close
Pygeum

What is pygeum

Pygeum also known as Pygeum africanum, African prune tree, African cherry, African plum, Red stinkwood or Prunus africana, has been used to improve symptoms of benign prostatic hyperplasia (BPH) and to improve sexual function in men. Pygeum bark extract has been used in Europe since the mid-1960s to treat men suffering from benign prostatic hyperplasia (BPH) 1. Currently, Pygeum (Tadenan) is the most commonly used medicine in France for BPH, backed by many double-blind studies pointing to its efficacy for reducing its symptoms 2. Derived from the tree bark, Pygeum extracts are traditionally used to manage lower urinary tract symptoms associated with benign prostatic hypertrophy (BPH) 3. Test tube and animal studies indicate that Pygeum extracts have bactericidal and fungicidal activity 4, antagonize the androgen receptor 5 and have antiproliferative and apoptotic effects against prostate cancer cells 6. Clinical studies suggest effectiveness of Pygeum 2, 7, 8, 9 and formulations containing Pygeum and other herbs 10 to improve urinary symptoms associated with BPH. This 1998 Cochrane review 9 found that Pygeum africanum is well tolerated, cheaper than many prescription medicines used for BPH (benign prostatic hyperplasia) and provides moderate relief from the urinary problems caused by an enlarged prostate. However, additional larger studies are needed to demonstrate usefulness of Pygeum compared with standard treatments in current use for BPH.

Pygeum africanum is a member of the Rosaceae family, an evergreen species found across the entire continent of Africa at altitudes of 3,000 feet or higher. Pygeum africanum is found in a number of African countries including Kenya, Madagascar, Uganda, and Nigeria. It grows up to 150 feet tall 11.

The active constituents of Pygeum extract include phytosterols (e.g., beta-sitosterol) that have anti-inflammatory effects by inhibiting production of pro-inflammatory prostaglandins in the prostate 11. Pygeum antagonizes 5-lipoxygenase metabolite production, and this action may contribute to its anti-inflammatory effects 12. Pygeum extract antimicrobial effects have been linked to inhibition of IL-7 mRNA expression 4. Pygeum also contains pentacyclic triterpenes (ursolic and oleanic acids) that have anti-edema properties, and ferulic acid nesters (n-docosanol and tetracosanol) that reduce prolactin levels and block the accumulation of cholesterol in the prostate. Prolactin is purported to increase the uptake of testosterone by the prostate and cholesterol increases binding sites for dihydrotestosterone (DHT) 13. The isolated compounds atraric acid and N-butylbenzene-sulfonamide were identified as androgen receptor antagonists, which play an important role in the development of prostate diseases 14. Antiproliferative and apoptotic effects of pygeum on prostate fibroblasts and myofibroblasts are due to downregulation of transforming growth factor B1 and inhibition of fibroblast growth factor 2-specific signaling 15.

How long does it take for pygeum to work?

Pygeum extract when used for benign prostatic hypertrophy (BPH) may take several weeks to see any beneficial effects.

Pygeum benefits

Bark from the Pygeum africanum tree was used by African tribes to treat urinary symptoms and gastric pain 16. In the 18th century, European travelers learned from South African tribes that Pygeum africanum was used to treat bladder discomfort and old man’s disease (enlarged prostate) 17.

Since 1969, bark extracts from Pygeum africanum have been available as prescription drugs in Europe and have been widely used to treat benign prostatic hyperplasia (BPH) 18. Pygeum africanum 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, and evaporation of the solvent 16.

Two components of Pygeum africanum bark extracts, atraric acid and N-butylbenzene-sulfonamide, are androgen receptor inhibitors, as indicated by both in test tube 19 and animal  studies 20. This activity is produced by each of these components at concentrations that are significantly lower than the clinically achieved concentration of the antiandrogen flutamide 21.

Beta-sitosterol is a member of the phytosterol family of phytochemicals. Pygeum africanum, saw palmetto (Serenoa repens), and some legumes can contain rather high concentrations of beta-sitosterol. 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 22. 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) 23. 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.

