Low Vitamin D Linked to Prostate Cancer Risk

By Jaimie Lazare

Vitamin D deficiency has been associated with an increased risk of prostate cancer, and replacing vitamin D may have preventive and therapeutic benefits that warrant further research.

Vitamin D freely diffuses into cells, binds to vitamin D receptors, and enters the nucleus of the cell, where it can modify various genes in the human genome, says Adam Murphy, MD, a urologist and an assistant professor of urology at Northwestern University Feinberg School of Medicine in Chicago. There are 300 different vitamin D response elements where vitamin D binds to activate genes. The expression of specific genes by vitamin D has various effects on the prostate. Vitamin D can affect normal prostate growth and differentiation, arrest the gland's growth in the cell cycle when it's already a mature cell, and trigger cell death, or apoptosis, of prostatic cells that are mutated, Murphy says.

Factors Affecting Vitamin D Level
Murphy says the concern centers on the fact that people who are vitamin D deficient live in areas that experience low sun exposure during several months of the year. The biggest predictor of vitamin D deficiency is the season in which blood is drawn; seasonal exposure to the sun can actually contribute to issues in controlling the definition of vitamin D deficiency. Men would need to be vitamin D deficient for some length of time for their deficiency to begin causing problems with normal growth pattern and differentiation of the prostate. So chronic sustained deficiency of vitamin D may contribute to the risk of prostate cancer, he says.

Murphy is coauthor of a study that identified an association between vitamin D deficiency and prostate cancer aggressiveness.1 The study evaluated men living in Chicago who have a greater likelihood of being chronically vitamin D deficient because of low sun exposure. Sun exposure contributes 90% of vitamin D levels among whites, and the remaining 10% results from diet and supplements. However, among blacks, vitamin D is less likely to occur from sun exposure. "African Americans are less effective at using the [ultraviolet B] rays from the sun to make vitamin D because melanin is an effective blocker of it," he says.

"The precursor molecules of vitamin D in the skin are converted by ultraviolet exposure to sunlight. Those precursor molecules are in less abundance per volume of skin in older adults than they are in younger adults," says F. Michael Gloth, III, MD, FACP, AGSF, CMD, chief medical officer at Moorings Park Healthy Living, a clinical professor in the department of geriatrics at Florida State University College of Medicine, an associate professor of medicine in the division of geriatric medicine & gerontology at the Johns Hopkins University School of Medicine, and an adjunct associate professor in the department of epidemiology and public health at the University of Maryland School of Medicine. "The actual conversion process is slower in older adults than it is in younger adults. So older adults are more susceptible to becoming vitamin D deficient."

"The other thing is we've done a pretty good job of educating people about skin cancers and the fact that they need to use sunscreen when they're outdoors," Gloth says. "That consequence has also decreased that ability of the sunlight to create vitamin D within the skin because sunscreens block that conversion."

Potentially Preventive, Not Curative
People who have cancer are more likely to have low vitamin D status than people who do not; the other way to look at it is if you are low in vitamin D, you may be more susceptible to diseases that require cellular differentiation, Gloth says.

Because cancers are undifferentiated cells that replicate without inhibition, there is a theory that low vitamin D status makes it easier for cells to dedifferentiate. So inadequate vitamin D levels may make it easier for individuals to develop cancers, Gloth says. Alternatively, if adequate vitamin D status is maintained, people may be more resistant to developing cancers. These are all hypotheses being studied in a number of different cancer trials, he says.

Gloth notes that vitamin D deficiency can occur even when individuals are abundantly exposed to sunlight, as demonstrated in a study conducted in Hawaii that found that vitamin D status varied tremendously among adults.2 The difference in vitamin D status was dictated more by genetic than environmental factors because people had plenty of sun exposure to obtain the conversion that they needed. "The component of genetic variability, in terms of what is normal for people, is an important concept to understand because it may be that some people can get by with a lower level of vitamin D than other people can," he says.

