The NREA (Nutraceutical Research & EducationAct)

Written by Michael Mannion

February 3-4, 2000, The Waldorf-Astoria, New York

(Also see the conference program as it was published on this web site.)

The 11th Nutraceutical Conference was well attended and highly successful. Representatives from the food, pharmaceutical, dietary supplement, herbal and health food industries, as well as from academia, publishing and government, explored where the Nutraceutical Revolution is today and where it is headed in the near future. A nutraceutical is a food, medical food or dietary supplement that has a medical-health benefit including the prevention and treatment of disease. The speakers were engaging and thought-provoking. Audience members offered challenging questions for the presenters and valuable insights of their own, based on their experiences in the new field of nutraceuticals.

The American public has recently embraced the promise of nutraceuticals–wholeheartedly and justifiably. According to a survey conducted for FIM, 74% of Americans say that they take nutraceuticals. And 51% of Americans told researchers that they take nutraceuticals at least once a day.

FIM, The Foundation for Innovation in Medicine, maintains that the nutraceutical industry is on the verge of a fundamental change, from a market-driven enterprise to a business that will be driven by the results of clinical research. Clinical studies of nutraceuticals will power the next phase of development. This is only a matter of when, not if.

At present, consumers face a major problem concerning nutraceuticals–the market is flooded with products for which unsubstantiated health claims are being made. Americans are increasingly becoming aware that the claims of many manufacturers are not substantiated by clinical research and this is causing them great concern. In a poll conducted for FIM, 68% responded that they are not extremely confident that the vitamins, minerals, herbal remedies and/or special foods they are taking for health reasons can actually help maintain health and/or cure disease

The public’s growing demand that nutraceutical companies demonstrate the safety and efficacy of their products, in combination with the industry’s increasing recognition of the enormous economic and medical-health potential of nutraceuticals, will inevitably lead manufacturers to perform clinical tests on their specific products. These clinical tests will lead, in turn, to a highly profitable market, one which is capable of generating enough profit to pay for further nutraceutical research.

The potential of a fully-realized nutraceutical market based on clinical research is enormous. About 140 million people–nearly half of the adult population in the United States–spend approximately $12 billion annually on dietary supplements (e.g., vitamins, minerals, herbal remedies). And an overwhelming majority of the public –74% in the FIM survey — would like to see clinical testing of nutraceutical products. People, both the healthy and patients with problems, want to know which of these substances actually help them, hurt them or have no effect at all.

However, there is one major obstacle in the way to the emergence of true nutraceutical companies: the unclear and confusing ground-rules for making health claims. For this reason, The Foundation for Innovation in Medicine (FIM) has proposed the Nutraceutical Research & Education Act (NREA), which was introduced in Congress on October 1, 1999 by Representative Frank Pallone (D-NJ). The NREA is based on the successful principles of the Orphan Drug Act.

During the two-day conference, a wide range of speakers provided practical information about the current state of the nutraceutical industry and useful guidance about how to move forward in this arena successfully. The highlights of the conference follow.


Stephen L. DeFelice, MD, the controversial and provocative founder and chairman of FIM, opened the conference with his characteristic ebullience and optimism. He caught most of those in attendance off guard with an unusual question, “Who in this audience is completely healthy, mentally and physically?” A few confident, brave hands went up but most in the audience were not certain they could claim to be completely healthy.

Dr. DeFelice noted that few of us are completely healthy and that this fact is the basis for the enormous potential for nutraceuticals. “We are all in this together,” he said, “because we are all sick to some degree either physically or mentally.” Fortunately for all of us, he observed, the Nutraceutical Revolution is at hand. “The medical promise for healing through the use of nutraceuticals and other natural substances is far, far greater than that of pharmaceutical artificial molecules,” Dr. DeFelice said. “The challenge is to deliver that promise to people.”

According to FIM’s chairman, massive misinformation about nutraceuticals floods the consumer daily. Dr. DeFelice noted that at present products with little clinical data to support their claims frequently sell very well, while nutraceuticals with good clinical data to support claims do not do as well. However, the dynamics at play in the Nutraceutical Revolution are forcing the industry to begin to supply the public with accurate information about its products.

“Who represents the patient?” Dr. DeFelice asked. The available products provide little or no clinical support to demonstrate to patients and non-patients that they really work. “Patients want prevention and treatment,” Dr. DeFelice said. “No one is even offering anything of substance in terms of prevention. The products promising effective treatment are currently on the shelves, but no one offers the clinical data to prove nutraceuticals work, so their promise remains unfulfilled.”

The information that does make its way to the public is often incomplete or misleading. For example, nutrition experts put forth a wide range of dietary recommendations to the public whose benefits are not supported by acceptable clinical evidence. Some recommend high-protein, low-carbohydrate diets. Other recommend low-protein, high carbohydrate diets. Still others promote low-fat diets. In addition, many health professionals tell their clients that dietary supplements are not necessary when the evidence in the medical-nutrition literature overwhelmingly indicates the value of and need for supplementation. Diet, oftentimes, is simply not enough to fight disease. Advice based on opinion, and not on clinical data, is necessarily contradictory and confusing.

The clinical data being compiled concerning heart disease offers a valuable contrast to what Dr. DeFelice calls “nutribabble”. Research shows that Vitamin E consumption may lead to a 40% reduction in the risk of heart attack. As little as one ounce of alcohol a dayówhether in wine, beer or spiritsómay reduce that risk by 40% as well. The powerful class of cholesterol-lowering drugs called statins also produce a 40% reduction in risk of heart attack. According to Dr. DeFelice, one published study of a large population of women reported that folic acid combined with moderate amounts of alcohol daily produced an 80% reduction in the risk of a heart attack. Physicians and patients can make sensible, reasonable decisions about health care based on clinical data such as the above.

Nearly 35 years ago, in a series of animal studies, Dr. DeFelice and his colleague, Colonel James Vick, demonstrated the potential medical value of carnitine in both the prevention and treatment of heart disease. One such study showed that carnitine administration blocked the cardiotoxicity of a very effective anticancer drug, Adriamycin. By using the cardioprotective carnitine in combination with the cardiotoxic adriamyicnóthat is, by combining a nutraceutical with a pharmaceutical/oncologists could possibly use higher doses of the anticancer drug. More cancer cells would be killed and more patients would be saved.

