One of the first questions asked in my college biochemistry class was "What is the difference between a drug and a poison?" Many answers were offered...but only one was correct, "the dose." After years of working with herbs and their regulatory status as dietary ingredients, another question arose, "What then is the difference between a food and a medicine?" There is no easy answer, even as this question becomes more pertinent with the explosion of functional foods.

In herbal medicine, often it is a plant's defensive or secondary compounds that make it useful therapeutically. These same secondary compounds also often make exotic foods unpalatable for mainstream tastes. However, as the functional food area grows, nature's bounty of traditionally used exotic foods will be a treasure chest for new product development.

Untapped Exotic Ingredients

Today, the functional food market is held back by issues that will determine how the blurring of foods and dietary supplements is regulated. The question of an herb's GRAS status has come to the forefront. Although there are experts who have sided with the Center for Science in the Public Interest (CSPI), like Dr. Varro Tyler who believe herbs are medicines and should not be regulated as GRAS, other experts take a different view.

For example, author Timothy Johns (Ph.D.) proposes that use of physiologically active herbs has spanned from the origins of the human diet. In his book, With Bitter Herbs They Shall Eat It ¹, Johns says "As our species has adapted to the use of plants, plants have become part of our internal ecology." In today's society of milk and honey, he adds "At a time when many people are able to indulge in foods their ancestors usually only wished for, it is clear that we were designed not for the reward, but for the struggle." Basically, we require a more traditional diet, rich in plants with secondary compounds.

Even as mainstream foods increasingly "reward" our palate with high fat, highly refined products, a backlash is occurring in the health food industry that manifests itself in the functional foods arena. The very ingredients that have made exotic foods undesirable for mainstream food development may be ones that make them all-star candidates as functional foods.

Consider the expanding popularity of gourmet lettuce greens. Bland iceberg lettuce had replaced bitter-tasting plants that were once part of more traditional diets. However, as consumers seek more variety, bitter lettuces have been re-popularized. Although not necessarily prized for their health attributes, these lettuces are superior nutritionally and have bitter compounds that may improve our digestion, and make them suitable companions to our daily meals. This is an example of our physiology being designed more for the "struggle" than for the "reward."

Other ingredients that blur the line between foods and dietary supplements include medicinal mushrooms, exotic fruits and roots. (See chart.)

Food as Traditional Medicine

Foods prescribed for health is a basis for traditional medicine systems across the globe. According to traditional Chinese medicine (TCM), the foundation of human health is based on the therapeutic use of foods.

Dr. Ira Goldrechrech, San Rafael, Calif., says that TCM advises the use of certain conventional foods, such as pork and fish, at certain times for human health maintenance. TCM also holds that adding certain herbs to food maintains human health. It could be argued that such herbs, long used in traditional food recipes, might be considered GRAS.

When visiting Laos a few years ago, I was in the field with some agronomists eating a traditional Lao meal. As we ate, a few of the Lao people would pick leaves from a plate of bitter tasting herbs sitting in the center of the table and swallow them along with their food. I was told that the herbs normally accompany meals and are eaten if a need was felt for health enhancement in an area for which the herb was known to be of benefit. None present were medical practitioners, yet they all knew which herb was good for what part of the body. Could these herbs be considered GRAS if the Lao, as part of their meal, have used them for thousands of years?

Global Exotic Functional Foods		Functionality and Traditional Use
Region	Food
Asia	Shiitake, (Lentinus edodes)other medicinal mushrooms properties.	A medicinal mushroom used in traditional Chinese medicine(TCM). Also popular as a food item in the U.S., research supports shiitake medicinal benefits including anti-tumor 3 Other medicinal mushrooms used as food include reishi and maitake.
	Sea Buckthorn (Hippophae rhamnoides)	Used for centuries in Europe and Asia, it exhibits a range of pharmacological activities: anti-inflammatory, antimicrobial, analgesic, and tissue-regeneration. Its fruits are nutritionally rich, and although primarily used in Europe in jams and jellies, they are gaining popularity for their medicinal uses.5
South America	Maca (Lepidium meyenii)	An Andean root crop used as a food staple in areas of Peru, it is also valued for its vitality and stamina-building benefits. Has recently gained attention for research supporting its aphrodisiac qualities.
	Guarana (Paullinea cupana)	IIt produces a red fruit high in caffeine content. Brazilians consume guarana popularly as a drink, and it is valued for its energy-giving properties. Today, guarana may be found in functional drink formulations and in dietary supplements for similar reasons.
Africa	Rooibos (Aspalathus linearis)	Used in South Africa and recently marketed in Europe and the U.S. as herbal tea. It has a unique flavor, is high in nutritional content, and claims to have numerous medicinal benefits, some of which may be due to its antioxidant content.7 Recent research at Rutgers confirms the antioxidant activity.
	Honeybush (Cyclopia spp.)	A native South African tea plant that is becoming popular for some of its functional benefits, such as promoting relaxation and gently relieving constipation. Recent work also shows this tea plant to exhibit antioxidant activity.
India	Garcinia (Garcinia cambogia)	Its fruit rind is used in traditional recipes in Indian and Ayervedic cooking. Popular in the U.S. for its use in weight loss due to its content of hydroxycitrate (HCA).
Europe	Hawthorn (Crataegus laevigata)	With fruit that look like tiny apples, it has a long history of use in foods, and for its therapeutic use in many ailments. Clinical studies support its heart-health promoting properties. Enjoys popularity as a dietary supplement in the U.S. and Europe.4
		Source: Kerry Hughes, EthnoPharm 4,5,6,7 See references at end of article.

