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Prostate Cancer

Prostate cancer is a major health concern for American men. Currently one in nine men will be diagnosed with prostate cancer in their lifetime (this is a statistic very similar to female breast cancer estimates). The number of diagnosed cases of prostate cancer has tripled in the last decade, due in part to improved testing procedures.

Approximately 200,000 new cases and 38,000 deaths are attributed to prostate cancer each year in the United States. Behind lung cancer, prostate cancer is the second most common cause of cancer mortality in men. Although the disease is relatively rare before age 50, experts speculate that most elderly men have at least traces of it.

The prostate is a gland in the male reproductive system that helps produce semen, the thick fluid that carries sperm cells. The walnut-sized gland is located beneath a man’s bladder and surrounds the upper part of the urethra, the tube that carries urine from the bladder. More than half of diagnosed cases originate in the prostate’s posterior section, which is nearest to the rectum. For men over 50, a digital rectal exam and a blood test called a PSA should be done every year. For men at higher risk (African Americans and men with a family history of prostate disease), screening should begin at age 40.

If routine screening (digital rectal exam) arouses suspicion, a doctor will inspect the prostate visually using ultrasonography. X-rays of the urinary tract, along with blood and urine studies, are routinely performed to aid diagnosis. Performing a biopsy will confirm cancer diagnosis. If a diagnosed cancer is thought likely to spread, doctors may arrange CT scans, bone scans, chest x-rays, or other imaging tests to see if the cancer has spread beyond the prostate.

Compared with most other cancers, prostate cancer behaves rather strangely. It often lies dormant for years, causing no symptoms and posing no threat to general health. Most men with prostate cancer die of other causes - many without ever realizing that they have the disease. But once prostate cancer “wakes up” and begins to spread, it is dangerous. Although the disease tends to progress slowly, it can be fatal if it spreads beyond the prostate gland itself.

Incidence of prostate cancer increases with age, and is linked to dietary factors, hereditary factors, stress, hormonal changes, and inactivity. It is very important to note that with detection at an early stage and application of proper therapeutic interventions, prostate cancer can often be cured.

Despite its seeming chaos, cancer is inherently a rational process that can be explained according to physiologic and biochemical principals. By understanding how the cancer process works and how the human body re-establishes health, effective lifestyle changes can be implemented, making life after cancer a medical reality.

Prostate cancer generally is slowly progressive and may cause no symptoms. In fact, 15% of men with prostate cancer die of idiopathic thromboembolism, which is the first sign of the disease. In late disease, symptoms of bladder outlet obstruction, urethral obstruction, and hematuria may appear. Metastases to the pelvis, ribs, and vertebral bodies may cause bone pain. Locally advanced prostate cancer may exhibit extension of induration to the seminal vesicles and fixation of the gland laterally.

Prostate cancer should be suspected on the basis of abnormal digital rectal findings, hypoechoic lesions on transrectal ultrasound (TRUS), or elevated levels of serum prostate-specific antigen (PSA).

The protein called PSA is used to help in diagnosis and also to measure the response to therapy. The PSA test is not infallible, however, because it tends to rise whenever the prostate becomes enlarged. It is important to note that the false positive rate with PSA may be as high as 50%. PSA is moderately elevated in 30 to 50% of patients with benign prostatic hyperplasia (depending on prostate size and degree of obstruction) and in 25 to 92% of those with prostate cancer (depending on tumor volume). PSA is also elevated due to mechanical pressure on the prostate, or inflammation of the prostate. Significantly elevated PSA levels suggest extracapsular extension of tumor or metastases. Newer assays that determine the proportion of free vs. bound PSA may decrease the frequency of biopsies in patients without cancer. PSA Density is the ratio of PSA to prostate size, and is used with biopsy to evaluate surgical options.

It is important to note that some prostate cancers do not produce PSA. In addition, PSA may be normal or decreased in advanced stages of prostate cancer, because the prostate “wears out”. In this senario, if the prostate is treated and treatment is working, the PSA will rise due to an increase in viable prostate tissue. Because of its uncertainty, experts recommend that the PSA test be given along with the digital rectal exam.