However, the needed clinical trials have not been done. The clinical data are not available to prove the effectiveness of this combination. As a result, over the past three decades, lives may have been lost that could have been saved by this combination of therapies.

It is Dr. DeFelice’s strong belief that the lack of clinical data prevents patients from getting the full benefits that nutraceuticals can provide. However, there is another down-side to the lack of clinical data/patients and non-patients do not have vital information about the toxicity of nutraceuticals themselves or about the interaction among other nutraceuticals, pharmaceuticals available by Prescription and over-the-counter products. This is true mainly because clinical studies have not been done to evaluate both the clinical efficacy and safety of single substances – either alone or in combination.

It is important to note that there are two types of toxicities ñ those that are highly visible and dramatic and those that are not. An example of the former is St. John’s Wort’s effect on reducing the drug levels of important therapeutic agents such as protease inhibitors used for the treatment of AIDS and cyclosporin used to prevent body organ transplant rejection. An example of the latter is when calcium is used for the prevention of post-menopausal osteoporosis. Calcium can cause significant constipation which can lead to significant mental and physical problems. This can lead to powerful mood changes which can have a negatively impact on family, friends and associates.

For example, most consumers, especially women, are aware of the benefits of taking calcium to help prevent osteoporosis. However, far fewer know that calcium can also cause constipation, which can become a significant mental and physical problem for many people.

Even though a lack of clinical data leaves consumers with confusing and contradictory information about nutraceuticals from a wide variety of sources or sometimes information that can cause harmóthe healthy and the sick are consuming these products at an unprecedented rate.

To help end the existing confusion, and to provide a framework within which true nutraceutical companies could flourish, Dr. DeFelice and FIM have proposed the NREA. “The NREA or something like it must happen,” Dr. DeFelice said. “Social forces are pushing for this. The NREA is necessary because the enormous medical-health benefit awaits discovery and unsubstantiated and false claims will not go away on their own.” People and physicians need accurate information about nutraceuticals and companies must be rewarded for performing the clinical trials on their products that will produce the information consumers need. According to Dr. DeFelice, the NREA will do a great deal to accomplish both of these goals.

The success of the Nutraceutical Revolution will depend on three factors: (1) clinical data; (2) support from medical experts; and (3) the delivery of nutraceutical information to the public and physicians through the mass media. According to Dr. DeFelice all three of these elements are essential to the successful creation of an informed public and medical community, and a true clinical research-based nutraceutical industry.

And the speakers at the conference provided much needed information to those who are helping to shape the Nutraceutical Revolution.

Lyn Ciocca, the president of Wellness Resources, spoke on “How a Nutraceutical Company Should Be Structured.” Ms. Ciocca began her presentation by referring to two recent articles that appeared in The New York Times. In late 1999, William Safire discussed the origin and spelling of the word “nutraceutical” in his column on language. Ms. Ciocca noted that Mr. Safire accepted Dr. DeFelice’s explanation for the origin of the word (he coined it) and its spelling. To her, this indicated that the field of nutraceuticals was entering public consciousness. However, although some progress was being made, a second Times article, which was highly critical of alternative medicine, showed that there is still a long way to go in achieving acceptance of nutraceuticals.

Ms. Ciocca’s report was based on one-to-one interviews she conducted with over 20 business leaders. She identified the following factors as critical to the success of a nutraceutical company: (1) scientific and medical evidence that supports health claims for products; (2) products that are clinically effective; (3) products that are designed to handle specific health conditions; (4) consumer acceptance of products; (5) products that are safe; and (6) products that offer a sufficient return on investment.

The experts who spoke with Ms. Ciocca all agreed that the safety and quality of nutraceutical products were of paramount concern. Also, customers need to perceive that they are getting a real benefit from the product and that the price of the product is worth the benefit gained. Scientific and medical support for nutraceuticals was a key element in making consumers feel that products are safe and effective.

In addition, those interviewed stressed the importance of taste for success in the nutraceutical food formulation marketplace. A product that does not taste goodóbe it a drink or a candy barówill not be accepted by consumers. The business executives also said that price and product familiarity played important roles in the success of a nutraceutical.

Looking at the bigger picture, Ms. Ciocca found that the ability to gain a proprietary position in the market was very important to the experts. This could be achieved through some form of patent protection, legal recognition of intellectual property rights or by the association of the new product with a line of products that are part of an existing, well-recognized and highly regarded brand name company.

According to Ms. Ciocca, the experts identified the following as necessary to insure a good return on investment: (1) good, skilled personnel; (2) sufficient capital; (3) an infrastructure capable of developing the product successfully; and (4) medical acceptance and endorsement of the nutraceutical product. Ms. Ciocca said that glucosamine, in her opinion, was a good example of a nutraceutical that was handled properly and successfully. In particular, she noted that a good job was done getting information about the potential benefits of glucosamine to both physicians and patients.

Over the next five years, Ms. Ciocca predicted increasing consumer interest in nutraceuticals and great potential for companies in this market. She said that media interest will continue to grow and that physicians are the key to success with consumers. She also pointed out that greater government regulation, heightened competition, corporate mergers and the rise of E-commerce will also shape tomorrow’s nutraceutical market.

Ms. Ciocca concluded that most companies are now poorly prepared to take advantage of the potential of the nutraceutical market. She stressed that companies need to build consumer trust through knowledge-based marketing; invest in medical-scientific research to support product claims; and begin to develop brand names that consumers know and trust. The industry, her investigation showed, is entering a new phase and must develop new competencies to succeed.

Dr. DeFelice commented that he would have thought that the major issue for the industry would be the fairness of the ground-rules to make medical-health claims, be they related to healthy people or patients.

On January 6, 2000, the FDA issued new structure/function regulations that will affect everyone in the nutraceutical field, according to Stephen H. McNamara, Esq. He provided an update on FDA regulations concerning medical foods and health-related claims. In addition, Mr. McNamara supplied everyone in the audience with a 40-page paper, “Use of Health-Related Claims in Food Labeling: A Review of the Current Legal/Regulatory Situation Including FDA’s January 6, 2000 Regulations on ëStructure/Function Claims.'” His focus was on a crucial areaómaking health-related claims that do not trigger the FDA to respond by invoking drug status for a nutraceutical. (Drug status refers to disease claims.)

