Aging Male. 2004 Jun;7(2):155-69
Preventing diseases of the prostate in the elderly using hormones and nutriceuticals.
Comhaire F, Mahmoud A.
Ghent University Hospital, Gent, Belgium.
The prostate has only one function, namely to secrete fluid containing substances that are needed for reproduction. This requires an extremely high concentration of androgens in the tissues. Benign prostatic hypertrophy (BPH) seems to be related to the long-term exposure of the prostate to the strong androgen 5alpha-dihydrotestosterone (DHT) and, possibly, to estrogens. The relation between prostate cancer and androgens is suggested to be U-shaped, with both extremes of androgen concentrations being associated with increased risk of invasive cancer. In the treatment of patients with BPH, the lipidic liposterolic extracts of Serenoa repens were as effective as the pharmaceutical inhibitors of the 5alpha-reductase enzyme or alpha1-adrenergic blockers in relieving urinary symptoms. In addition to moderately inhibiting the 5alpha-reductase activity, Serenoa seems to exert anti-inflammatory and complementary cellular actions with beneficial effects on the prostate. Unlike the pharmaceutical 5alpha-reductase inhibitors, finasteride and dutasteride, Serenoa does not suppress serum PSA, facilitating the follow-up and the early detection of prostate cancer. We suggest a strategy to prevent prostate cancer that aims at providing men with partial androgen deficiency correct testosterone substitution with a sustained release buccal bio-adhesive tablet. In addition, food supplementation with extracts of Serenoa repens and a combination of the antioxidants selenium, (cis)-lycopene and natural vitamin E, together with fish oil rich in long-chain polyunsaturated essential fatty acids of the omega-3 group seems warranted. Clearly, a holistic approach including careful clinical and biological monitoring of the aging man and his prostate remains mandatory.
Prostate Actions of Saw Palmetto
Becoming Clearer
By Donald J. Brown, ND
Healthnotes Newswire (June 7, 2001)—Men taking a saw palmetto herbal combination were found to have decreased amounts of dihydrotestosterone (DHT)—a hormone linked to benign prostatic hyperplasia (BPH)—in tissue samples taken from their prostates by needle biopsy.
The results of the study presented at Tuesday’s American Urological Association annual meeting in Anaheim, California and published this week in the journal Urology,1 confirm that a saw palmetto (Serenoa repens) supplement reduces levels of DHT—an action that is thought to contribute to the herb’s ability to treat mild to moderate BPH in men.
Tissue samples were obtained from the prostates of men with symptomatic BPH who had been taking a saw palmetto supplement (320 mg of saw palmetto per day combined with nettle root, pumpkin seed oil, lemon flavonoids, and vitamin A) or placebo for six months. Samples were also obtained from men with BPH who were either untreated or were taking the drug Proscar® (finasteride)—a prescription drug for BPH which is known to reduce DHT levels by inhibiting the enzyme 5-alpha reductase.
Men taking finasteride were found to have a sizable drop of 80% in prostate DHT levels compared to untreated men. By comparison, the saw palmetto supplement led to a 32% decrease in DHT levels.
While weaker than finasteride, saw palmetto’s effects on DHT were centered only in the prostate and did not affect blood levels of the hormone. Those in the finasteride group had a 70% decrease in blood levels of the hormone.
Prostate Gland and Hormones
DHT is the major male hormone in the prostate required for growth and maintenance of the gland. DHT is derived from testosterone—a conversion that occurs under the influence of the enzyme 5-alpha reductase. High levels of DHT are thought to contribute to an enlargement of the prostate and lead to BPH as men reach middle age. finasteride operates solely by inhibiting 5-alpha reductase. However, the drug is also associated with side effects, such as erectile dysfunction. The results of this study show a drop in DHT levels with saw palmetto use, which suggests but does not conclusively demonstrate 5-alpha reductase inhibition. Previous studies have indicated that saw palmetto may inhibit 5-alpha reductase.2
According to a critical review of clinical trials on saw palmetto published in 1998 in the Journal of the American Medical Association, saw palmetto is a safe and effective treatment for many of the symptoms associated with BPH.3 Affecting an estimated 50% of men over the age of 50, symptoms of BPH include weak or intermittent urine stream, painful urination, and increased frequency and urgency to urinate (especially at night).
The current study also highlights an important safety feature of saw palmetto: men taking the saw palmetto supplement had no change in blood levels of prostate-specific antigen (PSA)—an important marker used to detect prostate cancer. Drugs such as finasteride that alter PSA levels may potentially mask elevations and delay the diagnosis of prostate cancer. Saw palmetto’s lack of effect on PSA levels has been shown in previous clinical trials as well.4 5
While finasteride was a logical reference drug for evaluation of effect on DHT levels, further clinical trials are needed to compare the long-term effects of saw palmetto with the more commonly recommended class of BPH drugs known as alpha-blockers (e.g. Cardura®, Flomax®, and Hytrin®). Future studies should also determine whether the combination of ingredients used in the current study is superior to saw palmetto alone.
