The role of nutritional interventions in prostate cancer: A review
Mohammad Reza Nowroozi1, Ehsan Ghaedi2, Amir Behnamfar1, Erfan Amini1, Seyed Ali Momeni1, Maryam Mahmoudi3, Nima Rezaei4, Saied Bokaie5, Laleh Sharifi6
1 Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
2 Students' Scientific Research Center; Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
4 Research Center For Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN); Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
6 Uro-Oncology Research Center, Tehran University of Medical Sciences; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
|Date of Submission||07-Sep-2020|
|Date of Decision||22-Sep-2020|
|Date of Acceptance||25-Dec-2020|
|Date of Web Publication||27-May-2021|
Dr. Laleh Sharifi
Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
The high prevalence rate in conjunction with the long latency period made prostate cancer (PCa) an attractive and reasonable candidate for preventive measures. So far, several dietary and nutritional interventions have been implemented and studied with the aim of preventing the development or delaying the progression of PCa. Calorie restriction accompanied by weight loss has been shown to be associated with decreased likelihood of aggressive PCa. Supplements have played a major role in nutritional interventions. While genistein and lycopene seemed promising as preventive agents, minerals such as zinc and selenium were shown to be devoid of protective effects. The role of vitamins has been widely studied, with special emphasis on vitamins with antioxidant properties. Data related to Vitamin A and Vitamin C were rather controversial and positive effects were of insignificant magnitude. Vitamin E was associated with a decreased risk of PCa in high-risk groups like smokers. However, when it comes to Vitamin D, the serum levels might affect the risk of PCa. While deficiency of this vitamin was associated with increased risk, high serum levels imposed the risk of aggressive disease. Despite the seemingly promising effects of dietary measures on PCa, no firm recommendation could be made due to the limitations of the studies and evidence. However, the majority of these advices could be followed by the patients with the intent of living a healthy lifestyle.
Keywords: Diet, nutritional interventions, prostate cancer, supplements
|How to cite this article:|
Nowroozi MR, Ghaedi E, Behnamfar A, Amini E, Momeni SA, Mahmoudi M, Rezaei N, Bokaie S, Sharifi L. The role of nutritional interventions in prostate cancer: A review. J Res Med Sci 2021;26:29
|How to cite this URL:|
Nowroozi MR, Ghaedi E, Behnamfar A, Amini E, Momeni SA, Mahmoudi M, Rezaei N, Bokaie S, Sharifi L. The role of nutritional interventions in prostate cancer: A review. J Res Med Sci [serial online] 2021 [cited 2021 Jun 21];26:29. Available from: https://www.jmsjournal.net/text.asp?2021/26/1/29/316994
| Introduction|| |
Extensive evidence exists related to the role of different nutrients and diets in prostate cancer (PCa) development., In fact, several studies have shown that a healthy diet can prevent up to 40% of all cancers. PCa is the second most prevalent cancer in men; it imposes an overwhelming financial burden on medical systems. Therefore, it is justified to make every effort to prevent its development and halt its progression. The long latency period between the initial evidence of PCa and the development of overt disease provides us with the opportunity to affect the course of the disease through dietary and nutritional interventions. In this review, we intend to outline the dietary and nutritional interventions which have been implemented with the aim of modifying the risk of development and progression of PCa.
| Calorie Restriction and Weight Loss|| |
So far, obesity has reached epidemic proportions in developed countries due to the increased availability of food resources in addition to hereditary and behavioral and psychological factors. As such, the number of overweight and obese people has doubled worldwide in the past two decades.
Obesity has been found to be associated with PCa progression and aggressiveness. In addition, it was correlated with increased biochemical recurrence, poor nonsurgical treatments outcome, and higher cancer-specific mortality.,,, Therefore, it seems rational to assume that calorie restriction accompanied by weight loss can reduce the likelihood of aggressive form of PCa. Calorie restriction reportedly slows the progression of PCa in TRAMP mice and prolongs its survival. In addition, 30% calorie reduction in Hi-Myc transgenic mice delays PCa development. Moreover, it has been shown that weight loss of more than 11 pounds in a period of 10 years reduced the incidence of nonmetastatic high-grade PCa by 45%. However, a 6-month low-carbohydrate regimen in patients with biochemical recurrence was not associated with improvement in PSA doubling time compared to the control group. More studies are needed to assess the effects of weight loss on PCa progression.
| Supplementation|| |
Soy and Soy products
Epidemiologic studies have suggested that higher consumption of soy and soy products is associated with the reduced risk of PCa. The Adventist Health Study showed that participants who consumed soy milk more than once a day had a 70% lower risk of PCa (RR = 0.3). High concentrations of isoflavonoids in the prostate fluid may block cellular proliferation and also decrease the toxic byproducts of oxidation through its antioxidant activity.
