James Giese

As products move down the continuum from pharmaceuticals to dietary supplements to nutraceuticals to fortified foods to healthful foods, scientists are working to determine the mechanisms behind the effective folk medicine and to enlarge the concept of healthy eating. Smart researchers and marketers no longer consider healthful foods as a single category, but as a number of product categories that are representative of a variety of mechanisms that improve or preserve health.

Research Trends in Healthful Foods

The research that leads to knowledge about “healthy foods” and how to provide healthier ones proceeds along several fronts:

Clinical trials that determine which food components have effects on the well-being of individuals. Such clinical trials come in many forms. Some could be classified as feeding studies, on either laboratory animals or humans, and those may proceed on healthy volunteers or people with well-defined illnesses. They may be broad in scope, or very narrow, measuring the effect of a single component on a carefully defined parameter. Trials of this type become a part of the “preponderance of evidence” used for approving health label statements.

Research leading to identification of sources of nutrients, ways to improve the sources of these nutrients, characterizing them as active ingredients, and methods of refining and purifying them.

Research and engineering required to provide products, develop specifications for individual components, and apply these active ingredients in products that are acceptable to consumers.

This article presents some examples of the research behind products and processes that help develop foods with the special characteristics that improve, treat, or prevent disease to improve the longer lives that consumers can expect. This, of course, is the key—research by the World Health Organization noted that the differences between life expectancy and healthy life expectancy can be large, and depend on a variety of factors. In the United States, for instance, the healthy life expectancy is about 70 years, while life expectancy is considerably higher. Prosperous countries can expect their citizens to spend about 9% of their lives coping with chronic illness and disability. In countries where there are other problems, such as high rates of tuberculosis, HIV, malaria, and other diseases, life expectancy is shorter, and healthy life expectancy is still shorter. To the extent possible, knowledge about improvement of healthy life through diet is essential to the well-being of consumers and the economic status of countries.

The following are some of the current trends in the research being done in companies, universities, and government agencies that will contribute to better diets. Often, findings by clinical nutritionists trigger research into agronomic methods, food processing methods, and marketing of specific foods and components.

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Altering Meat, Milk, and Eggs through Animal Feeding
Meat, milk, and eggs are important parts of the human diet. While they rest near the “top” of the U.S. Dept. of Agriculture’s Food Guide Pyramid, they are very popular elements, and many people eat more of these products than are recommended. A promising method of changing the composition of animal based food products is by altering the feeding regimen of the food-producing animals.

In a paper presented at the 2000 IFT Annual Meeting, a group of researchers at Iowa State University looked at the influence of conjugated linoleic acid (CLA) and soy oil supplements in cattle rations on the CLA and fatty-acid composition of yogurt. They found that the supplementation of CLA and soy oil into the diets of cows can alter the nutritional quality of dairy products through the increase in CLA content and decrease in saturated fatty acid content.

Diets with CLA (1%, as fed) added, as the free acid or the calcium salt, to a control diet or to a diet supplemented with soy oil (5%, as fed) were fed to Holstein cows for 4 weeks. Processing the milk into yogurt and storage of the yogurt for 7 days did not affect the CLA content or percentage of individual fatty acids. The addition of CLA to the control diet increased the CLA content from 4.0 mg/100 g of fat to 9.2 mg/100 g of fat. Supplementation with soy oil and soy oil plus CLA increased the CLA content to 10.3 and 11.1 mg/100 of fat, respectively. Saturated fatty acid contents were reduced from 73% to 60% through the addition of CLA and to 45–48% through the addition of soy oil, with or without CLA, to the diets. The calcium salts of CLA were less effective than free CLA in increasing CLA content.

A number of papers have been published over the past several years, exploring the interaction between CLA and various diseases in animal studies. While the preponderance of evidence isn’t clear enough for the Food and Drug Administration to approve health claims based on the content of CLA in foods, there is growing evidence that it has some positive effects.

Researchers in the Animal Science Dept. at the University of Connecticut looked at the effect of dietary alpha-tocopherol supplementation on color and lipid stability in pork. Since myoglobin and lipid oxidation are major causes of quality deterioration in fresh pork, a process to enhance color and lipid stability would prove valuable to the pork industry, given the current trend of centralized packaging and distribution to retail markets. The researchers wanted to determine the effects of dietary alpha-tocopherol supplementation on color and lipid stability in ground pork and loin chops stored in modified-atmosphere packaging (MAP). They fed pigs diets that contained 48 or 170 mg of alpha-tocopherol acetate/kg of feed for 6 weeks prior to slaughter. They found that alpha-tocopherol supplementation reduced TBARS formation in fresh and salted pork but had no significant impact on color.