Before choosing to use saw palmetto supplements to treat BPH symptoms, men should discuss their condition with their urologist.
References:
1. Marks LS, Hess DL, Dorey FJ, et al. Tissue effects of saw palmetto and finasteride: Use of biopsy cores for in situ quantification of prostatic androgens. Urology 2001;57:999–1005.
2. Bayne CW, Ross M, Donnelly F, Habib FK. The selectivity and specificity of the actions of the lipido-sterolic extract of Serenoa repens (Permixon®) on the prostate. J Urol 2000;164:876–81.
3. Wilt TJ, Ishani A, Stark G, et al. Saw palmetto extracts for treatment of benign prostatic hyperplasia. A systematic review. JAMA 1998;280:1604–9.
4. Carraro JC, Raynaud JP, Koch G, et al. Comparison of phytotherapy (Permixon®) with finasteride in the treatment of benign prostatic hyperplasia. Prostate 1996;29:231–40.
5. Gerber GS, Zagaja GP, Bales GT, et al. Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: Effects in urodynamic parameters and voiding symptoms. Urology 1998;51:1003–7.
Physiology and Clinical Effects
Lycopene, found primarily in tomatoes, is a member of the carotenoid family—which includes beta-carotene and similar compounds found naturally in food—and has potent antioxidant capabilities.
A study conducted by Harvard researchers examined the relationship between carotenoids and the risk of prostate cancer.1 Of the carotenoids studied, only lycopene was clearly linked to protection. The men who had the greatest amounts of lycopene in their diet (6.5 mg per day or more) showed a 21% decreased risk of prostate cancer compared with those eating the least. This report suggests that lycopene may be an important tool in the prevention of prostate cancer. This study also reported that those who ate more than ten servings per week of tomato-based foods had a 35% decreased risk of prostate cancer compared with those eating less than 1.5 weekly servings. When the researchers looked at only advanced prostate cancer, the high lycopene eaters had an 86% decreased risk (although this did not reach statistical significance due to the small number of cases).
Contrary to popular opinion, research suggests that there is no preferential concentration of lycopene in prostate tissue.2 Although prostate cancer patients have been reported to have low levels of lycopene in the blood,3 and lycopene appears to be a potent inhibitor of human cancer cells in vitro ,4 evidence is conflicting concerning whether an increased intake of tomato products is protective against prostate cancer. Some studies, like the one discussed above, have reported that high consumption of tomatoes and tomato products reduces risk of prostate cancer.5 6 Other studies, however, are inconclusive,7 and some have found no protective association.8 9 10 11 12
There is some evidence that lycopene may be helpful in the treatment of prostate cancer. In a preliminary trial, 26 men with prostate cancer were randomly assigned to receive lycopene (15 mg BID) or no lycopene for three weeks before undergoing prostate surgery. Prostate tissue was then obtained during surgery and examined. Compared with the unsupplemented men, those receiving lycopene were found to have significantly less aggressive growth of cancer cells.13 In addition, a case report has been published of a 62-year-old man with advanced prostate cancer who experienced a regression of his tumor after starting 10 mg of lycopene per day and 300 mg of saw palmetto TID. As saw palmetto has not been previously associated with improvements in prostate cancer, the authors of the report attributed the response to the lycopene.14 Long-term controlled studies are needed to confirm these promising initial reports.
There is no evidence that tomato intake has any effect on benign prostatic hyperplasia (BPH).
Another study found that for the 25% of people with the greatest tomato intake, the risk for cancers of the gastrointestinal tract was 30–60% lower, compared with those who ate fewer tomatoes. These reduced risks were statistically significant.15 A study of women found that the 75% who ate the least amount of tomatoes had between 3.5 and 4.7 times the risk for pre-cancerous changes of the cervix (cervical intraepithelial neoplasia).16 Other researchers have also reported evidence suggesting that high dietary lycopene may be linked to protection from cervical dysplasia.17 While preliminary evidence also links dietary lycopene with protection from breast cancer,18 another study did not find this link.19
In a review of 72 studies,20 one researcher reported 57 associations between tomato intake or blood lycopene levels and decreased risk of cancer. Of these associations, 35 were statistically significant. The benefit was strongest for prostate, lung, and stomach cancers, although protective associations were also found for cancers of the pancreas, colon, rectum, esophagus, oral cavity, breast, and cervix. Because the data were from observational studies, a cause-and-effect relationship cannot be firmly established. However, the consistently lower risk of cancer associated with higher consumption of lycopene-containing tomatoes, provides a strong foundation for further research on lycopene.