Mr. McNamara stressed that it is essential for all involved to understand the FDA’s position completely. He emphasized that a clear comprehension of the FDA’s new regulations is imperative for all manufacturers so they do not inadvertently cause their product to be labeled a drug. “I’m personally troubled by the FDA actions,” Mr. McNamara said. He noted that there are often great disparities between FDA regulations and how people operate in the real world. He also explained how some aspects of the recent FDA rulings are not in line with the intent of Congress, as expressed in DSHEA. According to Mr. McNamara, the FDA needs to develop more conformity and consistency in its rulings.

Mr. McNamara took the audience through four “exceptional statements of nutritional support” that FDA allows companies to make: (1) a statement that “claims a benefit related to a classical nutrient deficiency disease and discloses the prevalence of such disease in the United States;” (2) a statement that “describes the role of a nutrient or dietary ingredient intended to affect the structure or function in humans;” (3) a statement that “characterizes the documented mechanism by which a nutrient or dietary ingredient acts to maintain such structure or function;” and (4) a statement that “describes general well-being from consumption of a nutrient or dietary ingredient.”

According to Mr. McNamara, any of the above four types of “statements of nutritional support” may be made in labeling for a dietary supplement, without the approval of the “health claim” regulation if “the manufacturer has substantiation that such a claim is truthful and not misleading;” the labeling prominently displays the following text, “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease;” and if the manufacturer notifies the FDA “no later than 30 days after the first marketing of the dietary supplement with such statement that such a statement is being made.”

Some examples of permissible and impermissible structure/function claims, according to the FDA regulations are:

Permissible: “helps to maintain cholesterol levels that are already within the normal range.”
Impermissible: “lowers cholesterol.”

Permissible: “maintains healthy lung function.”
Impermissible: “maintains healthy lungs in smokers.”

Permissible: “for the relief of occasional sleeplessness.’
Impermissible: “helps to reduce difficulty falling asleep.”

In Mr. McNamara’s view, the January 6, 2000 FDA regulations requires that every structure/function claim needs FDA notification and also needs a disclaimer along with the claim. The FDA did not propose this for comment. Mr. McNamara suggested that this FDA rule-making is bad law and that IT needs to be reconsidered. He said that he was very surprised that FDA took this procedural rule-making step, pointing out that the disclaimers now required did not need to be made before DSHEA. In his opinion, the new rules are clearly not in line with the intent of Congress.

Mr. McNamara asked the audience to look at the FDA rulings from a variety of viewpoints–such as that of consumers or the drug industryóas well as from the point of view of the dietary supplement industry. He said that the FDA actions would be interpreted differently depending on “whose ox gets gored.” Mr. McNamara said he believes these issues will be played out over the next few years. At times, the FDA may seem to be more permissive of structure/function claims, he noted, but overall, FDA is not very tolerant toward the dietary supplement industry.

Richard S. Rivlin, MD, Professor of medicine and Chief, Nutrition Division, New York Hospital-Cornell Medical Center spoke on “Nutraceuticals and Pharmaceuticals Taken Together: The Potential Benefits of Nutraceuticals Given with Cancer Chemotherapy Agents.” Dr. Rivlin began with as assessment of where we are today. He reviewed the role of diet in the development of cancer; the effects of cancer on the patient’s nutritional status; the effect of cancer treatment on nutritional status; and the nutritional management of the cancer patient.

Dr. Rivlin looked at the effect of cancer treatment on patients and explored what role nutraceuticals may play in cancer care. The American Institute for Cancer Research is now studying the use of antioxidants with chemotherapeutic pharmaceuticals and radiation therapy. Much clinical research has to be done in order to adequately assess the medical potential of these combinations.

In addition to a possible role in cancer treatment, nutraceuticals may play an important role in cancer prevention. Dr. Rivlin discussed a number of challenging questions that face the profession regarding nutraceuticals: How can funding be found to test nutraceuticals and cancer prevention? Should whole foods or single nutrients be used? How can the information being collected about the use of nutraceuticals and pharmaceuticals together in cancer patients best be communicated to physicians? What advice should be given to patients when information on nutraceuticals is so incomplete?

One new focus of research, Dr. Rivlin said, is where treatment and prevention overlap. For example, treatment and prevention intersect in the area of environmental carcinogens. Pesticides, herbicides and other chemical carcinogens that are illegal in the United States are still used in agriculture in other countries. These food products are imported into the U.S. and play a role in the onset of cancer in many people. According to Dr. Rivlin, nutraceuticals may have an important role to play in such situations by possibly helping to prevent cancer from occurring, limiting its extent when it does occur, and limiting or preventing metastases.

Dr. Rivlin looked at three nutraceuticals and reported on their known and potential health benefits: resveratrol, garlic and soy. Resveratrol has been an important part of Asian medicine for thousands of years. It is found in grape stems, peanuts and a number of weeds. It has long been a mainstay in Asia for heart disease and infections. Modern Western technology has succeeded in making resveratrol available and its anticancer properties are being studied. According to Dr. Rivlin, modern science is documenting the value of this ancient remedy. Resveratrol has been shown to inhibit carcinogenesis and to have great potential in the treatment and prevention of heart disease.

Garlic has a long and illustrious history in healing. It has been found in the palace of Knossos in Crete and is known to have been used as a performance-enhancing substance during the first Olympics. Hippocrates used garlic, believing it improved health, physical performance and strength. The benefits of garlic were discovered independently in India, China and Europe. Today, garlic is being studied for its value in the treatment and prevention of cancer. Dr. Rivlin reported on encouraging work in which garlic had a positive effect on human breast cancer cell lines and as part of an approach to prostate cancer. Garlic is being evaluated for its effectiveness in heart disease and other conditions.

Soy milk, tofu (coagulated soy milk) and miso soup all have anticancer properties, Dr. Rivlin reported. Soybeans, too, show powerful anticancer effects as well. These nutraceuticals contain isoflavones, which are believed to be the chemicals that are effective in fighting cancer. However, soy products may prove to be somewhat of a double-edged sword. The anticancer chemicals in soy are also estrogens, which may inhibit some forms of cancer and contribute to the development of others.

Dr. Rivlin stated that the potential for nutraceuticals, alone or together with pharmaceuticals, in the prevention and treatment of cancer and other diseases is enormous. However, it is AS yet untested. There is an exciting future ahead for resveratrol, garlic and soy, both alone and in conjunction with pharmaceuticals, but a great deal of research remains to be done before that potential is realized.