Stony hard induration or a nodule of the prostate on digital rectal examination suggests malignancy and must be differentiated from granulomatous prostatitis, prostatic calculi, and other more unusual prostatic diseases. However, a normal prostate on digital rectal examination does not exclude carcinoma.

Definitive diagnosis requires histologic confirmation, most commonly by TRUS (Trans Rectal Ultra Sound) - guided transrectal needle biopsy. This procedure can be done as an outpatient without anesthesia. Involvement of perineural lymphatics, if present, is diagnostic. TRUS may provide information for staging, particularly relative to capsular penetration and seminal vesicle invasion. Carcinoma is diagnosed incidentally when malignant changes are found in the tissue removed during surgery for suspected benign prostatic enlargement.

Prostate cancer frequently produces osteoblastic bony metastases. Detection on bone scan or x-ray in the presence of a stony hard prostate is usually diagnostic. Elevated serum acid phosphatase correlates well with the presence of metastases, particularly in lymph nodes. This enzyme may also be elevated benign prostatic hyperplasia (slight elevation after vigorous prostatic massage), multiple myeloma, and hemolytic anemia. Prostatic acid phosphatase and alkaline phosphatase are used to diagnose bone involvement. Although acid phosphatase and PSA levels decline after treatment and rise with recurrence, PSA is the most sensitive marker for monitoring cancer progression and response to therapy.

Other testing includes PSMA (prostate specific membrane antigen) and p-27, which are used to measure the aggressiveness of the cancer. IgF-1 and insulin are risk factor markers. Testosterone and DHEA measure promoting factors, and S-Phase measures cancer activity.

The prostate has three distinct lobes - two major lateral lobes and a small median lobe (which includes the posterior lobe, the most common site of cancer). Histologically, the prostate is a compound tubuloalveolar gland, with glandular spaces lined by epithelium. The glands are lined by two layers of cells: a basal layer of low cuboidal epithelium covered by a layer of columnar mucus-secreting cells. These glands all have a distinct basement membrane and are separated by an abundant fibromuscular stroma. Prostate cancer is usually glandular, similar to the histologic configuration of normal prostate. Small cell proliferation and large nucleoli are characteristic.

Benign nodular enlargements (BPH) are extremely common and occur so often in advancing age that they can also be almost construed as a normal aging process. The likely precursor to prostate cancer called PIN (prostatic intraepithelial neoplasia) and is graded as low grade (stage I) or high grade (stage II).

Adenocarcinoma of the prostate is the most common malignancy in men over 50 in the USA; the incidence increases with each decade of life. There are about 209,900 new cases/year in the USA (1997 estimate). The age-adjusted incidence per 100,000 among Japanese is 3-4, compared with the rate of 50-60 among American Caucasians. The rate among African-Americans is among the highest in the world.

Grading is based on architectural patterns and is commonly reported as the Gleason score: the primary (most prevalent) grade (1-5) plus the secondary (next most prevalent) grade (1-5); thus, it ranges from 2 (very well differentiated) to 10 (very poorly differentiated).

Staging ranges from A (tumor not palpable) to B (palpable, confined to prostate) to C (capsule penetrated and local tissues invaded) to D (spread to lymph nodes, bones, or other distant sites). Another commonly used staging system is based on TNM (Tumor/Lymph Node Involvement/Degree of Metastasis).

Cancer of the prostate can be anatomically staged as clinically localized or clinically advanced. Unfortunately, up to 50% of cancers may be clinically advanced at the time of discovery. The cancer is also usually graded histologically as either: well, moderately, or poorly differentiated. Small, well-differentiated cancers are least likely to spread. Most clinically localized cancers are of moderate grade. Generally, poorly differentiated cancers are likely to have spread even when they seem to be clinically localized. The 10-yr cancer-specific mortality rates for the three grades of prostate cancer are as follows: Less than 10% for well differentiated, 10% to 20% for moderately differentiated, and 30% to 60% for poorly differentiated cancers.