Genistein is the major isoflavone in soy products. Its effect on PCa cells has been widely studied. An animal study showed that dietary soy products may decrease the growth of transplantable human prostate carcinoma in mice. Although there are some data in favor of preventive role of genistein, a scarcity of evidence exists related to its use as a treating agent in PCa.
A randomized controlled trial (RCT) evaluated the effect of a combination of Vitamin E, selenium, and soy on progression from high-grade prostatic intraepithelial neoplasia (HGPIN) to PCa. The hazard ratio for this combination to prevent PCa was 1.03 (95% CI, 0.67–1.60; P = 0.88). Therefore, the authors believed that these agents have no role in the primary prevention of invasive PCa in men with HGPIN at biopsy. However, in a systematic review and meta-analysis conducted by Applegate et al., there was a statistically significant association between soy consumption and decreased risk of PCa.
Lycopene is a powerful antioxidant mostly present in tomatoes. Several epidemiological, experimental, and clinical studies over the past decade reported that consumption of tomatoes and tomato products is associated with a reduced risk of PCa. Lycopene is responsible for the red pigment of tomatoes and watermelon. It exists in prostate tissue in large amounts. A large cohort study reported that consumption of two to four servings of raw tomatoes weekly is associated with a 26% reduction of PCa risk. The risk is reduced even more (35%) by increasing the number of servings to more than 10. Other studies also reported an inverse association between serum lycopene level and PCa risk in subjects older than 65 years old.
In a trial, PCa patients consumed tomato sauce-based pasta for 21 days prior to radical prostatectomy. Lycopene consumption significantly decreased prostate-specific antigen (PSA) levels and leukocyte oxidative DNA damage. A decrease in PCa risk also has been shown in a large meta-analysis (relative risk [RR] = 0.78, 95% confidence interval [CI]: 0.66–0.92). It has been postulated that lycopene may exert its protective effects through saving 2-deoxy-guanosine from reactive oxygen species, decreasing insulin-like growth factor-1-induced cell proliferation,,, and decreasing carcinogen phosphorylation of tumor suppressor genes like p53. Moreover, lycopene has been noticed to be able to downregulate androgen metabolism and signaling in PCa.
Selenium theoretically plays a role in the pituitary–adrenal–gonadal axis and a clinical trial revealed that it may exert a protective effect against PCa development. Furthermore, another RCT showed that intake of 200 μg of selenized yeast was associated with a 49% reduction in the risk of PCa, especially in low baseline serum selenium levels and age of younger than 65 years with a PSA of <4 ng/mL. However, the protective effects of selenium have been contravened by upcoming trials. According to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) trial, neither selenium or Vitamin E alone nor their combination did not decrease PCa risk. In fact, selenium supplementation was associated with an increase in PCa risk. Based on this well-conducted study, the authors recommended against using these supplements as preventive agents., Later, a Mendelian randomization analysis confirmed SELECT findings and showed that not only selenium had no effect on PCa prevention but also was associated with advanced PCa.
Zinc with its antioxidant characteristics has been reported to be present in high amounts in the prostate tissue; in vitro studies showed that it inhibits PCa cell growth., In a study, dietary zinc was not found to be associated with a decrease in PCa risk overall. However, the risk of advanced PCa reduced with a greater intake of supplemental zinc. A comprehensive review claims that zinc supplementation is a credible approach for the prevention of PCa development.
Pomegranate extract was shown to be able to inhibit the growth of PCa cells and induce apoptosis of aggressive human PCa cells. An experimental study on human metastatic PCa cell lines revealed that pomegranate juice and peel extracts exert anti-cancer effects against PCa cells through the mechanistic target of rapamycin signaling cascade. In a Phase II RCT of men with rising PSA following radical prostatectomy or radiotherapy, daily consumption of pomegranate juice for several months led to prolongation of PSA doubling time implying that this supplement may slow down the progression of PCa., Thus, this agent might be used in PCa patients with the aim of improving their treatment outcomes and hopefully survival.
