Men's and Women's Products
Over the past few years, researchers have questioned several long-standing assumptions about the ability of dietary supplements to influence gender-related health conditions like prostate cancer and menopause. Other experts, however, have criticized some of these findings, noting that they were not based on randomized, double-blind, placebo-controlled trials, but rather on other types of studies intended to answer different scientific questions.
Flax lignans contain phytoestrogens that may impact women's
health. Photo courtesy of Frutarom.
Fortunately, the uncertainty may be short-lived. Several major clinical trials funded by the National Institutes of Health’s (NIH; Bethesda, MD) National Center for Complementary and Alternative Medicine (NCCAM) and Office of Dietary Supplements (ODS) are under way. Moreover, many dietary supplement manufacturers are working with NIH researchers and on their own smaller clinical studies. The results of these new trials could paint a clearer picture of the ability and limits of natural products to improve the health of both men and women.
One point of disagreement among experts is in the area of prostate health, a primary concern of men who use dietary supplements. According to the American Association for Cancer Research (AACR; Philadelphia), prostate cancer is the most common cancer in men and the second most common cause of cancer death in men. While age, race, and family history are factors that can influence a man’s risk of developing prostate cancer, nutrition may also play a role. Many researchers believe that certain herbs and nutrients may offer protection. However, other researchers maintain that some supplements may produce unpredictable results.
For instance, a new study published in the May 16, 2007, issue of the Journal of the National Cancer Institute (JNCI) questioned the value of multivitamins for prostate health. In the study, National Cancer Institute (NCI; Bethesda, MD) researchers analyzed data taken from 295,344 men enrolled in the National Institutes of Health–AARP Diet and Health Study. During five years of follow-up, the NCI researchers found 10,241 cases of prostate cancer, including 8765 localized cancers and 1476 advanced cancers.
While the NCI scientists didn’t find an association between multivitamin use and the risk of localized prostate cancer, they did find that men who took multivitamins more than once per day had an increased risk of developing advanced and fatal prostate cancer. Men who had a family history of prostate cancer and men who took selenium, beta-carotene, or zinc supplements had the strongest association.
According to Daniel Fabricant, PhD, vice president of scientific and regulatory affairs at the Natural Products Association (NPA; Washington, DC), the fact that the study is a cohort study, rather than a randomized, placebo-controlled trial, could explain its negative results. “The very nature of statistics is that any researcher with many outcome measures, as was the case in this study, will stumble upon a figure that suggests some kind of an effect where there is none, provided that numerous ways of checking the data are used, as again was the case in this study,” he said.
Cohort studies typically involve a large number of variables, noted Fabricant. “These missing observations are filled in by the authors’ evaluation of the numbers and then the resulting bias, of which there is a great deal in this study,” he said. “This is why the best studies ask one research question at a time, with one clear-cut outcome being measured. This is a large study that was originally intended to improve our general understanding of the relationship between diet and health. It wasn’t designed to speculate on the potential for risk.”
Not all of the news involving supplements and prostate health is negative, however. One supplement that may have a beneficial effect on prostate health is derived from the Amur cork tree (Phellodendron amurense), which grows in northeastern China and the Russian west. Last year, researchers from the University of Texas Health Science Center (San Antonio) working under a $500,000 grant from NCI found that Nexrutine, a Phellodendron amurense supplement manufactured by Next Pharmaceuticals (Salinas, CA), had an apparent anticancer effect on in vitro cultured prostate cancer cells.
Reporting in the June 2006 issue of the journal Neoplasia, Health Science Center associate professor of urology A. Pratap Kumar, PhD, noted that the extract seems to induce apoptosis in the cancer cells and inhibits the activity of CREB, a protein involved in cell death.
Following up on the 2006 study, Kumar published the results of a preclinical animal study in the May 1, 2007, issue of Clinical Cancer Research. In the 2007 study, Kumar’s team fed mice that were genetically manipulated to develop prostate cancer a diet containing either 300 mg/kg or 600 mg/kg of Nexrutine for 20 weeks. The researchers found that the extract significantly suppressed palpable tumors and also reduced the expression of marker compounds such as CREB and Akt, compared with tumors from control animals.
