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Vitamin D And Prostate Cancer

Clinical Trials Of Vitamin D Compounds In Prostate Cancer Therapy

Vitamin D and Prostate Cancer

Preclinical studies of 1,252D3 and analogs clearly demonstrate principles on which the conduct of clinical trials of these compounds in cancer therapy should be based. As we will see, such principles have often been ignored:

  • The anticancer activity of 1,252D3 is clearly dose dependent. Based on this concept, and in keeping with the general tenets of cancer drug development, clinical studies should be conducted utilizing the maximum safe dose of vitamin D compound
  • Maximum exposure to 1,252D3 compounds in animal studies is achieved if these agents are administered on an intermittent schedule. For example, clinical trials demonstrate that the maximum oral dose of calcitriol is 1.52.0 mcg QD .91 In contrast, intravenous calcitriol at a dose of 74 mcg weekly is safe and well tolerated .92 125 mcg per week is safe if combined with dexamethasone .85

Muindi and colleagues demonstrated that the systemic exposure to calcitriol achieved in murine models in which calcitriol is effective in suppressing cancer growth can be achieved in humans at high, but safe and tolerable oral and intravenous doses of calcitriol.88

Single-agent Vitamin D compounds

Dairy Foods And Calcium

Some research has shown that men who have a diet high in calcium may have a higher risk of developing prostate cancer. And men may be more likely to have prostate cancer that is more advanced or aggressive. But there is no evidence to say that excluding dairy foods and calcium from the diet will slow the growth of prostate cancer, or reduce the risk of the cancer coming back.

Men with prostate cancer should aim for a healthy balanced diet that includes adequate amounts of calcium. It plays an important part in the way our bodies work. For example it helps keep our bones strong and healthy and helps our muscle to work.

Adults need 700 mg of calcium each day, which most people can get from a balanced healthy diet. Choose low fat and low sugar dairy products.

Good sources of calcium include

  • dairy foods such as milk, cheese and yoghurts
  • tinned fish that contains the bones, for example, salmon or sardines
  • green leafy vegetables
  • nuts such as almonds and brazil nuts
  • seeds such as sesame seeds

Its difficult to give examples of specific amounts. But a daily 700mg of calcium could include all of the following:

  • a small tin of pilchards or sardines
  • a 50g portion of broccoli
  • 200 mls of milk

It is particularly important if you are having hormone therapy to have adequate amounts of calcium. This is because bone thinning is a side effect of this treatment.

Talk to your GP if you are struggling to eat a balanced diet and ask whether you need to take supplements.

Combination Therapies With Vitamin D Compounds

While 1,252D3 compounds have shown encouraging activity in preclinical models, single agents usually have limited effect in clinical cancer therapy. 1,252D3 compound-based combination therapies are being explored and enhance antitumor efficacy.

Glucocorticoids

Among the first compounds whose interaction with vitamin D was examined were glucocorticoids. Glucocorticoids have direct anticancer effects in their own right and are effective in reducing vitamin D-induced hypercalcemia. Glucocorticoids enhance VDR expression in many cell types. The extent to which this occurs varies with tissue type, tumor types, and species. Preclinical studies demonstrate synergistic antitumor effects of calcitriol and glucocorticoids in human prostate cancer xenografts, and the ability of dexamethasone to counteract calcitriol-induced hypercalcemia led to many clinical trials incorporating dexamethasone with calcitriol.8,65

Inhibitors of CYP24A1

Nonsteroidal anti-inflammatory drugs

As noted above, inhibition of prostaglandin synthesis may potentiate the activity of vitamin D compounds. A Phase II trial evaluating the combination of the nonselective nonsteroidal anti-inflammatory drug naproxen and high-dose calcitriol in patients with early recurrent prostate cancer demonstrated some benefits in terms of reduction in prostate-specific antigen doubling time.73

Retinoids

Cytotoxic agents

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Vitamin E: Questions And Answers

In This Section
  • Vitamin E and selenium.

SELECT results published in 2011 showed that men taking vitamin E alone had a 17% increase in prostate cancer risk compared with men who did not take vitamin E.

