Vitamin D Deficiency And Prostate Cancer: Is There A Link?

Prostate cancer is a significant cause of cancer-related mortality in men worldwide, ranking among the top five (1)

However, after ongoing research, we don’t know the exact causes of prostate cancer. Instead, we have a few risk factors.

While some risk factors such as genetics and race cannot be modified, others such as diet and physical activity can. (2) While some risk factors for prostate cancer, such as genetics and race, cannot be modified, others, like diet and physical activity, may play a role (2). Some studies have suggested that specific vitamins, including vitamin D, could potentially influence the risk of developing prostate cancer.

Vitamin D is a crucial nutrient in the human body. It helps our bones stay strong and keeps our levels of calcium and phosphate in check. (3)

Is there ongoing research into the potential relationship between vitamin D and prostate cancer, and could vitamin D supplements have a role in cancer prevention?

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Prostate cancer incidence and vitamin D

Interestingly, prostate cancer prevalence is reduced in countries with higher sun exposure. This is apparently due to an increase in vitamin D synthesis (5). However, the connection between prostate cancer and vitamin D appears to be inconclusive.

The World Cancer Research Fund Continuous Update Project evaluates the link between cancer and diet. They report divergent results in the scientific literature. Thus, they say it is still soon to raise any conclusion about prostate cancer and vitamin D (6).

For example, some studies show that vitamin D deficiency increases the risk. In contrast, others suggest that high concentrations have the exact same result.

The reason for these differences in the studies might be that they used small groups of people. But it also seems that our genes play a role in how vulnerable we are to prostate cancer. So, we need more research to really understand how vitamin D and prostate cancer are connected.

What about prostate cancer progression?

For individuals with a prostate cancer diagnosis, vitamin D appears to offer some promise as a supplementary treatment option. Randomized trials involving human subjects have suggested that vitamin D supplements may have a modestly positive effect, particularly in patients with preexisting vitamin D deficiency (8).

A recent systematic review and meta-analysis have shed further light on the potential relationship between vitamin D and prostate cancer progression. This comprehensive study examined circulating levels of vitamin D and their impact on survival rates.

In other words, patients with cancer survive for longer when they have higher vitamin D levels. They may even survive prostate cancer longer without experiencing any progression at all (9).

What the research says

If we consider the investigation so far, we can raise a few educated conclusions.

For instance, let us review the research on prostate cancer incidence, and vitamin D. A U-shaped association may explain what appears to be diverging results. In other words, both deficient levels and very high levels of vitamin D could be linked with a higher incidence.

What we need to reach is that point in the U-shaped curve where we get appropriate levels. Not low levels, and not very high levels, either. Some authors have reached this conclusion because (10):

  • Among people with vitamin D deficiency, the incidence is higher in those with the lowest level.
  • Among people with high vitamin D levels, the incidence is higher in those with the highest level.

So, a U-shaped association is a hypothesis currently on debate. It takes into consideration the studies so far, and it is an interesting proposal. Thus, according to research, the most recommended levels of vitamin D to prevent prostate cancer are under the range of 20 to 30 ng/ml. (11).

Further considerations

However, we should still consider that higher levels of vitamin D may be useful for other types of cancer. That’s especially the case of colorectal cancer. Therefore, there is not a single preventative recommendation for all patients. Instead, urology specialists should evaluate the risk and provide recommendations accordingly.

On the other hand, vitamin D appears to be very useful in controlling prostate cancer patients and increasing apoptosis (cell death).

Vitamin D is also useful for cell differentiation. This process prevents the conversion of new healthy cells. However, the exact mechanisms in patients with prostate cancer are still elusive. Some authors suggest that vitamin D influences testosterone levels, and that’s how it modulates prostate cancer. (12).

Vitamin D supplements and prostate cancer progression

Using vitamin D supplements in patients with cancer may slow down cancer progression.

For example, an open-label trial evaluated the effect of 4,000 UI of vitamin D in prostate cancer. These prostate cancer patients took the supplement every day for one year.

The PSA levels remained the same, but there were other changes. 55% of the patients reduced the number of positive cancer cores in biopsies in some cases. In other cases, the Gleason score was significantly reduced in localized prostate cancer (13).

Other recent studies have used vitamin D receptor agonists instead of vitamin D supplements. By stimulating vitamin D receptors, researchers found a 30% decline in PSA levels.

It only took 3 months to register this change in 85% of the studied patients. The reduction of PSA was higher than 50% in 76% of these patients. These are encouraging news. They show a potential therapeutic option in vitamin D supplements (14).

