BPH: The Natural Approach

A Concise Update of Important Issues Concerning Natural Health Ingredients

Reprinted with permission from THE STANDARD
Edited by Thomas G. Guilliams, Ph.D.

There are many conditions for which natural ingredients are therapeutic equivalents to the pharmaceutical alternative. Benign Prostatic Hyperplasia (BPH), in particular, is a condition where natural medicine seems to be far superior to the synthetic drugs, but the answer is more complete than simply Saw Palmetto Extracts.

BPH: A GENERAL REVIEW

BPH is an age-related non-malignant enlargement of the prostate gland. It is a hyperplasia, in that it is due to increased numbers of cells, as opposed to a hypertrophy (an increase in cell size). BPH is very common, effecting almost 10% of the men in their 4th decade and increasing every decade thereafter. According to the National Institute on Aging more than half of the men in their 60's have BPH and among men in their 70's and 80's the figure may be as high as 90%.

As the prostate enlarges, it causes compression of the urethra preventing the bladder from adequately releasing urine. Decreased caliber and force of urination are classic signs. Residual urine, distention of the bladder and more frequent urination (especially at night) and urinary tract infections are common. Enlargement of the prostate is usually confirmed by digital rectal examination.

There are two primary features involved with prostate enlargement. The major one being hyperplasia, the nonmalignant increase in the number of cells; and the second being prostatitis, the inflammation of the prostate. We shall consider hyperplasia first and then discuss the implications of inflammation.

Hyperplasia

Prostate cells, like most cells, are stimulated to grow by various growth factors. Several studies have shown that epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) are responsible for stimulating prostate cell growth (1,2). Studies have also linked increased levels of bFGF in the prostate with the occurrence of BPH (3). Basically, growth factors are ultimately responsible for the increase in cell proliferation; but they are not the root problem.

While these growth factors are common to many cell types, in the adult prostate they are stimulated primarily through the androgen receptor. The two major androgen hormones involved are testosterone (T) and dihydrotestosterone (DHT). When these hormones bind to the androgen receptors on prostate cells, a complex set of secondary messages are sent that signal the cell to produce and secrete growth factors. These growth factors then bind to growth factor receptors on the same or adjacent prostatic cells, causing another complex set of secondary signals, resulting in mitosis and cell growth (division). Understanding BPH requires an understanding of how all of these factors effect one another, and how the changing hormonal shifts in elderly men relate to BPH.

As men age, serum levels of testosterone drop while the levels of estrogens and prolactin increase. While these may have only subtle effects on other systems, the prostate gland is sensitive to these changes. Both testosterone and DHT bind to the androgen receptor, but DHT binds 5 times stronger than testosterone. Therefore, even though the levels of testosterone are lower, the conversion of testosterone to DHT via the enzyme 5-a-reductase, keeps the androgen receptors activated to stimulate growth factor production. This androgen receptor stimulation is increased by the action of another hormone, sex hormone binding globulin (SHBG) and estrogen. When SHBG is bound to its receptor on the prostate cells and is also attached to estrogen, it is able to sensitize (or amplify) the androgen signal (4,5,6). In fact, it may be the very minute increase in estrogen levels that convert a normal androgen signal to one that causes hyperplasia. Estrogens also play a role in inhibiting the degradation of testosterone and DHT via hydroxylation. Another factor that may play a role is the increased activity of the 5-a-reductase enzyme, and androgen binding when prolactin is bound to prostatic cells.

Inflammation

Prostatitis describes any inflammation of the prostate, whether it is caused by a bacterial infection or not. Inflammation of the prostate from bacterial infections is often related to BPH since the frequencies of urinary tract infections (UTI) increase as retention of urine in the bladder increases. Both chronic and acute bacterial prostatitis are seen and should be treated much like chronic and acute UTIs. A chronic, nonbacterial prostatitis has also been seen in a large group of men. This form of inflammation seems to be associated with an elevated white blood cell count and abnormal inflammatory cells in the prostate secretion. It is thought that this could possibly be some form of autoimmune response.

Regardless of the type of inflammation, metabolites such as leukotrienes, thromboxanes and prostaglandins; which are derived from arachidonic acid via the lipoxygenase or cyclooxygenase enzymes are involved. Anti-inflammatory agents that specifically block one or more of these pathways would be helpful in reducing the inflammatory symptoms associated with prostatitis.

