How to Reverse Markers of Prostate Cancer

Prostate cancer will be diagnosed in more than 180,000 American men this year. About 26,000 will die from metastatic disease that originates in the prostate gland.¹

The prostate-specific antigen (PSA) blood test enables early detection that leads to higher cure rates.²

Despite prostate cancer being the second leading cause of cancer mortality in American men,¹ there has been a raging debate as to whether screening for the PSA should be done.²

An argument against screening for PSA is that it can result in overtreatment and complications that would not occur had the man remained blissfully ignorant that he may harbor a prostate malignancy.

Our rebuttal is that early detection is saving thousands of American men agonizing deaths from metastatic prostate cancer each year.

The debate over PSA screening is mercifully turning in a more rational direction. This is occurring because of improvements in the quality of management of patients with low-grade prostate cancer in the United States.

Even more exciting are new findings that show substantial reductions in prostate cancer incidence, progression, and mortality in response to healthier lifestyle choices. This means that it’s never too late to proactively protect against this malignancy that impacts so many men.

In this issue of Life Extension^®, we describe novel curative procedures along with natural methods to prevent and reverse low-grade prostate disease.

In 2005, the results of a small study were released that showed that markers of prostate cancer were reversed in patients with clinically relevant disease who made comprehensive lifestyle changes. Such changes included eating a diet low in fat, but rich in fruits and vegetables, along with regular exercise.³

The findings showed that in the control group, PSA levels increased indicating progression (worsening) of their disease.

In the comprehensive lifestyle change group, PSA levels decreased, indicating a probable regression of their prostate malignancies. Those who complied most with the healthy lifestyle changes had the greatest reductions in PSA blood levels.

Most interesting from this same study was a finding that took blood serum from the participants and added it to a petri dish of dividing human prostate cancer cells. Recall both groups consisted of men with clinically relevant prostate cancer.

The control group’s serum inhibited tumor growth by 9%, whereas serum from the comprehensive lifestyle group inhibited tumor growth an astounding 70%.

This discovery indicates that healthy lifestyle choices result in the blood of a prostate cancer patient gaining powers that impede tumor growth.

This 2005 study was conducted by Dean Ornish, MD, and colleagues who speculated that the healthy lifestyles they advocated to reverse coronary artery disease might also help reverse prostate cancer.

This latter speculation should come as no surprise because the factors associated with health do not distinguish between heart disease and cancer, and in fact, the very same factors are implicated in all aspects of inflammation and aging. This is the integrative nature of health versus disease.

Expanding on This Pioneering Research

Over the past three years, an avalanche of new human research reveals which dietary constituents and lifestyle interventions increase or decrease prostate cancer risk.

For those with low-grade prostate cancer, this new data provides dietary guidelines that may enable one to control their disease with active surveillance, which is a more contemporary way of saying what used to be called “watchful waiting.”

Dr. Dean Ornish advocated an across-the-board very low-fat diet that was difficult to comply with. Newer studies are showing it is the type of fat one eats that dictates risk of dying from prostate cancer.

In a 2015 published study, a group of 926 men with nonmetastatic prostate cancer were evaluated over a median 10-year period.⁴ The diets of these men were categorized either as a “Prudent” pattern (characterized by a higher intake of vegetables, fruits, fish, legumes, and whole grains) or as a “Western” pattern (characterized by a higher intake of processed foods and red meats, as well as high-fat dairy products and refined grains).

In these 926 men with clinically diagnosed prostate cancer, those who consumed the “Western” pattern diet had a 2.53-fold increase in prostate cancer-specific mortality. This was especially evident for men who consumed the most saturated fat compared to polyunsaturated vegetable fats.⁴

Secondary analysis of the data by the same group of researchers found that men who consumed more than three servings of dairy foods daily had a 76% higher all-cause mortality risk and 141% higher prostate cancer-specific risk compared to men who consumed less than one serving a day of dairy food.⁵

These studies clearly showed higher mortality (death rates) in prostate cancer patients who consumed unhealthy “Western” pattern diets. It went further to show that higher intake of dairy foods increased risk of dying even more in men already diagnosed with prostate cancer.

