Nutritional Ingredients for Men's Health: Prostate Health

What kind of demand has Jarrow Formulas seen for prostate-health products, and what products does the brand offer in this area?

Jarrow Formulas has experienced steady sales with prostate-health products-and for obvious reasons. With an aging population base, demand continues to climb. Jarrow Formulas’ Prostate Optimizer is a comprehensive formula for prostate health. In addition, Jarrow Formulas offers Saw Palmetto, Ultra Saw Palmetto + Pygeum, Lycopene as Lyco-Sorb, Chrysin, and Vitamin D3.

Which are your top picks for prostate-health ingredients?
Many of the mechanisms for prostate-health ingredients are well worked out:

•       Saw Palmetto (Serenoa repens): Generally treated as the premier supplement for prostate health, it may inhibit the enzyme 5-alpha-reductase as one mechanism of action. Epethial contraction has been observed. The extract may reduce the symptoms of moderately symptomatic benign prostatic hyperplasia (BPH). However, the effectiveness of saw palmetto used alone is in doubt; the rate of success is greater in combination therapy. (Cochrane Database Syst Rev. 2009 Apr 15; (2): CD001423.)

•       Lycopene (tomato extract): Consumption of tomato products is associated with lower rates of prostate cancer. This finding has been confirmed by an inverse proportion of lycopene found in serum and prostate cancer. Epidemiological studies have been very supportive of lycopene in supporting prostate health. One or two small pilot trials have supported the anticancer effects of lycopene on prostate and other cancers, but few well-designed clinical trials have been conducted. (Oncology (Williston Park). 2010 Mar; 24(3): 296.) (Nutr Cancer. 2009 Nov; 61(6): 775-83.)

•       EPA and DHA Omega-3 Fatty Acids: Consumption of omega-3 fatty acids has been associated with a reduced risk of prostate cancer. The inhibition of COX-2 inflammatory processes may be one factor. Androgenic induction of prostate-specific antigen (PSA) protein has been shown to be repressed by DHA and EPA in a dose-dependent manner. In general, EPA and DHA may help reduce risk of cancer. “Without exception, these publications demonstrate that higher EPA (and possibly DHA) concentrations in the cell membrane, a validated measure for plasma fatty acids, is associated with lower cancer risk.” (Drug News Perspect. 2008 Nov; 21(9): 504-10.)

•       Stinging Nettles Extract (Urtica dioca): There is an antiproliferative effect on prostatic epithelial cells. In trials in combination with saw palmetto, average urinary flow increased, whereas the miction time decreased. This ingredient is approved for use in Germany against BPH. There is not a large volume of clinical research, but the research available indicates that stinging nettles extract may reduce lower urinary tract symptoms, including voiding issues and irritation, both alone and in combination therapy. (Urologia. 2010 Oct 2; 77(3): 180-186.) (J Herb Pharmacother. 2005; 5(4): 1-11.)

•       Cernitin Pollen Extract: This extract has been shown to improve the urinary-voiding rate, decrease residual urine, and reduce prostate volume. There are immunomodulatory effects as well, and an inhibition of the arachidonic cascade. (Zhonghua Nan Ke Xue. 2008 Jun; 14(6): 533-7.) (BJU Int. 2000 May; 85(7): 836-41.) (Cochrane Database Syst Rev. 2000; (2): CD001042.) (Br J Urol. 1993 Apr; 71(4): 433-8.) (Br J Urol. 1990 Oct; 66(4): 398-404.) (Arzneimittelforschung. 1991 Feb; 41(2): 162-7.)

•       Selenium: As most nutritional textbooks will affirm, selenium is necessary primarily as a component of glutathione peroxidase. Conditions of elevated inflammatory response, such as rheumatoid arthritis, can increase selenium requirements. However, there is little firm evidence that selenium confers greater benefits when ingested beyond replenishment levels for baseline demands. It is unlikely that chronic intakes above 200 mcg/day will yield additional benefits. One or more major trials for prostate cancer have demonstrated no benefit above placebo. (Nutr Cancer. 2010 Oct; 62(7): 896-918.) (JAMA. 2009 Jan 7; 301(1): 39-51.)

