A sun-sational study on vitamin D and cancer

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Anthony Tao

Sunny weather can make the difference between a bleak and mundane work day versus a day filled with joy and festivity. People generally feel better when the sun’s out. Foods taste better, music sounds livelier, and the air feels more hopeful. And the need for hope is perhaps most crucial for those suffering through the fear and pain of cancer.

However, the sun’s benefits are not limited to hope and sentimentality. Among other things, the sun is critical for the generation of active vitamin D, which has multiple roles in bone strength and immune function. Specifically, vitamin D in the blood changes cellular function by binding and acting on vitamin D receptors, or VDR. Interestingly, adequate vitamin D levels have been linked to better cancer prognosis.

For instance, high vitamin D diets have been linked to reduced cancer risks [1]. Furthermore, summer months have been associated with reduced aggressiveness of cancer, such as colorectal cancer [2]. In studies that grow tumors in a petri dish, direct application of synthetic vitamin D was shown to limit their growth [3]. This suggests that somehow, vitamin D receptors on cancer cells make them sensitive to the anti-tumor effects of vitamin D. Alternatively, low levels of vitamin D in the blood have been correlated with increased cancer risk [4].

Despite numerous studies conducted, the exact mechanism linking vitamin D to cancer progression remains elusive. It is unknown, for example, how vitamin D can influence anti-tumor immunity ‒ that is, the activity of cells in the immune system, which plays an important role in cancer killing. It is also unknown whether vitamin D can influence tumor progression by altering the gut microbiome, the flora of bacteria in our intestines that help with our digestion.

In a recent study, researchers at the Francis Crick Institute attempted to address this knowledge gap. They gave mice with melanoma, a type of skin cancer, a diet either deficient in vitamin D or containing an excess of vitamin D. Depriving these mice of vitamin D exacerbated their cancer progression by impairing anti-tumor immunity. In contrast, excess dietary vitamin D enhanced anti-tumor immunity and limited cancer growth.

The researchers originally hypothesized that the cancer-killing effects of vitamin D might be attributed to its direct effect on immune cells. However, they realized that the gut microbiome may play a role. What clued them into this possibility were several findings. For one, the anti-tumor effect of vitamin D disappeared when germ-free mice were used. These mice are specifically bred to have an absent microbiome. Secondly, fecal transplant from mice with a high vitamin D diet into mice with a vitamin D deficiency transferred the anti-tumor effects into the vitamin D-deficient mice. Fecal transplantation is a common method of transferring the gut microbiome from one subject to another. These findings suggest that vitamin D influences the gut microbiome, which in turn, influences anti-tumor immunity (Figure 1).

The question that remained was how does vitamin D alter the gut microbiome? To address this question, the researchers turned to metagenomics, which leverages large-scale DNA sequencing methods to identify and quantify thousands of different species of bacteria present in the gut. By comparing the gut microbiome of vitamin D-sufficient versus vitamin D-deficient mice, they found that vitamin D significantly enhances the population of a specific bacterial species known as Bacteroides fragilis (B. fragilis). Moreover, transplantation of this bacteria into vitamin D-deficient mice was capable of limiting cancer growth and enhancing anti-tumor immunity. Thus, the authors conclude that vitamin D enriches the gut microbiome for B. fragilis, which can enhance anti-tumor immunity to better attack cancers.

Overall, it is quite apparent that sunlight and vitamin D have a beneficial role in controlling cancer. The importance of the gut microbiome also highlights the importance of a healthy diet in minimizing cancer risk. Of course, it should go without saying that all vitamins and exposures should be done in moderation. Too much sun, for instance, is strongly correlated with the incidence of melanoma. Moreover, excess B. fragilis can induce a chronic inflammatory reaction in the colon, which elevates the risk of colon cancer. Striking a balance between sunlight exposure, dietary choices, and overall lifestyle habits can serve as a proactive and holistic approach to reducing cancer risk.  

Figure 1. Vitamin D promotes anti-tumor immunity by altering the gut microbiome.

Edited by Yonika Larasati

1. McDonnell, S. L. et al. Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. PLoS One 11, e0152441 (2016).

2. Moan, J., Lagunova, Z., Bruland, O. & Juzeniene, A. Seasonal variations of cancer incidence and prognosis. Dermatoendocrinol 2, 55–57 (2010).

3. Vaughan-Shaw, P. G. et al. Vitamin D treatment induces in vitro and ex vivo transcriptomic changes indicating anti-tumor effects. FASEB J 36, e22082 (2022).

4. Swarnkar, M., Kumar, K., Prasad, P. & Singhal, K. Association Between Vitamin D Deficiency and Tumor Characteristics in Breast Cancer Patients. Cureus 16, e62296 (2024).