Phytochemicals:
Nutrients Whose Time Has Come

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

From The July 2000 Issue of Nutrition Science News

by Marcia Zimmerman, C.N.

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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. [1]

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, [2]
• modify cellular receptor uptake of hormones, [3]
• convert to vitamin A, [4]
• repair DNA damage from toxic exposure, [5]
• detoxify carcinogens through the activation of the cytochrome P450 and Phase II liver enzyme systems, [6]
• serve as antioxidants to help prevent various forms of cancer, [7]
• cause apoptosis (cell death) in cancer cells, [8]
• enhance immune response, [9]
• help prevent cardiovascular disease, [10]
• help prevent osteoporosis, [11]
• help prevent macular degeneration and cataracts. [12]

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]

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Terpenes

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. [15]Yellow-orange carotenoids appear to protect against several cancers including breast, colorectal, lung, prostate and uterine. [16]

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 [17]as well as to lower uterine cancer risk. [18]

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. [19]

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. [20]

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. [21]

Limonoids and perillyl alcohol, monoterpenes found in mandarin oranges, appear to have specific cancer and cardioprotective effects. [22] 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. [23]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. [24]Animals have reduced high cholesterol levels when fed either soy protein, daidzein (a soy isoflavone) or soy germ. [25]

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Organosulfur Compounds

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. [26]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. [27]

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. [28] Allicin, allyl sulfides and allyl mercaptocysteine are also strong antioxidants. Specific allylic sulfides block the activity of toxins produced by bacteria and viruses. [29]Garlic and onions, like their cruciferous relatives, can also selectively alter liver detoxification enzyme systems to reduce toxic by-products. [30] Finally, garlic powder has been shown in numerous studies to lower cholesterol, often by as much as 10 percent. [31]

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. [32] 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. [33]

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Phenols

This large family of phytonutrients has more than 2,000 family members. [34] 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. [35]

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. [36]

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. [37] Hundreds of studies alone have been done on green tea catechins to assess their cardiovascular effects. [38] Red wine, grape juice, pine bark and grape seed extracts have been studied for their anticlotting, antioxidant, cardiovascular and anticancer effects. [39]

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. [40] Soy protein also protects against some cancers [41] and relieves menstrual and menopausal symptoms. [42] A synthetic isoflavone called ipriflavone has been shown to reverse osteoporosis. [43]

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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. [44] 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. [45]

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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. [46]It also protects the tripeptide glutathione, an important component in phase II detoxification enzymes. [47] 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. [48] 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. [49] 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. [50] These activities protect against cardiovascular disease, cancer and many other forms of chronic disease. [51] 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. [52] 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. [53]

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. [54] 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.

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Marcia Zimmerman, C.N., is founder and CEO of The Zimmerman Group in Alameda, Calif. Her next book, Eat Your Colors: A Nutraceutical Plan to Eat the Right Foods for Your Body Type, will be published by Henry Holt & Co. in 2001.

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Sidebars:

Phytochemical Families

Phytochemicals: From Test Tube to Store

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