Vitamin D₃ May Keep Low-Risk Prostate Cancers in Check

Pam Harrison

March 25, 2015

Vitamin D₃ supplementation after a prostate biopsy reduces inflammation and might even obviate the need for eventual prostatectomy or radiation therapy by keeping low-grade tumors from becoming aggressive, new research suggests.

"We don't know yet whether vitamin D treats or prevents prostate cancer," lead author Bruce Hollis, PhD, from Medical University of South Carolina in Charleston, said in a statement.

"At the minimum, what it may do is keep lower-grade cancers from going ballistic," he said.

The study was presented at the 249th National Meeting & Exposition of the American Chemical Society in Denver.

In a small pilot study, Dr Hollis and his colleagues investigated the effects of vitamin D₃ supplementation on prostate tissue specimens. They assigned 37 men scheduled to undergo elective prostatectomies to either vitamin D₃ 4000 IU/day or placebo for 2 months before surgery.

It is the standard of care to leave an interval of 2 months between initial biopsy and prostatectomy so that the inflammation caused by the biopsy procedure has time to resolve.

After prostatectomy, the glands were evaluated. Membrane changes and differences in gene expression were compared in the supplemented and unsupplemented men.

"We saw major changes in membrane lipids in glands from men who had taken vitamin D₃," Dr Hollis said during a press briefing.

"More important," he added, "we saw some really incredible molecular changes, and the number 1 gene that showed up on the heat map was growth differentiation factor 15 [GDF-15]," he said.

"Treatment with vitamin D, at 4000 IU per day, turns GDF-15 gene expression up, and that inhibits inflammatory processes," he explained.

In a previous study, a small group of men diagnosed with low-risk prostate cancer received 4000 IU of vitamin D₃ supplementation for 1 year (J Clin Endocrinol Metab. 2012;97:2315-2324). At 1-year rebiopsy, 55% of the men had a decrease in the number of positive biopsy cores or in Gleason score.

"When you look at this from historical standards for age-matched controls within the same practice, about 90% of tumors get worse or stay the same," Dr Hollis observed, "so this really was a pretty remarkable finding."

The Medical University of South Carolina is now in the process of conducting a randomized controlled trial of men diagnosed with early-stage low-risk prostate cancer, defined as a serum prostatic-specific antigen (PSA) level of 10 ng/mL or less and a Gleason score of 6 or less.

All subjects will be monitored with active surveillance for at least 1 year before definitive treatment is decided on.

The primary objective will be to test the hypothesis that vitamin D₃ 4000 IU/day for 12 months will result in a decrease in serum PSA levels in a significant number of men.

A secondary objective will be to compare prostate biopsy specimens before and after vitamin D₃ supplementation.

Inflammation is thought to drive many cancers, including those of the prostate, breast, and colon, Dr Hollis pointed out.

During his presentation, he described a study in which overall survival was 35% better in metastatic colorectal cancer patients with plasma 25-hydroxyvitamin D levels above 24.1 ng/mL than in those with levels from 2.2 to 10.8 ng/mL (hazard ratio, 0.65; 95% confidence interval, 0.51 - 0.83) (Cancer Epidemiol Biomarkers Prev. 2014;23:1628-1637).

Having treated thousands of patients with vitamin D₃ himself, Dr Hollis reported that the number of adverse events he has seen with vitamin D is exactly none.

"We had a reluctant urology division that eventually agreed to cooperate in our first study," Dr Hollis told Medscape Medical News.

At the end of that study, vitamin D₃ supplementation became the standard of care in our urology division, "so yes, doctors should be recommending vitamin D₃ for men with low-grade prostate cancer," he said.

Supplementation Not Supported by Data

This study adds to the already-existing literature supporting the beneficial effect of vitamin D₃ supplementation in the setting of prostate cancer, said Marc Garnick, MD, from the Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School in Boston, in an email to Medscape Medical News.

Vitamin D₃ "joins a multitude of other vitamins and dietary supplements" that have been shown to benefit men with prostate cancer. "As such, it deserves additional, well-controlled, adequately powered studies with appropriate follow-up and patient numbers that allow for meaningful conclusions," Dr Garnick stated.

He cautioned, however, that a sample of 37 men exposed to supplementation for 2 months is "entirely inadequate" for any conclusions other than hypotheses to be generated, and in no way enables a "practice-changing" policy.

He also criticized the "overly enthusiastic interpretation" of this small dataset in the absence of additional rigorous study.

"The medical world and the patients we serve have too often been inappropriately excited about preliminary findings, only to be disappointed and possibly harmed by practices that are premature and not fully tested," Dr Garnick explained.

He pointed to the disappointing results with soy protein, vitamin E, and selenium supplementation, none of which ever proved to be as helpful as originally touted.

And he mentioned the widely studied finasteride and dutasteride, which were thought to prevent prostate cancer from developing. After thousands of patients, years of study, and rigorous analyses, it was determined that these drugs are of no benefit and could, in fact, be harmful in this setting.

"In my opinion, for a physician practice to embrace the use of vitamin D₃ supplementation as the 'standard of care' outside the context of a clinical research study is not supported by the information at hand," Dr Garnick said.

"Moreover," he added, "the alteration of behavior that the current study addresses — that of a small cohort of low-risk prostate cancer patients — would take more than a decade of study, if not longer, to see if any benefit (or harm) was present."

This study was funded by the Gateway for Cancer Research, the Department of Veterans Affairs, the National Institutes of Health, and the South Caroline Clinical and Translational Research Institute. Dr Hollis has disclosed no relevant financial relationships.

249th National Meeting & Exposition of the American Chemical Society. Abstract AGFD 11. Presented March 22, 2015.


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