In another paper from the 2000 IFT Annual Meeting, Clemson University researchers looked at the effects of selected experimental diets for chickens on functional and chemical characteristics of egg albumen protein. Biosolids produced from broiler industry waste containing high nitrogen content is under study for use as an ingredient for chicken diets. However, effects on egg albumen produced from birds fed such diets is not well documented. A study was conducted to determine effects of such diets on egg albumen produced from treated hens. Functional properties of the eggs were similar to those of control eggs, but there were significant effects (P < 0.05) on content of selected amino acids among the albumens of eggs from differing strains of hens fed experimental diets, particularly glycine, valine, isoleucine, leucine, phenylalanine, histidine, and lysine. These results suggest that protein quality of albumen from differing strains may be affected to various degrees by these experimental diets.

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Several U.S. patents have been granted for methods that produce meat and egg products with enhanced nutritional quality by feeding the animals various dietary supplements:

Pilgrim’s Pride Corp., Pittsburgh, Tex., was issued U.S. patent 6,103,276 relating to the use of livestock feed compositions to produce eggs and meat of improved nutritional quality. The main example was the use of feed compositions with flaxseed, dietary grit, menhaden oil, soybean oil, and vitamin E to produce chicken eggs with improved essential fatty acid and vitamin E contents. The eggs were comparable in flavor to control eggs in taste tests, and there was no reduction in egg production.

According to this patent, in response to the decreased consumption and higher cost of obtaining fish with essential omega-6 and omega-3 fatty acids and vitamin E, health professionals have recommended the development and production of low-fat foods rich in these important nutrients. This patent describes a method for modifying poultry feeding practices, which leads to food products with improved nutritional quality. Unlike other previous methods to do the same thing, this method combines the use of whole flaxseed and grit, which promotes the grinding of flaxseed in vivo, to protect the essential fats from oxidation. The researchers claim to have increased the ability to produce food products with high levels of essential fatty acids (omega-3 and omega-6) without reducing production and without requiring increased dietary supplementation costs and procedures.

Another technology, the Egcel™ technology from DCV Inc., Wilmington, Del., has been used to produce nutritional supplements and functional foods. The proprietary technology, described by Don Pszczola in his Ingredients column in the March 1999 issue of Food Technology, allows for the commercial-scale production of specific antibodies and immunoregulatory factors, based on the vaccination of hens. Hyperimmunizing hens with inactivated multivalent bacterial vaccines results in the production of eggs containing antibodies against specific antigens, along with active, low-molecular-weight products with immunoregulatory properties. The products developed from this technology are said by the manufacturer to be considered GRAS in the U.S. The eggs and egg products contain factors effective for controlling cholesterol in serum and lipids in warm-blooded animals. These factors have beneficial effects on the vascular system by lowering or maintaining the levels of serum cholesterol and lipid deposits in animals consuming the eggs or egg products.

Animals containing more muscle and less fat are a major goal of food processors. There have been various methods for increasing muscle protein and reducing fat in animals. One of the more recent methods is described in U.S. patent 6,086,878. It consists of administering to the animal a composition including an antibody to neutralize the gastrointestinal neuro-modulator.

Improving Foods with Antioxidants 
A technology has been developed by Agritope, Inc., Portland, Ore., that makes possible the creation of novel plant varieties containing increased levels of naturally occurring phytochemicals that can be used in the formulation of health-promoting foods. Called MetaGene Metabolic Genomics Technology, it reportedly facilitates the rapid identification of the specific genes that regulate the levels of such phytochemicals as carotenoids, lycopene, flavonoids, isoflavones, vitamins, folic acid, and various elements and minerals.

In the first months of the program, scientists have used the technology to identify tomato lines with distinct properties, providing a direct link from these phytochemicals to the genes responsible for their production in a model plant, a dwarf tomato variety called Micro-Tom.

Tomato was selected for this platform because it possesses a wide array of phytochemicals at low levels, is extensively studied genetically, and is an excellent model for many other crops.

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Micro-Tom, originally developed at the University of Florida, is a true dwarf tomato and can be rapidly propagated at high density, making the generation of the botanical library extremely efficient. Patent applications on the technology have been filed, and the company plans to develop an extensive botanical library with robust databases to create a very powerful genomic source.

Currently, a botanical library of more than 5,000 lines has been produced for nutraceutical analyses. The company plans to generate more than 200,000 lines over the next several years. In addition to screening for increased levels of nutraceuticals, the botanical library can be used to screen for such new products as drugs, therapeutics, antimicrobial compounds, and colorants.

