalcia and I am 55 years old. I know lots of people who developed skin cancer and 4 with Melanoma, 2 died from it. Rickets are easily prevented and Osteomalicia, easily prevented and treated!
Doctors have responded to the Vitamin D hype that was originally sensationalized by Vitamin D experts, like Dr. Holick. Investigating his research, reveals how irresponsible and contradicting his advice is, which he has been promoting, actively, for years.
I believe Vitamin D (it’s really a hormone) to be essential to good health but doctors should get off the band wagon of promoting a “little” sun. Isn’t that the same as advising one cigarette a day to prevent weight gain? Are doctors just assuming people won’t stop drinking soda pop, instead of milk, so the sun is the lesser of two evils?
A little sun is all it takes to trigger Melanoma. Whether or not the perfect study with the high dose of Vitamin D proves Vitamin D prevents cancer, it’s irresponsible to promote “any” sun exposure. It does hurt immunity. That was proven many years ago. And it is cumulative, like all radiation. And what else don’t we know about the dangers of radiation? And why, in all these studies and treatments for low Vitamin D levels, do doctors and scientists always instruct to take the supplements and not UVR exposure?
DR Barbara J Boucher March 23, 2009
I much appreciate the effort and concern that has gone into the posting of all these comments. However, at the end of the day, the question as to whether adeqaute vitamin D status should be ensured in order to provide measurable protection against various cancers and against the many other disorders with which poor vitamin D status is associated cannot be resolved satisfactorily without adequately powered RCTs using adeqaute doses of vitamin D being carried out across various communities and ethnic groups. The sooner everyone involved in these circular arguments uses all thier energy and drive to ensure that such RCTs get done the sooner we will have the facts necessary to provide valid answers on these issues. This said, one major reason for being concerned about this particular IARC report is that funding bodies could find it difficult to support such trials, which many commentators on this site clearly want, whilst this report stands as it is. Hence the push to ensure that this issue is examined from every point of view. If such an examination fails to provide definitive answers, then RCTs of vitamin D supplementation must go forward.
Rickets was wiped out world-wide within a generation by cod liver oil and ‘fresh air’ but rickets is now increasingly common due to lack of supplementationn and our retreat from the sun and inadeqaute vitanin D status is common at all ages across the globe, almost 100 years after vitamin D was discovereed. Let us make sure that it isn’t another 100 years before we have the answers we need as to whether non-bony disorders can be reduced as dramatically as rickets and osteomalacia, by supplementation, even if we have to continue to avoid getting sunburnt by limiting our exposure to ultraviolet light.
Barbara J Boucher
Narek March 23, 2009
I think Ed Yong does an exellent job of making sence out of a confusing, contradicting issue about Vitamin D preventing cancer. If you analyze what these studies have and haven’t proven, the obvious conclusion is, there really isn’t any real evidence that Vitamin D prevents any cancers. And if people go ahead and expose their skin to UVR, in order to prevent cancer, the prevention might be worse than the disease.
Then William Grant presents that the scientists were obviously biased. But it’s obvious to me that he is the one that is biased with claims that haven’t been proven. Then “his” credible scientist happens to be DR. Michael F. Holick. Dr. Holick has been paid a huge amount of money by the Tanning Industry and his book, The UV Advantage, is riddled with flaws. He recommends using a lot of exposure to UVR from tanning beds in order to get the best kind of Vitamin D, from UVR instead of suplements. In “USA Today”, he posed in a tanning bed. How stupid is that?
The bottom line to all of this is, UVR is cumulative like all radiation. Your skin never forgets. Most of us have already had way too much. I think a great deal of the bias comes from people worshipping the sun like a religion. People want to believe it and it’s a quick fix. If Vitamin D is proven to be a cancer prevention, great! But why in the world expose our skin to the sun to get it?
At the beginning of the 20th century, the average life span was 49. Skin cancer doesn’t usual show up until after age 50. Every hour in this country, someone dies of Melanoma! It’s happened to people in my life. It is a truly horrible affliction!
