Pygeum

Pygeum is an extract made from the the bark of the Prunus africana tree. It is commonly sold as a supplement for prostate health.

This page features 38 unique references to scientific papers.

Summary

All Essential Benefits/Effects/Facts & Information

Pygeum is an herbal supplement derived from the bark of the Prunus africana tree.

Pygeum is often sold as a prostate health supplement, specifically to alleviate Benign Prostatic Hyperplasia (BPH), also called benign enlargement of the prostate.

Further research is needed to determine if pygeum does exert this protective effect. Though one meta-analysis showed pygeum supplementation provides overall benefits for BPH, subsequent studies suffered from poor design and do not provide strong evidence.

Pygeum has been shown to reduce BPH proliferation in vitro (in a test tube) by interfering with growth factors. It also has an anti-andorgenic effect on its receptor. Additional studies are needed to determine if this effect takes place inside the human body after oral supplementation.

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Things To Know

Do Not Confuse With

Pycnogeol (Pine bark extract)

Things to Note

  • Pygeum has demonstrated anti-androgenic potential in vitro, which is a mechanism that may have some benefits but is commonly not seen as ideal

Goes Well With

Caution Notice

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How to Take

Recommended dosage, active amounts, other details

Most prostate health supplements and scientific studies use a dose of 50-100mg of pygeum , taken daily.

Additional research is needed to determine the optimal dose of pygeum bark.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects pygeum has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
Symptoms of Benign Prostate Hyperplasmia Minor Very High See study
Urinary complications with Benign prostatic hyperplasia appear to be reduced with Pygeum supplementation in the range of 19-23% (including nocturia, residual urine volume, and urinary flow rate).

Studies Excluded from Consideration

  • Excluded as it is a duplication of another study already in the table[1]


Disagree? Join the Pygeum Discussion


1Sources and Composition

1.1. Sources

Pygeum is a term used to refer to the bark of Prunus africanum (sometimes referred to as Pygeum africanum) that is used for medicinal purposes, usually from traditional african medicine for the purpose of benign prostatic hyperplasmia, particularly in Europe.[1][2] The tree itself is known as the African cherry tree and the fruits it bears are accordingly known as african cherries[3] or african plums.[4]

It is marketed in Italy (Pigenil) and France (Tadenan), with the latter being a combination product with Saw Palmetto in a 4:1 ratio to Pygeum bark. Pygeum appears to have a history of usage as Tadenan against Benign prostatic hyperplasia.[5]

Pygeum is derived from the tree bark of the african cherry tree, and has relatively recent usage against benign prostatic hyperplasia but originates from traditional african medicine

1.2. Composition

The bark of Pygeum tends to contain

  • N-butylbenzenesulfonamide[6]

  • Atraric acid[7]

  • β-sitosterol (349-583mg/kg)[6][8] as well as β-sitostenone at 116–260 mg/kg[8]

  • Fatty acids of mostly linoleic acid (30.6%), palmitic (28.3%), oleic (24.90%), and stearic (10.58%) with trace linolenic, lauric, and myristic acids[9]

  • Docosanol[10] at 10-28mg/kg dry weight[8]

  • Behenic acid, Ursolic Acid (highly variable at 317-2000mg/kg),[8] and lignoceric acid[10]

  • Ferulic acid[11] at 30-90mg/kg[8]

  • Friedelin may[12] or may not[8] be detectable above 7mg/kg

The bioactives are mostly thought to be fatty acids, and although the main bioactives are not currently known they are suspected to be the antiandrogenic N-butylbenzenesulfonamide and Atraric acid


2Pharmacology

2.1. Excretion

One study assessing the urine of men following consumption of Pygeum has found 4 compounds that were significantly altered. These compounds were unable to be named, although molecular weights or formula was recorded.[13]

2.2. Enzymatic Interactions

Pygeum extract has been found to inhibit the aromatase enzyme in vitro with an IC50 value of 780mcg/mL with some efficacy at 100mcg/mL, and a mixture of Pygeum and Stinging Nettle failed to significant increase the potency of the IC50 value.[14]

5α-reductase has been found to be inhibited by Pygeum extract with an IC50 of 980mcg/mL, and was synergistic with Stinging Nettle (which inherently was weak in 5α-reductase inhibition, with the combination resulting in an IC50 of 240mcg/mL).[14]