Several factors may have affected study results, including the dose of vitamin E.

Clinical trials

  • In the Physicians Health Study II, men took either vitamin E supplements, vitamin C supplements, or both and were followed for about 8 years. The overall rates of prostate cancer were similar in the men who took vitamin E supplements and in those who did not. Vitamin E did not affect the number of new cases of cancer or the number of deaths from cancer.
  • A 2011 study of men who took part in The Carotene and Retinol Efficacy Trial found that, among those who were current smokers, higher blood levels of alpha-tocopherols and gamma-tocopherols were linked with lower risk of aggressive prostate cancer. In another study of men who were current smokers or who recently stopped smoking, higher blood levels of alpha-tocopherol were linked to a lower risk of prostate cancer.
  • Have any side effects or risks been reported from vitamin E?

    In the Physicians Health Study II and the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group, there was a higher number of strokes caused by a broken blood vessel in the brain in men who took vitamin E than in men who took a placebo.

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    Best Vitamin D Prostate Cancer Treatment

    Symptomatic treatment of an enlarged prostate usually involves a combination of medication and lifestyle changes. A diet rich in fruits and vegetables may be the best option if you suffer from chronic urination. It will help the body adjust to the increased size of the prostate. Also, taking regular urination intervals will help retrain the bladder to function properly. Inactivity also contributes to urine retention, and cold temperatures can increase the urge to urinate.

    Invasive treatment of enlarged prostate includes medication that relieves the pressure on the urethra and bladder. However, if the condition is severe, it may require surgical intervention. If treatment is not successful, the enlarged prostate can become a potentially life-threatening disease. As the hormone levels in the body change, the enlarged prostate can lead to various complications, including urinary retention and even cancer. This is why it is critical to see a doctor for further evaluation.

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    Multivitamins And Prostate Cancer

    I was sitting with apatient the other day, who came in for advice about his prostate cancer. We had already covered the rather long listof cancer-specific supplements he takes. Last on his list was a question about the multivitamin I had suggested afew years back and whether I still thought it his best choice. His question caused me to pause. A pause so long that it felt like when yourcomputer screen freezes and you need to force quit whatever you were doing. I didnt know what to tell him.

    Im no longer sure whetherprostate cancer patients should take a multivitamin.

    A year ago, in an articleon prostate cancer, I wrote, Taking a multivitamin is safe and probablyuseful. At the time, I cited thePhysicians Health Study randomized trial of regular multivitamin use thatreported a modest but significant reduction in total cancer incidence inmen. The men with a history of prior cancer had a 27% reduction in total cancerduring the study. Yet there had been significant effect on risk of prostatecancer.1

    I am no longer sure that mythinking was accurate. Research resultson nutrition and prostate cancer tend to be erratic and often conflict from onestudy to the next. In one study anutrient appears helpful and another the same substance seems harmful. Whats good one day is bad the next.

    How do we translate thatinto patient instructions? If youve hadprostate surgery be careful, but if you were treated by radiation, go ahead,eat all the folate you want?

    References

    Questions And Answers About Green Tea

  • What is green tea?

    Tea comes from the Camellia sinensis plant. The way tea leaves are processed determines whether green tea, black tea, or oolong tea is made. Green tea leaves are steamed and dried.

    The health benefits studied in green tea are thought to be from compounds called polyphenols. Polyphenols are a group of plant chemicals that include catechins . Catechins make up most of the polyphenols in green tea.

    Catechins in green tea can vary widely, depending on the source of the tea leaves and the way they are processed. This makes it hard to identify most of the chemical factors linked to the health benefits of green tea.

    Some studies suggest that green tea may protect against heart and blood vessel disease.

  • How is green tea given or taken?

    People usually drink green tea or take it as a dietary supplement.

  • Have any laboratory or animal studies been done using green tea?

    See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using green tea.