The utility of such a program may have great potential, as about 25% of all human therapeutic compounds are of plant origin. In recent years, there has been an increased awareness of the potential that natural compounds in plants may have in the prevention and treatment of diseases such as cancer, Alzheimer’s disease, diabetes, and cardiovascular disease. However, pharmaceutical companies have been downplaying the use of germplasm libraries in recent years, favoring the use of the information from the Human Genome Project to design specific drugs to repair functions.

Agritope is a genomics and biotechnology company that develops improved plant products and provides technology to the agricultural industry. Its fruit and vegetable division specializes in the development of improved fruit, vegetable, and flower varieties. Agrinomics LLC, its 50%-owned joint venture with Aventis CropScience, conducts a research, development, and commercialization program in the field of plant functional genomics.

Certain antioxidants, particularly lutein and zeaxanthin, found in spinach and other deep-green vegetables, are associated with a substantially reduced risk of developing macular degeneration. Protective antioxidants reduce the formation of radicals and reactive oxygen by decomposition of hydrogen peroxide without generating radicals, by quenching active singlet oxygen, and by trapping and quenching radicals before they reach a cellular target. An increased intake of the carotenoids lutein and zeaxanthin carotenoids has been found to be protective against macular degeneration. High blood levels of antioxidant vitamins C and E have also been shown to be protective against macular degeneration.

Lutein is being added to a variety of foods, and current research is being done to improve the bioavailability of lutein and other antioxidant materials. U.S. patent 6,075,058, assigned to Tufts University, discusses improved bioavailability without adding large quantities of foods. Lutein and zeaxanthin are mixed with olive oil, egg yolk phospholipid, cholesterol, and alpha-tocopherol and dispersed as an emulsion in saline solution. This mixture is then administered as a dietary supplement, and allows efficient uptake of the carotenoids into the bloodstream.

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Enhancing Mineral and Amino Acid Contents
Dairy researchers are focusing on ways to separate proteins and minerals in whey which can then be used for their health-promoting properties. With ion-exchange methods, whey proteins can be separated more thoroughly than previously possible, and by achieving this, researchers can take advantage of the proteins’ special biological and physical functions, especially in nutraceutical products.

Scientists at the University of Wisconsin-Madison, as well as other universities and companies, have separated and characterized several valuable proteins. One whey protein separated by an ion-exchange process is glycomacropeptide. In the U.S., one in 10,000 babies is reportedly born with a genetic disorder called phenylketonuria (PKU)—the inability to digest the amino acid phenylalanine. Babies born with PKU must follow a low-protein diet for the first few months of life. Glycomacropeptide is special in that it is missing this amino acid, making it a potentially rich source of protein for special diets.

Other whey proteins isolated include alpha-lactalbumin—a calcium-binding protein which enhances calcium absorption and remains clear when heated to pasteurization temperatures—and lactoferrin—an iron-binding protein which, when added to infant formula, helps babies absorb more iron from the formula and enhances the body’s ability to fight infection. Alpha-lactalbumin and lacto-ferrin are being produced and sold by companies that specialize in milk protein development, including Davisco and Glambia.

Researchers are looking at other health areas which may benefit from the use of whey proteins. For example, scientists at the Minnesota-South Dakota Dairy Foods Research Center discovered that the growth of a special biotherapeutic agent in whey may prove to be an effective and natural solution for gastric control.

Bacterial infection within the stomach caused by Helicobacter pylori is believed to lead to ulcers in the stomach lining or duodenum. Fermented whey was selected as the medium to grow bifidobacteria that would produce antimicrobials effective in the inhibition of H. pylori. Also, acetic and lactic acids, both of which are found with bifidobacteria in fermented cheese whey, contribute to the beneficial health effects. Although further work is required, researchers believe that in the future fermented whey could be used as a liquid ingredient in dairy products such as yogurt or in a beverage system. It is also possible that the fermented whey could be spray dried and still maintain its beneficial effects.

An enzymatically synthesized L-theanine, the primary amino acid found in green tea, was named Best New Product of 2000 at NutraCon. Called Suntheanine™, the product was developed by Taiyo Kagaku Co., Ltd., of Japan. The award—which recognizes scientific breakthroughs that can lead to the creation of safe, effective, useful products in the area of health—was based on research demonstrating the relaxation effects of the amino acid without inducing drowsiness. Such relaxation effects are characterized by the generation of alpha waves in the brain. In general, animals generate very weak electric pulses on the surface of the brain which are called brain waves. These brain waves are classified into four types—alpha, beta, delta, and theta—based on mental conditions. Generation of alpha waves is considered to be an index of relaxation.