Mike Barnes February 19, 2009
I agree with Dr Grant-in addition, the pharma industry knew about the anti cancer effects of vitamin D in the lab many years ago and spent billions trying to produce analogues of vitamin D that could be patented, but the biochemistry of the body out smarted the chemists and they failed. At the very least all the epidemiolgy data on vitamin D provides a strong signal that it has anticancer effects. So do the controlled studies that are needed. The signals have been there for years and yet still the needed studies have not been conducted. And Dr Yong when you do the studies dont use 400IU. Use a dose that has a chance to show an effect!!!!
William B. Grant January 20, 2009
My detailed critique of the IARC report has been published with open access at
http://www.landesbioscience.com/journals/dermatoendocrinology/toc/1/1
Grant WB. A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D. Dermato-Endocrinology. 2009;1(1):25-33.
Along with an accompanying editorial:
Holick MF. Shining Light on the Vitamin D-Cancer Connection IARC Report
Dermato-Endocrinology. 2009;1(1):4-6.
And a previous paper:
Grant WB. How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer? An examination using Hill’s criteria for causality. Dermato-Endocrinology. 2009;1(1):17-24.
“All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.”
~ Arthur Schopenhauer Quotes
It appears that the UVB/vitamin D/cancer theory is in Stage Two.
Ed Yong December 16, 2008
To answer your points:
Reason #1. The expert scientists were well-versed in the adverse effects of UV irradiance but not well-versed in the beneficial effects. Thus, they brought a bias to the review that was clearly evident in how they readily accepted observational evidence that UV increases the risk of melanoma and skin cancer but dismissed over 95% of the evidence that UVB reduces the risk of internal cancers. It seems apparent that they were trying to protect their message that UV irradiance should be avoided in order to reduce the risk of skin cancer and melanoma, even though vitamin D could be obtained from supplements rather than UVB irradiance.
The working group responsible for the report include over 20 experts in the field of vitamin D and many of them have been looking at the links between vitamin D and cancer with great interest. Your accusation of bias among the group’s members is not based on the evidence. In particular, the report states that some of the members were invited “because of their expertise in methodological issues”, which lends greater strength to the report’s analysis of the strengths and weaknesses of various studies.
Reason #2. The report did not fairly review the ecological studies. It is correct that latitude is not a good index of vitamin D production in Europe north of about 40˚, and that other factors such as diet, alcohol consumption, and smoking have more important impacts on cancer risk than does UVB (2). However, the Report did not reference or discuss an ecological study for the United States that used summertime UVB doses as well as indices for alcohol consumption, ethnic background, smoking, socioeconomic status, and urban/rural residence (3). This study, which used mortality rate data for two periods, 1950-69 and 1970-94, found inverse correlations with summertime UVB for 14 types of cancer, gastrointestinal tract, female other than cervical, urogenital cancers and lymphomas. In the United States, there is an asymmetry for summertime UVB doses with doses in the states east of the Rocky Mountains much lower than doses to the west due to higher surface elevation and thinner stratospheric ozone layer in the west. This pattern is readily apparent for most of the 14 types of cancer.
The report is not alone in criticising ecological studies in this area – several other reviews have pointed out the flaws in making causal conclusions based on such methods and we have nothing further to add regarding the weaknesses of these studies that we have not written about in the post. The future of research into vitamin D and cancer lies in clinical trials and large-scale observational studies that directly measure how much vitamin D people have in their blood (specifically, its metabolite, 25-hydroxyvitamin D).
Reason #3. Perhaps the most egregious error of the report was its summary dismissal of the only randomized controlled trial of vitamin D and cancer incidence in which sufficient vitamin D was used. This study involved over 1000 post-menopausal women in Nebraska who were divided into three groups and followed for four years. Those taking 1100 IU/day of vitamin D and 1500 mg/day of calcium had a 77% reduction in all-cancer risk between the ends of the first and fourth years (4). In comparison with those taking 1500 mg/day of calcium and those taking a placebo, a 35% reduction in all-cancer risk was attributed to the vitamin D dose.
