From The July 2000 Issue of Nutrition Science News
by Marcia Zimmerman, C.N.
So-called "super foods" offer the promise of preventing cancer, decreasing heart attacks and improving brain function. Some of the more notable products with health claims now on store shelves include potato chips that enhance memory, new-age drinks that improve your love life, a candy bar that reduces hot flashes, a cookie that helps you bulk up and lean out, and margarine that cuts cholesterol.
All of the above claims are due to plant-derived "super nutrients," called phytochemicals, that are helping to blur the line between food and medicine. They appeal to a better-educated public--one growing older, wealthier and more willing to self-medicate with foods and supplements. The question is whether these claims are valid. Do potato chips enhanced with unknown quantities of Ginkgo biloba really improve memory?
The scientific community has produced a growing body of evidence indicating how phytochemicals work to prevent disease. However, scientists are not sure if isolated, single phytochemicals offer the same benefits as those existing within chemically related groups, as occurs in whole-food sources. Authorities caution that choosing foods containing naturally occurring phytochemicals is still the best health insurance. 
Phytochemicals are a group of nutritive components found in herbs, fruits, vegetables, grains, legumes, nuts and spices. Animal foods contain a similar group of disease-preventing nutrients--the term zoochemical has been suggested for them. Phytochemicals and zoochemicals--unlike carbohydrates, fats, proteins, vitamins and minerals--are not considered essential for life and have therefore been assigned quasi-nutrient status. Several disease-preventive benefits have been proposed for phytochemicals and zoochemicals. Research shows individual nutrients can:
- facilitate cell-to-cell communication, 
- modify cellular receptor uptake of hormones, 
- convert to vitamin A, 
- repair DNA damage from toxic exposure, 
- detoxify carcinogens through the activation of the cytochrome P450 and Phase II liver enzyme systems, 
- serve as antioxidants to help prevent various forms of cancer, 
- cause apoptosis (cell death) in cancer cells, 
- enhance immune response, 
- help prevent cardiovascular disease, 
- help prevent osteoporosis, 
- help prevent macular degeneration and cataracts. 
Phytochemicals and zoochemicals can be grouped into five families based on their chemical structure and biological activity. The families include terpenes, organosulfur compounds, phenols, organic acids and polysaccharides, and lipids. See the chart, right, for an overview of the families, what they do and what foods contain them. [13,14]
Terpenes are a large class of compounds made up of single or multiple hydrocarbon units. Three groups include the carotenes, limonoids and saponins. By far the most important terpenes are tetraterpenoids--the carotenoids.
Carotenoids are found in fruits and vegetables and have several biological activities that promote health. At least 600 different carotenoids exist; they are well-known phytochemicals because their bright colors distinguish foods that contain them. Commonly consumed fruits and vegetables contain groups of 40 to 50 carotenoids, which are grouped into three categories based on their color.
Yellow and orange fruits and vegetables--such as apricots, mangos, peaches, carrots, sweet potatoes and winter squash--contain the greatest variety of carotenoids. Some of these are alpha-, beta-, delta- and gamma-carotenes; lutein; lycopene; neurosporene; phytofluene; phytoene; and xanthophylls. This group of fruits and vegetables provides vitamin A through bodily conversion of the alpha-, beta- and gamma-carotenes. They also protect DNA from damage, an occurance that can result in unrestrained cellular growth. Yellow-orange carotenoids appear to protect against several cancers including breast, colorectal, lung, prostate and uterine. 
Yellow and green fruits and vegetables--such as tangerines, chard, collards, sweet corn, kale, okra and spinach--contain lutein, zeaxanthin, alpha- and beta-carotene and beta-cryptoxanthin. Carotenoids from these fruits and vegetables appear to prevent age-related macular degeneration and cataracts
as well as to lower uterine cancer risk. 
Red carotenoids--common to berries, watermelon, rhubarb and tomatoes--contain an abundance of lycopene, zeta-carotene, phytofluene and phytoene. All of these carotenoids are free radical quenchers that may help prevent prostate cancer. 
Although carotenoids from foods have shown cancer-preventive benefits, the effects of using carotene supplements have been mixed. A widely publicized 1996 National Cancer Institute study was halted prematurely due to lack of efficacy and possible adverse effects among 18,000 high-risk lung cancer patients receiving beta-carotene and vitamin A supplements. Several reasons have been proposed for the surprising results, chief of which was the use of high doses of isolated beta-carotene rather than naturally occurring carotenoid complexes that may provide synergistic effects. 