R&D's Position on Mainstream Nutritionals

While the natural, nutritional products industry looks for opportunities with healthful ingredients in traditional uses outside the U.S., the 2001 Prepared Foods' R&D Survey queried manufacturers on their attitude toward more mainstream ingredients. The following results were obtained when R&D executives at food manufacturing companies were asked, "During the next two years, do you expect the following ingredient to become more or less important to the products for which you have R&D responsibility?"

--Claudia O'Donnell

R&D responding "more important" (%)
Ingredient	Nutritional companies	All Food companies
	(n=21)	(n=209)
Soy protein	67	43
Calcium	57	36
Vitamin E	52	29
Isoflavones	67	28
Omega 3	33	26
Beta-carotene	38	22
Probiotics	38	18
Green tea extracts	33	17
Whey protein	24	13
Oligosaccharides	38	13
Source: 2001 Prepared Foods R&D Survey; n=331

GRAS Status

On February 5, 2001, the FDA issued a letter formalizing its position on foods containing ingredients such as botanicals. (See the site.) The FDA expressed its concern that such ingredients are being added to conventional foods, but are not GRAS or approved food additives. An ingredient for functional food development must be either an approved food additive, or a GRAS substance, or one that has a likelihood of being declared GRAS.² The system of petitioning for GRAS status was modified in 1997 by including a notification process that is self-determining and does not require pre-approval. Companies can decide whether a food or food ingredient is GRAS based on either 1) scientific procedures, or 2) experience based on common use in foods.

With the first route, a company must provide scientific and safety evidence similar to the process for obtaining GRAS status for a food additive. With the second route, however, a company just needs to demonstrate that their ingredient has a substantial history of consumption for food use by a significant number of consumers.

GRAS notices are listed on the FDA website at: http://vm.cfsan.fda.gov/ ~rdb/opa-gras.html. One interesting example is the FDA's response to such a notice, Agency Response Letter GRAS Notice No. GRN 000013. In the letter, the agency responded with "no questions" (a positive response) for chrysanthemum and jellywort because there was "evidence of a history of consumption for food use." The FDA added that it was "aware that both chrysanthemum tea and the product 'Grass Jelly' made from jellywort have been consumed in China for at least one hundred years."

This is where the opportunity exists for product development. There are many "exotic foods" that exhibit functionality that may be determined as GRAS through common use in foods in other cultures. As consumers have been strong supporters of dietary supplements, they are sure to be even stronger supporters of products that exhibit functionality, but yet are as safe as common foods--as shown by centuries of human consumption.

SIDEBAR: Desperately Seeking Selenium

The typical American diet provides adults with 80 to 150 mcg of selenium per day--less than one half the amount considered optimal for the full protective potential of selenium, especially in cancer prevention. Thus, health professionals increasingly recommend extra dietary selenium supplementation.

In foods, selenium is primarily in the form of L(+) selenomethionine, a highly bioavailable form for both selenium and methionionine, an essential amino acid. In the 1970s, yeast with high selenomethionine levels became available for supplementation purposes. Today, yeast with 1,000 to 2,000 mcg selenium per g is on the market.

For more information on selenium forms, benefits, safety and regulatory status, see www.nutrasolutions.com or type "selenium yeast" in the search field at www.nutrasolutions.com/articles. See also Institut Rosell / Lallemand Inc. at www.lallemand.com.

References

1 Johns, T. 1990. With Bitter Herbs They Shall Eat It: Chemical Ecology and the Origins of Human Diet and Medicine. The University of Arizona Press, Tucson, Arizona.

2 Personal communications with Susan Brienza, Patton Boggs LLP, Denver, Colo.

3 Jones, K. 1998. Shiitake: a major medicinal mushroom. Alternative and Complementary Therapies. February: 53-59.

4 McKenna, D.J.; K. Hughes; and K. Jones (eds). 1998. (New edition in press.) Natural Dietary Supplements: A Desktop Reference. Institute for Natural Products Research: Marine on St. Croix, MN. www.naturalproducts.org

5 Li, T.S.C. 1999. "Sea Buckthorn: New Crop Opportunity." In: Janick, J. (ed.) Perspectives on New Crops and New Uses. ASHS Press: Alexandria, Virginia.

6 Zheng, B.L. et al. 2000. Effect of a lipidic extract from Lepidium meyenii on sexual behavior in mice and rats. Urology. 55: 598-602.

7 Joubert, E. and D. Ferreira. 1996. Antioxidants of rooibos tea--a possible explanation for its health promoting properties. The SA Journal of Food Science and Nutrition. 8(3): 79-83.