Practitioner's Guide to Nutritional Supplements

June 8, 2006

As more Americans are turning to complementary and alternative medicine (CAM) to address their health concerns, many practitioners have been struggling to remain knowledgeable about the latest research concerning natural products. More than a third of all American adults used some form of CAM from 1997 to 2004, according to a report by researchers from Harvard Medical School (Boston). And while the number of people using CAM has remained relatively steady since the 1990s, the types of CAM therapies they are using have been changing. Herbal medicine-the category that made the largest gains-grew by more than 50% from 1997 to 2004.

 

As more Americans are turning to complementary and alternative medicine (CAM) to address their health concerns, many practitioners have been struggling to remain knowledgeable about the latest research concerning natural products. More than a third of all American adults used some form of CAM from 1997 to 2004, according to a report by researchers from Harvard Medical School (Boston). And while the number of people using CAM has remained relatively steady since the 1990s, the types of CAM therapies they are using have been changing. Herbal medicine-the category that made the largest gains-grew by more than 50% from 1997 to 2004.

People use CAM for a variety of reasons. More than half think it helps make their conventional medical treatments more effective, according to the National Center for Complementary and Alternative Medicine (NCCAM). Moreover, about 13% think conventional medicine is too expensive. Perhaps more importantly, nearly a third think that conventional medicine will not treat their problems. An even greater worry for practitioners, according to survey data, is the lack of communication between CAM patients and their practitioners. According to NCCAM, only about 12% of CAM patients consult a licensed practitioner.

Each week, new study results discuss the potential uses, benefits, and risks of natural products. Unfortunately, the new research sometimes provides conflicting or incomplete information, making it difficult for practitioners to evaluate products. Nutritional Outlook’s Practitioner’s Guide to Nutritional Supplements won’t provide all the answers, but we hope it will make it easier for healthcare providers to sort through the information. This edition of the Guide includes useful backgrounds, research summaries, and consumer trends data for nine popular nutritional supplement categories.



Hoodia

BACKGROUND: Native to the Kalahari Desert in South Africa, Hoodia gordonii (Asclepiadaceae) is a slow-growing cactus in the milkweed family. The soft core of mature plants is eaten by indigenous Xhomani San tribesmen for energy and as a thirst and appetite suppressant. The South African Council for Scientific and Industrial Research (CSIR; Cape Town, South Africa) researched hoodia and applied for an appetite suppressant patent. Phytopharm (Cambridgeshire, UK), a British pharmaceutical company, licensed the patent from CSIR, and after an unsuccessful partnership with Pfizer (New York City), is currently developing a line of functional foods with Unilever (Rotterdam, The Netherlands).

HISTORY OF USE: Hoodia proponents point to its long history of safe use among the San tribe. The active ingredient was identified as a steroidal glycoside called P57. Researchers at Brown University (Providence, RI) speculated in a study published in the September 10, 2004, edition of Brain Research that P57 increases the content of ATP by 50–150% in hypothalamic neurons, thus triggering a feeling of satiety.

RESEARCH: Little research is available. Phytopharm conducted an unpublished clinical trial with two groups of morbidly obese volunteers. Half were given hoodia, half were given a placebo. After 15 days, the group receiving hoodia had reduced their food intake by approximately 1000 calories a day. Phytopharm also is collaborating with Unilever on a five-stage R&D program that includes safety and efficacy studies.

CONVENTIONAL WISDOM: Hoodia attained notoriety in 2004 as an ephedra replacement in diet products. Demand began to grow in earnest in November 2004 after 60 Minutes reporter Lesley Stahl tried hoodia and declared that she didn’t feel hungry or thirsty all day. Unfortunately, hoodia, like many botanicals, is in short supply and takes years to reach maturity. The Internet is teeming with products that claim to be efficacious, yet claims can be dubious. Unscrupulous tactics include promoting high dosages without disclosing how many servings are required, inflating the 20:1 extract ratio (20 pounds of plant is normally needed to produce one pound of material), and promoting unrealistic weight loss (30 pounds in 30 days without exercise).

CONSUMER TRENDS: Despite the lack of definitive research, consumers have taken a serious interest in hoodia. Demand has risen to the point where the San and several other South African organizations were forced to ask governments in South Africa, Switzerland, and Germany to put an end to illegal hoodia sales. However, consumer desire for weight loss will ensure a steady flow of hoodia products for some time to come.