Limonoids form an important class of monoterpenes naturally found in the peels of citrus fruits. In a six-month, double-blind, placebo-controlled European study, 215 patients with chronic bronchitis during winter took a daily dose of 3 gelcaps, each containing 300 mg of a German product standardized to deliver at least 75 mg of limonene as well as 20 mg of alpha-pinene and 75 mg of cineole (eucalyptol). The supplement was well-tolerated and reduced the need for antibiotics, the frequency and intensity of acute bronchitis flareups and bouts of coughing and expectoration. 
Limonoids and perillyl alcohol, monoterpenes found in mandarin oranges, appear to have specific cancer and cardioprotective effects.  In animal studies, results suggest the chemotherapeutic activity of these monoterpenes can be attributed to induction of both Phase I and Phase II detoxification enzymes in the liver. These enzymes are part of the body's protection against harmful substances.
Saponins are found primarily in legumes, with the greatest concentration occurring in soybeans. Recent experimental investigations suggest that saponins have cholesterol-lowering, anticancer and immuno-stimulatory properties. Anticancer properties of saponins appear to be the result of antioxidant effects, immune modulation and regulation of cell proliferation. Animals have reduced high cholesterol levels when fed either soy protein, daidzein (a soy isoflavone) or soy germ. 
Phytonutrients of this family contain various forms of sulfur, which give them their characteristic pungent aroma. They are often rejected by Americans because cooking intensifies their odor and strong taste. Paradoxically, cooking can also boost their protective powers. The organosulfur group includes the cruciferous vegetables, such as bok choy, broccoli, brussels sprouts, cabbage, kale and turnips, and the onion and mustard families. The sulfur compounds in these three groups are slightly different and, consequently, each has specific health benefits.
Glucosinolates are found in cruciferous vegetables and the mustard family. Broccoli glucosinolates are thought to activate protective liver enzymes that detoxify potential carcinogens and facilitate estrogen conversion into estrogen conjugates that are eliminated from the body.
Glucosinolates are converted into several biotransformation products in the human body, particularly indole-3-carbinol, thiosulfonates and isothiocyanates.
Indoles bind to chemical carcinogens and activate detoxification enzymes. The biotransformation products of indoles are formed when acted on by stomach acid. Cabbage is a rich source of one indole called indole-3-carbinol or I3C. For many years cabbage juice was consumed as a preventive and curative agent, especially for bowel disorders. It was thought to contain "cabbagen," or vitamin U. Later on, the I3C-vitamin C complex was identified as the likely active constituent in cabbage juice. Thus, the name was changed to "ascorbigen" and the vitamin designation was dropped. Today, I3C is better known as an antitumor agent. The primary mechanism for this may be activation of liver enzymes that generate products with anticancer effects. 
Thiosulfonates are most notably found in onions and garlic as well as in chives, leeks and shallots. When the plants are cut or smashed, sulfur compounds release biotransformation products including allicin, ajoene, allylic sulfides, vinyl dithin and D-allyl mercaptocysteine. Some of these are considered antiatherosclerotic and anticancer agents. Others are antibacterial, antiviral and antifungal.  Allicin, allyl sulfides and allyl mercaptocysteine are also strong antioxidants. Specific allylic sulfides block the activity of toxins produced by bacteria and viruses. Garlic and onions, like their cruciferous relatives, can also selectively alter liver detoxification enzyme systems to reduce toxic by-products.
 Finally, garlic powder has been shown in numerous studies to lower cholesterol, often by as much as 10 percent. 
Isothiocyanates are found in several cruciferae, including mustard greens and seeds, daikon, horseradish and wasabi. Isothiocyanates are readily metabolized by humans; a research team at Johns Hopkins University School of Medicine in Baltimore reports isothiocyanates protect by activating phase II anticarcinogenic enzymes and suppressing phase I cancer-promoting enzymes in the liver.  Inhibition of esophageal, lung and several other cancers has been shown in animal studies at Ohio State University. Here, scientists proposed that activation of cytochrome P450 enzymes was the likely cancer-protective method. 
This large family of phytonutrients has more than 2,000 family members.  The simplest compounds are single phenolic units found in abundance in culinary herbs. These include apiole (found in dill and parsley), carvacrol (oregano) and rosmarinol (rosemary). All have a long history of use as food preservatives. In humans, they act as antioxidants, antifungals, anti-infectives and antiseptics. 
Polyphenols, or multiphenolic complexes, have an even wider range of biological activities. The red, blue and purple pigments found in fruits, vegetables, tea and herbs are due to their polyphenol content. Specific examples include apples, blueberries, cranberries, eggplants, red currants, grapes, grape juice, purple bell peppers, raspberries, red wine, and green and black tea. Polyphenols found primarily in citrus fruits are collectively known as bioflavonoids. These include rutin, kaempferol, quercetin, hesperidin and narigenin. They are considered to have antihistaminic, anti-inflammatory, antioxidant, anticlotting, antitumor and vascular effects. 