The report’s analysis of the Nebraska trial was carefully considered and not, as you say, a “summary dismissal”. The trial’s weaknesses have been criticised elsewhere (see page 238 of the report for references) and the IARC report concludes that “the statistical analysis of the trial was not correct” and the “design of the trial was biased”. The group who received a placebo had unusually high rates of cancer, which would have increased the chances of finding that vitamin D supplements have a protective effect. The trial also found that calcium supplements alone reduce the risk of cancer to a similar extent as vitamin D and calcium supplements combined. The trial’s results were actually “negative for vitamin D”. We stress again that many of the scientists who contributed to the new report were chosen for their expertise in the methods used in scientific studies.
Reason #4. The Report considers the finding regarding vitamin D and bowel cancer to be a mere “association.” However, my review of the literature on vitamin D and cancer risk finds that UVB and vitamin D can be considered causal risk-reduction factors for cancer (5) when evaluated according to Koch’s postulates as enunciated by A. Bradford Hill (6). For example, the mechanisms whereby vitamin D reduces the risk of cancer are well known (7).
The report is very clear that the evidence for a causal link between vitamin D and bowel cancer is not strong enough at this stage. This is why they have called for clinical trials to demonstrate that restoring adequate vitamin D levels can lead to a lower risk of bowel cancer, or of dying from it. Note that we are not dismissing links between vitamin D and cancer. Elsewhere on our website, we say that there is growing evidence that vitamin D protects against bowel cancer. But we agree with the conclusions of the IARC report that the evidence regarding other cancers is weak and inconsistent. In contrast, the link between UV radiation and melanoma is readily accepted because it is supported by a large body of evidence from multiple types of research.
Reason #5. Finally, the Report was, in my opinion, disingenuous in pointing to vitamins that did not live up to their promise in reducing the risk of cancer as a reason to reject the UVB/vitamin D/cancer theory. After all, vitamin D supplementation did practically eliminate rickets.
The report did not, as you say, use the failed promise of other vitamins to “reject the UVB/vitamin D/cancer theory”. It did, however, suggest the unexpected results from these trials should give us reason to be cautious so as not to inadvertently cause public harm through unsubstantiated recommendations. The benefits of vitamin D in eliminating rickets was noted by the report but is irrelevant for discussions regarding cancer.
William B. Grant December 14, 2008
Vitamin D does protect against cancer
The IARC Report 5: Vitamin D and Cancer (1) should not be considered a definitive review of the evidence that solar ultraviolet-B (UVB) irradiance and vitamin D reduce the risk of cancer for the following reasons:
Reason #1. The expert scientists were well-versed in the adverse effects of UV irradiance but not well-versed in the beneficial effects. Thus, they brought a bias to the review that was clearly evident in how they readily accepted observational evidence that UV increases the risk of melanoma and skin cancer but dismissed over 95% of the evidence that UVB reduces the risk of internal cancers. It seems apparent that they were trying to protect their message that UV irradiance should be avoided in order to reduce the risk of skin cancer and melanoma, even though vitamin D could be obtained from supplements rather than UVB irradiance.
Reason #2. The report did not fairly review the ecological studies. It is correct that latitude is not a good index of vitamin D production in Europe north of about 40˚, and that other factors such as diet, alcohol consumption, and smoking have more important impacts on cancer risk than does UVB (2). However, the Report did not reference or discuss an ecological study for the United States that used summertime UVB doses as well as indices for alcohol consumption, ethnic background, smoking, socioeconomic status, and urban/rural residence (3). This study, which used mortality rate data for two periods, 1950-69 and 1970-94, found inverse correlations with summertime UVB for 14 types of cancer, gastrointestinal tract, female other than cervical, urogenital cancers and lymphomas. In the United States, there is an asymmetry for summertime UVB doses with doses in the states east of the Rocky Mountains much lower than doses to the west due to higher surface elevation and thinner stratospheric ozone layer in the west. This pattern is readily apparent for most of the 14 types of cancer.
