Connecting Health Studies and R&D

  "Connecting health studies with R&D is very important, but not without good sound science behind a functional food or supplement," says Kerin Franklin, vice president of research and development, Celestial Seasonings, Boulder, CO. "For the success of the industry as a whole, we're all responsible for the way we conduct and use health studies. Whether or not you are actually doing the study or you are using someone else's, you want to make sure that it's a sound, clinical trial done under FDA-type protocol."

  Sound trials almost invariably depend on double-blind, placebo-controlled clinical trials. Epidemiological studies can also be very helpful, notes Franklin, citing green-tea studies that have put the spotlight on lower incidence of certain cancers in Japan and China. Such studies are helpful for connecting general health trends with consumption of certain items, after which targeted clinical trials can be carried out.

  When designing or evaluating a clinical test, another important factor is safety. "The first thing I look for is a human-safety assessment," says Barry Swanson, Ph.D., professor in the department of food science and human nutrition, Washington State University, Pullman. "Many studies combine the adverse effects with the beneficial, but if you're looking at a single study for safety information and health benefits, you'd better have very good control of the situation.

  "Conduct as many tests as possible, but in most cases, these are not going to reach the zero-risk level that consumers might like to see," continues Swanson. He recommends that clinical-study timelines be as long as possible to reduce risk, but as short as possible to enhance benefits. (For background and more information on clinical-trial safety, see "The Human Side of Toxicology Testing" in the November 1994 issue of Food Product Design.)

  How can companies keep abreast of what's happening in the clinical health-study world? Through the general media, suggests Franklin, as well as by tapping in to what's happening at universities and monitoring scientific publications. "We also have strategic relationships with a number of trade organizations, such as the National Honey Board, Council for Responsible Nutrition, Herb Research Foundation, American Herbal Products Association and the Institute of Food Technologists," she adds.

  The level of a company's involvement in particular a study naturally varies along with the circumstances. ORAFTI's research, for example, is being carried out in numerous universities and medical centers, according to Kathy Niness, vice president, marketing and sales, North America. "The research is in all different stages, some well-proven, some in its early stages," she says. "We completely fund some studies, while funding a certain portion of others. At times we also obtain government grants for research, or simply provide test product." The products in this case are the company's inulin and oligofructose dietary fiber ingredients, which function as prebiotics; i.e., stimulate beneficial bacteria in the colon. (An AOAC-approved fiber-analysis method now exists for these fibers, incidentally.)

  While there's no specific, proven methodology for connecting health studies and R&D, some of the same common-sense principles that apply to product development in general are also applicable when transitioning from scientific-study data to food and beverage applications.

  "First, make sure your source of information is sound. If they're good studies, they will be peer-reviewed and published," says Franklin. The most credible data sets are invariably those that provide quantitative data. "To scientifically validate or peer-review a study, a specific biomarker must be part of that study," observes Swanson.

  "Our studies measure a definite, quantifiable end point," says Izzo. "In the gut-health area, typically we're looking at bifidobacteria levels. Hallmark studies in this area have measured both bifidobacteria levels and those of potentially harmful bacteria before and after ingestion of prebiotics."

  After establishing a study's credibility, consider exactly what was tested, recommends Franklin. "For instance, if a study claims beneficial results from drinking six cups of green tea every day for five years, you don't want to make a claim that drinking one cup a day for three weeks will have the same effect," she says. "You want to make sure you're not making claims based on your product rather than what was tested - use studies that are directly applicable."

  Also consider the delivery system that will carry the beneficial compound in question. Some substances might be subject to oxidation, susceptible to pH or other environmental factors, or their absorption and utilization by the body might be affected by the matrix or incidental ingredients. "Make sure the important compounds in a food or beverage product are able to hold their own against high heat and other processing conditions, as well as survive the duration of the intended shelf life," says Franklin. "You want to make sure that a given product is efficacious throughout its shelf life. Take the product through the whole preparation process, and be sure to check it in its final form."

  "With nutritional research, if you're not sure how much benefit your product has, or whether it functions in a certain area, one of the ways to go is to carry out animal research first to see if there's a positive indication, and then move on to human clinical studies," says Niness.

  "At this point, we would not go out and promote our products in terms of making any types of claims about cancer," says Izzo. "We've done a lot of animal work, so there are positive indications, but that science is not yet at the stage of human clinical trials."