Long-term local control - even cure - is possible in many patients. However, the potential for cure, even in patients with clinically localized cancer, depends on factors such as grade, stage, and pretreatment PSA level. For patients with low-grade, organ-confined tumors, survival is virtually identical to that for age-matched controls without prostate cancer.

Some older patients with localized prostate cancer, particularly if it is well-differentiated, may require no treatment (ie, watchful waiting), because the risk of death from other causes is greater than that from prostate cancer. Most patients, however, elect to undergo definitive therapy with radical prostatectomy or radiotherapy.

Radical prostatectomy involves removal of the prostate gland, seminal vesicles, and a certain amount of surrounding tissue. It is usually performed on men under the age of 65 when the disease is local to the prostate gland. There is a 1-2% mortality rate from the procedure. Complications include loss of sexual function, loss of bladder control, scarring of the urethral channel, anastomotic urinary leakage, blood clot formation, rectal injury, bowel injury, myocardial infarction, sepsis, and potential spread of cancer cells. Radical prostatectomy is advised for younger patients with long life expectancy; they have the lowest risk of urinary incontinence (about 2%), and about 50% will be able to maintain erectile potency (if at least one neurovascular bundle can be spared). Note that if there is metastasis or lymph node involvement, then radical prostatectomy is not indicated.

External beam radiation , an alternative to radical prostatectomy, is used in cases where the cancer is confined to the prostate gland and surrounding tissues (STAGES A, B, and C). Usually recommended to older men (over 65), side effects are fewer and less serious. They may include bladder inflammation, radiation enteritis, radiation cystitis, impotence, incontinence, scarring, fibrosis, diarrhea and bloody stools. While most men retain potency after treatment, as many as 50% eventually develop erectile dysfunction. Statistics have shown that the results of radical prostatectomy and external beam radiation are comparable in outcome up to ten years after treatment.

Brachytherapy involves the implantation of radioactive seeds directly into the prostate, using hollow needles guided by real-time imaging. Since these seeds deliver radiation directly to the prostate without affecting the surrounding tissue, higher doses of radiation can be used. The seeds remain permanently in place within the prostate and become inert in six to 12 months. Complications are usually minimal - usually urinary problems involving frequency, urgency, or difficulty with urination - and tend to diminish by the time the seeds have lost their radioactivity. Nearly 90% of the men receiving this treatment retain sexual function. Whether seed implants (brachytherapy interstitial irradiation) will produce equivalent results to external beam radiation is currently under evaluated.

Cryotherapy involves freezing the prostate tissue by inserting probes containing liquid nitrogen thought he perineum and into the prostate gland. This procedure is guided by ultrasound. Although the treatment is performed easily and recovery time is brief, the procedure can have many complications, including a 75% risk of impotence (failure to have or maintain an erection). In addition, long-term effectiveness of this treatment has not yet been established.

A standard form of therapy to treat prostate cancer that has gone beyond the prostate gland, hormone therapy is used to inhibit the production of the male hormone testosterone, thereby inhibiting the growth of the cancer as well. Hormone therapy is usually suggested as a primary treatment for older men or for men who have relapsed after surgery or radiation therapy. Significantly, eventual resistance to hormonal drugs is extremely common. Due to this, hormonal drugs may be used intermittently. Adverse effects of hormonal drugs includes hot flashes, impotence, decreased sex drive, breast enlargement, accelerated bone loss, weakness, muscle wasting, liver damage, nausea, diarrhea, alcohol intolerance, and reduced night vision.

Another method used to lower testosterone production is surgical removal of the testicles, called bilateral orchiectomy. This is a palliative rather than curative treatment, usually recommended for those with late stage (Stages C or D) cancer. In many cases the benefits of orchiectomy are temporary, and the cancer reappears. Bilateral orchiectomy or medical castration with luteinizing hormone-releasing hormone agonists decreases serum testosterone equivalently. The side effects of orchiectomy are similar to those of hormone therapy listed above.

There is no standard therapy for hormone refractory prostate cancer; cytotoxic and biologic agents are being investigated and may offer palliation and prolonged survival. However, their superiority over corticosteroids alone has not been proved. Chemotherapy is sometimes used in advanced stages of prostate cancer, but it has not been found to be very effective. Chemotherapeutic agents commonly used include vinblastine, etoposide mitoxantrone, and taxol.

