Cancer Preventive Foods and Ingredients

The National Cancer Institute's five year "Designer Foods" initiative will provide new insights into the links between diet and cancer and may generate an entirely new industry.

You ARE what you eat. Increasingly, we are learning the truth of that maxim. We have long known that every molecule in the human body originates from the diet, and that the absence of certain essential nutrients can create a predisposition to illness. However, we are only beginning to understand that many previously unappreciated components of our diet may prove important in preventing such chronic diseases as cancer (Pierson, 1992). Within the last decade, as research into the relationships between diet and cancer has proliferated, so, too, has the body of data from both epidemiological and animal studies that indicates vegetables, grains, and fruits may contain cancerpreventing substances.

In an effort to foster a greater understanding of how these substances may aid in cancer prevention, the National Cancer Institute's (NCI) Diet and Cancer Branch has recently embarked on a major initiative to study, assess, and develop experimental, or "designer" foods - processed foods that are supplemented with food ingredients naturally rich in cancerpreventing substances. To help administer this highly complex fiveyear project, the NCI has contracted with my firm Arthur D. Little, Inc., to provide technical support for the initiative.

Forging New Links

Over the past decade, specific relationships have been identified between dietary components and cancer (Bruce, 1987; Chen et al., 1988; Byers et al., 1990; Miller, 1990; Blot, 1991; WHO, 1991; Pierson, 1992; NAS, 1989). Heavy consumption of alcohol has been linked to higher incidences of cancers of the upper alimentary tract and liver. Diets high in fat appear to contribute to breast, pancreatic, and colorectal. cancers. At the same time, these studies have shown that fiber, vitamins A, C, and E, and numerous other substances appears to exhibit cancerpreventing properties.

Having identified these relationships, scientists are now seeking to forge the next links between diet and cancer: first, to determine more precisely which foods and ingredients alone and in combination- offer significant cancerpreventive properties; and, second, to actually design foods with enhanced levels of those substances.

Fig. 2 is a working list of close to 40 foods which have been indicated by animal and epidemiological studies as possibly possessing cancer-preventive properties. The hierarchical ranking is, at this point, empirical, and as new studies emerge these rankings may change. Additional studies, such as those included in the NCI Experimental Food Program, should help to identify more of these foods and clarify the relative importance of each.

To accomplish these goals, the NCI Experimental Food Program is focusing its efforts on phytochemicals. Technically, the term phytochemical refers to every naturally occurring chemical substance present in plants. For the purposes of the program, however, the NCI is studying only those phytochemicals that are biologically active. Usually these phytochemicals are present only in small amounts in such foods as vegetables, grains, and fruits.

Studies conducted over the past decade have indicated that approximately 14 classes of dietary phytochemicals are present in common foods (Fig. 3) and that such phytochemicals can interfere with and potentially block the biochemical pathways that lead to malignancy in animals. Therefore, the NCI study is intended -first and foremost- to provide an integrated scientific understanding of the roles these phytochemicals play in preventing cancer in mankind.

Roadblocks on the Path to Malignancy

While research has yet to determine every aspect of cancer development, we do know that tumor growth has two critical stages -initiation and promotion. A carcinogen can "initiate" or alter a cell, making it susceptible to cancerous growth. That growth does not occur, however, until one of several factors, called "promoters," acts on the altered cell. In breast cancer, the most common cause of cancer mortality in women, these factors ("promoters") include oxidative damage, the action of steroid hormones, and the action of certain kinds of prostaglandins (PGS). Fig. 4 is a highly simplified schematic illustrating how and at what stage certain phytochemicals can act to block the cancer promotion process, combatting the effects of certain carcinogens, initiators, and promoters.

Because foods are complex mixtures of various phytochemicals, studying them is a highly complex task. At present, the specific role of each phytochemical and the potential synergistic effects of different phytochemicals in the cancer prevention process are unknown. The intent of the NCI Experimental Food Program is to study the cancer-preventing properties of natural phytochemical combinations rather than to analyze the effect of specific phytochemicals. Nevertheless, existing data on the phytochemical composition of foods and their biological activity can serve as guidelines in the design and formulation of potential cancer-preventive foods. Similarly, changes that are known to occur in the chemical composition of foods during processing or through enzymatic action must also be taken into account.

Two foods included in the NCI study -licorice and garlic- help to illustrate the complexity of phytochemical composition and to explain why a detailed phytochemical mapping of each food being studied is a necessary prerequisite to additional investigation.

The phytochemicals recovered from licorice can be influenced by numerous factors (Zeng, et al, 1990). For instance, different varietal species of Chinese licorice root have been found to have wildly different phytochemical profiles. Even two licorice roots of the same variety, grown in different geographical regions in China can possess vastly different amounts and combinations of phytochemicals. Furthermore, extraction conditions and the solvents used in extraction can also dramatically influence the recovery of such important licorice root phytochemicals as coumarins and isoflavonoids.