Green tea and black tea
Polyphenolic antioxidant of tea has been reported to be able to prevent cancer formation in prostate cells. In a trial, 20 men who were scheduled for radical prostatectomy were randomly assigned to three groups of green tea, black tea, and caffeine-matched soda (as control group). The patients consumed these drinks in a daily fashion for 5 days prior to the operation. Green tea and black tea led to higher polyphenols concentration in prostate tissue compared to soda. Interestingly, the proliferation of PCa cells could be blocked by adding the serum of the patients who took green or black tea to the medium. In addition, the study verified the bioavailability of theaflavins in prostate tissue; where they may exert their preventive effects.
Several experimental and epidemiological studies have focused on the possible role of catechins and other tea polyphenols against PCa in humans. In a study, the authors did notice that green tea consumption was associated with a dose-dependent decrease in the risk of advanced PCa (RR = 0.52, 95% CI 0.28-0.96). In an RCT, 60 volunteers with high-grade PIN randomized to receive either green tea catechins or placebo and followed with two saturation biopsies within a year. Green tea catechins supplementation was associated with an almost 80% reduction in PCa diagnosis, from 53% to 11%. Recently, a meta-analysis revealed that drinking green tea of more than 7 cups/day can reduce the risk of PCa. In addition, the green tea catechins were found to be effective in preventing PCa (RR = 0.38, P = 0.02).
Findings regarding the possible preventive role of Vitamin E supplementation are conflicting. While some studies endorse beneficial role of Vitamin E as a preventive agent,, others reject this notion or are inconclusive. The early report of the SELECT showed that Vitamin E had no effect on PCa development. However, with longer follow-up, the study revealed that dietary supplementation of Vitamin E significantly increased the risk of PCa among healthy men.
Several studies claimed that the effect of Vitamin E supplementation on PCa risk could be varied based on the smoking history of the patients. As such, SELECT trial has shown that Vitamin E may help prevent PCa in smokers as opposed to nonsmokers; possibly due to the high oxidative stress conditions in smokers. In fact, in nonsmokers, Vitamin E excess could enhance PCa risk. Likewise, the prostate, lung, colorectal, and ovarian (PLCO) study showed a significant decrease in PCa aggressiveness among smokers following Vitamin E supplementation (doses in excess of 400 IU/day led to 71% reduction in risk of advanced PCa). In general, Vitamin E supplementation may only exert a protective effect against PCa in high-risk groups like smokers.
Animal studies showed that Vitamin C alone or in combination with Vitamin E inhibits PCa cell growth. A study claimed that higher intakes of fruits-including citrus fruits rich in Vitamin C-were associated with the higher incidence of PCa (OR = 1.51, 95% CI = 1.1–-2.01 for 4th quartile). This finding appears to contradict the hypothesis of the protective effects of Vitamin C. Moreover, an RCT showed that a daily intake of 400 IU Vitamin E and 500 mg of Vitamin C was not associated with a decrease in PCa risk. Vitamin C in doses higher than recommended dietary levels might have therapeutic effects in some cancers. A study showed that the administration of high-dose intravenous Vitamin C led to PSA reduction in 75% of prostatic cancer patients. However, this finding was no reproduced in another trial.
Vitamin A and β-carotene
Beta-carotene is a precursor of Vitamin A and is responsible for the orange pigment in plants and vegetables. In a case–control study, higher intake of carotene and beta-carotene was associated with a decline in PCa risk (OR = 0.70 and 0.72, respectively). A nested case–control study in the PLCO trial showed that higher concentrations of serum retinol were associated with a 42% reduction in aggressive (GS >7) PCa risk. In contrast, in carotene and retinol efficacy trial, the risk of PCa did not differ by taking a daily dose of β-carotene (30 mg) and retinyl palmitate (25,000 IU). However, when other dietary supplements accompanied this combination, the risk of aggressive PCa increased (RR = 1.52). Nevertheless, a recent study showed that daily intake of carrot (>3.2 g/day) might be associated with decreased PCa risk (OR: 0.35, CI: 0.21–0.58).