3Interactions with Hormones

3.1. Androgens

In a competitive ligand binding assay, Pygeum has been found to displace approximately 60% of DHT from the androgen receptor at a concentration of 5uL/mL, with the beta-sitosterol molecule being inactive.[15] The active molecule may be N-butylbenzenesulfonamide, which has been noted elsewhere to be a component of Pygeum[6] and an androgen receptor antagonist[16] although atraric acid is also suspected.[7]

Atraric acid has an IC50 value around 3μM while it exerts no significant inhibitory effect at 0.1μM and at 10μM exerts about 90% inhibition of signalling.[7] N-butylbenzenesulfonamide requires 100μM to exert 90% inhibition and has an IC50 value of approximately 10μM.[17] These potencies are less than the reference drug casodex (IC50 of 1uM[18]) but greater than that of the reference drug flutamide (116uM).[18][16]

Testosterone binding was not tested,[15] although androgen receptor blockers should also hinder the signalling of testosterone.

Compounds in Pygeum appear to be androgen receptor antagonists, which reduce signalling via the androgen receptor, and appears to be seemingly potent at this in vitro

3.2. Estrogen

In a mouse uterine cytosol (competitive ligand binding assay), Pygeum extract has been noted to displace 70% of estradiol from its receptor when Pygeum is at 5uL/mL concentration; this was not due to the beta-sitosterol content (which was inactive).[15] In PC-3 cells (prostatic cancer cells), a dose-dependent inhibition of signalling via the estrogen receptor (ERα) has been noted with Pygeum in the presence of estradiol[15] although it may activate signalling of the receptor when incubated in isolation.[19]

When investigating the two molecules known to have anti-androgenic effects, N-butylbenzenesulfonamide failed to activate the estogen receptor at the concentrations required to inhibit 90% of androgen receptor activity; at 10-fold higher concentrations, atraric acid had slight estrogenic effects.[17][20][16]

It is possible that Pygeum has a phytoestrogenic potential that interferes with estrogen signalling (which would establish it as a selective estrogen receptor modulator or SERM) but this is not fully elucidated or established in a living model


4Inflammation and Immunology

4.1. Mechanisms

In LPS-activated macrophages, the secretion of IL-6 has been noted to be abolished with Pygeum extract at the concentration of 100mcg/well, which was not significantly different than dexamethasone as active control; this study was confounded as the Pygeum product was a 4:1 ratio of Saw Palmetto and Pygeum.[21]


5Interactions with Organ Systems

5.1. Prostate

Pygeum extract has been noted to reduce the proliferation of prostatic fibroblasts and myofibroblasts in vitro (surgically obtained) with an ethanolic extract at 25mcg/mL, with near absolute inhibition of basal and both EGF/VEGF induced proliferation at 100mcg/mL, although this dose was minorly cytotoxic (highest effective concentration without cytotoxicity being established at 25-50mcg/mL).[22] This was then replicated with MDCK cells with dose-dependence also established with significance above 25mcg/mL,[22] and hindering the effects of these two growth factors on prostatic cells has been noted elsewhere[23] as well as hindering the growth promoting effects of IGF-1.[24]

One study comparing the efficacy of Pygeum extract on prostatic tissue (obtained surgically) in those with benign prostatic hyperplasia versus normal controls found that the extract, in vitro, was more effective in inhibiting the proliferation of hyperplasic cells (EC50 7.35µg/mL) relative to normal cells (EC50 18.68µg/mL) associated with a 7-fold reduction of TGFB1 mRNA in hyperplasic cells and [25]

These anti-proliferative effects have been confirmed in a human (n=1) during a preliminary assessment, where myofibroblast proliferation was reduced although there was no apparent effect on the prostatic epithelial cell line PNT2.[26]

Mechanistically, Pygeum may reduce prostatic cell proliferation and appears to be slightly more effective in cells undergoing benigin hyperplasia. Pygeum has been noted to interfere with prostatic growth factors