These recent and robust studies provide intriguing evidence that one’s diet has a tremendous impact on whether prostate cancer turns lethal and further validates the importance of annual PSA screening.

If a blood test shows a high or rising PSA level, this provides an early-warning indicator for a man to improve his diet and make other changes that are associated with reduced PSA and reduced mortality .

Equally important is the fact that a high or rising PSA level might require additional diagnostic tests as it could relate to a growing or metastasizing prostate cancer.

Blood Levels of Specific Nutrients Correlate with PSA Levels

Whether one is diagnosed with prostate cancer or worried about a steadily rising PSA, the objective is to get the PSA blood level down.

A study published in 2015 evaluated levels of carotenoids and vitamin E in the blood of men with recurring prostate cancer as evidenced by rising PSA. These were men who were previously treated with surgery or radiation but had recurring disease based on steadily elevating PSA blood levels.

After three months, men with higher blood levels of lutein and zeaxanthin showed lower PSA results. After six months, men with higher blood levels of vitamin E, lycopene, and cryptoxanthin had lower PSA readings.⁶

The researchers who conducted this study concluded that “…greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA [prostate cancer] recurrence.”

A 2014 study looked at men with recurring prostate cancer in relationship to their folate intake. The overall findings showed no relationship between folate intake and cancer recurrence.⁷

A secondary analysis of the data, however, looked at men initially treated by radical prostatectomy (surgical removal of prostate gland). In this surgery-treated group, those with the lowest intake of folate from foods and supplements had a 2.6-fold increase in the risk of cancer recurrence. In patients treated with external beam radiation and radioactive seed implantation (brachytherapy), there was no evidence of an association between prostate cancer progression and increased folate intake.⁷

A 2013 study on men with recurrent disease after radical prostatectomy showed that higher serum (blood) levels of folate was independently associated with a 58% reduced risk of biochemical recurrence (as measured by PSA analysis).⁸

The take-home lesson from these recent studies is the urgent need for those with prostate cancer to follow healthy eating patterns and those who wish to avoid contracting the disease to do the same.

Most Aging Men Have Cancer Cells in Their Prostate Gland

The prostate gland is especially vulnerable to malignant transformation, yet the vast majority of aging men that harbor prostate cancer cells never develop clinically relevant disease.

Unlike more virulent cancers, there are a number of natural barriers that enable prostate tumors to be contained within the prostate gland. Some of these barriers include nutrients, hormones, drugs, and dietary factors that influence the ability of prostate cancer cells to survive and propagate.

Any aging individual with a PSA reading over 1.0 ng/mL should be concerned that they may have an early-stage prostate issue that can respond to lifestyle/dietary alterations.

With the availability of low-cost blood testing, one can easily check their PSA level three months after initiating healthier lifestyle patterns to see if they are achieving a reduction in this biomarker (PSA) of potential prostate canceractivity.

What’s interesting is that the same healthy lifestyle patterns that reduce prostate cancer risk, reduce prostate cancer progression, and reduce prostate cancer death also have been shown to reduce risk of overall mortality.⁴

Studies Strongly Link Diet to Prostate Cancer

A wealth of published data strongly and consistently links what a man eats to his future risk of developing prostate cancer.

A study published in 2015 looked at men residing in rural Pakistan and found that frequent consumption of red meat and fat increased prostate cancer risk 3.4-fold.

This same study showed that greater consumption of vegetables, fruit, and fluids decreased prostate cancer risk by 79% to 91%!⁹

Another study published in 2015 looked at vitamin E intake in a large group of men. Compared to the highest versus lowest dietary intakes of alpha tocopherol, there was a 66% decreased risk of developing prostate cancer. When gamma tocopherol intake was evaluated, there was a 55% decreased risk in the highest versus lowest group.¹⁰

A study published in 2014 looked at the dietary patterns of Iranian men and found a strong protective effect against prostate cancer in response to higher intakes of fruits and vegetables. Men in the highest intake range of plant foods like cabbage, tomatoes, apples, and pomegranate had a 67% reduced prostate cancer risk.¹¹

A study of Italian men published in 2014 looked at dietary patterns and their association with a man’s odds of developing prostate cancer. Men who ate the most animal products or starchy foods had a 1.5-fold increased rate of prostate cancer. Men whose diets contained the most vitamins and fiber had a 7% decreased risk.¹²

These recent studies emanating from around the world consistently show substantial prostate cancer risk reductions in response to healthy dietary practices.

