Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®)–Health Professional Version

Other Prostate Health Supplements

Overview

Many widely available dietary supplements are marketed to support prostate health. African cherry (Pygeum africanum) and beta-sitosterol are two related supplements that have been studied as potential prostate cancer treatments. Note: A separate PDQsummary on PC-SPES is also available.

African Cherry/P. africanum

P. africanum is a tree from the Rosaceae family that grows in tropical zones. It is found in a number of African countries including Kenya, Madagascar, Uganda, and Nigeria. Bark from the P. africanum tree was used by African tribes to treat urinary symptoms and gastric pain.[1] In the 18th century, European travelers learned from South African tribes that P. africanum was used to treat bladder discomfort and old man’s disease (enlarged prostate).

Since 1969, bark extracts from P. africanum have been available as prescription drugs in Europe and have been widely used to treat benign prostatic hyperplasia.[2,3] The bark contains a number of compounds including saturated and unsaturated fatty acids, phytosterols (e.g., beta-sitosterol), pentacyclic triterpenoids (e.g., oleanolic acid), alcohols, and carbohydrates. The extract is obtained by macerating and solubilizing the bark in an organic solvent. The extract is then purified from the solvent.[1]

Two components of P. africanum bark extracts, atraric acid and N-butylbenzene-sulfonamide, are androgen receptor inhibitors, as indicated by both in vitro [4-6] and animalin vivo [7] studies. This activity is produced by each of these components at concentrationsthat are significantly lower than the clinically achieved concentration of the antiandrogen flutamide.[8]

Beta-Sitosterol

Beta-sitosterol is a member of the phytosterol family of phytochemicals. It is found ubiquitously in plants and has recently been classified as an invalid/improbable metabolic panacea (IMP) compound.[9] Pygeum africanum, saw palmetto (Serenoa repens), and some legumes can contain rather high concentrations. As a type of phytosterol (or plant sterol), beta-sitosterol has a similar structure to cholesterol. Phytosterols, including beta-sitosterol, reduce absorption of dietary cholesterol and their potential to protect against cardiovascular disease is under investigation. Mean plasma beta-sitosterol concentration in a small group of healthy male volunteers in Vienna, Austria, was 2.83 μg /mL(approximately 7 μM).[10] Interestingly, however, a rare condition caused by mutations in the adenosine triphosphate -binding cassette (ABC) transporter ABCG5 or ABCG8 genesresults in an inherited sterol storage disease with markedly increased serumconcentrations of plant sterols such as sitosterol and leads to premature atherosclerosis and large xanthomas.[11]

Research has also suggested that phytosterols may have anticarcinogenic properties, but the exact mechanisms are unknown.[12] Phytosterols may exert antitumor effects by acting on immune and hormonal systems, or by directly targeting cell cycles and inducing apoptosis in tumor cells.[13]

Beta-sitosterol at very high concentrations (i.e., 16 μM or 6.64 mg /mL) has been shown to significantly inhibit growth of PC-3 prostate cancer cells and induce apoptosis.[14,15] Beta-sitosterol is very poorly bioavailable, with an estimated 0.41% of dietary beta-sitosterol absorbed, and circulating blood levels of about 3 μg/mL to 9 μg/mL in individuals consuming diets containing normal to high amounts of plant-based foods (approximately 1,000 times less than the concentration used in the study).[10,16] Associated with these effects are decreasing levels of cell cycle regulators p21 and p27 in the cancer cells and an increased production of reactive oxygen species.