Vitamin D receptor signaling has been found to play role in the development and prognosis of PCas. Moreover, it has been reported that Calcitriol is able to inhibit the proliferation of PCa cell lines. A study conducted by John et al. showed that residential sunlight exposure is associated with lower PCa risk; the result which indirectly points to the protective effect of Vitamin D on PCa. Likewise, higher circulating 25(OH) D has been shown to be associated with a 57% reduction in the risk of lethal PCa. It has been proposed that Vitamin D binding protein may modulate the association between serum Vitamin D levels and the risk of advanced and lethal PCa.
However, some studies have put this effect into question as higher serum levels of Vitamin D were not associated with decreased PCa risk. In fact, it might be associated with the greater risk of aggressive PCa.,
Resveratrol known as a superior cancer chemopreventive agent is a stilbenoid with potential antioxidant properties which is found in high amounts in grapes skin. The results of pre-clinical studies in animals and cell lines led to the hypothesis that this agent may exert a preventive effect on cancers including PCa. In a recent study, researchers assessed the synergic effect of resveratrol and cisplatin on PCa cells viability and apoptosis. Resveratrol has been shown to promotes apoptosis in PCa cells and sensitizes these cells to cisplatin. Thus, despite the scarcity of clinical data, it seems worthwhile to consider resveratrol as a potential cancer-preventive agent in future clinical studies.
Indoles and isothiocyanates
Indoles are found in Brassica vegetables such as cabbage, broccoli, and Brussels sprouts. An in vitro study revealed that Indole-3-carbinol has anti-proliferative effects on PCa cells. Thus, it deserves to be considered as a potential chemotherapeutic agent and warrants further study. A study showed that higher consumption of cruciferous vegetables-as the main source of Isothiocyanates-is associated with reduced risk of PCa. Nevertheless, this association was not replicated by another trial.
| Conclusion|| |
The relatively indolent course of PCa provides us with the opportunity to intervene with the intention of preventing the disease using a variety of nutritional and lifestyle modifications. So far, many dietary and nutritional interventions have been studied such as calorie restriction and supplement consumption. Calorie restriction has been shown to be associated with the decreased likelihood of aggressive PCa. Supplements like pomegranate may improve PCa treatment outcomes. In addition, antioxidant products found in green and black tea seems to decrease the risk of advanced PCa. Furthermore, genistein in soy products and lycopene in tomatoes are associated with a decreased risk of PCa. However, minerals such as zinc and selenium are not proved to have a preventive effect on PCa. Regarding vitamins, data related to the preventive role of Vitamin A and Vitamin C are inconsistent and results are rather controversial. However, Vitamin E has a reportedly positive effect on preventing PCa in high-risk groups particularly smokers. Furthermore, it seems that Vitamin D deficiency is associated with an increased risk of PCa. Though, more aggressive phenotype of the disease is noticed with higher serum levels of this vitamin. In the nutshell, there are no conclusive evidence regarding the positive effect of nutritional interventions on PCa development and progression. Nevertheless, the majority of these instructions and protocols could be followed by the patients with the intent of living a healthy lifestyle.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kaiser A, Haskins C, Siddiqui MM, Hussain A, D'Adamo C. The evolving role of diet in prostate cancer risk and progression. Curr Opin Oncol 2019;31:222-9.
Matsushita M, Fujita K, Nonomura N. Influence of diet and nutrition on prostate cancer. Int J Mol Sci 2020;21:1447.
Sharifi L. Nutrition and Cancer. In: Mahmoudi M, Rezaei N, editors. Nutrition and Immunity. Cham: Springer; 2019.
Zhai Z, Zheng Y, Li N, Deng Y, Zhou L, Tian T, et al
. Incidence and disease burden of prostate cancer from 1990 to 2017: Results from the global burden of disease study. Cancer 2020;126:1969-78.
Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: United States. NCHS Data Brief 2015;219:1-8.
Wright ME, Chang SC, Schatzkin A, Albanes D, Kipnis V, Mouw T, et al
. Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality. Cancer 2007;109:675-84.
Zhong S, Yan X, Wu Y, Zhang X, Chen L, Tang J, et al
. Body mass index and mortality in prostate cancer patients: A dose-response meta-analysis. Prostate Cancer Prostatic Dis 2016;19:122-31.
Xie B, Zhang G, Wang X, Xu X. Body mass index and incidence of nonaggressive and aggressive prostate cancer: A dose-response meta-analysis of cohort studies. Oncotarget 2017;8:97584-92.