In Europe, researchers have found a statistically significant association between high dietary lycopene and a 48% lower risk of cardiovascular disease.21 Lycopene supplementation has also boosted immune function in the elderly. In that trial, 15 mg of lycopene per day increased natural killer cell activity by 28% in 12 weeks.22
Food Sources
Tomatoes and tomato-containing foods are high in lycopene. In the Harvard study, the only tomato-based food that did not correlate with protection was tomato juice. In an unblinded, controlled trial, lycopene supplementation, but not tomato juice, effectively increased the body’s lycopene stores.23 These studies suggest that the lycopene present in tomato juice is poorly absorbed. However, other research indicates that significant amounts of lycopene from tomato juice can, in fact, be absorbed.24 Other foods that contain lycopene include watermelon, pink grapefruit, and guava.
References:
1. Giovannucci E, Ascherio A, Rimm EB, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 1995;87:1767–76.
2. Kristal AR, Cohen JH. Invited commentary: tomatoes, lycopene, and prostate cancer. How strong is the evidence? Am J Epidemiol 2000;151:124–7 [review, discussion 128–30].
3. Rao AV, Fleshner N, Agarwal S. Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutr Cancer 1999;33:159–64.
4. Levy J, Bosin E, Feldman B, et al. Lycopene is a more potent inhibitory of human cancer cell proliferation than either alpha-carotene or beta-carotene. Nutr Cancer 1995;24:257–66.
5. Mills PK, Beeson WL, Phillips RL, Fraser GE. Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 1989;64:598–604.
6. Tzonou A, Signorello LB, Lagiou P, et al. Diet and cancer of the prostate: a case-control study in Greece. Int J Cancer 1999;80:704–8.
7. Norrish AE, Jackson RT, Sharpe SJ, Skeaff CM. Prostate cancer and dietary carotenoids. Am J Epidemiol 2000;151:119–23.
8. Deneo H-Pellegrini H, De Stefani E, Ronco A, Mendilaharsu M. Foods, nutrients and prostate cancer: a case-control study in Uruguay. Br J Cancer 1999;80:591–7.
9. Schuman L, Mandel J, Radke A. Some selected features of the epidemiology of prostate cancer: Minneapolis-St. Paul, Minnesota case-control study, 1976–1979. In: Magnus K (ed). Trends in cancer incidence: causes and implications. Washington, DC: Hemisphere Publishing Corporation, 1982, 345–54.
10. Key TJ, Silcocks PB, Davey GK, et al. A case-control study of diet and prostate cancer. Br J Cancer 1997;76:678–87.
11. Schuurman AG, Goldbohm RA, Dorant E, et al. Vegetable and fruit consumption and prostate cancer risk: a cohort study in The Netherlands. Cancer Epidemiol Biomarkers Prev 1998;7:673–80.
12. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996;334:1145–9.
13. Kucuk O, Sarkar FH, Sakr W, et al. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 2001;10:861–8.
14. Matlaga BR, Hall MC, Stindt D, Torti FM. Response of hormone refractory prostate cancer to lycopene. J Urol 2001;166:613.
15. Franceshci S, Bidoli E, La Vecchia C, et al. Tomatoes and risk of digestive-tract cancers. Int J Cancer 1994;59:181–4.
16. Van Eenwyk J, Davis FG, Bowne PE. Dietary and serum carotenoids and cervical intraepithelial neoplasia. Int J Cancer 1991;48:34–8.
17. Kanetsky PA, Gammon MD, Mandelblatt J, et al. Dietary intake and blood levels of lycopene: association with cervical dysplasia among non-hispanic, black women. Nutr Cancer 1998;31:31–40.
18. Dorgan JF, Sowell A, Swanson CA, et al. Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri. Cancer Causes Control 1998;9:89–97.
19. Jarvinen R, Knekt P, Seppanen R, Teppo L. Diet and breast cancer in a cohort of Finnish women. Cancer Lett 1997;114:251–3.
20. Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 1999;91:317–31.
21. Kohlmeyer L, Kark JD, Gomez-Gracia E, et al. Lycopene and myocardial infarction risk in the EUROMIC study. Am J Epidemiol 1997;146:618–26.
22. Corridan BM, O’Donohue MP, Morrissey PA. Carotenoids and immune response in elderly people. Proc Nutr Soc 1998;57:3A [abstr].
23. Paetau I, Rao D, Wiley ER, et al. Carotenoids in human buccal mucosa cells after 4 wk of supplementation with tomato juice or lycopene supplements. Am J Clin Nutr 1999;70:490–4.
24. Paetau I, Khachik F, Brown ED, et al. Chronic ingestion of lycopene-rich tomato juice or lycopene supplements significantly increases plasma concentrations of lycopene and related tomato carotenoids in humans. Am J Clin Nutr 1998;68:1187–95.
on cycle for prostate health I use:
30mg lycopene
1mg finasteride 320mg saw palmetto