In a nutshell, the recommended vitamin D level for prostate cancer patients is 30 ng/ml or more. Reaching 30 ng/ml appears to reduce mortality rates and cancer recurrence.

To achieve these levels, it will be appropriate to use vitamin D3 supplements. As we do, we should also monitor blood levels. In the future, it might be possible to use vitamin D receptor agonists, too. However, they still need more extensive clinical trials to evaluate the safety of these drugs (10).

Is there an explanation?

How can we explain the association between vitamin D and prostate cancer? The exact mechanism is unknown. However, there are many hypotheses we can consider. One of the most accepted mechanisms is through the anti-inflammatory potential of vitamin D.

Vitamin D inhibits the production of inflammatory cytokines. It acts in the macrophages and monocytes, but also in prostate cells. In these cells, it inhibits the expression of IL-6, IL-8, and TNF. They mediate inflammatory reactions.

Moreover, TNF and IL-6 upregulate the expression of calcium-sensing receptors (CaSR). High levels of CaSR increases the risk of lethal prostate cancer. Thus, by reducing levels of IL-6, vitamin D is thought to reduce CaSR. As a consequence, it reduces the risk of aggressive prostate cancer. This mechanism can be confirmed.

In the presence of calcitriol (metabolized from vitamin D), CaSR levels are reduced. Thus, the anti-inflammatory potential of vitamin D has a protective role in the progression of prostate cancer (10).

Other risk factors for prostate cancer

Vitamin D is apparently an important risk factor for prostate cancer. But it is not the only one. As mentioned above, there are many other modifiable and non-modifiable risk factors. According to the American Cancer Society, we can divide the risk factors into two types (2):

  • Endogenous risk factors: These risk factors are naturally found in your body, and the majority of them cannot be changed.
  • Exogenous risk factors: These risk factors come from the outside, and the majority of them are modifiable.

Thus, let us briefly review each one of them and how they affect prostate cancer incidence and progression.

Endogenous risk factors

The most important risk factors associated with your organism are as follows (2):

  • Family history: If you have family members with prostate cancer, your risk will be higher. That’s especially the case when it is a first-degree family member, including brothers and your father. The greater the number of relatives affected by prostate cancer, the higher risk you have to be diagnosed with the same disease.

  • Hormones: Prostate cancer cells depend on hormones to continue replicating. In this regard, it is similar to breast cancer. That’s why manipulating hormones is a form of therapy. In practice, low androgen bioactivity can be associated with a higher risk. But very high levels of testosterone for a long time can also increase the risk. The association between prostate cancer and testosterone is quite complex. Thus, there is not a single recommendation that works for all patients in this regard.

  • Race: Prostate cancer is more common in African Americans than Whites. Hispanic men are usually diagnosed earlier than white men. This difference is probably due to a difference in androgen levels and some genetic polymorphisms.

  • Age: As we age, a few changes take place in the body. DNA adducts accumulate over time, and oxidative stress increases. Free radicals are continuously changing body structures, and DNA becomes progressively damaged. Additionally, inflammation adds to the problem along with chronic disease. All of this causes an increase in the incidence of prostate cancer.

Exogenous risk factors

The most important risk factors associated with the environment are as follows (2):

  • Diet and nutrition: Many aspects of the diet influence prostate cancer risk. For example, high-fat food increases the risk of prostate cancer when it is predominantly saturated fat. But consuming unsaturated fats as in olive oil reduces the incidence. Studies have also suggested that low levels of vitamin A and carotenoids may increase the risk.

  • Minerals: Similarly, vitamin C and vitamin E protect the body with their antioxidant role. Minerals are also important to prevent prostate cancer. For example, doctors use zinc, selenium, and calcium in dietary supplements for prostate cancer patients because these minerals are linked to the risk of the disease.
  • Alcohol intake: Some studies suggest that higher consumption of alcohol increases the risk. However, other studies are showing diverging results.

  • Smoking: Smoking increases the levels of two things in your body: androgen (a male hormone) and cadmium (a harmful metal).

  • Endocrine disruptors: Being exposed to synthetic estrogens (hormones), detergents, plastics, and agricultural chemicals can increase the risk of prostate cancer. In some cases, harmful chemicals have been removed from the market because of this risk.

  • Cadmium exposure: Some studies suggest that exposure to cadmium increases the risk of prostate cancer. There’s a modest increase in risk, and it is not reported in all studies.

Conclusion

Prostate cancer and its associations with supplements and hormones are complex. However, we can still reach many conclusions in light of the evidence. Let us break down the finding in two, and consider prostate cancer prevention and progression as different entities.