SUMMARY: It is noteworthy that neither the Federal Trade Commission (Washington, DC) nor the Food and Drug Administration (FDA; Rockville, MD) has taken action against hoodia marketers. FDA did send a warning letter to Advantage Nutraceuticals (Fort Walton Beach, FL) regarding the label statements on a hoodia-containing product named Fat on Fire, but the statements were related to unauthorized health claims. More clinical work is needed before hoodia can move into the mainstream, but the history of use seems to be sufficient to allow products on the market.

Omega-3 Fatty Acids

BACKGROUND: In the early part of the 20th century, omega-3 products such as cod liver oil were commonly swallowed as general health tonics. By the end of the century, researchers had identified a host of specific benefits provided by omega-3s, including their power to lower triglycerides, reduce blood pressure, and lessen the risk of dangerous cardiovascular events. Omega-3s got a rare nod of support from the federal government in 2004 when the Agency for Healthcare Research and Quality (AHRQ; Rockville, MD), in collaboration with the National Institutes of Health’s (Bethesda, MD) Office of Dietary Supplements, released a series of evidence-based reports that confirmed that omega-3s could help reduce deaths from heart disease.

HISTORY OF USE: Consumers have used omega-3 oils for decades to address a range of medical concerns, including cardiovascular disease, mental and cognitive health, and arthritis. In the past, marine-based omega-3 oils primarily were consumed in supplement form. Today’s omega-3 products are either manufactured using technology that deodorizes and conceals the fishy taste and odor of omega-3s, or are derived from vegetarian sources. Because most new omega-3 products have neutral taste and odor characteristics, they are increasingly being incorporated into foods and beverages.

RESEARCH: While much of the earliest research on omega-3s concentrated on the relationship between diets high in fish and the risk of adverse cardiovascular events, current research tends to focus on the beneficial effects of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). For instance, the AHRQ reports found that while omega-3s don’t alter total, high-density, or low-density cholesterol, they do help reduce levels of triglycerides, which may contribute to heart disease. They also found that omega-3s might reduce the risk of coronary artery reblockage after an angioplasty, increase exercise capability in people with clogged arteries, and reduce the risk of irregular heartbeats in people who had recent heart attacks.

On the other hand, AHRQ concluded that omega-3 fatty acids have little effect on diabetes and arthritis, and only mixed effects on people with inflammatory bowel disease. The reports also noted that there was insufficient evidence to conclude whether or not omega-3 fatty acids are helpful for people with asthma. Based on the evidence, FDA announced in 2004 that it would allow a qualified health claim linking consumption of DHA and EPA to a lower risk of coronary heart disease.

CONVENTIONAL WISDOM: Because of the large body of evidence supporting their benefits, it’s likely that omega-3 products will continue to remain in the public eye.

CONSUMER TRENDS: The recent introduction over the past two years of new food products containing omega-3s, such as beverages, yogurts, breads, and desserts, suggests that consumers have finally embraced the notion that omega-3 oils can be both healthy and tasty. Worries about environmental pollutants and contaminants like heavy metals, however, may prompt some consumers to shy away from marine sources of omega-3s.

SUMMARY: Emerging science and improved manufacturing techniques for omega-3s are helping drive the category into the 21st century. Expect smooth seas ahead.

Functional Foods

BACKGROUND: Given their preference, most people would rather ingest their vitamins and nutrients from food. However, it’s not easy-a fact that accounts for the popularity of dietary supplements. Food choices are deeply personal, and people often choose foods that they know might not be good for them. And sometimes, the confusing nature of nutrition is a problem. During the 1990s, the Food Pyramid led people to believe that consuming large servings of carbohydrates was fine as long as fats were avoided. Today, food scientists have a better grasp of functional foods and how they might be formulated.