Prostate cancer is multifactorial in origin. The following is a brief listing of factors that are believed to promote prostate cancer. These etiological factors and their concomitant therapeutic interventions will be discussed in detail following this overview.

OVERVIEW OF RISK FACTORS:

Age - 30% of men 30-39 have undiagnosed microfocal prostate cancer. After age 50, both incidence and mortality go up exponentially. By age 80, undiagnosed microfocal cancer exceeds 75%.

Race - African American men have the highest mortality from prostate cancer in the world. This is due to socio-economic factors, later diagnosis, higher fat intake, less production of vitamin D from sunlight, and increased androgens (15% higher serum levels).

Family history - if a man has a first-degree relative with prostate cancer, his prostate cancer risk is approximately twice that of the general population; when both first- and second-degree relatives are affected, the risk increases about nine times. In a study of twins, genetics accounted for 57% of cancer risk and environment for 43% of cancer risk.

Dietary factors - prostate function is regulated by testosterone, a male sex hormone produced mainly in the testicles. The underlying factor linking diet and prostate cancer is probably hormonal. Fats from meat and dairy (including non-fat milk) stimulate production of testosterone and other hormones, and testosterone acts to speed the growth of prostate cancer.

Other dietary risk factors include: high intake of refined sugar and processed foods, low intake of fiber, fruit, and vegetables high in carotenes (specifically beta-carotene). High blood calcium is also associated with prostate cancer. In addition, cholesterol metabolites are damaging to cells and carcinogenic, and have been shown to accumulate in the hyperplastic or cancerous human prostate. Increasing fruits, vegetables and vitamins (one study showed a 45% risk reduction when subjects ate at least ten servings per week of tomato-based foods rich in lycopene) decreases risk.

Environmental factors - xenoestrogens from pollution, pesticides and herbicides contribute to BPH and prostate cancer. Welders, battery manufactures, rubber workers and workers exposed to the metal cadmium seem to be abnormally vulnerable to prostate cancer.

Reproductive factors - higher incidence in men with vasectomies, and in men with frequent sexual activity begun early in life, multiple sex partners, or a history of STD.

Smoking - associated with more aggressive disease, not increased incidence.

Alcohol - consumption influences weight and hormones.

Exercise - lack of exercise is a major factor in overall health.

Infectious disease - viral and fungal disease may contribute to cancer formation.

Mental emotional - cancer is associated with traumatic events such as death of a spouse or child, and divorce.

Stature - taller men have more prostate cancer

Disease is a rational process that can be analyzed and understood. Generally, disease occurs according to the following overall pathophysiologic process:

In practical terms, we see chronic inflammation (BPH) and degeneration (prostate cancer) both increase in incidence as men age. Clinically speaking, many of the same approaches and modalities of healing are applied for both BPH and prostate cancer. Therefore the following discussion includes treatment protocols for both disease states. Common to both is the etiology of hormonal influences:

The normal aging process in men favors the development of BPH (benign prostatic enlargement) and prostate cancer, due to a variety of factors including age-related alterations in hormone levels. BPH represents a male hormone (androgen) dependent disorder of metabolism. As men age there are many significant changes in hormone levels - testosterone (especially free testosterone) decreases after the fifth decade, while other hormones (prolactin, estrogen sex-hormone binding ligand, LH, FSH) are all increased. The ultimate effect of these changes is an increased concentration of DHT (dihydrotestosterone) within the prostate itself.

DHT is a very potent form of testosterone, and is responsible for the overproduction of prostate cells. The increase of DHT within the prostate cell is largely due to a decreased rate of removal. Testosterone and DHT are normally metabolized by enzymes into compounds that have a reduced attraction for receptor molecules in the prostate. These less active compounds can then be excreted. When testosterone and DHT are not being metabolized and excreted, their levels rise in the prostate cells.

