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Jennifer Grebow is editor-in-chief of Nutritional Outlook.
A healthy prostate and testosterone level-and ingredients that can help.
Getting men to talk about their feelings can be tough. But times may be changing. Thanks to drugs like Pfizer’s Viagra and AbbVie’s AndroGel testosterone ointment-think the “Low T” commercials you see on TV-what formerly were men’s private issues have moved into family rooms nationwide. This is important. Because in addition to unisex health concerns-heart health, brain health, joint health, etc.-prostate and testosterone status are a few of the physiological factors down there that can affect how a man feels everywhere.
As more men talk openly about their health concerns, they are also more likely to actively seek interventions to feel better. “As national advertising raises awareness around the issue of low testosterone, for instance, men will see that and start to think, ‘I don’t feel like I have as much energy as I used to, nor that my muscles recover as quickly from a workout as they used to; maybe I need a little testosterone,’” says Duffy MacKay, ND, vice president of scientific and regulatory affairs, Council for Responsible Nutrition (CRN; Washington, DC).
But do these types of ad campaigns cast “a wider net than necessarily needs to be cast,” as a university professor asked in 2010?1 Perhaps not all men-although some certainly do-need to turn to drugs to address issues like non-cancerous benign prostatic hyperplasia (BPH) or low testosterone. After all, in many men, BPH and low testosterone are natural, non–life threatening signs of aging. They manifest slowly over decades, and, as such, some may prefer to take a preventative, longer-term approach-often with fewer side effects-instead of a drug treatment-based approach. In short, they may prefer a dietary supplement.
“Things have changed a lot in the last three to five years. More men are now talking about low testosterone,” says Scott Hagerman, president and CEO of Chemi Nutra (White Bear Lake, MN).
But not every man low in testosterone is doing something about it. As Hagerman puts it, “A lot of men know what their car’s oil level is but they don’t know what their own testosterone level is.”
But they should. Testosterone’s scope goes well beyond negative media associations like anabolic steroids and doping. Dietary supplement firms describe how testosterone plays a key role in many crucial systemic functions-including bone density and heart health-in addition to sperm production, libido, and muscle building. Some researchers even link testosterone deficiency with diseases like diabetes, metabolic syndrome, and obesity.
Testosterone not only makes a man a man; maintaining healthy levels keeps a man healthy. Although there has been past speculation on links between prostate cancer and supraphysiological testosterone levels (testosterone levels that are way too high), “Researchers are now finding that, more often than not, a normal, healthy testosterone level aids quality of life, longevity, and avoidance of diseases,” Hagerman says. And, he points out, only injectable testosterone preparations have the ability to raise testosterone to hyper levels; no dietary supplement ingredient can do that.
What dietary supplements can do is help restore normal, youthful testosterone levels. Just as all bodily functions-brain, joints, etc.-decline with age, so, too, does testosterone production. Research shows levels may begin tapering naturally in men’s mid-thirties or early forties. Men can also develop hypogonadism, a condition in which the body fails to produce enough testosterone. These testosterone deficiencies mean men may feel a loss of libido and decreased energy, endurance, and strength.
Last year, Hagerman’s company secured a U.S. patent (#8,124,594) for a method of administering soy-derived phosphatidylserine (PS; a phospholipid) to increase testosterone levels following decline.
The patent addresses age-related testosterone decline. It also targets testosterone decline caused by chronic over-exercising. Hagerman explains: “If you exercise intensively, you can experience a decrease in testosterone through overuse of your endocrine system.”
While it is known that a weight-bearing workout temporarily increases testosterone levels during exercise, post-exercise, testosterone levels decline naturally. Testosterone is replenished during the recovery period-if there is a sufficient recovery period. But if one exercises vigorously and chronically, without sufficient recovery in between sessions to allow testosterone to regenerate, testosterone may not return to a healthy level. This is where PS may help.
According to Chemi Nutra, PS supplementation can help minimize this post-exercise drop in testosterone. How? By combating another hormone, called cortisol. While testosterone is an anabolic hormone that acts positively on muscles and sex glands, cortisol by contrast is a catabolic hormone, released as a part of the body’s response to stress, hydrolyzing muscle and breaking it down.
The body considers weight-bearing chronic over-exercise a form of stress and generates cortisol as a result. Testosterone-to-cortisol ratio is a term used to describe the balance between testosterone and cortisol. In response to intense exercise, the testosterone-to-cortisol ratio shifts to favor cortisol. As a result, cortisol level increases and testosterone level decreases-and muscle mass also decreases.
