We are increasingly bombarded with information on how diet and lifestyle affect our health. A very recent report suggested that French fry consumption at the age of only five increases the risk of breast cancer in middle-aged women. Clearly, we could be digging our graves with our teeth, perhaps unknowingly, from a very early age. Some recommendations, for example, "stop smoking," "eat less fat" or "get more exercise," are easy to understand, if not always easy to act upon. More confusing are the numerous reports concerning potential health beneficial effects of components in our diets. Such reports are now commonplace on both TV and radio - "researchers at this or that institute report that chemicals present in green tea, grapes, broccoli, etc., have the potential to improve cardiovascular health, reduce cancer risk, etc., etc." Often, these reports seem to come around in cycles, and it is not obvious whether a true scientific breakthrough has been made, or whether CNN or Fox have simply decided that cardiovascular disease is going to be this month's health focus. Stories such as "chemicals in dark chocolate are good for your health" will always grab viewer attention!

What is the scientific basis for these various claims linking specific chemicals in our diet to long-term health benefits? To de-mystify what is a confusing area, and not just for non-specialists, some simple definitions (shown in bold type in the paragraphs below) may help. All plants, including the crops that form an important part of our diets, contain chemicals called natural products, also known as secondary metabolites or phytochemicals. These are not the simple chemicals such as sugars, fats or amino acids, that all living organisms require for their cells to grow and divide. Rather, they are produced to protect the stationary plant from physical and biological insults such as high UV light, insect and animal consumption or attack by pathogenic microbes. Collectively, plants produce about 200,000 different natural products, and many of these interact in some way or other with systems in our bodies.

Natural products can act as drugs or be chemically modified to yield drugs. Well-known examples of this include the anticancer drug taxol from Pacific yew, morphine and codeine from opium poppy or aspirin from willow. Other natural products, such as strychnine and many non-protein amino acids, are highly toxic to animals and humans and are classed as poisons. Natural products found in our diets that lack the acute biological effects of drugs, but that may have long-term health benefits if consumed in reasonable amounts over long periods, often are called nutraceuticals. This is a confusing term, since, by analogy with the term pharmaceutical, it might appear to indicate a chemical that acts as a drug, but which is delivered through the diet. Such chemicals are indeed found in many of the so-called dietary or nutritional supplements on sale in health food stores. In some cases, these supplements contain compounds which, for all intents and purposes, act as drugs (for example, the anti-depressant chemicals in St. John's wort) and may indeed be toxic if taken in large quantities or over prolonged periods. "Natural" does not always mean safe, and the concept that "natural" remedies are "chemical free" is clearly ludicrous. Plants make powerful compounds (natural products) in order to protect themselves from their environment. That being said, many plant natural products do appear to lack human toxicity, and such chemicals are indeed common components of a normal diet; increasing our consumption of such chemicals, through food or dietary supplements, may be beneficial to our health, for the reasons outlined below.

The term antioxidant now commonly appears on food labels. Although long-term health-beneficial natural products have broadly different types of chemical structures, many of them are able to help remove active oxygen compounds, potentially harmful products generated during a number of natural processes in the body and associated with aging of cells and tissues. Failure to remove active oxygen compounds can, over the long term, lead to cardiovascular disease, cancer and various neurodegenerative disorders. Antioxidant activity may be the most important biological activity of health-protective plant natural products. Such antioxidants are abundant in fresh fruits, vegetables and nuts. The flavonoids represent a major class of antioxidant natural products that are found, at various levels, in all plants. These chemicals exist as different structural types. The condensed tannins are composed of linked flavonoid units and are abundant in tea, grape, barley, sorghum and various berries such as cranberry. In addition to providing general antioxidant protection, condensed tannins have been implicated as beneficial for urinary tract health, beauty (skin tone and hair retention) and sexual performance. The isoflavones are a special type of flavonoid found mostly in leguminous plants such as soybean, alfalfa or chickpeas. These chemicals have structures quite similar to that of estradiol, a natural mammalian estrogen, and can bind to human estrogen receptors. Isoflavones, and the chemically related lignans found in grains such as flaxseed, are therefore sometimes called phytoestrogens. Isoflavones are sold in dietary supplements for perceived benefits associated with, among others, reduction of hormone-dependent (e.g. breast and prostate) cancer risk and alleviation of post-menopausal conditions such as osteoporosis and hot flashes.