Derrick DeSilva, MD, president of the American Nutraceutical Association, talked on the usefulness of nutraceuticals in fighting the phenomenon of drug-induced depletion of natural substances of the body. Before discussing his main topic, Dr. DeSilva explained how his background has helped shape his medical views and practice. Born and raised in Sri Lanka, he saw the harmony of Eastern and Western medicine working together personified in his father, who was a Western physician, and in his grandfather, who was a healer. From his childhood on, Dr. DeSilva has known that combining the best of both forms of medicine to achieve healthóa balance of body, mind and spiritóonly made perfect sense.

In his work today, Dr. DeSilva combines nutraceuticals and pharmaceuticals. For example, all of his patients who are receiving a course of antibiotic therapy also receive probiotic agents. If a patient requires an anticonvulsant drug, Dr. DeSilva also prescribes Milk Thistle along with it. If a cholesterol-lowering statin is indicated, Dr. DeSilva will also suggest that the patient take CoQ10 as well. Patients taking cisplatinum will experience magnesium depletion. Therefore, Dr. DeSilva will recommend magnesium supplementation. Digoxin depletes the body of calcium and magnesium so patients taking this valuable drug swill also be prescribed supplements.

Beta-blockers, H2 receptor agonists (e.g., Zantac, Tagamet), cholesterol-lowering drugs and other staples of today’s pharmaceutical medicine, all deplete the body of much needed vitamins and minerals. In his practice, Dr. DeSilva makes sure that his patients benefit from the wise use of both nutraceuticals and pharmaceuticals.

In closing, he suggested that the key to good health might lie, not in drugs or in natural remedies alone, but in three simple activities: smiling, kissing and praying. According to Dr. DeSilva, all three of these activities play essential roles in achieving the harmony and balance of body, mind and spirit that are the hallmarks of good health.

The afternoon session began with a presentation by Antonino Amato, MD, the Medical Director of Sigma Tau Pharmaceuticals, Inc. Dr. Amato spoke on “Carnitine Deficiencies: An Example of the Largely Unrecognized ëPan Nutraceutical Insufficiency Syndrome,'” a term coined by Dr. DeFelice.

Dr. Amato introduced the audience to carnitine, a naturally occurring substance with many important body functions. Carnitine is 25% endogenous and 75% exogenous in origin; does not bind to protein; is filtered by the kidney and is 95% reabsorbed by the body. There is 10-100 times more carnitine in body tissue than in plasma; muscle has the highest concentration of carnitine in the body. Carnitine helps transport fatty acids into the mitochondria and produce ATP or energy. Carnitine not only helps shuttle fatty acids in, it also helps remove toxic wastes from the cells.

Among the clinical conditions associated with carnitine deficiency are cardiovascular disease, chronic obstructive pulmonary disease, neurological disorders, and kidney, liver and endocrine conditions. There is evidence that Muscular Dystrophy AIDS, CFS, low-sperm count and other health problems are also associated with carnitine deficiency. Certain drugs may cause carnitine deficiency as well.

Unfortunately, Dr. Amato said, carnitine deficiency often goes unrecognized. Although this deficiency occurs in conjunction with many conditions, it may be masked by the underlying disease, and therefore, it is rarely tested for by clinicians.

Carnitine has many cardioprotective effects; is the key to muscle metabolism; is essential to healthy kidney and liver function; and improves glucose and lipid metabolism. Despite it many proven benefits, carnitine remains the Cinderella of nutraceuticals, awaiting the recognition that is due it.

Stephen P. Giannetti, the publisher of Prevention Magazine, and Ed Slaughter, market research director of Prevention Magazine, gave a presentation entitled, “Functional Foods or Nutraceuticals: It’s All About Self-Care.” Mr. Gianetti presented the highlights of a study of the growing self-care movement that was conducted by Prevention. This landmark survey about dietary supplements was not conducted among readers of the esteemed magazine but among the general population of consumers. Nutrition and supplements are very important to consumers but they are also topics the public finds very confusing because of conflicting information about these subjects.

The survey clearly demonstrated that there is a big movement toward self-care in the United States today, especially among those 45-64 years of age. At 25 years of age, Americans spend on average $465 for health care. By age 65, the average American spends $2,647 on health each year. A recent survey by Kaiser Permanente found that 47% of Americans believe their health care provider is more interested in earning money than in providing good health care.

For a number of reasons, more and more Americansóabout 40 % now–are attempting to treat illness themselves or to prevent health problems from occurring in the first place. About 74.5 million Americans do not feel adequately cared for and have resorted to self-care in the past 12 months. The Prevention survey revealed that 72% of Americans use vitamins; from 59-77% use herbs; 15-20% use homeopathic remedies; and 20% use aromatherapy. (Five years ago, the percentage of Americans who used aromatherapy was nearly zero.) The study showed that shoppers who use prescription drugs and over-the-counter remedies also use complementary medicine techniques, herbs, vitamins and supplements and buy organic foods.

The results indicate that consumers are far ahead of the nutraceutical industry. According to Prevention, 106 million Americans use vitamins dailyóand only 11% use a multi-vitamin. Nearly 45 million people use herbs regularly and over 24 million take specialty supplements regularly. Chain drugstores, discount stores and supermarkets are the major outlets for these purchases, not health food stores. It is likely that supermarkets will soon be the biggest outlets for the great variety of nutraceuticals Americans use regularly.

Consumers are guided in their purchases by price, convenience and the selection available. Strikingly, consumers appear to be more concerned with a products’ perceived effectiveness than with concerns over safety. (In contrast, many medical professionals and business executives appear to be more concerned with safety first.)

Americans seem to believe in the healing powers of food. Nearly 50% of the public is actively seeking practical information about nutrition and health. Nearly every other person interviewed by Prevention believed that healthy eating naturally reduces the risk of disease, including major conditions such as heart disease and cancer. The survey showed that 54% of shoppers (representing 54.3 million households) recently purchased a food to achieve a specific health benefit. And 58% (about 57 million households) said that health concerns greatly affected their purchasing patterns.

Shoppers are more sophisticated than they were five years ago and the study showed that consumers use food to treat and to prevent illness. Self-care is a long-term trend that is here to stay. People who are practicing self-care use prescription drugs, over-the-counter products, vitamins and minerals, herbsóin other words, whatever seems to work. These individuals are taking responsibility for their own health.