Role of Obesity in Prostate Cancer Progression

Heavier men are at greater risk for benign and malignant prostate disease.

A study published in 2014 evaluated 565 men who were undergoing active surveillance for prostate cancer. Of this group, 124 were obese (body mass index [BMI] higher than 30 kg/m2).¹³

A follow-up finding showed that each 5-unit increase in the body mass index score was associated with a 1.5-fold increased risk of pathologic progression and 1.4-fold increased risk of therapeutic progression in these men with clinically relevant prostate cancer.

In the Patient Summary of this study, the authors concluded:

“Our study is the first to suggest that obesity is associated with a higher risk of cancer progression while on AS [active surveillance]. Further research is needed to determine if diet and exercise can decrease the risk of cancer progression while on AS [active surveillance].”¹³

The association between obesity and prostate cancer is well documented in the literature showing that men with the highest body mass index scores have the highest risk for advanced prostate cancer.¹⁴

The connection between obesity and low grade-chronic inflammation is partly to blame, providing a window of opportunity to reduce such risk through dietary changes. And this is precisely what was seen on a recent study by the British Journal of Nutrition. Researchers measured the “dietary inflammatory index” to predict the risk of prostate cancer. The results showed that men in the two highest dietary inflammatory index quartiles had a 32% increased risk compared to men in the lowest inflammatory index quartile.¹⁵

Why PSA Testing Is so Critical

If an elevated PSA reading meant that a man had to endure painful biopsies and other side effect-prone procedures, then it would be easier to accept the argument that aging men might choose to remain ignorant about the status of their prostate gland.

The stark reality, however, is that a friendly early warning in the form of a higher-than-desired PSA level provides an aging male with the ability to adjust his lifestyle in a manner that may potentially reverse the course of the disease, and in the process, reduce his overall mortality risk.

It is difficult for most men (including me) to consistently follow healthy eating patterns. Yet in response to an early warning sign (such as rising PSA), men will often turn around their lifestyle for the better.

When men call Life Extension^® asking about a rising PSA blood level, we often suggest comprehensive intervention be implemented along with active surveillance.

The objective is to make healthy lifestyle choices and ingest compounds that help circumvent every route that enables tumor cells to propagate and escape confinement within the prostate gland.

My Personal Triumph

When I was 48 years old, my PSA blood reading jumped to 1.4 ng/mL.

My reaction was nothing short of controlled panic. I had seen too many men’s PSA level increase to over 1.0 ng/mL and then steadily surge above 4.0 ng/mL in just a few years. At that point, some of these men had metastatic disease, while others were cured but left with impotence, incontinence, and chronic pain from treatment.

I made a personal commitment of not letting a prostate malignancy get the better of me. My reaction was to treat this PSA reading of 1.4 ng/mL as an early-warning sign that I had prostate cancer that required curative nontoxic treatment.

I adopted healthier dietary choices and initiated high doses of every nutrient and drug that had shown efficacy against prostate cancer. At age 61, my PSA is a low 0.3 ng/mL—a 79% reduction from 12 years ago.

Despite having a family history of prostate cancer, I’ve been able to keep my PSA level low by following sensible (but by no means perfect) dietary patterns and ensuring that I don’t miss taking nutrients, hormones, and drugs shown to reduce prostate cancer risk and reverse its progression.

PSA levels naturally rise with aging, yet there are a myriad of ways to control it. So far you’ve read mostly about foods that have been found to increase or decrease one’s odds of contracting and dying from prostate cancer.

