Nutritional Ingredients for Men's Health

January 28, 2011

Selenium has been a longtime contender in supporting prostate health. In recent years, several headlines have continued the discussion.

Selenium
Selenium has been a longtime contender in supporting prostate health. In recent years, several headlines have continued the discussion.

Most notably, the National Cancer Institute’s controversial $114 million Selenium and Vitamin E Cancer Prevention Trial (SELECT), touted as the largest-ever prostate cancer prevention trial, was halted early, in 2008. Researchers stated that neither vitamin supplement, alone or together, decreased incidence of prostate cancer and said they stopped the trial early because data showed a small, but not statistically significant, increase in prostate cancer incidence in the vitamin E group and a small, but also not statistically significant, increase in incidence of diabetes in the selenium group. However, neither occurrence could be proved to be caused by the supplements.

Among other study limitations, post-SELECT analyses revealed one significant problem: The form of selenium used in the trial was different than the high-selenium brewer’s yeast used in previous trials, such as the Nutritional Prevention of Cancer Trial, which showed a significant inverse relationship between selenium supplementation and risk of prostate cancer. SELECT used selenomethionine, which is a component of high-selenium brewer’s yeast. “L-selenomethionine is only one of more than 20 selenium-containing species in brewer’s yeast,” stated Ledesma et al. in a SELECT review.(1)

“For large, long-term clinical studies, the National Institutes of Health must have assurance that the product can be standardized and will be stable throughout the course of the trial. They could not achieve that with the yeast-based selenium and were forced to go with selenomethionine,” explains Andrew Shao, senior vice president, scientific and regulatory affairs, Council for Responsible Nutrition.

Another drawback Shao and other study reviewers note is that unlike in previous studies, the men enrolled in SELECT already had high baseline selenium levels.(2) “Thus, one could speculate that the benefit provided by supplemental selenium in a group that already was selenium replete would be incremental at best,” Shao explains. “This in turn could have translated into null results with respect to cancer risk.”

This theory was supported by a study published in December 2009 in Dose Response (3) in which researchers analyzed why the SELECT subjects, already replete with selenium, as well as the subjects with the highest plasma selenium concentrations prior to supplementation in the Nutritional Prevention of Cancer trial, did not benefit from additional selenium.

Instead, based on an animal study, the Dose Response researchers suggest a U-shaped dose-benefit model in which mid-range selenium levels (0.67 to 0.92 ppm, measured in toenail clippings) most effectively result in increased apoptosis, or the process of selectively deleting damaged cell populations, including cancerous cells.

“At first glance, it is puzzling why the null results of SELECT should [contradict] more than two decades of evidence from cellular and animal models and human epidemiological data showing that selenium exerts significant anticancer effects. But the apparent contradiction becomes far less troublesome if one posits that the anticancer effects of selenium are non-linearly dose-dependent,” the authors stated. “Clearly, when it comes to selenium and cancer prevention, more is not necessarily better. Not all men benefit from additional selenium.”

They added, “This new thinking prepares the ground for a paradigm shift-a shift away from continuous, daily supplementation as a means of cellular protection and toward intermittent strategies that make possible the purging of damaged, premalignant and malignant cells.”

“The future for selenium looks good from my standpoint, since it is starting to become more clear as to the impact of selenium on prostatic cells,” says Max Motyka, MS, RPh, director of sales and marketing for Albion (St. Clair Shores, MI). “This new finding [in the Dose Dependent study] suggests the good chance that the use and dose of selenium in prostate health may become defined.”

“Future research needs to be directed on whether men with low, suboptimal selenium levels (<0.8 ppm in toenails) can achieve prostate cancer risk-reduction through daily selenium supplementation,” he adds.

Saw Palmetto Extract
Benign prostatic hyperplasia (BPH), or an enlarged prostate gland, can block the urethral canal, resulting in lower urinary tract symptoms, also known as LUTS. LUTS can manifest in urgent, frequent, nocturnal, and incomplete urinating, as well as a weak urine stream. While BPH is noncancerous, its symptoms can cause extreme discomfort. If left untreated, they can, in severe cases, result in kidney damage. It’s estimated that BPH affects more than 50% of men in their sixties and as many as 90% of men over the age of 70.

Saw palmetto berry (Serenoa repens) extract has historically been a common therapy for reducing BPH symptoms, supported by numerous studies. It’s estimated that 2.5 million men in the United States are regular saw palmetto supplement users.(6) In some countries in Europe, saw palmetto is approved as a drug. BPH is primarily caused by an age-related overproduction of dihydrotestosterone (DHT). Saw palmetto can inhibit production of the testosterone enzyme 5-alpha-reductase, which works to convert testosterone in the prostate to the more-potent hormone DHT to stimulate-or, in the case of BPH, overstimulate-prostate tissue growth.

Among the many studies showing saw palmetto’s efficacy for BPH, notably, a 2008 meta-analysis published the Journal of the American Medical Association found, after examining 18 clinical trials, that saw palmetto improves urologic symptoms and flow measures, including reducing nocturia (25%), peak urine flow (24%), mean urine flow (28%), and residual urine flow (43%).(5)

In clinical tests comparing the efficacy of saw palmetto to commonly prescribed BPH drugs, saw palmetto has been most often compared to the pharmaceutical drug finesteride (Proscar). Results show that saw palmetto works equally well to alleviate BPH symptoms, although results can take six to eight weeks to take effect, compared to four weeks for drugs. More importantly, saw palmetto is said to work with fewer adverse events associated with BPH drugs, such as decreased libido, erectile and ejaculatory dysfunction, and impotence.(5) Saw palmetto has also been compared to the BPH drug tamsulosin, or Flomax, in trials that showed saw palmetto to be equally effective.(7,8) In addition, saw palmetto provides the benefit of preventing the binding of DHT to cell receptors in the prostate, as well as providing anti-inflammatory effects.

