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Meta-analysis: How vitamin D intake and overall serum level influence risk of melanoma or non-melanoma cancers

Posted on: September 2, 2014   by  Will Hunter


A recent meta-analysis from the European Journal of Cancer found that vitamin D status was not related to the risk of developing cutaneous melanoma, but was positively related to an increased risk of developing non-melanoma skin cancers.

The meta-analysis also found that dietary intake of vitamin D was not associated with either cutaneous melanoma or non-melanoma skin cancer and that vitamin D status was inversely associated with melanoma tumor thickness at diagnosis.

Cutaneous melanoma (CM) is a type of skin cancer that forms from melanocytes, the cells in the skin that produce the pigment melanin. It is especially prevalent among Caucasians living in regions with abundant sun exposure. It is the least common of the three main types of skin cancer, however it is the most aggressive and results in three quarters of the deaths from all skin cancers.

The other two types of skin cancer, basal cell carcinoma and squamous cell carcinoma, as well as a number of less common skin cancers, are classified as non-melanoma skin cancers (NMSC).

In vitro experiments have shown that vitamin D inhibits the growth of melanoma cell lines and demonstrates an anti-tumor effect. However, studying the effects of vitamin D in vivo is more difficult, as sun exposure, a determinant of vitamin D, is considered a risk factor for developing both CM and NMSC.

Studies analyzing the effect of vitamin D on the risk of skin cancer have produced inconsistent results. However, there are a couple of studies that show that higher vitamin D levels are associated with a better prognosis of CM, suggesting that vitamin D has a beneficial effect on individuals with CM.

Due to the inconclusiveness of the current research, Dr. Caini and his team conducted a comprehensive review and meta-analysis of the literature to evaluate the effect of vitamin D intake from food or supplements and vitamin D levels on the risk of developing CM or NMSC (basal cell or squamous cell cancers). They were also interested in the association between vitamin D and CM prognostic factors.

For this study, they only used tumor thickness as a CM prognostic factor because it is the most regularly reported and is the most important prognostic factor in non-metastatic melanoma.

The researchers searched multiple databases and selected 20 studies, including ones that had observational and experimental designs, which met their predetermined criteria for inclusion.

They then performed a comprehensive analysis on the data of all 20 studies. Here’s what they found:

  • Those with the highest vitamin D levels had a significant 64% increased risk of NMSC compared to those with the lowest levels.
  • Those with the highest vitamin D levels had a non-significant 46% increased risk of CM compared to those with the lowest levels.
  • Those who had the highest reported intake of vitamin D had a non-significant 14% decreased risk for CM and 3% increased risk for NMSC, compared to those with the lowest intake.
  • There was a significant inverse association between vitamin D levels and tumor thickness in CM patients, which means that lower vitamin D levels were related to increased tumor thickness.

In their conclusion, the researchers stated,

“We reviewed and meta-analysed the existing scientific literature on the association between vitamin D blood levels and intake and the risk and prognosis of skin cancer. We found no association between the blood levels of 25(OH)D and CM risk, and a statistically significant positive association with increasing risk of NMSC for high values of 25(OH)D. We also did not find any significant association with vitamin D dietary intake (through foods and/or supplements) and CM or NMSC. Finally, vitamin D serum levels seem to be inversely associated with CM thickness at diagnosis.”

The lack of an association between vitamin D blood levels and CM surprised the researchers, considering that vitamin D levels are strongly correlated with UV light exposure and that UV light is recognized as a main risk factor for this cancer.

While the results suggest that vitamin D taken from diet or supplementation does not have a protective effect against these skin cancers, each study used different doses for different durations.

The finding that vitamin D levels are associated with tumor thickness is intriguing, however the direction of causation can’t be determined due to the design of the studies analyzed.

Adding to the already complex relationship between vitamin D, sun exposure and skin cancer, this study suggests overall vitamin D status has different effects on risk of CM and NMSC compared to vitamin D intake just from food and supplements.

Before concrete conclusions can be drawn, more research is sorely needed to accurately determine at what point the risks outweigh the benefits from sun exposure and what exact aspects of sunlight are influencing these risks and benefits.

Clinical trials are needed to determine the effect vitamin D supplementation has on the progression of skin cancer.


Caini, S. et al. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis. European Journal of Cancer, 2014.

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