A distinct group of polyphenols known as the flavan-3-ols includes anthocyanidins, proanthocyanidins, catechins and tannins. These have been extensively studied for their antioxidant, anticancer, antitumor and cardioprotective effects.  Hundreds of studies alone have been done on green tea catechins to assess their cardiovascular effects.  Red wine, grape juice, pine bark and grape seed extracts have been studied for their anticlotting, antioxidant, cardiovascular and anticancer effects. 
Isoflavones from soy products and red clover have weak estrogenic activity and accordingly are known as phytoestrogens. Soy protein is a rich source of genistin, daidzin and glycetin, which the body converts into the active forms genistein, daidzein and glycetein. Isoflavones have been widely recognized as cardioprotective, prompting the U.S. Food and Drug Administration to allow a soy protein health claim (minimum 6.25 g daily) for cardiovascular health as part of a heart-healthy diet.  Soy protein also protects against some cancers  and relieves menstrual and menopausal symptoms.  A synthetic isoflavone called ipriflavone has been shown to reverse osteoporosis. 
Organic Acids and Polysaccharides
Phytochemicals in this group, which includes esters and lactones, are small to large complex carbon compounds found in grains, herbs, teas, a few vegetables and some fruits. These compounds act primarily as antioxidants, cancer preventives, liver protectants and inflammatory mediators.  They include the acids oxalic (found in spinach, rhubarb, tea and coffee), tartaric (apricots, apples), cinnamic (aloe [Aloe vera]), kava (Piper methysticum), caffeic (burdock [Arctium lappa]), hawthorn (Crataegus spp.), ferulic (oats, rice), gallic (tea), ellagic (guava [Psidium spp.]), chlorogenic (echinacea [Echinacea spp.]), salicylic (peppermint [Mentha piperita]) and tannic (nettles [Urtica spp.], tea, berries). Organic acids can form complexes with other phytochemicals to yield a new compound with even more powerful effects. For example, gallic acid complexes combine with polyphenolic catechins to form catechin gallates. Catechin-gallate complexes (esters) are antioxidants with enhanced anticancer and antitumor effects. 
Lipids and Zoochemicals
Phytochemical lipids include unsaturated fatty acids, oils, fat-soluble vitamins and fatty acid esters. This group of phytochemicals and zoochemicals acts on cellular membranes, thus affecting signaling, transport and receptor function. Some also act as enzyme cofactors (a prominent vitamin activity) and are antioxidants. The group includes isoprenoids that consist of multiple 5-carbon isoprene units and a long unsaturated side chain, omega-3 and omega-6 fatty acids, and the fatty acid ester conjugated linoleic acid.
Isoprenoids are antioxidants with the unique property of anchoring themselves in cell membranes. Vitamin E is the best-known isoprenoid; others include coenzyme Q-10 and lipoic acid. Vitamin E's primary function is to protect the phospholipid layers in membranes from free radical damage and facilitate receptor function. Vitamin E collaborates in a network with other antioxi-dants, including vitamin C, lipoic acid and co-Q10, in a system of electron shuffling that inactivates free radicals while boosting the antioxidant power of individual cycle participants. It also protects the tripeptide glutathione, an important component in phase II detoxification enzymes.  Vitamin E is actually a family of isoprenoids that includes beta-, delta- and gamma-tocotrienols and alpha-, beta-, delta- and gamma-tocopherols.
Tocotrienols appear to have tumor-inhibiting properties against breast cancer cells, a property tocopherols do not seem to have.  Researchers have observed that the biologic functions of tocopherols and tocotrienols appear unrelated, which underscores the need for both. Tocotrienols are also reported to lower cholesterol levels.  Tocotrienols naturally occur in grains and palm oil.
Omega-3 and Omega-6 Fatty Acids are found in dark-green leafy vegetables, grains, legumes, nuts and seeds. Alpha-linolenic, an omega-3 (n-3) fatty acid, and linoleic, an omega-6 fatty acid (n-6), are considered essential. Gamma-linolenic acid, or GLA (n-6), and eicosapentaenoic acid, or EPA (n-3), disrupt the proinflammatory prostaglandin E2 cascade, reducing inflammation and platelet aggregation and modulating immune response.  These activities protect against cardiovascular disease, cancer and many other forms of chronic disease.  Docosahexaenoic acid, or DHA (n-3), is an integral component of brain membranes. It has been effective in reducing disorders such as schizophrenia, depression and attention deficits.
