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Mariann Garner-Wizard Brenda Milot, ELS Diane Graves, MPH, RD Heather S Oliff, PhD Shari Henson Densie Webb, PhD
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FILE: §Isoflavonoids §Prostate Health HC 040138 - 248 Date: January 15, 2004 RE: A Case for Flavonoids to Promote Prostate Health
Katz AE. Flavonoid and botanical approaches to prostate health. The Journal of Alternative & Complementary Medicine 2002;8(6):813-821. Benign prostatic hyperplasia (BPH), an enlargement of the prostate gland which interferes with urination and may be a prelude to prostate cancer, affects as many as 90% of elderly men. Manifesting sometimes opposing symptoms, BPH generates considerable professional disagreement over diagnosis, treatment, and management. The author discusses both conventional and phytotherapeutic treatments, their benefits, and possible adverse effects. Patients with mild symptoms may undergo "watchful waiting," in effect, regular check-ups and tests where advisable to guard against the stealthy advent of cancer. However, when BPH significantly affects quality of life, patients may choose more active treatment. Conventional therapy consists of two options: surgery (transurethral resection or TURP), or prescription drugs (primarily finasteride, or medications such as terazosin or tamsulosin ("α-blockers"). While TURP removes excess prostatic tissue and finasteride shrinks the prostate by inhibiting 5-α-reductase, the α-blockers relax the smooth muscle in the bladder neck and prostate, thus easing urination. Potential risks of TURP include the general risk of surgery among elderly men and retrograde ejaculation in younger men. Potential adverse effects of finasteride include impotence, ejaculatory failure, decreased libido, and gynecomastia. Contraindicated for pregnant women, finasteride may cause developmental abnormalities in a male fetus. Finasteride lowers prostate-specific antigen (PSA) values by approximately 50% in men with BPH. High PSA is a risk factor for prostate cancer. However, in clinical trials, finasteride did not appear to lower the incidence of prostate cancer in men with BPH and high PSA. A large trial is currently underway to investigate the potential of finasteride to reduce incidence of prostate cancer. Adverse effects of α-blockers may include fatigue, postural hypotension, dizziness, nasal congestion, and impotence. Because of the potential risks and adverse effects and because of increased consumer awareness of potential benefits of dietary supplements on prostatic health, a growing number of BPH patients are choosing natural therapies. There is strong epidemiological evidence that a diet rich in isoflavones, found primarily in legumes, including soybeans (Glycine max), red clover (Trifolium pratense), chickpeas (Cicer arietinum; Garbanzo mediano), lentils (Lens culinaris), grams (Cajanus spp.), beans (Phaseolus vulgaris; others), and groundnuts (there are many nuts by this name around the world; this may refer to peanuts, Arachis hypogaea), may lower incidence of BPH and prostate cancer. Consumption of fish and various oilseeds
may also have a protective anticancer effect. Other indications that isoflavones may play a role in prostate health include documented mechanisms of isoflavone action and demonstrated in vivo activity, mostly in animal tests. Isoflavones, potent antioxidants, occur in agylcone or conjugated (glucoside) forms. Katz states that the agylcone isoflavones are biologically active at the receptor level. The four main agylcone isoflavones are formononetin and its demethylated product, daidzein, and biochanin A and its demethylated product, genistein. Of these, genistein may be the most studied. It can inhibit the growth of human breast and prostate cancer cells and inhibit angiogenesis. Many dietary supplements contain isoflavones, and there are others which may benefit prostate health. The author states that physicians seeking to select a natural therapy for BPH patients should look for one which relieves symptoms, is safe, provides sufficient quantities of active ingredients, and "has a mechanism of action which is understood." To assist this process, he briefly reviews several dietary supplements. Saw palmetto (Serenoa repens) has a history of use in botanical medicine for disorders of the urinary tract. It has been shown to inhibit 5-α-reductase, act as an α-blocker, and have antiestrogenic activity. It is generally well-tolerated and relieves symptoms of BPH, but its mechanisms of action are not known, and many different formulations, with differing amounts of active ingredients, are available. An extract of the bark of pygeum (Prunus africanum) may relieve BPH symptoms and is well-tolerated. It may reduce prostate swelling by inhibiting human growth factor. Katz does not discuss pygeum's availability in formulations providing sufficient amounts of its active ingredients, nor whether such ingredient(s) have been identified. Curbicin, derived