Benign Prostatic Hypertrophy

28th Nov 2005

Ward Dean, MD

Few men ever consider the walnut-sized fibrous gland located just below the bladder, until it starts to give them trouble. In fact, a 1995 survey in the London Times found that 89 percent of the men surveyed did not know where the prostate was located. After the age of 50, the prostate begins to hypertrophy, or increase in size. This is known as benign prostatic hypertrophy (BPH). The urethra (the tube that carries urine from the bladder) runs through the middle of the prostate. Consequently, when the prostate enlarges the urethra is compressed. (Fig. 1) This causes difficulty in urinating and requires many men to get up three or four times during the night to urinate. Other symptoms of BPH include hesitancy, dribbling, reduced force of the urinary stream, and occasional bleeding or infection. This condition may even proceed to the point of complete urinary obstruction.

Fifty to sixty percent of men between 40-60 years of age suffer from BPH, escalating to 75 percent of men by age 60 (Fig. 2).1 The projected annual cost of hospital care and surgical treatment for BPH in the United States is over $1 billion. In fact, this condition is so common that physicians routinely ask their over-50 male patients, not “whether” but “How many times do you have to get up at night to go to the bathroom?” I wonder how many men have seen the cartoon character “Calvin” on the back of a truck windshield urinating from one side of the vehicle to the other and said secretly to themselves, “I wish I could still do that?”

Causes of Prostatic Enlargement

Prostate hypertrophy and inflammation are believed to be due to the consequences of a number of age-related changes in the metabolism and levels of male steroid hormones.2 After the age of fifty, the level of free testosterone decreases, while levels of prolactin, estradiol, and sex hormone-binding globulin (SHBG) increase. Concentrations of dihydrotestosterone (DHT)— the active metabolite of testosterone—in the prostate increase, and binding of DHT to prostate tissue increases. DHT stimulates the prostate cells to enlarge, resulting in the swollen gland.

5-alpha reductase is the enzyme that converts testosterone into DHT. Consequently, one approach to preventing BPH has been to use substances that inhibit this enzyme, thereby blocking the formation of DHT, and its prostate-enlarging effect. Estrogen also seems to play a role in BPH by inhibiting the breakdown and removal of testosterone and DHT. The increased ratio of plasma estrogen/testosterone is due to the increased formation of estrogens formed by the conversion of androstenedione to estrone and estradiol by the enzyme, aromatase. Another approach to preventing or treating BPH is, therefore, to use aromatase inhibitors to prevent this estrogenic conversion.

Therapeutic Options for BPH

Until recently, outside of “watchful waiting,” surgery was about the only solution for this troublesome condition. Fortunately, less invasive and more physiological approaches to prevent and treat BPH are now available, based on our increased understanding of its causes. Clearly, a rational approach should include: (1) normalization of prostate nutrient levels; (2) restoration of steroid hormones to normal levels; (3) inhibition of excessive conversion of testosterone to DHT (dihydrotestosterone); (4) reduction of DHT receptor binding; and (5) reduction of prostatic inflammatory promoters such as prolactin.

Proscar® is a prescription drug which inhibits 5-alpha reductase. This drug has recently been introduced into the physician’s armamentarium for treatment of BPH. Use of Proscar results in a 20 percent decrease in prostate size in 50 percent of the men who are treated. Unfortunately, Proscar is fairly expensive, with the significant side effect of sexual dysfunction.2 Fortunately, however, there are nutritional alternatives which provide, without adverse effects, equivalent or greater benefits at reduced cost.

Saw Palmetto (Serenoa repens)

Extracts of saw palmetto berry are being used extensively throughout the world for the relief of BPH. Both the French and German governments approve lipo-philic extracts of saw palmetto berries for this purpose. Saw palmetto reduces prostate hypertrophy by blocking the conversion of testosterone to dihydrotestosterone by inhibiting 5-alpha reductase—just like its expensive prescription “cousin”—and by preventing the binding of DHT to androgen receptor cell sites. These actions increase the breakdown and excretion of DHT. Saw palmetto also interferes with the actions of inflammatory substances that contribute to prostate inflammation and reduces the pro-hypertrophic effects of estrogen and progesterone on the prostate.3-6

Positive results with saw palmetto have been confirmed in numerous open8-14 as well as double-blind, placebo-controlled clinical trials.15-19 All of these studies demonstrated statistically significant improvements in the symptoms of BPH, which included increased volume and rate of urine flow, alleviation of pain and night time urination, and reduced number of voidings per day. Overall, these studies showed a consistent benefit of saw palmetto extract, with virtually no side effects of any consequence. A striking characteristic of these studies is that most subjects experienced relief within days of beginning the therapy, with benefits continuing to improve over time — in many cases, as much as one year of continuing improvement! Most studies however, were terminated after 30, 60 or 90 days. “A striking characteristic of these studies is that most subjects experienced relief within days of beginning the therapy, with benefits continuing to improve over time, in many cases, as much as one year of continuing improvement!”

Most recently, University of Chicago researchers studied the effects of saw palmetto extract versus placebo on 85 men, 45 years of age or older.20 The researchers evaluated the subjects based upon three measurements: the International Prostate Symptom Score, a sexual function questionnaire, and the urinary flow rate. At the end of the study, the subjects treated with saw palmetto experienced significant improvement and reduction of symptoms such as frequent urination both during the night and day and interruptions in urination. The researchers stated that their study provides the most conclusive evidence to date that saw palmetto can benefit men with prostate problems.

Of particular interest was a study that compared Proscar with saw palmetto extract that found that saw palmetto had fewer side effects, provided an equivalent or greater benefit, and was a more affordable form of treatment.21,22 The optimum dose of saw palmetto in most clinical studies was 320 mg per day.