Although Pygeum exact mechanism of action is still unclear, in animal models Pygeum has been shown to modulate bladder contractility by reducing the sensitivity of the bladder to electrical stimulation, phenylephrine, adenosine triphosphate, and carbachol 24. Pygeum also has anti-inflammatory activity, by decreasing production of leukotrienes and other 5-lipoxygenase metabolites (lower concentrations of Pygeum can be used to decrease 5-lipoxygenase metabolites when first dissolved in dimethylsulfoxide) 25. Furthermore, Pygeum inhibits fibroblast production, increases adrenal androgen secretion, and restores the secretory activity of prostate and bulbourethral epithelium 26.

Basic fibroblast growth factor (bFGF) is hypothesized to play a role in the development of BPH and Pygeum has been shown to have a significant inhibitory effect on cell proliferation induced by bFGF 27. Furthermore, in patients with abnormally low prostatic acid phosphatase activity, Pygeum extract can restore acid phosphatase activity and total protein secretion, although it is more effective in patients without prostatic inflammation 28.

Benign prostatic hyperplasia

In one of the largest placebo-controlled, double-blind studies (n=263) 29, Pygeum administered at a dosage of 100 mg per day for 60 days improved urinary maximum flow by 17.2 percent, increased voided volume by 12 percent, decreased residual volume by 24.5 percent, decreased nocturia by 31 percent, decreased daytime frequency by 19.4 percent, and resulted in overall improvement of 50 percent. Sixty-five percent of the subjects reported an improvement in this study as compared to 31 percent in the placebo group 30.

A year 2000 literature review analyzed studies from 1966-2000 containing a total of 18 randomized, controlled trials involving 1,562 men 31. The reviewers concluded that, compared with placebo, Pygeum africanum provided a significant improvement in the combined outcome of urological symptoms and flow measures. In addition, subjects taking Pygeum extract were more than twice as likely to report an improvement in overall symptoms; nocturia was reduced by 19 percent and residual urine volume by 24 percent; and peak urine flow was increased by 23 percent 31.

A lengthy 1995 literature review of the use of Pygeum extract for BPH also yielded positive findings for its efficacy 24. Twelve double-blind, placebo-controlled studies of Pygeum extract were analyzed in which 358 patients received Pygeum extract and 359 received placebo 32. Taken as a whole, the results show a statistically significant benefit for Pygeum extract over placebo. Unfortunately, most of the studies had small patient numbers, although one study with 126 subjects showed a statistically significant benefit for Pygeum extract in maximum urinary flow rate, voided volume, residual volume, nocturia, daytime frequency and impression of improvement scored by physicians and patients 32.

In an experiment with 209 subjects with BPH using a parallel-group, double-blind, comparative phase (group A, 50 mg twice daily; group B, 100 mg once daily) and a ten-month open phase (100 mg once daily), the average International Prostate Symptom Score  improved by 38 percent in group A and 35 percent in group B 7. Furthermore, the quality of life (QOL) index improved 28 percent in both groups, and the maxi-mum urinary flow rate (Qmax) increased 16 per-cent in group A and 19 percent in group B.12 After12 months, the IPSS decreased an average of 46percent and the Qmax increased 15 percent 7. In another open phase trial testing the efficacy of Pygeum (Tadenan), a plant extract from Pygeum, 85 patientshad significant improvements in International Prostate Symptom Score (40%), quality of life (32%), and nocturnal frequency (32%). Improvements in Qmax, average urinary flow, and urine volume were also statistically significant 33.

In four relatively small studies, Pygeum was compared with: (1) sitosterin (n=53), (2) Urticae radix extract (n=42), (3) non-steroidal anti-inflammatory or anti-infective treatment (n=39), or (4) non-steroidal antiinflammatory treatment only (n=49) 34. Although the results favored Pygeum extract over the other treatment groups, only a small number of patients were studied, and no statistical comparisons were made among treatments 34.