The sidebar on the next page provides a partial list of individual nutrients shown to lower PSA and/or reduce prostate cancer risk and progression.

Prostate Cancer Deaths Sharply Higher in United Kingdom

A British man diagnosed with prostate cancer is at least twice as likely to die of the disease as an American is. One study found men in the United Kingdom were six times more likely to die over a five-year period.^71,72

There are a number of reasons for this, but the factor that most stands out is lack of national PSA screening in Britain compared to the United States.

Prostate cancer mortality (death) rates peaked in the early 1990s at almost identical rates in both countries until year 1994, when PSA screening was launched in the United States but not in Britain.

Death rates from prostate cancer declined four times more in the United States compared to Britain in the years that coincided with higher PSA screening in the United States. Patients aged 75 or older in the United States saw the largest and longest-lasting decline in mortality.^73,74

These sharply higher prostate cancer death rates in Britain are even more striking when one realizes there are five times more men of African descent in the United States compared to Britain.

The incidence of prostate cancer in men of African descent is far higher, as is its aggressiveness. This means there should be a higher rate of Americans dying of prostate cancer than the British. Since the advent of widespread PSA testing, however, prostate cancer mortality has plummeted in the United States, but remained stubbornly high in Britain.

There are other factors causing so many more British men to perish from prostate cancer including a socialized medical system that often delays treating prostate cancer until painful bone metastasis develop. This is especially the case with elderly men who are most vulnerable to the adverse impact of rationed health care.

The sad reality, however, is that the failure of the British system relating to screening and early treatment results in 49% of British prostate cancer victims dying within five years compared to less than 9% in the United States.⁷²

To put this in further perspective, prostate cancer is diagnosed in 47,300 men every year in Britain and there are around 10,800 deaths per year from the disease.⁷⁵ In the United States, about 180,000 men are diagnosed with prostate cancer (approximately four times as many) and only 26,120 die of it.¹ Based on a population ratio calculation, a far higher percentage of diagnosed British men die of prostate cancer compared to their American counterparts.

The fact that there is a debate about the value of widespread PSA screening is ludicrous in light of these striking differences in survival rates between Britain and the United States.

Looming Prostate Cancer Epidemic

We are in the midst of a lifesaving technology going in reverse. The consequence will be thousands of needless deaths from metastatic prostate cancer.

Our federal government has taken a vehement stand against PSA screening. So much so that physicians may be financially penalized if they prescribe a PSA blood test to a healthy man.⁸⁷

The initial results are that far fewer men are being diagnosed with prostate cancer.

This does not mean prostate cancer incidence is dropping. It only means that fewer early-stage curable and/or manageable prostate cancers are being detected.

The impact of this decrease in PSA screening will be an explosion of metastatic (advanced) prostate cancer cases in the coming years, just the way it was in the days preceding the introduction of the PSA blood test.

None of this has to happen. Newer imaging procedures, along with precision cryoablation techniques, can facilitate the diagnosis and eradication of early-stage prostate cancers. A fascinating article about a more advanced prostate cancer treatment option is described in this month’s issue.

In cases of low-risk prostate cancer diagnosed early, men can be educated about diet, lifestyle changes, and ways to diminish exposure to factors that cancer depends upon for growth, invasion, and metastasis. This method is best termed proactive integrative care.

This means that not every diagnosis of prostate cancer equates with surgery, radiation, or other forms of side-effect prone treatment.

Reawakening to Value of PSA Screening

Aging males have been lulled into a false sense of security when it comes to prostate cancer risk. They are hearing that annual PSA screening is no longer deemed necessary by our medical “authorities.”

Despite this edict, low-cost PSA blood tests remain available to enlightened individuals. Those who understand how to rationally utilize the results can successfully intervene in response to any evidence of pathology uncovered by a PSA test.

Unlike most malignancies, prostate cancer is usually responsive to early- and later-stage interventions including lifestyle change and hormone modulation.