 GLA comes from seed oils such as primrose, borage and black currant. EPA and DHA are zoochemicals found in fish, especially salmon, herring, tuna, trout and whitefish. Conjugated linoleic acid (CLA), a series of derivatives of linoleic acid, is found in cooked beef. It reduces some cancers in animal models. 
Phytosterols occur in most plant species, with significant amounts found in the seeds of green and yellow vegetables. Golden vegetables such as corn, oats, rice, soy, wheat and yams provide phytosterols. They reduce dietary cholesterol absorption, to which they are structurally similar, through a mechanism of competitive uptake in the digestive system and perhaps through reduction of cholesterol synthesis in the body.  Elevated blood cholesterol has long been implicated as a significant risk factor in cardiovascular disease.
The health and disease-fighting benefits of phytochemicals have been widely touted in the media. In turn, this has sparked wide public interest and demand for new and better information on phytochemicals--what they are, how they work, and which foods and supplements contain them. With a greater understanding of biochemistry and human physiology, phytochemicals could well drive the food and supplements industry forward through the 21st century.
1. United States Department of Agriculture. Beltsville human nutrition research center report; 2000 Apr 2.
2. Kelly GS. Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide. Altern Med Rev 1999;4(2):96-103.
3. Potter SM. Overview of proposed mechanisms for the hypo-cholesterolemic effect of soy. J Nutr 1995 Mar;125(3 Suppl):606S-11S.
4. Shils ME, et al. Modern nutrition in health and disease: 8th ed. Philadelphia: Lea & Febiger 1994. p 290.
5. Jenkinson AM, et al. The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes. FASEB 1999 Dec;13(15):2138-42.
6. Persky V, Van Horn L. Epidemiology of soy and cancer: perspectives and directions. J Nutr 1995;125(3 Suppl):709S-12S.
7. Steinmetz KA, Potter JD. Vegetables, fruit and cancer prevention: a review. J Am Diet Assoc 1996 Dec;96(10):1027-39.
8. Mo H, Elson CE. Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids. J Nutr 1999 Apr;129(4):804-13.
9. Zhang R, et al. Enhancement of immune function in mice fed with high doses of soy daidzein. Nutr Cancer 1997;29:24-8.
10. Gaziano JM, et al. A prospective study of consumption of carotenoids in fruits and vegetables and decreased cardiovascular mortality in the elderly. Ann Epidemiol 1995 Jul;5(4):255-60.
11. Head KA. Ipriflavone: an important bone-building isoflavone. Altern Med Rev 1999 Feb;4(1):10-22.
12. Seddon JM, et al. Dietary carotenoids, vitamin A, C, and E, and advanced age-related macular degeneration: eye disease case-control study group. JAMA 1994 Nov 9;272(18):1413-20.
13. Duke J. Handbook of biologically active phytochemicals and their activities. Boca Raton (FL): CRC Press; 1992. p 99, 131.
14. Tang W, Eisenbrand G. Chinese drugs of plant origin. Berlin, Germany: Springer-Verlag; 1992. p 582-4, 724-5.
15. Collins AR, et al, Serum carotenoids and oxidative DNA damage in human lymphocytes. Carcinogenesis 1998 Dec;19(12):2159-62.
16. Dragsted LO, et al. Cancer-protective factors in fruits and vegetables: biochemical and biological background. Pharmacol Toxicol 1993;72 (Suppl 1):116-35.
17. Sommerburg O, et al. Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol 1998 Aug;82(8):907-10.
18. Batieha AM, et al. Serum micronutrients and the subsequent risk of cervical cancer in a population-based nested case-control study. Can Epidem Biom Prev 1993;2:335-9.
19. Khachik F, et al. Lutein, lycopene and their oxidative metabolites in chemoprevetion of cancer. J Cell Biochem Suppl 1995;22:236-46.
20. Klausner RD, et al. Clinical intervention trials of beta-carotene supplements. National Institutes of Health Press Conference; 1996 Jan 18.
21. Meister R, et al. Efficacy and tolerability of myrtol standardized in long-term treatment of chronic bronchitis. A double-blind, placebo-controlled study. Study Group Investigators. Arzneimittelforschung 1999;49(4):351-8.
22. Maltzman TH, et al. Effects of monoterpenes on in vivo DMBA-DNA adduct formation and on phase I hepatic metabolizing enzymes. Carcinogenesis 1991 Nov;12(11):2081-7.
23. Elegbede J, et al. Effects of anticarcinogenic monoterpenes on phase II hepatic metabolizing enzymes. Carcinogenesis 1993;14(6):1221-3.