from pumpkinseeds (from Cucurbita pepo) and saw palmetto (Serenoa repens) show promise in treating symptoms of BPH. Soy, featured in most of the epidemiological data that shows reduced incidence of prostate cancer with a high-isoflavone diet, contains high quantities of the conjugated isoflavones genistin and daidzin. Eight ounces (about 230 g) of soy foods are recommended for daily consumption; however, Katz writes that this amount may be impractical to consume and may produce bloating or gas. Soy supplements may substitute for dietary soy, but, for best effect, he says, should contain 12 to 20 mg of the agylcones genistein and daidzein. Extract of red clover has a long tradition of medicinal use, and Katz writes, "Unlike the extracts from other ... herbs described above, the formulation of red clover, extracted from... leaves and flowers, is well established." Red clover extract contains all four main agylcone isoflavones. It has been shown to reduce symptoms of BPH and is generally well-tolerated. Dosage studies have been performed, not only in men with BPH, but in women suffering from symptoms of menopause. Katz concludes that supplements containing isoflavones are most promising for treating BPH, and that those containing the highest quantities of agylcone isoflavone are "likely to be most effective"; he adds that "[t]he issue then becomes choosing the best supplement to deliver these agents." To this end Katz provides a table, adapted from Setchell KDR, et al. (Journal of Nutrition 2001; 131(Suppl):1362S-1375S), which accompanied a study of isoflavone content and bioavailability in commercial supplements. According to Setchell's analysis, of the supplements listed, Trinovin®, manufactured by Novogen, Inc. (Stamford, CT), while it contains only the third-highest amount of total isoflavones (73.59 +/- 1.33 mg/g), has over twice the proportion of agylcones of its nearest competitor (95.6% as opposed to 47.2% of only 10.21 +/- 0.35 mg/g total isoflavones), and comes within one-tenth of a milligram of meeting its content per capsule as claimed on the label. Katz' study was supported by an unrestricted educational grant from Novogen. Interestingly, Promensil®, another Novogen red clover product which appears in Setchell's original chart and has even more total isoflavones (78.15 +/-1.61 mg/g), with an even greater proportion of aglycones (99.9%) and also has more isoflavone content than the label claim (41.7 mg on a label claim of 40 mg per capsule), is omitted from Katz' adapted table (as are a few other products, none of which approached the level of isoflavones or percentage of aglycones in either Novogen product.) The difference in composition, if any, between these two products is not given in the Setchell study. Setchell argues that, while aglycone isoflavones are absorbed faster than glycosides, glycosides are more bioavailable and are the major form of phytoestrogens found in blood plasma.
It would seem that research on the relative benefits of various isoflavones remains to be done. If Katz is correct that supplements containing the highest quantities of aglycone isoflavones may be most effective for maintaining prostate health, then Trinivin® (which Katz does not endorse or even mention by name) or its sister product Promensil® may be the best value. If not, then soy products containing higher levels of glucoside isoflavones may be preferable. This paper does not offer conclusive evidence to assist physicians - or health food store clerks - in making recommendations to BPH patients. Katz' discussion omits the fact that epidemiological studies do not necessarily show cause and effect relationships for disease. The better prostate health of men who consume diets rich in isoflavones may be due to other factors. Also, this paper begs the issue of whether supplements are preferable or equal to dietary consumption in a variety of foods as part of a balanced diet. BPH and prostate cancer may be conditions which could be largely prevented by such a diet; thus reducing the need for disease treatment. Even with these provisos, this is a valuable contribution to an important area of study. Novogen's funding may seem in part self-serving, but certainly no more so than in the realm of prescription pharmaceuticals. As long as potential conflicts are disclosed, supplement makers' funding plays a vital role in defining supplements' potential benefits and challenges the makers of other products to fund investigations into those products' mechanisms of action, sufficiency of active ingredients, long-term safety, and benefits. Katz' criteria for physician recommendation of dietary supplements are not unreasonable, although his conclusions in this case, may be premature. Mariann Garner-Wizard
Enclosure: Referenced article reprinted with permission from Mary Ann Liebert, Inc., 2 Madison Ave., Larchmont, NY 10438; Telephone (914)834-3100; Fax: (914)834-3582; email: info@liebertpub.com.
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