In terms of safety, studies have shown saw palmetto’s safe use-notably, the one-year, 225-subject Saw Palmetto for Treatment of Enlarged Prostates (STEP) study supported by the National Center for Complementary and Alternative Medicine.(6) Importantly, saw palmetto is said to act without interfering with testosterone levels or affecting prostate specific antigen (PSA) levels, a commonly used biomarker in detecting prostate cancer.

Valensa (Eustis, FL) is a leading supplier of saw palmetto berry extract in the United States, offering its USPlus saw palmetto extract, which is produced using the company’s DeepExtract technology. DeepExtract is a non-chemical-solvent process that utilizes supercritical carbon dioxide extraction to yield more micronutrients from the raw material.

Valensa recently stepped up its public campaign to raise awareness about saw palmetto quality. Due to high demand, saw palmetto is often adulterated.

Specifically, Valensa is highlighting the distinctions between saw palmetto forms, underlining that while numerous studies point to the efficacy of the extract form for BPH, no studies support the use of saw palmetto in dried, ground-up powder form, in which active ingredients can be quite low.

“There is a solid body of evidence based on a number of clinical trials that show the 320 mg/day dosage of pure saw palmetto oil extract offers support to men experiencing the common effects of BPH. There have been no studies done on similar levels of the powder-form products,” says Rudi E. Moerck, PhD, Valensa’s president and CEO.

“Just because both product forms start with saw palmetto berries, it doesn’t mean they are equivalent when it comes to achieving the results we expect from saw palmetto oil extracts,” he adds.

Valensa says that a lot of supplement capsules on the market contain the powder, and not the extract.

“Saw palmetto powders are usually sold in 230- to 500-mg capsules that mimic their oil-extract counterparts in size. These powder-form products contain only about 10 to 12% of the oil extract that has been studied in all of the successful clinical trials,” the company says. “At this rate, users would need to consume between 7 and 10 capsules a day to ingest the 320-mg oil extract dose supported by the trials.”

Valensa estimates that up to 50% of the saw palmetto supplements sold in the United States are powder-form supplements. By contrast, it says, in Europe, where in some places saw palmetto is regulated as a drug, oversight is tighter and therefore the powder form is not common there.

Cranberry
In the area of BPH and prostate health, cranberry can now also be considered a player. Decas Botanical Synergies LLC (Carver, MA) helped fund a clinical study recently published in the British Journal of Nutrition (4) that examined whether Decas’s PACran cranberry powder (Vaccinium macrocarpon) could benefit men with LUTS symptoms, elevated PSA levels, negative prostate biopsy, and clinically confirmed chronic nonbacterial prostatitis.

Conducted for six months on 42 men, the study administered PACran capsules containing 1500 mg to half of the men. The control group received no cranberry treatment. All of the subjects had LUTS, elevated PSA levels, and/or BPH.

Though the mechanism of action was not defined, based on such measurements as the International Prostate Symptom Score (measuring LUTS), quality of life, maximal and average urinary flow rate, prostate bladder voiding, post-void residual volume, and PSA levels, the supplemented subjects were found to benefit from cranberry supplementation. In contrast to the control group, supplemented subjects saw statistically significant improvements in urination parameters, including rate of urine flow, average flow, total volume, and post-void residual urine volume; and a total lower PSA level at the end of the study.

Moreover, these results were achieved with no influence on blood testosterone or serum C-reactive protein levels, the researchers said.

“The results of the present trial are the first firm evidence that cranberries may ameliorate LUTS, independent of benign prostatic hyperplasia or C-reactive protein level,” the researchers stated.

“This is the first study to evaluate the effect of cranberry on prostate health,” says Dan Souza, director of sales and marketing for Decas. He says the company is embarking on additional research to identify the mechanisms of action for PACran’s support of prostate health, and that the ingredient now has a functional food health claim in Korea.

“Decas will continue to build upon and strengthen the science behind PACran in the prostate-health market,” he says.

References

1. Ledesma MC et al., “Selenium and vitamin E for prostate cancer: Post-SELECT status,” Molecular Medicine, published online ahead of print September 21, 2010.

2. Dunn BK et al., “A nutrient approach to prostate cancer prevention: The Selenium and Vitamin E Cancer Prevention Trial (SELECT),” Nutrition and Cancer, vol. 62, no. 7 (October 2010): 896-918.

3. Chiang EC et al., “Defining the optimal selenium dose for prostate cancer risk reduction: Insights from the U-shaped relationship between selenium status, DNA damage, and apoptosis,” Dose Response, vol. 8, no. 3 (December 2009): 285-300.

4. Vidlar A et al., “The effectiveness of dried cranberries (Vaccinium macrocarpon) in men with lower urinary tract symptons,” British Journal of Nutrition, vol. 104, no. 8 (October 2010): 1181-1189.

5. Wilt TJ et al., “Saw palmetto extracts for treatment of benign prostatic hyperplasia,” JAMA, vol. 280, no. 18 (November 11, 1998): 1604-1609.

6. Avins AL et al., “A detailed safety assessment of a saw palmetto extract,” Complement Ther Med., vol. 16, no. 3 (June 2008): 147-154.

7. Hizli F et al., “A prospective study of the efficacy of Serenoa repens, tamsulosin, and Serenoa repens plus tamsulosin treatment for patients with benign prostate hyperplasia,” Intl Urol Nephrol., 2007; Jan 4 (Epub ahead of print.)

8. Debruyne F et al., “Comparison of phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostate hyperplasia: A 1-year randomized international study,” European Urology, vol. 41 (2002): 497-506.