Food for Thought
Childhood experiences can profoundly affect the rest of our lives. For some people, it was a specific person; for others, it was a memorable event. For Julie Carrier, associate professor of biological engineering, it was wheat bread.
Carrier smiles as she recalls her mother, whose interest in nutrition led her to open the first health food store in her home town in 1968. While her mother focused on whole-food sources, for Carrier it all seemed to come down to wheat bread. “I think now of all of the wonderful breads that I had back then,” she laughs. “But everyone else at school had white bread, and the last thing a kid wants is to be different from everyone else.”
From this inauspicious beginning Carrier developed an interest in science that culminated in a bachelor’s degree in agricultural engineering and a doctorate in chemical engineering. Her growing interest in functional foods took shape with her work on ginkgolide production from Ginkgo biloba cells and led to her current research on extraction techniques for nutraceuticals.
“I have always been interested in the extraction of the health-beneficial compounds from plants,” explained Carrier. “I am not against herbal medicine, but I want to put some engineering in there.”
THE FUNCTION OF FOOD
Julie Carrier, associate professor of biological engineering, uses extraction techniques to examine the properties of compounds found in neutraceuticals, foods or parts of foods that provide medical or health benefits. Carrier’s research helps bring precision to a largely unregulated, multi-billion dollar industry.
First used in 1989, the term nutraceuticals was coined by the Foundation for Innovation in Medicine to describe a rapidly developing area of biomedical research. Also known as functional foods or designer foods, nutraceuticals are foods or parts of foods that provide medical or health benefits, including the prevention or treatment of disease. This includes a wide range of products from isolated nutrients, dietary supplements and diet plans to herbal products to genetically engineered foods and processed food products like cereals and beverages.
While labels like “designer foods” make these seem like a modern innovation, in reality the use of foods in the treatment of diseases and injuries predates recorded history. By the time writing emerged, the use of particular herbs and plants to treat specific maladies was well established.
“We have really lost touch with the fact that before World War II medicine was basically herbal,” explained Carrier. “There was a science to what apothecaries did. They had a knowledge base that they applied.”
The 1950s and 1960s saw the rise of the pharmaceutical companies, and medicine drifted away from functional foods to clinically quantifiable doses of regulated drugs. This shift highlighted some of the problems with food as medicine. Not only did its use require a sophisticated knowledge of plants, but dosage amounts were difficult to determine.
However, by the 1980s, public interest in and demand for functional foods was growing dramatically. By 1996, “health-promoting ingredients” were identified as one of the most important trends in the food industry. More recently, a survey reported in Food Processing magazine found that functional foods/nutraceuticals were the most important factors in new product development.
Today, consumers spend a staggering amount on nutraceuticals each year. Using the broadest definition of functional foods, a 1995 Canadian report estimated that the market was $250 billion in the United States. A 2002 German study that used a far narrower definition placed the U.S. market at $30 billion, with a five percent annual growth rate.
While the actual dollar figures may vary, there is agreement that nutraceuticals represent a huge, growing industry segment. With that kind of market at stake, more and more companies have moved into the production of functional foods. Although this trend began with food producers, such as Quaker Oats, non-food manufacturers, such as Johnson & Johnson’s McNeil Consumer Products, have moved into the area.
Ginkgo biloba and Echinacea, commonly known as purple coneflower, contain compounds known to confer health benefits to humans. However, the exact location of the compounds in the plants makes all the difference when creating neutraceuticals and dietary supplements. University of Arkansas researchers seek to determine the amounts of different compounds in the roots, stems, leaves and flowers of various plants.
While U.S. consumers are accustomed to relying on the Food and Drug Administration (FDA) to ensure product safety, the FDA does not regulate nutraceuticals because they are classified as dietary supplements. In 1994 the U.S. Congress passed the Dietary Supplement Health and Education Act (DSHEA), which attempted to define the claims that a manufacturer can make for a product that is classified as a dietary supplement.
