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Could vitamin D help to improve cancer survival?

Could vitamin D help to improve cancer survival?

Recent research, some of which we helped fund, suggests that  melanoma and bowel cancer patients with high levels of vitamin D – the “sunshine vitamin” – may survive for longer.

But should people with these cancers be rushing for the sun lounger or sunbed?  And does this conflict with our advice about staying safe in the sun?


How is vitamin D linked to cancer?

Ed has already written at length about vitamin D, UV exposure and cancer, so we’d recommend reading his two posts (Does vitamin D protect against cancer? and Do we need more sunlight to make enough vitamin D?) as background.

In summary, there’s tantalising evidence that vitamin D could play a role in preventing some cancers, in some circumstances.  But ‘everyday’ casual sun exposure – rather than sunbathing – probably gives most people enough vitamin D.

The studies
The link between cancer survival and vitamin D comes from two scientific papers. The first is from Professor Julia Newton-Bishop and her Cancer Research UK-funded team in Leeds, along with colleagues in Birmingham and the US.   They measured the levels of vitamin D in the blood of 872 melanoma patients at the time they were diagnosed, and cross-matched these with clinical information about how each patient fared.

The second study was carried out by researchers at the Dana Farber Cancer Institute in the US, and involved 1,017 bowel cancer patients. Although these researchers didn’t directly measure the levels of vitamin D in the patients’ blood, the scientists asked them questions about their diet, supplement use and sun exposure.  This enabled them to work out an estimate of vitamin D levels in the blood at the time of diagnosis.

Both studies compared the patients with the highest levels of vitamin D to those with the lowest, to look for links between their vitamin D levels and how their disease progressed.

What did the studies find?

In the first study, melanoma patients with the lowest levels of vitamin D were a third (30 per cent) more likely to relapse after treatment than those with the highest levels. And those with the highest levels of vitamin D tended to have thinner (i.e. generally less dangerous) tumours when they were diagnosed.

In the US study, patients with highest estimated vitamin D scores were half as likely to die from bowel cancer, compared to people with lowest scores.  Although the researchers only used so-called proxy measures, rather than actually measuring vitamin levels in the blood, it’s certainly an interesting finding that warrants further investigation.

What does it mean?
The results suggest that people with melanoma or bowel cancer might benefit from increasing their vitamin D levels, either through diet, supplements or UV exposure.  But it’s important to note that vitamin D supplements (and excessive amounts in the diet) can potentially cause harm if taken in large doses without medical supervision.

We strongly advise cancer patients to talk to their doctor if they are concerned, before considering taking supplements – especially since there’s evidence that some vitamin supplements can have unintended consequences.   Moreover, vitamin D from supplements doesn’t appear to be regulated in the body as tightly as vitamin D from the sun – and there’s still a lot of uncertainty over what the ‘best’ dose is.

And we certainly don’t recommend that patients go overboard on the beach or sunbeds to top up their vitamin D. We know that we all need a bit of sunshine in our lives.  But we also know that excessive UV exposure (from the sun or sunbeds) and  sunburn are major risk factors for melanoma.

Through our SunSmart campaign we encourage everyone to enjoy the sun safely, and  most people make more than enough vitamin D after a just a short time in the sun –  less than the time it takes to burn.

Certain groups of people – the very young, the very old, the housebound, and people who wear full-body coverings – may benefit from vitamin D supplementation.  And researchers are currently discussing whether  very fair people (who redden or burn in strong sun in a matter of minutes) who excessively protect themselves from UV may actually not make enough vitamin D. But this is currently an idea that needs more research.

What next?
The area of vitamin D and cancer is fascinating and controversial, and scientists around the world are actively discussing and studying it.

Here at Cancer Research UK we’re continually reviewing the scientific evidence around vitamin D, sun exposure and cancer risk and adjusting our health messages whenever new evidence emerges. And we’re actively funding research into vitamin D levels and how this relates to UV exposure, to try to illuminate some of the grey areas in this most intriguing of topics.

