R&D Issues: GRAS Botanicals
But, isn't all food functional?” This often-asked question expresses the confusion felt by many in the food industry over the concept of “functional foods.” Even “empty calorie” food and beverages provide needed calories, if little else, to the human body. And, at the other extreme, more than a few plants have historical use not only as a food but for their medicinal benefits as well. (See Functional Foods…Back to the Future, PF, March 2001, p. 35.)
The question becomes less abstract as regulations strive to define what types of direct or implied claims, whether they be disease, structure-function, nutrient content or health, can be made for a product. Which claims are permitted are determined by the category that a product falls into, such as dietary supplements, over-the-counter pharmaceuticals, “conventional” or medical foods. Even the category in which a company positions its product can be controversial. Would PepsiCo's SoBe line with non-GRAS (generally recognized as safe) botanicals be more appropriately positioned as a dietary supplement than as a conventional beverage?
Food ingredients also face regulations that are more “artificial than natural” at times. That is, individual ingredients fall under broad, and as a result, sometimes arbitrary regulatory guidelines. Much time and expense are needed for individual components to navigate the regulatory pathway in order to make a health claim.
Psyllium (Plantago ovata or P. ispaghula) is one “medicinal botanical” for which the effort was made. It has traditionally been touted for its ability to assist with intestinal health, to relieve constipation and for high blood pressure. More recently, it's said to be of benefit in maintenance of cholesterol levels.1 In 1998, the FDA allowed certain psyllium-containing foods, such as breakfast cereal, to make the claim that it helped reduce the risk of heart disease.
A rich history of medicinal use exists for many other plant materials. A number of spices, herbs and flavoring compounds enjoy both a GRAS status and also a growing body of research that supports their disease-preventing abilities based on a number of known and theorized mechanisms.
The Importance of Antioxidants
The human body is in a constant battle to keep from aging. One aspect of aging occurs when lipid-containing biological systems, whether a manufactured food or a living organism, are oxidized.
When an oxygen free radical removes an electron from a fat molecule, a lipid free radical is formed, which, in turn, works to replace the electron by taking it from other molecules, including DNA. Rapidly replicating cells may not have time to repair damaged DNA before dividing and cancer can result. Oxidative stress leads to other diseases as well. For example, oxidized low-density lipoproteins are implicated in atherosclerosis.
Antioxidants, when present at low concentrations compared with that of an oxidizable substrate, significantly delay or prevent the oxidation of that substrate. GRAS plant extracts, such as rosemary oleoresin, are commonly added to preserve processed meats and other food products. The exact mechanism of how an antioxidant functions in the body is not always known, but research is beginning to show that many antioxidants acting synergistically are most optimal for health.
Flavor compounds that are good antioxidants include eugenol (the main flavoring in cloves and allspice), thymol (thyme and oregano) as well as vanillin and guaiacol. The antioxidant activity of various spice extracts, when quantified by an analytical test that compares the compound to Trolox, a vitamin E analogue, shows oregano (Origanum spp.) to be an excellent antioxidant with a Trolox equivalent mmol/l of almost 3. Thyme (Thymus vulgaris) and sage (Salvia officinalis) run about 2.5, cinnamon (Cinnamomum cassia) and rosemary (Rosemarinus officinalis) are at about 1.7 and nutmeg (Myristica fragrans) and black pepper (Piper nigrum) are at about 0.6.
Rosemary and sage contain carnosic acid that through oxidation reactions generates carnosol, rosemanol and other antioxidants. The antioxidants in rosemary and sage are unusually beneficial in that as they oxidize, the oxidation products rearrange to form new antioxidants. Although the exact mechanism is not known, rosemary extract and carnosol isolated from rosemary oleoresin have shown some anticancer activity when studied in skin and mammary cancer models.