Improved rates of successful treatment of low-grade prostate cancers have led researchers at the University of California-San Francisco to conclude that prior arguments against widespread PSA screening are now less compelling.⁸⁸ More physicians today recognize that many early-stage prostate cancers don’t require aggressive treatment to effectively manage the disease.

This was reinforced in articles published late last year in the Journal of the American Medical Association (November 17, 2015) showing that discontinuing PSA screening will result in a sharp increase in prostate cancer death rates that may not become symptomatically apparent until year 2022.⁸⁹ These articles also describe improved methods of active surveillance in response to rising PSA levels.

What both sides overlook is that many prostate cancers are reversible in response to lifestyle changes and nontoxic approaches. This means that men can take charge now to reduce risk, even if they have not yet developed a clinically relevant prostate malignancy.

If a man with reversible disease is to initiate these natural approaches, he should first assess the health of his prostate gland, which is why annual PSA blood testing starting at age 40 is so critical. And if there is a family history of prostate cancer, as well as a family history of other cancers that increases a man’s risk of prostate cancer, such as breast cancer and/or colorectal cancer, then the PSA testing should begin at age 35.

You have read in this article about human clinical findings showing robust reductions in prostate cancer risk and improved treatment outcomes in response to healthier living patterns. This indicates a logical recipe utilizing safe and natural approaches in response to a rising PSA level.

Annual Blood Test Super Sale

Most Americans delay getting lab tests until after outward symptoms of serious disease develop.

The reasons for blood test deferrals include not knowing which tests to order, difficulty in finding a physician to prescribe proper blood tests, inability to access blood test results, and lack of affordability.

Life Extension^® resolved these problems 20 years ago by offering comprehensive blood test panels direct to health-conscious consumers at low prices with quick turnaround times, free access to health advisors to review results, and convenient drawing time usually with no appointment needed.

Every year on April 1, we announce our Blood Test Super Sale that slashes the price of our comprehensive panels by 50%.

This annual event prompts health-conscious consumers to order our Male or Female Blood Test Panels to identify health problems in time to take corrective actions.

A description of these popular blood test panels appears on the next page. Our Male Panel includes the PSA test that we consider critical for all men over age 40.

To order these tests at savings of 50%, call .1-800-208-3444.

