Vitamin D is all the rage currently; everyone seems to be asking if vitamin D has a role in this disease or that disease. Only last week, I was asked if vitamin D had a role to play in eczema; as far as I am aware, there have been no large, good quality studies that have investigated this nor shown a role.
What diseases does vitamin D have a role in then?
There have been some studies, however, in recent years suggesting that high levels of vitamin D in the blood may be associated with a decreased risk of colorectal cancer and possibly breast cancer.
[Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-81.]
Other studies suggest that the risk may actually be U- shaped, in that low levels of vitamin D in the blood and also very high levels may be associated with an increased risk of disease progression, especially concerning breast cancer and cardiovascular disease.
[Goodwin PJ, Ennis M, Pritchard KI et al. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol 2009; 27: 3757-3763.}
[Wang TJ, Pencina MJ, Booth SL et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117: 503-11.]
What can I do about my levels of vitamin D?
The amount of vitamin D in the blood is determined by sun exposure, the level of pigmentation of the skin (ie how dark your skin is) and by diet and supplementation from vitamin tablets. Sunlight stimulates vitamin D production in the skin and darker-skinned individuals tend to have lower levels of vitamin D than paler-skinned individuals at the same latitude.
So what does vitamin D have to do with melanoma?
Dermatologists have preached for many years the benefits of sun avoidance. Exposure to ultraviolet (UV) radiation from the sun is the primary risk factor in the development of skin cancers, namely malignant melanoma, and also squamous cell carcinomas and basal cell carcinomas. The UV rays in sunlight cause DNA damage to the cells in the skin, which after a lot of sun, can give rise to skin cancers.
Interestingly though, there have been some studies in recent years showing associations in melanoma patients between lower vitamin D levels in the blood at the time of diagnosis and thicker (ie worse) tumours and a worse prognosis (ie future outlook).
[Newton-Bishop JA, Beswick S, Randerson-Moor J et al. Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma. J Clin Oncol 2009; 27: 5439-44.]
[Hutchinson PE, Osborne JE, Pringle JH. Higher serum 25-hydroxyvitamin D3 levels at presentation are associated with improved survival from melanoma, but there is no evidence that later prevailing levels are protective. J Clin Oncol, 2010: 28(27): e492-493; author reply 494-495.]
[Randerson-Moor JA, Taylor JC, Elliott F et al. Vitamin D receptor gene polymorphisms, serum 25-hydroxyvitamin D levels and melanoma: UK case-control comparisons and a meta-analysis of published VDR data. Eur J Cancer 2009; 45(18): 3271-3281.]
That doesn’t make sense! So, should patients with melanoma expose their skin to more sun?
Clearly, the advice cannot be to expose the skin of these patients to more sunlight in an attempt to produce more vitamin D. These patients have already developed one skin cancer and are at an increased risk of developing more.
However, the issue that is controversial is whether we should be monitoring vitamin D levels in melanoma patients and also whether melanoma patients should be receiving vitamin D supplementation to improve their outlook.
What evidence is there for this?
The evidence so far is not helpful either way. Vitamin D levels are consistently low in studies all over the world, whether you have melanoma or not and irrespective of the colour of your skin and yet, the optimal level of vitamin D in the blood is unclear and not agreed upon.
A level of 60-75 nmol/L is suggested in the scientific papers but this level is taken because any level higher than this causes suppression of a hormone released by the brain which is involved in vitamin D and calcium balance (parathyroid hormone or PTH).
Not knowing to which level to supplement could be dangerous as high levels of vitamin D could be just as dangerous as too little.
There is some evidence that melanoma cells possess a receptor for vitamin D and proliferate less in the presence of vitamin D in laboratory studies. Also, some papers suggest that there is an inherited genetic variation in the protein that binds vitamin D which also affects vitamin D levels in the blood and also the occurrence and outcome of malignant melanoma.
[Denzer N, Vogt T and Reichart J. Vitamin D receptor (VDR) polymorphisms and skin cancer: a systematic review. Dermato-Endocrinol 2011; 3(3): 205-10.]
[Davies JR, Chang YM, Snowden JH et al. The determinants of serum vitamin D levels in participants in a melanoma case-control study living in a temperate climate. Cancer Causes Control 2011; 22(10): 1471-82.]
However, more recent studies looking at the genetics of the proteins involved in vitamin D have shown no association with melanoma risk or prognosis (how patients will do going forwards), and another paper found no association between vitamin D levels in the blood and risk of melanoma in men.
[Schäfer A, Emmert S, Kruppa J et al. No association of vitamin D metabolism-related polymorphisms and melanoma risk as well as melanoma prognosis: a case-control study. Arch Dermatol Res 2012; 304: 353-61.]
[Major JM, Kiruthu C, Weinstein SJ et al. Pre-diagnostic circulating vitamin D and risk of melanoma in men. PLoS ONE 2012; 7(4): e35112.
To top it all off (and make it even more confusing) the most recent study, published in November 2012, takes us full circle back to the beginning of the argument. The study in question is a large study with over 28 years of follow up data and including over 600 patients.
[Afzal S, Nordestgaard BG, Bojesen SE. Plasma 25-hydroxyvitamin D and risk of non-melanoma and melanoma skin cancer: A prospective cohort study. J Invest Dermatol 2012. Epub ahead of print.]
This study showed that increasing vitamin D levels in the blood were associated with an increased risk of melanoma and also of what we call non-melanoma skin cancers, ie squamous cell carcinomas and basal cell carcinomas.
This would make logical sense as we know that the more the skin is exposed to the sun, the more vitamin D it produces and we also know that the more we expose our skin to the sun the higher the risk of skin cancer.
There is a clear need for more research in this area but for now, there is no convincing evidence for vitamin D testing nor for vitamin D supplementation in melanoma patients.
Regards,
Sandy
Dr Sandy Flann, Consultant Dermatologist