What consumers urgently need is accurate, consistent advice on using nutraceuticals, foods and dietary supplements, to prevent illness and treat disease. The survey found that, basically, consumers go to the store with health problems seeking health solutions. The information uncovered by the Prevention survey provides invaluable information for everyone involved in the Nutraceutical Revolution.

Linda S. Gilbert, the president of HealthFocus, Inc., gave a presentation on “Consumer Attitudes Toward Nutraceuticals,” in which she focused on consumer priorities regarding foods and dietary supplements. She conducted a survey that consisted of a telephone pre-recruit followed by a 300-question mailing to over 2,000 people who were the primary grocery shoppers in their household. Ms. Gilbert said that there was a high completion rate in her survey.

Regarding food, “What we found,” Ms. Gilbert said, “is that taste is queen and pleasure is king.” According to 46% of those surveyed, it is possible to be overweight and healthy and to be physically attractive and overweight. The consumers who were involved in self-care were confident in their views. They liked herbal remedies and nutritional solutions to health problems. Three out of four consumers believed that they had special health needs and were looking for individualized nutritional solutions. They were not seeking new products; they were looking for simple answers.

Those surveyed turned to healthy nutritional choices to satisfy the needs of the body, mind and spirit; to feel good emotionally; and to improve their self-esteem. The Baby Boomers expressed a sense of entitlement concerning good health. Many were aware that they will live an entire lifetime longer than a person born in 1900 and they are determined to live a healthy lifetime. Between 60-70% of those surveyed saw a connection between nutrition and health, although only 17% said they were happy with their eating habits. Fewer than 50% said they were careful eaters. And 42% told the researchers that they were seeking only small, gradual changes in their diets.

The majority of respondents said taste came first when eating. And about 50% said they would not sacrifice taste for health benefits. In this area, as in so many others, Boomers believe they can “have it all.” Although 50% of those surveyed said they believed vegetables and fruits promote health, especially broccoli, oranges, tomatoes and spinach, only 10% felt soy was good for you. Taste seems to be the major factor in shaping this view.

While a majority of respondents said they prefer to get health benefits from food, 62% said they don’t have the time to do this. Instead, they take supplements. Ms. Gilbert reported that consumers are trying many different things: fortified foods, dietary supplements, vitamins, minerals and herbs. Over 50% of Americans believe that foods can reduce the need for prescription and over-the-counter drugs. A whopping 79% believe that foods can prevent cancer and heart disease. The results of Ms. Gilbert’s survey demonstrate that Americans really believe in the food-health connection.

Ms. Gilbert said that brands that promote a positive benefit from using their products do better than brands that focus on avoiding negatives and suggested that companies keep this important finding in mind when developing and marketing a nutraceutical product. She recommended that companies use one of the following platforms when creating a brand and positioning it: prevention; health enhancement; wellness; nurturing or cosmetic. She stressed that the number one consumer concern is “taste, taste, taste” and that the number two key to success with nutraceuticals is a positive message about a simple, familiar, natural solution for the consumer.

Peter Goldman, MD, Professor Emeritus, Department of Nutrition, Harvard School of Public Health, spoke on “Physicians and the Nutraceutical Dilemma.” Dr. Goldman began his remarks by noting that the surveys reported on by earlier speakers did not include any physicians among those questioned. He brought an important perspective to the conference dialogue, namely that of a physician at a major medical center whose career has spanned great changes in the practice of medicine in the United States.

Dr. Goldman said that some of his colleagues were skeptical of his involvement with Harvard’s Dr. David Eisenberg in studying complementary medicine. “Although the skepticism is not as bad today as it was a few years ago,” he observed. Dr. Goldman has noticed a great disparity in attitude between older and younger physicians toward complementary medicine and subjects such as nutraceuticals. Older physicians seem alienated from the new movements in medicine, though “the rules of the game have changed dramatically,” he said.

The great change in the economics of the practice of medicine is of concern to older physicians, but so is the state of patient care. Powerful prescription drugs are marketed directly to consumers; HMOs demand that physicians see far too many patients each day; and the empowerment of patients presents certain difficulties for many physicians, especially older ones. According to Dr. Goldman, many physicians now see themselves as advisors to their patients. This is a profound change in the physician-patient relationship. These changes have been accepted by the younger generation of physicians but cause difficulty for a good number of older physicians. They were trained and practiced in a very different social and medical environment, one in which the physician was turned to as an authority figure, not as a partner. The fact that such basic shifts in the practice of medicine are occurring in a relatively short period of time compounds the problem.

In Dr. Goldman’s view, the majority of physicians see the clinical evidence for the effectiveness of nutraceuticals as poor. He recognizes that there is little money available for clinical trials of nutraceuticals that could provide the kind of information physicians want. But to the average doctor, the promise of nutraceuticals is not supported by hard clinical data. In addition, according to Consumer Reports, there are about 20,000 possible nutraceuticals, making it nearly impossible for the busy clinician to keep up with developments in the field.

Dr. Goldman acknowledged that there is also bias in the conventional medical community against nutraceuticals. Adverse effects of natural remedies are always widely reported in the medical literature. When a remedy such as feverfew is evaluated, and three studies show it to be effective against migraine, while one investigation shows it to be ineffective, the one negative report will receive most of the attention. In contrast, few people are aware that 15 years ago, when the blockbuster drug Tagamet was the subject of randomized, controlled, double-blind clinical trials, only 13 of 27 trials showed the drug to have a statistically significant positive clinical effect.

The design of clinical trials plays a big role in the outcome, whether a pharmaceutical or a nutraceutical is being evaluated. Different researchers may use different dosages or even different types of products with patients, making it impossible to truly compare the studies. Sampling errors also play a role in producing different outcomes in clinical trials. Finally, the evidence compiled in studies must be interpreted and this, too, can lead to different interpretations of the results.

Dr. Goldman concluded his remarks with a few observations about the importance of the placebo effect in medicine. He said that about 40% of patients respond positively to placebos when they receive them. What is the role of placebo in health care today, he asked. Today, many physicians give patients prescriptions for drugs when they would prefer not to do so. This is done, not solely for medical reasons, but because of patient demand and also to keep from losing their patients to another doctor. Do placebos have a place in medicine in these circumstances? Dr. Goldman left the question open.