Chronic prostatitis

Pygeum extract (100 mg/d for 5-7weeks) was used to treat 47 patients with chronic prostatitis (8 septic, 39 non-septic) in an open-label study. Eighty-nine percent of patients experienced complete remission of symptoms; whereas, there were no improvements in three septic patients and two non-septic patients 34. In another study, Pygeum extract (200 mg/day for 60 days) was used either alone or in combination with antibiotics to treat 18 patients suffering from sexual disturbances due to either BPH or chronic prostatitis 35. Pygeum improved all the urinary parameters investigated by medical history and prostatic transrectalechography and improved sexual function despite the fact there were no significant differences found between hormonal levels and nocturnal penile tumescence and rigidity monitoring before and after therapy 35. The authors stated that the results should be confirmed by other investigators but suggested Pygeum extract may be beneficial in the treatment of patients with sexual/reproductive dysfunction 35.

Obstruction-induced contractile dysfunction

The obstructive component of the enlarged prostate often results in bladder outlet obstruction (BOO) due to increased outlet resistance. Bladder outlet obstruction results in detrusor muscle hypertrophy, hyperplasia and instability, as well as collagen deposition. Pygeum extract (Tadenan) was tested in four groups of New Zealand white rabbits to determine its ability to protect the bladder from contractile dysfunction caused by experimentally-induced bladder outlet obstruction 36. In this study, Tadenan had a significant outcome of reducing the effect of bladder outlet obstruction on bladder mass and reversing the contractile response secondary to urethral obstruction. These improvements were associated with Pygeum’s ability to alter the expression of myosin isoforms (the contractile proteins in muscle fibers) 36. A similar study also found Pygeum extract (Tadenan) was able to reverse bladder dysfunction induced by mild bladder outlet obstruction and improve bladder function with severe bladder outlet obstruction 37. Pygeum extract (Tadenan) has also been proven effective protection when administered as a pretreatment to rabbits prior to experimentally-induced bladder outlet obstruction 38.

Pygeum dosage

The doses of Pygeum extract used in randomized clinical trials ranged between 75 to 200 mg per day 9. Pygeum extract is usually administered at a dose (standardized to contain 14% triterpenes including beta-sitosterol and 0.5% n-docosanol) of 50-100 mg twice daily 39. The efficacy of Pygeum extract at 50 mg twice daily and 100 mg once daily has been shown to be equivalent 7.

Pygeum side effects

The majority of the studies report an absence of any significant adverse effects of Pygeum, although there have been rare complaints of diarrhea, constipation, dizziness, gastric pain and visual disturbances 24. One study demonstrated continued satisfactory safety profiles in 174 human subjects after 12 months of 100 mg daily doses 7. Toxicological studies have likewise shown very good tolerability after oral administration. Administration of Pygeum to dog and rat subjects equivalent to 560 times the therapeutic dose for six-month periods resulted in no adverse effects on hematological, biochemical, or anatomical/pathological parameters. Pygeum extract had no effect on fertility in male rats and rabbits at doses up to80 mg/kg/day – a safety margin of 50 times thetherapeutic dose. Furthermore, in animal studies and test tube studies of mutagenicity showed a complete absence of mutagenic or clastogenic potential. In fact, many of the constituents of Pygeum have anticarcinogenic and antimutagenic properties in animal studies and test tube studies 2.