Chemi Nutra, in partnership with Increnovo LLC (Milwaukee), has performed its own studies showing that soy-derived PS helps to suppress cortisol, thus allowing the testosterone-to-cortisol ratio to stay in favor of testosterone. Most recently, a 10-subject study on healthy, exercising males published in the Journal of the International Society of Sports Nutrition2 found that PS significantly increased the testosterone-to-cortisol ratio in favor of testosterone, with subjects showing higher plasma testosterone levels compared to placebo. (During the 10-day, double-blind, placebo-controlled, crossover study, subjects were given 600 mg of PS, or a placebo, daily.)
Regarding PS’s suppression of cortisol, the researchers did note that “Not all research supports these conclusions. In a recent investigation observing the effects of S-PS [soy-phosphatidylserine] on oxidative stress following intermittent running, the cortisol response was not attenuated.” However, they pointed out, “The key differences between this investigation and previous studies are the intensity of exercise and daily dose used during supplementation.” Namely, they said, the level of exercise in their study was more intense, suggesting that PS may have a “rate-limited effect that is dependent upon the intensity level, which indicates that the effect is based on a nutritional improvement rather than a pharmacological effect.”
Overall, the researchers concluded, “These findings suggest that PS is an effective supplement for combating exercise-induced stress.” Chemi Nutra is now marketing its PS for both aging men and sports nutrition, Hagerman says.
Another company, InterHealth Nutraceuticals Inc. (Benicia, CA), also had athletes and testosterone levels in mind when it began distributing a dietary supplement ingredient called ZMA. As InterHealth explains, ZMA, developed by SNAC System Inc. (San Carlos, CA) more than a decade ago, increases total and free testosterone levels in athletes-and, thus, muscle strength and muscle power. It posits ZMA may also increase insulin-like growth factor (IGF-1). Both testosterone and IGF-1 are involved in muscle recovery and regeneration.
ZMA comprises a proprietary blend of zinc (30 mg zinc monomethionine aspartate), magnesium (450 mg magnesium aspartate), and vitamin B6 (10.5 mg). Zinc and magnesium are key to muscle strength and function. Several enzymes, for instance, use zinc to metabolize energy in muscle. Studies on zinc in general-not on ZMA-also show that zinc may decrease cortisol. Magnesium is also key to muscle function-particularly, for relaxing muscle.
Studies show that athletes tend to be low in both zinc (hypozincemia) and magnesium due to sweating and other factors, all of which leads to fatigue and loss of endurance. This is where ZMA helps, InterHealth says, providing highly bioavailable zinc and magnesium and, as a result, boosting muscle strength and testosterone levels. (The vitamin B6 helps increase the absorption of zinc and magnesium.)
ZMA is backed by one eight-week, double-blind, placebo-controlled, randomized trial performed on 27 college football players, published in the Journal of Exercise Physiology.3 (There are also a lot more studies linking zinc and magnesium in general with athletic performance.) Researchers looked for effects of ZMA on anabolic hormones and muscle function. They found that supplementation with ZMA significantly increased levels of zinc, magnesium, free and total testosterone, and IGF-1, significantly increasing strength and “suggesting that ZMA may have anabolic effects,” InterHealth says.
ZMA is not just for athletes, InterHealth scientist Francis Lau, PhD, FACN, adds: “It can be marketed to any man who wants to keep a healthy lifestyle.”
Supplement formulators would do well to keep an eye out for new research on testosterone. “This whole notion of raising testosterone to healthy, beneficial levels through natural products is somewhat of a new target,” says CRN’s MacKay. “The research is still emerging.” Still, he cautions marketers to evaluate research carefully. For instance, testing testosterone levels can be tricky, especially because levels rise and fall throughout the day (and after workouts, as discussed). Additionally, a reasonable baseline testosterone level is important. Baseline levels shouldn’t be unrealistically low in order to show more dramatic results post-intervention; they should reflect real-world numbers.
Testosterone talk is indeed growing, but prostate health remains the main selling point in the supplements aisle, for now. Suppliers will tell you that prostate health is still the number-one concern when men-or men’s supplement manufacturers-come looking for ingredients.
“If someone comes up to us at a trade show to formulate a men’s product, more often than not they’re looking to target the prostate,” says Colleen May, public relations representative for Graminex LLC (Deshler, OH). “I’ve noticed that marketers are more concerned lately with overall prostate health-because if the prostate’s not comfortable, nothing’s going to be comfortable.”