Nancy M. Childs, PhD, is Professor of Food marketing at St. Joseph’s University. She is also associated with The Nutraceutical Institute, an alliance of Rutgers, the State University of New Jersey and Saint Joseph’s University. Dr. Childs presented a talk on “Advancing Nutraceutical Research Through Stakeholder Alliances.” She focused her remarks on four main topics: industry segments and trends; research priorities; stakeholder differences; and the implications of her findings.

Dr. Childs described a complex and diverse nutraceutical industry composed of a number of main players: large pharmaceutical companies; large food companies; mid-sized and small companies; herbal and other health food companies; HMOs and insurers; healthcare providers; retailers; regulators; farmers/growers; consumers; and activists.

According to Dr. Child’s, certain trends were discernible. She elaborated on such societal shifts as the move from a focus on therapy to prevention; a de-emphasis on the role of the physician; the empowerment of a nutritionally aware consumer; the demand for customization and convenience; and the dramatic changes in the demographics of disease.

Recent research has indicated the emerging need for the development of proven, effective substances; the formulation of niche products; increased education about nutraceuticals; the creation of marketing strategies based on information; and third-party payer reimbursement for those who pursue a healthy lifestyle. Dr. Child’s identified clinical safety as the major item influencing nutraceutical research, followed by regulatory concerns. She noted that much remained to be done in terms of critical issues such as the role of third-party payers, self-regulation of the industry and the proprietary needs of nutraceutical companies.

In Dr. Child’s view, the critical drivers for research are safety, standards for efficacy and commercial viability and marketability. She said that research priority clusters included safety, standardization and efficacy, marketability and commercial viability and education. Dr. Childs observed that education is given a lot of lip service with very little follow-through.

Among the industry “alliances” identified by Dr. Child’s were those among what she termed providers and protectors, namely healthcare providers, HMOs/insurers, regulators and activists. Dr. Child’s also saw that alliances could be formed out of commercial necessity among small nutraceutical, mid-sized and large food companies and large pharmaceutical corporations. And she saw alliances among “industry extremes,” which she defined as retailers, growers and health food and other nutraceutical companies.

Safety, according to Dr. Childs, was the common denominator among all the participants in the industry alliances. Safety is the bottom line for short-term and long-term success with nutraceuticals by any measure. Interestingly, she reported that education was a top priority only for consumers.

Dr. Childs’s research has important implications for the emerging nutraceutical industry. While research is strongly supported overall, there are inherent conflicts in research goals, exemplified by the differing concerns of companies and consumers. It is unlikely, in Dr. Child’s view, that full consensus will be reached among all the participants in the industry alliances.

Mark Blumenthal. PhD, Executive Director of the American Botanical Council, gave a talk on “The Impact of German Nutraceutical Research in the United States.” He reminded the audience that nutraceuticals are considered to be drugs in Germany and are sold as such. These products are an integral part of mainstream health care. They are not viewed as “fringe” or “alternative” approaches, separate from the practice of conventional medicine. They are an important part of health care and are not relegated to the margins of medicine or the periphery of clinical practice. They are included in the Complete German Commission E Monograph, an exhaustive review providing the product information Americans are familiar with through prescription package inserts. Mr. Blumenthal said that the German monographs could be a potential model for the United States.

Another significant difference between Germany and the U.S. involves physician education. Dr. Blumenthal said that all German physicians study phyto-medicine as part of their medical school training. Phyto-medicine is not considered “alternative” medicine in Germany.

In Germany and Europe, clinical research drives the sales of the top selling herbs, which include the top 12 herbs in the American market. The clinical evidence of safety and effectiveness translates directly into sales in Europe.

Dr. Blumenthal discussed in detail the clinical trials that showed the effectiveness of many herbal remedies, among them black cohosh, echinacea, saw palmetto, St. John’s Wort, milk thistle, hawthorn, horse chestnut, garlic and ginkgo biloba. He said there were valuable and compelling studies on these products, published in peer-reviewed journals, demonstrating their value for consumers.

However, he also added that the question of phyto-equivalence remains to be answered. How do researchers know that the same materials are used, for example, in a study of echinacea? There are three different types of echinacea plants used in commercial preparations and different species have different chemistries, Dr. Blumenthal noted. In the studies of ginkgo biloba, two different types of plants were used. With Saw palmetto, no one type of plant dominated in the 18 clinical trials Dr. Blumenthal mentioned. Even when labeled exactly the same, herbal products may perform differently because of use of different parts of the plant, differences in manufacturing procedures, and many other factors involved in creating a product when there is no standardization in the field.

This dilemma, among many others, remains to be solved by those who are creating the Nutraceutical Revolution in the United States.

Stephen L. DeFelice, M.D. opened the session on Friday morning with his talk, “The Cost, Medical Health Claim and Research Connection. Also, Is There a Difference Between a Medical and a Health Claim?” According to Dr. DeFelice, industry is blind to the potential of the nutraceutical market, which he described as “the biggest market opportunity of my lifetime.” The food industry, the health food industry and other industries, in his view, are doing virtually nothing to take advantage of this enormous market.

There is no major research and development effort underway , no clinical work by companies on their products, Dr. DeFelice said. He observed that we now have a commodity market, not a proprietary market. He urged industry to begin to patent and perform clinical research “on your specific products.” According to Dr. DeFelice, the existing health-disease regulations will not have a major impact on the Nutraceutical revolution that is underway. Over fifty percent of Americans are taking nutraceuticals nowówith no knowledgeable, authoritative guidance. What is needed, he said, is for clinical research to be encouraged and for the industry to learn how to use that research to make a profit.

Since the thalidomide tragedy, Dr. DeFelice said, questions of safety and toxicity have become the number one concerns of both consumers and regulators. “We don’t have an efficacy-oriented society,” he said. This attitude contributes to the great cost of an NDA and doing the clinical testing necessary to bring a product to the market. What is the result when research costs too much, he asked. “A market-driven nutraceutical industry in which no real credible information on the clinical benefits of products is available.”

According to Dr. DeFelice, amidst all of the massive lobbying of Congress, no one talks to the Senators and Congressmen about the need to do clinical research or what is necessary for medical discovery. He observed that there has never been a Congressional hearing on the medical discovery process itself and how to both improve and accelerate it. “The status quo is unacceptable,” he said.