  • Overall, population studies suggest that green tea may help protect against prostate cancer in Asian populations. Prostate cancer deaths in Asia are among the lowest in the world.
  • Clinical trials

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    Saw palmetto is known for its ability to ease prostate cell growth, increase urine flow, and reduce urinary frequency and nighttime urination.

    It may also aid in relieving painful urination and difficulty in starting and stopping urine flow. With regular use, Natureâs Way Saw Palmetto Berries 585 mg â 180 Vegan Capsules may help improve overall prostate health and function.

    Level Of Certainty Of Evidence

    Has a vitamin D deficiency been linked to prostate cancer?

    The level of certainty of evidence provided from all studies will be assessed using the Grading of Recommendations Assessment, Development and Evaluation system . GRADE classifies the confidence in an estimate into four levels: high, moderate, low, and very low. Estimates of effect can be either up or downgraded based on several of the following criteria:

    • Study limitations

    • Inconsistency of results

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    First Human Interventional Trial

    In late 2004, Woo, Vieth, and colleagues from the University of Toronto presented a groundbreaking paper at the November NIH conference on vitamin D and cancer. They showed that 2,000 units of simple vitamin D3 either reduced or prevented further increases in PSA in the majority of men with advancing prostate cancer. For the first time, a human interventional trial indicted that simple vitamin D was effective in fighting cancer.

    Vitamin D And Prostate Cancer

    Richard Martin and his team observed association between vitamin D and more aggressive cancers, which indicates the potential role for vitamin D manipulation to control the progression of prostate cancer

    • Topic:Prostate cancer

    Association of circulating vitamin D metabolite levels with incidence and progression of screen-detected prostate cancer.

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    Missing Link Between Vitamin D And Prostate Cancer

    US Pharm. 2014 39:HS2.

    Denver, COCompelling evidence has been found that inflammation may be the link between vitamin D and prostate cancer. A recent University of Colorado Cancer Center study that investigated which genes vitamin D turns on or off in prostate cancer found that gene GDF-15, which is known to be upregulated by vitamin D, is absent in samples of human prostate cancer driven by inflammation. In a sophisticated computer algorithm analysis of immunohistochemical data, researchers were able to quantify expression of GDF-15 protein and inflammatory cells. GDF-15 was uniformly low in tissue samples containing inflammation. Researchers believe that these findings will lead to identification of new targets for treatment of prostate and other cancers.

    To comment on this article, contact [email protected]

    Purpose Of This Summary

    Vitamin D Deficiency and Prostate Cancer

    This PDQ cancer information summary has current information about the use of nutrition and dietary supplements for reducing the risk of developing prostate cancer or for treating prostate cancer. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

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    Questions And Answers About Vitamin D

  • What is vitamin D?

    Vitamin D is a fat-soluble vitamin found in fatty fish, fish liver oil, and eggs. Vitamin D may also be added to dairy products.

    Vitamin D has many actions in the body, including the following:

  • See the Laboratory/Animal/Preclinical Studies section of the health professional version of Prostate Cancer, Nutrition, and Dietary Supplements for information on laboratory and animal studies done using vitamin D.

  • Have any studies of vitamin D been done in people?

    Population studies and clinical trials have been done to study the effects of vitamin D on prostate cancer. The results of these studies have been mixed. Some studies have shown a link between Vitamin D levels and prostate cancer, and others have not. There is not enough evidence to know whether giving vitamin D can prevent prostate cancer.

    Combined studies

  • A 2008 review of 45 studies found no link between taking vitamin D and prostate cancer risk.
  • A 2009 study found that men with low levels of sun exposure had an increased risk of prostate cancer and advanced disease.
  • A 2011 review of 25 studies found no link between either vitamin D in the diet or blood levels of vitamin D and the risk of prostate cancer.
  • Population studies