The phytochemical composition of garlic is also changed when the clove is processed (Block, 1985). Raw garlic cloves contain the phytochemical allin. When crushed, the garlic's enzymes convert allin to allicin, which in turn can be converted to other allylic sulfur compounds and amino acids. Aqueous alcohol extraction and aging of the extract can, however, help convert the allicin into far less toxic phytochemicals such as diallylsufide, S-allyl-L-cysteine, and S-allylmercaptocysteine. The lower relative toxicity of these compounds- which retain their antimutagenic and antitumorigenic properties -make the aged garlic a more appropriate test food for increased levels of human consumption. Knowing the effects of these and other factors, the researchers involved in the NCI program must carefully identify and monitor the various foods selected for inclusion in the diverse studies.

Attacking Many Fronts

In order to address these and numerous other complexities within the program's five-year time frame, NCI has established four key areas, all of which are being implemented concurrently during the first years of the program. The four key areas will be addressed by the following studies:

- Phytochemical Compliance Markers. By analyzing phytochemicals in the food as well as in the biological fluid of study participant, these tests determine the degree to which those participating in clinical trials are complying with their dietary regimen.

- Nutritional Pharmacology. To further understand and elucidate the ways in which specific phytochemicals work to block the pathways that lead to certain cancers. These short-term dietary studies attempt to modulate the metabolism of healthy humans and enhance the detoxification of harmless medications.

- Food Safety. Because foods contain phytochemicals that are biologically active, they may also be toxic when consumed at higher than normal levels. These laboratory animal studies are intended to test for unexpected side effects that may arise when consumption levels are significantly increased.

- Pre-Clinical Knowledge Building. Studies, again using laboratory animals in order to determine toxicities, which attempt to identify synergies between various foods and ingredients. Are the properties of garlic and licorice, for instance, even more effective when combined than when the two foods operate alone?

As is typical of any research program, progress is continually monitored, assessed, and modified in order to meet the study's objectives. As currently conceived, the program will move forward on two main fronts. The first is to add new foods to the study until all key foodstuffs have received a preliminary evaluation. The second will consist of more intensive studies of those foods indicating greatest promise. During the first year of the program, six foods (garlic, licorice, soybeans, flax, umbelliferous vegetables, and citrus) were evaluated in 21 separate studies. As the program advances, intervention studies may be advisable, offering people at high risk of certain cancers the opportunity to eat foods designed to fend off the biological changes that lead to neoplasia.

Technical support will be provided by my firm throughout the five-year program. In this capacity, we will obtain, and develop as necessary, the various food needs of the program. We will also store, monitor, distribute, and coordinate the diverse activities of as many as 100 study sites over the life of the program. In addition, we will assist NCI in the selection, prioritization, procurement, and development of cancer-preventive designer foods, will aid in the preparation of Investigational New Drug Applications and Drug Master Files, and will summarize research results and disseminate those results and other relevant information to researchers at each site and around the world.

An interesting facet of the pro gram is the development of cancer-preventive designer foods enriched with naturally occurring phytochemicals but formulated to be stable, safe, and palatable. This is a challenging task for which my firm, with years of experience in product development and sensory evaluation research, is particularly well-suited.

A New Industry?

Although it will be many years before designer foods are stocked on supermarket shelves, the NCI's Experimental Food Program, if successful, will lead to a new generation of foods, which will cause the interface between food and drug to become increasingly transparent. The program may even spawn a new industry -foods for disease prevention. Such an industry has the potential to be much larger and broader than the vitamin industry and would offer consumers phytochemically enriched foods designed to prevent cancer and, possibly, other diseases as well. In the future, we may see the emergence of phytochemical soups, phytochemica processed meats, even phytochemical cocktails and ice cream. It is not inconceivable that foods that once contributed to illness and disease may be reconstructed in the next decade or two to offer significant health benefits.

References

Block, E. 1985. The chemistry of garlic and onions. Sci. Am. 252: 114-119.

Blot, W. 1991. Alcohol and cancer. Presented at Nutrition and Cancer Symposium in Atlanta, Ga., April 19, 1991.

Bruce, A. 1987. Dietary recommendations in cancer prevention. Ann. Clin. Res. 19: 313-320.
Byers, T., LaChance, P., Pierson, H. 1990. New directions: The diet-cancer link. Patient Care 24: 34-48.

Chen, L.H., Boissonneault, G.A., and Glauert, H.P. 1988. Vitamin C, Vitamin E and cancer (Review). Anticancer Res. 8: 739-748.

NAS. 1989. Diet and health: Implications for reducing chronic disease risk. National Academy of Sciences, Washington, D.C.

Miller, A.B. 1990. Diet and cancer (Review). Reviews in Oncology 29: 87-95.

Pierson, H. 1992. Diet as a factor in cancer and cancer prevention. Cancer Medicine. In press.

WHO, 1991. "Diet, Nutrition, and the Prevention of Chronic Diseases."

Zeng, L. Zhang, R., Weng, T., and Lou, 2.1990 Determination of nine flavonoids and conmarins in licorice root by high performance liquid chromatography. J. Chromatog. 513:247-254.