To begin to change the status quo, Dr. DeFelice said in 1989 he pulled together a small group of people to discuss how to go about getting Congress to pass needed legislation regarding the nutraceutical industry. The Orphan Drug Act was the model that he proposed. It reduced costs for research and allowed companies to make a profit and served the health needs of the public. The result of the discussions the group engaged in is the Nutraceutical Research and Education Act (NREA), which was introduced in Congress by Representative Frank Pallone, Jr. (D-NJ). (Click here for he complete text of the NREA is available here.)

In Dr. DeFelice’s opinion, the NREA offers a workable and practical solution to many of the difficulties facing the emerging nutraceutical industry. It changes the “rules of the game” so that clinical research costs for nutraceuticals are affordable and dramatically lower than research costs for pharmaceuticals. Provisions of the NREA would also reward companies that invest in clinical research on their products by allowing them to use their clinical data to make profits.

Dr. DeFelice deferred a more thorough look at the specifics and the benefits of the NREA until later in the program.

Christine Lewis, PhD, Acting Director, The Office of Nutritional Products, Labeling & Dietary Supplements of the Food and Drug Administration, discussed the nature of this new FDA division. Dr. Lewis said that two smaller resource-strapped offices had been merged, producing one larger resource-strapped office. In her view, this merger highlights nutrition as an entity within FDA and also helps stakeholders identify where to go within FDA for answers to their concerns. Dr. Lewis said that no functions were lost in the merger and that the office was now taking a proactive position to ensure success with its mission.

Dr. Lewis said that the new FDA office has developed a ten-year strategic plan concerning dietary supplements. A major theme of her officeóleveraging and partneringóis evident in the focus of the plan. Stakeholder input is an integral part of the new plan in which five strategy teams will work on areas that are of concern to FDA: (1) safety; (2) improved reporting of adverse effects; (3) publishing of GMPs; (4) stronger enforcement of FDA regulations; (5) increased regulation of dietary supplements.

Elements of the plan-which can be seen as a marketing strategy for educating Congressóinclude such issues as safety, efficacy, distinguishing the boundaries between foods, drugs and dietary supplements, enforcement, developing science-based information on dietary supplements and FDA outreach to the industry. According to Dr. Lewis, FDA is very interested in collaborative work with outside sources.

FDA is concerned with oversight of human studies; developing medical-based standards for studies of dietary supplements; and creating a broad-based research agenda in which the Agency collaborates with others in partnership. The theme of partnership and leveraging is so important to Dr. Lewis that she told the audience she is thinking of getting a T-shirt that reads “Born to Leverage.”

“We can be visionary and creative in our work,” Dr. Lewis said. She promised that her office would make an honest effort to leverage with others to get important and necessary work done.

William Wardell, MD, PhD, Senior Scientific Officer and executive Director of the Institute for Drug Research, Covance looked at “Pharmaceutical Clinical Research Costs.” Dr. Wardell addressed three issues: the cost of research into conventional drugs; the cost of herbals studied in the conventional system; and costs under a new method of evaluating herbs.

Dr. Wardell said that estimates of drug development costs range from $297 million to as high as $500 million, depending on the methodology used. In his evaluation, the true out-of-pocket costs to develop one specific drug (excluding the costs of the failures of other products and the costs of capital) is about $75 million. These figures, while still high, begin to make research look more feasible.

His research showed that it would take 3-8 years and cost $7-30 million for a botanical remedy, with thousands of years of clinical experience supporting its safety and efficacy, to meet conventional drug NDA approval standards. Instead, he proposed another review process for nutraceuticals, one that would only go as far as Phase II clinical trials in the drug model. Under these procedures, the same botanical approval would generally take from six months to one and a half years and cost between $750,000 and $2.5 million.

There are many unknown factors in nutraceutical research. For example, how does a company choose the right botanical to test out of the legion available. It is not known beforehand which ones will prove to be successful. Which positive results are due to the placebo effect and which to the botanical product? How is the problem of the inconsistency of the product from lot to lot to be handled? These and other vital questions remain to be answered.

Dr. Wardell suggested that companies testing nutraceuticals might want to perform their clinical research in the country of origin of the product. In addition, further cost savings could be obtained by performing clinical trials in academic institutions, Dr. Wardell suggested. Antonio C. Martinez, II, Esq., Attorney at Law, Government and regulatory Affairs Counsel, described the NREA in detail. He provided the audience with an informative paper on the NREA and the complete text of the NREA bill (H.R. 3001) that was introduced in Congress on October 1, 1999.

Mr. Martinez said that the new structure/function regulations introduced by the FDA in January 2000 might prove troubling for many with nutraceutical products. Companies need to look at the FDA regulations thoroughly and understand the gray zones. He stressed the need to develop a system that will benefit companies that undertake clinical research on their products and that will allow them to use the clinical data to successfully commercialize them.

Mr. Martinez went through some of the key elements in his paper on “The FDA Final Rule on Structure/Function Claims Issued January 6, 2000, highlighting certain critical points. According to Mr. Martinez, it will be more difficult to draw the line between legal and illegal claims; the FDA will look to explicit or implied disease claims; and third party literature use will become more difficult. He did note “one bright star” in the new regulationsóit will be possible now to make claims about normal conditions that are associated with the aging process, menopause, PMS, teenage acne, minor pain currently not considered to be due to disease and a wide range of other conditions. (Click here to reference the DeFelice Commentary, “Time to Correct the Epistemologic Chaos that Prevents Nutraceutical Clinical Discovery”, October 12, 1999.)

Mr. Martinez offered examples of claims that FDA considers unacceptable because symptoms may imply disease (e.g., “relief of heartburn,” “relief of bronchospasm); unacceptable because the product name implies drug treatment (e.g., herbal Prozac, herbal Phen-Fen); or unacceptable because the claim refers to a class of drugs (e.g., antibiotics, antidepressants). He also provided examples of acceptable structure/function claims: “improves absentmindedness,” “relieves stress and frustration,” “for relief of sour stomach,” “arouses or increases sexual desire and improves sexual performance.”

Mr. Martinez urged everyone to let their congressmen and senators know what is needed regarding delivering the medical-health value of nutraceuticals as well as truthful information. He pointed out that politics plays a big role in what does and does not happen in terms of regulations and laws.