    Sun Exposure Skin Type And Reduced Risk

    In 2001, Luscombe and colleagues at the School of Medicine in North Straffordshire Hospital in England published three studies linking ultraviolet exposure and skin type to the development of prostate cancer. They found that cumulative outdoor exposure, outdoor occupations and skin type was associated with reduced risk of advanced stage tumors. They also found that childhood sunburns dramatically reduced the risk of developing prostate cancer, probably because those with fair skin are more likely to burn but also find it easier to make vitamin D in their skin. Furthermore, they found that people who have difficulty making the skin pigment

    metastasis, can be made to respond to calcitriol by adding drugs which inhibit the breakdown of calcitriol. This raised the possibility that prostate cancers which did not respond to vitamin D could be made responsive by the addition of a metabolic inhibitor. Farhan and colleagues at the University of Vienna Medical School soon showed that the isoflavonoid found in soybeans, called , is a powerful metabolic inhibitor of the enzyme that breaks down calcitriol. Zhao XY, Feldman D. The role of vitamin D in prostate cancer. Steroids. 2001 MarMay 66:293300.Farhan H, Wahala K, Adlercreutz H, Cross HS. Isoflavonoids inhibit catabolism of vitamin D in prostate cancer cells. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Sep 25 777:2618.

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    Findings On Vitamin D And Prostate Cancer

    Dr. Bruce Hollis, a GrassrootsHealth scientist panel member, was one of the first to study giving larger doses of vitamin D to participants, something that was difficult to get approval for before 2010.

    Hollis and colleagues ran an intervention study at the Medical University of South Carolina on 52 men who had been diagnosed with stage 1 prostate cancer. They purposely did not conduct an RCT as they wished to give everyone in the study vitamin D. They used a dose of 4,000 IU/day of vitamin D for one full year while the participants were on a wait and see approach with their cancer.

    In the video below, Dr. Hollis describes the study and its findings in detail.

    The overall result was that almost 60% had a reduction in tumors as opposed to doing nothing .

    Of the 52 men, 15 went from a Gleason score of 6 to a Gleason score of 0 .

    Prostate Cancer Nutrition And Dietary Supplements Patient Version

    Results of a Prostate Cancer/Vitamin D Trial: Effectiveness Safety Recommendations
    On This Page

    Complementary and alternative medicine is a form of treatment used in addition to or instead of standard treatments.

    In the United States, about 1 out of every 8 men will be diagnosed with prostate cancer. It is the most second-most common cancer in men in the United States. CAM use among men with prostate cancer is common. Studies of why men with prostate cancer decide to use CAM show that their choice is based on medical history, beliefs about the safety and side effects of CAM compared to standard treatments, and a need to feel in control of their treatment.

    CAM treatments used by men with prostate cancer include certain foods, dietary supplements, herbs, vitamins, and minerals.

    Different types of research have been done to study the use of CAM in prostate cancer. These study types include the following:

    CAM treatments have been studied to see if their use lowers the risk of prostate cancer, kills prostate cancer cells, or lowers the risk that cancer will come back after treatment. Most of these studies used prostate-specific antigen levels to find out whether the treatment worked. This is a weaker measure of how well the treatment works than direct measures, such as fewer new cases of prostate cancer, or smaller tumor size or lower rate of recurrence after treatment for prostate cancer.

    This PDQ summary has sections about the use of specific foods and dietary supplements to prevent or treat prostate cancer:

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    Dietary Vitamin D And Risk Of Prostate Cancer

    The association between dietary vitamin D intake and prostate cancer risk has been examined in several epidemiologic studies.3Results of these studies are negative or conflicting however, limiteddata indicate a possible link. One study concluded that men in the U.S.have a 10-fold greater risk of developing prostate cancer compared withmen in Japan.10 The increased risk has been linked to thedifference in diet between American and Japanese men. Japanese men have ahigher consumption of fatty fish, and thus an increased amount ofvitamin D and omega-3 fatty acids. Omega-3 fatty acids dissociatevitamin D metabolites from binding proteins, thereby increasing activelevels of these metabolites in the blood.3 In another study, Ahn et al noted a reduced risk of prostate cancer with greater intake of supplemental vitamin D.11A 40% risk reduction occurred in patients receiving more than 600 IU ofsupplemental vitamin D versus those not receiving it. However, dietaryintake of vitamin D was not associated with adecreased or increased risk of prostate cancer.11

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