Kat

This st0ry has also been covered on the NHS Choices blog


References:
Ng, K., et al (2009). Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer British Journal of Cancer, 101 (6), 916-923 DOI: 10.1038/sj.bjc.6605262

Newton-Bishop, J. et al (2009). Serum 25-Hydroxyvitamin D3 Levels Are Associated With Breslow Thickness at Presentation and Survival From Melanoma Journal of Clinical Oncology DOI: 10.1200/JCO.2009.22.1135

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Comments

Kevan Gelling January 19, 2010

Cancer Research UK does fund some vitamin D research. The results from one such piece, published in this month’s Journal of Investigative Dermatology, are in:

“UK guidance advising casual short exposures to UVB in summer sunlight … three times weekly for 6 weeks, while wearing T-shirt and shorts … SUBOPTIMAL vitamin D status is attained after a summer’s short (13  minutes) sunlight exposures to 35% skin surface area”

I trust Cancer Research UK will update their advice accordingly, so that we can all obtain an OPTIMAL vitamin D status

—-
Rhodes, L. E. et al. Recommended summer sunlight exposure levels can produce sufficient (>/=20 ng ml(-1)) but not the proposed optimal (>/=32 ng ml(-1)) 25(oh)d levels at uk latitudes. The Journal of investigative dermatology (2010). URL http://dx.doi.org/10.1038/jid.2009.417.

Kevan Gelling November 17, 2009

I’ll see what I can do ;-)

If someone is willing to put their hands up, then could I suggest a RCT of colon cancer prevention with high dosage D supplementation.

The IARC review of vitamin D concluded “results show evidence for an increased risk of colorectal cancer and colorectal adenoma with low serum 25-hydroxyvitamin D levels” and CRUK website states “vtamin [sic] D does somehow help to reduce the risk of bowel cancer”, which would suggest a more favourable consideration for any request.

Colon cancer is a very common cancer, which should help minimise the trial size.

Kat Arney November 16, 2009

Hi Kevan,

To answer this specific question, “if someone was able to present such a proposal for a suitable large scale RCT, would Cancer Research UK fund it?”:

As we’ve explained above, our funding process enables us to fund the highest quality applications across a range of areas. So the answer is yes – if a high quality proposal was made, then it would go to our committee and compete for funding on its merits.
Kat

Kevan Gelling November 14, 2009

Here’s a game that you might like to play:

Whenever a new genetic ‘breakthrough’ is announced, go to Google Scholar, type “vitamin D” and the name of the linked gene, enzyme, etc.

Almost everytime you’ll find a result comes back with evidence that VDRs (vitamin D receptors) are active in the discovery’s metabolic pathway.

Here are some to start you off – PARP, NOTCH, P53

mbarnes01 November 14, 2009

I also found the statement “Vitamin Ds role in cancer prevention is not cut and dried” somewhat amusing. New oncology drugs get into clinical trials based on a few in vitro cell cultures and xenograft studies in mice. Both of these models have been shown to have little correlation with clinical activity but they continue to be used simply because nothing else better has been found, hardly, a “cut and dried’ situation.
However let me address Kevin Gellings question “would they fund a controlled study with vitamin D should it be proposed.’’ I propose the answer is a resounding “No” for the very same reasons they have not taken the initiative to start such a study. Present day oncology researchers have all built their careers on the genetic basis of cancer. This is the present ‘group think ‘ , cancer is a genetic disease and we will cure it by mapping out the genome of tumors, identifying the genetic mutations that drive the tumor and developing drugs that work against each of those mutations hence tailoring drug therapy to each individual patients tumors genetic profile. This strategy has produced next to nothing in terms of improving patient survival. Any claimed improvement in survival (minor as it is) is almost certainly due to early diagnosis and better standards of general medical support i.e. treatment of anemia and concurrent infections. To set up a study with vitamin D in cancer prevention/treatment and have it work would prove that the oncology community went down the wrong path which has been the basis of their whole career. Imagine the embarrassment of having ignored almost 30 years of increasing data on vitamin D (Garlands original proposal that vitamin D levels explained the difference is cancer rates at different latitudes was published in 1979).
In the US such a study is about to start. It is called the VITAL Study and is due to start 2010 in 20,000 patients. In this study subjects will receive placebo or vitamin D (2000IU) plus fish oil (1gm). It just so happens that fish oil contains Vitamin A, which has been shown to impair the absorption of Vitamin D and hence its effect. So in their wisdom, our experts have managed to come up with a trial design where vitamin D is combined with the one substance on planet earth that can impair its effect. To be fair the study is actually a four arm study so each substance will be examined alone, but why confound the question. We simply need a large study comparing vitamin D to placebo in cancer prevention. However most of the vitamin D experts would say that the extent of the data on vitamin D preventing cancer is now so extensive, that to conduct such a study is unethical. There is no known downside to correcting vitamin D deficiency. To expose people to placebo will answer an academic question but exposes that population to what many would consider an unnecessary and unethical risk. I for one will not be participating in the trial and will continue to take my 6000IU of vitamin D3 per day