Treatment Options

Several reviews exist on the current treatment approaches to BPH (7,8). What follows is a general overview and not a comprehensive review.

Surgery

Various forms of surgery are available to remove portions of the prostate. These tend to treat the enlargement with good success but have unpleasant side effects such as decreased sexual function (impotence, pain, ejaculatory dysfunction) and bladder incontinence. Newer procedures such as trans-urethral resections or incisions can be done to remove portions of the prostate. These procedures work well for removing portions of the prostate, but do little to address the process that caused the enlargement to begin with. Complications of scar tissue and infections are not uncommon in these procedures.

Drugs

Two types of drugs are primarily used, 5-a-reductase inhibitors and alpha andrenoceptor blockers (alphablockers). Finasteride (Proscar) is the most used 5-a-reductase inhibitor. It blocks the conversion of testosterone to DHT. Finasteride often requires 6 months to a full year before significant results are evident. Alpha-blockers such as terazosin, prazosin and others act by relaxing the muscles around the prostate, relieving many of the symptoms of BPH. While having a more immediate effect on symptoms, it does not change the underlying problems associated with the enlarged prostate (7,8,9).

THE NATURAL APPROACH

Diet

It has been reported that a high protein diet inhibits 5-a-reductase activity, while a low protein diet stimulates the enzyme. No large clinical studies have confirmed these results, and other health conditions may play a greater role in dictating the type of diet for the individual with BPH. It has been shown that the combination of the amino acids glycine, alanine, and glutamic acid relieves many of the symptoms of BPH in several studies. These studies are quite old (10,11), and further research may be warranted as additional support during BPH.

The use of Essential Fatty Acids (EFAs) is important at all times, but BPH sufferers often are deficient in EFAs.The use of EFAs in the form of Flaxseed Oil will provide both omega-3 (linolenic) and omega-6 (linoleic), but much more linolenic. Linolenic acid is a precursor to many of the "good" prostaglandins, which will help suppress much of the prostaglandin-induced inflammation.

Zinc

Zinc intake and absorption is critical for the prostate, especially during BPH. Zinc has been shown to reduce the size of the prostate and the symptoms in many of the patients with BPH (12,13). Zinc is involved in various aspects of androgen metabolism. As has been discussed earlier, estrogen levels are increased in elderly men. Estrogen not only inhibits the hydroxylation of Testosterone and DHT; it also prevents the absorption of zinc. Zinc has been shown to inhibit the activity of 5-a-reductase (14). Zinc also reduces prolactin binding to prostate receptors (15). While the exact levels of supplemental zinc have not been determined experimentally, a dose of approximately 50 mg (325% USRDA) should be both adequate and safe. Since zinc is known to reduce the absorption of copper, it is wise to include copper (1 or 2 mg) with a daily zinc supplementation regimen.

Saw Palmetto Extract

The Liposterolic extract of Saw Palmetto fruits (Serenoa repens, or Sabal serulata) has been used extensively and for many years as the drug of choice for BPH in Europe and has been getting more and more attention here in the United States. The fatty acids include capric, caprylic, caproic, lauric, palmytic, and oleic. The phytosterols include b-sitosterol, stigmasterol and others. The liposterolic extract of Saw Palmetto has three major activities that improve BPH symptomology, they include: Inhibition of 5-a-reductase (16, 17, 18, 19); Inhibiting the binding of DHT to prostatic cells (20); and Inhibiting both Lipoxygenase and Cyclooxygenase (arachidonic acid cascades) (21). Saw Palmetto, by competing with both the enzyme and receptor that stimulates growth factor secretion, inhibits hyperplasia.

A three-year trial of 309 men, comparing Saw Palmetto Extract to Finasteride (Proscar) showed a significant increase in urinary flow rate and a 50% decrease in residual urine volume associated with the Saw Palmetto group. While the finasteride group also showed improvements, they were not as significant as the Saw Palmetto group, and there were almost 6 times more dropouts in the finasteride group due to unpleasant side effects (22). There have been many clinical trials done with Saw Palmetto extracts showing effective treatment of BPH.