African Americans, for example, generally have good bone strength despite having relatively lower vitamin D status, Gloth says. Since vitamin D is so important for bone status, the question becomes: How can African Americans have a better bone status when they have lower vitamin D levels? "It may be that there is a genetic difference in terms of how they use vitamin D and how much they need," Gloth says.

He adds that the genetic component would have an impact in terms of bone strength, but what about other cellular functions such as differentiation as it relates to the development of certain cancers later in life? We don't know for certain what role vitamin D is actually playing and how much of an impact that it has on certain cancers. But the prevalence of specific cancer types among African Americans and vitamin D deficiency does present an intriguing question that deserves more research, Gloth says.

"I don't think the data are strong enough yet to tell us that it is going to be preventive. I think where we are right now is that it possibly could be preventive," Gloth says. "I think we're fairly comfortable that it can be preventive for a lot of other medical issues, and given its safety and the inexpensive proposition of taking vitamin D, it really doesn't make sense not to take a vitamin D supplement."

"Vitamin D is an adjunctive treatment that has the potential for prevention of prostate cancer. It'll slow it down, but it's not enough to cure it or be an effective treatment by itself. So it isn't going to be a big treatment for prostate cancer in terms of affecting life expectancy or death rates," Murphy says. "If it's metastatic, it's still a good idea to [replete vitamin D levels] because these people are already having advanced bone loss, and bone fractures are a big source of morbidity for people with advanced prostate cancer. So it's good to give it even then, but it's not a cure for prostate cancer. It's just slowing it down and protecting the bone in that setting."

Vitamin D is a relatively inexpensive and safe way to help reduce the likelihood of falls risk and fractures. Recognizing that alone is probably helpful and would encourage people, particularly older adults, to make sure their vitamin D status is adequate, Gloth says. People who have a normal vitamin D status are not going to benefit from getting more vitamin D. The benefit seems to occur in people who are deficient and who then are repleted into a normal vitamin D status, he says.

The prevention of osteoporosis among the elderly is a priority for geriatric patients, Murphy says. Despite low vitamin D levels among African Americans, they tend to have higher bone density and fewer fractures. But if black men are placed on hormone therapy, their rate of bone loss increases, and they're actually at a higher risk for fractures, he says.

Screening Recommendations
Prostate cancer screening has been fairly controversial because of the Grade D recommendation from the US Preventive Services Task Force on prostate-specific antigen (PSA) screening. The recommendation was meant for men who have a low risk of developing prostate cancer. However, there's been a decrease in PSA screening rates and overall detection of prostate cancer and an increase in the grade and stage of prostate cancer, so prostate cancer is becoming more and more aggressive when we detect it, Murphy says. The American Urological Association and American Cancer Society recommend screening men between the ages of 50 and 55 for PSA and continuing at least to the age of 69. For those who may have an increased risk of prostate cancer, screening should begin at the age of 40, or 10 years before a patient's family member was diagnosed with prostate cancer, he says.

For the older adult population, whether we're thinking about prostate cancer or any of the other sequelae of vitamin D deficiency, we don't even need to measure vitamin D; the American Geriatrics Society recommends against measuring vitamin D, and rather making sure that older adults get somewhere between 800 IU and 4,000 IU daily, Gloth says.

Murphy says an annual PSA blood test and a rectal exam is administered, and there are also new assays available. One is Prostate Health Index and the other is 4K Score, Murphy says. Patients should talk to their physicians about getting screened for prostate cancer with PSA and some of the other markers. While there are contrasting opinions, the different guidelines emphasize the importance of PSA screening being a shared decision-making process between the physician and the patient, he says.

— Jaimie Lazare is a freelance writer based in Brooklyn, New York.

References
1. Nyame YA, Murphy AB, Bowen DK, et al. Associations between serum vitamin D and adverse pathology in men undergoing radical prostatectomy. J Clin Oncol. 2016;34(12):1345-1349.

2. Binkley N, Novotny R, Krueger D, et al. Low vitamin D status despite abundant sun exposure. J Clin Endocrinol Metab. 2007;92(6):2130-2135.