In fact, says Christi Irlbeck, global product manager for the human nutrition and health division at Kemin Industries (Des Moines, IA), market research ranks prostate problems as one of men’s top three health concerns.
One of the most commonly discussed prostate issues is benign prostatic hyperplasia, or BPH, a non-cancerous enlargement of the prostate. In some men, an enlarged prostate triggers a cascade of other uncomfortable lower urinary tract symptoms (LUTS), including frequent and urgent need to urinate-yet, at the same time, difficulty urinating-and nocturia (frequent waking up at night to urinate). Irlbeck notes that “60% of men aged 40 and over will be affected by at least mild LUTS in their lifetime, so you’re hitting a huge population.”
All of these symptoms can directly affect quality of life, says Eden Somberg, MS, L.Ac., technical specialist, Frutarom (North Bergen, NJ). With such immediate and pressing symptoms, men-even those who typically do not take dietary supplements or other health interventions-may be driven to shop for a solution.
To help with an overactive bladder, Frutarom offers an ingredient called GoLess, a proprietary blend of the company’s EFLA 940 pumpkin seed extract (Cucurbita pepo L.) and its SoyLife 40% soy germ isoflavones.
“One thing I like about GoLess is that it can make a profound and rapid difference to aging men-and women, as it’s been clinically tested on both-suffering from frequent urination and related symptoms,” says Somberg. “Many may be hesitant to lead a more active social life, or even take long car rides because they may have to urinate so frequently, or the urge to urinate interrupts their activities and sleep. So it interferes with both daily activities and sleep-daytime and nighttime health. That’s what’s so unique about GoLess; starting from week one or week two, you’re going to generally see a positive change, studies show. It can make an impactful difference on quality of life fairly quickly-which we don’t always get to say about supplements. We like to think that, but we can’t always say that.”
How does GoLess do this? The company says that pumpkin seed extract has been historically used for urination problems, while soy isoflavones, a class of phytoestrogens, help balance hormone levels in the body. Based on in vitro and in vivo studies, Frutarom posits that this combination acts in two primary ways: on a hormonal level, resulting in anabolic, muscle-strengthening effects; and by directly relaxing muscles, which the company says results in decreased frequency of urination.
Between 2001 and 2010, Frutarom completed three human clinical trials on GoLess in women and one human clinical study in men. (Most of the studies were published in the Japanese Journal of Medicine and Pharmaceutical Science.) Results showed that supplementation caused a significant decrease in key symptoms of an overactive bladder and improved sleep and quality of life overall.
GoLess may have a third effect, in men. According to in vitro studies, EFLA 940 pumpkin seed extract may inhibit 5-alpha-reductase, an enzyme involved in converting testosterone to the more-active form dihydrotestosterone (DHT). Some speculate that DHT, due to its androgenic effects, may cause prostate enlargement. (Another Frutarom ingredient, LinumLife, derived from flax lignans, also focuses on inhibiting DHT, supporting prostate health while helping to reduce hair loss.) Rudi Moerck, PhD, president and CEO of Valensa International (Eustis, FL), explains that preventing testosterone’s conversion to DHT at the same time prevents testosterone from depleting-and, as discussed earlier, maintaining testosterone levels is beneficial on many fronts.
Saw palmetto (Serenoa repens) also acts on the 5-alpha-reductase pathway. As one of the best-studied ingredients for BPH-approved as a drug in many countries outside the United States-saw palmetto is by far the leading ingredient in the prostate supplements category, according to recent numbers from market researcher SPINS, and indeed in herbal supplements overall.
But research on saw palmetto hasn’t all been positive. In recent years, several high-profile studies have questioned the herb’s efficacy over placebo-most recently, the STEP trial published in The New England Journal of Medicine in 2006;4 a 2009 Cochrane review;5 and, more recently, the CAMUS study published in The Journal of the American Medical Association (JAMA) in 2011.6
Saw palmetto supplier Valensa, as well as some other dietary supplement members, questions the validity of these studies. For instance, regarding the 2011 JAMA study, Moerck points out that the researchers stated in their conclusion that their broad eligibility criteria meant that some subjects were younger, less symptomatic, and may have had LUTS for reasons other than BPH.
“So, in other words, the study started off with men who had low BPH, low prostate antibodies, high urinary flow rates, and really had no signs of BPH, or, shall we say, very minor signs of BPH. Plus, the age group was younger than the average BPH patient,” Moerck says. “So it looks like they didn’t have a really good cross-section of people with prostate problems.”