  For both health claims and structure-function claims, Izzo observes, human clinical trials are the gold standard. "In the areas of testing inulin and oligofructose's effects on digestive health/gastrointestinal tract function and calcium absorption, there have been double-blind, placebo-controlled human clinical trials," he says. In the opinion of leading scientists in the area, these trials have been well-designed and correctly carried out, says Izzo, so he is very comfortable in asserting that his company is making no unjustified claims about its ingredients' benefits.

  Niness notes that, depending on the company, certain R&D personnel like to see just a summary of research, while others want to peruse the actual papers. "If desired, we'll sit down and discuss the ins and outs of the studies with them," she says.

  At times, it may be beneficial for a company to undertake its own study. For example, "the calcium-absorption research we did was really more defensive than offensive research," says Niness. "Because certain types of fibers have been known to bind minerals and prevent absorption in the GI tract, we wanted to make sure that our ingredients did not do that.

  "When we did the early studies," continues Niness, "not only did we find that inulin and oligofructose do not prevent absorption, they actually increase it. In human clinical studies, we observed quite dramatic absorption increases, on the order of 25% to 30%."

  Celestial Seasonings also recently took a somewhat defensive stance, paying for and conducting a human clinical trial in response to recent study results indicating that echinacea might not be as effective in fighting the rhinovirus-caused common cold as has been suggested. "The recommendation is to start taking echinacea as soon as you start coming down with a cold," says Franklin. "We wanted to find out if echinacea actually does anything, and if so, what does it do?

  "We wanted to make sure we did our trial in a very controlled and statistically significant manner - four people does not constitute a clinical trial," continues Franklin. "We didn't just ask subjective questions, like 'are you feeling well?'; 'did you get any colds' and 'do you have a sore throat,' although we did ask those questions and follow FDA-recognized methods for using that kind of qualitative data. Instead, we drew blood from our subjects and tested for certain markers indicative of an immune response."

  Researchers found that subjects taking echinacea exhibited increased levels of properdin, one of the body's key immune-response compounds. Properdin, a blood-serum protein, attacks foreign matter and destroys bacteria, abnormal red blood cells and viruses.

  Does an increased level of properdin automatically signal the death knell for a marauding rhinovirus? Not necessarily, but a heightened immune response is an excellent indicator that the body is working to fight off foreign invaders, which is the response researchers were looking for.

  An additional factor important to the echinacea equation is the form used. "We not only tested to see if echinacea is effective, but we also tested several different types of echinacea," says Franklin. "We were trying to show that all echinaceas are not created equal. The problem is that a lot of companies are selling a standardized extract, and while we believe in standardization, the extraction process can often leave a lot of compounds behind."

  Arabinogalactan, one of the polysaccharide compounds left behind during extraction, may be an important indicator of echinacea's overall immune-system action. "We believe that echinacea works because several compounds work together in synergy, and so we think it's very important to have whole-plant echinacea, with all compounds intact, and not just standardized extract," says Franklin. The company is currently manufacturing and selling the type of echinacea - standardized to arabinogalactan - that did best in the clinical trial, in a line of tea and supplement products.

  For companies interested in commissioning their own research, whether "offensive" or "defensive," one resource is the University of Guelph's Human Nutraceutical Research Unit (www.uoguelph.ca/hnru), which offers assistance with determining the feasibility of human trials and with carrying out double-blind, placebo-controlled research, including study design, capsule preparation, statistical analysis and a written report. Cost is based on the length of the study, the number of subjects and the particular biochemical parameters measured.

  To validate assertions about particular ingredients or products, many studies eventually culminate in the submission of a claim to the FDA. For example, according to Jane Crowther, sales and technology manager for Reedville, VA-based Omega Protein, "an omega-3 health-claim task force was formed several months ago, consisting of two dietary-supplement industry trade associations, a fishing-industry trade association, and omega-3 manufacturers."

  Omega Protein is no stranger to dealing with the FDA, as it happens. Its omega-3-containing refined-oil ingredient made from menhaden, a herring-like fish, has been approved by the FDA at certain levels for use as a food ingredient. That approval process, says Crowther, was in process for 15 years.

  The current omega-3 health-claim task force has submitted its clinical-study evidence to the FDA, an action that will result in a health claim or a structure-function claim. "We hope to receive input from the FDA at some point this year," says Crowther. "Then, the next step will be for the FDA to accept comments and hold a public forum."

  Without a doubt, it's an attainable goal for companies to effectively connect health studies with R&D. When the outcome of such connections is a food, beverage or ingredient that could make us all healthier humans, the trials and testing it takes are indeed well rewarded.

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