Cancer PreventionTheories traditionally have focused on the ability of antioxidants to prevent the formation or to terminate free radicals as the main mechanism of action in cancer prevention. However, repair/replacement mechanisms may be as or more important than free radical mediation. Some of these recovery systems include:
- The activation
systems that remove foreign chemicals, such as
P-450 enzymes and glutathione-S-transferase;
- Inhibition of substances that form and/or activate carcinogens;
- Activation of DNA repair systems;
- Support for normal cell life cycle by assisting cells to properly divide.
Plant extracts have been tested for their anticarcinogenic or antitumorigenic activities in vitro (outside the body). The HL-60 test measures the ability of compounds to suppress the replication of a model tissue, Human Leukemia 60 cells. A compound's IC50 value is the concentration needed to obtain 50% of a particular effect, in this case, the spice extract concentration needed to inhibit 50% HL-60 cell growth. Very strong anti-tumorigenic activities have been found for many crude spice extracts. For example, the IC50 value for nutmeg is 3.52 ppm, 1.66 ppm for cinnamon, 1.24 ppm for thyme, 0.86 ppm for mint (Mentha spp.), 0.69 ppm for rosemary, 0.70 ppm sage (Salvia officinalis), 0.95 ppm for black pepper and only 0.45 ppm for basil (Ocimum basilicum).
In another study 4, HL-60 cells treated with the methanolic extract of Alpinia oxyphylla Miquel, a member of the ginger family used in oriental herbal medicine, significantly reduced the viability of the cancerous HL-60 cells as well as inhibited DNA synthesis.
The small intestine and the colon epithelial tissues have some of the most rapidly dividing cells in the body; however, cancer is 30 times more prevalent in the colon than in the small intestine. One thought is that intestinal bacteria convert dietary procarcinogens into carcinogens. Bile acids are deconjugated to produce secondary bile acids that act as tumor promoters. There is also some evidence that fecal bacteria generate superoxide free radicals that produce mutagens and genotoxins.
GRAS botanicals and extracts such as garlic and cinnamon and specific flavorful, volatile phenolic compounds such as eugenol, menthol and thymol exhibit bacteriostatic properties. Is it possible that they could inhibit the growth of high superoxide radical generating bacteria?
Other less striking health benefits associated with antimicrobial capabilities include anticariogenicity (dental cavity prevention) and the benefits associated with probiotic microbes that inhibit certain intestinal flora. Such benefits include increased nutrient absorption and/or utilization and enhanced immunity. Yet other researchers are investigating even farther ranging benefits, such as the insulin-potentiating effect associated with whole cinnamon spice.
It's often been said the world of pharmaceuticals and foods are blurring. To find yet another example of this, one may need to look no further than a home spice cabinet. NS
References:1 Leung AY, et al. 1996. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics, 2d ed. New York: John Wiley & Sons. P.427-9.
2 Pearson, D. et. al. 1997. Inhibition of Endothelial Cell-Mediated Oxidation of Low-Density Lipoprotein by Rosemary and Plant Phenolics, J. Agric. Food Chem. 45: 578-582.
3 Huang, M-T et al. 1994. Inhibition of Skin Tumorigenesis by Rosemary and Its Constituents Carnosol and Ursolic Acid. Cancer Research. 54:701-708.
4 Lee, E. et al. 1998. Carcinogenesis 8:1377-81.
SIDEBAR - Teas: The Ultimate GRAS BotanicalsThe North American marketplace for functional teas is heating up. Functional teas are a combination of teas and/or other botanicals (spices, herbs) formulated or specially fortified to produce specific physiological or psychological benefits beyond inherent benefits afforded by a single ingredient. The category includes products for energy, medicinal use and weight loss.
Many of these functional tea beverages are fortified with vitamins, botanical extracts and higher flavoring levels to mask unpleasant tastes. Like their counterparts in ready-to-drink (RTD) bottle and cans, functional tea bags offer consumers the promise of convenient energy, stamina, immune support and even weight loss. While there is ongoing controversy with functional RTD's as to whether or not significant amounts of nutrients are added to be efficacious, an even greater issue with functional tea bags is solubility performance into the finished brewed cup.
Brian Keating, Sage Group International LLC