Pygeum Africanum

Extracts of the African herb Pygeum africanum have also shown impressive results in relieving symptoms of BPH. The action of pygeum extract in counteracting prostate hypertrophy is believed to be due to a number of mechanisms, which include its ability to: (1) inhibit the basic fibroblast growth factor induced cellular proliferation;23 (2) inhibit aromatase;24 (3) restore secretory activity of the prostatic epithelium;25 and (4) increase prostatic secretions.26

In one study, 18 patients with BPH or chronic prostatitis, many of whom also had sexual disturbances, received an extract of pygeum. After 60 days, all urinary parameters that were investigated were improved, and sexual disturbances were relieved.27 In a placebo-controlled French trial of 120 patients, the pygeum group experienced significant reductions in the number of urinations and more complete bladder emptying than the placebo group.28

An international, multi-center, double-blind, controlled trial of pygeum extract in 263 patients with BPH over a 60 day period showed improved urinary symptoms in 66 percent of the patients.29 Italian placebo-controlled studies confirmed these benefits.23-25 Most of the clinical studies with pygeum used dosages ranging from 75-150 mg per day.

Stinging Nettle (Urtica dioica)

Extracts of stinging nettle are used routinely in Europe to treat BPH. Stinging nettle shares several mechanisms with Pygeum and saw palmetto, but has several actions that are unique. The known mechanisms of stinging nettles on the prostate include its ability to: (1) inhibit aromatase;30 (2) reduce the binding activity of SHBG;31,32 (3) inhibit prostate membrane Na+, K+-ATPase activity;33 (4) block epidermal growth factor receptors;34 and (5) block 5-alpha reductase.35

Stinging nettle has been tested and found to be effective in BPH as a single nutrient,36-39 or in combination with Pygeum.40 Extracts of stinging nettle when used alone were superior to placebo, but efficacy was enhanced when combined with Pygeum. The dosages of stinging nettle in the clinical studies was 300 mg per day.

Beta Sitosterol

Beta-sitosterol, one of the main subcomponents of a group of plant sterols known as phytosterols, is a white, waxy substance with a chemical structure very similar to that of cholesterol. Research into beta-sitosterol has shown beneficial effects against a wide variety of human ailments, including BPH. Beta sitosterol is the key ingredient in a prescription formulation in Europe, Azuprostat-beta-sitosterol, which has been demonstrated to improve prostate symptom scores and quality of life, and reduce urine volume and residual urine levels. The research team reported that “beta-sitosterol itself is an effective option in the treatment of BPH.”41 Beta-sitosterol was also found to reduce the growth of human prostate cancer cells,42 and appears to be one of the key compounds in soybeans that suppresses carcinogenesis.43

Lycopene

More than 500 types of carotenoids exist in nature. The most common carotenoids include alpha carotene, beta carotene, lycopene, lutein, and beta cryptoxanthin.

In one study, a group of scientists evaluated prostate cancer risk in comparison to dietary intake of specific carotenoids. They found that of 43 fruits and vegetables examined, only tomato-based products (tomato sauce, tomatoes, and pizza—but not tomato juice) and strawberries were found to be protective against prostate cancer. The researchers attributed the protective effect of these tomato-based foods to their high lycopene content.

Lycopene is highly lipophilic (fat soluble) and requires fat for proper intestinal absorption. This is probably the reason for the lack of efficacy of tomato juice. Strawberries are not a good source of lycopene, and the reason for the protective effect of strawberries was not known. Thus, it would seem reasonable to include a high concentration of tomato-based foods (or a lycopene supplement) and strawberries in a prostate cancer preventive nutritional program.

Although researchers believed that tomato-based products may help prevent prostate cancer, they now have evidence that lycopene may also benefit patients already suffering from the disease. A study in the December 19, 2001 Journal of the National Cancer Institute, reported on 32 men with prostate cancer who were about to undergo radical prostatectomy.44 They began a three-week diet of pasta with tomato sauce–the equivalent of roughly 30 mg of lycopene daily–prior to their surgery. This resulted in markedly increased prostate lycopene concentrations, accompanied by a 21.3 percent reduction in leukocyte oxidative DNA damage. In addition, serum PSA levels (a marker for prostate cancer) dropped 17.5 percent, from a mean of 10.9 ng/mL before the diet to 8.7 ng/mL after the diet. Another impressive result of the study was the rate that DNA damage declined in the patients consuming diets high in lycopene. Oxidative DNA damage in prostate tissue from the men consuming high-lycopene diets was 28.3 percent less than in tissue samples from seven randomly selected prostate cancer patients not consuming a high-lycopene diet.

Most recently, Giovanucci reviewed eight epidemiological studies which reported that those with the highest tomato or lycopene consumption had a 30 percent to 40 percent reduction in prostate cancer risk.45 The largest study, in male health professionals, found that consumption of two to four servings of tomato sauce per week was associated with about a 35 percent reduction of total prostate cancer and a 50 percent reduction of advanced (extraprostatic) prostate cancer. In the largest study of blood lycopene levels, very similar risk reductions were observed for total and advanced prostate cancer. Those with the highest lycopene levels had the lowest incidence of prostate cancer.

Conclusion

Beta Sitosterol, and extracts from Saw palmetto, Pygeum africanum, and Stinging nettle have all demonstrated efficacy when used in the treatment and prevention of benign prostatic hypertrophy (BPH). Because of their multiplicity of actions, it should be no surprise that when these phytonutrients are combined, they are even more effective than when used individually. Combined with the prostate cancer-protecting carotenoid lycopene (and beta sitosterol), men no longer need to consider the years over 50 as “The Prostatic Age.”

References:

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Saw Palmetto Extract 160 mg,- 240 softgels

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