•       Milk Thistle Extract: Many of the glutathione-based benefits expected with selenium can be had with milk thistle extract. It is considered a promising new approach to cancer prevention and treatment, including for prostate cancer, but difficulties in achieving tissue penetration make the efficacy of normal supplementation unclear. (Prostate. 2010 Jun 1; 70(8): 848-55.) (Anticancer Agents Med Chem. 2010 Mar; 10(3): 186-95.)

•       Cranberry (Vaccinium macrocarpon): Only recently has any research appeared concerning cranberries and prostate health. One interesting clinical trial demonstrated significant benefit against lower urinary tract symptoms. “In contrast to the control group, patients in the cranberry group had statistically significant improvement in International Prostate Symptom Score-urination parameters, including voiding parameters (rate of urine flow, average flow, total volume, and post-void residual urine volume), and lower total PSA level on day 180 of the study.” This study used 1500 mg dried cranberry powder per day for six months. There was no influence on blood testosterone or serum CRP levels, therefore these were not the mechanisms of action. (Br J Nutr. 2010 Oct; 104(8): 1181-9.)

Although there likely are more studies on saw palmetto than on any single ingredient for prostate health, the benefits reported would appear to be greater and to appear faster with cernitin pollen extract. Combination formulas would seem to offer advantages over single ingredients.

 What dosages does Jarrow recommend for these ingredients?

•       Saw Palmetto (Serenoa repens) berry extract is standardized to contain 85 to 95% of the active fatty acids and sterols, including beta-sitosterol: 300 mg or more

•       Lycopene (tomato extract): 5 to 10 mg

•       EPA and DHA: in the range of 275 mg or more

•       Stinging Nettles Extract (Urtica dioca): 100 to 275 mg

•       Cernitin Pollen Extract: 250 to 375 mg, but with clear superiority of benefits at 750 mg/day

•       Selenium: Not more than 200 mcg/day

How has the science for these ingredients-specifically saw palmetto, lycopene, and selenium-supported their efficacy for prostate health? Is more research needed to draw a conclusive link? Which of them has the strongest support?
Lycopene has the greatest support for protection against prostate cancer, but not for BPH. Using it in conjunction with vitamin D3 obviously offers advantages. FDA allows for a qualified health claim, indicating relatively strong support for this ingredient.

Selenium is essential for glutathione metabolism, but evidence is controversial that elevated levels of intake beyond basic requirements provide any benefits.

Saw palmetto has been the subject of the most studies, but reviews of these trials now, as was the case 10 years ago, continue to be mixed, at best. To be sure, there are a few studies that have been positive with regard to benefits for BPH. (Minerva Urol Nefrol. 2010 Dec; 62(4): 335-40.) Nevertheless, most clinical trials have yielded null results (i.e., no better than placebo). For instance, a 2009 review of 30 randomized trials failed to find convincing support of the superiority of saw palmetto over placebo for any of the prostate symptoms examined. (Cochrane Database Syst Rev. 2009 Apr 15; (2): CD001423.) Similarly negative findings have appeared at the usually recommended dosages even after a year of use. (Clin Trials. 2009 Dec; 6(6): 628-36.) Only combinations, such as when used in conjunction with lycopene and selenium, have shown significant benefits. (Urol Int. 2010; 84(4): 400-6.) This may be due to the combination’s stronger impact on inflammation than of any one ingredient. (Urology. 2010 Nov 24. [Epub ahead of print])

Again, combination products have demonstrated effectiveness, whereas saw palmetto taken alone generally has not. When taken for three months, a combination of natural products (cernitin, saw palmetto, B-sitosterol, and vitamin E) compared to placebo significantly lessened nocturia and frequency and diminished the overall symptomatology of BPH as indicated by an improvement in the total American Urological Association Symptom Index score. (Int Urol Nephrol. 2001; 33(2): 217-25.)

Cernitin Pollen Extract has much better support for success against BPH than does saw palmetto. (Zhonghua Nan Ke Xue. 2008 Jun; 14(6): 533-7.) (BJU Int. 2000 May; 85(7): 836-41.) (Cochrane Database Syst Rev. 2000; (2): CD001042.)

What are other ingredients that may be promising for prostate health in the future?
One of the most interesting ingredients is EFLA®940 Pumpkin Seed Extract (Cucurbita pepo). It helps reduce aromatase and the binding of 5-alpha-reductase, while improving the voiding actions of the bladder. Japanese clinical data from Frutarom supports the efficacy of this extract. Results have been shown previously with another pumpkin seed extract used in Germany. (Forsch Komplementarmed Klass Naturheilkd. 2000 Aug; 7(4): 200-4.)