Standard dosages of Saw Palmetto Extracts are those which yield from 270 to 305 mg of fatty acids per day (often 320 mg of an 85- 95% fatty acid extract). Fatty acid extracts of 85-95% are oil extracts and are in soft gel capsules. Powdered extracts are also available and are usually standardized anywhere from 20% to 55% fatty acids.

Nettles Root Extract

Extracts of Stinging Nettle root (Urtica dioica L.) have been used, singly or in combination with other botanicals for the condition of BPH (22, 24, 25). Nettles root extract, as well as Saw Palmetto extract, are both approved by the German government as treatments for BPH. While the mechanism has not been fully elucidated, two activities have been identified in nettle root extracts that may be responsible for the activity. The first is the inhibition of prostate Na+/K+ ATPase enzyme (26). By inhibiting this crucial enzyme, prostate cells are prevented from proliferating and therefore, this inhibits hyperplasia. The second activity is an interference of the human sex-hormone binding globulin (SHBG). By interfering with SHBG and its receptor, nettles root extracts prevent the estrogen-induced amplification of the androgen signal, which is thought to be one of the major players in BPH (27,28). A common mixture of 120 mg of nettles root extract with 160 mg of saw palmetto is used for many clinical trials.

Pygeum Extract

The Extract of Pygeum africanum bark has been used for more than 20 years in France in patients suffering from BPH. The mechanism has not been fully worked out, but a few of the activities are known. Pygeum extracts are known to inhibit the proliferative effects of growth factors such as EGF, bFGF, and IGF-I. This activity was able to inhibit the prostatic growth in an animal model, even when the cells were stimulated to grow (29). This activity makes pygeum extract an excellent synergist with saw palmetto because routes other than the androgen receptor may stimulate growth signals. Additionally, Pygeum extracts antagonize the production of metabolites in the 5-Lipoxygenase pathway (30). This activity will further reduce the inflammatory process in the prostate. Pygeum extracts have been dosed anywhere from 50-200 mg per day with excellent results.

CONCLUSION

The natural treatment approach to BPH is one of the triumphs of natural medicine. It is quite unfortunate that more health care professionals have not taken advantage of these approaches with the millions of patients with this condition. The mechanisms are clear, the results even more clear, and physicians should feel more than confident using any number of products with these ingredients.