References
  1. Isaacs JT. Importance of the natural history of benign prostatic hyperplasia in the evaluation of pharmacologic intervention. Prostate 1990:3:1-7.
  2. Ishani A, MacDonald R, Nelson D, Rutks I, Wilt TJ. Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis. Am J Med. 2000 Dec 1;109(8):654-64. doi: 10.1016/s0002-9343(00)00604-5
  3. Abera B. Medicinal plants used in traditional medicine by Oromo people, Ghimbi District, Southwest Ethiopia. J Ethnobiol Ethnomed. 2014 May 8;10:40. doi: 10.1186/1746-4269-10-40
  4. Mwitari PG, Ayeka PA, Ondicho J, Matu EN, Bii CC. Antimicrobial activity and probable mechanisms of action of medicinal plants of Kenya: Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus. PLoS One. 2013 Jun 13;8(6):e65619. doi: 10.1371/journal.pone.0065619
  5. Papaioannou M, Schleich S, Prade I, Degen S, Roell D, Schubert U, Tanner T, Claessens F, Matusch R, Baniahmad A. 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 Aug;13(8B):2210-23. doi: 10.1111/j.1582-4934.2008.00426.x
  6. Larré S, Camparo P, Comperat E, Boulbés D, Haddoum M, Baulande S, Soularue P, Costa P, Cussenot O. Biological effect of human serum collected before and after oral intake of Pygeum africanum on various benign prostate cell cultures. Asian J Androl. 2012 May;14(3):499-504. doi: 10.1038/aja.2011.132
  7. 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 Sep;54(3):473-8. doi: 10.1016/s0090-4295(99)00147-8
  8. Barlet A, Albrecht J, Aubert A, Fischer M, Grof F, Grothuesmann HG, Masson JC, Mazeman E, Mermon R, Reichelt H, et al. Wirksamkeit eines Extraktes aus Pygeum africanum in der medikamentösen Therapie von Miktionsstörungen infolge einer benignen Prostatahyperplasie: Bewertung objektiver und subjektiver Parameter. Eine placebokontrollierte doppelblinde Multizenterstudie [Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo-controlled double-blind multicenter study]. Wien Klin Wochenschr. 1990 Nov 23;102(22):667-73. German.
  9. Wilt, T., Ishani, A., Mac Donald, R., Rutks, I., & Stark, G. (2002). Pygeum africanum for benign prostatic hyperplasia. The Cochrane database of systematic reviews, 1998(1), CD001044. https://doi.org/10.1002/14651858.CD001044
  10. Coulson S, Rao A, Beck SL, Steels E, Gramotnev H, Vitetta L. A phase II randomised double-blind placebo-controlled clinical trial investigating the efficacy and safety of ProstateEZE Max: a herbal medicine preparation for the management of symptoms of benign prostatic hypertrophy. Complement Ther Med. 2013 Jun;21(3):172-9. doi: 10.1016/j.ctim.2013.01.007
  11. Pygeum africanum (Prunus africana)(African plum tree). Alternative Medicine Review Volume 7, Number 1, 2002. https://altmedrev.com/wp-content/uploads/2019/02/v7-1-71.pdf
  12. Paubert-Braquet M, Cave A, Hocquemiller R, Delacroix D, Dupont C, Hedef N, Borgeat P. Effect of Pygeum africanum extract on A23187-stimulated production of lipoxygenase metabolites from human polymorphonuclear cells. J Lipid Mediat Cell Signal. 1994 May;9(3):285-90.
  13. Murray MT. The Healing Power of Herbs.Rocklin, CA: Prima Publishing; 1995:286-293.
  14. 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 Jan 30;332(1-2):1-8. doi: 10.1016/j.mce.2010.09.013
  15. Quiles MT, Arbós MA, Fraga A, de Torres IM, Reventós J, Morote J. Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH). Prostate. 2010 Jul 1;70(10):1044-53. doi: 10.1002/pros.21138
  16. Brackman FG, Edgar A, Coates PM: Pygeum. In: Coates PM, Betz JM, Blackman MR, et al., eds.: Encyclopedia of Dietary Supplements. 2nd ed. Informa Healthcare, 2010, pp 650-5.
  17. PDQ Integrative, Alternative, and Complementary Therapies Editorial Board. Prostate Cancer, Nutrition, and Dietary Supplements (PDQ®): Health Professional Version. 2021 Mar 22. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK83261
  18. Levin RM, Das AK. A scientific basis for the therapeutic effects of Pygeum africanum and Serenoa repens. Urol Res. 2000 Jun;28(3):201-9. doi: 10.1007/s002409900098