So, what does all this mean for agriculture? People generally want to lead longer, healthier lives, but often find it difficult to change age-old habits of poor diet and physical inactivity. Commonly consumed crop plants are potential delivery vehicles for the chemicals that might help people attain their health goals. However, some of these chemicals are present in our major dietary crops at low levels (the many years of crop breeding to reduce the levels of toxic chemicals found in the progenitor wild plants has sometimes resulted in the loss of beneficial chemicals at the same time) or are, at present, limited to particular plant types. For example, the major dietary sources of isoflavones are soy products such as tofu. Sales of such products are increasing in the western world (they are common dietary components in Asia where they have been directly linked to decreased cancer risk), but they may never become truly popular. Scientists in the Plant Biology Division at the Noble Foundation have discovered the genes involved in isoflavone and condensed tannin production in plants and, using genetic engineering, have been able to introduce these chemicals, and other flavonoids, into plants or plant tissues that do not naturally produce them. The only change to the plant is the introduced isoflavone or tannin. This opens up the possibility of converting your favorite fruit or vegetable into a delivery vehicle for health-beneficial phytochemicals, with added value to the crop for the farmer.

The technology is in place to make "designer foods" a reality. What is still required, however, is a better understanding of the effects of long-term dietary exposure of the human system to phytochemicals. Much of the research to date has relied on two types of studies - feeding pure phytochemicals or crude chemical extracts to animals or monitoring health trends in human populations linked to dietary surveys. In spite of many hundreds of scientific publications based on these approaches, questions concerning efficacy and safety remain. The genetically modified plants produced at the Noble Foundation provide an excellent tool for monitoring the effects of introduced phytochemicals in a true dietary context, since the only variable is the phytochemical, and it is delivered in the only biologically appropriate form, namely as a part of the plant. Such studies, initially using animal models, should, in the future, result in the establishment of "recommended daily doses" of phytochemicals, such as are now provided for various vitamins. These values will serve as a benchmark for the levels that need to be produced in crop plants in order for a dietary benefit to be claimed. In the future, improved diagnostic and genetic tests may result in specific dietary recommendations from health care providers based on phytochemical intake. Such plant-based preventative medicine will rely on agriculture, either for delivering "health-enhanced" crops for direct consumption or for providing the material for chemical extraction of phytochemicals for delivery in dietary supplements.

What about Oklahoma agriculture? There is no reason why our region should not be at the forefront of the application of biotechnology to agriculture, but livestock, rather than crops, is the major source of income for our farmers and ranchers. Not surprisingly, however, plant natural products affect livestock as well as humans. Indeed, isoflavones were first discovered in clovers in the 1940s based on their ability to interfere with reproduction in sheep. Condensed tannins have potential beneficial effects on both animal performance and environmental pollution. By binding to dietary plant proteins in the rumen, they reduce the production of methane gas, thereby preventing pasture bloat, and, at the same time, allow more plant protein to exit the rumen, thereby reducing urinary nitrogen excretion and increasing animal weight gain, milk production or wool yield. As part of a program of the Consortium for Alfalfa Improvement, an association of scientists at the Noble Foundation, the U.S. Dairy and Forage Research Center at Madison, Wis., and Forage Genetics International of West Salem, Wis., Noble Foundation Plant Biology Division scientists are introducing genes for condensed tannin accumulation into alfalfa for forage quality improvement, with anticipated benefits for the cattle industry.

In recognition of the increasingly realized importance and economic value of plant natural product research, the Noble Foundation has recently begun a $4 million expansion of the Plant Biology Division's Lablink building, to create a new Center for Plant Natural Product and Metabolomics Research. The center will contain state-of the-art equipment for the isolation and characterization of plant natural products, with particular emphasis on mass spectrometry approaches for profiling large numbers of plant chemicals simultaneously. These technologies will be coupled with the latest molecular genetic approaches for isolating and modifying genes involved in natural product formation and transferring them to various target plant species. Strategic collaborations with biomedical groups outside the Noble Foundation will evaluate compounds and engineered plants to assess their potential utility for dietary disease prevention. Human disease prevention will be only one component of the center's focus, which remains essentially agricultural. Important projects will continue to address forage quality in legumes and grasses, plant protection through engineering of natural antimicrobial compounds (for example, to combat cotton root rot disease of alfalfa) and the use of agronomically viable plants to produce novel pharmaceutical compounds. This new center will act as a catalyst for economic development of natural product-based technologies to improve the competitiveness and profitability of the state's agriculture industry.

Dr. Rick Dixon is director of the Plant Biology Division at the Noble Foundation.