HISTORY OF USE: Last year, an expert panel convened by the Institute of Food Technologists (Chicago) defined functional foods as “foods and food components that provide a health benefit beyond basic nutrition (for the intended population). Examples may include conventional foods; fortified, enriched, or enhanced foods; and dietary supplements. These substances provide essential nutrients often beyond quantities necessary for normal maintenance, growth, and development, and/or other biologically active components that impart health benefits or desirable physiological effects.” The panel defined nutrients as “traditional vitamins, minerals, and essential fatty acids for which recommended intakes have been established, and other components that include phytonutrients or bioactives present in foods for which a physical or physiological effect has been scientifically documented, or for which a substantial body of evidence exists for a plausible mechanism, but for which a recommended intake and function have not been definitively established.” Common functional food nutrients include carotenoids, dietary fiber, flavonoids, isothiocyanates, phenols, plant stanols and sterols, phytoestrogens, and soy protein.

RESEARCH: A large and growing body of scientific work points to the benefits of consuming functional foods and beverages. The Food and Drug Administration (FDA; Rockville, MD) allows health claims based on significant scientific agreement in the scientific literature. Functional food ingredients in this group include calcium, soluble fiber, sugar alcohols, soy protein, and plant sterols/stanols. FDA also allows qualified claims for nutrients that do not meet the “significant scientific agreement” standard. Between July 2003 and October 2005, 75 petitions were submitted. FDA has issued qualified claims for 16 nutrients. Research is under way at all levels of the industry, including suppliers. VDF FutureCeuticals (Momence, IL), for example, recently investigated the possibility that isothiocyanate-rich foods from a blend of selected seed sprouts could help lower blood levels of oxLDLs and protein carbonyls, two reactive oxygen species (ROS) that may contribute to a wide variety of pathological conditions. Initial chemical analysis had shown that the product, SproutGarden, was high in sulforaphane. Later, in experiments that monitored quinone reductase activity in vitro, SproutGarden demonstrated potency as a phase 2 protein (P2P) inducer. The research illustrates why functional foods hold such promise. The body has an indigenous system that creates antioxidants when ROS levels increase. The phase 2 protein group includes enzymes, such as quinone reductase (QR), heme oxygenase-1, catalase, superoxide dismutase, and thioredoxin, that are capable of neutralizing free radicals, and, according to VDF FutureCeuticals, carcinogens.

SproutGarden was evaluated in three clinical case studies, each three weeks long. The goal: monitor any changes in oxLDL and protein carbonyl blood levels in healthy participants. OxLDL and carbonyl proteins were measured in collected sera using ELISA methods provided by Mercodia Inc., and Biocell Corp. Ltd., respectively. All other parameters were measured using a Cholestech system.

The results are typical of preliminary functional food nutrient studies. Encouraging evidence supported the concept of management of undesirable oxidative by-products, (“damaged molecules”), in the blood with food materials rich in P2P inducers. However, HDL blood levels increased, signaling the need for further clinical investigation.

CONVENTIONAL WISDOM: When it comes to functional foods, consumers talk a good game, but they really do not understand the science behind the nutrients. An April 5 Harris Interactive poll found that many consumers are aware of the impact of whole grains, antioxidants, and saturated and trans fats on their health, and in some cases, this knowledge led to increased consumption of these nutrients. On the other hand, the survey found that consumers had major misconceptions about nutrients. About 79% correctly identified trans fats as bad for their health, while 51% checked the same answer for plant sterols.

CONSUMER TRENDS: Functional food sales are booming. To an aging population anxiously watching healthcare costs, functional foods appear to be an inexpensive and important health regimen. Food and beverage companies are watching as well. At the Guelph Food Technology Centre Functional Foods symposium in April, Clare Hasler, executive director of the Robert Mondavi Institute for Wine and Food Science (Davis, CA), pointed out that dark chocolate retail sales rose 24.6% in the last three years, fruit smoothies increased 40% since 2005, and antioxidant-rich Pom Wonderful grew from zero in 2002 to $60 million in 2005.

SUMMARY: Functional foods are dominated by fortified waters and drinks, but watch for a gradual shift to fiber-rich grains and enriched snacks. Momentum is building toward the day when the majority of foods will claim to be functional.

Saw Palmetto

BACKGROUND: Saw palmetto (Serenoa repens), also known as Sabal serrulatum, is a small dwarf palm found throughout the American southeast. Supplements derived from the fruit, or berries, of saw palmetto may provide relief from symptoms caused by benign prostatic hypertrophy (BPH) or an enlarged prostate gland, possibly through the mechanism of 5-a-reductase activity.