Under DSHEA, dietary supplement labels can make general claims (e.g., promotes eye health) without prior approval from the FDA. However, they cannot claim to prevent, treat, cure, mitigate or diagnose a disease. It specifically forbids implied disease claims, such as “prevents bone fragility in post-menopausal women” and those implied by the product name (e.g., CirculCure), a description of contents (e.g., contains aspirin) or pictures or symbols
DSHEA does permit manufacturers to make health maintenance claims, non-disease claims and claims for minor, common symptoms associated with life stages without providing evidence. For example, a product may be promoted to “maintain a healthy circulatory system,” to “help you relax” or “enhance muscles,” or “for common symptoms of PMS.”
In 2000, the FDA relaxed DSHEA to allow claims about common conditions associated with aging, pregnancy, menopause and adolescence. However, serious diseases associated with these conditions, such as osteoporosis or toxemia, are still subject to regulation.
Manufacturers are required to notify the FDA of claims for a product within 30 days after it is put on the market. However, the FDA has no regulatory authority and can only police labeling on a complaint basis.
PROBLEMS AND POTENTIALS
The lack of onerous regulations and the potential for substantial profits led to a proliferation of nutraceutical manufacturers in the 1980s. However, small companies soon realized that there were also significant problems.
The spiny milk thistle may look hostile, but it contains four compounds that are called silymarin. Research has shown that these compounds have beneficial effects in the treatment of liver diseases, including cirrhosis and hepatitis. Recent studies also suggest it may help suppress the growth of some cancers.
Most of the problems in nutraceutical manufacture derive from the fact that the plants that contain them are not well-characterized. For many plants, scientists do not even know what the active ingredients in the plant are or how to extract them.
“In many instances that we do know, the beneficial ingredient varies according to the growth stage of the plant,” explained Carrier. “In other cases, the active ingredient is only found in one part of the plant. Other plants may have high quantities of the active ingredient at the time of harvest, but by the time they are shipped from China, for instance, it has degraded to nothing.”
Echinacea is a classic case in point. It contains elements that have long been known to have therapeutic properties for a variety of conditions. However, for Echinacea the problem is location. While all of the plant may contain traces of the active ingredient, it is primarily found in the roots of three- or four- year-old plants. However, because Echinacea is a perennial and uprooting it destroys the plant, some harvesters merely use the stems, leaves or flowers, which contain little or no active ingredients. Although it is accurately labeled as containing Echinacea, the product contains little or no active ingredients.
Problems with plant characterization lead to problems with dosages. Because of variations in plant materials, the actual amount of an active ingredient in a given supplement may vary widely among manufacturers and even among lots from the same manufacturer. And some products, particularly “blends,” contain plant materials, but no active ingredients at all.
Because dietary supplements can interact with prescription drugs like heart medication or cholesterol-lowering medicines, supplement dosage variation can cause serious medical problems for doctors and patients alike. Very few doctors are trained in the appropriate use or dosage of dietary supplements. That problem is compounded by the fact that most patients do not tell their doctor about the supplements they are taking because they think of them as food, rather than medicine.
“Some supplements, such as St. John’s Wort, can interact with prescription medications and either make them more potent or counteract their effects,” said Carrier. “But even if the doctor is familiar with the supplement and the patient tells the physician what they are taking, it is impossible to adjust the dosage of medicine to compensate because it is impossible to tell what is actually in each pill without laboratory testing. For the same brand, there can be significant lot-to-lot variation.”
TESTING AND RESEARCH
Researchers extract chemical compounds from milk thistle using different liquids—like water or ethanol—to determine which solvent most effectively extracts compounds from pills, powders, seeds or other plant material.
Unlike pharmaceuticals, nutraceuticals do not have a wide profit margin, so there is little money available in companies to support research or testing. However, if the problems associated with dosage and drug interaction are to be overcome, research is essential.
Carrier is also interested in issues associated with handling these products. Noting that there is not much science behind they way they are harvested and dried, she points out that this may have a substantial impact on product quality.