In human subjects, alpha waves were generated on the occipital and parietal regions of the brain surface within 40 min after oral administration of 50–200 mg of theanine, signifying relaxation without causing drowsiness.

Studies have also shown that in addition to its relaxation effects, L-theanine has the ability to control blood pressure within normal healthy ranges and the ability to control the irritability effects caused by caffeine. For example, in hypertensive rats, the amino acid decreased blood pressure significantly.

The product is highly soluble in water and is stable at acidic and neutral pH when exposed to sterilization temperatures. According to the manufacturer, the product offers particular potential for designing foods and medical foods targeting relaxation and the reduction of stress.

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Presently, more than 50 food products containing the amino acid are being sold in Japan. In 1999, it was introduced into European markets. In the U.S., it has dietary supplement status, and the first products will enter the market in 2000. Also, its approval as a food additive in the U.S. is currently being sought. In addition to its award at NutraCon, it received the Food Ingredient Research Award at Food Ingredients Europe in 1998.

Taiyo Kagaku Co. received IFT’s 2000 Food Technology Industrial Achievement Award for the launching and commercialization of decaffeinated green tea polyphenols/catechins (Sunphenon® DCF-1). Polyphenols from green tea extracts are said to have various biochemical and physiological activities, including antioxidant, antimicrobial, and antiviral abilities, as well as anticaries and deodorant effects. Because green tea leaves contain relatively high levels of caffeine which can cause irritation of the gastrointestinal tract and sleeplessness in some people, it is helpful that caffeine be removed when green tea extract is used as material for beverages, confections, health foods, supplements, and other functional products.The manufacturer is represented in the U.S. by Taiyo International, Edina, Minn.

A nutrition delivery system using a special technology for dispersing insoluble iron in liquid formulations has been developed by Taiyo Kagaku Co. Called SunActive Fe, the product, a preparation of ferric pyrophosphate and emulsifiers, is said to offer superior functionality over conventional systems. It earned the Most Innovative Food Ingredient Bronze Award at Food Ingredients Europe in 1999.

According to the manufacturer, this product disperses insoluble iron in liquid formulations without any precipitation. The product has no unpleasant iron flavor or taste, and does not affect the formulation’s final flavor.

In comparison to other products (ferric pyrophosphate, sodium ferrous citrate, and ferrous sulfate), the system is claimed to be the most stable iron source in liquid form. At 121°C, 20 min, it is heat stable, did not turn to a brownish color, and exhibited no iron separation. Furthermore, it was stable when formulated into products containing high salt or sugar concentration. Other characteristics include high bioavailability, sustained release of iron, and mild on the stomach.

Developed specifically for the dairy and beverage industry, the system has been used in a variety of products in Japan, including an iron-fortified yogurt (1.5 mg of iron); a vitamin, mineral, and amino acid beverage; a yogurt drink delivering 4 mg of iron per serving; and an iron fortified milk providing 1.5 mg/100 mL.

The knowledge that many Americans consume less calcium than the recommended dietary allowances, along with the clear threat of osteoporosis as consumers age, has unleashed a lot of interest in bioavailable forms of calcium and combinations that make calcium easier to consume without increasing the fat content of the diet. The Procter & Gamble Co., Cincinnati, Ohio, has done a great deal of work on bioavailability of calcium, and has licensed some of the combinations to juice processors.

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Exploring the Role of Phytoestrogens
Isoflavones are produced by numerous legumes and grasses, including many plants commonly consumed by humans and livestock. Soy isoflavones include compounds such as daidzin, genistin, daidzein, and genistein. It has recently been recognized that isoflavones contained in vegetable proteins may have a detrimental impact on mammals that consume the vegetable protein. The concentration of isoflavones in plant protein isolates or concentrates, such as soy protein isolates, can be as high as 3,000 μg/g of protein. Isoflavones also provide the bitter or “beany” taste to vegetable proteins, may reduce the bioavailability of essential minerals, and may influence the nutritional value of proteins.

In contrast to the negative aspects of isoflavones, it has been suggested that isoflavones may inhibit the growth of human cancer cells. Estrogens have two opposing effects on cancer, depending on dosage. Large doses inhibit breast cancer tumor development, while small doses seem to promote tumor growth. This duality extends to phytoestrogens or isoflavones. Isoflavones may stimulate or inhibit tumor growth.