HISTORY OF USE: People in the United States have used saw palmetto for more than 200 years, beginning with Native Americans, who employed the plant as a food source and for various medicinal uses, including as a tonic, expectorant, antiseptic, and treatment for urogenital problems. Saw palmetto is more commonly used as a medicinal product in some European countries than in the United States. The herb is sometimes combined with other botanical or natural ingredients, including nettle root (Urtica dioica) and the bark of the African plum tree (Pygeum africanum).

RESEARCH: The National Library of Medicine contains more than 200 citations for articles that refer to saw palmetto. A review of 21 clinical trials involving more than 3000 volunteers by the Cochrane Collaboration (Oxford, UK) found that saw palmetto provides mild to moderate improvement in urinary symptoms and flow measures. Another review of 18 studies involving nearly 3000 men published in the November 11, 1998, issue of the Journal of the American Medical Association found that while the existing evidence base was limited due to the short duration of most studies, saw palmetto appeared to produce improvements to urine flow that were similar to the drug finasteride, but with fewer side effects. A recent study that appeared in the February 9, 2006, issue of the New England Journal of Medicine (NEJM) by Stephen Bent, MD, a staff physician at the San Francisco VA Medical Center, et al., reported that saw palmetto was no more effective than a placebo at relieving BPH symptoms. The NEJM study involved 225 men, who received either 160 mg of saw palmetto or a placebo daily for a year. Some botanical experts, however, including American Botanical Council (ABC; Austin, TX) founder Mark Blumenthal, have expressed concern with the study because many of the volunteers suffered from moderate to severe symptoms of BPH, rather than the mild to moderate symptoms that were studied in previous trials. A major study funded by the National Institutes of Health (NIH; Bethesda, MD) that will examine the effects of saw palmetto and another herbal treatment is reported to be in the final planning stages.

CONVENTIONAL WISDOM: Bad press from the NEJM article should do little to derail overall enthusiasm for saw palmetto, currently one of the most popular supplements in the United States. Saw palmetto has a long history of use, few side effects, and significant clinical substantiation. In addition, more than 50% of men over age 60 and more than 90% of men over age 70 may be affected by BPH, according to NIH.

CONSUMER TRENDS: Saw palmetto is consistently among the top-selling herbal ingredients. One 2002 survey estimated that more than 2 million men in the United States used saw palmetto to alleviate symptoms of BPH.

SUMMARY: Given the number of men who suffer from BPH, interest in saw palmetto is likely to remain high through the foreseeable future.

Chondroitin Sulfate

BACKGROUND: Practitioners seeing anyone over the age of 15 are virtually guaranteed to encounter chondroitin. Consumers consider chondroitin safe and effective. It is one of the most popular dietary supplements available, with annual sales of stand-alone and combination products near $400 million. Chondroitin is often sold with glucosamine and MSM (methylsulfonylmethane).

HISTORY OF USE: Chondroitin came on the market in the 1960s. It has been widely studied-approximately 1110 human clinical trials have been performed in the last five years alone. However, in spite of the sheer number of trials, experts cannot reach consensus on its effectiveness, although nearly all agree that it is well tolerated over a 6- to 24-month period and has few if any side effects. Chondroitin is usually taken to relieve the symptoms of osteoarthritis, particularly pain in the knees, hips, and fingers. A daily dose of 1200 mg is typical, and is often taken in conjunction with 1500 mg of glucosamine.

RESEARCH: While chondroitin has been the subject of thousands of positive human and animal studies, its efficacy remains in doubt. The most recent controversy is the National Center for Complementary and Alternative Medicine’s (NCCAM) GAIT study. The medical community points to the nearly 1600-patient, four-year, double-blind, placebo-controlled, positive-controlled study as evidence that chondroitin is not effective by itself or in combination with glucosamine. Others believe that the study supports its effectiveness, particularly for patients with moderate-to-severe pain.

On the medical side, Stephen E. Straus, MD, NCCAM director, said that the rigorous, large-scale, well-designed GAIT study showed that the combination of glucosamine and chondroitin sulfate appeared to help people with moderate-to-severe pain from knee osteoarthritis, but not those with mild pain. Lead researcher David Clegg, MD, qualified the results even further. He believes that the benefits in the moderate-to-severe group were a function of the small size of the subgroup, and should be confirmed in another study.