24. Rao AV. Anticarcinogenic properties of plant saponins. Second international symposium on the role of soy in preventing and treating chronic disease. Brussels, Belgium; 1996 Sep 15-18.
25. Hendrick S, et al. Are saponins and/or other soybean components responsible for hypocholesterolemic effects of soybean foods? Third international symposium on the role of soy in preventing and treating chronic disease. Washington, D.C.; 1999 Oct 31-Nov 3.
26. Kall MA, et al. Effects of dietary broccoli on human drug metabolizing activity. Cancer Lett 1997;114(1-2):169-70.
27. Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole carbinol. Nutr Cancer 1991;16:59-66.
28. Lash LJ. Garlic dietary supplements: an assessment of product information provided by garlic manufacturers. Minnesota Pharmacist 1999 Mar;53(2):13-4.
29. Reuter HD, et al. Therapeutic effects and applications of garlic and its preparations. In: Koch JP, Lawson LD (editors). Garlic: the science and therapeutic application of Allium sativum L and related species. Baltimore: Williams and Wilkins, 1996. p 60, 135-212.
30. Brady JF, et al. Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem Res Toxicol 1991 Nov/Dec;4(6):642-7.
31. Silagy C, Neil A. Garlic as a lipid lowering agent--a meta-analysis. J R Coll Phys London 1994;28:39-45.
32. Shapiro TA, et al. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev 1998;7(12):1091-100.
33. Stoner GD, Morse MA. Isothiocyanates and plant polyphenols as inhibitors of lung and esophageal cancer. Cancer Lett 1997 Mar 19;114(1-2):113-9.
34. King A, Young G. Characteristics and occurrence of phenolic phytochemicals. J Amer Diet Assoc 1999;99(2):213-8.
35. Tabak M, et al. Cinnamon extracts' inhibitory effect on Helicobacter pylori. J Ethnopharmacol 1999 Nov;67(3):269-77.
36. Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food and Chem Toxicol 1995;33(12):1061-80.
37. Sato M, et al. Cardioprotective effects of grape seed proanthocyanidins against ischemic reperfusion injury. J Mol Cell Cardiol 1999 Jun;31(6):1289-97.
38. Tijburg LB, et al. Tea flavonoids and cardiovascular diseases: a review. Crit Rev Food Sci Nutr 1997;37:771-85.
39. Renaud W, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992;339:1523-6.
40. Potter SM. Soy protein and cardiovascular disease: the impact of bioactive components in soy. Nutr Rev 1998;56(8):231-5.
41. Moyad MA. Soy, disease prevention, and prostate cancer. Semin Urol Oncol 1999;17(2):97-102.
42. Duncan AM, et al. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol Metab 1999 Oct;84(10):3479-84.
43. Scheiber MD, Rebar RW. Isoflavones and postmenopausal bone health: a viable alternative to estrogen therapy? Menopause 1999 Fall;6(3):233-41.
44. Craig W. Phytochemicals: guardians of our health. J Am Dietetic Assoc 1997;97(Suppl 2):S199-204.
45. Liao S, Hiipakka RA. Selective inhibition of steroid 5 alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatchin-3-gallate. Biochem Biophys Res Comm 1995;214(3):833-8.
46. Liebler DC. The role of metabolism in the antioxidant function of vitamin E. Crit Rev Toxicol 1993;23(2):147-69.
47. Suttorp N, et al. Antioxidant defense mechanisms of endothelial cells: glutathione redox cycle versus catalase. Am J Physiol 1986;251(5 pt 1):C671-80.
48. Elson CE. Suppression of mevalonate pathway activities by dietary isoprenoids: protective roles in cancer and cardiovascular disease. J Nutr 1995 Jun;125(6 Suppl):1666S-72S.
49. Quareshi AA, et al. Lowering of serum cholesterol in hyper-cholesterolemic humans by tocotrienols (palmvitee). Am J Clin Nutr 1991 Apr;53(4 Suppl):1021S-6S.
50. Horrobin DF. Interactions between n-3 and n-6 essential fatty acids (EFAs) in the regulation of cardiovascular disorders and inflammation. Prostaglandins Leukot Essent Fatty Acids 1991;44:127-31.
51. Horrobin DF. Omega-6 and omega-3 essential fatty acids in atherosclerosis. Seminars in thrombosis and hemostasis 1993;19(2):129-37.
52. Hibbeln JR, Salem N. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr 1995;62:1-9.
53. Cesano A, et al. Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Anticancer Res 1998;18(3A):1429-34.
54. Miettinen TA, et al. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 1990 Jan;131(1):20-31.
Return to the NUTRITION ARCHIVES Section