He continues, “The bigger picture is this: There have been a lot of studies on saw palmetto and BPH, and most of them have been very positive.”
Saw palmetto may have other benefits for men suffering from BPH, he adds. For instance, a 2011 study7 observed an improvement in sexual function with saw palmetto. (BPH is often linked to reduced ejaculate volume, erectile dysfunction, and decreased libido.)
Studies show that tomato-derived lycopene also inhibits 5-alpha-reductase, in addition to providing antioxidant protection. And, thanks to a new, 2011-published PLoS One study8 performed on LycoRed’s (Beer Sheva, Israel) tomato extract, researchers have an even better idea of how this ingredient may play a role in prostate health-specifically, in terms of gene expression.
To be clear, LycoRed specifies that its ingredients are not simply the single-agent lycopene molecule but instead are proprietary tomato extracts standardized to include a specific ratio of six carotenoids and phytonutrients that naturally occur in the tomato. This is important, LycoRed says, because research shows these phytonutrients act synergistically to achieve health benefits.
In the PLoS One study, researchers looked, in vitro, at the effects of supplementation of LycoRed’s tomato extract, fish oil, or placebo on gene expression in the biopsied prostate tissue of men with non-aggressive prostate cancer. (This was the study’s secondary endpoint.) The researchers said that while they did not necessarily identify any specific, individual genes that experienced significant change from supplementation, they did identify some in vivo pathways between the ingredients and progression of prostate cancer.
For the tomato extract as well as fish oil, researchers saw these ingredients modulate an Nrf2-mediated oxidative stress response pathway. “Studies in mice have shown that the loss of Nrf2 function correlated with increased reactive oxygen species and DNA damage leading to the transformation of normal prostate tissue,” they said. “Taken together, the modulation of the Nrf2 signaling pathway may be an important molecular mechanism involved in chemoprevention by several agents, including lycopene and fish oil.”
Additionally, among other findings, the tomato extract was shown to modulate androgen metabolism, with androgen playing a key role in both BPH prostate enlargement and prostate cancer.
Fish oil was found to modulate genes involved in metabolic pathways of normal prostate tissue.
Tal Offer, PhD, LycoRed’s product development manager, says this is a very important study because it’s the first to demonstrate modulation by tomato phytonutrients of two regulatory pathways important for the progression of prostate cancer.
LycoRed’s goal is to further study ingredient combinations that may act synergistically with its tomato extract to protect prostate health. In addition to omega-3, one of the strongest contenders is curcumin (Curcuma longa). “We find tomato extract and curcumin to be very synergistic, especially in prostate health. We see some dramatic results,” says Golan Raz, vice president of dietary supplements and scientific commercialization. Saw palmetto and zinc are others. Raz says the aim is to “show that when you take a composition that acts in a synergistic way, you can get much better results in a much lower dose.”
Take an enlarged prostate, add some low-grade, chronic inflammation-and one can imagine how systemic inflammation is not a friend to the prostate nor to BPH. Those complementary ingredients LycoRed mentions-omega-3 fatty acids, curcumin, and zinc-benefit the prostate because of their anti-inflammatory effects. And so might some other ingredients.
Last year, Kemin launched AssuriTea Men’s Health, a novel green and black tea blend, which joined other AssuriTea ingredients AssuriTea Wellbeing (green and black tea) and AssuriTea Green (green tea). As the company explains, the proprietary formulation of catechins and theaflavins in AssuriTea Men’s Health promotes healthy urologic function in men suffering from LUTS. (Both AssuriTea Men’s Health and AssuriTea Wellbeing comprise an all-natural, water-extracted green and black tea blend and offer high polyphenol levels, the firm says; the difference is that each ingredient targets a different health platform and has different recommended conditions of use.)
“The difference is that with AssuriTea Wellbeing, we’ve done some clinical studies involving lower-level doses, primarily to look at antioxidant benefits,” says Michael Ceddia, Kemin’s vice president of research, development, and quality. “We knew that with AssuriTea Men’s Health, however, due to the subjects with LUTS we were targeting, that we would have to be at a higher dosage level for efficacy.”