Others disagree. Jason Theodosakis, MD, one of six members of the GAIT oversight committee and author of The Arthritis Cure, believes that the study should be deemed invalid. First, the placebo rate was high, 60% compared with an estimated 35%. Second, Celebrex, the positive control, was not statistically significant in 12 out of 14 outcomes. Third, patients who dropped out of the regime were counted as negative results and may have skewed the data. And fourth, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale used to measure responses may not have been sensitive enough to register improvements in patients with mild symptoms.

CONVENTIONAL WISDOM: In spite of the very public debate over the GAIT results, chondroitin use is expected to increase. Simply put, baby boomers are getting older, and statistics indicate that they put more stress on their joints and bones than previous generations.

Obesity is a factor. An Arthritis Foundation–funded study performed by the Beth Israel Deaconess Medical Center and the Harvard School of Medicine (Boston) found that the percentage of obesity in baby boomers between ages 25 and 44 was nearly identical to that of the previous generation between ages 35 and 54. At the same time, arthritis prevalence among obese patients rose from 3% in 1971 to 18% in 2002. In a related finding, 20% of obese people were likely to develop arthritis in 1971 compared to 60% in 2002.

There is valid concern about product quality. In his book The Arthritis Cure, Theodosakis points out that unethical marketers may try to cut costs by providing less chondroitin than listed on the label, using smaller dosages, substituting cheaper, less-active or inactive compounds, or using low-quality chondroitin. A ConsumerLab.com (White Plains, NY) test of 49 different joint and bone products found two instances where the amount of chondroitin in the product was significantly less than the amount listed on the label. Healthcare experts all recommend that patients use quality name brands.

CONSUMER TRENDS: Hundreds of chondroitin products are on the shelf as stand-alone or combination formulas. With 20 million Americans suffering from osteoarthritis, expect more patients to ask about chondroitin and its fellow supplements glucosamine and MSM.

SUMMARY: The GAIT trial raises more questions than it answers about natural products for joint health. Chondroitin may work in combination with other ingredients to improve moderate-to-severe knee pain, or it may be ineffective. More research is needed.

CoQ10

BACKGROUND: Ubiquinone, also known as CoQ10, is a vitaminlike substance with antioxidant properties that helps cells convert nutrients to ATP in the mitochondria.

HISTORY OF USE: Since CoQ10 is absorbed and used within cells throughout the body, researchers have theorized about a wide list of applications.

RESEARCH: CoQ10 relational studies have been performed for angina, cardiomyopathy, periodontal disease, type 2 diabetes, hypertension, muscular dystrophy, Alzheimer’s disease, and breast cancer, among others. CoQ10 has been used, recommended, or studied for all of these conditions, but remains controversial as a treatment. The strongest results suggest that 30–360 mg daily may benefit patients with hypertension. Exact dosages have yet to be determined.

CONVENTIONAL WISDOM: Compared with other supplements, CoQ10 is expensive to manufacture. Some health experts also have expressed concern about possible drug interactions, and Japan’s decision to grant Foods for Specified Health Use (FOSHU) status to CoQ10 has strained supplies. Companies such Kaneka (Osaka, Japan) have responded by ratcheting up CoQ10 production and building new facilities. Nevertheless, the supply and demand imbalance has driven up prices, and in some cases, led to unscrupulous companies marketing supplements that have little or no CoQ10.

Vitamin E

BACKGROUND: One of the most controversial supplements on the market today is also one of the most venerable: vitamin E. Just a decade ago, researchers seemed excited about the prospects of this essential fat-soluble nutrient because observational studies had implied an inverse relationship between vitamin E intake and the prevalence of heart disease and cancer. More-recent clinical intervention trials, however, have not borne out those expectations, leading many experts to conclude that vitamin E’s effects are more nuanced than previously thought.

HISTORY OF USE: Consumers have been using vitamin E as a supplement for decades. Data from the National Health and Nutrition Examination Survey (NHANES) indicate that from 1988 to 1994, most Americans didn’t get enough of the nutrient to meet recommended dietary intake levels. However, a report written in 2000 by the Institute of Medicine (Washington, DC) suggests that true vitamin E intake levels were not being reported accurately.