For longer life,

William Faloon

References

1. Available at: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics. Accessed March 14, 2016.
2. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet. 2014;384(9959):2027-35.
3. Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065-9; discussion 9-70.
4. Yang M, Kenfield SA, Van Blarigan EL, et al. Dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality. Cancer Prev Res (Phila). 2015;8(6):545-51.
5. Yang M, Kenfield SA, Van Blarigan EL, et al. Dairy intake after prostate cancer diagnosis in relation to disease-specific and total mortality. Int J Cancer. 2015;137(10):2462-9.
6. Antwi SO, Steck SE, Zhang H, et al. Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer. Cancer Epidemiol. 2015;39(5):752-62.
7. Tomaszewski JJ, Richman EL, Sadetsky N, et al. Impact of folate intake on prostate cancer recurrence following definitive therapy: data from CaPSURE. J Urol. 2014;191(4):971-6.
8. Moreira DM, Banez LL, Presti JC, Jr., et al. High serum folate is associated with reduced biochemical recurrence after radical prostatectomy: results from the SEARCH Database. Int Braz J Urol. 2013;39(3):312-8; discussion 9.
9. Bashir MN, Malik MA. Case-control study of diet and prostate cancer in a rural population of Faisalabad, Pakistan. Asian Pac J Cancer Prev. 2015;16(6):2375-8.
10. Antwi SO, Steck SE, Su LJ, et al. Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP). Prostate. 2015;75(13):1419-35.
11. Askari F, Parizi MK, Jessri M, et al. Fruit and vegetable intake in relation to prostate cancer in Iranian men: a case-control study. Asian Pac J Cancer Prev. 2014;15(13):5223-7.
12. Rosato V, Edefonti V, Bravi F, et al. Nutrient-based dietary patterns and prostate cancer risk: a case-control study from Italy. Cancer Causes Control. 2014;25(4):525-32.
13. Bhindi B, Kulkarni GS, Finelli A, et al. Obesity is associated with risk of progression for low-risk prostate cancers managed expectantly. Eur Urol. 2014;66(5):841-8.
14. Hsing AW, Sakoda LC, Chua SC. Obesity, metabolic syndrome, and prostate cancer. The Am J Clin Nutr. 2007;86(3):843S-57S.
15. Shivappa N, Bosetti C, Zucchetto A, et al. Association between dietary inflammatory index and prostate cancer among Italian men. Br J Nutr. 2014:1-6.
16. Abdull Razis AF, Noor NM. Cruciferous vegetables: dietary phytochemicals for cancer prevention. Asian Pac J Cancer Prev. 2013;14(3):1565-70.
17. Garikapaty VP, Ashok BT, Chen YG, et al. Anti-carcinogenic and anti-metastatic properties of indole-3-carbinol in prostate cancer. Oncol Rep. 2005;13(1):89-93.
18. Chiao JW, Wu H, Ramaswamy G, et al. Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis. 2004;25(8):1403-8.
19. Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer Lett. 2008;269(2):291-304.
20. Chinni SR, Li Y, Upadhyay S, et al. Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene. 2001;20(23):2927-36.
21. Garikapaty VP, Ashok BT, Tadi K, et al. 3,3’-Diindolylmethane downregulates pro-survival pathway in hormone independent prostate cancer. Biochem Biophys Res Commun. 2006;340(2):718-25.
22. Leitzmann MF, Stampfer MJ, Michaud DS, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr. 2004;80(1):204-16.
23. Chavarro JE, Stampfer MJ, Li H, et al. A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1364-70.
24. Norrish AE, Skeaff CM, Arribas GL, et al. Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study. Br J Cancer. 1999;81(7):1238-42.
25. Terry P, Lichtenstein P, Feychting M, et al. Fatty fish consumption and risk of prostate cancer. Lancet. 2001;357(9270):1764-6.
26. Aronson WJ, Kobayashi N, Barnard RJ, et al. Phase II prospective randomized trial of a low-fat diet with fish oil supplementation in men undergoing radical prostatectomy. Cancer Prev Res (Phila). 2011;4(12):2062-71.
27. Dorai T, Cao YC, Dorai B, et al. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001;47(4):293-303.
28. Hong JH, Ahn KS, Bae E, et al. The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo. Prostate Cancer Prostatic Dis. 2006;9(2):147-52.
29. Teiten MH, Gaascht F, Eifes S, et al. Chemopreventive potential of curcumin in prostate cancer. Genes Nutr. 2010;5(1):61-74.
30. Piantino CB, Salvadori FA, Ayres PP, et al. An evaluation of the anti-neoplastic activity of curcumin in prostate cancer cell lines. Int Braz J Urol. 2009;35(3):354-60; discussion 61.