Elevated estrogen plays a role by inhibiting the metabolizing enzymes. Estrogen stimulates epidermal growth factor, and promotes cell proliferation and formation of fibrous tissue. Estrogen receptors are abundant in prostate cell nuclei, and some researchers believe that estrogen itself, or a decreased DHT:estrogen ratio may be involved in the abnormal growth of the prostate. Estrogen clearance is modulated by the liver, and liver disease (alcoholism, hepatitis, etc.) tends to increase circulating estrogen levels. Exogenous estrogens are found in meat and dairy products and in environmental pollutants. Many pesticides and food contaminants can increase the formation of DHT.

In addition to a decreased rate of excretion of the male hormones, there is an increased uptake in the prostate due to the hormone prolactin. Prolactin levels are increased by beer and stress and decreased by zinc and vitamin B6.

Nutritional supplements for BPH and prostate cancer:

In 1941, Dr. William Cooper and James Hart wrote about using flaxseed in the treatment of BPH.¹  In this study, nineteen men were given 2,000 mg of flaxseed oil per day. The dose was given for three days and then reduced to 1,300 mg per day for several weeks. After that time, a maintenance dose of less then 1,000 mg was used. All patients began retaining less urine; 63% had no residual urine at the conclusion of the testing. Night time urination problems stopped in 68%. All patients noted less fatigue and leg pain along with an increase in sexual libido. Dribbling was eliminated in 95% of the cases. Urine stream was more forceful and the size of the prostate was reduced. Unfortunately, there has been no recent follow-up to this preliminary research.

Other researchers have noticed that the portion of the seminal fluid for which the prostate is responsible is high in the mineral Zinc may act as a 5-AR (5 alpha reductase) inhibitor. Zinc levels in prostate tissue are significantly increased in BPH and significantly decreased in prostate cancer.

In a study of nineteen males, those with BPH had normal levels of zinc in the blood, which did not increase when zinc supplements were given. However, their semen zinc levels increased. This group was given 150 mg of zinc for two months, which was then dropped to 50-100 mg. In fourteen of the nineteen men (74%), the prostate shrunk in size. Unfortunately, this study was never published, and there is no other study using men as subjects. This was verified by rectal palpation, X-ray, and endoscopy.²  Animal studies have confirmed this finding, but only using locally injected zinc. While the research supporting zinc is therefore very weak, some doctors of natural medicine nonetheless recommend its use.³

Because zinc competes with copper for absorption, when recommending this amount of zinc most nutritionally oriented doctors suggest also taking at least 2 or 3 mg of copper.

Another group of researchers looked at the amino acid content (the building blocks of protein) of prostate fluid. The group determined that the fluid contained high amounts of three key amino acids: Glycine, Alanine and Slutamine. A controlled study of forty-five men with BPH was then done.

After three months, 66% of the patients treated with this amino acid mixture showed reduced urinary urgency, 50% had less delay in starting urine flow, 46% had less difficulty in maintaining flow, and 43% had reduced frequency. No side effects were observed.⁴

Beta-sitosterol is another nutrient that may benefit men with BPH. One double-blind study of 100 men showed that beta-sitosterol, taken either as 20 mg of beta-sitosterol three times per day or a placebo for six months, improved urine flow, reduced the size of the prostate, and led to subjective feelings of improvement of BPH.⁵

Pollen has been reported to improve symptoms of BPH, possibly through an anti-inflammatory effect.⁶

Are there any side effects or interactions?

(Refer to the individual supplement for complete information.) Toxicity has not been reported with regard to flaxseed. Zinc intake in excess of 300 mg per day may impair immune function.⁷  Although the preliminary research is contradictory, patients with Alzheimer’s disease should avoid zinc supplements until further studies clarify the role of zinc in this disease.^{8 9}  Zinc inhibits copper absorption, which can lead to anemia and lower levels of HDL cholesterol (“good” cholesterol).^{10 11 12}  Copper intake should be increased if zinc supplementation continues for more than a few days (except for individuals with Wilson’s disease).¹³  Many zinc supplements, to prevent copper inhibition, include copper in the formulation.