Despite the apparent contradictions in the evidence, we can use vitamin D to prevent prostate cancer.

Following the same recommendation may also reduce the risk of prostate cancer. However, keep in mind that the ideal blood levels should be 20-30 ng/ml. A higher or lower concentration of vitamin D is linked to an increased risk of prostate cancer. Taking supplements could be helpful, especially in countries with limited sun exposure. You can also get vitamin D from fortified foods and other sources like fatty fish, eggs, and fortified cereals.

In men with prostate cancer, vitamin D recommendations are not the same. All of the available data points out at vitamin D as a useful tool to prevent advanced prostate cancer. It reduces the mortality and progression of prostate cancer. It counteracts the effect of high-calcium diets in prostate tumors.

Thus, it can be useful in patients with prostate cancer and bone mineralization problems. In these men, the ideal level of vitamin D is 30-50 ng/ml, especially if they are at risk of osteoporosis.

The best way to use vitamin D for prostate health is by taking into consideration the recommendations above and measuring serum levels until reaching the appropriate dose of vitamin D supplements.

Sources

  1. Zhou, C. K., Check, D. P., Lortet‐Tieulent, J., Laversanne, M., Jemal, A., Ferlay, J., … & Devesa, S. S. (2016). Prostate cancer incidence in 43 populations worldwide: an analysis of time trends overall and by age group. International journal of cancer, 138(6), 1388-1400.
  2. Bostwick, D. G., Burke, H. B., Djakiew, D., Euling, S., Ho, S. M., Landolph, J., … & Timms, B. (2004). Human prostate cancer risk factors. Cancer: Interdisciplinary International Journal of the American Cancer Society, 101(S10), 2371-2490.
  3. Feldman, D., Krishnan, A. V., Swami, S., Giovannucci, E., & Feldman, B. J. (2014). The role of vitamin D in reducing cancer risk and progression. Nature reviews cancer, 14(5), 342-357.
  4. Holick, M. F. (2007). Vitamin D deficiency. New England Journal of Medicine, 357(3), 266-281.
  5. Loke, T. W., Sevfi, D., & Khadra, M. (2011). Prostate cancer incidence in Australia correlates inversely with solar radiation. BJU international, 108, 66-70.
  6. World Cancer Research Fund International. (2014). Continuous update project report: diet, nutrition, physical activity, and prostate cancer.
  7. Mondul, A. M., Shui, I. M., Yu, K., Travis, R. C., Stevens, V. L., Campa, D., … & Crawford, E. D. (2013). Genetic variation in the vitamin D pathway in relation to risk of prostate cancer—results from the breast and prostate cancer cohort consortium. Cancer Epidemiology and Prevention Biomarkers, 22(4), 688-696.
  8. Vaughan-Shaw, P. G., O’sullivan, F., Farrington, S., Theodoratou, E., Campbell, H., Dunlop, M. G., & Zgaga, L. (2017). The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British journal of cancer, 116(8), 1092-1110.
  9. Vaughan-Shaw, P. G., O’sullivan, F., Farrington, S., Theodoratou, E., Campbell, H., Dunlop, M. G., & Zgaga, L. (2017). The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British journal of cancer, 116(8), 1092-1110.
  10. Capiod, T., Delongchamps, N. B., Pigat, N., Souberbielle, J. C., & Goffin, V. (2018). Do dietary calcium and vitamin D matter in men with prostate cancer?. Nature Reviews Urology, 15(7), 453-461.
  11. Ross, A. C., Manson, J. E., Abrams, S. A., Aloia, J. F., Brannon, P. M., Clinton, S. K., … & Kovacs, C. S. (2011). The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. The Journal of Clinical Endocrinology & Metabolism, 96(1), 53-58.
  12. Robles, L. A., Dawe, K., Martin, R. M., Higgins, J. P., & Lewis, S. J. (2019). Does testosterone mediate the relationship between vitamin D and prostate cancer? A systematic review and meta-analysis protocol. Systematic reviews, 8(1), 52.
  13. Marshall, D. T., Savage, S. J., Garrett-Mayer, E., Keane, T. E., Hollis, B. W., Horst, R. L., … & Gattoni-Celli, S. (2012). Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. The Journal of Clinical Endocrinology & Metabolism, 97(7), 2315-2324.
  14. 14. Medioni, J., Deplanque, G., Ferrero, J. M., Maurina, T., Rodier, J. M. P., Raymond, E., … & Renaux, S. (2014). Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients. Clinical Cancer Research, 20(17), 4471

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