31. Nakamura K, Yasunaga Y, Segawa T, et al. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol. 2002;21(4):825-30.
32. Chaudhary LR, Hruska KA. Inhibition of cell survival signal protein kinase B/Akt by curcumin in human prostate cancer cells. J Cell Biochem. 2003;89(1):1-5.
33. Pang X, Yi Z, Zhang X, et al. Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Res. 2009;69(14):5893-900.
34. Yuan HQ, Kong F, Wang XL, et al. Inhibitory effect of acetyl-11-keto-beta-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells. Biochem Pharmacol. 2008;75(11):2112-21.
35. Lu M, Xia L, Hua H, et al. Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells. Cancer Res. 2008;68(4):1180-6.
36. Soares Nda C, Teodoro AJ, Oliveira FL, et al. Influence of lycopene on cell viability, cell cycle, and apoptosis of human prostate cancer and benign hyperplastic cells. Nutr Cancer. 2013;65(7):1076-85.
37. Rafi MM, Kanakasabai S, Reyes MD, et al. Lycopene modulates growth and survival associated genes in prostate cancer. J Nutr Biochem. 2013;24(10):1724-34.
38. Wertz K. Lycopene effects contributing to prostate health. Nutr Cancer. 2009;61(6):775-83.
39. Trejo-Solis C, Pedraza-Chaverri J, Torres-Ramos M, et al. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid Based Complement Alternat Med. 2013;2013:705121.
40. Wan L, Tan HL, Thomas-Ahner JM, et al. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. Cancer Prev Res (Phila). 2014;7(12):1228-39.
41. Chen P, Zhang W, Wang X, et al. Lycopene and risk of prostate cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2015;94(33):e1260.
42. Lu QY, Hung JC, Heber D, et al. Inverse associations between plasma lycopene and other carotenoids and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2001;10(7):749-56.
43. Siddiqui IA, Zaman N, Aziz MH, et al. Inhibition of CWR22Rnu1 tumor growth and PSA secretion in athymic nude mice by green and black teas. Carcinogenesis. 2006;27(4):833-9.
44. Chuu CP, Chen RY, Kokontis JM, et al. Suppression of androgen receptor signaling and prostate specific antigen expression by (-)-epigallocatechin-3-gallate in different progression stages of LNCaP prostate cancer cells. Cancer Lett. 2009;275(1):86-92.
45. McLarty J, Bigelow RL, Smith M, et al. Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. Cancer Prev Res (Phila). 2009;2(7):673-82.
46. Bettuzzi S, Brausi M, Rizzi F, et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006;66(2):1234-40.
47. Pandey M, Gupta S. Green tea and prostate cancer: from bench to clinic. Front Biosci (Elite Ed). 2009;1:13-25.
48. Demark-Wahnefried W, Robertson CN, Walther PJ, et al. Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen. Urology. 2004;63(5):900-4.
49. Demark-Wahnefried W, Polascik TJ, George SL, et al. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev. 2008;17(12):3577-87.
50. McCann MJ, Gill CI, Linton T, et al. Enterolactone restricts the proliferation of the LNCaP human prostate cancer cell line in vitro. Mol Nutr Food Res. 2008;52(5):567-80.
51. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004;11(4):887-92.
52. Gallardo-Williams MT, Chapin RE, King PE, et al. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol. 2004;32(1):73-8.
53. Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004;216(1):21-9.
54. Chang S, Erdman JW, Jr., Clinton SK, et al. Relationship between plasma carotenoids and prostate cancer. Nutr Cancer. 2005;53(2):127-34.
55. Zhang J, Dhakal I, Stone A, et al. Plasma carotenoids and prostate cancer: a population-based case-control study in Arkansas. Nutr Cancer. 2007;59(1):46-53.
56. Jiang Q, Wong J, Ames BN. Gamma-tocopherol induces apoptosis in androgen-responsive LNCaP prostate cancer cells via caspase-dependent and independent mechanisms. Ann N Y Acad Sci. 2004;1031:399-400.
57. Galli F, Stabile AM, Betti M, et al. The effect of alpha- and gamma-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation. Arch Biochem Biophys. 2004;423(1):97-102.
58. Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst. 2000;92(24):2018-23.
59. Bao BY, Yeh SD, Lee YF. 1alpha,25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases. Carcinogenesis. 2006;27(1):32-42.