RESEARCH: The history of vitamin E research illustrates the problems that can happen when observational studies are pitted against intervention trials. For instance, in a study based on data from nearly 90,000 women that was reported in the May 20, 1993, edition of the New England Journal of Medicine (NEJM) by Meier Stamfer, MD, a professor at the Harvard School of Public Health (Boston) et al., women who had the highest intake of vitamin E were 30–40% less likely to develop heart disease over an eight-year period than other women.

However, data from the Heart Outcomes Prevention Evaluation (HOPE) Trial that was published in the January 20, 2000, edition of NEJM showed that volunteers who took 400 IU of vitamin E for 4.5 years had the same risk of developing cardiovascular events as volunteers who took a placebo. Critics pointed out, however, that the HOPE trial, unlike the earlier 1993 study, used volunteers who were already at high risk of developing a cardiovascular event. Similarly, critics have also noted that more than half of the studies included in a review of 19 vitamin E trials that was reported by Johns Hopkins (Baltimore) researchers in the November 10, 2004, edition of the Annals of Internal Medicine were based on studies that tested vitamin E’s use in combination with other supplements; the Johns Hopkins review concluded that vitamin E was associated with a higher overall risk of death. More-recent data gleaned from the HOPE trial that appeared in the March 16, 2006, edition of the Journal of the American Medical Association indicate that vitamin E does not prevent major cardiovascular events or cancer and may in fact raise the risk of heart failure in some individuals.

CONVENTIONAL WISDOM: Vitamin E is down but not out. The nutrient’s popularity took a big hit over the past few years thanks to the 2004 Annals of Internal Medicine review and several other disappointing studies. However, industry attempts to contextualize the research have been vigorous. Moreover, newer research looking into other applications and forms of vitamin E may generate positive news.

CONSUMER TRENDS: Demand for vitamin E has dropped significantly in the past two years, perhaps by 19%, according to some experts. However, some suppliers are reporting higher demand, particularly for specialty forms of the nutrient.

SUMMARY: Research is split over the effects of vitamin E. Observational studies show that it may help protect healthy people from developing disease later in life. But intervention studies suggest that it does not help people who are already sick or at risk of developing disease. In a way, the debate over vitamin E mirrors the debate over supplements in general: Do nutrients work better when taken for treatment or to simply maintain health?

Lycopene

BACKGROUND: Researchers have speculated for decades about the potential health benefits of lycopene, a carotenoid found in tomatoes and other fruits that may be linked to lower rates of cancer. In vitro and animal studies show that lycopene is a strong antioxidant. Moreover, epidemiological studies suggest that diets rich in lycopene may lead to a lower incidence of cancer. However, there is little evidence that directly ties lycopene itself to cancer prevention.

HISTORY OF USE: Scientists have studied lycopene since the early 20th century, but starting in the late 1980s, researchers began to explore lycopene’s purported antioxidant and anticancer effects more closely. Lycopene later became a featured ingredient in multivitamin formulations such as Bayer’s (Morristown, NJ) One-A-Day in 2002.

RESEARCH: A landmark review of 72 studies involving lycopene written by Edward Giovannucci, MD, a nutrition and epidemiology professor at the Harvard School of Public Health (Boston), appeared in the February 17, 1999, edition of the Journal of the National Cancer Institute (JNCI). Giovannucci found 57 studies that reported inverse associations between tomato intake or blood lycopene levels and cancer risk, including 35 that were statistically significant, with evidence being strongest for cancers of the prostate, lung, and stomach. Giovannucci warned, however, that the data were only based on epidemiological studies and did not prove that lycopene accounted for the effects of a tomato-rich diet on cancer. Noting the existence of other possibly beneficial tomato compounds, Giovannucci called for more research.

Further studies conducted in animal and in vitro models appeared to support Giovannucci’s idea that lycopene alone might not be responsible for the beneficial effects of tomatoes. In a study conducted by Stephen Clinton, MD, a professor of hematology and oncology at Ohio State University Cancer Center (Columbus, OH), that was published in the November 4, 2003, edition of JNCI, rats with prostate cancer that were fed a diet containing whole tomato products lived longer than rats that were fed a similar diet that only contained lycopene. In an accompanying editorial, other experts suggested that whole-food approaches to supplementation might be preferable because lycopene, carotenoids, and other tomato phytonutrients could interact with each other to produce a beneficial effect. Since then, other more-recent studies have focused on the effects of tomato nutrient complexes. Early results from some of these studies have been promising, but again researchers are still unsure about the exact relationship between lycopene and disease.