Kevan Gelling November 13, 2009

Vitamin D’s role in cancer prevention may not be “cut and dried”, but there’s a lot of circumstantial evidence.

Ecological studies are conclusive – cancer is linked to latitude and race. Cohort and prospective studies are conclusive – cancer is linked to vitamin D (as the two studies above demonstrate). Laboratory experiments are conclusive – calcitriol (the active form of vitamin D) has many anti-cancer regulatory properties including propagation, differentiation, apoptosis and angiogenesis (e.g. research published this month shows that calcitriol suppresses aromatase in breast cancer – PMID 19906814).

Small RCTs have shown beneficial effects of vitamin D levels for colon, breast and prostate cancer (Garland et al. 2006). The one large RCT that has been conducted show a 77% all-cancer risk reduction (Lappe et al, 2007). This RCT has been criticised because, with results this good, mistakes must have been made.

There is one missing step – a large scale RCT that can confirm (or deny) these findings.

“We can usually only fund trials if we get high-quality research proposals for a specific project”.

So the ‘million pound question’ is, if someone was able to present such a proposal for a suitable large scale RCT, would Cancer Research UK fund it?

Kat Arney November 12, 2009

Thanks for your comment.

As a charity our ‘money pot’ is not infinite. Our grant awarding committees already receive far more applications than we can fund. This means that we have to focus on funding only the very highest quality research that will have the maximum impact in beating cancer. But it’s not entirely true that we are entirely passive in this process and don’t shape the research agenda.

Last year we carried out in-depth reviews of all our research, which culminated in the production of our five-year research strategy (see http://scienceblog.cancerresearchuk.org/2008/11/28/our-five-year-strategy/). This highlighted areas in which to increase our investment – such as radiotherapy research, early diagnosis of cancer, and research into difficult-to-treat cancers such as lung, pancreatic and oesophageal cancers. These areas were prioritised because it was felt – after a great deal of consideration and consultation with experts – that extra research effort in these areas would make a significant impact on cancer survival. We have also initiated programmes of investment in cancer imaging and drug development.

These are large and significant programmes of research, rather than individual trials or studies, supported by a large body of scientific evidence and expert opinion that they will make a significant impact. They are still administered through the process of competitive grant awards, enabling us to fund the highest quality research – we will not fund research unless it stands up to scientific scrutiny and will provide significant results.

We fund a significant amount of research into cancer prevention – mainly through our Population research committee. This includes funding trials testing the benefits of certain supplements for prevention (for example the CRISP-1 trial).

As we have discussed many times already on this blog, the evidence for vitamin D’s role in cancer prevention is not cut and dried, and we are actively involved in discussions with other organisations about it. We are already funding the work of Dr Rhodes (as mentioned above) to try and answer some of these questions, and any other researchers working in the field in the UK are welcome to apply for funding. Our role in funding research is well known and publicised throughout the UK research community, and there is certainly not a dearth of applications for any of our committees.

Kat

mbarnes01 November 12, 2009

So what you are saying Kat, is that cancer research does not take the initiative to suggest a study and look for investigators interested in conducting the study but can only be passive and respond to requests for funding if someone else comes up with the idea. Progress tends to more dramatic when proactive steps are taken!

Kat Arney November 12, 2009

Hi Gwyn,

Cancer Research UK funding is given out in the form of grants – we can usually only fund trials if we get high-quality research proposals for a specific project.