Which ingredients have an FDA-approved health claim for prostate health?
There is a qualified health claim for tomato in various forms for reducing the risk of prostate cancer.

Regarding selenium and FDA’s now-amended health claim linking selenium with reduced risk of prostate cancer, can you comment on how this amended claim is useful when in fact it still contains strong language against selenium for reduced prostate risk? While FDA amended the claim to comply with First Amendment rights, does the still-strong language against selenium indicate that the agency still believes there is not conclusive science supporting selenium’s benefits for prostate health?
It is always a good thing when government agencies are told by the courts that they must obey the law, especially the Constitution. Hence, it can only be viewed as positive that in Alliance for Natural Health v. Sebelius before the United States District Court for the District of Columbia, the court reaffirmed six previous rulings and required FDA to honor the First Amendment. This was a ruling against prior restraint and in support of access to information that could be found in any large library. The fact that FDA remains skeptical regarding selenium and continues to express that skepticism is within its institutional prerogative inasmuch selenium remains an intensely controversial supplement.

As for the industry’s response to the SELECT trial, one element is that the supplement industry at large remains wed to the same once fashionable, but now highly questionable, assumptions that underlay the SELECT trial.

The SELECT hypothesis of reduced prostate cancer rested on problematic models of antioxidant mechanisms of action. Selenium at normal dietary levels is required for glutathione peroxidase activity, yet there is little or no evidence that an increased intake of selenium beyond the minimum required to activate the enzymes involved in glutathione metabolism is beneficial. Moreover, the anticancer effect found in several in vitro and animal trials actually represents selenium’s potential pro-oxidant actions leading to apoptosis in faster-growing cells and in cells with altered glutathione metabolism, such as cancer cells. This is partly discussed in “Selenium: a double-edged sword for defense and offence in cancer.” (Arch Toxicol. 2010 Dec; 84(12): 919-38.)

Regarding the non-significant increase in diabetes Type 2 found in the selenium-only arm of the SELECT trial, it likely is just that-not significant. For the past several years, dueling studies have appeared showing alternately that selenium either prevents or promotes diabetes. My guess is that at normal physiologic levels of intake, it does neither.

As for vitamin E as alpha-tocopheryl acetate used in the study, this, again, represents, in part, an outdated model. This form of vitamin E for a long time was considered to be an especially effective scavenger of radicals targeting lipids and cell membranes. The classic attitude up through roughly the year 2005 was that “RRR-alpha-tocopherol is the most abundant form in nature and has the highest biological activity.” (J Physiol Biochem. 2001 Mar; 57(2): 43-56.) However, at high levels of intake, alpha-tocopheryl acts as a pro-oxidant, not an antioxidant. (Arterioscler Thromb Vasc Biol. 1996 May;16(5):687-96) Moreover, elevated chronic alpha-tocopherol intake from any source may compromise mitochondrial ubiquinol metabolism. Excessive oxidative degradation of tocopherol can potentially interfere with mitochondrial electron transfer. (Gregor W, Staniek K, Nohl H, Gille L., “Distribution of tocopheryl quinone in mitochondrial membranes and interference with ubiquinone-mediated electron transfer,” Biochem Pharmacol. 2006 May 28; 71(11): 1589-601.)

Many of the benefits of selenium and vitamin E suggested by epidemiological studies, in fact, probably are the result of a multitude of major and minor constituents found in the diet along with selenium and vitamin E in those studies.

Dallas Clouatre, PhD, earned his A.B. from Stanford and his PhD from the University of California at Berkeley. A Fellow of the American College of Nutrition, he is a prominent industry consultant and recently joined the Editorial Advisory Board of Nutritional Outlookmagazine. He is the author of numerous books. Recent publications include “Grape Seed Extract” in the Encyclopedia Of Dietary Supplements(2nd edition, 2010), “Tocotrienols in Vitamin E: Hype or Science?” and “Vitamin E – Natural vs. Synthetic” in Tocotrienols: Vitamin E Beyond Tocopherols (2009), “Kava Kava: Examining New Reports of Toxicity” in Toxicology Letters (2004) and Anti-Fat Nutrients (4th edition).