One mechanism by which isoflavones may manifest their anti-tumor effect is by blocking estrogen receptors and uncoupling receptor-mediated response. Thus, the ability of endogenous estrogens to support tumor growth would be reduced. There is also indirect, demographic support for an isoflavone-mediated reduction in cancers of hormone-responsive tissues, from the observation that women in countries whose citizens consume primarily vegetarian diets have a lower incidence of breast cancer than women in countries whose citizens eat more meat. An additional beneficial effect of isoflavones is alleviation of vasomotor symptoms in menopausal women. The Chinese have historically used herbal medicine to treat “hot flashes.”

Soy protein consumption has been linked with reduced risk of heart disease, partly because of the antioxidant effect of some of the phytochemicals, and partly because of fat reduction. Recent work suggests that soy isoflavones may assist in reducing oxidation of low-density lipoproteins. If the verdict is that isoflavones have a place in healthy foods, a question of dosage is appropriate. If additional isoflavones would be useful in soy, isoflavone concentration can be increased either by bioengineering or by selective breeding. Knowledge of the soy genome and the availability of germplasm banks can help. Another way of getting more isoflavone in a specific soy protein is by isolating and concentrating the isoflavones from plant material, and adding the concentrate to ordinary soy product.

Ion-exchange technology has been known for a great number of years, and has been used to isolate phytochemicals. Recent U.S. patent 6,020,471, assigned to Abbott Laboratories, Abbott Park, Ill., uses an anion-exchange resin, which separates isoflavones using an alcohol or organic solvent as a release agent. A plant protein slurry is run through the column, and can be homogenized or heated prior to ion exchange.

Novogen, Inc., Wilmington, Del., was granted U.S. patent 6,004,558 for the preparation of therapeutic extracts of leguminous plants from which the isoflavones genistein, daidzein, formononetin, and biochanin and/or their glycosides have been removed. The patent also relates to therapeutic uses of such extracts in the treatment, prophylaxis, amelioration of, or defense against a variety of cancers. The patent was based on International Patent Application PCT/AU93/00230, which describes isoflavone-containing extracts of a plant, such as legumes and clovers, and therapeutic uses for such isoflavone containing extracts. The isoflavone extracts described contain genistein, daidzein, formononetin, and biochanin.

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An isoflavone extract prepared according to the patent produced major degenerative changes (including apoptosis) as shown by a prostatectomy specimen surgically removed from a patient with moderately high-grade adenocarcinoma. The inventors claim that extracts of isoflavone-containing plants, such as soy or clover, from which genistein, daidzein, formononetin, and biochanin have been removed have significant anti-cancer activity.

But there are other methods that can be added to ion exchange to improve the efficiency of increasing isoflavones in soy protein, or removing them from soy products to be used alone or combined with other compounds. Researchers from Archer Daniels Midland, Decatur, Ill., found that temperature-sensitive differential solubilities could be used to separate the fractions from a water-based soy molasses or soy whey feed stream. The heated feed stream is passed through an ultrafiltration membrane with a cutoff that selects certain sizes of isoflavone molecules. By using the specific temperature that separates the specific isoflavone, the ultrafiltration membrane concentrates the solids, which are then adsorbed by resins in a chromotography column. The output stream from the columns can be spray dried, centrifuged, or filtered to produce a concentrated form of the specific isoflavone needed. The process is disclosed in U.S. patent 6,033,714.

Protein Technologies International, St. Louis, Mo., has developed methods for recovery of isoflavones by converting the isoflavones to isoflavone glucosides and recovering the glucosides (U.S. patent 6,083,553) and by using an extractant with a pH above the isoelectric point of the protein material (U.S. patent 6,015,785). U.S. patent 5,994,508 uses pH adjustment to concentrate the isoflavones, then uses cool temperatures to separate the specific proteins.

What’s on the Horizon 
Research trends are pretty clear in the area of healthy foods. Determining which compounds in foodstuffs are active ingredients, how the activity produces a result, and how to characterize and define the active ingredient precedes the work that determines how to separate, enhance, and purify the compound. All of the steps are important.

Universities are more likely to perform the first three activities, and companies usually work on the engineering and development steps, either as an inhouse activity or in concert with university or government groups.

But there is more to healthy foods than moving nutraceuticals into the mainstream. On the horizon is research that will help us understand the role of components so that foods are formulated to maximize positive vitamin and mineral interactions; modify rations to produce eggs, milk, and meat that balance human nutritional needs; and learn about the effect of altering the composition of soil to produce improved fruits, grains, and vegetables.