REFERENCES

1. Marengo SR, and Chung LW.An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor. J Androl. 1994; 15(4): 277-286
2. Levine AC, M. Ren, GK Huber, and A Kirschenbaum. The effects of androgen, estrogen, and growth factors on the proliferation of cultured fibroblast derived from human fetal and adult prostates. Endocrinology 1992, 130(4): 2413-2419
3. Story, MT; KA Hopp, DA Meier, FP Begun, and RK Lawson. Influence of transforming growth factor beta 1 and other growth factors on basic fibroblast growth factor level and proliferation of cultured human prostate-derived fibroblasts. Prostate 1993; 22(3): 183-197
4. Rosner W, DJ Hryb,MS Khan,AM Nakhla, and NA Romas. Sex hormone-binding globulin: anatomy and physiology of a new regulatory system. J Steroid Biochem Mol Biol 1991; 40(4-6): 813-820
5. Nakhla AM, NA Romas, W Rosner. Estradiol activates the prostate androgen receptor and prostate-specific antigen secretion through the intermediacy of sex hormone-binding globulin. J Biol Chem 1997; 272(11):6838-6841
6. Farnsworth WE. Roles of estrogen and SHBG in prostate physiology. Prostate 1996; 28(1): 17-23
7. Tammela,T. Benign prostatic hyperplasia. Practical treatment guidelines.Drugs Aging 1997 10 (5):349-366
8. Ruud Bosch, JL. Conservative non-instrumental treatment of benign prostatic hyperplasia. Urol Res 1997; 25 Suppl 2:S107-S114
9. Vahlensieck W., PG Fabricius and U Hell. Drug therapy of benign prostatic hyperplasia (abstract) Fortschr Med 1996 114(31): 407-411
10. Dumrau F, Benign prostatic hyperplasia: Amino acid therapy for symptomatic relief. Am J Ger 1962 10:426-30
11. Feinblatt HM and JC Gant.Palliative treatment of benign prostatic hypertrophy: Value of glycine,alanine,glutamic acid combination.J Maine Med Assoc 1958; 49: 99-102
12. Bush IM, et al; Zinc and the Prostate. Presented at the annual meeting of the AMA,1974
13. Fahim M, et al; Zinc treatment for the reduction of hyperplasia of the prostate. Fed Proc 35:361, 1976
14. Leake A, GD Chisholm, and FK Habib. The effect of zinc on the 5-a-reduction of testosterone by the hyperplastic human prostate gland. J Steroid Biochem 1984; 20(2): 651-655
15. Leake A, GD Chisholm, and FK Habib. Interaction between prolactin and zinc in the human prostate gland. J Endocrinol 1984; 102(1): 73-76
16. Delos, S; C Iehle,PM Martin,JP Raynaud.Inhibition of the activity of 'basic' 5-a-reductase (type 1) detected in DU 145 cells and expressed in insect cells. J Steroid Biochem Mol Biol 1994; 48(4): 347-352
17. Iehle C et.al.,Human prostatic steroid 5-a-reductase isoforms- a comparative study of selective inhibitors.J Steroid Biochem Mol Biol 1995; 54(5-6): 273-279
18. Delos S. et.al., Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts. J Steroid Biochem Mol Biol 1995; 55(3-4): 375-383
19. Weisser H, S Tunn, B Behnke, M Krieg. Effects of the sabal serrulata extracts IDS 89 and its subfractions on 5 alpha-reductase activity in human benign prostatic hyperplasia. Prostate 1996; 28(5): 300-306
20. El-Sheikh MM, MR Dakkak, and A Saddique.The effects of Permixon on androgen receptors. Acta Obstet Gynecol Scand 1988; 67(5): 397-399
21. Breu W et al., Anti-inflammatory activity of sabal fruit extracts prepared with supercritical carbon dioxide. In vitro antagonists of cyclooxegenase and 5-lipoxygenase metabolism.Arzneimittelforschung 1992; 42(4): 547-551
22. Bach, D., M Schmitt, L Ebeling. Phytopharmaceutical and synthetic agents in the treatment of benign prostatic hyperplasia (BPH). Phytomedicine 3/ 4: 309-313
23. Sokeland J, J. Albreight, C Martin. Comparison of the therapeutic efficacy of a Sabal/Urtica extract with finasteride in patients with benign prostatic hyperplasia (stages 1 and 2). Presented at the 2nd International Congress on Phytomedicine. (Reviewed in the Quarterly Review of Natural Medicine, Summer 1997 Ed. D Brown)
24. Krzeski T, M Kazon, A Borkowski, A Witeska, and J Kuczera. Combined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: a double-blind comparison of two doses.Clin Ther 1993; 15(6): 1011-1020
25. Hartman, RW, M Mark and F Soldai. Inhibition of 5-a-reductase and aromatase by PHL-00801 (Prostatonin), a combination of PY 102 (Pygeum africanum) and UR 102 (Urtica dioica) extracts. Phytomedicine 3/2: 121-128
26. Hirano T,M Homma,K Oka.Effects of stinging nettle root extracts and their steroidal components on the Na+,K+- ATPase of the benign prostatic hyperplasia. Planta Med 1994; 60(1): 30-33
27. Gansser D, G Spiteller. Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts. Z Naturforsch [C] 1995; 50(1-2): 98-104
28. Hryb DJ,MS Khan,NA Romas,W Rosner.The effect of extracts of the roots of the stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic membranes. Planta Med 1995; 61(1): 31-32
29. Yablonsky F,V Nicolas,JP Riffaud,F Bellamy.Antiproliferative effects of Pygeum africanum extracts on rat prostatic fibroblasts.J Urol 1997; 157(6): 2381-2387
30. Paubert-Braquet M et. al. Effects of Pygeum africanum extracts on A23187- stimulated production of lipoxygenase metabolites from human polymorphonuclear cells. J Lipid Mediat Cell Signal 1994; 9(3): 285-290
31. Pizzorno, Joseph; and M. Murray; A Textbook of Natural Medicine, John Bastyr College Publication.