References

Brackman FG, Edgar A, Coates PM: Pygeum. In: Coates PM, Betz JM, Blackman MR, et al., eds.: Encyclopedia of Dietary Supplements. 2nd ed. New York, NY: Informa Healthcare, 2010, pp 650-5.
Ishani A, MacDonald R, Nelson D, et al.: Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis. Am J Med 109 (8): 654-64, 2000. [PUBMED Abstract]
Levin RM, Das AK: A scientific basis for the therapeutic effects of Pygeum africanum and Serenoa repens. Urol Res 28 (3): 201-9, 2000. [PUBMED Abstract]
Papaioannou M, Schleich S, Prade I, et al.: The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate cancer cell growth. J Cell Mol Med 13 (8B): 2210-23, 2009. [PUBMED Abstract]
Papaioannou M, Schleich S, Roell D, et al.: NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth. Invest New Drugs 28 (6): 729-43, 2010. [PUBMED Abstract]
Schleich S, Papaioannou M, Baniahmad A, et al.: Extracts from Pygeum africanum and other ethnobotanical species with antiandrogenic activity. Planta Med 72 (9): 807-13, 2006. [PUBMED Abstract]
Shenouda NS, Sakla MS, Newton LG, et al.: Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo. Endocrine 31 (1): 72-81, 2007. [PUBMED Abstract]
Handratta VD, Vasaitis TS, Njar VC, et al.: Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. J Med Chem 48 (8): 2972-84, 2005. [PUBMED Abstract]
Nelson KM, Dahlin JL, Bisson J, et al.: The Essential Medicinal Chemistry of Curcumin. J Med Chem 60 (5): 1620-1637, 2017. [PUBMED Abstract]
Duchateau G, Cochrane B, Windebank S, et al.: Absolute oral bioavailability and metabolic turnover of β-sitosterol in healthy subjects. Drug Metab Dispos 40 (10): 2026-30, 2012. [PUBMED Abstract]
Tsubakio-Yamamoto K, Nishida M, Nakagawa-Toyama Y, et al.: Current therapy for patients with sitosterolemia--effect of ezetimibe on plant sterol metabolism. J Atheroscler Thromb 17 (9): 891-900, 2010. [PUBMED Abstract]
Awad AB, Fink CS: Phytosterols as anticancer dietary components: evidence and mechanism of action. J Nutr 130 (9): 2127-30, 2000. [PUBMED Abstract]
Bradford PG, Awad AB: Phytosterols as anticancer compounds. Mol Nutr Food Res 51 (2): 161-70, 2007. [PUBMED Abstract]
Awad AB, Burr AT, Fink CS: Effect of resveratrol and beta-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells. Prostaglandins Leukot Essent Fatty Acids 72 (3): 219-26, 2005. [PUBMED Abstract]
Scholtysek C, Krukiewicz AA, Alonso JL, et al.: Characterizing components of the Saw Palmetto Berry Extract (SPBE) on prostate cancer cell growth and traction. Biochem Biophys Res Commun 379 (3): 795-8, 2009. [PUBMED Abstract]
Muti P, Awad AB, Schünemann H, et al.: A plant food-based diet modifies the serum beta-sitosterol concentration in hyperandrogenic postmenopausal women. J Nutr 133 (12): 4252-5, 2003. [PUBMED Abstract]

Changes to This Summary (06/05/2019)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Vitamin D

Added text to state that vitamin D has also been combined with radiation in an in vitrostudy.

Added text to state that however, in a cross-sectional analysis of 119 men undergoing prostatectomy, tumor proliferation as indicated by Ki-67 measured in prostate tissue demonstrated an inverse correlation between serum 1,25(OH)D and Ki-67 in tumor cells, providing early evidence of antiproliferative property of vitamin D. No correlation was observed between 25(OH)D and biomarker of tumor proliferation (Ki-67) (cited Rosenberg et al. as reference 32).

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of nutrition and dietary supplements for reducing the risk of developing prostate cancer or for treating prostate cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

be discussed at a meeting,
be cited with text, or
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Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Prostate Cancer, Nutrition, and Dietary Supplements are:

Donald I. Abrams, MD (UCSF Osher Center for Integrative Medicine)
Sangeeta Agarawal, MS, RN, CAS (Helpsy, Inc.)
Jinhui Dou, PhD (Yiling Pharmaceutical, Inc.)
Nagi B. Kumar, PhD, RD, FADA (Fellow of the American Dietetic Association)
Channing J Paller, MD (Johns Hopkins Hospital)
Jeffrey D. White, MD (National Cancer Institute)

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PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Prostate Cancer, Nutrition, and Dietary Supplements. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/prostate-supplements-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389500]

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