Professor Reinhold Vieth at the University of Toronto is one of my heroes. It was his 1999 review paper on vitamin D, which I must have read ten times, a paper freely available for all to read, that first convinced me vitamin D would change the face of modern medicine. He outlined the difference between physiological doses (up to 10,000 IU/day) and pharmacological doses (50,000 to 100,000 IU/day), writing that pharmacological doses would have been studied long ago if vitamin D was a drug that could be patented.
So far, only patentable and expensive analogues of activated vitamin D have received the financial support to undergo the sort of rigorous testing needed to be approved as therapeutic agents by the FDA. They have been studied in a variety of illnesses, mostly cancer, but with minimal success. The key issue is how much activated vitamin D one can get into a cancerous tumor, say prostate cancer, by giving an activated vitamin D analogue.
Normally, the amount of activated vitamin D in a tissue like the prostate is largely determined by its regulated production within that tissue. What has been discovered the hard way, has been that the approach of providing the activated vitamin D by mouth so that some of it reaches the prostate, actually ends up overdosing the whole body when all you want to do is affect the prostate. What has never been answered is whether you can increase the amount of activated vitamin D in a tumor, like prostate cancer, simply by providing the body with enough plain vitamin D so that the tissue has enough to take care of its own needs.
The prostate gland is one of the few organs that can both make 25(OH)D and activate it as well. Unlike some other cancers, many prostate cancers retain the ability to activate vitamin D, so theoretically you may be able to get high doses of activated vitamin D inside prostate cancer cells by simply giving plain vitamin D, although this has remained theoretical until Professor Vieth’s latest paper.
This is important in treating cancer because based on what we know from laboratory experiments is that high levels of activated vitamin D inside cancer cells produce anticancer effects. Activated vitamin D retards cancer growth (proliferation), promotes cellular specialization (differentiation), promotes death of injured or aging cells (apoptosis), and reduces the ability of tumors to highjack a blood supply (angioneogenesis).
Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R. Randomized Clinical Trial of Vitamin D3 Doses on Prostatic Vitamin D Metabolite Levels and Ki67 Labeling in Prostate Cancer Patients. J Clin Endocrinol Metab. 2013 Mar 5.
We first blogged on this study after it was presented to the public at the American Association for Cancer Research conference last April. It has just now finally been published in a journal, with a detailed look into their methodology and findings.
In the above double blind randomized controlled trial, lead author Dennis Wagner and colleagues, working under the supervision of Professor Vieth, randomized 66 men awaiting prostate cancer surgery to one of three groups, 400 IU/day, 10,000 IU/day or 40,000 IU/day. The patients took the vitamin D for the average of 33 days leading up to their radical prostatectomy. Final 25(OH)D levels were not detailed in the text, but Figure 1 shows final 25(OH)D to be about 22 ng/ml in the 400 IU/day group, about 55 ng/ml in the 10,000 IU/day group, and about 120 ng/ml in the 40,000 IU/day group.
One of the primary end points of the study was confirmed: prostate levels of activated vitamin D were dose dependent and were the highest in the 40,000 IU/day group (p<.03). The second primary end point, that dose of vitamin D would determine level of a prostate growth (proliferative) marker (Ki67) was not met, but Ki67 levels did vary with prostate activated vitamin D levels (p<.05). Patients in the highest quartile of prostate activated vitamin D levels showed significantly lower Ki67 levels than did the lowest quartile. Also, serum levels of PSA and PTH were lower in the combined high dose groups then in the 400 IU/day group (p<.02). All measures of vitamin D dose safety confirmed that the doses were safe in the short term and not different between groups.
The authors wrote:
“In conclusion, our clinical trial data support the hypothesis that prostatic in vivo vitamin D metabolism can be modulated by high oral vitamin D dosing. Furthermore, the decrease in Ki67 labeling and modest declines in serum PSA and PTH with higher prostate calcitriol achieved with vitamin D doses (10 000 and 40 000 IU/d) suggest a potential clinical benefit. Lastly, the vitamin D doses (400–40 000 IU/d) were well tolerated by prostate cancer patients without signs of toxicity. Further studies are needed to validate the potential utility of moderate-dose vitamin D3 supplementation in prostate cancer prevention and of higher doses of vitamin D as part of the treatment for prostate cancer.”
Published simultaneously, were more results of the same clinical trial, these were from the laboratory of Larissa Nonn, University of Chicago. Those authors demonstrated that presence in the prostate of the higher activated vitamin D rose what is called micro-RNA, a relatively recently discovered class of RNA that regulates the way genes are expressed. In this case, several key tumor-suppressive micro-RNA levels were higher as a result of the higher activated vitamin D in the prostate. All of this points to the conclusion that simple vitamin D nutrition is a good thing in the context of prostate cancer.