Representative Frank Pallone, Jr. (D-NJ) addressed the conference about the NREA. He described it as a simple bill that is easy to read and understand. Rep. Pallone said he considers the NREA to be a starting piece of legislation that builds on DSHEA. He noted that it didn’t seem at first that DSHEA would pass but grassroots political action resulted in 300 members of Congress sponsoring the legislation. Rep. Pallone said that the NREA also needs grassroots political support.

The NREA would require clinical trials that would then allow companies to make a claim application for their specific products to a Nutraceutical Board. It is important to note that the clinical studies must be conducted on the specific product that is commercialized. The NREA Nutraceuticals Board will make its decisions on a case-by-case basis. The legislation would also allow companies to make an exclusive marketing claim for their product for a ten-year period. In addition, the NREA would allow small nutraceutical firms an antitrust exemption so they could join forces to conduct the necessary clinical research. The details of the NREA will be fleshed out, the congressman said, after the bill is introduced and will incorporate input from the public, industry representatives and professionals in the health field.

Rep. Pallone said he could not emphasize enough the need for political involvement from people in all sectors of the nutraceutical industry. It is paramount that those involved make their wishes known to their representatives. Political action is vital to the passage of the NREA.

Adrianne Bendich, PhD, Associate Director-New Products Research, SmithKline Beecham Consumer Healthcare, presented a talk entitled, “Nutraceuticals Can Significantly Reduce health Care Costs: Case Studies.”

Dr. Bendich looked at three health conditions: heart disease, adverse birth outcomes, and osteoporosis. She examined how cost analyses can be used to improve public health and reduce health care costs.

Dietary supplements have a role to play in managing heart disease. Antioxidants, such as vitamins E, appear to have a positive effect in cardiovascular disease, the nation’s number one killer. Folic acid and B12 are able to reduce homocysteine levels. And certain multivitamins can also reduce homocysteine levels. Dietary supplements are also valuable in preventing birth defects and problems associated with low birth weight. Clinically significant osteoporosis affects six million American adults and this condition can be helped by calcium and vitamin D supplementation.

According to Dr. Bendich, meta-analyses of published papers showed that vitamin E produced a 38% reduction in cardiovascular disease; vitamin supplementation reduced perinatal and prenatal problems by 30-40%. These numbers translate into tremendous cost savings: $20 billion a year for heart disease; $3 billion a year for birth defects; and $2 billion a year for osteoporosis.

The evidence indicates that while prevention is more expensive than treatment at first, the overall net benefit to society economically outweighs the initial costs. The benefits in terms of reduced or eliminated pain and suffering cannot be measured. According to Dr. Bendich, “health economics makes cents.” In her view, 70% of diseases and associated costs are preventable and nutraceuticals play an important role in such preventive efforts.

The conference concluded with a vigorous panel discussion. Panelist included Vic P. Micati, former President Pfizer Europe and Executive Vice-President, Pfizer Pharmaceuticals Group and Vice President, Pfizer, Inc.; Robert A. Hoerr, MD, PhD, President, Research-based Dietary Ingredient Association (RDIA) and President and CEO of GalaGen, Inc.; Paul Lachance, PhD, Executive Director of The Nutraceutical Institute and Professor of Nutrition & Food Science, Rutgers, The State University; Representative Pallone; Christine Lewis, PhD of the FDA; and Stephen L. DeFelice, MD, Chairman of FIM (Click here for complete list of participants of the conference.)

Mr. Micati said that there was an understandable reluctance for companies to invest in nutraceuticals but believes that the NREA would make a significant difference in this area. He observed that protecting a claim is more difficult than protecting a patent. The lack of clear ground rules for making truthful claims based on the results of clinical studies is a powerful inhibiting factor to establish a clinical research-based nutraceutical industry.

Dr. Hoerr said that DSHEA limits what health claims can be made and how studies can be designed. He emphasized that clinical data should be reviewed on a case-by-case basis. He also called for more participation by the academic community and assessing the data which support the proposed claims.

Dr. Lachance said that decreased health care costs might be the “hook” that will bring the support needed for passage of the NREA. Lower costs should appeal to both the public and members of Congress. Dr. Lachance also said it was time to rewrite the outdated, 60-year old Food and Drug laws to put them in line with today’s new technologies, products and attitudes. In his opinion, an intelligent product delivery system, with traceability through all stages, from the field to the consumer, is urgently needed. In addition, new ways of thinking are also needed.

Dr. Lewis reiterated the major themes of her talkóthe FDA’s desire to partner and leverage with outside sources; the importance of good clinical research on dietary supplements; and the desire to work creatively with stakeholders and all participants in the emerging nutraceutical marketplace.

Representative Pallone again emphasized the need for political action at the grassroots level, particularly at a time when the next election is sure to bring about major changes in government, in both the Congress and the White House.

Dr. DeFelice again touched on the benefits of the NREA for everyone involved in the Nutraceutical Revolution and urged all in attendance to become actively involved in supporting its passage. “Without the clinical research necessary to discover the enormous medical-health benefits of nutraceuticals, the status quo of a market and unsubstantiated claims-driven industry will continue. All of us will pay the unfortunate price of suffering needlessly and/or dying prematurely.”

About the Author:

Michael Mannion has been a Professional writer since 1975 and is uniquely positioned in his field. Mr. Mannion is one of the few writers today who has a strong background in both established, conventional, mainstream medicine and alternative/complementary health. In addition, Mr. Mannion has extensive contacts with top MDs and prominent complementary care practitioners.

He has written on a wide range of subjects, often before they become well-known. For example, he researched and wrote on genetic engineering in 1977; hospice care in 1978; medical marijuana in 1979; the dangers of medical radiation in 1979; carcinogens in the workplace in 1979; and the cigarette-induced epidemic of lung cancer in women in1981.

He was the Director of Professional Education Publications for the American Cancer Society and the Managing Editor of the Society’s clinical journal, Ca-A Cancer Journal for Clinicians. Mr. Mannion is the author of 365 Everyday Health Tips: A Daily Guide to Improving Health and Increasing Energy (1996); The Pharmacist’s Guide to OTC’s and Natural Remedies (1999); How to Help Your Teenager Stop Smoking (2000); and two forthcoming books, Frankenstein Foods: Genetically Modified Foods and Your Health (2000) and The New American Medicine (2000). In addition, his 1978 novel, Colleen, is being re-published along with his new novel, Erin’s Daughters.