Vitamin D and Skin Cancer – More Than Just Skin Deep?

There has been an explosion of research into vitamin D for many years now. The research is telling us that vitamin D has far more wide ranging effects than we ever would have believed in the past. Almost every organ in the body has receptors for vitamin D. Why? Nature doesn’t do things like that without a reason. Those reasons are slowly becoming apparent. Low vitamin D is a risk factor for other cancers, autoimmune diseases, diabetes, cognition, autism, all cause mortality and the list continues.

The link between low vitamin D and cancers got me wondering. What is the link between vitamin D and the different types of skin cancers? If skin cancers are as a result of cumulative sun exposure then I would expect that skin cancer patients would have adequate to high levels of vitamin D. That seems a logical conclusion. Right?

Last year with the break during the festive season I thought that I would answer my own question and do a PubMed search on Vitamin D + Melanoma. Yes I research for fun! Sad but true. However, it didn’t take long to find out something very interesting.

  1. Vitamin D levels in skin cancer patients were low
  2. Individuals with newly diagnosed skin cancer were not outdoor workers (tradesmen, landscapers and the like) but office workers. What?

Just recently the advertisements have started in the media to “Slip, Slop, Slap” to prevent skin cancer. So I thought it would be interesting to revisit the research that has been published in the last 12 to 24 months in relation to vitamin D and the development of skin cancers. Some of the research did not surprise me as it confirmed the findings above, however some other research is beginning to concern me.

Sun Exposure and Melanoma

The relationship between sun exposure and melanoma risk is complex. There are many variables like skin types (red or blond hair with freckles), location, vitamin D receptor polymorphisms, etc. Sun exposure or ultraviolet (UV) radiation has always been considered to induce direct (UVB) and indirect (UVA) oxidative DNA damage that can lead to carcinogenesis. Recent studies suggest that UVA radiation plays a role in the development of melanoma, not necessarily through direct DNA damage but through oxidative stress, free radical generation, and the degradation of vitamin D. As mentioned above if malignant melanoma were related to cumulative sun exposure, one would expect that outdoor workers would have a greater incidence of melanoma than indoor workers. However, the incidence of malignant melanoma is actually increasing among indoor workers who receive three to nine times less solar UV radiation than outdoor workers.

It seems that the risk factor is sunburn. Those with chronic sun exposure without sunburn have a reduced incidence of malignant melanoma compared with those with recreational (intermittent) sun exposure. So what may be going on here?  Chronic, repeated sun exposure may allow the skin to get accustomed to UV radiation by increasing melanin production, thereby reducing the risk of sunburn. Hence it is suggested that sunburns, and not cumulative sun exposure, leads to the increased risk for malignant melanoma. Now these studies are not done in countries like Australia (described as “melanoma capital of the world”) that have very high sun exposure. Indeed in Australia occupational sun exposure appears to be associated only with melanoma of the head and neck.

So the counselling and public awareness campaigns perhaps should be concentrating more on sunburn as a risk factor for malignant melanoma rather than avoidance of sun exposure.

Sunscreens and Risk of Melanoma

We expect that the use of sunscreens should decrease the risk of malignant melanoma. However, when used improperly sunscreens can potentially increase the risk for malignant melanoma by conferring a false sense of protection against sunburn. This false sense of protection can lead to more time spent in the sun, paradoxically causing a greater incidence of sunburns. A number of studies have shown a correlation between the use of sunscreen and increased incidence of sunburn. In a Swedish study, children aged 2 to 7 whose parents had applied sunscreen on them were more likely to experience sunburn than those who received little or no sunscreen. An Australian study published in 2011, showed that consistent daily application of both UVA and UVB-filtering broad-spectrum sunscreen resulted in a decreased incidence of melanoma compared with control. What should be noted about this study is that the control group was also allowed to use sunscreen as well, but was not guided as to type of sunscreen used or the frequency of application. Therefore, only daily, consistent use of broad-spectrum sunscreen, but not intermittent use of sunscreen, was associated with decreased risk of malignant melanoma. Also, participants in the intervention group were given free unlimited broad-spectrum sunscreen, but not the control group. Therefore the financial feasibility of this intervention needs to be considered. It was suggested that part of the reason the control group applied sunscreen less frequently may possibly have to do with cost. The cost to the individual for this intervention may hamper compliance.