60. Shui IM, Mucci LA, Kraft P, et al. Vitamin D-related genetic variation, plasma vitamin D, and risk of lethal prostate cancer: a prospective nested case-control study. J Natl Cancer Inst. 2012;104(9):690-9.
61. Beer TM, Myrthue A. Calcitriol in the treatment of prostate cancer. Anticancer Res. 2006;26(4a):2647-51.
62. Vijayakumar S, Mehta RR, Boerner PS, et al. Clinical trials involving vitamin D analogs in prostate cancer. Cancer J. 2005;11(5):362-73.
63. Crescioli C, Maggi M, Luconi M, et al. Vitamin D3 analogue inhibits keratinocyte growth factor signaling and induces apoptosis in human prostate cancer cells. Prostate. 2002;50(1):15-26.
64. John EM, Schwartz GG, Koo J, et al. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res. 2005;65(12):5470-9.
65. Lou YR, Qiao S, Talonpoika R, et al. The role of vitamin D3 metabolism in prostate cancer. J Steroid Biochem Mol Biol. 2004;92(4):317-25.
66. Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol. 2010;6(3):457-70.
67. Vazquez-Martin A, Oliveras-Ferraros C, Lopez-Bonet E, et al. AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor. Cell Cycle. 2009;8(22):3679-83.
68. Choi YK, Park KG. Metabolic roles of AMPK and metformin in cancer cells. Mol Cells. 2013;36(4):279-87.
69. Schiewer MJ, Knudsen KE. AMPed up to treat prostate cancer: novel AMPK activators emerge for cancer therapy. EMBO Mol Med. 2014;6(4):439-41.
70. Available at: https://www.lifeextension.com/magazine/2014/ss/ampk/page-01. Accessed March 15, 2016.
71. Sachdeva A, van der Meulen JH, Emberton M, et al. Evaluating variation in use of definitive therapy and risk-adjusted prostate cancer mortality in England and the USA. BMJ Open. 2015;5(2):e006805.
72. Coleman MP, Quaresma M, Berrino F, et al. Cancer survival in five continents: a worldwide population-based study (CONCORD). Lancet Oncol. 9(8):730-56.
73. Collin SM, Martin RM, Metcalfe C, et al. Prostate-cancer mortality in the USA and UK in 1975-2004: an ecological study. Lancet Oncol. 2008;9(5):445-52.
74. Available at: http://www.dailymail.co.uk/health/article-560161/prostate-cancer-death-rate-falls-times-faster-u-s-uk-routine-screening.html. Accessed March 15, 2016.
75. Available at: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer#heading-zero. Accessed March 15, 2016.
76. Rahman MI, Chagoury ME, Zhong Y, et al. Selections from current literature: PSA screening for prostate cancer. Fam Pract. 1996;13(6):544-9.
77. Potosky AL, Feuer EJ, Levin DL. Impact of screening on incidence and mortality of prostate cancer in the United States. Epidemiol Rev. 2001;23(1):181-6.
78. Kopec JA, Goel V, Bunting PS, et al. Screening with prostate specific antigen and metastatic prostate cancer risk: a population based case-control study. J Urol. 2005;174(2):495-9; discussion 9.
79. Available at: http://drcatalona.com/quest/quest_spring09_3.htm. Accessed March 15, 2016.
80. Available at: http://www.uspreventiveservicestaskforce.org/page/document/recommendationstatementfinal/prostate-cancer-screening. Accessed March 15, 2016.
81. Available at: http://www.nytimes.com/2011/10/12/us/politics/9-9-9-plan-psa-tests-and-tax-holidays-debated-by-republicans.html. Accessed March 15, 2016.
82. Available at: http://www.medpagetoday.com/publichealthpolicy/healthpolicy/36647. Accessed March 15, 2016.
83. Available at: http://thechart.blogs.cnn.com/2012/05/21/task-force-psa-tests-do-more-harm-than-good. Accessed March 15, 2016.
84. Available at: http://vitals.nbcnews.com/_news/2012/05/21/11796812-halting-psa-testing-the-right-thing-to-do-bioethicist-says?d=1. Accessed March 15, 2016.
85. Available at: http://abcnews.go.com/health/cancerpreventionandtreatment/uspstf-scuttles-recommendations-psa-screening-test/story?id=16398686. Accessed March 15, 2016.
86. Available at: http://cpr.heart.org/ahaecc/cprandecc/aboutcprfirstaid/historyofcpr/ucm_475751_history-of-cpr.jsp. Accessed March 21, 2016.
87. Available at: http://www.wsj.com/articles/doctors-could-be-penalized-for-ordering-prostate-tests-1447993920. Accessed March 21, 2016.
88. Carlsson S, Leapman M, Carroll P, et al. Who and when should we screen for prostate cancer? Interviews with key opinion leaders. BMC Medicine. 2015;13:288.
89. Penson DF. The pendulum of prostate cancer screening. JAMA. 2015;314(19):2031-3.