“Our finding that Nexrutine is able to inhibit prostate cancer in a preclinical model is very encouraging,” Kumar said. “Since cancer arises due to defects in multiple signaling pathways, developing agents that target multiple signaling pathways may be an ideal approach for successful cancer management.”
Other clinical trials currently edging toward completion should shed more light on the potential health contributions of dietary supplements. For instance, NCI’s Selenium and Vitamin E Cancer Prevention Trial (SELECT), which closed enrollment in 2004, is one of the first large-scale studies specifically designed to test the effects of particular antioxidants on cancer prevention. Unlike other previous cohort studies involving antioxidants, SELECT is a randomized, placebo-controlled trial involving more than 35,000 men age 50 and older. NCI researchers began enrolling volunteers in 2001 and expect the study to end in 2011.
Industry support for SELECT has been considerable. Sabinsa Corp. (Piscataway, NJ) provided the selenium and selenium placebo capsules; DSM Nutritional Products Inc. (Parsippany, NJ) supplied the bulk vitamin E and vitamin E placebo oils; and Tischon Corp. (Westbury, NY) encapsulated the vitamin E and vitamin E placebos.
If the role of supplements in men’s health seems confusing, the role of supplements in women’s health seems doubly so. Many natural ingredients, such as soy, have a long history of use as a source of relief from the symptoms of menopause. However, new research on soy suggests that it may not benefit all women.
Soy isoflavones show promise for several conditions related to women’s health. Yet, considerable confusion exists over the different types of isoflavones as well as their effects on the body. Because the chemical structure of isoflavones resembles the structure of estrogen molecules, soy isoflavones may interact with estrogen receptors by mimicking or inhibiting the properties of estrogen. While some researchers believe that soy may be helpful for some menopausal symptoms such as hot flashes and osteoporosis, a 2005 review of soy research by the U.S. Department of Health and Human Services (Washington, DC) Agency for Healthcare Research and Quality found soy’s effects on menopause to be inconsistent.
Combination Softgels Target Men and Women
Omega-3s, lignans, and borage oil each are popular ingredients for women’s health. Bioriginal (Saskatoon, SK, Canada) recently launched a new softgel that combines all three ingredients in a convenient and synergistic supplement.
Bioriginal included the omega-3 eicosapentaenoic acid (EPA) to enhance calcium absorption and maintain healthy bones. Lignans are thought to balance estrogen levels, while borage oil contains the moisturizer gamma linoleic acid (GLA), which may also help provide relief for some symptoms of menopause such as night flushes, breast discomfort, and irritability. The company simultaneously released a similar men’s health softgel containing fish oil, borage oil, and lycopene.
“Consumer demands are becoming more and more complex,” says Adrian Hughes, PhD, Bioriginal’s director of new business and technical support. “Manufacturers need to respond to this by adopting a more targeted approach. Our multibenefit softgel range offers them the opportunity to create sought-after supplement lines for specific target audiences. The initial response to these products has been great and we look forward to extending the range in the future.”
One condition related to menopause that may be improved by soy isoflavones is osteoporosis, which affects about 33% of all postmenopausal women. According to the National Osteoporosis Foundation (Washington, DC), women may lose up to 20% of their bone mass five to seven years after entering menopause.
In a study published in the June 8, 2006, online issue of the European Journal of Nutrition, researchers from Sun Yat-sen University (Guangzhou, China) reported that soy germ isoflavones may help slow estrogen-related bone loss in postmenopausal women. In the study, the researchers divided 90 women into three groups, which received a placebo, 84 mg of soy isoflavones, or 126 mg of isoflavones for six months. The study used SoyLife soy germ isoflavones supplied by Acatris (Minneapolis), which was acquired by Frutarom (North Bergen, NJ) last October.
After analyzing blood samples and x-rays from the beginning and end of the study, the researchers concluded that the soy germ isoflavones had a dose-dependent effect on reducing bone loss at the spine and femoral neck. Jocelyn Mathern, RD, technical specialist at Frutarom, called the research “another step in advancing soy germ isoflavones as a safe, effective option.”