Zinc competes for absorption with iron,^{14 15} calcium,¹⁶ and magnesium.¹⁷  A supplement will prevent mineral imbalances that can result from taking high doses of zinc for extended periods of time.

Many people have allergies to inhaled pollens, although such reactions to ingested pollen are rare. Otherwise no significant adverse effects have been reported.

In Europe, herbal supplements have become one of the leading methods for managing early stages of BPH. Successful treatment of BPH is an ongoing process. Men with BPH will probably need to take one or a combination of these herbs indefinitely. Any nutritional support for BPH should be done after consulting a doctor.

The fat-soluble extract of the Saw Palmetto berry has become the leading natural treatment for BPH. This extract, when used regularly, has been shown to help keep symptoms in check.¹⁸  Saw palmetto may inhibit 5-alpha-reductase, the enzyme that converts testosterone to its more active form, dihydrotestosterone (DHT). Saw palmetto also blocks DHT from binding in the prostate.¹⁹  Studies have used 320 mg of the standardized (85% liposterolic acids) herbal extract, capsules, or tablets per day. In a recent study, a group of 305 patients with mild to moderate symptoms of BPH was given 160 mg of saw palmetto twice a day for three months; the study reported an 88% success rate.²⁰

Since saw palmetto reduces levels of 5-alpha-reductase, an additional benefit of this herb may be reduced risk of developing prostate cancer. While no tests have been done to show that reducing this enzyme’s activity will reduce prostate cancer risk, lower levels of this enzyme are detected in men in countries with lower incidence of prostate cancer.²¹

An extract from the bark of the African tree pygeum has also been used for BPH. Approved for use in Germany, France, and Italy, pygeum has anti-inflammatory and decongesting properties that help with early-stage BPH.²²  Studies have used 50-100 mg of pygeum (standardized to 13% sterols) herbal extract, capsules, or tablets twice per day. Pygeum africanum contains three compounds that help the prostate: pentacyclic triterpenoids have a diuretic action; phytosterols act as an anti-inflammatory; ferulic esters help rid the prostate of any cholesterol deposits that accompany BPH.

Another herb for BPH is a concentrated extract made from the roots of the nettle plant Uritica dioica. The root extract may increase the volume and maximum flow of urine in men with early-stage BPH.²³  It has been successfully combined with both saw palmetto and pygeum for treatment of BPH. An appropriate amount appears to be 120 mg nettle root extract, capsules, or tablets twice per day or a 2-4 ml tincture three times daily.

Are there any side effects or interactions?

(Refer to the individual herb for complete information.) No significant side effects have been noted in clinical studies with saw palmetto extracts. Side effects from pygeum are very rare, but they include mild gastrointestinal irritation in some patients. Allergic reactions to nettle are rare. However, when contact is made with the skin, fresh nettles can cause a rash.

Movement and Exercise:

Physically active men have a much lower risk of prostate cancer than their less active counterparts. Deep breathing increases oxygen and causes a 15-fold increase in lymph flow. From the energetic perspective of Chinese medicine, the prostate is situated in the pelvic basin, which is prone to stagnation and easily manifests symptoms when confronted with the work, sex, and dietary habits of modern civilization.

Modern man usually works sitting, thus severely compromising proper circulation in the lower abdomen and pelvic area. In comparison to men living in traditional societies, his sexual life tends to be unbalanced (alternating between extremely high frequencies at young age while being rather inactive in midlife due to stress or symptoms of premature aging).

It is imperative to include exercise and movement in the treatment of prostate disease. Most highly recommended is walking. It is more important to walk regularly - say 20 minutes every day - then to do irregular and unnecessarily strenuous walking. Stretching exercises after the daily walk will help to maintain flexibility and decrease muscle aches and strains.

Other activities that are highly recommended are swimming, tai chi, chi gong, dancing and yoga. In addition, regular ejaculation is often indicated. Television and sedentary activities should be avoided, and activities that challenge the body and mind should be increased. It is important to find activities that are enjoyable and affordable; otherwise, it will be difficult to continue to do them on a regular basis and to permanently incorporate them into a healthy lifestyle.