For example, in her Echinacea research, Carrier found that at least one compound, echinacoside, is very sensitive to heat. If the Echinacea roots are dried at too high a temperature, the echinacoside can be damaged or even destroyed, substantially reducing the quality and effectiveness of the Echinacea.
Once the active ingredients are identified and characterized, the problem of extraction arises. It is one thing to know what works and where it occurs in the plant and when it is present; it is another to remove it from the plant without destroying its usefulness. Very little is known about appropriate techniques to extract the active ingredients from plants.
“A manufacturer may have the very best of intentions and be acting in good faith and still produce an inferior product,” said Carrier. “These are very complex problems and they require some science and engineering to solve.
Ed Clausen, professor of chemical engineering, and graduate student Sunny Wallace use a high performance liquid chromatograph to quantify the amounts of certain compounds found in dietary supplements. By comparing extraction processes, Clausen and Carrier have determined that hot water can be used as an effective replacement for hexane, a toxic compound currently used by industry.
Extraction of active compounds brings together Carrier’s agricultural and chemical engineering training. She began her career working on the extraction of ginkgolide from the cells of Ginkgo biloba at Canada’s McGill University, and did post-doctoral research on terpenoid enzymes at the University of Leiden, The Netherlands. As an associate professor of agricultural and bioresource engineering at the University of Saskatchewan, Canada, Carrier worked with Echinacea, feverfew, milk thistle and St. John’s Wort.
“Not only does she have a lot of background in this area, but she has developed some really good analytical methods, which were not available before,” said Ed Clausen, professor of chemical engineering.
Clausen and Carrier are working with graduate students Sunny Wallace, Katie Seward, Senthil Subramanian and Lijun Duan to develop novel extraction techniques for nutraceuticals. Their current research focuses on milk thistle, which is well-characterized and has both important potential benefit and dosage considerations. Milk thistle contains a group of four compounds commonly called silymarin.
Milk thistle is a common herb that has been used in the treatment of liver problems for more than 2000 years. Although the entire plant contains silymarin, the highest concentration is in the seeds. Milk thistle is toxic to livestock, but it has been shown to have a beneficial effect in the treatment of liver diseases, including cirrhosis and hepatitis. Recent studies have shown it to be beneficial in the treatment of Amanita mushroom poisoning and suggest it may be useful in suppressing the growth of some cancers, including cancer of the tongue and prostate cancer.
However, although milk thistle has many potential uses, it also has some drawbacks, particularly with drug interactions. In 2001 researchers at the University of Pittsburgh found indications that milk thistle may increase the levels of some medications, such as methadone, heart drugs, antibiotics (erythromycin), anti-seizure drugs, antidepressants, antihistamines, anti-psychotics, sedatives, statins and transplant drugs (cyclosporin) or lower the levels of estrogen and the anti-parasite drug mepron.
Carrier and Clausen wanted to develop a safer, less expensive way to extract the four components of silymarin. “Under certain temperature and pressure conditions, water begins to act like an organic solvent,” explained Clausen. “Although this is a known phenomenon, it has not been applied to food and pharmaceutical processing before.”
Current industrial processing techniques use a solvent, such as hexane, to extract the desired compounds from the plant. The solvents must then be removed before the compound can be used. Water extraction is a cost-effective alternative because it eliminates the solvent-recovery stage. In addition, water is less expensive than most industrial solvents.
“Water extraction allows us to reduce the number of steps in the process,” Carrier explained. “And because it is environmentally benign, it doesn’t present many of the problems encountered with use and disposal of many industrial solvents.”
Clausen and Carrier compared their hot-water extraction process with a standard chemical extraction process. They found that similar concentrations of the compounds were obtained by using both processes.
“It has always amazed me that a chemical as toxic as hexane is used as a solvent in processing soybeans, for example,” said Clausen. “I think it has largely been a matter of using something you know works rather than trying to find a less-toxic alternative.”