Researchers apply to us with proposals, which are then scrutinised by a committee of experts. An application for funding the kind of trial you propose would be examined in the same way as any other grant. There’s more information about the process here: http://scienceblog.cancerresearchuk.org/2009/10/27/the-multi-million-pound-question/

Best wishes,
Kat

Dr Gwyn Harris November 11, 2009

While the work you are funding with Professor Rhodes does appear interesting, I am curious to know why a randomised controlled trial of vitamin d supplementation vs placebo for cancer prevention is not being carried out?
Observational data suggests that a once per 6 months oral boost of vitamin d (60,000iu?) could significantly cut the rate of ca bowel, which is the 3rd most common cancer in the UK. Surely this is an obvious area for cancer UK funding?

mike October 1, 2009

The Canadian Cancer Society has been recommending that everyone take vitamin D to prevent cancer for over two years. If you would like to see the data that led to this go to http://www.vitaminD3world.com

Kevan Gelling September 28, 2009

Hi Kat,

The rate of melanoma is rising dramatically for indoor workers but not those who work outside (Cooke 1984 – http://www.ncbi.nlm.nih.gov/pubmed/6746119).

UVB creates vitamin D3 in the skin. Most is absorbed into the body, but some may be converted into an active form of the vitamin – calcitriol – which can kill melanoma cells.

Recent research from the US Food and Drug Agency (www.ncbi.nlm.nih.gov/pubmed/19155143) has shown that indoor workers are exposed to higher levels of UVA light.

So, by following SunSmart’s sun avoidance advice (“we recommend using sunscreens together with shade or clothing” = < 4% of available UVB light), we could be sitting at our desks without a tan that would protect us from UVA and without vitamin D3 in our skin which can kill cancerous melanoma cells.

The facts are:
– the full physiology of melanoma is not yet understood
– the SunSmart solution has not been scientifically proven

Mike September 25, 2009

Hello Kat
Firstly no one is suggesting we go out into the sun and burn, but based on the multiple studies to data keeping your vitamin D levels has no down side. Those that live in sunny areas have levels of 70-90ngs/ml and in the UK you are lucky is your level is 20ng/ml. The Canadian Cancer Society have been recommending that everyone take vitamin D supplements for over two years unyet your organiziation remains silent and does not address the issue. Cancer reasearch is now funding Professor Rhodes who is a dermatologist. What about starting the prospective double blind trials on cancer prevention that everyone in the cancer industry states need to be done before we can start correcting a deficiency. These should have been done 20 years ago. There is now as much data on vitamin D preventing cancer as there was on smoking causing cancer-what are we waiting for!!!

Kat Arney September 25, 2009

Thanks for your comments everyone.

We know for a fact that excessive exposure to ultraviolet light is significant risk factor for skin cancer. This has been shown time and again in large scientific studies (for example http://info.cancerresearchuk.org/cancerstats/types/skin/riskfactors/, IARC, Solar and ultraviolet radiation. Monographs on the evaluation of carcinogenic risks to humans. 1992, Lyon: IARC Press and http://www.iarc.fr/en/publications/pdfs-online/wrk/wrk1/ArtificialUVRad&Skin5.pdf) .

It is true that messages about safe sun exposure and vitamin D are complex and difficult to communicate. Sunburn increases the risk of melanoma skin cancer and we would not want to see people deliberately getting burnt in order to boost their vitamin D levels. Furthermore, it is impossible to give a “one size fits all” message – different skin types produce different amounts of vitamin D, and people’s diets and UV exposure vary widely.

We don’t do things ‘covertly’ – and we don’t take decisions on messages unilaterally but on consensus. As more evidence about vitamin D and cancer has come to light, we have adjusted our SunSmart messages over time, as befits a research-based organisation. For example, we have worked with a large group of experts from various fields as new evidence emerges, and, once we felt the balance of the literature on vit D and cancer warranted it, we altered the wording of leaflets to reflect the changing situation with regard to vitamin D. We have provided plenty of information and discussion about this on our SunSmart website/ and here on the blog.

Based on the current weight of scientific evidence, our SunSmart advice is to enjoy the sun safely, and take care not to burn. The rate of melanoma is rising dramatically in the UK, and we have a responsibility to promote awareness of how to prevent the disease.