Hu MB, Liu SH, Jiang HW, Bai PD, Ding Q. Obesity affects the biopsy-mediated detection of prostate cancer, particularly high-grade prostate cancer: A dose-response meta-analysis of 29,464 patients. PLoS One 2014;9:e106677.
Bonorden MJ, Rogozina OP, Kluczny CM, Grossmann ME, Grambsch PL, Grande JP, et al
. Intermittent calorie restriction delays prostate tumor detection and increases survival time in TRAMP mice. Nutr Cancer 2009;61:265-75.
Blando J, Moore T, Hursting S, Jiang G, Saha A, Beltran L, et al
. Dietary energy balance modulates prostate cancer progression in Hi-Myc mice. Cancer Prev Res (Phila) 2011;4:2002-14.
Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV, et al
. Body mass index, weight change, and risk of prostate cancer in the cancer prevention study II nutrition cohort. Cancer Epidemiol Biomarkers Prev 2007;16:63-9.
Freedland SJ, Allen J, Jarman A, Oyekunle T, Armstrong AJ, Moul JW, et al
. A randomized controlled trial of a 6-month low-carbohydrate intervention on disease progression in men with recurrent prostate cancer: Carbohydrate and prostate study 2 (CAPS2). Clin Cancer Res 2020;26:3035-43.
Hedlund TE, Maroni PD, Ferucci PG, Dayton R, Barnes S, Jones K, et al
. Long-term dietary habits affect soy isoflavone metabolism and accumulation in prostatic fluid in caucasian men. J Nutr 2005;135:1400-6.
Zhou JR, Gugger ET, Tanaka T, Guo Y, Blackburn GL, Clinton SK. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr 1999;129:1628-35.
Perabo FG, Von Löw EC, Ellinger J, von Rücker A, Müller SC, Bastian PJ. Soy isoflavone genistein in prevention and treatment of prostate cancer. Prostate Cancer Prostatic Dis 2008;11:6-12.
Fleshner NE, Kapusta L, Donnelly B, Tanguay S, Chin J, Hersey K, et al
. Progression from high-grade prostatic intraepithelial neoplasia to cancer: A randomized trial of combination Vitamin-E, soy, and selenium. J Clin Oncol 2011;29:2386-90.
Applegate CC, Rowles JL, Ranard KM, Jeon S, Erdman JW. Soy consumption and the risk of prostate cancer: An updated systematic review and meta-analysis. Nutrients 2018;10:40.
Giovannucci E. A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med (Maywood) 2002;227:852-9.
Campbell JK, Canene-Adams K, Lindshield BL, Boileau TW, Clinton SK, Erdman JW Jr. Tomato phytochemicals and prostate cancer risk. J Nutr 2004;134:3486S-92S.
Canene-Adams K, Campbell JK, Zaripheh S, Jeffery EH, Erdman JW Jr. The tomato as a functional food. J Nutr 2005;135:1226-30.
Etminan M, Takkouche B, Caamaño-Isorna F. The role of tomato products and lycopene in the prevention of prostate cancer: A meta-analysis of observational studies. Cancer Epidemiol Biomarkers Prev 2004;13:340-5.
Karas M, Amir H, Fishman D, Danilenko M, Segal S, Nahum A, et al
. Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells. Nutr Cancer 2000;36:101-11.
Soares ND, Elias MB, Lima Machado C, Trindade BB, Borojevic R, Teodoro AJ. Comparative analysis of lycopene content from different tomato-based food products on the cellular activity of prostate cancer cell lines. Foods 2019;8:201.
Tjahjodjati , Sugandi S, Umbas R, Satari M. The protective effect of lycopene on prostate growth inhibitory efficacy by decreasing insulin growth factor-1 in Indonesian human prostate cancer cells. Res Rep Urol 2020;12:137-43.
Johary A, Jain V, Misra S. Role of lycopene in the prevention of cancer. Int J Nutr Pharmacol Neurol Dis 2012;2:167. [Full text]
Applegate CC, Rowles JL 3rd
, Erdman JW Jr. Can lycopene impact the androgen axis in prostate cancer?: A systematic review of cell culture and animal studies. Nutrients 2019;11:633.