Reason #3. Perhaps the most egregious error of the report was its summary dismissal of the only randomized controlled trial of vitamin D and cancer incidence in which sufficient vitamin D was used. This study involved over 1000 post-menopausal women in Nebraska who were divided into three groups and followed for four years. Those taking 1100 IU/day of vitamin D and 1500 mg/day of calcium had a 77% reduction in all-cancer risk between the ends of the first and fourth years (4). In comparison with those taking 1500 mg/day of calcium and those taking a placebo, a 35% reduction in all-cancer risk was attributed to the vitamin D dose.
Reason #4. The Report considers the finding regarding vitamin D and bowel cancer to be a mere “association.” However, my review of the literature on vitamin D and cancer risk finds that UVB and vitamin D can be considered causal risk-reduction factors for cancer (5) when evaluated according to Koch’s postulates as enunciated by A. Bradford Hill (6). For example, the mechanisms whereby vitamin D reduces the risk of cancer are well known (7).
Reason #5. Finally, the Report was, in my opinion, disingenuous in pointing to vitamins that did not live up to their promise in reducing the risk of cancer as a reason to reject the UVB/vitamin D/cancer theory. After all, vitamin D supplementation did practically eliminate rickets.
Thus, the IARC Report should not be used as the basis for health policies with respect to vitamin D and cancer.
Disclosure
I receive funding from the UV Foundation (McLean, VA), the Vitamin D Society (Canada), and the European Sunlight Association (Brussels). However, none of these organizations has reviewed this response.
References
1. IARC report: Vitamin D and Cancer (Nov. 25, 2008)
http://www.iarc.fr/en/Media-Centre/IARC-News/Vitamin-D-and-Cancer
2. Grant WB. An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer. 2002;94:272-81.
3. Grant WB, Garland CF. The association of solar ultraviolet B (UVB) with reducing risk of cancer: multifactorial ecologic analysis of geographic variation in age-adjusted cancer mortality rates. Anticancer Res. 2006;26:2687-99.
4. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-91.
5. Grant WB. How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk of cancer? An examination using Hill’s criteria for causality. Dermato-Endocrinology, 2008 epub.
http://www.landesbioscience.com/journals/dermatoendocrinology/article/Grant2DE1-1.pdf
6. Hill AB. The Environment and Disease: Association or Causation? Proc R Soc Med 1965; 58:295-300.
7. Ingraham BA, Bragdon B, Nohe A. Molecular basis of the potential of vitamin D to prevent cancer. Curr Med Res Opin. 2008;24:139-49.
William B. Grant April 27, 2009
Since we UVB/vitamin D/cancer scientists are still upset with the IARC Working Group 5 Report, Vitamin D and Cancer, fourteen of us wrote an open letter to the new IARC Director, Christopher P. Wild, Ph.D., which has just been published in Dermato-Endocrinology:
Cedric F. Garland, William B. Grant, Barbara J. Boucher, Heide S. Cross, Frank C. Garland, Oliver Gillie, Edward D. Gorham, Robert P. Heaney, Michael F. Holick, Bruce W. Hollis, Johan E. Moan, Meinrad Peterlik, Jörg Reichrath and Armin Zittermann. Open Letter to IARC Director Christopher P. Wild: Re IARC Working Group Report 5—Vitamin D and Cancer. Dermato-Endocrinology 2009 March/April;1(2):119-120.
http://www.landesbioscience.com/journals/dermatoendocrinology/article/8512/
Access to this open letter is free, but one must register to download the letter.
In Director Wild’s response, he defended the IARC Report, condidering it a balanced presentation of the current state of hte evidence. While he declined an offer to have his letter published alongside ours, why not read our letter and see whether you think his response was appropriate. You might also go to http://www.pubmed.gov and search using “vitamin D cancer” to find papers that have appeared since a few months before the end of 2008 and, therefore, were not included in the IARC Report preparation.