Hydrotherapy:

Hydrotherapy is a special technique that greatly enhances recovery from many acute and chronic illnesses. It has been used successfully by hundreds of naturopathic physicians for over a century. These simple treatments improve the circulation of blood and lymph, promote better digestion, and increase the elimination of toxins. Hydrotherapy works so well because it acts to stimulate the body's own healing force.

In the treatment of BPH and prostate cancer, the most common hydrotherapy techniques are constitutional hydrotherapy and the sitz bath.

1. Hart JP, Cooper WL. Vitamin F in the treatment of prostatic hypertrophy. Report Number 1, Lee Foundation for Nutritional Research, Milwaukee, Wisconsin, 1941.

2. Bush IM et al. Zinc and the prostate. Presented at the annual meeting of the American Medical Association Chicago, 1974.

3. Fahim MS, et al. Zinc treatment for reduction of hyperplasia. Fed Proc 1976;35(3):361.

4. Damrau F. Benign prostatic hypertrophy: Amino acid therapy for symptomatic relief. J Am Geriatrics Soc 1962;10(5):426-430.

5. Berges RR, Windeler J, Trampisch HJ, et al. Randomized, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995;345:1529-32.

6. Horii A, Iwai S, Maekawa M, Tsujita M. Clinical evaluation of Cernilton in the treatment of the benign prostatic hypertrophy. Hinyokika Kiyo 1985;31:739-45 (in Japanese).

7. Chandra RK. Excessive intake of zinc impairs immune responses. JAMA 1984;252(11):1443.

8. Bush AI, Pettingell WH, Multhaup G, et al. Rapid induction of alzheimer A8 amyloid formation by zinc. Science 1994;265:1464-5.

9. Sardi B. Winning over the public: The battle between pharmaceuticals and nutritional supplements. Townsend Letter for Doctors and Patients 1996;#156:74-9.

10. Broun ER, Greist A, Tricot G, Hoffman R. Excessive zinc ingestion: A reversible cause of sideroblastic anemia and bone marrow depression. JAMA 1990;264:1441-3.

11. Resiser S, et al. Effect of copper intake on blood cholesterol and its lipoprotein distribution in men. Nutr Rep Internat 1987;36(3):641-9.

12. Sandstead HH. Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am J Clin Nutr 1995;61(suppl):621S-4S (review).

13. Fischer PWF, Giroux A, Labbe MR. Effect of zinc supplementation on copper status in adult man. Am J Clin Nutr 1984;40(4):743-6.

14. Dawson EB, Albers J, McGanity WJ. Serum zinc changes due to iron supplementation in teen-age pregnancy. Am J Clin Nutr 199;50:848-52.

15. Crovton RW, Gvozdanovic D, Gvozdanovic S, et al. Inorganic zinc and the intestinal absorption of ferrous iron. Am J Clin Nutr 1989;50:141-4.

16. Argiratos V, Samman S. The effect of calcium carbonate and calcium citrate on the absorption of zinc in healthy female subjects. Er J Clin Nutr 1994;48:198-204.

17. Spencer H, Norris C, Williams D. Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. J Coll Nutr 1994;13:479-84.

18. Schneider HJ, Honold E, Mashur T. Treatment of benign prostatic hyperplasia. Results of a surveillance study in the practices of urological specialists using a combined plant-base preparation. Fortschr Med 1995; 113:37-40.

19. Koch E, Biber A. Pharmacological effects of sabal and urtica extracts as a basis for a rational medication of benign prostatic hyperplasia. Urologe 1994; 334:90-95

20. Braeckman J. The extract of Serenoa repens in the treatment of benign prostatic hyperplasia: A multicenter open study. Cur Ther Res 1994;55(7):776785

21. Ross RK, et al. 5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 1992;339:887-9

22. Andro MC, Riffaud JP. Pygeum africanum extract for the treatment of patients with benign prostatic hyperplasia: A review of 25 year of published experience. Curr Ther Res 1995; 56:796-817.

23. Koch E, Biber A. Pharmacological effects of sabal and urtica extracts as a basis for a rational medication of benign prostatic hyperplasia. Urologe 1994; 334:90-95.