How does the ingredient work? The green tea’s catechins act as antioxidants, while the black tea’s theaflavins and thearubigins have anti-inflammatory effects. To demonstrate this, the company performed a study (A Katz et al.) presented at last year’s American Urological Association annual meeting. (It has been submitted to The Journal of Urology for publication.) The 12-week, randomized, double-blind, placebo-controlled trial was done on 46 men with moderate to severe cases of LUTS. Researchers found that 1000 mg of AssuriTea Men’s Health daily significantly reduced LUTS in as little as six weeks. The company explains that the ingredient was shown to moderate a key inflammatory marker and improve urologic health and function, sexual desire, and quality of life in men with LUTS.
But not just any green and black tea blend will work. “It’s getting the combination right-the amount of green and black tea-and then also finding the specific types of green and black tea that will give you the potent levels of catechins and theaflavins you need,” Ceddia says. “The majority of green teas out there are just not high enough in basic levels of catechins to begin with, and when you produce black tea via fermentation, you don’t necessarily get the level of theaflavins you need to have effect.”
As an aside, the company observed secondary effects in its study that it hopes to further explore, including benefits to blood pressure and fasting glucose.
Graminex’s Flower Pollen Extract is another ingredient studied for its anti-inflammatory effects. This ingredient is a standardized extract of rye pollen (Secale cereal), corn pollen (Zea mays), and timothy pollen (Phleum pretense). The combination is said to act in an anti-inflammatory manner by preventing the enzymes 5-lipoxygenase and cyclo-oxygenase from converting into inflammatory prostaglandins and leukotrienes linked to BPH. It has also been shown to stop the arachadonic acid cascade, which can lead to prostate swelling.
Graminex Flower Pollen Extract has been studied in numerous clinical trials-the majority done more than a decade ago-involving LUTS and BPH. It’s also approved as a drug in many countries, including Russia, Japan, China, Germany, and Argentina. Furthermore, Graminex features the ingredient in its own finished products for prostate health, PollenAid and Prostanex (which also contains saw palmetto).
And, finally, back to omega-3 fatty acids.
Researchers in a 504-patient Iranian study published in the British Journal of Nutrition late last year9 examined how daily supplementation with omega-3 fatty acid EPA (specifically, the EPAX 5500 TG ingredient provided by Norway-based omega-3 supplier EPAX AS), omega-6 fatty acid gamma-linolenic acid, or antioxidant CoQ10 affects prostate-specific antigen (PSA) levels. PSA levels are tested as a risk marker for prostate cancer.
The researchers found that EPA and CoQ10 supplementation lowered PSA levels, while gamma-linolenic acid increased levels. Researchers stated that EPA’s mechanism of action was likely its anti-inflammatory effects via mediation of inflammatory enzyme cyclo-oxygenase.
However, Harry Rice, PhD, vice president of regulatory and scientific affairs for the Global Organization for EPA and DHA Omega-3s (GOED; Salt Lake City), heeds caution.
“While I think the research reported in the British Journal of Nutrition was well designed and executed, the relevance of PSA, which was used as the primary endpoint measurement, is very controversial and was even noted as such by the authors.” In fact, he points out, the U.S. Preventive Services Task Force now recommends against PSA-based screening for prostate cancer, stating that it is not necessarily the best indicator. “So, from my perspective, research conducted to determine if there is a correlation between long-chain omega-3s and PSA is of limited value in drawing conclusions about the prostate benefits of omega-3s.”
But, he does add, “That doesn’t mean, however, that omega-3s don’t reduce the risk of prostate cancer or aren’t beneficial as adjuvant therapeutic agents in the treatment of prostate cancer.”
If anything, he says, better and more research is needed to establish a link. “To date, the majority of studies attempting to correlate long-chain omega-3 intake and prostate cancer risk reduction/prevention have not included blood biomarker assessments,” instead relying on food intake records or food frequency questionnaires. Studies using more-objective measurements, such as blood biomarkers, would, he says, lead to better-controlled and more consistent results.
There are a host of other ingredients not discussed in this article-beta-sitosterol and Pygeum africanum come to mind-that have been well studied for support on prostate and men’s health. The thing to remember is that a lot of these conditions-BPH and low testosterone-happen over the long-term. Taking a preventative routine using natural ingredients can help in the fight to keep a man healthy well into his later years.
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3. LR Brilla et al., “Effects of a novel zinc-magnesium formulation on hormones and strength,” Journal of Exercise Physiology, vol. 3, no. 4 (October 2000).
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8. MJ Magbanua, “Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation,” PLoS ONE, vol. 6, no. 9 (September 2011).
9. MR Safarinejad et al., “Effects of EPA y-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomized, double-blind trial,” British Journal of Nutrition, published online ahead of print November 30, 2012: 1-8.
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