COMMENTARY

Vitamin D and Colon Cancer

David J. Kerr, CBE, MD, DSc, FRCP, FMedSci

Disclosures

July 02, 2014

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Hello. I am David Kerr, Professor of Cancer Medicine at University of Oxford. I have had a long-standing interest in the biology of the treatment of colorectal cancer. I have always been fascinated by the potential role of vitamin D.

Recently, I picked up a very interesting new type of analysis that was conducted by Professor Theodoratou and colleagues and reported in the British Medical Journal.[1] It was something called an "umbrella review." I haven't come across this term before, but it's when a school of professionals make an overview of meta-analyses across the literature for a topic, such as vitamin D. They performed this umbrella review not just for cancer but across all of health, including much work in musculoskeletal disorders, cardiovascular disorders, and cancers.

They found 107 systematic literature reviews, 74 meta-analyses of observational studies of plasma vitamin D concentrations, and 87 meta-analyses of randomized controlled trials of vitamin D -- a huge body of literature that has been summarized and reviewed repeatedly, with a whole variety of nicely methodologically and statistically strong results. Where does it take us?

The role of vitamin D in colorectal cancer prevention, and possibly in treatment, is biologically plausible. We know that there are receptors there. The enzymes responsible for the activation of vitamin D to 1,25 dihydroxyvitamin D -- the biochemistry machinery -- is presently known in vitro in animal models. Vitamin D has important effects on cell growth, cell morphology, and cell cytokinetics -- a whole range of biological factors that would be relevant and germane to the control of cancer.

There are many observational studies. A vast literature has been summarized many times over. The conclusion of this umbrella review was that in cancer, particularly colorectal cancer, the evidence is suggestive of benefit for vitamin D.

The authors pointed out that despite biological plausibility and a positive trend toward improvements in outcomes, in terms of prevention and in terms of reducing elements of disease recurrence, there were insufficient prospective randomized trials. There is a key gap in the knowledge -- the defining evidence, the "home run" if you like -- that we would require to be utterly convinced of the role that vitamin D plays in the prevention and treatment of colorectal cancer.

There is a big question about the dose of vitamin D. Should we seek to replenish and to treat toward what we think is the internationally recognized normal range? Should we be giving the recommended dose of 400-600 IU per day? Should we be going higher? There are trials of 3000-4000 IU per day.

What is interesting is that for those of us who live in the north (I'm Scottish, as you can tell by the accent), there is no doubt that there is an inverse correlation between vitamin D levels and the propensity to develop colorectal cancer. In the northern and darker Scandinavian countries, Scotland, Iceland, Norway, Sweden, and Denmark, there is a relative lack of vitamin D, with long, dark nights and short, often wintery summers.

When I worked in Qatar -- probably the sunniest place on earth -- when we systematically checked vitamin D levels with my colleague there, Dr. Kakil Rasul, we found very high levels of hypovitaminosis D in the sunniest place on earth. That seemed to be because it was too hot to go out, and therefore in common with Qatari citizens, we spent a lot of our life indoors in air-conditioned boxes, moving from an air-conditioned car to a shopping mall to an office; rarely did we go out in the sun.

In Australia, the land of the sun, there has been a huge campaign to reduce overexposure to the sun and risk for melanoma. There are very high levels of hypovitaminosis D there, too. There are no definitive answers.

I lean toward saying that vitamin supplementation at a safe, normal range of delivery seems like a reasonable thing to do with the likelihood of having some benefit, but there is absolutely no hard evidence for this. Along with aspirin, vitamin D might be one of those things that we should consider taking. For patients who live in the north and have had resection of colorectal cancer, it may be worthwhile.

I can't say anything stronger than that, but watch the literature, and let's look out for a planned prospective randomized trial to give us definitive evidence that we require to make stronger recommendations than a vaguely intuitive feeling from an old, tired, over-the-hill oncologist like myself.

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