Fight against cancer: Vitamin D helps slow melanoma growth and spread, says study

07 Nov 2019 --- Vitamin D contributed to slowing the growth of melanoma cells and stopped their spread to the lungs of mice. These were the findings of a University of Leeds study, which found that the vitamin influences the behavior of a signaling pathway within the cells. The researchers have highlighted that insights from this study could be used to boost the effects of immunotherapy and lead to new ways to treat the skin cancer. However, experts are flagging that the results should not be interpreted as an excuse for people to stay in the sun for excessive periods of time.

“Our work suggests that we should avoid vitamin D deficiency at all points of the year, rather than aim for high levels. Therefore, modest supplementation all year round seems sensible in Northern Europe. The UK Scientific Advisory Committee on Nutrition suggests 400 IU per day as a total amount from foods and supplements, and I believe this to be good advice for all of us – especially melanoma patients. Published literature also suggests that what we have said about melanoma also applied to bowel cancer,” Professor Julia Newton-Bishop from the University of Leeds and an author of the study, tells NutritionInsight.

It was already known that lower bodily levels of vitamin D were linked to worse outcomes for people with melanoma, but the mechanism was unknown. Newton-Bishop details a 2009 study where her team found that people taking vitamin D supplements were less likely to have a recurrence of melanoma.

This time, the research team examined the gene that makes vitamin D receptor (VDR), a protein on the surface of the melanoma cells that vitamin D to bind to the cell’s surface. The gene’s activity was explored in 703 human melanoma tumors, as well as 353 human melanoma tumors that had spread from the initial site.

Tumors with lower VDR levels had a higher activity of genes linked to cancer growth and spread.It was found that the tumors with low levels of the VDR gene grew faster, as well as having a lower activity of the genes that control pathways helping the immune system fight cancer cells. This was discovered through cross-referencing the activity of the VDR gene with other patient characteristics, such as the thickness of their tumor and how fast their tumor grew. 

A causal biological pathway
The team also wanted to see if the amounts of VDR in human melanoma cells were associated with genetic changes that happen when tumors become more aggressive. Indeed, tumors with lower VDR levels had a higher activity of genes linked to cancer growth and spread, especially those controlling the Wnt/β-catenin signaling pathway, which helps to modulate a variety of biological processes within the cell, such as its growth.

“This study allowed us to identify that the biological pathway is most likely causal. Since we started working on the biological correlates of vitamin D, a role for the beta-catenin pathway in defining immune responses to melanoma has become recognized. That we found an association between vitamin D and its receptor together determining activation of the beta-catenin pathways, therefore, is consistent with data suggesting that VDR and the beta-catenin pathway are both important in melanoma,” notes Newton-Bishop.

She continues that a major obstacle was overcoming the degree of caution surrounding the role of vitamin D in many aspects of health. It also took numerous years to recruit sufficient numbers of patients to these studies. They are designed to build large data sets powerful enough to generate convincing data for a causal relationship between vitamin D deficiency and melanoma.

The researchers then used mice to check whether VDR levels changed the cancer’s ability to spread. They found that increasing the amount of VDR on the melanoma cells reduced the activity of the Wnt/β-catenin pathway, and slowed down the growth of the melanoma cells. They also found that the cancer was less likely to spread to their lungs.

Safe sunbathing?
There is an irony that sun exposure is both the main source of vitamin D and is connected to melanoma. “However, we know that the sort of sun exposure that causes melanoma is something of an extreme – predominantly intense exposure leading to sunburn – in people who are already vulnerable. These are pale-skinned people, those with a family history of melanoma, and those with many moles,” says Newton-Bishop.In Northern Europe, it is not possible to generate enough vitamin D from sun exposure in winter.

Her view is that regular sun exposure that is unassociated with red or burnt the skin is likely to be beneficial but sunburn to be harmful. However, what is gentle and what is sufficient in terms of sun exposure will depend on skin type.

“There is a balance to be struck when spending time in the sun. Some sunlight helps us produce vitamin D, but sunburn or too much exposure can cause melanoma. The amount of time you need in the sun to make enough vitamin D depends on your skin type, time of day or year and where you are in the world. Overall, the balance is probably less time outside than you think – minutes rather than hours,” Weilin Wu, Health Information Officer at Cancer Research UK, tells NutritionInsight.

Furthermore, in Northern Europe, it is not possible to generate enough vitamin D from sun exposure in winter. “During these months, the only option is to derive sufficient vitamin D from fortified foods or supplements,” advises Newton-Bishop. 

A recent slew of studies have highlighted the potential of vitamin D. Earlier this year, it was found vitamin D supplementation reduces the risk of cancer death by 16 percent. Meanwhile, patients with Parkinson’s disease were found to have significantly lower levels of vitamin D in their blood, and a separate study found that supplementation of the vitamin may slow the progression of Type 2 diabetes. 

By Katherine Durrell