Mike – in answer to your question “How is it that organizations such as cancer research UK have still not conducted these studies or even started them?” Cancer Research UK is funding the work of Professor Lesley Rhodes in Manchester precisely to try and answer some of these questions.

Kat

Kevan Gelling September 24, 2009

> “We know that we all need a bit of sunshine in our lives”

After the success of the SunSmart campaign I suspect most people don’t know this.

The original SunSmart message was sun = bad (from SunSmart 2003 leaflet: ‘there is no such thing as a safe tan’, ‘the sun is most dangerous in the middle of the day’ and ‘apply sunscreen … before you go outside’). The current SunSmart campaign has been subtly (and silently) changed to allow for some sun exposure, but only in the shade (50% less UVB) and “together with” a sunscreen of SPF 15+ (93% less UVB).

> “vitamin D supplements .. cause harm if taken in large does without medical supervision”

The 2003 FSA advice is out-dated, based on the incorrect assumption that vitamin D2 and D3 are equivalent and was influenced by discredited research (www.vitamindcouncil.org/worst_science.shtml).

In the US, the NIH has updated its advice (ods.od.nih.gov/factsheets/vitamind.asp) and notes ‘substantially larger doses administered for a short time or periodically (e.g., 50,000 IU/week for 8 weeks) do not cause toxicity’

> “most people make more than enough vitamin D after a just a short time in the sun”

This is contrary to recent research that suggests that a majority of the population in the UK and the US do not have enough vitamin D.

And prospective studies suggest that in Scotland, because of sun strength, it is highly unlikely that even the most dedicated sun-worshipper in Scotland could make enough vitamin D by sun exposure alone.

> ” continually reviewing the scientific evidence”

CRUK has been keen to point out the flaws in current vitamin D research – as the saying goes “correlation does not show causation”. This is a noble (and maybe the proper) position to take, however, this approach has not been applied to its own advice. SunSmart has been based on a correlation between sunburn and melanoma (sun = sunburn, therefore sun = skin cancer), but where is the evidence showing causation? And, more importantly, where are the large-scale RCTs that show that the SunSmart solution – avoid the sun – reduces melanoma and does not have any “unintended consequences”?

It has been calculated that for every skin cancer death that SunSmart has prevented, 2000 deaths have been caused because of a lack of vitamin D (Lucas, R.M., et al., Estimating the global disease burden due to ultraviolet radiation exposure. Int J Epidemiol 2008).

mike September 24, 2009

The data on vitamin D playing a major role in cancer prevention has been evolving for 30 years and still all we hear is the need for further studies. How is it that organizations such as cancer research UK have still not conducted these studies or even started them. Folk who live in sunny areas have vitamin D levels of 50-70ng/ml. You are lucky if your levels of over 20 living in the UK. Correct your deficiency and worry about the clinical trials later.

Pete September 22, 2009

As an ex cancer suffer, I recommend all who will listen to take 5,000 to 10,000IU of D a day. It is a pity I only read the literature AFTER I got cancer, otherwise I may have been able to avoid it.

If nothing else the reduced risk of infection from vitamin d will make the chemotherapy easier.

Those who have listened have been able to stop taking statins and blood pressure tablets as they no longer need them. They catch less colds and are much healthier. They are also less likely to burn in the sun.

Pete September 22, 2009

People do not get enough vitamin d from casual sun exposure, otherwise why did recent research show that 70% of USA children were deficient. Neither is sun bathing any use as you cannot make vitamin d all year round. The risks from supplements is massively overstated in the none specialist literature, it has become an urban myth. See Vitamin D and Cancer Mini-Symposium: The Risk of Additional Vitamin D, REINHOLD VIETH, doi:10.1016/j.annepidem.2009.01.009, this presents data that shows that 10,000IU of d3 a day plus sun exposure does not lead to toxicity (most people need this amount to reach optimum levels).

The eatwell.gov website has failed to keep up with modern research and the levels recommended are stupidly low (400IU a day). With full body exposure at midday the body makes 10,000 to 20,000IU a day, Why would it make so much if it needed so little. The site says most people get enough vitamin d from food and sun which given the research published giving peoples vitamin d levels is also rubbish.