  19. Papaioannou M, Schleich S, Roell D, Schubert U, Tanner T, Claessens F, Matusch R, Baniahmad A. NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth. Invest New Drugs. 2010 Dec;28(6):729-43. doi: 10.1007/s10637-009-9304-y
  20. Shenouda NS, Sakla MS, Newton LG, Besch-Williford C, Greenberg NM, MacDonald RS, Lubahn DB. Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo. Endocrine. 2007 Feb;31(1):72-81. doi: 10.1007/s12020-007-0014-y
  21. Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, Newman D Jr, Farquhar R, Guo Z, Qiu Y, Brodie AM. 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 Apr 21;48(8):2972-84. doi: 10.1021/jm040202w
  22. Scholtysek C, Krukiewicz AA, Alonso JL, Sharma KP, Sharma PC, Goldmann WH. Characterizing components of the Saw Palmetto Berry Extract (SPBE) on prostate cancer cell growth and traction. Biochem Biophys Res Commun. 2009 Feb 13;379(3):795-8. doi: 10.1016/j.bbrc.2008.11.114
  23. Duchateau G, Cochrane B, Windebank S, Herudzinska J, Sanghera D, Burian A, Müller M, Zeitlinger M, Lappin G. Absolute oral bioavailability and metabolic turnover of β-sitosterol in healthy subjects. Drug Metab Dispos. 2012 Oct;40(10):2026-30. doi: 10.1124/dmd.112.046623
  24. Andro MC, Riffaud JP. Pygeum africanum extract for the treatment of patients with benign prostatic hyperplasia: a review of 25 years of published experience. Curr Ther Res 1995;56:796-817.
  25. Paubert-Braquet M, Cave A, Hocquemiller R,et al. Effect of Pygeum africanum extract on A23187-stimulated production of lipoxygenase metabolites from human polymorphonuclear cells. J Lipid Mediat Cell Signal 1994;9:285-290.
  26. Robinette CL. Sex-hormone induced inflammation and fibromuscular proliferation in the rat lateral prostate. Prostate 1988;12:271-286.
  27. Paubert-Braquet M, Monboisse JC, Servent-Saez N, et al. Inhibition of bFGF and EGF-induced proliferation of 3T3 fibroblasts by extract of Pygeum africanum (Tadenan). Biomed Pharmacother 1994;48:43-47.
  28. Luchetta G, Weill A, Becker N, et al. Reactivation of the secretion from the prostatic gland in cases of reduced fertility. Biological study of the seminal fluid modifications. Urol Int 1984;39:222-224.
  29. Barlet A, Albrecht J, Aubert A, et al. Efficacyof Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo con-trolled double-blind multicenter study. WienKlin Wochenschr 1990;102:667-673. [German]
  30. Barlet A, Albrecht J, Aubert A, et al. Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo con-trolled double-blind multicenter study. WienKlin Wochenschr 1990;102:667-673. [German]
  31. 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 2000;109:654-664.
  32. Andro MC, Riffaud JP. Pygeum africanum extract for the treatment of patients with benign prostatic hyperplasia: a review of 25years of published experience. Curr Ther Res 1995;56:796-817.
  33. Breza J, Dzurny O, Borowka A, et al. Efficacy and acceptability of Tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multi centre trial in central Europe. Curr Med Res Opin 1998;14:127-139.
  34. Andro MC, Riffaud JP. Pygeum africanum extract for the treatment of patients with benign prostatic hyperplasia: a review of 25 years of published experience. Curr Ther Res1995;56:796-817.
  35. Carani C, Salvioli V, Scuteri A, et al. Urologi-cal and sexual evaluation of treatment of benign prostatic disease using Pygeum africanum at high doses. Arch Ital Urol Nefrol Androl 1991;63:341-345. [Italian]
  36. Gomes CM, Disanto ME, Horan P, et al. Improved contractility of obstructed bladders after Tadenan treatment is associated with reversal of altered myosin isoform expression. J Urol 2000;163:2008-2013.
  37. Levin RM, Das AK, Haugaard N, et al. Beneficial effects of Tadenan therapy after two weeks of partial obstruction in the rabbit. Neurourol Urodyn 1997;16:583-599.
  38. Levin RM, Riffaud JP, Bellamy F, et al. Protective effect of Tadenan on bladder function secondary to partial outlet obstruction. J Urol 1996;155:1466-1470.
  39. Murray M, Pizzorno J. Encyclopedia of Natural Medicine. Rocklin, CA: PrimaPublishing; 1998:762.
Health Jade Team

The author Health Jade Team

Health Jade