Clark LC, Dalkin B, Krongrad A, Combs GF Jr., Turnbull BW, Slate EH, et al
. Decreased incidence of prostate cancer with selenium supplementation: Results of a double-blind cancer prevention trial. Br J Urol 1998;81:730-4.
Duffield-Lillico AJ, Dalkin BL, Reid ME, Turnbull BW, Slate EH, Jacobs ET, et al
. Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: An analysis of the complete treatment period of the nutritional prevention of cancer trial. BJU Int 2003;91:608-12.
Klein EA, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR, et al
. SELECT: The next prostate cancer prevention trial. Selenum and Vitamin E cancer prevention trial. J Urol 2001;166:1311-5.
Klein EA, Thompson IM Jr., Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, et al
. Vitamin E and the risk of prostate cancer: The selenium and Vitamin E cancer prevention trial (SELECT). JAMA 2011;306:1549-56.
Kristal AR, Stanford JL, Cohen JH, Wicklund K, Patterson RE. Vitamin and mineral supplement use is associated with reduced risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 1999;8:887-92.
Powell SR. The antioxidant properties of zinc. J Nutr 2000;130:1447S-54S.
Liang JY, Liu YY, Zou J, Franklin RB, Costello LC, Feng P. Inhibitory effect of zinc on human prostatic carcinoma cell growth. Prostate 1999;40:200-7.
Gonzalez A, Peters U, Lampe JW, White E. Zinc intake from supplements and diet and prostate cancer. Nutr Cancer 2009;61:206-15.
Costello LC, Franklin RB. A comprehensive review of the role of zinc in normal prostate function and metabolism; And its implications in prostate cancer. Arch Biochem Biophys 2016;611:100-12.
Malik A, Mukhtar H. Prostate cancer prevention through pomegranate fruit. Cell Cycle 2006;5:371-3.
Chaves FM, Pavan IC, da Silva LG, de Freitas LB, Rostagno MA, Antunes AE, et al
. Pomegranate juice and peel extracts are able to inhibit proliferation, migration and colony formation of prostate cancer cell lines and modulate the Akt/mTOR/S6K signaling pathway. Plant Foods Hum Nutr 2020;75:54-62.
Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ, et al
. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res 2006;12:4018-26.
Jarrard DF, Filon M, Huang W, Kim K, Havighurst T, Konety BR, et al
. A phase IIa randomized placebo-controlled trial of pomegranate fruit extract/POMx in subjects with clinically localized prostate cancer undergoing active surveillance. Am Soc Clin Oncol 2020;38 (6 Suppl):285.
Miyata Y, Shida Y, Hakariya T, Sakai H. Anti-cancer effects of green tea polyphenols against prostate cancer. Molecules 2019;24:193.
Henning SM, Aronson W, Niu Y, Conde F, Lee NH, Seeram NP, et al
. Tea polyphenols and theaflavins are present in prostate tissue of humans and mice after green and black tea consumption. J Nutr 2006;136:1839-43.
Siddiqui IA, Adhami VM, Saleem M, Mukhtar H. Beneficial effects of tea and its polyphenols against prostate cancer. Mol Nutr Food Res 2006;50:130-43.
Kurahashi N, Sasazuki S, Iwasaki M, Inoue M, Tsugane S, JPHC Study Group. Green tea consumption and prostate cancer risk in Japanese men: A prospective study. Am J Epidemiol 2008;167:71-7.
Brausi M, Rizzi F, Bettuzzi S. Chemoprevention of human prostate cancer by green tea catechins: Two years later. A follow-up update. Eur Urol 2008;54:472-3.
Guo Y, Zhi F, Chen P, Zhao K, Xiang H, Mao Q, et al
. Green tea and the risk of prostate cancer: A systematic review and meta-analysis. Medicine (Baltimore) 2017;96:e6426.
Abraham A, Kattoor AJ, Saldeen T, Mehta JL. Vitamin E and its anticancer effects. Crit Rev Food Sci Nutr 2019;59:2831-8.
Heinonen OP, Koss L, Albanes D, Taylor PR, Hartman AM, Edwards BK, et al
. Prostate cancer and supplementation with α-tocopherol and β-carotene: Incidence and mortality in a controlled trial. J National Cancer Inst 1998;90:440-6.
Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al
. Effect of selenium and Vitamin E on risk of prostate cancer and other cancers: The selenium and Vitamin E cancer prevention trial (SELECT). JAMA 2009;301:39-51.