In regards to prostatic hyperplasia, a 2002 Cochrane meta-analysis[27] was able to note 18 trials comparing Pygeum (17 of which to placebo control) with no comparison against reference drugs; overall, the analysis of studies meeting inclusion criteria (minimal due to lack of extractable data, reducing the total sample of 1562 down to 430) noted that Pygeum was associated with a 19% reduction in nocturia that was not statistically significant (3 trials assessed with an effect size of -0.9 and 95% CI of -2.0 to 0.1), 24% improvement in residual urine volume (2 trials; effect size of 2.5 with a 95% CI of 0.3-5.0), and 23% increase in peak urine flow (4 trials; effect size of -13 with a 95% CI of -23 to -3).[27] Symptoms of benign prostatic hyperplasia, as assessed by physician, were reduced in the Pygeum group relative to placebo (5 trials assessed, 64% of patients reporting an improvement in symptoms in Pygeum relative to 30% in placebo);[27][28] this meta-analysis is duplicated in Medline.[29]

Beyond the meta-analysis, a trial using 25mg Pygeum (confounded with the inclusion of 300mg Stinging Nettle) has failed to benefit symptoms of prostatic hyperplasia to a larger degree than placebo treatment.[30] Another trial using this combination therapy has noted benefit, but measured the observed benefits relative to baseline rather than a placebo control.[31]

One trial using 50mg of Pygeum extract twice daily for 2 months in an open-label trial has noted that treatment with Pygeum is associated with reduced symptoms of Benign prostatic hyperplasia (40% reduction) and concomitant improvements in self-reported quality of life (32% improvement, although more variable) and reduction in nocturia (32%);[32] This trial did not have a placebo control,[32] and a subsequent study that was blinded but comparing 50mg twice daily against 100mg Pygeum daily for 2 months found that both were effective to similar degrees in reducing symptoms of benign prostatic hyperplasia and appeared to retain efficacy when held at the same dose over 10 months of an open-label follow-up period.[33]

There 'appears' to be a great deal of evidence as assessed by the meta-analysis mentioned previously, but a good deal of this evidence is not located online and appears to be intertwined with European usage of Pygeum as a phytopharmaceutical against Benign prostatic hyperplasia

When looking at the evidence in Pubmed, 50-100mg Pygeum supplementation daily is not clearly associated with beneficial effects on symptoms associated with benign prostatic hyperplasia

5.2. Bladder

Diabetic cystopathy is a condition affecting the bladders of diabetic persons which is characterized by abnormal functioning (decreased bladder sensation, poor contractility and increased post-void residual urine diagnosed with urodynamics, uroflow and measurement of post-void residual urine) although it appears to lack a precise definition and pathological understanding.[34][35][36] In general, it is bladder dysfunction associated with high blood sugar and/or insulin.

In diabetic rats fed 100mg/kg Pygeum extract for 4 weeks, Pygeum was associated with attentuating the changes observed in the bladder tissue of diabetic rats relative to control by approximately 50% (in reference to Maximal bladder volume and bladder pressure) which correlated with improvements in antioxidant enzyme concentrations and a reduction in iNOS expression in the urogenital region; there was no influence of Pygeum on serum glucose.[37]


6Interactions with Cancer Metabolism

6.1. Prostate

In vitro with PC-3 and LNCaP prostate cancer cells, the IC50 of Pygeum extract appears to be approximately 2.5mcg/mL and isolated beta-sitosterol was noted to inhibit LNCaP but not PC-3. These changes were associated with cell accumulation in S phase and increased apoptosis.[15]

A subsequent in vivo test using TRAMP (TRansgenic Adenocarcinoma of the Mouse Prostate[38]) mice designed to develop prostate cancer noted that the 62.5% occurrence of prostate cancer in control mice over 5 months was reduced to 35% in mice fed Pygeum (0.128g/kg).[15]