CONVENTIONAL WISDOM: Lycopene has the potential to become a blockbuster but consumers could be disappointed if its benefits are oversold. Products that hedge their bets by combining lycopene with other potentially helpful phytonutrients will have an edge. FDA is similarly cautious; in 2005, the agency rejected a request to permit a cancer health claim for lycopene, opting instead for a more limited claim that applied to tomato products.

CONSUMER TRENDS: Because cooking tomatoes helps raise concentrations of lycopene, conventional food manufacturers could take the wind out of supplement sales by continuing to very effectively tout the benefits of processed tomato products like ketchup, salsa, and spaghetti sauce.

SUMMARY: The research is promising, but more data are needed. In 2005, Giovannucci said he thought the timing was “premature” for a claim but added that he strongly supports more research to determine whether lycopene acts alone or in combination with other nutrients.

Lutein

BACKGROUND: Unlike most dietary supplements that gradually take years to build up awareness in health stores, lutein quickly appeared in the mass market when Wyeth (Madison, NJ) included the carotenoid in its Centrum line. Commercialized in the early 1990s, lutein has since become a staple in eye-health formulations, often appearing on the label with zeaxanthin.

HISTORY OF USE: While lutein does not have the long history of use associated with most supplements, it has been the subject of dozens of published studies showing that 6- to 20-mg doses may protect against age-related macular degeneration (AMD). If future studies validate this hypothesis, lutein will make a significant impact on AMD, which the National Institutes of Health’s (Bethesda, MD) National Eye Institute (NEI) believes accounts for more than 50% of all blinding conditions.

Much is at stake. The Eye Diseases Prevalence Research Group (EDPRG) estimates that approximately 1.2 million Americans live with neovascular AMD, another 970,000 cope with geographic atrophy, and 3.6 million have bilateral large drusen. In the next 20 years, these statistics are expected to increase by 50%.

RESEARCH: In 2001, NEI’s AREDS study found that supplements containing a mixture of similar antioxidants such as vitamins C and E, beta-carotene, and zinc lowered the risk of advanced AMD by 25% in people at high risk of developing the condition, but had no effect on those with no AMD or in the condition’s early stages. However, lutein was not included in the study because it was not commercially available during the planning phase. Its reputation subsequently emerged unscathed.

Most experts believe that while a definitive study is still necessary, lutein is backed by credible science that shows it can decrease the risk of developing advanced AMD. The belief is based on dozens of small but well-designed studies. In November 1994, an NEI-supported study indicated that consumption of foods rich in carotenoids such as green, leafy vegetables like collard greens, kale, and spinach was associated with a reduced risk of developing AMD. In 1999, data from the Nurses Health Study showed a reduced likelihood of cataract surgery with increasing intakes of lutein and zeaxanthin. And in 2004, the North Chicago VA Medical Center released its Lutein Antioxidant Supplementation Trial (LAST), which showed improvement in several key visual functions among AMD patients. Stuart Richer, OD, PhD, chief of optometry at the North Chicago VA Medical Center and associate professor at the Illinois College of Optometry, said lutein was “by no means a cure for AMD, but the study does show improvement among several disease symptoms in AMD patients.”

CONVENTIONAL WISDOM: Health practitioners are cautiously optimistic about lutein. Most are waiting for AREDS II, a multicenter randomized trial with 4000 participants. AREDS II will assess how high doses of lutein and zeaxanthin with and without omega-3 fatty acids affect AMD and cataracts. It will be a long wait. Recruiting is expected to continue through 2007. When the study gets under way, participants will be followed for a minimum of five years. In the meantime, other studies will have to fill the gap.

CONSUMER TRENDS: An aging population facing AMD did not put much stock in the 2001 AREDS trial. According to Health Business Consulting (Warwick, RI), lutein sales hit $65 million in 2002, and growth in the 10–12% range is projected through 2005.

SUMMARY: Lutein may be the real thing. Research is ongoing, but most studies point to lutein as a positive intervention for AMD.