Gohagan JK, Prorok PC, Hayes RB, Kramer BS. The prostate, lung, colorectal and ovarian (PLCO) cancer screening trial of the national cancer institute: History, organization, and status. Control Clin Trials 2000;21:251S-72S.
Taper HS, Jamison JM, Gilloteaux J, Gwin CA, Gordon T, Summers JL. In vivo
reactivation of DNases in implanted human prostate tumors after administration of a Vitamin C/K3 combination. J Histochem Cytochem 2001;49:109-19.
Jain MG, Hislop GT, Howe GR, Ghadirian P. Plant foods, antioxidants, and prostate cancer risk: Findings from case-control studies in Canada. Nutr Cancer 1999;34:173-84.
Gunawardena K, Campbell LD, Meikle AW. Combination therapy with Vitamins C plus E inhibits survivin and human prostate cancer cell growth. Prostate 2004;59:319-27.
van Gorkom GN, Lookermans EL, Van Elssen CH, Bos GM. The effect of Vitamin C (Ascorbic Acid) in the treatment of patients with cancer: A systematic review. Nutrients 2019;11:977.
Mikirova N, Casciari J, Rogers A, Taylor P. Effect of high-dose intravenous Vitamin C on inflammation in cancer patients. J Transl Med 2012;10:189.
Nielsen TK, Højgaard M, Andersen JT, Jørgensen NR, Zerahn B, Kristensen B, et al
. Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: A single-arm phase II trial. Transl Androl Urol 2017;6:517-28.
Bosetti C, Talamini R, Montella M, Negri E, Conti E, Franceschi S, et al
. Retinol, carotenoids and the risk of prostate cancer: A case-control study from Italy. Int J Cancer 2004;112:689-92.
Schenk JM, Riboli E, Chatterjee N, Leitzmann MF, Ahn J, Albanes D, et al
. Serum retinol and prostate cancer risk: A nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 2009;18:1227-31.
Neuhouser ML, Barnett MJ, Kristal AR, Ambrosone CB, King IB, Thornquist M, et al
. Dietary supplement use and prostate cancer risk in the carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev 2009;18:2202-6.
Van Hoang D, Pham NM, Lee AH, Tran DN, Binns CW. Dietary carotenoid intakes and prostate cancer risk: A case-control study from vietnam. Nutrients 2018;10:70.
Trump DL, Aragon-Ching JB. Vitamin D in prostate cancer. Asian J Androl 2018;20:244-52.
] [Full text]
LaMonica C, Weigel N. Vitamin D and prostate cancer. Exp Biol Med 2004;229:277-84.
John EM, Dreon DM, Koo J, Schwartz GG. Residential sunlight exposure is associated with a decreased risk of prostate cancer. J Steroid Biochem Mol Biol 2004;89-90:549-52.
Shui IM, Mucci LA, Kraft P, Tamimi RM, Lindstrom S, Penney KL, 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;104:690-9.
Yuan C, Shui IM, Wilson KM, Stampfer MJ, Mucci LA, Giovannucci EL. Circulating 25-hydroxyvitamin D, Vitamin D binding protein and risk of advanced and lethal prostate cancer. Int J Cancer 2019;144:2401-7.
Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, et al
. Serum Vitamin D and risk of prostate cancer in a case-control analysis nested within the european prospective investigation into cancer and nutrition (EPIC). Am J Epidemiol 2009;169:1223-32.
Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, et al
. Serum Vitamin D concentration and prostate cancer risk: A nested case-control study. J Natl Cancer Inst 2008;100:796-804.
Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al
. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275:218-20.
Stewart JR, Artime MC, O'Brian CA. Resveratrol: A candidate nutritional substance for prostate cancer prevention. J Nutr 2003;133:2440S-3S.
Martínez-Martínez D, Soto A, Gil-Araujo B, Gallego B, Chiloeches A, Lasa M. Resveratrol promotes apoptosis through the induction of dual specificity phosphatase 1 and sensitizes prostate cancer cells to cisplatin. Food Chem Toxicol 2019;124:273-9.
Zhang J, Hsu BA, Kinseth BA, Bjeldanes LF, Firestone GL. Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cells. Cancer 2003;98:2511-20.
Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 2000;92:61-8.
Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev 2003;12:1403-9.