Scientific Support & Reference Citations

References

  1. Hutchison A, et al The efficacy of drugs for the treatment of LUTS/BPH, a study in 6 European countries . Eur Urol. (2007)
  2. Edgar AD, et al A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS . Neurourol Urodyn. (2007)
  3. Stewart KM The African cherry (Prunus africana): can lessons be learned from an over-exploited medicinal tree . J Ethnopharmacol. (2003)
  4. Strong KM African plum and benign prostatic hypertrophy . J Herb Pharmacother. (2004)
  5. Paubert-Braquet M, et al Effect of Pygeum africanum extract on A23187-stimulated production of lipoxygenase metabolites from human polymorphonuclear cells . J Lipid Mediat Cell Signal. (1994)
  6. Schleich S, et al Extracts from Pygeum africanum and other ethnobotanical species with antiandrogenic activity . Planta Med. (2006)
  7. Schleich S, et al Activity-guided isolation of an antiandrogenic compound of Pygeum africanum . Planta Med. (2006)
  8. Kadu CA, et al Bioactive constituents in Prunus africana: geographical variation throughout Africa and associations with environmental and genetic parameters . Phytochemistry. (2012)
  9. Ganzera M, Croom EM, Khan IA Determination of the Fatty Acid content of pumpkin seed, pygeum, and saw palmetto . J Med Food. (1999)
  10. Hass MA, et al Identification of components of Prunus africana extract that inhibit lipid peroxidation . Phytomedicine. (1999)
  11. Triterpenes from Prunus africana bark
  12. Catalano S, et al New constituents of Prunus africana bark extract . J Nat Prod. (1984)
  13. 10 Metabolomics profiles of prostatic secretions from patients treated by Pygeum Africanum for low urinary tract symptoms related to benign prostatic hyperplasia
  14. Hartmann RW, Mark M, Soldati F Inhibition of 5 α-reductase and aromatase by PHL-00801 (Prostatonin®), a combination of PY102 (Pygeum africanum) and UR102 (Urtica dioica) extracts . Phytomedicine. (1996)
  15. Shenouda NS, et al Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo . Endocrine. (2007)
  16. Roell D, Baniahmad A The natural compounds atraric acid and N-butylbenzene-sulfonamide as antagonists of the human androgen receptor and inhibitors of prostate cancer cell growth . Mol Cell Endocrinol. (2011)
  17. Papaioannou M, et al NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth . Invest New Drugs. (2010)
  18. Handratta VD, 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. (2005)
  19. Mathé G, et al The so-called phyto-estrogenic action of Pygeum africanum extract . Biomed Pharmacother. (1995)
  20. Papaioannou M, 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. (2009)
  21. Bach SM, et al Chemical constituents, anti-inflammatory and antioxidant activities of bark extracts from Prunus tucumanensis Lillo . Nat Prod Res. (2012)
  22. Boulbès D, et al Pygeum africanum extract inhibits proliferation of human cultured prostatic fibroblasts and myofibroblasts . BJU Int. (2006)
  23. Inhibition of bFGF and EGF-induced proliferation of 3T3 fibroblasts by extract of Pygeum africanum (Tadenan®)
  24. Yablonsky F, et al Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts . J Urol. (1997)
  25. Quiles MT, et al Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH) . Prostate. (2010)
  26. Larré S, et al Biological effect of human serum collected before and after oral intake of Pygeum africanum on various benign prostate cell cultures . Asian J Androl. (2012)
  27. Wilt T, et al Pygeum africanum for benign prostatic hyperplasia . Cochrane Database Syst Rev. (2002)
  28. Barry M Review: Pygeum africanum extracts improve symptoms and urodynamics in symptomatic benign prostatic hyperplasia . ACP J Club. (2002)
  29. Ishani A, et al Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis . Am J Med. (2000)
  30. Melo EA, et al Evaluating the efficiency of a combination of Pygeum africanum and stinging nettle (Urtica dioica) extracts in treating benign prostatic hyperplasia (BPH): double-blind, randomized, placebo controlled trial . Int Braz J Urol. (2002)
  31. Krzeski T, et al Combined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: double-blind comparison of two doses . Clin Ther. (1993)
  32. Breza J, et al Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe . Curr Med Res Opin. (1998)
  33. Chatelain C, Autet W, Brackman F Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension . Urology. (1999)
  34. Kaplan SA, Blaivas JG Diabetic cystopathy . J Diabet Complications. (1988)
  35. Urologic Complications of Diabetes
  36. Diabetic Cystopathy—What Does it Mean?
  37. Wang D, et al Pygeum africanum: effect on oxidative stress in early diabetes-induced bladder . Int Urol Nephrol. (2010)
  38. Foster BA, et al Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model . Cancer Res. (1997)

(Common misspellings for Pygeum include pigeum, pygum, pygium, pygem, pigeim, pigium)

(Editors who contributed to this page include dbarvinok, )