Soy may also have some beneficial effects on breast cancer, but the science is less clear. Last April, scientists from Georgetown University Medical Center (Washington, DC) and Johns Hopkins School of Medicine (Baltimore, MD) conducted a meta-analysis of all available published data and concluded that while soy may be associated with a small reduction in the risk of breast cancer, there aren’t enough data to recommend the use of soy supplements for that purpose. Published in the April 5, 2006, issue of JNCI, the meta-analysis covered 18 epidemiological studies that examined the relationship between soy intake and breast cancer risk.
“Because soy foods and soy supplements are widely used, we conducted this first true meta-analysis to understand what role soy foods might have on breast cancer risk,” wrote Robert Clarke, PhD, a professor at Georgetown’s Lombardi Comprehensive Cancer Center. “This objective examination of all of the studies tells us that currently, the data are not adequate to provide a clear answer to recommend soy foods to prevent breast cancer.”
The time when a woman is exposed to soy and soy isoflavones may be an important factor, according to William Helferich, PhD, a professor of food science and human nutrition at the University of Illinois (Urbana-Champagne, IL), who presented research in May at the Diet and Optimum Health conference held May 16–19 in Portland, OR, which was sponsored by the Linus Pauling Institute at Oregon State University (Corvallis). Helferich has found that feeding the soy isoflavone genistein to young female rats lowered the incidence of chemically induced mammary tumors. However, genistein also stimulates the growth of estrogen-responsive tumors and interferes with drugs that target estrogen receptors, such as Tamoxifen.
“The resolution of this paradox may lie in the timing of estrogen administration,” Helferich wrote, noting that exposure to genistein before puberty causes mammary gland differentiation. “A differentiated cell undergoes less proliferation and therefore is less likely to progress through the cancer process. However, if the estrogen is administered to an animal after the development of an estrogen-responsive tumor, the growth of this tumor will be stimulated.”
Like soy isoflavones, lignans contain phytoestrogens that also may impact women’s health. Common sources of lignans include seeds, beans, broccoli, and berries. In the June 2006 European Journal of Cancer Prevention, scientists found an inverse association between the lignan enterolactone and premenopausal breast cancer risk.
Some of the newest data on lignans come from researchers at RMIT University (Melbourne, VC, Australia). Preliminary data from the campus suggest that flax lignans may affect breast cancer risk by being converted into enterolactone and enterodiol, which may exert antiestrogenic effects. According to Leah Williamson, a postgraduate researcher at RMIT’s department of food science and technology, the estrogen-mimicking effect of lignans enables breast cells to reproduce at a slower rate, lowering the risk of mutations. Williams will present the data at several upcoming conferences in Europe, including the 10th European Nutrition Conference, which will be held July 10–13 in Paris.
Building on the growing body of research supporting lignans, several dietary supplement ingredient manufacturers recently created new lignan products derived from a variety of natural sources. For example, Linnea Inc.’s (Locarno, Switzerland) HMRLignan (7-hydroxymatairesinol), launched in 2005, is a lignan enterolactone precursor extracted from Norway spruce (Picea abies). In March of this year, Pizzey’s Milling (Gurnee, IL) introduced MeadowPure, an ingredient that combines flax lignans and omega-3s from fish oil. Additionally, in May, Sanmark LLC (Greensboro, NC) unveiled Lignate SDG30-WS, a water-soluble 30% flax lignan extract that provides the monomer form of secoisolariciresinol diglucoside (SDG), one of the primary lignans in flax.
THE BATTLE OF THE SEXES
In 1973, Bobby Riggs and Billie Jean King competed in the Battle of the Sexes, a tennis match that was one of the most widely watched sports events of all time. Today, the Battle of the Sexes has moved from the tennis court to the laboratory. Researchers still don’t know enough about how many supplement ingredients affect men and women to render a verdict one way or the other, but that hasn’t stopped advocates and opponents of natural products from lobbing the data back and forth in search of an answer. It will take more clinical trials to make things clearer. Until then, expect more excitement, competition, and maybe even a few wild cards, in the fields of men’s and women’s health.