Vitamin D Levels and Melanoma

There are numerous current and retrospective studies that show low serum vitamin D is associated with a higher incidence of colorectal, lung, breast and other types of cancers. This association with low vitamin D levels is also showing that there is an increased risk for the worst development of the disease and poorer overall prognosis. Additional studies show higher vitamin D status to be associated with a lower incidence of cancer.

I could never get my head around anything more than basic statistics, and I know that statistics can be “massaged” to get the results you are looking for. So I like to look at the raw data where I can. The table below shows vitamin D levels in cutaneous (skin) melanoma patients versus controls. If you look at the numbers you can clearly see the shift with low vitamin D status in melanoma patients compared to controls.

articleImage5

Source: 25-OH Vitamin D and Interleukin-8: Emerging Biomarkers in Cutaneous Melanoma Development and Progression.

In May 2015 an Australian study was published that investigated 100 melanoma patients in Brisbane, Australia. The patients were recruited just days after their diagnosis. Their vitamin D levels were tested, their tumour thickness was measured and their progress was monitored. The conclusion of the study: “Vitamin D deficiency at the time of melanoma diagnosis is associated with thicker tumours that are likely to have a poorer prognosis. Ensuring vitamin D levels of 50 nmol/L or higher in this population could potentially result in 18% of melanomas having Breslow thickness of <0.75 mm rather than ≥0.75 mm.”

 Vitamin D and Vitamin A – Keep them apart?

Since vitamin A metabolites and vitamin D bind to the same receptor, there is a hypothesis that high vitamin A levels may reduce the levels of vitamin D. The Western Price Foundation has raised this issue some time ago as has Dr Mercola, and there has been quite a bit of discussion since to downplay the issue. Note that we are only talking about dietary supplementation of vitamin D here. In relation to the antagonistic effect of vitamin A, a study in 2013 found that high vitamin A levels may reduce the protective effect of vitamin D. High levels of vitamin A were associated with a higher risk of melanoma specific death. The suggestion is that vitamin D supplementation alone might be preferable than preparations containing vitamin D and A in the prevention of melanoma.

Nutrition and Melanoma

An interesting study in 2014, reviewed and looked at the role of nutrition and other natural compounds in the prevention and treatment of melanoma. They found that: “Grape seed proanthocyanidins, epigallocatechin-3-gallate, resveratrol, rosmarinic acid, lycopene, and fig latex have demonstrated clear anticancer effects toward melanoma. The roles of selenium, vitamin D, and vitamin E, however, have been more controversial.” So there is definitely a protective effect from the consumption of fruit and vegetables as well as herbs that contain these compounds in the prevention and treatment of melanoma.

When to Get Maximal Vitamin D From Sun Exposure?

There are different ultraviolet (UV) rays from the sun including UV-A and UV-B. The variations in UV-A (relevant to melanoma) and UV-B (relevant to melanoma and vitamin D production) over the day is dependent on the position of the sun in the sky. In a study that looked at the optimal UV-B : UV-A ratio to obtain vitamin D, they found that this is maximised at noon. Their conclusion was: “The best way to obtain a given dose of vitamin D with minimal carcinogenic risk is through a non-burning exposure in the middle of the day, rather than in the afternoon or morning.” This goes against the advice being given, where it is recommended to go out early morning or late afternoon and avoid sun exposure at midday.

Vitamin D and Cardiovascular Risk

There is a growing body of evidence to show that vitamin D may increase cardiovascular risk. In adults, observational studies have found that lower vitamin D levels are associated with metabolic syndrome, obesity, hypertension, diabetes, myocardial infarction, stroke and overall cardiovascular death. In older children and adolescents, lower vitamin D levels have also been associated with traditional cardiovascular disease risk factors including obesity, elevated systolic blood pressure, decreased high density lipoprotein (HDL) cholesterol, and insulin resistance. A recent study looked at vitamin D levels in 1 to 5 year old children, and lipid blood levels. Their findings also showed an association between low vitamin D and higher non-fasting triglycerides and total cholesterol. There is some suggestion that higher cholesterol levels are as a result of the body trying to produce sufficient vitamin D. If the body is low in vitamin D, it ramps up the production of cholesterol in the hope that more can be converted into vitamin D. An interesting hypothesis to consider.

A Sign of Worse Things to Come?

My concern is that the cost of vitamin D testing is no longer covered by the Medicare benefits schedule and fewer patients will be able to claim a rebate for their vitamin D screen. In the past 10 years, there has been an almost 4,000 per cent jump in the number of patients having their vitamin D levels checked. So the Government has decided to limit the eligibility for a rebate to people with deeply pigmented skin, osteoporosis or those with chronic lack of sun exposure. Considering the link between low vitamin D levels and many other chronic diseases, the cost of prevention is minimal compared to the long-term cost of having to treat these diseases in the future. If you don’t test you will never know if you are low. Most tissues in the body have receptors for vitamin D. They are there for a reason! Get your vitamin D levels checked regularly – prevention is better than cure!

So the message to myself

I need to stop spending hours of time on my computer researching and get outside into the sun – BUT don’t get burnt and eat a lot of antioxidant foods. Hope to see you outside for lunch with lots of coloured fruit and vegetables!

References

Vitamin D and melanoma. Field S, Davies J, Bishop DT, Newton-Bishop JA. Dermatoendocrinol. 2013 Jan 1;5(1):121-9.

Sunscreen and melanoma: is our prevention message correct? Planta MB. J Am Board Fam Med. 2011 Nov-Dec;24(6):735-9

Reduced melanoma after regular sunscreen use: randomized trial follow-up. Green AC, Williams GM, Logan V, Strutton GM. J Clin Oncol 2011;29(3): 257–63.

25-OH Vitamin D and Interleukin-8: Emerging Biomarkers in Cutaneous Melanoma Development and Progression. Corina-Daniela Ene,1 Amalia-Elena Anghel, Monica Neagu, and Ilinca Nicolae. Mediators of Inflammation. Volume 2015 (2015).

Association between Vitamin D and Circulating Lipids in Early Childhood. Birken CS, Lebovic G, Anderson LN, McCrindle BW, Mamdani M, Kandasamy S, Khovratovich M, Parkin PC, Maguire JL; TARGet Kids! collaboration. PLoS One. 2015 Jul 15;10(7).

Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort. Lindqvist PG, Epstein E, Landin-Olsson M, Ingvar C, Nielsen K, Stenbeck M, Olsson H. J Intern Med. 2014 Jul;276(1):77-86.

Bidirectional associations between circulating vitamin D and cholesterol levels: The Rotterdam Study. Vitezova A, Voortman T, Zillikens MC, Jansen PW, Hofman A, Uitterlinden AG, Franco OH, Kiefte-de Jong JC. Maturitas. 2015 Dec;82(4):411-7. Epub 2015 Aug 21.

Daily seasonal and latitudinal variations in solar ultraviolet A and B radiation in relation to vitamin D production and risk for skin cancer. Grigalavicius M, Moan J, Dahlback A, Juzeniene A. Int J Dermatol. 2015 Nov 6.

Do vitamin A serum levels moderate outcome or the protective effect of vitamin D on outcome from malignant melanoma? Field S, Elliott F, Randerson-Moor J, Kukalizch K, Barrett JH, Bishop DT, Newton-Bishop JA. Clin Nutr. 2013 Dec;32(6):1012-6.

Low Serum 25-Hydroxyvitamin D Concentrations Are Associated with Increased Risk for Melanoma and Unfavourable Prognosis. Benjamin Bade, Alexander Zdebik, Stefan Wagenpfeil, Stefan Gräber, Jürgen Geisel, Thomas Vogt, and Jörg R.PLoS One. 2014; 9(12): e112863.

Nutrition: the future of melanoma prevention? Tong LX, Young LC. J Am Acad Dermatol. 2014 Jul;71(1):151-60.

On the Possible Link Between Vitamin D Deficiency and Cardiovascular Disease. Should We D-Lighten Our Lives?Pelle G. Lindqvist. Circulation. 2014; 129:e413-e414.

Serum level of vitamin D3 in cutaneous melanoma. Oliveira Filho RS, Oliveira DA, Martinho VA, Antoneli CB, Marcussi LA, Ferreira CE. Einstein (Sao Paulo). 2014 Oct-Dec;12(4):473-6.

Vitamin D deficiency at melanoma diagnosis is associated with higher Breslow thickness. Wyatt C, Lucas RM, Hurst C, Kimlin MG. PLoS One. 2015 May 13;10(5).